NCBI Home Page NCBI Site Search page NCBI Guide that lists and describes the NCBI resources
Conserved domains on  [gi|442626607|ref|NP_001260206|]
View 

zizimin, isoform I [Drosophila melanogaster]

Protein Classification

C2_Dock-D and DHR-2_Lobe_A domain-containing protein( domain architecture ID 10966832)

protein containing domains DOCK_C-D_N, PH_DOCK-D, C2_Dock-D, and DHR-2_Lobe_A

Graphical summary

 Zoom to residue level

show extra options »

Show site features     Horizontal zoom: ×

List of domain hits

 Name Accession Description Interval E-value
DHR2_DOCK_D cd11694
Dock Homology Region 2, a GEF domain, of Class D Dedicator of Cytokinesis proteins; DOCK ...
 1815-2228 0e+00

Dock Homology Region 2, a GEF domain, of Class D Dedicator of Cytokinesis proteins; DOCK proteins are atypical guanine nucleotide exchange factors (GEFs) that lack the conventional Dbl homology (DH) domain. As GEFs, they activate small GTPases by exchanging bound GDP for free GTP. They are divided into four classes (A-D) based on sequence similarity and domain architecture; class D, also called the Zizimin subfamily, includes Dock9, 10 and 11. Class D Docks are specific GEFs for Cdc42. Dock9 plays important roles in spine formation and dendritic growth. Dock10 and Dock11 are preferentially expressed in lymphocytes. All DOCKs contain two homology domains: the DHR-1 (Dock homology region-1), also called CZH1 (CED-5, Dock180, and MBC-zizimin homology 1), and DHR-2 (also called CZH2 or Docker). The DHR-1 domain binds phosphatidylinositol-3,4,5-triphosphate. This alignment model represents the DHR-2 domain of class D DOCKs, which contains the catalytic GEF activity for Cdc42. Class D DOCKs also contain a Pleckstrin homology (PH) domain at the N-terminus.


:

Pssm-ID: 212567  Cd Length: 376  Bit Score: 677.91  E-value: 0e+00
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442626607 1815 ELRHTWLVTMARNHEQNGNLSEAACCHLHIAALMCEYLRLKggctlswsstafgkistnipldeqglkldagaqdsqyte 1894
Cdd:cd11694     1 ELRKTWLESMARIHEKNGNFSEAAMCYIHIAALVAEYLKRK--------------------------------------- 41

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442626607 1895 QMLLEQLKLCADFLDRAERFECLGELYKLILPMYERDRSYQDLAHCYEHLTQAYNKIVEVNRSGKRMLGRFYRVVFYGLM 1974
Cdd:cd11694    42 DLLLELLEACVEGLWKAERYELLGELYKLIIPIYEKRRDFEQLADCYRTLHRAYEKVVEVMESGKRLLGTYYRVAFYGQA 121

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442626607 1975 YFEEDHAIEFVYKEPKLTSLSEISERLAKQYKEKFGADVVKMIMDSSPVKVDELDAKLAYIQVTHVIPFFSKDELDQRLN 2054
Cdd:cd11694   122 FFEEEDGKEYIYKEPKVTSLSEISERLLKLYGDKFGSENVKLIQDSGKVNPKDLDPKYAYIQVTHVTPYFDEKELEDRKT 201

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442626607 2055 EFEQNHDVDTFMYETPFTKSGAARGSVEEQWKRKTVIKTQYSFPYVLKRIPVKSREIIELSPIEVAIDEMQSKVSELEEI 2134
Cdd:cd11694   202 EFERNHNIRRFVFETPFTLSGKARGAVEEQWKRRTILTTSHSFPYVKKRIPVVQREIIELSPIEVAIDEMQSKVKELEEL 281

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442626607 2135 IL-PPADVKKLQLRLQGSVAVTVNAGPLAYAHAFLDAKVVNNFSMDRVGDLKDVFRDFIVVCQKALFLNERIISADQKEY 2213
Cdd:cd11694   282 IStEPVDMKKLQLRLQGSVSVQVNAGPLAYARAFLEPTTVKNYPDDQVEDLKDVFRDFIKACGQALELNERLIKEDQREY 361

                         410
                  ....*....|....*
gi 442626607 2214 HHVLKENYEKLCQAL 2228
Cdd:cd11694   362 HEVLKENYRKMVKEL 376
C2_Dock-D cd08697
C2 domains found in Dedicator Of CytoKinesis (Dock) class C proteins; Dock-D is one of 4 ...
 793-981 3.94e-94

C2 domains found in Dedicator Of CytoKinesis (Dock) class C proteins; Dock-D is one of 4 classes of Dock family proteins. The members here include: Dock9/Zizimin1, Dock10/Zizimin3, and Dock11/Zizimin2/ACG (activated Cdc42-associated GEF). Dock-D are Cdc42-specific GEFs. In addition to the C2 domain (AKA Dock homology region (DHR)-1, CED-5, Dock180, MBC-zizimin homology (CZH) 1) and the DHR-2 (AKA CZH2, or Docker), which all Dock180-related proteins have, Dock-D members contain a functionally uncharacterized domain and a PH domain upstream of the C2 domain. DHR-2 has the catalytic activity for Rac and/or Cdc42, but is structurally unrelated to the DH domain. The C2/DHR-1 domains of Dock180 and Dock4 have been shown to bind phosphatidylinositol-3, 4, 5-triphosphate (PtdIns(3,4,5)P3). The PH domain broadly binds to phospholipids and is thought to be involved in targeting the plasma membrane. The C2 domain was first identified in PKC. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.


:

Pssm-ID: 176079  Cd Length: 185  Bit Score: 302.32  E-value: 3.94e-94
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442626607  793 FCNHLYVYPLSLQFDSQKLFSRARNITVVVELRDGDGEYSKPLKCIYGRPGQDLLVSQIACpVLHHNVTPTWYEEIKLRL 872
Cdd:cd08697     1 YKNHLYVYPLHLKYDSQKTFAKARNIAVCIEFRDSDEEDAKPLKCIYYGPGGGFTTSAYAA-VLHHNQNPEFYDEIKIEL 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442626607  873 PLGLFPEHHLLFSFYHVSCNLSKKRDANAAFETPIGYAWLPLLQKN-RICLEEQQLPVAATL---PVGYLSIQPLgwgkg 948
Cdd:cd08697    80 PTQLHEKHHLLFTFYHVSCDINKKGKKKDGVETPVGYAWLPLLKDKgRLNSEEQTPPVANLLpnyPDGYLSIQPH----- 154

                         170       180       190
                  ....*....|....*....|....*....|...
gi 442626607  949 ncGPDIQWIDNQRNLYTVGLRLDSTVLTADQHL 981
Cdd:cd08697   155 --GPEVKWVDGGKPLFKVSTHLVSTVYTQDQHL 185
PH_DOCK-D cd13267
Dedicator of cytokinesis-D subfamily Pleckstrin homology (PH) domain; DOCK-D subfamily (also ...
 278-405 9.89e-57

Dedicator of cytokinesis-D subfamily Pleckstrin homology (PH) domain; DOCK-D subfamily (also called Zizimin subfamily) consists of Dock9/Zizimin1, Dock10/Zizimin3, and Dock11/Zizimin2. DOCK-D has a N-terminal DUF3398 domain, a PH-like domain, a Dock Homology Region 1, DHR1 (also called CZH1), a C2 domain, and a C-terminal DHR2 domain (also called CZH2). Zizimin1 is enriched in the brain, lung, and kidney; zizimin2 is found in B and T lymphocytes, and zizimin3 is enriched in brain, lung, spleen and thymus. Zizimin1 functions in autoinhibition and membrane targeting. Zizimin2 is an immune-related and age-regulated guanine nucleotide exchange factor, which facilitates filopodial formation through activation of Cdc42, which results in activation of cell migration. No function has been determined for Zizimin3 to date. The N-terminal half of zizimin1 binds to the GEF domain through three distinct areas, including CZH1, to inhibit the interaction with Cdc42. In addition its PH domain binds phosphoinositides and mediates zizimin1 membrane targeting. DOCK is a family of proteins involved in intracellular signalling networks. They act as guanine nucleotide exchange factors for small G proteins of the Rho family, such as Rac and Cdc42. There are 4 subfamilies of DOCK family proteins based on their sequence homology: A-D. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


:

Pssm-ID: 270087  Cd Length: 126  Bit Score: 192.93  E-value: 9.89e-57
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442626607  278 SQADTITKQGYLLKGPDSASDrMFANIGNKSFKRRYCYLRQEIDGTYILELHKDEKQGEAKATIVMDFCTDVVQNPKRGR 357
Cdd:cd13267     1 SGESGITKEGYLYKGPENSSD-SFISLAMKSFKRRFFHLKQLVDGSYILEFYKDEKKKEAKGTIFLDSCTGVVQNSKRRK 79

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*...
gi 442626607  358 FCFELRMtTGHKSFTLAAENEQDFKDWLSKISSVLAQNRAQEEKRNAS 405
Cdd:cd13267    80 FCFELRM-QDKKSYVLAAESEAEMDEWISKLNKILQSSKEQSIQKKRS 126
DOCK_C-D_N super family cl13339
Dedicator of cytokinesis C/D, N terminal; This entry represents the N-terminal domain of the ...
 37-81 2.02e-13

Dedicator of cytokinesis C/D, N terminal; This entry represents the N-terminal domain of the DOCK-C subfamily (DOCK 6, 7, 8) and DOCK-D subfamily (DOCK 9, 10, 11). DOCK family members are evolutionarily conserved guanine nucleotide exchange factors (GEFs) for Rho-family GTPases, required during several cellular processes, such as cell motility and phagocytosis. DOCK proteins are categorized into four subfamilies based on their sequence homology: DOCK-A (DOCK1/180, 2, 5), DOCK-B subfamily (DOCK3, 4), DOCK-C subfamily (DOCK6, 7, 8), DOCK-D subfamily (DOCK9, 10, 11).


The actual alignment was detected with superfamily member pfam11878:

Pssm-ID: 463380  Cd Length: 112  Bit Score: 68.45  E-value: 2.02e-13
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*
gi 442626607    37 VVEPIDFEAFIAKNKTVIQNDPQRELLIYPTDDVSEIIMPRKQRT 81
Cdd:pfam11878    3 VVEPLDYEEFISQHLTQIENDPLRDLLLFPDDDIEVSVIPRECRT 47
 
Name Accession Description Interval E-value
DHR2_DOCK_D cd11694
Dock Homology Region 2, a GEF domain, of Class D Dedicator of Cytokinesis proteins; DOCK ...
 1815-2228 0e+00

Dock Homology Region 2, a GEF domain, of Class D Dedicator of Cytokinesis proteins; DOCK proteins are atypical guanine nucleotide exchange factors (GEFs) that lack the conventional Dbl homology (DH) domain. As GEFs, they activate small GTPases by exchanging bound GDP for free GTP. They are divided into four classes (A-D) based on sequence similarity and domain architecture; class D, also called the Zizimin subfamily, includes Dock9, 10 and 11. Class D Docks are specific GEFs for Cdc42. Dock9 plays important roles in spine formation and dendritic growth. Dock10 and Dock11 are preferentially expressed in lymphocytes. All DOCKs contain two homology domains: the DHR-1 (Dock homology region-1), also called CZH1 (CED-5, Dock180, and MBC-zizimin homology 1), and DHR-2 (also called CZH2 or Docker). The DHR-1 domain binds phosphatidylinositol-3,4,5-triphosphate. This alignment model represents the DHR-2 domain of class D DOCKs, which contains the catalytic GEF activity for Cdc42. Class D DOCKs also contain a Pleckstrin homology (PH) domain at the N-terminus.


Pssm-ID: 212567  Cd Length: 376  Bit Score: 677.91  E-value: 0e+00
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442626607 1815 ELRHTWLVTMARNHEQNGNLSEAACCHLHIAALMCEYLRLKggctlswsstafgkistnipldeqglkldagaqdsqyte 1894
Cdd:cd11694     1 ELRKTWLESMARIHEKNGNFSEAAMCYIHIAALVAEYLKRK--------------------------------------- 41

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442626607 1895 QMLLEQLKLCADFLDRAERFECLGELYKLILPMYERDRSYQDLAHCYEHLTQAYNKIVEVNRSGKRMLGRFYRVVFYGLM 1974
Cdd:cd11694    42 DLLLELLEACVEGLWKAERYELLGELYKLIIPIYEKRRDFEQLADCYRTLHRAYEKVVEVMESGKRLLGTYYRVAFYGQA 121

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442626607 1975 YFEEDHAIEFVYKEPKLTSLSEISERLAKQYKEKFGADVVKMIMDSSPVKVDELDAKLAYIQVTHVIPFFSKDELDQRLN 2054
Cdd:cd11694   122 FFEEEDGKEYIYKEPKVTSLSEISERLLKLYGDKFGSENVKLIQDSGKVNPKDLDPKYAYIQVTHVTPYFDEKELEDRKT 201

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442626607 2055 EFEQNHDVDTFMYETPFTKSGAARGSVEEQWKRKTVIKTQYSFPYVLKRIPVKSREIIELSPIEVAIDEMQSKVSELEEI 2134
Cdd:cd11694   202 EFERNHNIRRFVFETPFTLSGKARGAVEEQWKRRTILTTSHSFPYVKKRIPVVQREIIELSPIEVAIDEMQSKVKELEEL 281

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442626607 2135 IL-PPADVKKLQLRLQGSVAVTVNAGPLAYAHAFLDAKVVNNFSMDRVGDLKDVFRDFIVVCQKALFLNERIISADQKEY 2213
Cdd:cd11694   282 IStEPVDMKKLQLRLQGSVSVQVNAGPLAYARAFLEPTTVKNYPDDQVEDLKDVFRDFIKACGQALELNERLIKEDQREY 361

                         410
                  ....*....|....*
gi 442626607 2214 HHVLKENYEKLCQAL 2228
Cdd:cd11694   362 HEVLKENYRKMVKEL 376
C2_Dock-D cd08697
C2 domains found in Dedicator Of CytoKinesis (Dock) class C proteins; Dock-D is one of 4 ...
 793-981 3.94e-94

C2 domains found in Dedicator Of CytoKinesis (Dock) class C proteins; Dock-D is one of 4 classes of Dock family proteins. The members here include: Dock9/Zizimin1, Dock10/Zizimin3, and Dock11/Zizimin2/ACG (activated Cdc42-associated GEF). Dock-D are Cdc42-specific GEFs. In addition to the C2 domain (AKA Dock homology region (DHR)-1, CED-5, Dock180, MBC-zizimin homology (CZH) 1) and the DHR-2 (AKA CZH2, or Docker), which all Dock180-related proteins have, Dock-D members contain a functionally uncharacterized domain and a PH domain upstream of the C2 domain. DHR-2 has the catalytic activity for Rac and/or Cdc42, but is structurally unrelated to the DH domain. The C2/DHR-1 domains of Dock180 and Dock4 have been shown to bind phosphatidylinositol-3, 4, 5-triphosphate (PtdIns(3,4,5)P3). The PH domain broadly binds to phospholipids and is thought to be involved in targeting the plasma membrane. The C2 domain was first identified in PKC. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.


Pssm-ID: 176079  Cd Length: 185  Bit Score: 302.32  E-value: 3.94e-94
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442626607  793 FCNHLYVYPLSLQFDSQKLFSRARNITVVVELRDGDGEYSKPLKCIYGRPGQDLLVSQIACpVLHHNVTPTWYEEIKLRL 872
Cdd:cd08697     1 YKNHLYVYPLHLKYDSQKTFAKARNIAVCIEFRDSDEEDAKPLKCIYYGPGGGFTTSAYAA-VLHHNQNPEFYDEIKIEL 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442626607  873 PLGLFPEHHLLFSFYHVSCNLSKKRDANAAFETPIGYAWLPLLQKN-RICLEEQQLPVAATL---PVGYLSIQPLgwgkg 948
Cdd:cd08697    80 PTQLHEKHHLLFTFYHVSCDINKKGKKKDGVETPVGYAWLPLLKDKgRLNSEEQTPPVANLLpnyPDGYLSIQPH----- 154

                         170       180       190
                  ....*....|....*....|....*....|...
gi 442626607  949 ncGPDIQWIDNQRNLYTVGLRLDSTVLTADQHL 981
Cdd:cd08697   155 --GPEVKWVDGGKPLFKVSTHLVSTVYTQDQHL 185
DHR-2_Lobe_A pfam06920
DHR-2, Lobe A; This entry represents a conserved region within a number of eukaryotic ...
 1801-1953 3.37e-66

DHR-2, Lobe A; This entry represents a conserved region within a number of eukaryotic dedicator of cytokinesis proteins (DOCK), which are guanine nucleotide exchange factors (GEFs), that activate some small GTPases by exchanging bound GDP for free GTP such as Rac. These proteins have a DOCK-homology region 1 (DHR-1, also known as DOCK-type C2 domain) at the N-terminus and a DHR-2 (also known as DOCKER domain) at the C-terminal. The DHR-2 is a GEF catalytic domain organized into three lobes, A, B and C, with the Rho-family binding site and catalytic centre generated entirely from lobes B and C. This entry represents Lobe A, formed from an antiparallel array of alpha helices that adopts a tetratricopeptide repeat-like fold, which through extensive contacts with lobe B, stabilizes DHR-2 domain.


Pssm-ID: 462040 [Multi-domain]  Cd Length: 154  Bit Score: 221.01  E-value: 3.37e-66
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442626607  1801 ELQYSLANSYASTPELRHTWLVTMARNHEQNGNLSEAACCHLHIAALMCEYLRLKGGCTLSWSSTAFGKISTNIPLDEQG 1880
Cdd:pfam06920    1 DLQYSLANSYKSSPDLRLTWLENLAEKHLENGNFSEAAQCLIHIAALIAEYLKLKGKIPNPLGASAFEKISPNILREESA 80

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 442626607  1881 LKLDAGAQDS-QYTEQMLLEQLKLCADFLDRAERFECLGELYKLILPMYERDRSYQDLAHCYEHLTQAYNKIVE 1953
Cdd:pfam06920   81 LKDDSGVCDSpHFTEDGLVGLLEEAIDYLDKAERYELAIELYKLLLPIYESRRDYKKLSECHGKLAEAYEKIVE 154
DOCK-C2 pfam14429
C2 domain in Dock180 and Zizimin proteins; The Dock180/Dock1 and Zizimin proteins are atypical ...
 790-980 6.04e-57

C2 domain in Dock180 and Zizimin proteins; The Dock180/Dock1 and Zizimin proteins are atypical GTP/GDP exchange factors for the small GTPases Rac and Cdc42 and are implicated cell-migration and phagocytosis. Across all Dock180 proteins, two regions are conserved: C-terminus termed CZH2 or DHR2 (or the Dedicator of cytokinesis) whereas CZH1/DHR1 contain a new family of the C2 domain.


Pssm-ID: 464171  Cd Length: 185  Bit Score: 195.90  E-value: 6.04e-57
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442626607   790 YTSFCNHLYVYPLSLQFDSQKlFSRARNITVVVELRDGDGEyskPL-KCIYGRPGQDLlVSQIACPVLHHNVTPTWYEEI 868
Cdd:pfam14429    1 PGDYRNDLYVTPKSGNFSKQK-KSSARNIEVTVEVRDSDGE---PLpNCIYGGSGGPF-VTEFKSTVYYHNKSPTWYEEI 75

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442626607   869 KLRLPLGLFPEHHLLFSFYHVSCNLSKKRDanaafETPIGYAWLPLLQKNR--ICLEEQQLPVAAT--LPVGYLSiQPLG 944
Cdd:pfam14429   76 KIALPAELTPKHHLLFTFYHVSCDEKKDKV-----EKPFGYAFLPLLDDDGafLRDGEHTLPVYKYdeLPPGYLS-LPWS 149

                          170       180       190
                   ....*....|....*....|....*....|....*.
gi 442626607   945 WGKGNCGPDIQWIDNQRNLYTVGLRLDSTVLTADQH 980
Cdd:pfam14429  150 SGGEKESSALPGLKGGKDLFKVRTRLCSTKYTQDEH 185
PH_DOCK-D cd13267
Dedicator of cytokinesis-D subfamily Pleckstrin homology (PH) domain; DOCK-D subfamily (also ...
 278-405 9.89e-57

Dedicator of cytokinesis-D subfamily Pleckstrin homology (PH) domain; DOCK-D subfamily (also called Zizimin subfamily) consists of Dock9/Zizimin1, Dock10/Zizimin3, and Dock11/Zizimin2. DOCK-D has a N-terminal DUF3398 domain, a PH-like domain, a Dock Homology Region 1, DHR1 (also called CZH1), a C2 domain, and a C-terminal DHR2 domain (also called CZH2). Zizimin1 is enriched in the brain, lung, and kidney; zizimin2 is found in B and T lymphocytes, and zizimin3 is enriched in brain, lung, spleen and thymus. Zizimin1 functions in autoinhibition and membrane targeting. Zizimin2 is an immune-related and age-regulated guanine nucleotide exchange factor, which facilitates filopodial formation through activation of Cdc42, which results in activation of cell migration. No function has been determined for Zizimin3 to date. The N-terminal half of zizimin1 binds to the GEF domain through three distinct areas, including CZH1, to inhibit the interaction with Cdc42. In addition its PH domain binds phosphoinositides and mediates zizimin1 membrane targeting. DOCK is a family of proteins involved in intracellular signalling networks. They act as guanine nucleotide exchange factors for small G proteins of the Rho family, such as Rac and Cdc42. There are 4 subfamilies of DOCK family proteins based on their sequence homology: A-D. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270087  Cd Length: 126  Bit Score: 192.93  E-value: 9.89e-57
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442626607  278 SQADTITKQGYLLKGPDSASDrMFANIGNKSFKRRYCYLRQEIDGTYILELHKDEKQGEAKATIVMDFCTDVVQNPKRGR 357
Cdd:cd13267     1 SGESGITKEGYLYKGPENSSD-SFISLAMKSFKRRFFHLKQLVDGSYILEFYKDEKKKEAKGTIFLDSCTGVVQNSKRRK 79

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*...
gi 442626607  358 FCFELRMtTGHKSFTLAAENEQDFKDWLSKISSVLAQNRAQEEKRNAS 405
Cdd:cd13267    80 FCFELRM-QDKKSYVLAAESEAEMDEWISKLNKILQSSKEQSIQKKRS 126
DOCK_C-D_N pfam11878
Dedicator of cytokinesis C/D, N terminal; This entry represents the N-terminal domain of the ...
 37-81 2.02e-13

Dedicator of cytokinesis C/D, N terminal; This entry represents the N-terminal domain of the DOCK-C subfamily (DOCK 6, 7, 8) and DOCK-D subfamily (DOCK 9, 10, 11). DOCK family members are evolutionarily conserved guanine nucleotide exchange factors (GEFs) for Rho-family GTPases, required during several cellular processes, such as cell motility and phagocytosis. DOCK proteins are categorized into four subfamilies based on their sequence homology: DOCK-A (DOCK1/180, 2, 5), DOCK-B subfamily (DOCK3, 4), DOCK-C subfamily (DOCK6, 7, 8), DOCK-D subfamily (DOCK9, 10, 11).


Pssm-ID: 463380  Cd Length: 112  Bit Score: 68.45  E-value: 2.02e-13
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*
gi 442626607    37 VVEPIDFEAFIAKNKTVIQNDPQRELLIYPTDDVSEIIMPRKQRT 81
Cdd:pfam11878    3 VVEPLDYEEFISQHLTQIENDPLRDLLLFPDDDIEVSVIPRECRT 47
PH smart00233
Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The ...
 283-393 3.78e-11

Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The domain family possesses multiple functions including the abilities to bind inositol phosphates, and various proteins. PH domains have been found to possess inserted domains (such as in PLC gamma, syntrophins) and to be inserted within other domains. Mutations in Brutons tyrosine kinase (Btk) within its PH domain cause X-linked agammaglobulinaemia (XLA) in patients. Point mutations cluster into the positively charged end of the molecule around the predicted binding site for phosphatidylinositol lipids.


Pssm-ID: 214574 [Multi-domain]  Cd Length: 102  Bit Score: 61.80  E-value: 3.78e-11
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442626607    283 ITKQGYLLKGPDSasdrmfaniGNKSFKRRYCYLRqeiDGT-YILELHKDEKQGEAKATIVMDFCT---DVVQNPKRGRF 358
Cdd:smart00233    1 VIKEGWLYKKSGG---------GKKSWKKRYFVLF---NSTlLYYKSKKDKKSYKPKGSIDLSGCTvreAPDPDSSKKPH 68

                            90       100       110
                    ....*....|....*....|....*....|....*
gi 442626607    359 CFELRMTTGhKSFTLAAENEQDFKDWLSKISSVLA 393
Cdd:smart00233   69 CFEIKTSDR-KTLLLQAESEEEREKWVEALRKAIA 102
PH pfam00169
PH domain; PH stands for pleckstrin homology.
 283-393 2.37e-09

PH domain; PH stands for pleckstrin homology.


Pssm-ID: 459697 [Multi-domain]  Cd Length: 105  Bit Score: 56.80  E-value: 2.37e-09
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442626607   283 ITKQGYLLKgpdsasdrmFANIGNKSFKRRYCYLRQeiDGTYILELHKDEKQGEAKATIVMDFCTDV---VQNPKRGRFC 359
Cdd:pfam00169    1 VVKEGWLLK---------KGGGKKKSWKKRYFVLFD--GSLLYYKDDKSGKSKEPKGSISLSGCEVVevvASDSPKRKFC 69

                           90       100       110
                   ....*....|....*....|....*....|....*.
gi 442626607   360 FELRMT--TGHKSFTLAAENEQDFKDWLSKISSVLA 393
Cdd:pfam00169   70 FELRTGerTGKRTYLLQAESEEERKDWIKAIQSAIR 105
 
Name Accession Description Interval E-value
DHR2_DOCK_D cd11694
Dock Homology Region 2, a GEF domain, of Class D Dedicator of Cytokinesis proteins; DOCK ...
 1815-2228 0e+00

Dock Homology Region 2, a GEF domain, of Class D Dedicator of Cytokinesis proteins; DOCK proteins are atypical guanine nucleotide exchange factors (GEFs) that lack the conventional Dbl homology (DH) domain. As GEFs, they activate small GTPases by exchanging bound GDP for free GTP. They are divided into four classes (A-D) based on sequence similarity and domain architecture; class D, also called the Zizimin subfamily, includes Dock9, 10 and 11. Class D Docks are specific GEFs for Cdc42. Dock9 plays important roles in spine formation and dendritic growth. Dock10 and Dock11 are preferentially expressed in lymphocytes. All DOCKs contain two homology domains: the DHR-1 (Dock homology region-1), also called CZH1 (CED-5, Dock180, and MBC-zizimin homology 1), and DHR-2 (also called CZH2 or Docker). The DHR-1 domain binds phosphatidylinositol-3,4,5-triphosphate. This alignment model represents the DHR-2 domain of class D DOCKs, which contains the catalytic GEF activity for Cdc42. Class D DOCKs also contain a Pleckstrin homology (PH) domain at the N-terminus.


Pssm-ID: 212567  Cd Length: 376  Bit Score: 677.91  E-value: 0e+00
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442626607 1815 ELRHTWLVTMARNHEQNGNLSEAACCHLHIAALMCEYLRLKggctlswsstafgkistnipldeqglkldagaqdsqyte 1894
Cdd:cd11694     1 ELRKTWLESMARIHEKNGNFSEAAMCYIHIAALVAEYLKRK--------------------------------------- 41

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442626607 1895 QMLLEQLKLCADFLDRAERFECLGELYKLILPMYERDRSYQDLAHCYEHLTQAYNKIVEVNRSGKRMLGRFYRVVFYGLM 1974
Cdd:cd11694    42 DLLLELLEACVEGLWKAERYELLGELYKLIIPIYEKRRDFEQLADCYRTLHRAYEKVVEVMESGKRLLGTYYRVAFYGQA 121

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442626607 1975 YFEEDHAIEFVYKEPKLTSLSEISERLAKQYKEKFGADVVKMIMDSSPVKVDELDAKLAYIQVTHVIPFFSKDELDQRLN 2054
Cdd:cd11694   122 FFEEEDGKEYIYKEPKVTSLSEISERLLKLYGDKFGSENVKLIQDSGKVNPKDLDPKYAYIQVTHVTPYFDEKELEDRKT 201

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442626607 2055 EFEQNHDVDTFMYETPFTKSGAARGSVEEQWKRKTVIKTQYSFPYVLKRIPVKSREIIELSPIEVAIDEMQSKVSELEEI 2134
Cdd:cd11694   202 EFERNHNIRRFVFETPFTLSGKARGAVEEQWKRRTILTTSHSFPYVKKRIPVVQREIIELSPIEVAIDEMQSKVKELEEL 281

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442626607 2135 IL-PPADVKKLQLRLQGSVAVTVNAGPLAYAHAFLDAKVVNNFSMDRVGDLKDVFRDFIVVCQKALFLNERIISADQKEY 2213
Cdd:cd11694   282 IStEPVDMKKLQLRLQGSVSVQVNAGPLAYARAFLEPTTVKNYPDDQVEDLKDVFRDFIKACGQALELNERLIKEDQREY 361

                         410
                  ....*....|....*
gi 442626607 2214 HHVLKENYEKLCQAL 2228
Cdd:cd11694   362 HEVLKENYRKMVKEL 376
DHR2_DOCK11 cd11700
Dock Homology Region 2, a GEF domain, of Class D Dedicator of Cytokinesis 11; Dock11, also ...
 1814-2228 4.95e-149

Dock Homology Region 2, a GEF domain, of Class D Dedicator of Cytokinesis 11; Dock11, also called Zizimin2 or activated Cdc42-associated GEF (ACG), is an atypical guanine nucleotide exchange factor (GEF) that lacks the conventional Dbl homology (DH) domain. As a GEF, it activates the small GTPase Cdc42 by exchanging bound GDP for free GTP. Dock11 is predominantly expressed in lymphocytes and is found in high levels in germinal center B lymphocytes after T cell dependent antigen immunization. DOCK proteins are divided into four classes (A-D) based on sequence similarity and domain architecture; class D includes Dock9, 10 and 11. All DOCKs contain two homology domains: the DHR-1 (Dock homology region-1), also called CZH1 (CED-5, Dock180, and MBC-zizimin homology 1), and DHR-2 (also called CZH2 or Docker). The DHR-1 domain binds phosphatidylinositol-3,4,5-triphosphate. This alignment model represents the DHR-2 domain of Dock11, which contains the catalytic GEF activity for Cdc42. Class D DOCKs also contain a Pleckstrin homology (PH) domain at the N-terminus.


Pssm-ID: 212573  Cd Length: 413  Bit Score: 469.09  E-value: 4.95e-149
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442626607 1814 PELRHTWLVTMARNHEQNGNLSEAACCHLHIAALMCEYLRLK----GGCTlswsstAFGKISTNIplDEQG-LKLDAGAQ 1888
Cdd:cd11700     1 PELRKTWLDSMAKIHVKNGDFSEAAMCYVHVAALVAEFLHRKklfpSGCA------AFKKITPNI--DEEGaMKEDIGMM 72

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442626607 1889 DSQYTEQMLLEQLKLCADFLDRAERFECLGELYKLILPMYERDRSYQDLAHCYEHLTQAYNKIVEVNRSGKRMLGRFYRV 1968
Cdd:cd11700    73 DVHYSEEVLVELLEQCVDGLWKAERYELISEISKLIIPIYEKRREFEKLTQLYRTLHGAYAKILEVMHTGKRLLGTFFRV 152

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442626607 1969 VFYGLMYFEEDHAIEFVYKEPKLTSLSEISERLAKQYKEKFGADVVKMIMDSSPVKVDELDAKLAYIQVTHVIPFFSKDE 2048
Cdd:cd11700   153 AFYGQGFFEEEDGKEYIYKEPKLTGLSEISHRLLKLYGEKFGSENVKIIQDSNKVNQKDLDPKYAHIQVTYVKPYFDDKE 232

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442626607 2049 LDQRLNEFEQNHDVDTFMYETPFTKSGAARGSVEEQWKRKTVIKTQYSFPYVLKRIPVKSREIIELSPIEVAIDEMQSKV 2128
Cdd:cd11700   233 MAERKTEFERNHNIQRFVFETPYTLSGKKQGGVEEQCKRRTILTTANSFPYVKKRIPVNGEKQTNLKPIDVATDEIKDKT 312

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442626607 2129 SELEEIILP-PADVKKLQLRLQGSVAVTVNAGPLAYAHAFLDAKVVNNFSMDRVGDLKDVFRDFIVVCQKALFLNERIIS 2207
Cdd:cd11700   313 AELQKLCSNqDVDMIQLQLKLQGCVSVQVNAGPLAYARAFLDDSQASKYPNKKVKELKEMFRKFIQACSIALELNERLIK 392

                         410       420
                  ....*....|....*....|.
gi 442626607 2208 ADQKEYHHVLKENYEKLCQAL 2228
Cdd:cd11700   393 EDQVEYHEGLKSNFRDMVKEL 413
DHR2_DOCK9 cd11698
Dock Homology Region 2, a GEF domain, of Class D Dedicator of Cytokinesis 9; Dock9, also ...
 1815-2231 1.40e-148

Dock Homology Region 2, a GEF domain, of Class D Dedicator of Cytokinesis 9; Dock9, also called Zizimin1, is an atypical guanine nucleotide exchange factor (GEF) that lacks the conventional Dbl homology (DH) domain. As a GEF, it activates the small GTPase Cdc42 by exchanging bound GDP for free GTP. It plays important roles in spine formation and dendritic growth. DOCK proteins are divided into four classes (A-D) based on sequence similarity and domain architecture; class D includes Dock9, 10 and 11. All DOCKs contain two homology domains: the DHR-1 (Dock homology region-1), also called CZH1 (CED-5, Dock180, and MBC-zizimin homology 1), and DHR-2 (also called CZH2 or Docker). The DHR-1 domain binds phosphatidylinositol-3,4,5-triphosphate. This alignment model represents the DHR-2 domain of Dock9, which contains the catalytic GEF activity for Cdc42. Class D DOCKs also contain a Pleckstrin homology (PH) domain at the N-terminus.


Pssm-ID: 212571  Cd Length: 415  Bit Score: 467.97  E-value: 1.40e-148
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442626607 1815 ELRHTWLVTMARNHEQNGNLSEAACCHLHIAALMCEYLRLKG----GCTlswsstAFGKISTNIPlDEQGLKLDAGAQDS 1890
Cdd:cd11698     1 ELRKTWLDSMARIHVKNGDLSEAAMCYVHVAALVAEYLTRKGmfrqGCT------AFRVITPNID-EEASMMEDVGMQDV 73

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442626607 1891 QYTEQMLLEQLKLCADFLDRAERFECLGELYKLILPMYERDRSYQDLAHCYEHLTQAYNKIVEVNRSGKRMLGRFYRVVF 1970
Cdd:cd11698    74 HFNEDVLMELLEQCADGLWKAERYELIADIYKLIIPIYEKRRDFERLAHLYDTLHRAYSKVTEVMHSGKRLLGTYFRVAF 153

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442626607 1971 YGLMYFEEDHAIEFVYKEPKLTSLSEISERLAKQYKEKFGADVVKMIMDSSPVKVDELDAKLAYIQVTHVIPFFSKDELD 2050
Cdd:cd11698   154 FGQGFFEDEDGKEYIYKEPKLTPLSEISQRLLKLYSDKFGSENVKMIQDSGKVNPKDLDSKYAYIQVTHVTPYFDEKELQ 233

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442626607 2051 QRLNEFEQNHDVDTFMYETPFTKSGAARGSVEEQWKRKTVIKTQYSFPYVLKRIPVKSREIIELSPIEVAIDEMQSKVSE 2130
Cdd:cd11698   234 ERKTDFERSHNIRRFMFEMPFTQSGKRQGGVEEQCKRRTILTAIHCFPYVKKRIPVMYQHHTDLNPIEVAIDEMSKKVAE 313

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442626607 2131 LEEII-LPPADVKKLQLRLQGSVAVTVNAGPLAYAHAFLDAKVVNNFSMDRVGDLKDVFRDFIVVCQKALFLNERIISAD 2209
Cdd:cd11698   314 LRQLCsSAEVDMIKLQLKLQGSVSVQVNAGPLAYARAFLDDTNTKRYPDNKVKLLKEVFRQFVEACGQALAVNERLIKED 393

                         410       420
                  ....*....|....*....|..
gi 442626607 2210 QKEYHHVLKENYEKLCQALSEL 2231
Cdd:cd11698   394 QLEYQEEMKANYREMAKELSEI 415
DHR2_DOCK10 cd11699
Dock Homology Region 2, a GEF domain, of Class D Dedicator of Cytokinesis 10; Dock10, also ...
 1814-2231 3.34e-142

Dock Homology Region 2, a GEF domain, of Class D Dedicator of Cytokinesis 10; Dock10, also called Zizimin3, is an atypical guanine nucleotide exchange factor (GEF) that lacks the conventional Dbl homology (DH) domain. As a GEF, it activates the small GTPase Cdc42 by exchanging bound GDP for free GTP. Dock10 is preferentially expressed in lymphocytes and may play a role in interleukin-4 induced activation of B cells. It may also play a role in the invasion of tumor cells. DOCK proteins are divided into four classes (A-D) based on sequence similarity and domain architecture; class D includes Dock9, 10 and 11. All DOCKs contain two homology domains: the DHR-1 (Dock homology region-1), also called CZH1 (CED-5, Dock180, and MBC-zizimin homology 1), and DHR-2 (also called CZH2 or Docker). The DHR-1 domain binds phosphatidylinositol-3,4,5-triphosphate. This alignment model represents the DHR-2 domain of Dock10, which contains the catalytic GEF activity for Cdc42. Class D DOCKs also contain a Pleckstrin homology (PH) domain at the N-terminus.


Pssm-ID: 212572  Cd Length: 446  Bit Score: 451.04  E-value: 3.34e-142
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442626607 1814 PELRHTWLVTMARNHEQNGNLSEAACCHLHIAALMCEYLRLKG-------------------------------GCTLSW 1862
Cdd:cd11699     1 PELRRTWLESMAKIHARNGDLSEAAMCYIHIAALIAEYLKRKGywkmekictssmlpedsqvydsnlllttstgGSMFSM 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442626607 1863 SSTAFGKISTNIPlDEQGLKLDAGAQDSQYTEQMLLEQLKLCADFLDRAERFECLGELYKLILPMYERDRSYQDLAHCYE 1942
Cdd:cd11699    81 GWPAFLSITPNIK-EEGAMKEDSGMQDTPYNENTLVEQLELCVDYLWKSERYELIADVNKPVIAVFEKQRDFKRLSELYY 159

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442626607 1943 HLTQAYNKIVEVNRSGKRMLGRFYRVVFYGLMYFEEDHAIEFVYKEPKLTSLSEISERLAKQYKEKFGADVVKMIMDSSP 2022
Cdd:cd11699   160 DIHRSYLKVAEVVNSEKRLFGRYYRVAFYGQGFFEEEEGKEYIYKEPKLTGLSEISQRLLKLYADKFGADNVKIIQDSNK 239

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442626607 2023 VKVDELDAKLAYIQVTHVIPFFSKDELDQRLNEFEQNHDVDTFMYETPFTKSGAARGSVEEQWKRKTVIKTQYSFPYVLK 2102
Cdd:cd11699   240 VNPKELDPKFAYIQVTYVTPYFDEKEQEDRKTDFEMHHNINRFVFETPFTLSGKKHGGVEEQCKRRTILTTSHSFPYVKK 319

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442626607 2103 RIPVKSREIIELSPIEVAIDEMQSKVSELEEI-ILPPADVKKLQLRLQGSVAVTVNAGPLAYAHAFLDAKVVNNFSMDRV 2181
Cdd:cd11699   320 RIQVVSQTSTELNPIEVAIDEMSKKVSELNQLcTMEEVDMIRLQLKLQGSVSVKVNAGPMAYARAFLEETNAKKYPDNQV 399

                         410       420       430       440       450
                  ....*....|....*....|....*....|....*....|....*....|
gi 442626607 2182 GDLKDVFRDFIVVCQKALFLNERIISADQKEYHHVLKENYEKLcqaLSEL 2231
Cdd:cd11699   400 KLLKEIFRQFAEACGQALDVNERLIKEDQLEYQEEMRSHYRDM---LSEL 446
DHR2_DOCK_C cd11695
Dock Homology Region 2, a GEF domain, of Class C Dedicator of Cytokinesis proteins; DOCK ...
 1814-2228 1.90e-119

Dock Homology Region 2, a GEF domain, of Class C Dedicator of Cytokinesis proteins; DOCK proteins are atypical guanine nucleotide exchange factors (GEFs) that lack the conventional Dbl homology (DH) domain. As GEFs, they activate small GTPases by exchanging bound GDP for free GTP. They are divided into four classes (A-D) based on sequence similarity and domain architecture; class C, also called the Zizimin-related (Zir) subfamily, includes Dock6, 7 and 8. Class C DOCKs have been shown to have GEF activity for both Rac and Cdc42. Dock6 regulates neurite outgrowth. Dock7 plays a critical roles in the early stages of axon formation, neuronal polarity, and myelination. Dock8 regulates T and B cell numbers and functions, and plays essential roles in humoral immune responses and the proper formation of B cell immunological synapses. All DOCKs contain two homology domains: the DHR-1 (Dock homology region-1), also called CZH1 (CED-5, Dock180, and MBC-zizimin homology 1), and DHR-2 (also called CZH2 or Docker). The DHR-1 domain binds phosphatidylinositol-3,4,5-triphosphate. This alignment model represents the DHR-2 domain of Class C Docks, which contains the catalytic GEF activity for Rac and Cdc42.


Pssm-ID: 212568  Cd Length: 368  Bit Score: 382.80  E-value: 1.90e-119
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442626607 1814 PELRHTWLVTMARNHEQNGNLSEAACCHLHIAALmceylrlkggctlswsstafgkistnipldeqGLKldagaqdsqyt 1893
Cdd:cd11695     2 PDLRLTWLQNMAEKHYERKNFAEAAQCLVHAAAL--------------------------------GLV----------- 38

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442626607 1894 eqMLLEQlklCADFLDRAERFECLGELYKLILPMYERDRSYQDLAHCYEHLTQAYNKIVEvNRSGKRMLGRFYRVVFYGL 1973
Cdd:cd11695    39 --GLLEQ---AAESFSKAGMYEAVNEVYKLLIPILEANRDYKKLAEIHGKLQDAFTKIEK-QQGGKRMFGTYFRVGFYGS 112

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442626607 1974 MYFEEDHAiEFVYKEPKLTSLSEISERLAKQYKEKFGADVVKMIMDSSPVKVDELDAKLAYIQVTHVIPFFSKDELDQRL 2053
Cdd:cd11695   113 KFGDLDGK-EFIYKEPAITKLPEISHRLETFYGERFGEERVEVIKDSNPVDTSKLDPDKAYIQITYVEPYFDEYELKERT 191

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442626607 2054 NEFEQNHDVDTFMYETPFTKSGAARGSVEEQWKRKTVIKTQYSFPYVLKRIPVKSREIIELSPIEVAIDEMQSKVSELEE 2133
Cdd:cd11695   192 TYFERNYNLRRFMYATPFTPDGKAHGELAEQYKRKTILTTENSFPYVKTRLQVVNREEIVLTPIEVAIEDVQKKTRELAA 271

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442626607 2134 -IILPPADVKKLQLRLQGSVAVTVNAGPLAYAHAFLDAKVVNNFSMDR-VGDLKDVFRDFIVVCQKALFLNERIISADQK 2211
Cdd:cd11695   272 aTTQEPPDPKMLQMVLQGSIGTTVNQGPLEVANVFLSDIPLDPKELDRhQNKLRLCFKEFSKKCYDALEKNKELIGPDQK 351

                         410
                  ....*....|....*..
gi 442626607 2212 EYHHVLKENYEKLCQAL 2228
Cdd:cd11695   352 EYQKELERNYENFKEKL 368
DHR2_DOCK cd11684
Dock Homology Region 2, a GEF domain, of Dedicator of Cytokinesis proteins; DOCK proteins ...
 1815-2224 3.79e-110

Dock Homology Region 2, a GEF domain, of Dedicator of Cytokinesis proteins; DOCK proteins comprise a family of atypical guanine nucleotide exchange factors (GEFs) that lack the conventional Dbl homology (DH) domain. As GEFs, they activate the small GTPases Rac and Cdc42 by exchanging bound GDP for free GTP. They are also called the CZH (CED-5, Dock180, and MBC-zizimin homology) family, after the first family members identified. Dock180 was first isolated as a binding partner for the adaptor protein Crk. The Caenorhabditis elegans protein, Ced-5, is essential for cell migration and phagocytosis, while the Drosophila ortholog, Myoblast city (MBC), is necessary for myoblast fusion and dorsal closure. DOCKs are divided into four classes (A-D) based on sequence similarity and domain architecture: class A includes Dock1 (or Dock180), 2 and 5; class B includes Dock3 and 4; class C includes Dock6, 7, and 8; and class D includes Dock9, 10 and 11. All DOCKs contain two homology domains: the DHR-1 (Dock homology region-1), also called CZH1, and DHR-2 (also called CZH2 or Docker). This alignment model represents the DHR-2 domain of DOCK proteins, which contains the catalytic GEF activity for Rac and/or Cdc42.


Pssm-ID: 212566 [Multi-domain]  Cd Length: 392  Bit Score: 356.99  E-value: 3.79e-110
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442626607 1815 ELRHTWLVTMARNHEQNGNLSEAACCHLHIAALmceylrlkggctLSWSSTAFGKISTNIPLdeqglkldagaQDSQYTE 1894
Cdd:cd11684     1 ELYIRYLHKLADLHEERGNYVEAALCLLLHADL------------YAWDLKALVPALAESLS-----------FPEQTSF 57

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442626607 1895 QMLLEQLKLCADFLDRAERFECLGELYKLILPMYERDRSYQDLAHCYEHLTQAYNKIVEVnrsgKRMLGRFYRVVFYGLM 1974
Cdd:cd11684    58 ERKEALYKKAIDLFDKGKAWEFAIALYKELIPQYENNFDYAKLSEVHRKIAKLYEKIAEK----DRLFPTYFRVGFYGKG 133

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442626607 1975 YFEEDHAIEFVYKEPKLTSLSEISERLAKQYKEKfgadvvKMIMDSSPVKVDELDAKLAYIQVTHVIPFFSKDEL----D 2050
Cdd:cd11684   134 FPESLRGKEFIYRGPEFERLGDFCERLKSLYPGA------EIIQSSEEPDDEILDSEGQYIQITSVEPYFDDEDLvsraA 207

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442626607 2051 QRLNEFEQNHDVDTFMYETPFTKSGAAR-GSVEEQWKRKTVIKTQYSFPYVLKRIPVKSREIIELSPIEVAIDEMQSKVS 2129
Cdd:cd11684   208 PGVRQFYRNNNINTFVYERPFTKGGKKSqNEITDQWKERTILTTEESFPTILRRSEVVSIEEIELSPIENAIEDIEKKTE 287

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442626607 2130 ELEEII-----LPPADVKKLQLRLQGSVAVTVNAGPLAYAHAFLDAKVVNNFSMDR-VGDLKDVFRDFIVVCQKALFLNE 2203
Cdd:cd11684   288 ELRSLInkyrsGDSPNVNPLQMLLQGTVDAAVNGGPVAYAEAFLSEEYLSNYPEAEkVKKLKEAFEEFLEILKRGLALHA 367

                         410       420
                  ....*....|....*....|.
gi 442626607 2204 RIISADQKEYHHVLKENYEKL 2224
Cdd:cd11684   368 KLCPPEMAPLHEELEEGFEKL 388
DHR2_DOCK6 cd11702
Dock Homology Region 2, a GEF domain, of Class C Dedicator of Cytokinesis 6; Dock6, also ...
 1813-2228 1.28e-106

Dock Homology Region 2, a GEF domain, of Class C Dedicator of Cytokinesis 6; Dock6, also called Zizimin-related 1 (Zir1), is an atypical guanine nucleotide exchange factor (GEF) that lacks the conventional Dbl homology (DH) domain. As a GEF, it activates the small GTPases Rac and Cdc42 by exchanging bound GDP for free GTP. It is widely expressed and shows highest expression in the dorsal root ganglion and the brain. It regulates neurite outgrowth. DOCK proteins are divided into four classes (A-D) based on sequence similarity and domain architecture; class C includes Dock6, 7 and 8. All DOCKs contain two homology domains: the DHR-1 (Dock homology region-1), also called CZH1 (CED-5, Dock180, and MBC-zizimin homology 1), and DHR-2 (also called CZH2 or Docker). The DHR-1 domain binds phosphatidylinositol-3,4,5-triphosphate. This alignment model represents the DHR-2 domain of Dock6, which contains the catalytic GEF activity for Rac and/or Cdc42.


Pssm-ID: 212575  Cd Length: 423  Bit Score: 348.15  E-value: 1.28e-106
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442626607 1813 TPELRHTWLVTMARNHEQNGNLSEAACCHLHIAALMCEYLRLKGGCT-LSWSSTAFGKISTNIpLDEQGLKLDAGAQDSQ 1891
Cdd:cd11702     1 SPDLRLTWLQNMAGKHSERGNHAEAAHCLVHSAALVAEYLSMLEDCRhLPVGCVSFQNISSNV-LEESAVSDDILSPDEE 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442626607 1892 -------YTEQMLLEQLKLCADFLDRAERFECLGELYKLILPMYERDRSYQDLAHCYEHLTQAYNKIVEVNRSGKRMLGR 1964
Cdd:cd11702    80 gicsgkyFTELGLVGLLEQAAASFNMGGLYEAVNEVYKILIPIHEANRDYKKLAVVHGKLQEAFNKITNQSSGWERMFGT 159

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442626607 1965 FYRVVFYGLMYFEEDHAiEFVYKEPKLTSLSEISERLAKQYKEKFGADVVKMIMDSSPVKVDELDAKLAYIQVTHVIPFF 2044
Cdd:cd11702   160 YFRVGFYGCKFGDLDEQ-EFVYKEPSITKLAEISHRLEEFYTERFGDEVVEIIKDSNPVDKSKLDPNKAYIQITYVEPFF 238

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442626607 2045 SKDELDQRLNEFEQNHDVDTFMYETPFTKSGAARGSVEEQWKRKTVIKTQYSFPYVLKRIPVKSREIIELSPIEVAIDEM 2124
Cdd:cd11702   239 DTYELKDRVTYFDKNYNLRTFLFCTPFTLDGRAHGELHEQYKRKTILTTSHAFPYIKTRINVLHREEIVLIPVEVAIEDM 318

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442626607 2125 QSKVSELE-EIILPPADVKKLQLRLQGSVAVTVNAGPLAYAHAFLdAKVVNNFSMDRVGD-LKDVFRDFIVVCQKALFLN 2202
Cdd:cd11702   319 QKKTQELAfATHQDPADAKMLQMVLQGCVGTTVNQGPLEVAQVFL-SEIPEDPKLFRHHNkLRLCFKDFTKRCEDALRKN 397

                         410       420
                  ....*....|....*....|....*.
gi 442626607 2203 ERIISADQKEYHHVLKENYEKLCQAL 2228
Cdd:cd11702   398 KALIGPDQKEYHRELERNYQRLREAL 423
DHR2_DOCK8 cd11701
Dock Homology Region 2, a GEF domain, of Class C Dedicator of Cytokinesis 8; Dock8, also ...
 1812-2228 2.55e-104

Dock Homology Region 2, a GEF domain, of Class C Dedicator of Cytokinesis 8; Dock8, also called Zizimin-related 3 (Zir3), is an atypical guanine nucleotide exchange factor (GEF) that lacks the conventional Dbl homology (DH) domain. As a GEF, it activates the small GTPases Rac1 and Cdc42 by exchanging bound GDP for free GTP. Dock8 is highly expressed in the immune system and it regulates T and B cell numbers and functions. It plays essential roles in humoral immune responses and the proper formation of B cell immunological synapses. Dock8 deficiency is a primary immune deficiency that results in extreme susceptibility to cutaneous viral infections, elevated IgE levels, and eosinophilia. It was originally described as an autosomal recessive form of hyper IgE syndrome (AR-HIES). DOCK proteins are divided into four classes (A-D) based on sequence similarity and domain architecture; class C includes Dock6, 7 and 8. All DOCKs contain two homology domains: the DHR-1 (Dock homology region-1), also called CZH1 (CED-5, Dock180, and MBC-zizimin homology 1), and DHR-2 (also called CZH2 or Docker). The DHR-1 domain binds phosphatidylinositol-3,4,5-triphosphate. This alignment model represents the DHR-2 domain of Dock8, which contains the catalytic GEF activity for Rac and/or Cdc42.


Pssm-ID: 212574  Cd Length: 422  Bit Score: 341.63  E-value: 2.55e-104
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442626607 1812 STPELRHTWLVTMARNHEQNGNLSEAACCHLHIAALMCEYLRLKGGCT-LSWSSTAFGKISTNIpLDEQGLKLDAGAQDS 1890
Cdd:cd11701     1 TSPDLRLTWLQNMAEKHTKRKCFTEAAMCLVHAAALVAEYLSMLEDHSyLPVGSVSFQNISSNV-LEESAVSDDILSPDE 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442626607 1891 Q-------YTEQMLLEQLKLCADFLDRAERFECLGELYKLILPMYERDRSYQDLAHCYEHLTQAYNKIVevNRSGKRMLG 1963
Cdd:cd11701    80 DgvcsgryFTENGLVGLLEQAAELFSTGGLYETVNEVYKIVIPILEAHRDFRKLASTHDKLQKAFDNII--NKGHKRMFG 157

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442626607 1964 RFYRVVFYGLMYFEEDHAiEFVYKEPKLTSLSEISERLAKQYKEKFGADVVKMIMDSSPVKVDELDAKLAYIQVTHVIPF 2043
Cdd:cd11701   158 TYFRVGFYGSKFGDLDEQ-EFIYKEPAITKLPEISHRLEGFYGQCFGDDVVEVIKDSTPVDKSKLDPNKAYIQITFVEPY 236

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442626607 2044 FSKDELDQRLNEFEQNHDVDTFMYETPFTKSGAARGSVEEQWKRKTVIKTQYSFPYVLKRIPVKSREIIELSPIEVAIDE 2123
Cdd:cd11701   237 FDDYEMKDRVTYFEKNFNLRRFMYTTPFTLDGRPRGELSEQYKRKTILTTMHAFPYIKTRINVIQKEEFDLTPIEVAIED 316

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442626607 2124 MQSKVSELEEII-LPPADVKKLQLRLQGSVAVTVNAGPLAYAHAFL-----DAKVVNNFSmdrvgDLKDVFRDFIVVCQK 2197
Cdd:cd11701   317 MQKKTRELAEAThQEPPDAKMLQMVLQGSVGATVNQGPLEVAQVFLaeipaDPKLYRHHN-----KLRLCFKEFIMRCGE 391

                         410       420       430
                  ....*....|....*....|....*....|.
gi 442626607 2198 ALFLNERIISADQKEYHHVLKENYEKLCQAL 2228
Cdd:cd11701   392 AVEKNKRLITADQREYQQELKKNYNKLRENL 422
DHR2_DOCK7 cd11703
Dock Homology Region 2, a GEF domain, of Class C Dedicator of Cytokinesis 7; Dock7, also ...
 1774-2233 4.29e-98

Dock Homology Region 2, a GEF domain, of Class C Dedicator of Cytokinesis 7; Dock7, also called Zizimin-related 2 (Zir2), is an atypical guanine nucleotide exchange factor (GEF) that lacks the conventional Dbl homology (DH) domain. As a GEF, it activates the small GTPases Rac1 and Cdc42 by exchanging bound GDP for free GTP. It plays a critical role in the initial specification of axon formation in hippocampal neurons. It affects neuronal polarity by regulating microtubule dynamics. Dock7 also plays a role in controlling myelination by Schwann cells. It may also play important roles in the function and distribution of dermal and follicular melanocytes. DOCK proteins are divided into four classes (A-D) based on sequence similarity and domain architecture; class C includes Dock6, 7 and 8. All DOCKs contain two homology domains: the DHR-1 (Dock homology region-1), also called CZH1 (CED-5, Dock180, and MBC-zizimin homology 1), and DHR-2 (also called CZH2 or Docker). The DHR-1 domain binds phosphatidylinositol-3,4,5-triphosphate. This alignment model represents the DHR-2 domain of Dock7, which contains the catalytic GEF activity for Rac and/or Cdc42.


Pssm-ID: 212576  Cd Length: 473  Bit Score: 325.50  E-value: 4.29e-98
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442626607 1774 DLTRRVRTVLMATAQMQAHHMDPERLLELQYSLANSYASTPELRHTWLVTMARNHEQNGNLSEAACCHLHIAALMCEYLR 1853
Cdd:cd11703     1 DLVFNLHMILSDTVKMKEHQEDPEMLIDLMYRIAKGYQTSPDLRLTWLQNMAGKHSERSNHAEAAQCLVHSAALVAEYLS 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442626607 1854 -LKGGCTLSWSSTAFGKISTNIpLDEQGLKLDAGAQDSQ-------YTEQMLLEQLKLCADFLDRAERFECLGELYKLIL 1925
Cdd:cd11703    81 mLEDRKYLPVGCVTFQNISSNV-LEESAVSDDVVSPDEEgicsgkyFTEAGLVGLLEQAAASFSMAGMYEAVNEVYKVLI 159

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442626607 1926 PMYERDRSYQDLAHCYEHLTQAYNKIVevNRSGKRMLGRFYRVVFYGLMYFEEDHAiEFVYKEPKLTSLSEISERLAKQY 2005
Cdd:cd11703   160 PIHEANRDAKKLATIHGKLQEAFSKIV--HQDGKRMFGTYFRVGFYGTKFGDLDEQ-EFVYKEPAITKLAEISHRLEGFY 236

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442626607 2006 KEKFGADVVKMIMDSSPVKVDELDAKLAYIQVTHVIPFFSKDELDQRLNEFEQNHDVDTFMYETPFTKSGAARGSVEEQW 2085
Cdd:cd11703   237 GERFGEDVVEVIKDSNPVDKCKLDPNKAFIQITYVEPYFDTYEMKDRITYFDKNYNLRRFMYCTPFTLDGRAHGELHEQF 316

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442626607 2086 KRKTVIKTQYSFPYVLKRIPVKSREIIELSPIEVAIDEMQSKVSELE-EIILPPADVKKLQLRLQGSVAVTVNAGPLAYA 2164
Cdd:cd11703   317 KRKTILTTSHAFPYIKTRINVIHKEEIILTPIEVAIEDMQKKTQELAfATHQDPADPKMLQMVLQGSVGTTVNQGPLEVA 396

                         410       420       430       440       450       460       470
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 442626607 2165 HAFL-----DAKVVNNFSMDRVgdlkdVFRDFIVVCQKALFLNERIISADQKEYHHVLKENYEKLCQALSELLD 2233
Cdd:cd11703   397 QVFLseipsDPKLFRHHNKLRL-----CFKDFTKRCEDALRKNKSLIGPDQKEYQRELERNYHRLKEALQPLIN 465
C2_Dock-D cd08697
C2 domains found in Dedicator Of CytoKinesis (Dock) class C proteins; Dock-D is one of 4 ...
 793-981 3.94e-94

C2 domains found in Dedicator Of CytoKinesis (Dock) class C proteins; Dock-D is one of 4 classes of Dock family proteins. The members here include: Dock9/Zizimin1, Dock10/Zizimin3, and Dock11/Zizimin2/ACG (activated Cdc42-associated GEF). Dock-D are Cdc42-specific GEFs. In addition to the C2 domain (AKA Dock homology region (DHR)-1, CED-5, Dock180, MBC-zizimin homology (CZH) 1) and the DHR-2 (AKA CZH2, or Docker), which all Dock180-related proteins have, Dock-D members contain a functionally uncharacterized domain and a PH domain upstream of the C2 domain. DHR-2 has the catalytic activity for Rac and/or Cdc42, but is structurally unrelated to the DH domain. The C2/DHR-1 domains of Dock180 and Dock4 have been shown to bind phosphatidylinositol-3, 4, 5-triphosphate (PtdIns(3,4,5)P3). The PH domain broadly binds to phospholipids and is thought to be involved in targeting the plasma membrane. The C2 domain was first identified in PKC. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.


Pssm-ID: 176079  Cd Length: 185  Bit Score: 302.32  E-value: 3.94e-94
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442626607  793 FCNHLYVYPLSLQFDSQKLFSRARNITVVVELRDGDGEYSKPLKCIYGRPGQDLLVSQIACpVLHHNVTPTWYEEIKLRL 872
Cdd:cd08697     1 YKNHLYVYPLHLKYDSQKTFAKARNIAVCIEFRDSDEEDAKPLKCIYYGPGGGFTTSAYAA-VLHHNQNPEFYDEIKIEL 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442626607  873 PLGLFPEHHLLFSFYHVSCNLSKKRDANAAFETPIGYAWLPLLQKN-RICLEEQQLPVAATL---PVGYLSIQPLgwgkg 948
Cdd:cd08697    80 PTQLHEKHHLLFTFYHVSCDINKKGKKKDGVETPVGYAWLPLLKDKgRLNSEEQTPPVANLLpnyPDGYLSIQPH----- 154

                         170       180       190
                  ....*....|....*....|....*....|...
gi 442626607  949 ncGPDIQWIDNQRNLYTVGLRLDSTVLTADQHL 981
Cdd:cd08697   155 --GPEVKWVDGGKPLFKVSTHLVSTVYTQDQHL 185
DHR-2_Lobe_A pfam06920
DHR-2, Lobe A; This entry represents a conserved region within a number of eukaryotic ...
 1801-1953 3.37e-66

DHR-2, Lobe A; This entry represents a conserved region within a number of eukaryotic dedicator of cytokinesis proteins (DOCK), which are guanine nucleotide exchange factors (GEFs), that activate some small GTPases by exchanging bound GDP for free GTP such as Rac. These proteins have a DOCK-homology region 1 (DHR-1, also known as DOCK-type C2 domain) at the N-terminus and a DHR-2 (also known as DOCKER domain) at the C-terminal. The DHR-2 is a GEF catalytic domain organized into three lobes, A, B and C, with the Rho-family binding site and catalytic centre generated entirely from lobes B and C. This entry represents Lobe A, formed from an antiparallel array of alpha helices that adopts a tetratricopeptide repeat-like fold, which through extensive contacts with lobe B, stabilizes DHR-2 domain.


Pssm-ID: 462040 [Multi-domain]  Cd Length: 154  Bit Score: 221.01  E-value: 3.37e-66
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442626607  1801 ELQYSLANSYASTPELRHTWLVTMARNHEQNGNLSEAACCHLHIAALMCEYLRLKGGCTLSWSSTAFGKISTNIPLDEQG 1880
Cdd:pfam06920    1 DLQYSLANSYKSSPDLRLTWLENLAEKHLENGNFSEAAQCLIHIAALIAEYLKLKGKIPNPLGASAFEKISPNILREESA 80

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 442626607  1881 LKLDAGAQDS-QYTEQMLLEQLKLCADFLDRAERFECLGELYKLILPMYERDRSYQDLAHCYEHLTQAYNKIVE 1953
Cdd:pfam06920   81 LKDDSGVCDSpHFTEDGLVGLLEEAIDYLDKAERYELAIELYKLLLPIYESRRDYKKLSECHGKLAEAYEKIVE 154
DOCK-C2 pfam14429
C2 domain in Dock180 and Zizimin proteins; The Dock180/Dock1 and Zizimin proteins are atypical ...
 790-980 6.04e-57

C2 domain in Dock180 and Zizimin proteins; The Dock180/Dock1 and Zizimin proteins are atypical GTP/GDP exchange factors for the small GTPases Rac and Cdc42 and are implicated cell-migration and phagocytosis. Across all Dock180 proteins, two regions are conserved: C-terminus termed CZH2 or DHR2 (or the Dedicator of cytokinesis) whereas CZH1/DHR1 contain a new family of the C2 domain.


Pssm-ID: 464171  Cd Length: 185  Bit Score: 195.90  E-value: 6.04e-57
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442626607   790 YTSFCNHLYVYPLSLQFDSQKlFSRARNITVVVELRDGDGEyskPL-KCIYGRPGQDLlVSQIACPVLHHNVTPTWYEEI 868
Cdd:pfam14429    1 PGDYRNDLYVTPKSGNFSKQK-KSSARNIEVTVEVRDSDGE---PLpNCIYGGSGGPF-VTEFKSTVYYHNKSPTWYEEI 75

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442626607   869 KLRLPLGLFPEHHLLFSFYHVSCNLSKKRDanaafETPIGYAWLPLLQKNR--ICLEEQQLPVAAT--LPVGYLSiQPLG 944
Cdd:pfam14429   76 KIALPAELTPKHHLLFTFYHVSCDEKKDKV-----EKPFGYAFLPLLDDDGafLRDGEHTLPVYKYdeLPPGYLS-LPWS 149

                          170       180       190
                   ....*....|....*....|....*....|....*.
gi 442626607   945 WGKGNCGPDIQWIDNQRNLYTVGLRLDSTVLTADQH 980
Cdd:pfam14429  150 SGGEKESSALPGLKGGKDLFKVRTRLCSTKYTQDEH 185
PH_DOCK-D cd13267
Dedicator of cytokinesis-D subfamily Pleckstrin homology (PH) domain; DOCK-D subfamily (also ...
 278-405 9.89e-57

Dedicator of cytokinesis-D subfamily Pleckstrin homology (PH) domain; DOCK-D subfamily (also called Zizimin subfamily) consists of Dock9/Zizimin1, Dock10/Zizimin3, and Dock11/Zizimin2. DOCK-D has a N-terminal DUF3398 domain, a PH-like domain, a Dock Homology Region 1, DHR1 (also called CZH1), a C2 domain, and a C-terminal DHR2 domain (also called CZH2). Zizimin1 is enriched in the brain, lung, and kidney; zizimin2 is found in B and T lymphocytes, and zizimin3 is enriched in brain, lung, spleen and thymus. Zizimin1 functions in autoinhibition and membrane targeting. Zizimin2 is an immune-related and age-regulated guanine nucleotide exchange factor, which facilitates filopodial formation through activation of Cdc42, which results in activation of cell migration. No function has been determined for Zizimin3 to date. The N-terminal half of zizimin1 binds to the GEF domain through three distinct areas, including CZH1, to inhibit the interaction with Cdc42. In addition its PH domain binds phosphoinositides and mediates zizimin1 membrane targeting. DOCK is a family of proteins involved in intracellular signalling networks. They act as guanine nucleotide exchange factors for small G proteins of the Rho family, such as Rac and Cdc42. There are 4 subfamilies of DOCK family proteins based on their sequence homology: A-D. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270087  Cd Length: 126  Bit Score: 192.93  E-value: 9.89e-57
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442626607  278 SQADTITKQGYLLKGPDSASDrMFANIGNKSFKRRYCYLRQEIDGTYILELHKDEKQGEAKATIVMDFCTDVVQNPKRGR 357
Cdd:cd13267     1 SGESGITKEGYLYKGPENSSD-SFISLAMKSFKRRFFHLKQLVDGSYILEFYKDEKKKEAKGTIFLDSCTGVVQNSKRRK 79

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*...
gi 442626607  358 FCFELRMtTGHKSFTLAAENEQDFKDWLSKISSVLAQNRAQEEKRNAS 405
Cdd:cd13267    80 FCFELRM-QDKKSYVLAAESEAEMDEWISKLNKILQSSKEQSIQKKRS 126
C2_Dock-C cd08696
C2 domains found in Dedicator Of CytoKinesis (Dock) class C proteins; Dock-C is one of 4 ...
 795-981 7.04e-42

C2 domains found in Dedicator Of CytoKinesis (Dock) class C proteins; Dock-C is one of 4 classes of Dock family proteins. The members here include: Dock6/Zir1, Dock7/Zir2, and Dock8/Zir3. Dock-C members are GEFs for both Rac and Cdc42. In addition to the C2 domain (AKA Dock homology region (DHR)-1, CED-5, Dock180, MBC-zizimin homology (CZH) 1) and the DHR-2 (AKA CZH2, or Docker), which all Dock180-related proteins have, Dock-C members contain a functionally uncharacterized domain upstream of the C2 domain. DHR-2 has the catalytic activity for Rac and/or Cdc42, but is structurally unrelated to the DH domain. The C2/DHR-1 domains of Dock180 and Dock4 have been shown to bind phosphatidylinositol-3, 4, 5-triphosphate (PtdIns(3,4,5)P3). The C2 domain was first identified in PKC. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.


Pssm-ID: 176078  Cd Length: 179  Bit Score: 152.51  E-value: 7.04e-42
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442626607  795 NHLYVYPLSLQFDSQKlfSRARNITVVVELRDGDGEYSKPLKCIYGRPGQDLLvSQIACPVLHHNVTPTWYEEIKLRLPL 874
Cdd:cd08696     3 NLLYVYPQSLNFSNRL--GSARNIAVKVQLMSGEDESQALPVIFKGSSPEEFL-TEAYTAVTYHNKSPDFYDEIKIKLPA 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442626607  875 GLFPEHHLLFSFYHVSCnlsKKRDANAAFETPIGYAWLPLLQKNRICLEEQQLPVAATLPVGYLSIQPLgwgkGNCGPDI 954
Cdd:cd08696    80 DLTDNHHLLFTFYHISC---QKKQEGGSVETPIGYTWLPLLRNGRLQSGEFNLPVSLEKPPSNYSPDSP----EVKLPGT 152

                         170       180
                  ....*....|....*....|....*..
gi 442626607  955 QWIDNQRNLYTVGLRLDSTVLTADQHL 981
Cdd:cd08696   153 KWVDNHKGVFSVSVEAVSSVHTQDSYL 179
DHR-2_Lobe_C pfam20421
DHR-2, Lobe C; DOCK (dedicator of cytokinesis) proteins are guanine nucleotide exchange ...
 2130-2231 1.81e-39

DHR-2, Lobe C; DOCK (dedicator of cytokinesis) proteins are guanine nucleotide exchange factors (GEFs) that activate some small GTPases, such as Rac or Cdc42, by exchanging bound GDP for free GTP to control cell migration, morphogenesis, and phagocytosis. These proteins share a DOCK-type C2 domain (also termed the DOCK-homology region (DHR)-1) at the N-terminal, and the DHR-2 domain (also termed the DOCKER domain) at the C-terminal. DHR-2 is the GEF catalytic domain organized into three lobes A, B and C, with the Rho-family binding site and catalytic centre generated entirely from lobes B and C. This entry represents Lobe C which form an antiparallel four alpha-helical bundle and contains a loop known as the nucleotide sensor characterized by a conserved valine residue essential for catalytic activity.


Pssm-ID: 466570 [Multi-domain]  Cd Length: 103  Bit Score: 142.35  E-value: 1.81e-39
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442626607  2130 ELEEIIL-PPADVKKLQLRLQGSVAVTVNAGPLAYAHAFLDAKVVNNFSMDRVGDLKDVFRDFIVVCQKALFLNERIISA 2208
Cdd:pfam20421    1 ELEAAINaPPPNIKTLQMVLQGSVDVQVNAGPLEYAEAFLSEKNVDNYPAEKVEKLKEEFRDFLKVCGEALRLNKKLISE 80

                           90       100
                   ....*....|....*....|...
gi 442626607  2209 DQKEYHHVLKENYEKLCQALSEL 2231
Cdd:pfam20421   81 DQREYQEELEEGFEKLKEKLEPY 103
C2_DOCK180_related cd08679
C2 domains found in Dedicator Of CytoKinesis 1 (DOCK 180) and related proteins; Dock180 was ...
 795-981 1.43e-38

C2 domains found in Dedicator Of CytoKinesis 1 (DOCK 180) and related proteins; Dock180 was first identified as an 180kd proto-oncogene product c-Crk-interacting protein involved in actin cytoskeletal changes. It is now known that it has Rac-specific GEF activity, but lacks the conventional Dbl homology (DH) domain. There are 10 additional related proteins that can be divided into four classes based on sequence similarity and domain organization: Dock-A which includes Dock180/Dock1, Dock2, and Dock5; Dock-B which includes Dock3/MOCA (modifier of cell adhesion) and Dock4; Dock-C which includes Dock6/Zir1, Dock7/Zir2, and Dock8/Zir3; and Dock-D, which includes Dock9/Zizimin1, Dock10/Zizimin3, and Dock11/Zizimin2/ACG (activated Cdc42-associated GEF). Most of members of classes Dock-A and Dock-B are the GEFs specific for Rac. Those of Dock-D are Cdc42-specific GEFs while those of Dock-C are the GEFs for both. All Dock180-related proteins have two common homology domains: the C2 domain (AKA Dock homology region (DHR)-1, CED-5, Dock180, MBC-zizimin homology (CZH) 1) and the DHR-2 (AKA CZH2, or Docker). DHR-2 has the catalytic activity for Rac and/or Cdc42, but is structurally unrelated to the DH domain. The C2/DHR-1 domains of Dock180 and Dock4 have been shown to bind phosphatidylinositol-3, 4, 5-triphosphate (PtdIns(3,4,5)P3). The C2 domain was first identified in PKC. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.


Pssm-ID: 176061  Cd Length: 178  Bit Score: 142.85  E-value: 1.43e-38
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442626607  795 NHLYVYPLSLQFDSQKlfSRARNITVVVELRDGDGEYSKPlkCIYgRPGQDLLVSQIACPVLHHNVTPTWYEEIKLRLPL 874
Cdd:cd08679     3 NDLYVYPQSGELSKAK--SKGRNIEITVEVRDDDGDIIEP--CIS-APGSGSELRSEYTSVVYYHKNPVFNDEIKIQLPA 77

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442626607  875 GLFPEHHLLFSFYHVSCnlskKRDANAAFETPIGYAWLPLLQKNRICLE--EQQLPVAA------TLPVGYLSIQPLGWG 946
Cdd:cd08679    78 DLTPQHHLLFTFYHVSS----KKKQGDKEETPFGYAFLPLMDKDGAFIKdgDHTLPVYKydkrpdVGPSGYLSLPSTLAN 153

                         170       180       190
                  ....*....|....*....|....*....|....*
gi 442626607  947 KGNCGPdiqwidnqrnLYTVGLRLDSTVLTADQHL 981
Cdd:cd08679   154 GKSSKD----------TFKIKTRLCSTILTQDKSL 178
DHR-2_Lobe_B pfam20422
DHR-2, Lobe B; DOCK (dedicator of cytokinesis) proteins are guanine nucleotide exchange ...
 2020-2096 1.34e-34

DHR-2, Lobe B; DOCK (dedicator of cytokinesis) proteins are guanine nucleotide exchange factors (GEFs) that activate some small GTPases, such as Rac or Cdc42, by exchanging bound GDP for free GTP to control cell migration, morphogenesis, and phagocytosis. These proteins share a DOCK-type C2 domain (also termed the DOCK-homology region (DHR)-1) at the N-terminal, and the DHR-2 domain (also termed the DOCKER domain) at the C-terminal. DHR-2 is the GEF catalytic domain organized into three lobes A, B and C, with the Rho-family binding site and catalytic centre generated entirely from lobes B and C. This entry represents Lobe B which adopts an unusual architecture of two antiparallel beta sheets disposed in a loosely packed orthogonal arrangement. This lobe changes its position relative to lobe C and the bound GTPase, which suggests that lobe B distinguishes between the switch 1 conformations of Rac1 and Cdc42.


Pssm-ID: 466571 [Multi-domain]  Cd Length: 77  Bit Score: 127.72  E-value: 1.34e-34
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 442626607  2020 SSPVKVDELDAKLAYIQVTHVIPFFSKDELDQRLNEFEQNHDVDTFMYETPFTKSGAARGSVEEQWKRKTVIKTQYS 2096
Cdd:pfam20422    1 SNPVDESILDPDKAYIQITSVEPYFDDSELNDRVTYFERNNNVNRFVFETPFTKSGKAQGEFEEQWKRRTILTTEHS 77
DHR2_DOCK_A cd11697
Dock Homology Region 2, a GEF domain, of Class A Dedicator of Cytokinesis proteins; DOCK ...
 1892-2224 2.70e-22

Dock Homology Region 2, a GEF domain, of Class A Dedicator of Cytokinesis proteins; DOCK proteins are atypical guanine nucleotide exchange factors (GEFs) that lack the conventional Dbl homology (DH) domain. As GEFs, they activate small GTPases by exchanging bound GDP for free GTP. They are divided into four classes (A-D) based on sequence similarity and domain architecture; class A includes Dock1, 2 and 5. Class A DOCKs are specific GEFs for Rac. Dock1 interacts with the scaffold protein Elmo and the resulting complex functions upstream of Rac in many biological events including phagocytosis of apoptotic cells, cell migration and invasion. Dock2 plays an important role in lymphocyte migration and activation, T-cell differentiation, neutrophil chemotaxis, and type I interferon induction. Dock5 functions upstream of Rac1 to regulate osteoclast function. All DOCKs contain two homology domains: the DHR-1 (Dock homology region-1), also called CZH1 (CED-5, Dock180, and MBC-zizimin homology 1), and DHR-2 (also called CZH2 or Docker). The DHR-1 domain binds phosphatidylinositol-3,4,5-triphosphate. This alignment model represents the DHR-2 domain of class A DOCKs, which contains the catalytic GEF activity for Rac and/or Cdc42. Class A DOCKs also contain an SH3 domain at the N-terminal region and a PxxP motif at the C-terminus.


Pssm-ID: 212570  Cd Length: 400  Bit Score: 102.02  E-value: 2.70e-22
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442626607 1892 YTEQMLLEQLKL-CADFLDRAERFECLGELYKLILPMYERDR-SYQDLAHCYEHLTQAYNKIVEVNRSGKRmlgrFYRVV 1969
Cdd:cd11697    54 QTHRQLKEALYYdIIDYFDKGKMWECAISLCKELAEQYENETfDYLQLSELLKRMATFYDNIMKTLRPEPE----YFRVG 129

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442626607 1970 FYGLMY--FEEDHAieFVYKEPKLTSLSEISERLAKQYKEKfgadvvKMIMDSSPVKVDELDAKLAYIQVTHVIP----- 2042
Cdd:cd11697   130 YYGQGFpsFLRNKV--FIYRGKEYERLSDFSARLLNQFPNA------ELMNTLTPPGDEIKESPGQYLQINKVDPvmder 201

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442626607 2043 --FFSKDELDQRLNEFEQNhDVDTFMYETPFTKSgaARGSVEE---QWKRKTVIKTQYSFPYVLKRIPVKSREIIELSPI 2117
Cdd:cd11697   202 prFKGKPVSDQILNYYKVN-EVQRFTFSRPFRRG--TKDPDNEfanMWLERTTLTTAYKLPGILRWFEVVSTSTVEISPL 278

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442626607 2118 EVAIDEMQSKVSELEEIIL-----PPADVKKLQLRLQGSVAVTVNAGPLAYAHAFLDAKVVNNFSMDR--VGDLKDVFRD 2190
Cdd:cd11697   279 ENAIETMEDTNKKIRDLILqhqsdPTLPINPLSMLLNGIVDAAVMGGIANYEKAFFTEEYLDEHPEDQelIERLKDLIAE 358

                         330       340       350
                  ....*....|....*....|....*....|....
gi 442626607 2191 FIVVCQKALFLNERIISADQKEYHHVLKENYEKL 2224
Cdd:cd11697   359 QIPLLEAGLKIHKQKAPESLRPLHERMEECFAKM 392
DHR2_DOCK_B cd11696
Dock Homology Region 2, a GEF domain, of Class B Dedicator of Cytokinesis proteins; DOCK ...
 1828-2228 2.38e-19

Dock Homology Region 2, a GEF domain, of Class B Dedicator of Cytokinesis proteins; DOCK proteins are atypical guanine nucleotide exchange factors (GEFs) that lack the conventional Dbl homology (DH) domain. As GEFs, they activate small GTPases by exchanging bound GDP for free GTP. They are divided into four classes (A-D) based on sequence similarity and domain architecture; class B includes Dock3 and 4. Dock3 is a specific GEF for Rac and it regulates N-cadherin dependent cell-cell adhesion, cell polarity, and neuronal morphology. It promotes axonal growth by stimulating actin polymerization and microtubule assembly. Dock4 activates the Ras family GTPase Rap1, probably indirectly through interaction with Rap regulatory proteins. It plays a role in regulating dendritic growth and branching in hippocampal neurons, where it is highly expressed. All DOCKs contain two homology domains: the DHR-1 (Dock homology region-1), also called CZH1 (CED-5, Dock180, and MBC-zizimin homology 1), and DHR-2 (also called CZH2 or Docker). The DHR-1 domain binds phosphatidylinositol-3,4,5-triphosphate. This alignment model represents the DHR-2 domain of class B DOCKs, which contains the catalytic GEF activity for Rac and/or Cdc42. Class B DOCKs also contain an SH3 domain at the N-terminal region and a PxxP motif at the C-terminus.


Pssm-ID: 212569  Cd Length: 391  Bit Score: 92.89  E-value: 2.38e-19
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442626607 1828 HEQNGNLSEAACCHLhiaaLMCEylrlkggcTLSWSStafgkistniplDEQGLKLDAGAQ-DSQYTEQMLLEQLKlcad 1906
Cdd:cd11696    14 HLQAENYTEAAFTLL----LYAE--------LLSWSS------------DPLPADLHHPSQpEWQRKEALYLKILQ---- 65

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442626607 1907 FLDRAERFECLGELYKLILPMYERDRSYQDLAHCYEHLTQAYNKIVEvnrsGKRMLGRFYRVVFYGLMY--FEEDHaiEF 1984
Cdd:cd11696    66 YFDRGKCWEKGIPLCRELAELYESLYDYAKLSHILRMEASFYDNILT----QLRPEPEYFRVGFYGKGFplFLRNK--QF 139

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442626607 1985 VYKEPKLTSLSEISERLAKQYKEkfgadvVKMIMDSSPVKVDELDAKLAYIQVTHVIPF------FSKDELDQRLNEFEQ 2058
Cdd:cd11696   140 VYRGLDYERIGAFTQRLQSEFPQ------AHILTKNTPPDDAILQADGQYIQICNVKPVperrpvLQMVGVPDKVRSFYR 213

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442626607 2059 NHDVDTFMYETPFTKSGAAR-GSVEEQWKRKTVIKTQYSFPYVLKRIPVKSREIIELSPIEVAIDEMQSKVSELEEIIL- 2136
Cdd:cd11696   214 VNDVRKFQYDRPIHKGPIDKdNEFKSLWIERTTLVTEHSLPGILRWFEVVSREVEEIPPVENACETVENKNQELRSLISq 293

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442626607 2137 ----PPADVKKLQLRLQGSVAVTVNAGPLAYAHAFLDAKVVNNFSMD--RVGDLKDVFRDFIVVCQKALFLNERIISADQ 2210
Cdd:cd11696   294 yqadPTRNINPFSMRLQGVIDAAVNGGIAKYQEAFFTPEFILSHPEDaeHIARLRELILEQVQILEAGLALHGKLAPPEV 373

                         410
                  ....*....|....*...
gi 442626607 2211 KEYHHVLKENYEKLCQAL 2228
Cdd:cd11696   374 RPLHKRLVERFTQMKQSL 391
DHR2_DOCK3 cd11704
Dock Homology Region 2, a GEF domain, of Class B Dedicator of Cytokinesis 3; Dock3, also ...
 1928-2228 2.94e-15

Dock Homology Region 2, a GEF domain, of Class B Dedicator of Cytokinesis 3; Dock3, also called modifier of cell adhesion (MOCA), is an atypical guanine nucleotide exchange factor (GEF) that lacks the conventional Dbl homology (DH) domain. As a GEF, it activates small GTPases by exchanging bound GDP for free GTP. Dock3 is a specific GEF for Rac. It regulates N-cadherin dependent cell-cell adhesion, cell polarity, and neuronal morphology. It promotes axonal growth by stimulating actin polymerization and microtubule assembly. DOCK proteins are divided into four classes (A-D) based on sequence similarity and domain architecture; class B includes Dock3 and 4. All DOCKs contain two homology domains: the DHR-1 (Dock homology region-1), also called CZH1 (CED-5, Dock180, and MBC-zizimin homology 1), and DHR-2 (also called CZH2 or Docker). The DHR-1 domain binds phosphatidylinositol-3,4,5-triphosphate. This alignment model represents the DHR-2 domain of Dock3, which contains the catalytic GEF activity for Rac and/or Cdc42. Class B DOCKs also contain an SH3 domain at the N-terminal region and a PxxP motif at the C-terminus.


Pssm-ID: 212577  Cd Length: 392  Bit Score: 80.44  E-value: 2.94e-15
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442626607 1928 YERDRSYQDLAHCYEHLTQAYNKIVEvnrsGKRMLGRFYRVVFYGLMYfeedhaiEFVYKEPKLTSLSEISERLaKQYKE 2007
Cdd:cd11704    87 YESLYDYQSLSWIRKMEAAYYDNIME----QQRLEPEFFRVGFYGRKF-------PFFLRNKEYVCRGHDYERL-EAFQQ 154

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442626607 2008 KFGADVVKMIMDSSPVKVDE--LDAKLAYIQVTHVIPF------FSKDELDQRLNEFEQNHDVDTFMYETPFTKSGAAR- 2078
Cdd:cd11704   155 RMLSEFPQAIAMQHPNHPDDgiLQCDAQYLQIYAVTPIpdnmdvLQMDRVPDRIKSFYRVNNVRKFRYDRPFHKGPKDKe 234

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442626607 2079 GSVEEQWKRKTVIKTQYSFPYVLKRIPVKSREIIELSPIEVAIDEMQSKVSELEEIILP------PADVKKLQLRLQGSV 2152
Cdd:cd11704   235 NEFKSLWIERTTLTLTHSLPGISRWFEVERRELVEVSPLENAIQVVENKNQELRTLISQyqhkqlHGNINLLSMCLNGVI 314

                         250       260       270       280       290       300       310
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 442626607 2153 AVTVNAGPLAYAHAFLDAKVVNNFSMD--RVGDLKDVFRDFIVVCQKALFLNERIISADQKEYHHVLKENYEKLCQAL 2228
Cdd:cd11704   315 DAAVNGGIARYQEAFFDKDYISKHPGDaeKITQLKELMQEQVHVLGVGLAVHEKFVHPEMRPLHKKLIDQFQMMRSSL 392
DHR2_DOCK5 cd11708
Dock Homology Region 2, a GEF domain, of Class A Dedicator of Cytokinesis 5; Dock5 is an ...
 1892-2180 1.05e-13

Dock Homology Region 2, a GEF domain, of Class A Dedicator of Cytokinesis 5; Dock5 is an atypical guanine nucleotide exchange factor (GEF) that lacks the conventional Dbl homology (DH) domain. As a GEF, it activates small GTPases by exchanging bound GDP for free GTP. It functions upstream of Rac1 to regulate osteoclast function. DOCK proteins are divided into four classes (A-D) based on sequence similarity and domain architecture; class A includes Dock1, 2 and 5. All DOCKs contain two homology domains: the DHR-1 (Dock homology region-1), also called CZH1 (CED-5, Dock180, and MBC-zizimin homology 1), and DHR-2 (also called CZH2 or Docker). The DHR-1 domain binds phosphatidylinositol-3,4,5-triphosphate. This alignment model represents the DHR-2 domain of Dock5, which contains the catalytic GEF activity for Rac and/or Cdc42. Class A DOCKs, like Dock5, are specific GEFs for Rac and they contain an SH3 domain at the N-terminal region and a PxxP motif at the C-terminus.


Pssm-ID: 212581  Cd Length: 400  Bit Score: 75.75  E-value: 1.05e-13
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442626607 1892 YTEQMLLEQL-KLCADFLDRAERFECLGELYKLILPMYERDR-SYQDLAHCYEHLTQAYNKIVEvnrsGKRMLGRFYRVV 1969
Cdd:cd11708    54 YTQQELKERLyQEIISFFDKGKMWEKAIELSKELADMYENQVfDYEGLGNLLKKQAQFYENIMK----AMRPQPEYFAVG 129

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442626607 1970 FYGLMYFEEDHAIEFVYKEPKLTSLSEISERLAKQYkekfgADVVKMiMDSSPVKVDELDAKLAYIQVTHVIPFFS---- 2045
Cdd:cd11708   130 YYGQGFPSFLRNKIFIYRGKEYERLEDFSLKLLTQF-----PNAEKM-TSTSPPGDEIKSSTKQYVQCFTVKPVMNlpsh 203

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442626607 2046 -KDEL--DQRLNEFEQNhDVDTFMYETPFTKSGA-ARGSVEEQWKRKTVIKTQYSFPYVLKRIPVKSREIIELSPIEVAI 2121
Cdd:cd11708   204 yKDKPvpEQILNYYRAN-EVQQFQYSRPFRKGEKdPDNEFATMWIERTTFTTAYRFPGILKWFEVKQISTEEISPLENAI 282

                         250       260       270       280       290       300
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 442626607 2122 DEMQ---SKVSEL--EEIILPPADVKKLQLRLQGSVAVTVNAGPLAYAHAFLDAKVVNNFSMDR 2180
Cdd:cd11708   283 ETMEltnEKISNLvqQHAWDRSLPVHPLSMLLNGIVDPAVMGGFSNYEKAFFTEKYLQEHPEDQ 346
DOCK_C-D_N pfam11878
Dedicator of cytokinesis C/D, N terminal; This entry represents the N-terminal domain of the ...
 37-81 2.02e-13

Dedicator of cytokinesis C/D, N terminal; This entry represents the N-terminal domain of the DOCK-C subfamily (DOCK 6, 7, 8) and DOCK-D subfamily (DOCK 9, 10, 11). DOCK family members are evolutionarily conserved guanine nucleotide exchange factors (GEFs) for Rho-family GTPases, required during several cellular processes, such as cell motility and phagocytosis. DOCK proteins are categorized into four subfamilies based on their sequence homology: DOCK-A (DOCK1/180, 2, 5), DOCK-B subfamily (DOCK3, 4), DOCK-C subfamily (DOCK6, 7, 8), DOCK-D subfamily (DOCK9, 10, 11).


Pssm-ID: 463380  Cd Length: 112  Bit Score: 68.45  E-value: 2.02e-13
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*
gi 442626607    37 VVEPIDFEAFIAKNKTVIQNDPQRELLIYPTDDVSEIIMPRKQRT 81
Cdd:pfam11878    3 VVEPLDYEEFISQHLTQIENDPLRDLLLFPDDDIEVSVIPRECRT 47
DHR2_DOCK1 cd11707
Dock Homology Region 2, a GEF domain, of Class A Dedicator of Cytokinesis 1; Dock1, also ...
 1893-2187 2.28e-12

Dock Homology Region 2, a GEF domain, of Class A Dedicator of Cytokinesis 1; Dock1, also called Dock180, is an atypical guanine nucleotide exchange factor (GEF) that lacks the conventional Dbl homology (DH) domain. As a GEF, it activates small GTPases by exchanging bound GDP for free GTP. Dock1 interacts with the scaffold protein Elmo and the resulting complex functions upstream of Rac in many biological events including phagocytosis of apoptotic cells, cell migration and invasion. In the nervous system, it mediates attractive responses to netrin-1 and thus, plays a role in axon outgrowth and pathfinding. DOCK proteins are divided into four classes (A-D) based on sequence similarity and domain architecture; class A includes Dock1, 2 and 5. All DOCKs contain two homology domains: the DHR-1 (Dock homology region-1), also called CZH1 (CED-5, Dock180, and MBC-zizimin homology 1), and DHR-2 (also called CZH2 or Docker). The DHR-1 domain binds phosphatidylinositol-3,4,5-triphosphate. This alignment model represents the DHR-2 domain of Dock1, which contains the catalytic GEF activity for Rac and/or Cdc42. Class A DOCKs, like Dock1, are specific GEFs for Rac and they contain an SH3 domain at the N-terminal region and a PxxP motif at the C-terminus.


Pssm-ID: 212580  Cd Length: 400  Bit Score: 71.22  E-value: 2.28e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442626607 1893 TEQMLLEQL-KLCADFLDRAERFECLGELYKLILPMYERDR-SYQDLAHCYEHLTQAYNKIVEVNRSGKRmlgrFYRVVF 1970
Cdd:cd11707    55 TQGQLKDQLyQEIIHYFDKGKMWEEAIALGKELAEQYENEMfDYEQLSELLKKQAQFYENIVKVIRPKPD----YFAVGY 130

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442626607 1971 YGLMYFEEDHAIEFVYKEPKLTSLSEISERLAKQYKEkfgADVVKMimdSSPVKVDELDAKLAYIQVTHVIP-------F 2043
Cdd:cd11707   131 YGQGFPTFLRNKMFIYRGKEYERREDFEARLLTQFPN---AEKMKT---TSPPGDDIKNSSGQYIQCFTVKPllelppkF 204

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442626607 2044 FSKdELDQRLNEFEQNHDVDTFMYETPFTKSGA-ARGSVEEQWKRKTVIKTQYSFPYVLKRIPVKSREIIELSPIEVAID 2122
Cdd:cd11707   205 QNK-PVSEQIVSFYRVNEVQRFQYSRPVRKGEKdPDNEFANMWIERTTYVTAYKLPGILRWFEVKSVFMVEISPLENAIE 283

                         250       260       270       280       290       300       310
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 442626607 2123 EMQ---SKVSELEEIIL--PPADVKKLQLRLQGSVAVTVNAGPLAYAHAFLDAKVVNNFSMD--RVGDLKDV 2187
Cdd:cd11707   284 TMQltnEKINNMVQQHLndPNLPINPLSMLLNGIVDPAVMGGFANYEKAFFTEKYMQEHPEDheKIEKLKDL 355
DHR2_DOCK4 cd11705
Dock Homology Region 2, a GEF domain, of Class B Dedicator of Cytokinesis 4; Dock4 is an ...
 1908-2221 3.20e-12

Dock Homology Region 2, a GEF domain, of Class B Dedicator of Cytokinesis 4; Dock4 is an atypical guanine nucleotide exchange factor (GEF) that lacks the conventional Dbl homology (DH) domain. As a GEF, it activates small GTPases by exchanging bound GDP for free GTP. It plays a role in regulating dendritic growth and branching in hippocampal neurons, where it is highly expressed. It may also regulate spine morphology and synapse formation. Dock4 activates the Ras family GTPase Rap1, probably indirectly through interaction with Rap regulatory proteins. DOCK proteins are divided into four classes (A-D) based on sequence similarity and domain architecture; class B includes Dock3 and 4. All DOCKs contain two homology domains: the DHR-1 (Dock homology region-1), also called CZH1 (CED-5, Dock180, and MBC-zizimin homology 1), and DHR-2 (also called CZH2 or Docker). The DHR-1 domain binds phosphatidylinositol-3,4,5-triphosphate. This alignment model represents the DHR-2 domain of Dock4, which contains the catalytic GEF activity for Rac and/or Cdc42. Class B DOCKs also contain an SH3 domain at the N-terminal region and a PxxP motif at the C-terminus.


Pssm-ID: 212578  Cd Length: 391  Bit Score: 70.83  E-value: 3.20e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442626607 1908 LDRAERFECLGELYKLILPMYERDRSYQDLAHCYEHLTQAYNKIVEvnrsGKRMLGRFYRVVFYGLMYFEEDHAIEFVYK 1987
Cdd:cd11705    67 FDRGKCWENGIILCRKLAEQYESYYDYRNLSKMRMMEASLYDKIMD----QQRLEPEFFRVGFYGKKFPFFLRNKEFVCR 142

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442626607 1988 EPKLTSLSEISERLAKQYKEkfgadVVKMIMDSSPvkvDE--LDAKLAYIQVTHVIPFFSKDELDQR------LNEFEQN 2059
Cdd:cd11705   143 GHDYERLEAFQQRMLNEFPH-----AIAMQHANQP---DEtiFQAEAQYLQIYAVTPIPESQEVLQRdgvpdnIKSFYKV 214

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442626607 2060 HDVDTFMYETPFTKSGAAR-GSVEEQWKRKTVIKTQYSFPYVLKRIPVKSREIIELSPIEVAIDEMQSKVSELEEIIL-- 2136
Cdd:cd11705   215 NHIWRFRYDRPFHKGTKDKeNEFKSLWVERTTLTLVQSLPGISRWFEVEKREVVEMSPLENAIEVLENKNQQLRTLISqc 294

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442626607 2137 ---PPADVKKLQLRLQGSVAVTVNAGPLAYAHAFLDAKVVNNFSMD--RVGDLKDVFRDFIVVCQKALFLNERIISADQK 2211
Cdd:cd11705   295 qtrQMQNINPLTMCLNGVIDAAVNGGVSRYQEAFFVKEYILNHPEDgdKITRLRELMLEQAQILEFGLAVHEKFVPQDMR 374

                         330
                  ....*....|
gi 442626607 2212 EYHHVLKENY 2221
Cdd:cd11705   375 PLHKKLVDQF 384
PH smart00233
Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The ...
 283-393 3.78e-11

Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The domain family possesses multiple functions including the abilities to bind inositol phosphates, and various proteins. PH domains have been found to possess inserted domains (such as in PLC gamma, syntrophins) and to be inserted within other domains. Mutations in Brutons tyrosine kinase (Btk) within its PH domain cause X-linked agammaglobulinaemia (XLA) in patients. Point mutations cluster into the positively charged end of the molecule around the predicted binding site for phosphatidylinositol lipids.


Pssm-ID: 214574 [Multi-domain]  Cd Length: 102  Bit Score: 61.80  E-value: 3.78e-11
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442626607    283 ITKQGYLLKGPDSasdrmfaniGNKSFKRRYCYLRqeiDGT-YILELHKDEKQGEAKATIVMDFCT---DVVQNPKRGRF 358
Cdd:smart00233    1 VIKEGWLYKKSGG---------GKKSWKKRYFVLF---NSTlLYYKSKKDKKSYKPKGSIDLSGCTvreAPDPDSSKKPH 68

                            90       100       110
                    ....*....|....*....|....*....|....*
gi 442626607    359 CFELRMTTGhKSFTLAAENEQDFKDWLSKISSVLA 393
Cdd:smart00233   69 CFEIKTSDR-KTLLLQAESEEEREKWVEALRKAIA 102
DHR2_DOCK2 cd11706
Dock Homology Region 2, a GEF domain, of Class A Dedicator of Cytokinesis 2; Dock2 is a ...
 1888-2224 4.28e-10

Dock Homology Region 2, a GEF domain, of Class A Dedicator of Cytokinesis 2; Dock2 is a hematopoietic cell-specific, class A DOCK and is an atypical guanine nucleotide exchange factor (GEF) that lacks the conventional Dbl homology (DH) domain. As a GEF, it activates small GTPases by exchanging bound GDP for free GTP. It plays an important role in lymphocyte migration and activation, T-cell differentiation, neutrophil chemotaxis, and type I interferon induction. DOCK proteins are divided into four classes (A-D) based on sequence similarity and domain architecture; class A includes Dock1, 2 and 5. All DOCKs contain two homology domains: the DHR-1 (Dock homology region-1), also called CZH1 (CED-5, Dock180, and MBC-zizimin homology 1), and DHR-2 (also called CZH2 or Docker). The DHR-1 domain binds phosphatidylinositol-3,4,5-triphosphate. This alignment model represents the DHR-2 domain of Dock2, which contains the catalytic GEF activity for Rac and/or Cdc42. Class A DOCKs, like Dock2, are specific GEFs for Rac and they contain an SH3 domain at the N-terminal region and a PxxP motif at the C-terminus.


Pssm-ID: 212579  Cd Length: 421  Bit Score: 64.24  E-value: 4.28e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442626607 1888 QDSQYTEQMLLEQL-KLCADFLDRAERFECLGELYKLILPMYERD-RSYQDLAHCYEHLTQAYNKIVEVNRSGKRmlgrF 1965
Cdd:cd11706    68 QQHPQTQRQLKETLyETIIGYFDKGKMWEEAISLCKELAEQYEMEiFDYELLSQNLIQQAKFYESIMKILRPKPD----Y 143

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442626607 1966 YRVVFYGLMYFEEDHAIEFVYKEPKLTSLSEISERLAKQYkekfgADVVKMIMDSSPVKvDELDAKLAYIQVTHVIP--- 2042
Cdd:cd11706   144 FAVGYYGQGFPSFLRNKVFIYRGKEYERREDFQMQLMSQF-----PNAEKLNTTSAPGD-DIKNSPGQYIQCFTVQPvle 217

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442626607 2043 ----FFSKDELDQRLNEFEQNHdVDTFMYETPFTKsgaarGSVEEQ------WKRKTVIKTQYSFPYVLKRIPVKSREII 2112
Cdd:cd11706   218 ehprLKNKPVPDQIINFYKSNY-VQRFHYSRPVRK-----GPVDPEnefasmWIERTTFVTAYKLPGILRWFEVTHMSQT 291

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442626607 2113 ELSPIEVAIDEMQSKVSELEEII--------LPpadVKKLQLRLQGSVAVTVNAGPLAYAHAFLDAKVVNNFSMDR--VG 2182
Cdd:cd11706   292 TISPLENAIETMSTTNEKILMMInqyqsdesLP---INPLSMLLNGIVDPAVMGGFAKYEKAFFTEEYVRDHPEDQdkLT 368

                         330       340       350       360
                  ....*....|....*....|....*....|....*....|..
gi 442626607 2183 DLKDVFRDFIVVCQKALFLNERIISADQKEYHHVLKENYEKL 2224
Cdd:cd11706   369 RLKDLIAWQIPLLGAGIKIHGKRVTDDLRPFHERMEECFKQL 410
PH cd00821
Pleckstrin homology (PH) domain; PH domains have diverse functions, but in general are ...
 285-388 9.27e-10

Pleckstrin homology (PH) domain; PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 275388 [Multi-domain]  Cd Length: 92  Bit Score: 57.55  E-value: 9.27e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442626607  285 KQGYLLKgpdsasdrmFANIGNKSFKRRYCYLRQEIdgtyiLELHKDEKQGEAKATIVMD---FCTDVVQNPKRGRFCFE 361
Cdd:cd00821     1 KEGYLLK---------RGGGGLKSWKKRWFVLFEGV-----LLYYKSKKDSSYKPKGSIPlsgILEVEEVSPKERPHCFE 66

                          90       100
                  ....*....|....*....|....*..
gi 442626607  362 LRmTTGHKSFTLAAENEQDFKDWLSKI 388
Cdd:cd00821    67 LV-TPDGRTYYLQADSEEERQEWLKAL 92
PH pfam00169
PH domain; PH stands for pleckstrin homology.
 283-393 2.37e-09

PH domain; PH stands for pleckstrin homology.


Pssm-ID: 459697 [Multi-domain]  Cd Length: 105  Bit Score: 56.80  E-value: 2.37e-09
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442626607   283 ITKQGYLLKgpdsasdrmFANIGNKSFKRRYCYLRQeiDGTYILELHKDEKQGEAKATIVMDFCTDV---VQNPKRGRFC 359
Cdd:pfam00169    1 VVKEGWLLK---------KGGGKKKSWKKRYFVLFD--GSLLYYKDDKSGKSKEPKGSISLSGCEVVevvASDSPKRKFC 69

                           90       100       110
                   ....*....|....*....|....*....|....*.
gi 442626607   360 FELRMT--TGHKSFTLAAENEQDFKDWLSKISSVLA 393
Cdd:pfam00169   70 FELRTGerTGKRTYLLQAESEEERKDWIKAIQSAIR 105
PH_ACAP cd13250
ArfGAP with coiled-coil, ankyrin repeat and PH domains Pleckstrin homology (PH) domain; ACAP ...
 285-393 9.48e-09

ArfGAP with coiled-coil, ankyrin repeat and PH domains Pleckstrin homology (PH) domain; ACAP (also called centaurin beta) functions both as a Rab35 effector and as an Arf6-GTPase-activating protein (GAP) by which it controls actin remodeling and membrane trafficking. ACAP contain an NH2-terminal bin/amphiphysin/Rvs (BAR) domain, a phospholipid-binding domain, a PH domain, a GAP domain, and four ankyrin repeats. The AZAPs constitute a family of Arf GAPs that are characterized by an NH2-terminal pleckstrin homology (PH) domain and a central Arf GAP domain followed by two or more ankyrin repeats. On the basis of sequence and domain organization, the AZAP family is further subdivided into four subfamilies: 1) the ACAPs contain an NH2-terminal bin/amphiphysin/Rvs (BAR) domain (a phospholipid-binding domain that is thought to sense membrane curvature), a single PH domain followed by the GAP domain, and four ankyrin repeats; 2) the ASAPs also contain an NH2-terminal BAR domain, the tandem PH domain/GAP domain, three ankyrin repeats, two proline-rich regions, and a COOH-terminal Src homology 3 domain; 3) the AGAPs contain an NH2-terminal GTPase-like domain (GLD), a split PH domain, and the GAP domain followed by four ankyrin repeats; and 4) the ARAPs contain both an Arf GAP domain and a Rho GAP domain, as well as an NH2-terminal sterile-a motif (SAM), a proline-rich region, a GTPase-binding domain, and five PH domains. PMID 18003747 and 19055940 Centaurin can bind to phosphatidlyinositol (3,4,5)P3. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270070  Cd Length: 98  Bit Score: 54.53  E-value: 9.48e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442626607  285 KQGYLLKGpdsASDRMfanignKSFKRRYCylrqEIDGTYILELHKDEKQGEAKATIVMDFCT-DVVQNPKRgRFCFELr 363
Cdd:cd13250     1 KEGYLFKR---SSNAF------KTWKRRWF----SLQNGQLYYQKRDKKDEPTVMVEDLRLCTvKPTEDSDR-RFCFEV- 65

                          90       100       110
                  ....*....|....*....|....*....|
gi 442626607  364 mTTGHKSFTLAAENEQDFKDWLSKISSVLA 393
Cdd:cd13250    66 -ISPTKSYMLQAESEEDRQAWIQAIQSAIA 94
C2_Dock-B cd08695
C2 domains found in Dedicator Of CytoKinesis (Dock) class B proteins; Dock-B is one of 4 ...
 813-918 1.42e-08

C2 domains found in Dedicator Of CytoKinesis (Dock) class B proteins; Dock-B is one of 4 classes of Dock family proteins. The members here include: Dock3/MOCA (modifier of cell adhesion) and Dock4. Most of these members have been shown to be GEFs specific for Rac, although Dock4 has also been shown to interact indirectly with the Ras family GTPase Rap1, probably through Rap regulatory proteins. In addition to the C2 domain (AKA Dock homology region (DHR)-1, CED-5, Dock180, MBC-zizimin homology (CZH) 1) and the DHR-2 (AKA CZH2, or Docker), which all Dock180-related proteins have, Dock-B members contain a SH3 domain upstream of the C2 domain and a proline-rich region downstream. DHR-2 has the catalytic activity for Rac and/or Cdc42, but is structurally unrelated to the DH domain. The C2/DHR-1 domains of Dock180 and Dock4 have been shown to bind phosphatidylinositol-3, 4, 5-triphosphate (PtdIns(3,4,5)P3). The C2 domain was first identified in PKC. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.


Pssm-ID: 176077  Cd Length: 189  Bit Score: 56.62  E-value: 1.42e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442626607  813 SRARNITVVVELRDGDGEYSKplKCIYGRPGQDLlVSQIACPVLHHNVTPTWYEEIKLRLPLGLFPEHHLLFSFYHVScn 892
Cdd:cd08695    20 STAKNIEVTMVVLDADGQVLK--DCISLGSGEPP-CSEYRSFVLYHNNSPRWNETIKLPIPIDKFRGSHLRFEFRHCS-- 94

                          90       100
                  ....*....|....*....|....*.
gi 442626607  893 lSKKRDANAAFetpiGYAWLPLLQKN 918
Cdd:cd08695    95 -TKDKGEKKLF----GFSFVPLMRED 115
C2_Dock-A cd08694
C2 domains found in Dedicator Of CytoKinesis (Dock) class A proteins; Dock-A is one of 4 ...
 795-918 1.46e-08

C2 domains found in Dedicator Of CytoKinesis (Dock) class A proteins; Dock-A is one of 4 classes of Dock family proteins. The members here include: Dock180/Dock1, Dock2, and Dock5. Most of these members have been shown to be GEFs specific for Rac. Dock5 has not been well characterized to date, but most likely also is a GEF specific for Rac. In addition to the C2 domain (AKA Dock homology region (DHR)-1, CED-5, Dock180, MBC-zizimin homology (CZH) 1) and the DHR-2 (AKA CZH2, or Docker), which all Dock180-related proteins have, Dock-A members contain a proline-rich region and a SH3 domain upstream of the C2 domain. DHR-2 has the catalytic activity for Rac and/or Cdc42, but is structurally unrelated to the DH domain. The C2/DHR-1 domains of Dock180 and Dock4 have been shown to bind phosphatidylinositol-3, 4, 5-triphosphate (PtdIns(3,4,5)P3). The C2 domain was first identified in PKC. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.


Pssm-ID: 176076  Cd Length: 196  Bit Score: 57.03  E-value: 1.46e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442626607  795 NHLYVYPLSLQFDS-QKlfSRARNITVVVELRDGDGeysKPLKCIYGRPGQDLLVSQIACPVLHHNVTPTWYEEIKLRLP 873
Cdd:cd08694     3 NDLYLTLVQGDFDKgSK--TSDKNVEVTVSVCNEDG---KIIPGVISLGAGEEPIDEYKSVIYYQVDKPKWFETFKVAIP 77

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*
gi 442626607  874 LGLFPEHHLLFSFYHVSCNLSKKRDanaafETPIGYAWLPLLQKN 918
Cdd:cd08694    78 IEDFKSSHLRFTFKHRSSNEAKDKS-----EKPFALSFVKLMQEN 117
PH_Gab2_2 cd13384
Grb2-associated binding protein family pleckstrin homology (PH) domain; The Gab subfamily ...
 281-391 2.35e-08

Grb2-associated binding protein family pleckstrin homology (PH) domain; The Gab subfamily includes several Gab proteins, Drosophila DOS and C. elegans SOC-1. They are scaffolding adaptor proteins, which possess N-terminal PH domains and a C-terminus with proline-rich regions and multiple phosphorylation sites. Following activation of growth factor receptors, Gab proteins are tyrosine phosphorylated and activate PI3K, which generates 3-phosphoinositide lipids. By binding to these lipids via the PH domain, Gab proteins remain in proximity to the receptor, leading to further signaling. While not all Gab proteins depend on the PH domain for recruitment, it is required for Gab activity. Members here include insect, nematodes, and crustacean Gab2s. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 241535  Cd Length: 115  Bit Score: 53.99  E-value: 2.35e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442626607  281 DTITKQGYLLKGPDSAsdrmfaNIGNKSFKRRYCYLRQ-EIDGTYILELHKDEKQGEAKATIVMDFCTDV-----VQNPK 354
Cdd:cd13384     1 TEVVYEGWLTKSPPEK------RIWRAKWRRRYFVLRQsEIPGQYFLEYYTDRTCRKLKGSIDLDQCEQVdagltFETKN 74

                          90       100       110
                  ....*....|....*....|....*....|....*..
gi 442626607  355 RGRFCFELRMTTGHKSFTLAAENEQDFKDWLSKISSV 391
Cdd:cd13384    75 KLKDQHIFDIRTPKRTYYLVADTEDEMNKWVNCICTV 111
PH_Ses cd13288
Sesquipedalian family Pleckstrin homology (PH) domain; The sesquipedalian family has 2 ...
 285-389 7.94e-07

Sesquipedalian family Pleckstrin homology (PH) domain; The sesquipedalian family has 2 mammalian members: Ses1 and Ses2, which are also callled 7 kDa inositol polyphosphate phosphatase-interacting protein 1 and 2. They play a role in endocytic trafficking and are required for receptor recycling from endosomes, both to the trans-Golgi network and the plasma membrane. Members of this family form homodimers and heterodimers. Sesquipedalian interacts with inositol polyphosphate 5-phosphatase OCRL-1 (INPP5F) also known as Lowe oculocerebrorenal syndrome protein, a phosphatase enzyme that is involved in actin polymerization and is found in the trans-Golgi network and INPP5B. Sesquipedalian contains a single PH domain. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270105 [Multi-domain]  Cd Length: 120  Bit Score: 49.93  E-value: 7.94e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442626607  285 KQGYLLKGPDSasdrmfanigNKSFKRRYCYLRQEIdgtyileLHKDEKQG--EAKATIVMDFCTdVVQNPKRGRFCFEL 362
Cdd:cd13288    10 KEGYLWKKGER----------NTSYQKRWFVLKGNL-------LFYFEKKGdrEPLGVIVLEGCT-VELAEDAEPYAFAI 71

                          90       100
                  ....*....|....*....|....*...
gi 442626607  363 RMT-TGHKSFTLAAENEQDFKDWLSKIS 389
Cdd:cd13288    72 RFDgPGARSYVLAAENQEDMESWMKALS 99
PH_Gab-like cd13324
Grb2-associated binding protein family Pleckstrin homology (PH) domain; Gab proteins are ...
 286-391 5.06e-06

Grb2-associated binding protein family Pleckstrin homology (PH) domain; Gab proteins are scaffolding adaptor proteins, which possess N-terminal PH domains and a C-terminus with proline-rich regions and multiple phosphorylation sites. Following activation of growth factor receptors, Gab proteins are tyrosine phosphorylated and activate PI3K, which generates 3-phosphoinositide lipids. By binding to these lipids via the PH domain, Gab proteins remain in proximity to the receptor, leading to further signaling. While not all Gab proteins depend on the PH domain for recruitment, it is required for Gab activity. There are 3 families: Gab1, Gab2, and Gab3. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270133  Cd Length: 112  Bit Score: 47.41  E-value: 5.06e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442626607  286 QGYLLKGPDSASDRMFAnignksFKRRYCYLR--QEIDGTYILELHKDEKQGEAKATIVMDFCTDVVQ----NPKRGRFC 359
Cdd:cd13324     4 EGWLTKSPPEKKIWRAA------WRRRWFVLRsgRLSGGQDVLEYYTDDHCKKLKGIIDLDQCEQVDAgltfEKKKFKNQ 77

                          90       100       110
                  ....*....|....*....|....*....|..
gi 442626607  360 FELRMTTGHKSFTLAAENEQDFKDWLSKISSV 391
Cdd:cd13324    78 FIFDIRTPKRTYYLVAETEEEMNKWVRCICQV 109
PH_Cla4_Ste20 cd13279
Pleckstrin homology (PH) domain; Budding yeast contain two main p21-activated kinases (PAKs), ...
 305-388 6.72e-06

Pleckstrin homology (PH) domain; Budding yeast contain two main p21-activated kinases (PAKs), Cla4 and Ste20. The yeast Ste20 protein kinase is involved in pheromone response, though the function of Ste20 mammalian homologs is unknown. Cla4 is involved in budding and cytokinesis and interacts with Cdc42, a GTPase required for polarized cell growth as is Pak. Cla4 and Ste20 kinases share a function in localizing cell growth with respect to the septin ring. They both contain a PH domain, a Cdc42/Rac interactive binding (CRIB) domain, and a C-terminal Protein Kinase catalytic (PKc) domain. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270097  Cd Length: 92  Bit Score: 46.47  E-value: 6.72e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442626607  305 GNKSF--KRRYCYLRQEIdgtyiLELHKDEKQGEAKATIVMDFCTDVVQNPKRgRFCFELRMTTGHKSFTLAAENEQDFK 382
Cdd:cd13279    13 GLLSFrwSKRYLVLREQS-----LDFYKNESSSSASLSIPLKDISNVSRTDLK-PYCFEIVRKSSTKSIYISVKSDDELY 86


                  ....*.
gi 442626607  383 DWLSKI 388
Cdd:cd13279    87 DWMDDI 92
PH1_ARAP cd13253
ArfGAP with RhoGAP domain, ankyrin repeat and PH domain Pleckstrin homology (PH) domain, ...
 284-394 1.28e-05

ArfGAP with RhoGAP domain, ankyrin repeat and PH domain Pleckstrin homology (PH) domain, repeat 1; ARAP proteins (also called centaurin delta) are phosphatidylinositol 3,4,5-trisphosphate-dependent GTPase-activating proteins that modulate actin cytoskeleton remodeling by regulating ARF and RHO family members. They bind phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P3) and phosphatidylinositol 3,4-bisphosphate (PtdIns(3,4,5)P2) binding. There are 3 mammalian ARAP proteins: ARAP1, ARAP2, and ARAP3. All ARAP proteins contain a N-terminal SAM (sterile alpha motif) domain, 5 PH domains, an ArfGAP domain, 2 ankyrin domain, A RhoGap domain, and a Ras-associating domain. This hierarchy contains the first PH domain in ARAP. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270073  Cd Length: 94  Bit Score: 45.84  E-value: 1.28e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442626607  284 TKQGYLLKGPDSASDRMFanignksfKRRYCYLrqeiDGTYiLELHKDEKQGEAKATIVMdFCTDVVQNPKRGRFcfelR 363
Cdd:cd13253     1 IKSGYLDKQGGQGNNKGF--------QKRWVVF----DGLS-LRYFDSEKDAYSKRIIPL-SAISTVRAVGDNKF----E 62

                          90       100       110
                  ....*....|....*....|....*....|.
gi 442626607  364 MTTGHKSFTLAAENEQDFKDWLSKISSVLAQ 394
Cdd:cd13253    63 LVTTNRTFVFRAESDDERNLWCSTLQAAISE 93
PH_IRS cd01257
Insulin receptor substrate (IRS) pleckstrin homology (PH) domain; Insulin receptor substrate ...
 283-396 7.33e-05

Insulin receptor substrate (IRS) pleckstrin homology (PH) domain; Insulin receptor substrate (IRS) molecules are mediators in insulin signaling and play a role in maintaining basic cellular functions such as growth and metabolism. They act as docking proteins between the insulin receptor and a complex network of intracellular signaling molecules containing Src homology 2 (SH2) domains. Four members (IRS-1, IRS-2, IRS-3, IRS-4) of this family have been identified that differ as to tissue distribution, subcellular localization, developmental expression, binding to the insulin receptor, and interaction with SH2 domain-containing proteins. IRS molecules have an N-terminal PH domain, followed by an IRS-like PTB domain which has a PH-like fold. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.cytoskeletal associated molecules, and in lipid associated enzymes.


Pssm-ID: 269959  Cd Length: 106  Bit Score: 43.82  E-value: 7.33e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442626607  283 ITKQGYLLKgpdsasdrmfanigNKSFKRRYCYLRQEIDGTYI-LELHKDEKQ----GEAKATIVMDFCTDVvqNPK--- 354
Cdd:cd01257     3 VRKSGYLKK--------------LKTMRKRYFVLRAESHGGPArLEYYENEKKfrrnAEPKRVIPLSSCFNI--NKRada 66

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|..
gi 442626607  355 RGRFCFELrmTTGHKSFTLAAENEQDFKDWLSKISSVLAQNR 396
Cdd:cd01257    67 KHKHLIAL--YTKDECFGLVAESEEEQDEWYQALLELQRPAR 106
PH_ASAP cd13251
ArfGAP with SH3 domain, ankyrin repeat and PH domain Pleckstrin homology (PH) domain; ASAPs ...
 284-402 4.90e-04

ArfGAP with SH3 domain, ankyrin repeat and PH domain Pleckstrin homology (PH) domain; ASAPs (ASAP1, ASAP2, and ASAP3) function as an Arf-specific GAPs, participates in rhodopsin trafficking, is associated with tumor cell metastasis, modulates phagocytosis, promotes cell proliferation, facilitates vesicle budding, Golgi exocytosis, and regulates vesicle coat assembly via a Bin/Amphiphysin/Rvs domain. ASAPs contain an NH2-terminal BAR domain, a tandem PH domain/GAP domain, three ankyrin repeats, two proline-rich regions, and a COOH-terminal Src homology 3 (SH3) domain. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270071  Cd Length: 108  Bit Score: 41.58  E-value: 4.90e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442626607  284 TKQGYLLKGPDSASDRMFanignksfKRRYCylrqEIDGTYILELHKDEkqgeAKATIVMDFCTDVVQNPKRGRFCFELr 363
Cdd:cd13251    11 EKSGYLLKKSEGKIRKVW--------QKRRC----SIKDGFLTISHADE----NKPPAKLNLLTCQVKLVPEDKKCFDL- 73

                          90       100       110
                  ....*....|....*....|....*....|....*....
gi 442626607  364 mTTGHKSFTLAAENEQDFKDWLskisSVLAQNRAQEEKR 402
Cdd:cd13251    74 -ISHNRTYHFQAEDENDANAWM----SVLKNSKEQALNK 107
PH_KIFIA_KIFIB cd01233
KIFIA and KIFIB protein pleckstrin homology (PH) domain; The kinesin-3 family motors KIFIA ...
 281-393 5.74e-04

KIFIA and KIFIB protein pleckstrin homology (PH) domain; The kinesin-3 family motors KIFIA (Caenorhabditis elegans homolog unc-104) and KIFIB transport synaptic vesicle precursors that contain synaptic vesicle proteins, such as synaptophysin, synaptotagmin and the small GTPase RAB3A, but they do not transport organelles that contain plasma membrane proteins. They have a N-terminal motor domain, followed by a coiled-coil domain, and a C-terminal PH domain. KIF1A adopts a monomeric form in vitro, but acts as a processive dimer in vivo. KIF1B has alternatively spliced isoforms distinguished by the presence or absence of insertion sequences in the conserved amino-terminal region of the protein; this results in their different motor activities. KIF1A and KIF1B bind to RAB3 proteins through the adaptor protein mitogen-activated protein kinase (MAPK) -activating death domain (MADD; also calledDENN), which was first identified as a RAB3 guanine nucleotide exchange factor (GEF). PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 269939  Cd Length: 103  Bit Score: 41.42  E-value: 5.74e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442626607  281 DTITKQGYLlkgpdsasdrMFANIGNKSFKRRYCYLRQeidgTYILeLHKDEKQGEAK-----ATIVMDFCTDVVQNPKR 355
Cdd:cd01233     4 PVVSKRGYL----------LFLEDATDGWVRRWVVLRR----PYLH-IYSSEKDGDERgvinlSTARVEYSPDQEALLGR 68

                          90       100       110
                  ....*....|....*....|....*....|....*...
gi 442626607  356 gRFCFELrmTTGHKSFTLAAENEQDFKDWLSKISSVLA 393
Cdd:cd01233    69 -PNVFAV--YTPTNSYLLQARSEKEMQDWLYAIDPLLA 103
PH_RhoGap24 cd13379
Rho GTPase activating protein 24 Pleckstrin homology (PH) domain; RhoGap24 (also called ...
 326-392 1.13e-03

Rho GTPase activating protein 24 Pleckstrin homology (PH) domain; RhoGap24 (also called ARHGAP24, p73RhoGAp, and Filamin-A-associated RhoGAP) like other RhoGAPs are involved in cell polarity, cell morphology and cytoskeletal organization. They act as GTPase activators for the Rac-type GTPases by converting them to an inactive GDP-bound state and control actin remodeling by inactivating Rac downstream of Rho leading to suppress leading edge protrusion and promotes cell retraction to achieve cellular polarity and are able to suppress RAC1 and CDC42 activity in vitro. Overexpression of these proteins induces cell rounding with partial or complete disruption of actin stress fibers and formation of membrane ruffles, lamellipodia, and filopodia. Members here contain an N-terminal PH domain followed by a RhoGAP domain and either a BAR or TATA Binding Protein (TBP) Associated Factor 4 (TAF4) domain. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 241530  Cd Length: 114  Bit Score: 40.72  E-value: 1.13e-03
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 442626607  326 LELHKDEKQGEAKATIVMDfCTDVVQNP----KRGRFCFEL-------RMTTGHKSFTLAAENEQDFKDWLSKISSVL 392
Cdd:cd13379    31 LYYFKDEDETKPLGTIFLP-GNRVTEHPcneeEPGKFLFEVvpggdreRMTANHETYLLMASTQNDMEDWVKSIRRVI 107
PH_SIP3 cd13280
Snf1p-interacting protein 3 Pleckstrin homology (PH) domain; SIP3 interacts with SNF1 protein ...
 311-386 1.64e-03

Snf1p-interacting protein 3 Pleckstrin homology (PH) domain; SIP3 interacts with SNF1 protein kinase and activates transcription when anchored to DNA. It may function in the SNF1 pathway. SIP3 contain an N-terminal Bin/Amphiphysin/Rvs (BAR) domain followed by a PH domain. BAR domains form dimers that bind to membranes, induce membrane bending and curvature, and may also be involved in protein-protein interactions. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270098  Cd Length: 105  Bit Score: 39.93  E-value: 1.64e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442626607  311 RRYCYLRQEIDGTYILELHKD-----EKQGeakatiVmdFCTDVVQNPKRGR-FCFELRmtTGHK-SFTLAAENEQDFKD 383
Cdd:cd13280    22 RRWCFVKNGVFGMLSLSPSKTyveetDKFG------V--LLCSVRYAPEEDRrFCFEVK--IFKDiSIILQAETLKELKS 91


                  ...
gi 442626607  384 WLS 386
Cdd:cd13280    92 WLT 94
PH_SWAP-70 cd13273
Switch-associated protein-70 Pleckstrin homology (PH) domain; SWAP-70 (also called ...
 283-399 5.04e-03

Switch-associated protein-70 Pleckstrin homology (PH) domain; SWAP-70 (also called Differentially expressed in FDCP 6/DEF-6 or IRF4-binding protein) functions in cellular signal transduction pathways (in conjunction with Rac), regulates cell motility through actin rearrangement, and contributes to the transformation and invasion activity of mouse embryo fibroblasts. Metazoan SWAP-70 is found in B lymphocytes, mast cells, and in a variety of organs. Metazoan SWAP-70 contains an N-terminal EF-hand motif, a centrally located PH domain, and a C-terminal coiled-coil domain. The PH domain of Metazoan SWAP-70 contains a phosphoinositide-binding site and a nuclear localization signal (NLS), which localize SWAP-70 to the plasma membrane and nucleus, respectively. The NLS is a sequence of four Lys residues located at the N-terminus of the C-terminal a-helix; this is a unique characteristic of the Metazoan SWAP-70 PH domain. The SWAP-70 PH domain binds PtdIns(3,4,5)P3 and PtdIns(4,5)P2 embedded in lipid bilayer vesicles. There are additional plant SWAP70 proteins, but these are not included in this hierarchy. Rice SWAP70 (OsSWAP70) exhibits GEF activity toward the its Rho GTPase, OsRac1, and regulates chitin-induced production of reactive oxygen species and defense gene expression in rice. Arabidopsis SWAP70 (AtSWAP70) plays a role in both PAMP- and effector-triggered immunity. Plant SWAP70 contains both DH and PH domains, but their arrangement is the reverse of that in typical DH-PH-type Rho GEFs, wherein the DH domain is flanked by a C-terminal PH domain. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270092  Cd Length: 110  Bit Score: 38.82  E-value: 5.04e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442626607  283 ITKQGYLLKgpdsASDRMfanignKSFKRRYCYLRqeidgTYILELHKDEKQGEAKATIVMD--FCTDVVQNPKRGRFCF 360
Cdd:cd13273     8 VIKKGYLWK----KGHLL------PTWTERWFVLK-----PNSLSYYKSEDLKEKKGEIALDsnCCVESLPDREGKKCRF 72

                          90       100       110
                  ....*....|....*....|....*....|....*....
gi 442626607  361 ELrmTTGHKSFTLAAENEQDFKDWLSKISSVLAQNRAQE 399
Cdd:cd13273    73 LV--KTPDKTYELSASDHKTRQEWIAAIQTAIRLSQEGK 109
PH_Bud4 cd13278
Bud4 Pleckstrin homology (PH) domain; Bud4 is an anillin-like yeast protein involved in the ...
 282-396 9.49e-03

Bud4 Pleckstrin homology (PH) domain; Bud4 is an anillin-like yeast protein involved in the formation and the disassembly of the double ring structure formed by the septins during cytokinesis. Bud4 acts with Bud3 and and in parallel with septin phosphorylation by the p21-activated kinase Cla4 and the septin-dependent kinase Gin4. Bud4 is regulated by the cyclin-dependent protein kinase Cdk1, the master regulator of cell cycle progression. Bud4 contains an anillin-like domain followed by a PH domain. In addition there are two consensus Cdk phosphorylation sites: one at the N-terminus and one right before the C-terminal PH domain. Anillins also have C-terminal PH domains. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 241432  Cd Length: 139  Bit Score: 38.73  E-value: 9.49e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442626607  282 TITKQGYLL-KGPDSasdrmfanignKSFKRRYCYLrqeiDGTYILELHKDEKQgeAKATIVMDFCTDVV----QNPKRG 356
Cdd:cd13278    18 KITKEGYLLqEGGDC-----------EYWRRRFFKL----QGTKLVAYHEVTRK--PRATINLLKVVDVVddddARERTS 80

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|..
gi 442626607  357 RF------------CFELRMTTGHKsFTLAAENEQDFKDWLSKISSVLAQNR 396
Cdd:cd13278    81 SFkrnftdlvlfeeCFRLVFANGEV-IDFYADSKEEKADWYSKLKEVVELNR 131
 
Blast search parameters
Data Source: Precalculated data, version = cdd.v.3.21
Preset Options:Database: CDSEARCH/cdd   Low complexity filter: no  Composition Based Adjustment: yes   E-value threshold: 0.01

References:

  • Wang J et al. (2023), "The conserved domain database in 2023", Nucleic Acids Res.51(D)384-8.
  • Lu S et al. (2020), "The conserved domain database in 2020", Nucleic Acids Res.48(D)265-8.
  • Marchler-Bauer A et al. (2017), "CDD/SPARCLE: functional classification of proteins via subfamily domain architectures.", Nucleic Acids Res.45(D)200-3.
Help | Disclaimer | Write to the Help Desk
NCBI | NLM | NIH