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Conserved domains on  [gi|1907198461|ref|XP_036010950|]
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dedicator of cytokinesis protein 6 isoform X4 [Mus musculus]

Protein Classification

DUF3398 and C2_Dock-C domain-containing protein( domain architecture ID 10570939)

protein containing domains DUF3398, C2_Dock-C, and DHR2_DOCK

Graphical summary

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List of domain hits

 Name Accession Description Interval E-value
DHR2_DOCK super family cl06123
Dock Homology Region 2, a GEF domain, of Dedicator of Cytokinesis proteins; DOCK proteins ...
 1590-2012 0e+00

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.


The actual alignment was detected with superfamily member cd11702:

Pssm-ID: 471388  Cd Length: 423  Bit Score: 926.33  E-value: 0e+00
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907198461 1590 SPDLRLTWLQNMAGKHAELGNHAEAAQCMVHAAALVAEYLALLEDSRHLPVGCVSFQNVSSNVLEESAISDDILSPDEEG 1669
Cdd:cd11702      1 SPDLRLTWLQNMAGKHSERGNHAEAAHCLVHSAALVAEYLSMLEDCRHLPVGCVSFQNISSNVLEESAVSDDILSPDEEG 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907198461 1670 FCSGKNFTELGLVGLLEQAAGYFTMGGLYEAVNEVYKNLIPILEAHRDYKKLAAVHGKLQEAFTKIMHQSSGWERVFGTY 1749
Cdd:cd11702     81 ICSGKYFTELGLVGLLEQAAASFNMGGLYEAVNEVYKILIPIHEANRDYKKLAVVHGKLQEAFNKITNQSSGWERMFGTY 160

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907198461 1750 FRVGFYGTRFGDLDEQEFVYKEPSITKLAEISHRLEEFYTERFGDDVVEIIKDSNPVDKSKLDPQKAYIQITYVEPHFDT 1829
Cdd:cd11702    161 FRVGFYGCKFGDLDEQEFVYKEPSITKLAEISHRLEEFYTERFGDEVVEIIKDSNPVDKSKLDPNKAYIQITYVEPFFDT 240

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907198461 1830 YELKDRVTYFDRNYGLRAFLFCTPFTPDGRAHGELAEQHKRKTLLSTEHAFPYIKTRIRVCHREETVLTPVEVAIEDMQK 1909
Cdd:cd11702    241 YELKDRVTYFDKNYNLRTFLFCTPFTLDGRAHGELHEQYKRKTILTTSHAFPYIKTRINVLHREEIVLIPVEVAIEDMQK 320

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907198461 1910 KTRELAFATEQDPPDAKMLQMVLQGSVGPTVNQGPLEVAQVFLSEIPEDPKLFRHHNKLRLCFKDFCKKCEDALRKNKAL 1989
Cdd:cd11702    321 KTQELAFATHQDPADAKMLQMVLQGCVGTTVNQGPLEVAQVFLSEIPEDPKLFRHHNKLRLCFKDFTKRCEDALRKNKAL 400

                          410       420
                   ....*....|....*....|...
gi 1907198461 1990 IGPDQKEYHRELERHYSRLREAL 2012
Cdd:cd11702    401 IGPDQKEYHRELERNYQRLREAL 423
C2_Dock-C cd08696
C2 domains found in Dedicator Of CytoKinesis (Dock) class C proteins; Dock-C is one of 4 ...
 545-722 1.53e-103

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: 328.93  E-value: 1.53e-103
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907198461  545 YRNLLFVYPHSLNFSSRQGSVRNLAVRIQYMAGEDQSQALPVIFGKSSCSEFTREAFTPVVYHNKSPEFYEEFKLRLPAC 624
Cdd:cd08696      1 YRNLLYVYPQSLNFSNRLGSARNIAVKVQLMSGEDESQALPVIFKGSSPEEFLTEAYTAVTYHNKSPDFYDEIKIKLPAD 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907198461  625 VTENHHLFFTFYHVSCQPRP-GTALETPVGFTWIPLLQHGRLRTGPFCLPVSVDQPPPSYSVLTPDVALPGMRWVDGHKG 703
Cdd:cd08696     81 LTDNHHLLFTFYHISCQKKQeGGSVETPIGYTWLPLLRNGRLQSGEFNLPVSLEKPPSNYSPDSPEVKLPGTKWVDNHKG 160

                          170
                   ....*....|....*....
gi 1907198461  704 VFSVELTAVSSVHPQDPHL 722
Cdd:cd08696    161 VFSVSVEAVSSVHTQDSYL 179
DOCK_C-D_N pfam11878
Dedicator of cytokinesis C/D, N terminal; This entry represents the N-terminal domain of the ...
 48-157 5.20e-45

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: 158.59  E-value: 5.20e-45
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907198461   48 TEVIEPLDFEDVLLSRPPEVEPGPLRDLIEFPVDDLELLKQPRECRTTESGVPEDG--QLDAQVRAAVEMYSEDWVIVRR 125
Cdd:pfam11878    1 PKVVEPLDYEEFISQHLTQIENDPLRDLLLFPDDDIEVSVIPRECRTLQPTVPEEAekEADPLVRECIKTYTSDWHVVNY 80

                           90       100       110
                   ....*....|....*....|....*....|..
gi 1907198461  126 RYQHLSTAYSPITTETQREWQKGLTCQVFEQD 157
Cdd:pfam11878   81 KYEDYSGDFRQLPKSKRRERPEKLPKQVFEID 112
 
Name Accession Description Interval E-value
DHR2_DOCK6 cd11702
Dock Homology Region 2, a GEF domain, of Class C Dedicator of Cytokinesis 6; Dock6, also ...
 1590-2012 0e+00

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: 926.33  E-value: 0e+00
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907198461 1590 SPDLRLTWLQNMAGKHAELGNHAEAAQCMVHAAALVAEYLALLEDSRHLPVGCVSFQNVSSNVLEESAISDDILSPDEEG 1669
Cdd:cd11702      1 SPDLRLTWLQNMAGKHSERGNHAEAAHCLVHSAALVAEYLSMLEDCRHLPVGCVSFQNISSNVLEESAVSDDILSPDEEG 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907198461 1670 FCSGKNFTELGLVGLLEQAAGYFTMGGLYEAVNEVYKNLIPILEAHRDYKKLAAVHGKLQEAFTKIMHQSSGWERVFGTY 1749
Cdd:cd11702     81 ICSGKYFTELGLVGLLEQAAASFNMGGLYEAVNEVYKILIPIHEANRDYKKLAVVHGKLQEAFNKITNQSSGWERMFGTY 160

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907198461 1750 FRVGFYGTRFGDLDEQEFVYKEPSITKLAEISHRLEEFYTERFGDDVVEIIKDSNPVDKSKLDPQKAYIQITYVEPHFDT 1829
Cdd:cd11702    161 FRVGFYGCKFGDLDEQEFVYKEPSITKLAEISHRLEEFYTERFGDEVVEIIKDSNPVDKSKLDPNKAYIQITYVEPFFDT 240

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907198461 1830 YELKDRVTYFDRNYGLRAFLFCTPFTPDGRAHGELAEQHKRKTLLSTEHAFPYIKTRIRVCHREETVLTPVEVAIEDMQK 1909
Cdd:cd11702    241 YELKDRVTYFDKNYNLRTFLFCTPFTLDGRAHGELHEQYKRKTILTTSHAFPYIKTRINVLHREEIVLIPVEVAIEDMQK 320

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907198461 1910 KTRELAFATEQDPPDAKMLQMVLQGSVGPTVNQGPLEVAQVFLSEIPEDPKLFRHHNKLRLCFKDFCKKCEDALRKNKAL 1989
Cdd:cd11702    321 KTQELAFATHQDPADAKMLQMVLQGCVGTTVNQGPLEVAQVFLSEIPEDPKLFRHHNKLRLCFKDFTKRCEDALRKNKAL 400

                          410       420
                   ....*....|....*....|...
gi 1907198461 1990 IGPDQKEYHRELERHYSRLREAL 2012
Cdd:cd11702    401 IGPDQKEYHRELERNYQRLREAL 423
C2_Dock-C cd08696
C2 domains found in Dedicator Of CytoKinesis (Dock) class C proteins; Dock-C is one of 4 ...
 545-722 1.53e-103

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: 328.93  E-value: 1.53e-103
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907198461  545 YRNLLFVYPHSLNFSSRQGSVRNLAVRIQYMAGEDQSQALPVIFGKSSCSEFTREAFTPVVYHNKSPEFYEEFKLRLPAC 624
Cdd:cd08696      1 YRNLLYVYPQSLNFSNRLGSARNIAVKVQLMSGEDESQALPVIFKGSSPEEFLTEAYTAVTYHNKSPDFYDEIKIKLPAD 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907198461  625 VTENHHLFFTFYHVSCQPRP-GTALETPVGFTWIPLLQHGRLRTGPFCLPVSVDQPPPSYSVLTPDVALPGMRWVDGHKG 703
Cdd:cd08696     81 LTDNHHLLFTFYHISCQKKQeGGSVETPIGYTWLPLLRNGRLQSGEFNLPVSLEKPPSNYSPDSPEVKLPGTKWVDNHKG 160

                          170
                   ....*....|....*....
gi 1907198461  704 VFSVELTAVSSVHPQDPHL 722
Cdd:cd08696    161 VFSVSVEAVSSVHTQDSYL 179
DHR-2_Lobe_A pfam06920
DHR-2, Lobe A; This entry represents a conserved region within a number of eukaryotic ...
 1578-1735 5.92e-68

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: 226.02  E-value: 5.92e-68
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907198461 1578 DLMYRIARGYQGSPDLRLTWLQNMAGKHAELGNHAEAAQCMVHAAALVAEYLALLeDSRHLPVGCVSFQNVSSNVL-EES 1656
Cdd:pfam06920    1 DLQYSLANSYKSSPDLRLTWLENLAEKHLENGNFSEAAQCLIHIAALIAEYLKLK-GKIPNPLGASAFEKISPNILrEES 79

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1907198461 1657 AISDDilspdeEGFCSGKNFTELGLVGLLEQAAGYFTMGGLYEAVNEVYKNLIPILEAHRDYKKLAAVHGKLQEAFTKI 1735
Cdd:pfam06920   80 ALKDD------SGVCDSPHFTEDGLVGLLEEAIDYLDKAERYELAIELYKLLLPIYESRRDYKKLSECHGKLAEAYEKI 152
DOCK-C2 pfam14429
C2 domain in Dock180 and Zizimin proteins; The Dock180/Dock1 and Zizimin proteins are atypical ...
 545-721 6.74e-60

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: 203.99  E-value: 6.74e-60
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907198461  545 YRNLLFVYPHSLNFSSRQGSV-RNLAVRIQYMAGEdqSQALP-VIFGKSSCsEFTREAFTPVVYHNKSPEFYEEFKLRLP 622
Cdd:pfam14429    4 YRNDLYVTPKSGNFSKQKKSSaRNIEVTVEVRDSD--GEPLPnCIYGGSGG-PFVTEFKSTVYYHNKSPTWYEEIKIALP 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907198461  623 ACVTENHHLFFTFYHVSCQPRPgTALETPVGFTWIPLLQHGR--LRTGPFCLPVS-VDQPPPSYSVLT-------PDVAL 692
Cdd:pfam14429   81 AELTPKHHLLFTFYHVSCDEKK-DKVEKPFGYAFLPLLDDDGafLRDGEHTLPVYkYDELPPGYLSLPwssggekESSAL 159

                          170       180
                   ....*....|....*....|....*....
gi 1907198461  693 PGMRwvdGHKGVFSVELTAVSSVHPQDPH 721
Cdd:pfam14429  160 PGLK---GGKDLFKVRTRLCSTKYTQDEH 185
DOCK_C-D_N pfam11878
Dedicator of cytokinesis C/D, N terminal; This entry represents the N-terminal domain of the ...
 48-157 5.20e-45

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: 158.59  E-value: 5.20e-45
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907198461   48 TEVIEPLDFEDVLLSRPPEVEPGPLRDLIEFPVDDLELLKQPRECRTTESGVPEDG--QLDAQVRAAVEMYSEDWVIVRR 125
Cdd:pfam11878    1 PKVVEPLDYEEFISQHLTQIENDPLRDLLLFPDDDIEVSVIPRECRTLQPTVPEEAekEADPLVRECIKTYTSDWHVVNY 80

                           90       100       110
                   ....*....|....*....|....*....|..
gi 1907198461  126 RYQHLSTAYSPITTETQREWQKGLTCQVFEQD 157
Cdd:pfam11878   81 KYEDYSGDFRQLPKSKRRERPEKLPKQVFEID 112
 
Name Accession Description Interval E-value
DHR2_DOCK6 cd11702
Dock Homology Region 2, a GEF domain, of Class C Dedicator of Cytokinesis 6; Dock6, also ...
 1590-2012 0e+00

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: 926.33  E-value: 0e+00
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907198461 1590 SPDLRLTWLQNMAGKHAELGNHAEAAQCMVHAAALVAEYLALLEDSRHLPVGCVSFQNVSSNVLEESAISDDILSPDEEG 1669
Cdd:cd11702      1 SPDLRLTWLQNMAGKHSERGNHAEAAHCLVHSAALVAEYLSMLEDCRHLPVGCVSFQNISSNVLEESAVSDDILSPDEEG 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907198461 1670 FCSGKNFTELGLVGLLEQAAGYFTMGGLYEAVNEVYKNLIPILEAHRDYKKLAAVHGKLQEAFTKIMHQSSGWERVFGTY 1749
Cdd:cd11702     81 ICSGKYFTELGLVGLLEQAAASFNMGGLYEAVNEVYKILIPIHEANRDYKKLAVVHGKLQEAFNKITNQSSGWERMFGTY 160

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907198461 1750 FRVGFYGTRFGDLDEQEFVYKEPSITKLAEISHRLEEFYTERFGDDVVEIIKDSNPVDKSKLDPQKAYIQITYVEPHFDT 1829
Cdd:cd11702    161 FRVGFYGCKFGDLDEQEFVYKEPSITKLAEISHRLEEFYTERFGDEVVEIIKDSNPVDKSKLDPNKAYIQITYVEPFFDT 240

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907198461 1830 YELKDRVTYFDRNYGLRAFLFCTPFTPDGRAHGELAEQHKRKTLLSTEHAFPYIKTRIRVCHREETVLTPVEVAIEDMQK 1909
Cdd:cd11702    241 YELKDRVTYFDKNYNLRTFLFCTPFTLDGRAHGELHEQYKRKTILTTSHAFPYIKTRINVLHREEIVLIPVEVAIEDMQK 320

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907198461 1910 KTRELAFATEQDPPDAKMLQMVLQGSVGPTVNQGPLEVAQVFLSEIPEDPKLFRHHNKLRLCFKDFCKKCEDALRKNKAL 1989
Cdd:cd11702    321 KTQELAFATHQDPADAKMLQMVLQGCVGTTVNQGPLEVAQVFLSEIPEDPKLFRHHNKLRLCFKDFTKRCEDALRKNKAL 400

                          410       420
                   ....*....|....*....|...
gi 1907198461 1990 IGPDQKEYHRELERHYSRLREAL 2012
Cdd:cd11702    401 IGPDQKEYHRELERNYQRLREAL 423
DHR2_DOCK7 cd11703
Dock Homology Region 2, a GEF domain, of Class C Dedicator of Cytokinesis 7; Dock7, also ...
 1551-2023 0e+00

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: 820.86  E-value: 0e+00
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907198461 1551 DLMFNLHMILTDTVKMKEHQEDPEMLMDLMYRIARGYQGSPDLRLTWLQNMAGKHAELGNHAEAAQCMVHAAALVAEYLA 1630
Cdd:cd11703      1 DLVFNLHMILSDTVKMKEHQEDPEMLIDLMYRIAKGYQTSPDLRLTWLQNMAGKHSERSNHAEAAQCLVHSAALVAEYLS 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907198461 1631 LLEDSRHLPVGCVSFQNVSSNVLEESAISDDILSPDEEGFCSGKNFTELGLVGLLEQAAGYFTMGGLYEAVNEVYKNLIP 1710
Cdd:cd11703     81 MLEDRKYLPVGCVTFQNISSNVLEESAVSDDVVSPDEEGICSGKYFTEAGLVGLLEQAAASFSMAGMYEAVNEVYKVLIP 160

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907198461 1711 ILEAHRDYKKLAAVHGKLQEAFTKIMHQSSGweRVFGTYFRVGFYGTRFGDLDEQEFVYKEPSITKLAEISHRLEEFYTE 1790
Cdd:cd11703    161 IHEANRDAKKLATIHGKLQEAFSKIVHQDGK--RMFGTYFRVGFYGTKFGDLDEQEFVYKEPAITKLAEISHRLEGFYGE 238

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907198461 1791 RFGDDVVEIIKDSNPVDKSKLDPQKAYIQITYVEPHFDTYELKDRVTYFDRNYGLRAFLFCTPFTPDGRAHGELAEQHKR 1870
Cdd:cd11703    239 RFGEDVVEVIKDSNPVDKCKLDPNKAFIQITYVEPYFDTYEMKDRITYFDKNYNLRRFMYCTPFTLDGRAHGELHEQFKR 318

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907198461 1871 KTLLSTEHAFPYIKTRIRVCHREETVLTPVEVAIEDMQKKTRELAFATEQDPPDAKMLQMVLQGSVGPTVNQGPLEVAQV 1950
Cdd:cd11703    319 KTILTTSHAFPYIKTRINVIHKEEIILTPIEVAIEDMQKKTQELAFATHQDPADPKMLQMVLQGSVGTTVNQGPLEVAQV 398

                          410       420       430       440       450       460       470
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1907198461 1951 FLSEIPEDPKLFRHHNKLRLCFKDFCKKCEDALRKNKALIGPDQKEYHRELERHYSRLREALQPLLTQRLPQL 2023
Cdd:cd11703    399 FLSEIPSDPKLFRHHNKLRLCFKDFTKRCEDALRKNKSLIGPDQKEYQRELERNYHRLKEALQPLINRKIPQL 471
DHR2_DOCK8 cd11701
Dock Homology Region 2, a GEF domain, of Class C Dedicator of Cytokinesis 8; Dock8, also ...
 1590-2012 0e+00

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: 728.37  E-value: 0e+00
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907198461 1590 SPDLRLTWLQNMAGKHAELGNHAEAAQCMVHAAALVAEYLALLEDSRHLPVGCVSFQNVSSNVLEESAISDDILSPDEEG 1669
Cdd:cd11701      2 SPDLRLTWLQNMAEKHTKRKCFTEAAMCLVHAAALVAEYLSMLEDHSYLPVGSVSFQNISSNVLEESAVSDDILSPDEDG 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907198461 1670 FCSGKNFTELGLVGLLEQAAGYFTMGGLYEAVNEVYKNLIPILEAHRDYKKLAAVHGKLQEAFTKIMHQssGWERVFGTY 1749
Cdd:cd11701     82 VCSGRYFTENGLVGLLEQAAELFSTGGLYETVNEVYKIVIPILEAHRDFRKLASTHDKLQKAFDNIINK--GHKRMFGTY 159

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907198461 1750 FRVGFYGTRFGDLDEQEFVYKEPSITKLAEISHRLEEFYTERFGDDVVEIIKDSNPVDKSKLDPQKAYIQITYVEPHFDT 1829
Cdd:cd11701    160 FRVGFYGSKFGDLDEQEFIYKEPAITKLPEISHRLEGFYGQCFGDDVVEVIKDSTPVDKSKLDPNKAYIQITFVEPYFDD 239

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907198461 1830 YELKDRVTYFDRNYGLRAFLFCTPFTPDGRAHGELAEQHKRKTLLSTEHAFPYIKTRIRVCHREETVLTPVEVAIEDMQK 1909
Cdd:cd11701    240 YEMKDRVTYFEKNFNLRRFMYTTPFTLDGRPRGELSEQYKRKTILTTMHAFPYIKTRINVIQKEEFDLTPIEVAIEDMQK 319

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907198461 1910 KTRELAFATEQDPPDAKMLQMVLQGSVGPTVNQGPLEVAQVFLSEIPEDPKLFRHHNKLRLCFKDFCKKCEDALRKNKAL 1989
Cdd:cd11701    320 KTRELAEATHQEPPDAKMLQMVLQGSVGATVNQGPLEVAQVFLAEIPADPKLYRHHNKLRLCFKEFIMRCGEAVEKNKRL 399

                          410       420
                   ....*....|....*....|...
gi 1907198461 1990 IGPDQKEYHRELERHYSRLREAL 2012
Cdd:cd11701    400 ITADQREYQQELKKNYNKLRENL 422
DHR2_DOCK_C cd11695
Dock Homology Region 2, a GEF domain, of Class C Dedicator of Cytokinesis proteins; DOCK ...
 1590-2012 0e+00

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: 726.40  E-value: 0e+00
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907198461 1590 SPDLRLTWLQNMAGKHAELGNHAEAAQCMVHAAALvaeylalledsrhlpvgcvsfqnvssnvleesaisddilspdeeg 1669
Cdd:cd11695      1 SPDLRLTWLQNMAEKHYERKNFAEAAQCLVHAAAL--------------------------------------------- 35

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907198461 1670 fcsgknftelGLVGLLEQAAGYFTMGGLYEAVNEVYKNLIPILEAHRDYKKLAAVHGKLQEAFTKIMHQSsGWERVFGTY 1749
Cdd:cd11695     36 ----------GLVGLLEQAAESFSKAGMYEAVNEVYKLLIPILEANRDYKKLAEIHGKLQDAFTKIEKQQ-GGKRMFGTY 104

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907198461 1750 FRVGFYGTRFGDLDEQEFVYKEPSITKLAEISHRLEEFYTERFGDDVVEIIKDSNPVDKSKLDPQKAYIQITYVEPHFDT 1829
Cdd:cd11695    105 FRVGFYGSKFGDLDGKEFIYKEPAITKLPEISHRLETFYGERFGEERVEVIKDSNPVDTSKLDPDKAYIQITYVEPYFDE 184

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907198461 1830 YELKDRVTYFDRNYGLRAFLFCTPFTPDGRAHGELAEQHKRKTLLSTEHAFPYIKTRIRVCHREETVLTPVEVAIEDMQK 1909
Cdd:cd11695    185 YELKERTTYFERNYNLRRFMYATPFTPDGKAHGELAEQYKRKTILTTENSFPYVKTRLQVVNREEIVLTPIEVAIEDVQK 264

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907198461 1910 KTRELAFATEQDPPDAKMLQMVLQGSVGPTVNQGPLEVAQVFLSEIPEDPK-LFRHHNKLRLCFKDFCKKCEDALRKNKA 1988
Cdd:cd11695    265 KTRELAAATTQEPPDPKMLQMVLQGSIGTTVNQGPLEVANVFLSDIPLDPKeLDRHQNKLRLCFKEFSKKCYDALEKNKE 344

                          410       420
                   ....*....|....*....|....
gi 1907198461 1989 LIGPDQKEYHRELERHYSRLREAL 2012
Cdd:cd11695    345 LIGPDQKEYQKELERNYENFKEKL 368
DHR2_DOCK_D cd11694
Dock Homology Region 2, a GEF domain, of Class D Dedicator of Cytokinesis proteins; DOCK ...
 1592-2012 2.74e-131

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: 416.74  E-value: 2.74e-131
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907198461 1592 DLRLTWLQNMAGKHAELGNHAEAAQCMVHAAALVAEYLALledsrhlpvgcvsfqnvssnvleesaisddilspdeegfc 1671
Cdd:cd11694      1 ELRKTWLESMARIHEKNGNFSEAAMCYIHIAALVAEYLKR---------------------------------------- 40

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907198461 1672 sgKNFtelgLVGLLEQAAGYFTMGGLYEAVNEVYKNLIPILEAHRDYKKLAAVHGKLQEAFTKIMHQSSGWERVFGTYFR 1751
Cdd:cd11694     41 --KDL----LLELLEACVEGLWKAERYELLGELYKLIIPIYEKRRDFEQLADCYRTLHRAYEKVVEVMESGKRLLGTYYR 114

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907198461 1752 VGFYGT-RFGDLDEQEFVYKEPSITKLAEISHRLEEFYTERFGDDVVEIIKDSNPVDKSKLDPQKAYIQITYVEPHFDTY 1830
Cdd:cd11694    115 VAFYGQaFFEEEDGKEYIYKEPKVTSLSEISERLLKLYGDKFGSENVKLIQDSGKVNPKDLDPKYAYIQVTHVTPYFDEK 194

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907198461 1831 ELKDRVTYFDRNYGLRAFLFCTPFTPDGRAHGELAEQHKRKTLLSTEHAFPYIKTRIRVCHREETVLTPVEVAIEDMQKK 1910
Cdd:cd11694    195 ELEDRKTEFERNHNIRRFVFETPFTLSGKARGAVEEQWKRRTILTTSHSFPYVKKRIPVVQREIIELSPIEVAIDEMQSK 274

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907198461 1911 TRELAFATEQDPPDAKMLQMVLQGSVGPTVNQGPLEVAQVFLSEIPEdPKLFRHH-NKLRLCFKDFCKKCEDALRKNKAL 1989
Cdd:cd11694    275 VKELEELISTEPVDMKKLQLRLQGSVSVQVNAGPLAYARAFLEPTTV-KNYPDDQvEDLKDVFRDFIKACGQALELNERL 353

                          410       420
                   ....*....|....*....|...
gi 1907198461 1990 IGPDQKEYHRELERHYSRLREAL 2012
Cdd:cd11694    354 IKEDQREYHEVLKENYRKMVKEL 376
DHR2_DOCK cd11684
Dock Homology Region 2, a GEF domain, of Dedicator of Cytokinesis proteins; DOCK proteins ...
 1592-2012 1.99e-120

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: 386.27  E-value: 1.99e-120
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907198461 1592 DLRLTWLQNMAGKHAELGNHAEAAQCMVHAAALVAEYLalledsrhlpvgcvsfqnvssnvleesaisDDILSPDEEGFC 1671
Cdd:cd11684      1 ELYIRYLHKLADLHEERGNYVEAALCLLLHADLYAWDL------------------------------KALVPALAESLS 50

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907198461 1672 SGKNFTELGLVGLLEQAAGYFTMGGLYEAVNEVYKNLIPILEAHRDYKKLAAVHGKLQEAFTKIMHQssgwERVFGTYFR 1751
Cdd:cd11684     51 FPEQTSFERKEALYKKAIDLFDKGKAWEFAIALYKELIPQYENNFDYAKLSEVHRKIAKLYEKIAEK----DRLFPTYFR 126

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907198461 1752 VGFYGTRF-GDLDEQEFVYKEPSITKLAEISHRLEEFYTERfgddvvEIIKDSNPVDKSKLDPQKAYIQITYVEPHFDTY 1830
Cdd:cd11684    127 VGFYGKGFpESLRGKEFIYRGPEFERLGDFCERLKSLYPGA------EIIQSSEEPDDEILDSEGQYIQITSVEPYFDDE 200

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907198461 1831 ELK----DRVTYFDRNYGLRAFLFCTPFTPDGRA-HGELAEQHKRKTLLSTEHAFPYIKTRIRVCHREETVLTPVEVAIE 1905
Cdd:cd11684    201 DLVsraaPGVRQFYRNNNINTFVYERPFTKGGKKsQNEITDQWKERTILTTEESFPTILRRSEVVSIEEIELSPIENAIE 280

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907198461 1906 DMQKKTRELAFATEQ----DPPDAKMLQMVLQGSVGPTVNQGPLEVAQVFLSEIPEDPKLFRHH-NKLRLCFKDFCKKCE 1980
Cdd:cd11684    281 DIEKKTEELRSLINKyrsgDSPNVNPLQMLLQGTVDAAVNGGPVAYAEAFLSEEYLSNYPEAEKvKKLKEAFEEFLEILK 360

                          410       420       430
                   ....*....|....*....|....*....|..
gi 1907198461 1981 DALRKNKALIGPDQKEYHRELERHYSRLREAL 2012
Cdd:cd11684    361 RGLALHAKLCPPEMAPLHEELEEGFEKLFKEL 392
DHR2_DOCK11 cd11700
Dock Homology Region 2, a GEF domain, of Class D Dedicator of Cytokinesis 11; Dock11, also ...
 1591-2012 9.46e-108

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: 350.83  E-value: 9.46e-108
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907198461 1591 PDLRLTWLQNMAGKHAELGNHAEAAQCMVHAAALVAEYLallEDSRHLPVGCVSFQNVSSNVLEESAISDDILSPDeegf 1670
Cdd:cd11700      1 PELRKTWLDSMAKIHVKNGDFSEAAMCYVHVAALVAEFL---HRKKLFPSGCAAFKKITPNIDEEGAMKEDIGMMD---- 73

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907198461 1671 csgKNFTELGLVGLLEQAAGYFTMGGLYEAVNEVYKNLIPILEAHRDYKKLAAVHGKLQEAFTKIMHQSSGWERVFGTYF 1750
Cdd:cd11700     74 ---VHYSEEVLVELLEQCVDGLWKAERYELISEISKLIIPIYEKRREFEKLTQLYRTLHGAYAKILEVMHTGKRLLGTFF 150

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907198461 1751 RVGFYG-TRFGDLDEQEFVYKEPSITKLAEISHRLEEFYTERFGDDVVEIIKDSNPVDKSKLDPQKAYIQITYVEPHFDT 1829
Cdd:cd11700    151 RVAFYGqGFFEEEDGKEYIYKEPKLTGLSEISHRLLKLYGEKFGSENVKIIQDSNKVNQKDLDPKYAHIQVTYVKPYFDD 230

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907198461 1830 YELKDRVTYFDRNYGLRAFLFCTPFTPDGRAHGELAEQHKRKTLLSTEHAFPYIKTRIRVCHREETVLTPVEVAIEDMQK 1909
Cdd:cd11700    231 KEMAERKTEFERNHNIQRFVFETPYTLSGKKQGGVEEQCKRRTILTTANSFPYVKKRIPVNGEKQTNLKPIDVATDEIKD 310

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907198461 1910 KTRELAFATEQDPPDAKMLQMVLQGSVGPTVNQGPLEVAQVFLSEIPEDPKLFRHHNKLRLCFKDFCKKCEDALRKNKAL 1989
Cdd:cd11700    311 KTAELQKLCSNQDVDMIQLQLKLQGCVSVQVNAGPLAYARAFLDDSQASKYPNKKVKELKEMFRKFIQACSIALELNERL 390

                          410       420
                   ....*....|....*....|...
gi 1907198461 1990 IGPDQKEYHRELERHYSRLREAL 2012
Cdd:cd11700    391 IKEDQVEYHEGLKSNFRDMVKEL 413
DHR2_DOCK9 cd11698
Dock Homology Region 2, a GEF domain, of Class D Dedicator of Cytokinesis 9; Dock9, also ...
 1592-2012 1.48e-104

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: 342.01  E-value: 1.48e-104
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907198461 1592 DLRLTWLQNMAGKHAELGNHAEAAQCMVHAAALVAEYLALLEDSRHlpvGCVSFQNVSSNVLEESAISDDILSPDeegfc 1671
Cdd:cd11698      1 ELRKTWLDSMARIHVKNGDLSEAAMCYVHVAALVAEYLTRKGMFRQ---GCTAFRVITPNIDEEASMMEDVGMQD----- 72

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907198461 1672 sgKNFTELGLVGLLEQAAGYFTMGGLYEAVNEVYKNLIPILEAHRDYKKLAAVHGKLQEAFTKIMHQSSGWERVFGTYFR 1751
Cdd:cd11698     73 --VHFNEDVLMELLEQCADGLWKAERYELIADIYKLIIPIYEKRRDFERLAHLYDTLHRAYSKVTEVMHSGKRLLGTYFR 150

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907198461 1752 VGFYGTRF-GDLDEQEFVYKEPSITKLAEISHRLEEFYTERFGDDVVEIIKDSNPVDKSKLDPQKAYIQITYVEPHFDTY 1830
Cdd:cd11698    151 VAFFGQGFfEDEDGKEYIYKEPKLTPLSEISQRLLKLYSDKFGSENVKMIQDSGKVNPKDLDSKYAYIQVTHVTPYFDEK 230

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907198461 1831 ELKDRVTYFDRNYGLRAFLFCTPFTPDGRAHGELAEQHKRKTLLSTEHAFPYIKTRIRVCHREETVLTPVEVAIEDMQKK 1910
Cdd:cd11698    231 ELQERKTDFERSHNIRRFMFEMPFTQSGKRQGGVEEQCKRRTILTAIHCFPYVKKRIPVMYQHHTDLNPIEVAIDEMSKK 310

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907198461 1911 TRELAFATEQDPPDAKMLQMVLQGSVGPTVNQGPLEVAQVFLSEIPEDPKLFRHHNKLRLCFKDFCKKCEDALRKNKALI 1990
Cdd:cd11698    311 VAELRQLCSSAEVDMIKLQLKLQGSVSVQVNAGPLAYARAFLDDTNTKRYPDNKVKLLKEVFRQFVEACGQALAVNERLI 390

                          410       420
                   ....*....|....*....|..
gi 1907198461 1991 GPDQKEYHRELERHYSRLREAL 2012
Cdd:cd11698    391 KEDQLEYQEEMKANYREMAKEL 412
C2_Dock-C cd08696
C2 domains found in Dedicator Of CytoKinesis (Dock) class C proteins; Dock-C is one of 4 ...
 545-722 1.53e-103

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: 328.93  E-value: 1.53e-103
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907198461  545 YRNLLFVYPHSLNFSSRQGSVRNLAVRIQYMAGEDQSQALPVIFGKSSCSEFTREAFTPVVYHNKSPEFYEEFKLRLPAC 624
Cdd:cd08696      1 YRNLLYVYPQSLNFSNRLGSARNIAVKVQLMSGEDESQALPVIFKGSSPEEFLTEAYTAVTYHNKSPDFYDEIKIKLPAD 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907198461  625 VTENHHLFFTFYHVSCQPRP-GTALETPVGFTWIPLLQHGRLRTGPFCLPVSVDQPPPSYSVLTPDVALPGMRWVDGHKG 703
Cdd:cd08696     81 LTDNHHLLFTFYHISCQKKQeGGSVETPIGYTWLPLLRNGRLQSGEFNLPVSLEKPPSNYSPDSPEVKLPGTKWVDNHKG 160

                          170
                   ....*....|....*....
gi 1907198461  704 VFSVELTAVSSVHPQDPHL 722
Cdd:cd08696    161 VFSVSVEAVSSVHTQDSYL 179
DHR2_DOCK10 cd11699
Dock Homology Region 2, a GEF domain, of Class D Dedicator of Cytokinesis 10; Dock10, also ...
 1591-2015 1.40e-102

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: 337.40  E-value: 1.40e-102
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907198461 1591 PDLRLTWLQNMAGKHAELGNHAEAAQCMVHAAALVAEYLA---------------LLEDSRH---------------LPV 1640
Cdd:cd11699      1 PELRRTWLESMAKIHARNGDLSEAAMCYIHIAALIAEYLKrkgywkmekictssmLPEDSQVydsnlllttstggsmFSM 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907198461 1641 GCVSFQNVSSNVLEESAISDDILSPDEEgfcsgknFTELGLVGLLEQAAGYFTMGGLYEAVNEVYKNLIPILEAHRDYKK 1720
Cdd:cd11699     81 GWPAFLSITPNIKEEGAMKEDSGMQDTP-------YNENTLVEQLELCVDYLWKSERYELIADVNKPVIAVFEKQRDFKR 153

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907198461 1721 LAAVHGKLQEAFTKIMHQSSGWERVFGTYFRVGFYGTRFGDLDE-QEFVYKEPSITKLAEISHRLEEFYTERFGDDVVEI 1799
Cdd:cd11699    154 LSELYYDIHRSYLKVAEVVNSEKRLFGRYYRVAFYGQGFFEEEEgKEYIYKEPKLTGLSEISQRLLKLYADKFGADNVKI 233

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907198461 1800 IKDSNPVDKSKLDPQKAYIQITYVEPHFDTYELKDRVTYFDRNYGLRAFLFCTPFTPDGRAHGELAEQHKRKTLLSTEHA 1879
Cdd:cd11699    234 IQDSNKVNPKELDPKFAYIQVTYVTPYFDEKEQEDRKTDFEMHHNINRFVFETPFTLSGKKHGGVEEQCKRRTILTTSHS 313

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907198461 1880 FPYIKTRIRVCHREETVLTPVEVAIEDMQKKTRELAFATEQDPPDAKMLQMVLQGSVGPTVNQGPLEVAQVFLSEIPEDP 1959
Cdd:cd11699    314 FPYVKKRIQVVSQTSTELNPIEVAIDEMSKKVSELNQLCTMEEVDMIRLQLKLQGSVSVKVNAGPMAYARAFLEETNAKK 393

                          410       420       430       440       450
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 1907198461 1960 KLFRHHNKLRLCFKDFCKKCEDALRKNKALIGPDQKEYHRELERHYsrlREALQPL 2015
Cdd:cd11699    394 YPDNQVKLLKEIFRQFAEACGQALDVNERLIKEDQLEYQEEMRSHY---RDMLSEL 446
DHR-2_Lobe_A pfam06920
DHR-2, Lobe A; This entry represents a conserved region within a number of eukaryotic ...
 1578-1735 5.92e-68

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: 226.02  E-value: 5.92e-68
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907198461 1578 DLMYRIARGYQGSPDLRLTWLQNMAGKHAELGNHAEAAQCMVHAAALVAEYLALLeDSRHLPVGCVSFQNVSSNVL-EES 1656
Cdd:pfam06920    1 DLQYSLANSYKSSPDLRLTWLENLAEKHLENGNFSEAAQCLIHIAALIAEYLKLK-GKIPNPLGASAFEKISPNILrEES 79

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1907198461 1657 AISDDilspdeEGFCSGKNFTELGLVGLLEQAAGYFTMGGLYEAVNEVYKNLIPILEAHRDYKKLAAVHGKLQEAFTKI 1735
Cdd:pfam06920   80 ALKDD------SGVCDSPHFTEDGLVGLLEEAIDYLDKAERYELAIELYKLLLPIYESRRDYKKLSECHGKLAEAYEKI 152
DOCK-C2 pfam14429
C2 domain in Dock180 and Zizimin proteins; The Dock180/Dock1 and Zizimin proteins are atypical ...
 545-721 6.74e-60

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: 203.99  E-value: 6.74e-60
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907198461  545 YRNLLFVYPHSLNFSSRQGSV-RNLAVRIQYMAGEdqSQALP-VIFGKSSCsEFTREAFTPVVYHNKSPEFYEEFKLRLP 622
Cdd:pfam14429    4 YRNDLYVTPKSGNFSKQKKSSaRNIEVTVEVRDSD--GEPLPnCIYGGSGG-PFVTEFKSTVYYHNKSPTWYEEIKIALP 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907198461  623 ACVTENHHLFFTFYHVSCQPRPgTALETPVGFTWIPLLQHGR--LRTGPFCLPVS-VDQPPPSYSVLT-------PDVAL 692
Cdd:pfam14429   81 AELTPKHHLLFTFYHVSCDEKK-DKVEKPFGYAFLPLLDDDGafLRDGEHTLPVYkYDELPPGYLSLPwssggekESSAL 159

                          170       180
                   ....*....|....*....|....*....
gi 1907198461  693 PGMRwvdGHKGVFSVELTAVSSVHPQDPH 721
Cdd:pfam14429  160 PGLK---GGKDLFKVRTRLCSTKYTQDEH 185
DHR-2_Lobe_C pfam20421
DHR-2, Lobe C; DOCK (dedicator of cytokinesis) proteins are guanine nucleotide exchange ...
 1913-2015 7.55e-47

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: 163.53  E-value: 7.55e-47
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907198461 1913 ELAFATEQDPPDAKMLQMVLQGSVGPTVNQGPLEVAQVFLSEIPEDPKLFRHHNKLRLCFKDFCKKCEDALRKNKALIGP 1992
Cdd:pfam20421    1 ELEAAINAPPPNIKTLQMVLQGSVDVQVNAGPLEYAEAFLSEKNVDNYPAEKVEKLKEEFRDFLKVCGEALRLNKKLISE 80

                           90       100
                   ....*....|....*....|...
gi 1907198461 1993 DQKEYHRELERHYSRLREALQPL 2015
Cdd:pfam20421   81 DQREYQEELEEGFEKLKEKLEPY 103
C2_DOCK180_related cd08679
C2 domains found in Dedicator Of CytoKinesis 1 (DOCK 180) and related proteins; Dock180 was ...
 545-722 1.68e-46

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: 165.58  E-value: 1.68e-46
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907198461  545 YRNLLFVYPHSLNFSSRQGSVRNLAVRIQYMAGEDQSqALPVIFGkSSCSEFTREAFTPVVYHNKSPEFYEEFKLRLPAC 624
Cdd:cd08679      1 LRNDLYVYPQSGELSKAKSKGRNIEITVEVRDDDGDI-IEPCISA-PGSGSELRSEYTSVVYYHKNPVFNDEIKIQLPAD 78

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907198461  625 VTENHHLFFTFYHVSCQPRPGTALETPVGFTWIPLL--QHGRLRTGPFCLPVSVDQPPPSYSVLTpDVALPGMRWVDGHK 702
Cdd:cd08679     79 LTPQHHLLFTFYHVSSKKKQGDKEETPFGYAFLPLMdkDGAFIKDGDHTLPVYKYDKRPDVGPSG-YLSLPSTLANGKSS 157

                          170       180
                   ....*....|....*....|.
gi 1907198461  703 G-VFSVELTAVSSVHPQDPHL 722
Cdd:cd08679    158 KdTFKIKTRLCSTILTQDKSL 178
C2_Dock-D cd08697
C2 domains found in Dedicator Of CytoKinesis (Dock) class C proteins; Dock-D is one of 4 ...
 545-722 6.87e-46

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: 164.03  E-value: 6.87e-46
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907198461  545 YRNLLFVYPHSLNFSSRQGSV--RNLAVRIQYMAGEDQ-SQALPVIFGKSSCSeFTREAFTPVVYHNKSPEFYEEFKLRL 621
Cdd:cd08697      1 YKNHLYVYPLHLKYDSQKTFAkaRNIAVCIEFRDSDEEdAKPLKCIYYGPGGG-FTTSAYAAVLHHNQNPEFYDEIKIEL 79

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907198461  622 PACVTENHHLFFTFYHVSC-QPRPGT---ALETPVGFTWIPLLQ-HGRLRTGPFCLPVSVDQP--PPSYSVLTPDValPG 694
Cdd:cd08697     80 PTQLHEKHHLLFTFYHVSCdINKKGKkkdGVETPVGYAWLPLLKdKGRLNSEEQTPPVANLLPnyPDGYLSIQPHG--PE 157

                          170       180
                   ....*....|....*....|....*...
gi 1907198461  695 MRWVDGHKGVFSVELTAVSSVHPQDPHL 722
Cdd:cd08697    158 VKWVDGGKPLFKVSTHLVSTVYTQDQHL 185
DOCK_C-D_N pfam11878
Dedicator of cytokinesis C/D, N terminal; This entry represents the N-terminal domain of the ...
 48-157 5.20e-45

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: 158.59  E-value: 5.20e-45
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907198461   48 TEVIEPLDFEDVLLSRPPEVEPGPLRDLIEFPVDDLELLKQPRECRTTESGVPEDG--QLDAQVRAAVEMYSEDWVIVRR 125
Cdd:pfam11878    1 PKVVEPLDYEEFISQHLTQIENDPLRDLLLFPDDDIEVSVIPRECRTLQPTVPEEAekEADPLVRECIKTYTSDWHVVNY 80

                           90       100       110
                   ....*....|....*....|....*....|..
gi 1907198461  126 RYQHLSTAYSPITTETQREWQKGLTCQVFEQD 157
Cdd:pfam11878   81 KYEDYSGDFRQLPKSKRRERPEKLPKQVFEID 112
DHR-2_Lobe_B pfam20422
DHR-2, Lobe B; DOCK (dedicator of cytokinesis) proteins are guanine nucleotide exchange ...
 1803-1879 6.97e-37

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: 133.89  E-value: 6.97e-37
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1907198461 1803 SNPVDKSKLDPQKAYIQITYVEPHFDTYELKDRVTYFDRNYGLRAFLFCTPFTPDGRAHGELAEQHKRKTLLSTEHA 1879
Cdd:pfam20422    1 SNPVDESILDPDKAYIQITSVEPYFDDSELNDRVTYFERNNNVNRFVFETPFTKSGKAQGEFEEQWKRRTILTTEHS 77
DHR2_DOCK_B cd11696
Dock Homology Region 2, a GEF domain, of Class B Dedicator of Cytokinesis proteins; DOCK ...
 1691-2012 3.00e-17

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: 86.34  E-value: 3.00e-17
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907198461 1691 YFTMGGLYEAVNEVYKNLIPILEAHRDYKKLAavHGKLQEA--FTKIMHQssgwERVFGTYFRVGFYGTRFGD-LDEQEF 1767
Cdd:cd11696     66 YFDRGKCWEKGIPLCRELAELYESLYDYAKLS--HILRMEAsfYDNILTQ----LRPEPEYFRVGFYGKGFPLfLRNKQF 139

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907198461 1768 VYKEPSITKLAEISHRLE-EFYTerfgddvVEIIKDSNPVDKSKLDPQKAYIQITYVEP------HFDTYELKDRVTYFD 1840
Cdd:cd11696    140 VYRGLDYERIGAFTQRLQsEFPQ-------AHILTKNTPPDDAILQADGQYIQICNVKPvperrpVLQMVGVPDKVRSFY 212

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907198461 1841 RNYGLRAFLFCTPF-TPDGRAHGELAEQHKRKTLLSTEHAFPYIKTRIRVCHREETVLTPVEVAIEDMQKKTRELAFATE 1919
Cdd:cd11696    213 RVNDVRKFQYDRPIhKGPIDKDNEFKSLWIERTTLVTEHSLPGILRWFEVVSREVEEIPPVENACETVENKNQELRSLIS 292

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907198461 1920 QDPPDAK----MLQMVLQGSVGPTVNQGPLEVAQVFLSE--IPEDPKLFRHHNKLRLCFKDFCKKCEDALRKNKALIGPD 1993
Cdd:cd11696    293 QYQADPTrninPFSMRLQGVIDAAVNGGIAKYQEAFFTPefILSHPEDAEHIARLRELILEQVQILEAGLALHGKLAPPE 372

                          330
                   ....*....|....*....
gi 1907198461 1994 QKEYHRELERHYSRLREAL 2012
Cdd:cd11696    373 VRPLHKRLVERFTQMKQSL 391
DHR2_DOCK_A cd11697
Dock Homology Region 2, a GEF domain, of Class A Dedicator of Cytokinesis proteins; DOCK ...
 1691-1954 1.95e-13

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: 74.67  E-value: 1.95e-13
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907198461 1691 YFTMGGLYEAVNEVYKNLIPILEAHR-DYKKLAAVHGKLQEAFTKIMHQSsgweRVFGTYFRVGFYGTRFGD-LDEQEFV 1768
Cdd:cd11697     70 YFDKGKMWECAISLCKELAEQYENETfDYLQLSELLKRMATFYDNIMKTL----RPEPEYFRVGYYGQGFPSfLRNKVFI 145

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907198461 1769 YKEPSITKLAEISHRLEEFYTErfgddvVEIIKDSNPVDKSKLDPQKAYIQITYVEPHFDTY-ELKDR------VTYFDR 1841
Cdd:cd11697    146 YRGKEYERLSDFSARLLNQFPN------AELMNTLTPPGDEIKESPGQYLQINKVDPVMDERpRFKGKpvsdqiLNYYKV 219

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907198461 1842 NYGLRaFLFCTPF---TPDGRahGELAEQHKRKTLLSTEHAFPYIKTRIRVCHREETVLTPVEVAIEDMQKKTRELAFAT 1918
Cdd:cd11697    220 NEVQR-FTFSRPFrrgTKDPD--NEFANMWLERTTLTTAYKLPGILRWFEVVSTSTVEISPLENAIETMEDTNKKIRDLI 296

                          250       260       270       280
                   ....*....|....*....|....*....|....*....|
gi 1907198461 1919 EQDPPDAKM----LQMVLQGSVGPTVNQGPLEVAQVFLSE 1954
Cdd:cd11697    297 LQHQSDPTLpinpLSMLLNGIVDAAVMGGIANYEKAFFTE 336
DHR2_DOCK3 cd11704
Dock Homology Region 2, a GEF domain, of Class B Dedicator of Cytokinesis 3; Dock3, also ...
 1683-2012 1.84e-12

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: 71.58  E-value: 1.84e-12
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907198461 1683 GLLEQAAGYFTMGGLYEAVNEVYKNLIPILEAHRDYKKLAAVHGKLQEAFTKIMHQssgwERVFGTYFRVGFYGTRFG-D 1761
Cdd:cd11704     58 GLCRKIIHYFNKGKSWEFGIPLCRELAFQYESLYDYQSLSWIRKMEAAYYDNIMEQ----QRLEPEFFRVGFYGRKFPfF 133

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907198461 1762 LDEQEFVYKEPSITKLAEISHRLEEFYTERFGddvveiIKDSNPVDKSKLDPQKAYIQITYVEP---HFDTYELK---DR 1835
Cdd:cd11704    134 LRNKEYVCRGHDYERLEAFQQRMLSEFPQAIA------MQHPNHPDDGILQCDAQYLQIYAVTPipdNMDVLQMDrvpDR 207

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907198461 1836 VTYFDRNYGLRAFLFCTPF--TPDGRAHgELAEQHKRKTLLSTEHAFPYIKTRIRVCHREETVLTPVEVAIEDMQKKTRE 1913
Cdd:cd11704    208 IKSFYRVNNVRKFRYDRPFhkGPKDKEN-EFKSLWIERTTLTLTHSLPGISRWFEVERRELVEVSPLENAIQVVENKNQE 286

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907198461 1914 L-----AFATEQDPPDAKMLQMVLQGSVGPTVNQGPLEVAQVFLSE--IPEDPKLFRHHNKLRLCFKDFCKKCEDALRKN 1986
Cdd:cd11704    287 LrtlisQYQHKQLHGNINLLSMCLNGVIDAAVNGGIARYQEAFFDKdyISKHPGDAEKITQLKELMQEQVHVLGVGLAVH 366

                          330       340
                   ....*....|....*....|....*.
gi 1907198461 1987 KALIGPDQKEYHRELERHYSRLREAL 2012
Cdd:cd11704    367 EKFVHPEMRPLHKKLIDQFQMMRSSL 392
DHR2_DOCK2 cd11706
Dock Homology Region 2, a GEF domain, of Class A Dedicator of Cytokinesis 2; Dock2 is a ...
 1626-1958 3.06e-12

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: 71.17  E-value: 3.06e-12
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907198461 1626 AEYLALLEDSRHLPVGCVSFQNVSSNVLEESAI---SDDILSPDEEGFCSGKNFTELGLV-GLLEQAAGYFTMGGLYEAV 1701
Cdd:cd11706     19 AMYIRYLYKLRDLHLDCENYTEAAYTLLLHTRLlkwSDEQCASQVMQTGQQHPQTQRQLKeTLYETIIGYFDKGKMWEEA 98

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907198461 1702 NEVYKNLIPILEAH-RDYKKLAAV---HGKLQEAFTKIMHQSSgwervfgTYFRVGFYGTRFGD-LDEQEFVYKEPSITK 1776
Cdd:cd11706     99 ISLCKELAEQYEMEiFDYELLSQNliqQAKFYESIMKILRPKP-------DYFAVGYYGQGFPSfLRNKVFIYRGKEYER 171

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907198461 1777 LAEISHRLEEFYTerfgdDVVEIIKDSNPVDKSKLDPQKaYIQITYVEPHFDTY-ELKDR------VTYFDRNYgLRAFL 1849
Cdd:cd11706    172 REDFQMQLMSQFP-----NAEKLNTTSAPGDDIKNSPGQ-YIQCFTVQPVLEEHpRLKNKpvpdqiINFYKSNY-VQRFH 244

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907198461 1850 FCTPFT-----PDGrahgELAEQHKRKTLLSTEHAFPYIKTRIRVCHREETVLTPVEVAIEDMQKKTRELAFATEQDPPD 1924
Cdd:cd11706    245 YSRPVRkgpvdPEN----EFASMWIERTTFVTAYKLPGILRWFEVTHMSQTTISPLENAIETMSTTNEKILMMINQYQSD 320

                          330       340       350       360
                   ....*....|....*....|....*....|....*....|...
gi 1907198461 1925 AKM----LQMVLQGSVGPTVNQGPLEVAQVFLSEI-----PED 1958
Cdd:cd11706    321 ESLpinpLSMLLNGIVDPAVMGGFAKYEKAFFTEEyvrdhPED 363
DHR2_DOCK5 cd11708
Dock Homology Region 2, a GEF domain, of Class A Dedicator of Cytokinesis 5; Dock5 is an ...
 1684-1980 4.33e-12

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: 70.36  E-value: 4.33e-12
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907198461 1684 LLEQAAGYFTMGGLYEAVNEVYKNLIPILEAHR-DYKKLAAVHGKLQEAFTKIMHQSsgweRVFGTYFRVGFYGTRFGD- 1761
Cdd:cd11708     63 LYQEIISFFDKGKMWEKAIELSKELADMYENQVfDYEGLGNLLKKQAQFYENIMKAM----RPQPEYFAVGYYGQGFPSf 138

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907198461 1762 LDEQEFVYKEPSITKLAEISHRL-EEFyterfgDDVVEIIKDSNPVDKSKLDPqKAYIQITYVEP------HFDTYELKD 1834
Cdd:cd11708    139 LRNKIFIYRGKEYERLEDFSLKLlTQF------PNAEKMTSTSPPGDEIKSST-KQYVQCFTVKPvmnlpsHYKDKPVPE 211

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907198461 1835 RVTYFDRNYGLRAFLFCTPF-----TPDGrahgELAEQHKRKTLLSTEHAFPYIKTRIRVCHREETVLTPVEVAIEDMQK 1909
Cdd:cd11708    212 QILNYYRANEVQQFQYSRPFrkgekDPDN----EFATMWIERTTFTTAYRFPGILKWFEVKQISTEEISPLENAIETMEL 287

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907198461 1910 KTRELAFATEQDPPDAKM----LQMVLQGSVGPTVNQGPLEVAQVF-----LSEIPEDP---KLFRH------------- 1964
Cdd:cd11708    288 TNEKISNLVQQHAWDRSLpvhpLSMLLNGIVDPAVMGGFSNYEKAFftekyLQEHPEDQekiELLKQlialqmpllaegi 367

                          330       340       350
                   ....*....|....*....|....*....|
gi 1907198461 1965 --------------HNKLRLCFKDFCKKCE 1980
Cdd:cd11708    368 rihgeklteqlkplHERLVSCFKDLRAKVE 397
DHR2_DOCK4 cd11705
Dock Homology Region 2, a GEF domain, of Class B Dedicator of Cytokinesis 4; Dock4 is an ...
 1713-2012 1.96e-08

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: 58.89  E-value: 1.96e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907198461 1713 EAHRDYKKLAAVHGKLQEAFTKIMHQssgwERVFGTYFRVGFYGTRFGD-LDEQEFVYKEPSITKLAEISHRLEEFYTER 1791
Cdd:cd11705     88 ESYYDYRNLSKMRMMEASLYDKIMDQ----QRLEPEFFRVGFYGKKFPFfLRNKEFVCRGHDYERLEAFQQRMLNEFPHA 163

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907198461 1792 FGddvveiIKDSNPVDKSKLDPQKAYIQITYVEPHFDTYEL------KDRVTYFDRNYGLRAFLFCTPFTPDGR-AHGEL 1864
Cdd:cd11705    164 IA------MQHANQPDETIFQAEAQYLQIYAVTPIPESQEVlqrdgvPDNIKSFYKVNHIWRFRYDRPFHKGTKdKENEF 237

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907198461 1865 AEQHKRKTLLSTEHAFPYIKTRIRVCHREETVLTPVEVAIEDMQKKTRELAFATEQ----DPPDAKMLQMVLQGSVGPTV 1940
Cdd:cd11705    238 KSLWVERTTLTLVQSLPGISRWFEVEKREVVEMSPLENAIEVLENKNQQLRTLISQcqtrQMQNINPLTMCLNGVIDAAV 317

                          250       260       270       280       290       300       310
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1907198461 1941 NQGPLEVAQVFLSE--IPEDPKLFRHHNKLRLCFKDFCKKCEDALRKNKALIGPDQKEYHRELERHYSRLREAL 2012
Cdd:cd11705    318 NGGVSRYQEAFFVKeyILNHPEDGDKITRLRELMLEQAQILEFGLAVHEKFVPQDMRPLHKKLVDQFFVMKSSL 391
DHR2_DOCK1 cd11707
Dock Homology Region 2, a GEF domain, of Class A Dedicator of Cytokinesis 1; Dock1, also ...
 1684-2013 9.39e-08

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: 56.58  E-value: 9.39e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907198461 1684 LLEQAAGYFTMGGLYEAVNEVYKNLIPILEAHR-DYKKLAAVHGKLQEAFTKIMHQSsgweRVFGTYFRVGFYGTRFGD- 1761
Cdd:cd11707     63 LYQEIIHYFDKGKMWEEAIALGKELAEQYENEMfDYEQLSELLKKQAQFYENIVKVI----RPKPDYFAVGYYGQGFPTf 138

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907198461 1762 LDEQEFVYKEPSITKLAEISHRLeefyTERFGDdvVEIIKDSNPVDKSKLDPQKAYIQITYVEPHFDT------YELKDR 1835
Cdd:cd11707    139 LRNKMFIYRGKEYERREDFEARL----LTQFPN--AEKMKTTSPPGDDIKNSSGQYIQCFTVKPLLELppkfqnKPVSEQ 212

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907198461 1836 VTYFDRNYGLRAFLFCTPF-----TPDgrahGELAEQHKRKTLLSTEHAFPYIKTRIRVCHREETVLTPVEVAIEDMQKK 1910
Cdd:cd11707    213 IVSFYRVNEVQRFQYSRPVrkgekDPD----NEFANMWIERTTYVTAYKLPGILRWFEVKSVFMVEISPLENAIETMQLT 288

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907198461 1911 TRELAFATEQDPPDAKM----LQMVLQGSVGPTVNQGPLEVAQVFLSE--IPEDPKLFRHHNKLRLCFKDFCKKCEDALR 1984
Cdd:cd11707    289 NEKINNMVQQHLNDPNLpinpLSMLLNGIVDPAVMGGFANYEKAFFTEkyMQEHPEDHEKIEKLKDLIAWQIPFLAEGIR 368

                          330       340
                   ....*....|....*....|....*....
gi 1907198461 1985 KNKALIGPDQKEYHRELERHYSRLREALQ 2013
Cdd:cd11707    369 IHGEKVTEALRPFHERMEACFRQLKEKVE 397
C2_Dock-A cd08694
C2 domains found in Dedicator Of CytoKinesis (Dock) class A proteins; Dock-A is one of 4 ...
 579-661 1.05e-03

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: 42.39  E-value: 1.05e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907198461  579 DQSQALPVIFGKSSCSEFTREAFTPVVYHNKSPEFYEEFKLRLPACVTENHHLFFTFYHVSCQPRPGTAlETPVGFTWIP 658
Cdd:cd08694     34 EDGKIIPGVISLGAGEEPIDEYKSVIYYQVDKPKWFETFKVAIPIEDFKSSHLRFTFKHRSSNEAKDKS-EKPFALSFVK 112


                   ...
gi 1907198461  659 LLQ 661
Cdd:cd08694    113 LMQ 115
C2_Dock-B cd08695
C2 domains found in Dedicator Of CytoKinesis (Dock) class B proteins; Dock-B is one of 4 ...
 589-663 3.94e-03

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: 40.44  E-value: 3.94e-03
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1907198461  589 GKSSCSEFtrEAFtpVVYHNKSPEFYEEFKLRLPACVTENHHLFFTFYHVSCQPRPGTALetpVGFTWIPLLQHG 663
Cdd:cd08695     48 GEPPCSEY--RSF--VLYHNNSPRWNETIKLPIPIDKFRGSHLRFEFRHCSTKDKGEKKL---FGFSFVPLMRED 115
 
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.
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