NCBI Home Page NCBI Site Search page NCBI Guide that lists and describes the NCBI resources
Conserved domains on  [gi|1870200937|ref|NP_001372258|]
View 

C2 domain-containing protein 5 isoform m [Homo sapiens]

Protein Classification

C2 domain-containing protein( domain architecture ID 48786)

C2 domain-containing protein may be a Ca2+-dependent membrane-targeting protein that binds a wide variety of substances including phospholipids, inositol polyphosphates, and intracellular proteins through its C2 domain

Gene Ontology:  GO:0005509
PubMed:  9632630|8976547

Graphical summary

 Zoom to residue level

show extra options »

Show site features     Horizontal zoom: ×

List of domain hits

 Name Accession Description Interval E-value
C2 super family cl14603
C2 domain; The C2 domain was first identified in PKC. C2 domains fold into an 8-standed ...
 5-85 4.95e-43

C2 domain; 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.


The actual alignment was detected with superfamily member cd08688:

Pssm-ID: 472691 [Multi-domain]  Cd Length: 110  Bit Score: 152.08  E-value: 4.95e-43
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1870200937   5 LKVKIVAGRHLPVMDRASDLTDAFVEV-----------------------------DDEDLQDEPLQITVLDHDTYSAND 55
Cdd:cd08688     1 LKVRVVAARDLPVMDRSSDLTDAFVEVkfgsttyktdvvkkslnpvwnsewfrfevDDEELQDEPLQIRVMDHDTYSAND 80

                          90       100       110
                  ....*....|....*....|....*....|
gi 1870200937  56 AIGKVYIDIDPLLYSEAATVISGWFPIYDT 85
Cdd:cd08688    81 AIGKVYIDLNPLLLKDSVSQISGWFPIYDT 110
 
Name Accession Description Interval E-value
C2_KIAA0528-like cd08688
C2 domain found in the Human KIAA0528 cDNA clone; The members of this CD are named after the ...
 5-85 4.95e-43

C2 domain found in the Human KIAA0528 cDNA clone; The members of this CD are named after the Human KIAA0528 cDNA clone. All members here contain a single C2 repeat. No other information on this protein is currently known. 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: 176070 [Multi-domain]  Cd Length: 110  Bit Score: 152.08  E-value: 4.95e-43
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1870200937   5 LKVKIVAGRHLPVMDRASDLTDAFVEV-----------------------------DDEDLQDEPLQITVLDHDTYSAND 55
Cdd:cd08688     1 LKVRVVAARDLPVMDRSSDLTDAFVEVkfgsttyktdvvkkslnpvwnsewfrfevDDEELQDEPLQIRVMDHDTYSAND 80

                          90       100       110
                  ....*....|....*....|....*....|
gi 1870200937  56 AIGKVYIDIDPLLYSEAATVISGWFPIYDT 85
Cdd:cd08688    81 AIGKVYIDLNPLLLKDSVSQISGWFPIYDT 110
C2 pfam00168
C2 domain;
3-82 3.18e-11

C2 domain;


Pssm-ID: 425499 [Multi-domain]  Cd Length: 104  Bit Score: 60.80  E-value: 3.18e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1870200937   3 GKLKVKIVAGRHLPVMDRaSDLTDAFVEVD---------------------DEDL-------QDEPLQITVLDHDTYSAN 54
Cdd:pfam00168   1 GRLTVTVIEAKNLPPKDG-NGTSDPYVKVYlldgkqkkktkvvkntlnpvwNETFtfsvpdpENAVLEIEVYDYDRFGRD 79

                          90       100
                  ....*....|....*....|....*...
gi 1870200937  55 DAIGKVYIDIDPLLYSEaatVISGWFPI 82
Cdd:pfam00168  80 DFIGEVRIPLSELDSGE---GLDGWYPL 104
C2 smart00239
Protein kinase C conserved region 2 (CalB); Ca2+-binding motif present in phospholipases, ...
 4-68 4.39e-07

Protein kinase C conserved region 2 (CalB); Ca2+-binding motif present in phospholipases, protein kinases C, and synaptotagmins (among others). Some do not appear to contain Ca2+-binding sites. Particular C2s appear to bind phospholipids, inositol polyphosphates, and intracellular proteins. Unusual occurrence in perforin. Synaptotagmin and PLC C2s are permuted in sequence with respect to N- and C-terminal beta strands. SMART detects C2 domains using one or both of two profiles.


Pssm-ID: 214577 [Multi-domain]  Cd Length: 101  Bit Score: 49.02  E-value: 4.39e-07
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1870200937    4 KLKVKIVAGRHLPVMDRaSDLTDAFVEV-----------------------------DDEDLQDEPLQITVLDHDTYSAN 54
Cdd:smart00239   1 TLTVKIISARNLPPKDK-GGKSDPYVKVsldgdpkekkktkvvkntlnpvwnetfefEVPPPELAELEIEVYDKDRFGRD 79

                           90
                   ....*....|....
gi 1870200937   55 DAIGKVYIDIDPLL 68
Cdd:smart00239  80 DFIGQVTIPLSDLL 93
 
Name Accession Description Interval E-value
C2_KIAA0528-like cd08688
C2 domain found in the Human KIAA0528 cDNA clone; The members of this CD are named after the ...
 5-85 4.95e-43

C2 domain found in the Human KIAA0528 cDNA clone; The members of this CD are named after the Human KIAA0528 cDNA clone. All members here contain a single C2 repeat. No other information on this protein is currently known. 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: 176070 [Multi-domain]  Cd Length: 110  Bit Score: 152.08  E-value: 4.95e-43
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1870200937   5 LKVKIVAGRHLPVMDRASDLTDAFVEV-----------------------------DDEDLQDEPLQITVLDHDTYSAND 55
Cdd:cd08688     1 LKVRVVAARDLPVMDRSSDLTDAFVEVkfgsttyktdvvkkslnpvwnsewfrfevDDEELQDEPLQIRVMDHDTYSAND 80

                          90       100       110
                  ....*....|....*....|....*....|
gi 1870200937  56 AIGKVYIDIDPLLYSEAATVISGWFPIYDT 85
Cdd:cd08688    81 AIGKVYIDLNPLLLKDSVSQISGWFPIYDT 110
C2 pfam00168
C2 domain;
3-82 3.18e-11

C2 domain;


Pssm-ID: 425499 [Multi-domain]  Cd Length: 104  Bit Score: 60.80  E-value: 3.18e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1870200937   3 GKLKVKIVAGRHLPVMDRaSDLTDAFVEVD---------------------DEDL-------QDEPLQITVLDHDTYSAN 54
Cdd:pfam00168   1 GRLTVTVIEAKNLPPKDG-NGTSDPYVKVYlldgkqkkktkvvkntlnpvwNETFtfsvpdpENAVLEIEVYDYDRFGRD 79

                          90       100
                  ....*....|....*....|....*...
gi 1870200937  55 DAIGKVYIDIDPLLYSEaatVISGWFPI 82
Cdd:pfam00168  80 DFIGEVRIPLSELDSGE---GLDGWYPL 104
C2 cd00030
C2 domain; The C2 domain was first identified in PKC. C2 domains fold into an 8-standed ...
 5-82 1.13e-08

C2 domain; 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: 175973 [Multi-domain]  Cd Length: 102  Bit Score: 53.61  E-value: 1.13e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1870200937   5 LKVKIVAGRHLPVMDRaSDLTDAFVEV---------------------------DDEDLQDEPLQITVLDHDTYSANDAI 57
Cdd:cd00030     1 LRVTVIEARNLPAKDL-NGKSDPYVKVslggkqkfktkvvkntlnpvwnetfefPVLDPESDTLTVEVWDKDRFSKDDFL 79

                          90       100
                  ....*....|....*....|....*
gi 1870200937  58 GKVYIDIDPLLYSEaaTVISGWFPI 82
Cdd:cd00030    80 GEVEIPLSELLDSG--KEGELWLPL 102
C2 smart00239
Protein kinase C conserved region 2 (CalB); Ca2+-binding motif present in phospholipases, ...
 4-68 4.39e-07

Protein kinase C conserved region 2 (CalB); Ca2+-binding motif present in phospholipases, protein kinases C, and synaptotagmins (among others). Some do not appear to contain Ca2+-binding sites. Particular C2s appear to bind phospholipids, inositol polyphosphates, and intracellular proteins. Unusual occurrence in perforin. Synaptotagmin and PLC C2s are permuted in sequence with respect to N- and C-terminal beta strands. SMART detects C2 domains using one or both of two profiles.


Pssm-ID: 214577 [Multi-domain]  Cd Length: 101  Bit Score: 49.02  E-value: 4.39e-07
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1870200937    4 KLKVKIVAGRHLPVMDRaSDLTDAFVEV-----------------------------DDEDLQDEPLQITVLDHDTYSAN 54
Cdd:smart00239   1 TLTVKIISARNLPPKDK-GGKSDPYVKVsldgdpkekkktkvvkntlnpvwnetfefEVPPPELAELEIEVYDKDRFGRD 79

                           90
                   ....*....|....
gi 1870200937   55 DAIGKVYIDIDPLL 68
Cdd:smart00239  80 DFIGQVTIPLSDLL 93
C2_ArfGAP cd04038
C2 domain present in Arf GTPase Activating Proteins (GAP); ArfGAP is a GTPase activating ...
 2-73 4.77e-05

C2 domain present in Arf GTPase Activating Proteins (GAP); ArfGAP is a GTPase activating protein which regulates the ADP ribosylation factor Arf, a member of the Ras superfamily of GTP-binding proteins. The GTP-bound form of Arf is involved in Golgi morphology and is involved in recruiting coat proteins. ArfGAP is responsible for the GDP-bound form of Arf which is necessary for uncoating the membrane and allowing the Golgi to fuse with an acceptor compartment. These proteins contain an N-terminal ArfGAP domain containing the characteristic zinc finger motif (Cys-x2-Cys-x(16,17)-x2-Cys) and C-terminal C2 domain. C2 domains were first identified in Protein Kinase C (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: 176003 [Multi-domain]  Cd Length: 145  Bit Score: 44.24  E-value: 4.77e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1870200937   2 PGKLKVKIVAGRHLPVMDRASdlTDAFV-------------------EVDDEDLQ------DEPLQITVLDHDTYSANDA 56
Cdd:cd04038     1 LGLLKVRVVRGTNLAVRDFTS--SDPYVvltlgnqkvktrvikknlnPVWNEELTlsvpnpMAPLKLEVFDKDTFSKDDS 78

                          90
                  ....*....|....*..
gi 1870200937  57 IGKVYIDIDPLLysEAA 73
Cdd:cd04038    79 MGEAEIDLEPLV--EAA 93
C2B_RasA1_RasA4 cd04025
C2 domain second repeat present in RasA1 and RasA4; RasA1 and RasA4 are GAP1s (GTPase ...
 30-80 1.02e-03

C2 domain second repeat present in RasA1 and RasA4; RasA1 and RasA4 are GAP1s (GTPase activating protein 1s ), Ras-specific GAP members, which suppresses Ras function by enhancing the GTPase activity of Ras proteins resulting in the inactive GDP-bound form of Ras. In this way it can control cellular proliferation and differentiation. Both proteins contain two C2 domains, a Ras-GAP domain, a plextrin homology (PH)-like domain, and a Bruton's Tyrosine Kinase (BTK) zinc binding domain. 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. This cd contains the second C2 repeat, C2B, and has a type-I topology.


Pssm-ID: 175991 [Multi-domain]  Cd Length: 123  Bit Score: 40.16  E-value: 1.02e-03
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 1870200937  30 EVDDEDLQDEPLQITVLDHDTYSANDAIGKVYIDIDPLLYSEAATvisGWF 80
Cdd:cd04025    52 EFELMEGADSPLSVEVWDWDLVSKNDFLGKVVFSIQTLQQAKQEE---GWF 99
C2B_Synaptotagmin-7 cd08405
C2 domain second repeat present in Synaptotagmin 7; Synaptotagmin is a membrane-trafficking ...
 34-62 3.35e-03

C2 domain second repeat present in Synaptotagmin 7; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. Synaptotagmin 7, a member of class 2 synaptotagmins, is located in presynaptic plasma membranes in neurons, dense-core vesicles in endocrine cells, and lysosomes in fibroblasts. It has been shown to play a role in regulation of Ca2+-dependent lysosomal exocytosis in fibroblasts and may also function as a vesicular Ca2+-sensor. It is distinguished from the other synaptotagmins by having over 12 splice forms. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. 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. This cd contains the second C2 repeat, C2B, and has a type-I topology.


Pssm-ID: 176050 [Multi-domain]  Cd Length: 136  Bit Score: 38.94  E-value: 3.35e-03
                          10        20
                  ....*....|....*....|....*....
gi 1870200937  34 EDLQDEPLQITVLDHDTYSANDAIGKVYI 62
Cdd:cd08405    78 ERLRETTLIITVMDKDRLSRNDLIGKIYL 106
C2E_Ferlin cd04037
C2 domain fifth repeat in Ferlin; Ferlins are involved in vesicle fusion events. Ferlins and ...
 41-64 4.26e-03

C2 domain fifth repeat in Ferlin; Ferlins are involved in vesicle fusion events. Ferlins and other proteins, such as Synaptotagmins, are implicated in facilitating the fusion process when cell membranes fuse together. There are six known human Ferlins: Dysferlin (Fer1L1), Otoferlin (Fer1L2), Myoferlin (Fer1L3), Fer1L4, Fer1L5, and Fer1L6. Defects in these genes can lead to a wide range of diseases including muscular dystrophy (dysferlin), deafness (otoferlin), and infertility (fer-1, fertilization factor-1). Structurally they have 6 tandem C2 domains, designated as (C2A-C2F) and a single C-terminal transmembrane domain, though there is a new study that disputes this and claims that there are actually 7 tandem C2 domains with another C2 domain inserted between C2D and C2E. In a subset of them (Dysferlin, Myoferlin, and Fer1) there is an additional conserved domain called DysF. 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. This cd contains the fifth C2 repeat, C2E, and has a type-II topology.


Pssm-ID: 176002 [Multi-domain]  Cd Length: 124  Bit Score: 38.30  E-value: 4.26e-03
                          10        20
                  ....*....|....*....|....
gi 1870200937  41 LQITVLDHDTYSANDAIGKVYIDI 64
Cdd:cd04037    65 LKISVMDYDLLGSDDLIGETVIDL 88
 
Blast search parameters
Data Source: Precalculated data, version = cdd.v.3.21
Preset Options:Database: CDSEARCH/cdd   Low complexity filter: no  Composition Based Adjustment: yes   E-value threshold: 0.01

References:

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