NCBI Home Page NCBI Site Search page NCBI Guide that lists and describes the NCBI resources
Conserved domains on  [gi|110590998|pdb|2CJT|A]
View 

Chain A, UNC-13 HOMOLOG A

Protein Classification

unc-13 family C2 domain-containing protein( domain architecture ID 10170495)

unc-13 family C2 domain-containing protein, similar to unc-13 homolog A (UNC13A) and B (UNC13B)

Gene Ontology:  GO:0005544|GO:0005509
PubMed:  8976547|9632630

Graphical summary

 Zoom to residue level

show extra options »

Show site features     Horizontal zoom: ×

List of domain hits

 Name Accession Description Interval E-value
C2A_Munc13 cd08394
C2 domain first repeat in Munc13 (mammalian uncoordinated) proteins; C2-like domains are ...
 4-130 1.17e-86

C2 domain first repeat in Munc13 (mammalian uncoordinated) proteins; C2-like domains are thought to be involved in phospholipid binding in a Ca2+ independent manner in both Unc13 and Munc13. Caenorabditis elegans Unc13 has a central domain with sequence similarity to PKC, which includes C1 and C2-related domains. Unc13 binds phorbol esters and DAG with high affinity in a phospholipid manner. Mutations in Unc13 results in abnormal neuronal connections and impairment in cholinergic neurotransmission in the nematode. Munc13 is the mammalian homolog which are expressed in the brain. There are 3 isoforms (Munc13-1, -2, -3) and are thought to play a role in neurotransmitter release and are hypothesized to be high-affinity receptors for phorbol esters. Unc13 and Munc13 contain both C1 and C2 domains. There are two C2 related domains present, one central and one at the carboxyl end. Munc13-1 contains a third C2-like domain. Munc13 interacts with syntaxin, synaptobrevin, and synaptotagmin suggesting a role for these as scaffolding proteins. 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 first C2 repeat, C2A, and has a type-II topology.


:

Pssm-ID: 176040 [Multi-domain]  Cd Length: 127  Bit Score: 248.13  E-value: 1.17e-86
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
2CJT_A        4 MSLLCVGVKKAKFDGAQEKFNTYVTLKVQNVKSTTIAVRGSQPSWEQDFMFEINRLDLGLTVEVWNKGLIWDTMVGTVWI 83
Cdd:cd08394   1 MSLLCVLVKKAKLDGAPDKFNTYVTLKVQNVKSTTIAVRGSQPCWEQDFMFEINRLDLGLVIELWNKGLIWDTLVGTVWI 80

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*..
2CJT_A       84 PLRTIRQSNEEGPGEWLTLDSQAIMADSEICGTKDPTFHRILLDAHF 130
Cdd:cd08394  81 PLSTIRQSNEEGPGEWLTLDSEVNMKNGQIVGTKDPTFHRILLDVRF 127
 
Name Accession Description Interval E-value
C2A_Munc13 cd08394
C2 domain first repeat in Munc13 (mammalian uncoordinated) proteins; C2-like domains are ...
 4-130 1.17e-86

C2 domain first repeat in Munc13 (mammalian uncoordinated) proteins; C2-like domains are thought to be involved in phospholipid binding in a Ca2+ independent manner in both Unc13 and Munc13. Caenorabditis elegans Unc13 has a central domain with sequence similarity to PKC, which includes C1 and C2-related domains. Unc13 binds phorbol esters and DAG with high affinity in a phospholipid manner. Mutations in Unc13 results in abnormal neuronal connections and impairment in cholinergic neurotransmission in the nematode. Munc13 is the mammalian homolog which are expressed in the brain. There are 3 isoforms (Munc13-1, -2, -3) and are thought to play a role in neurotransmitter release and are hypothesized to be high-affinity receptors for phorbol esters. Unc13 and Munc13 contain both C1 and C2 domains. There are two C2 related domains present, one central and one at the carboxyl end. Munc13-1 contains a third C2-like domain. Munc13 interacts with syntaxin, synaptobrevin, and synaptotagmin suggesting a role for these as scaffolding proteins. 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 first C2 repeat, C2A, and has a type-II topology.


Pssm-ID: 176040 [Multi-domain]  Cd Length: 127  Bit Score: 248.13  E-value: 1.17e-86
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
2CJT_A        4 MSLLCVGVKKAKFDGAQEKFNTYVTLKVQNVKSTTIAVRGSQPSWEQDFMFEINRLDLGLTVEVWNKGLIWDTMVGTVWI 83
Cdd:cd08394   1 MSLLCVLVKKAKLDGAPDKFNTYVTLKVQNVKSTTIAVRGSQPCWEQDFMFEINRLDLGLVIELWNKGLIWDTLVGTVWI 80

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*..
2CJT_A       84 PLRTIRQSNEEGPGEWLTLDSQAIMADSEICGTKDPTFHRILLDAHF 130
Cdd:cd08394  81 PLSTIRQSNEEGPGEWLTLDSEVNMKNGQIVGTKDPTFHRILLDVRF 127
C2 pfam00168
C2 domain;
6-102 8.39e-12

C2 domain;


Pssm-ID: 425499 [Multi-domain]  Cd Length: 104  Bit Score: 57.33  E-value: 8.39e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
2CJT_A          6 LLCVGVKKAKF---DGAQEKFNTYVTLKV---QNVKSTTIAVRGSQPSWEQDFMFEI-NRLDLGLTVEVWNKG-LIWDTM 77
Cdd:pfam00168   2 RLTVTVIEAKNlppKDGNGTSDPYVKVYLldgKQKKKTKVVKNTLNPVWNETFTFSVpDPENAVLEIEVYDYDrFGRDDF 81

                          90       100
                  ....*....|....*....|....*
2CJT_A         78 VGTVWIPLRTIRQSneEGPGEWLTL 102
Cdd:pfam00168  82 IGEVRIPLSELDSG--EGLDGWYPL 104
C2 smart00239
Protein kinase C conserved region 2 (CalB); Ca2+-binding motif present in phospholipases, ...
 6-96 1.92e-10

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: 53.65  E-value: 1.92e-10
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
2CJT_A           6 LLCVGVKKAKF---DGAQEKFNTYVTLKVQN----VKSTTIAVRGSQPSWEQDFMFEINRLDLG-LTVEVWNKGLIW-DT 76
Cdd:smart00239   1 TLTVKIISARNlppKDKGGKSDPYVKVSLDGdpkeKKKTKVVKNTLNPVWNETFEFEVPPPELAeLEIEVYDKDRFGrDD 80

                           90       100
                   ....*....|....*....|
2CJT_A          77 MVGTVWIPLRTIRQSNEEGP 96
Cdd:smart00239  81 FIGQVTIPLSDLLLGGRHEK 100
 
Name Accession Description Interval E-value
C2A_Munc13 cd08394
C2 domain first repeat in Munc13 (mammalian uncoordinated) proteins; C2-like domains are ...
 4-130 1.17e-86

C2 domain first repeat in Munc13 (mammalian uncoordinated) proteins; C2-like domains are thought to be involved in phospholipid binding in a Ca2+ independent manner in both Unc13 and Munc13. Caenorabditis elegans Unc13 has a central domain with sequence similarity to PKC, which includes C1 and C2-related domains. Unc13 binds phorbol esters and DAG with high affinity in a phospholipid manner. Mutations in Unc13 results in abnormal neuronal connections and impairment in cholinergic neurotransmission in the nematode. Munc13 is the mammalian homolog which are expressed in the brain. There are 3 isoforms (Munc13-1, -2, -3) and are thought to play a role in neurotransmitter release and are hypothesized to be high-affinity receptors for phorbol esters. Unc13 and Munc13 contain both C1 and C2 domains. There are two C2 related domains present, one central and one at the carboxyl end. Munc13-1 contains a third C2-like domain. Munc13 interacts with syntaxin, synaptobrevin, and synaptotagmin suggesting a role for these as scaffolding proteins. 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 first C2 repeat, C2A, and has a type-II topology.


Pssm-ID: 176040 [Multi-domain]  Cd Length: 127  Bit Score: 248.13  E-value: 1.17e-86
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
2CJT_A        4 MSLLCVGVKKAKFDGAQEKFNTYVTLKVQNVKSTTIAVRGSQPSWEQDFMFEINRLDLGLTVEVWNKGLIWDTMVGTVWI 83
Cdd:cd08394   1 MSLLCVLVKKAKLDGAPDKFNTYVTLKVQNVKSTTIAVRGSQPCWEQDFMFEINRLDLGLVIELWNKGLIWDTLVGTVWI 80

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*..
2CJT_A       84 PLRTIRQSNEEGPGEWLTLDSQAIMADSEICGTKDPTFHRILLDAHF 130
Cdd:cd08394  81 PLSTIRQSNEEGPGEWLTLDSEVNMKNGQIVGTKDPTFHRILLDVRF 127
C2 pfam00168
C2 domain;
6-102 8.39e-12

C2 domain;


Pssm-ID: 425499 [Multi-domain]  Cd Length: 104  Bit Score: 57.33  E-value: 8.39e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
2CJT_A          6 LLCVGVKKAKF---DGAQEKFNTYVTLKV---QNVKSTTIAVRGSQPSWEQDFMFEI-NRLDLGLTVEVWNKG-LIWDTM 77
Cdd:pfam00168   2 RLTVTVIEAKNlppKDGNGTSDPYVKVYLldgKQKKKTKVVKNTLNPVWNETFTFSVpDPENAVLEIEVYDYDrFGRDDF 81

                          90       100
                  ....*....|....*....|....*
2CJT_A         78 VGTVWIPLRTIRQSneEGPGEWLTL 102
Cdd:pfam00168  82 IGEVRIPLSELDSG--EGLDGWYPL 104
C2 smart00239
Protein kinase C conserved region 2 (CalB); Ca2+-binding motif present in phospholipases, ...
 6-96 1.92e-10

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: 53.65  E-value: 1.92e-10
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
2CJT_A           6 LLCVGVKKAKF---DGAQEKFNTYVTLKVQN----VKSTTIAVRGSQPSWEQDFMFEINRLDLG-LTVEVWNKGLIW-DT 76
Cdd:smart00239   1 TLTVKIISARNlppKDKGGKSDPYVKVSLDGdpkeKKKTKVVKNTLNPVWNETFEFEVPPPELAeLEIEVYDKDRFGrDD 80

                           90       100
                   ....*....|....*....|
2CJT_A          77 MVGTVWIPLRTIRQSNEEGP 96
Cdd:smart00239  81 FIGQVTIPLSDLLLGGRHEK 100
C2 cd00030
C2 domain; The C2 domain was first identified in PKC. C2 domains fold into an 8-standed ...
 7-102 1.66e-09

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: 51.30  E-value: 1.66e-09
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
2CJT_A        7 LCVGVKKAKFDGAQEKF---NTYVTLKVQNVKS--TTIAVRGSQPSWEQDFMFEINRLDLG-LTVEVWNKGLIW-DTMVG 79
Cdd:cd00030   1 LRVTVIEARNLPAKDLNgksDPYVKVSLGGKQKfkTKVVKNTLNPVWNETFEFPVLDPESDtLTVEVWDKDRFSkDDFLG 80

                        90       100
                ....*....|....*....|...
2CJT_A       80 TVWIPLRTIRQSNEEGPgEWLTL 102
Cdd:cd00030  81 EVEIPLSELLDSGKEGE-LWLPL 102
C2B_MCTP_PRT_plant cd08378
C2 domain second repeat found in Multiple C2 domain and Transmembrane region Proteins (MCTP); ...
 25-86 4.20e-06

C2 domain second repeat found in Multiple C2 domain and Transmembrane region Proteins (MCTP); plant subset; MCTPs are involved in Ca2+ signaling at the membrane. Plant-MCTPs are composed of a variable N-terminal sequence, four C2 domains, two transmembrane regions (TMRs), and a short C-terminal sequence. It is one of four protein classes that are anchored to membranes via a transmembrane region; the others being synaptotagmins, extended synaptotagmins, and ferlins. MCTPs are the only membrane-bound C2 domain proteins that contain two functional TMRs. MCTPs are unique in that they bind Ca2+ but not phospholipids. 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-II topology.


Pssm-ID: 176024 [Multi-domain]  Cd Length: 121  Bit Score: 42.69  E-value: 4.20e-06
                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....
2CJT_A       25 TYVTLKVQNVKSTTIAV-RGSQPSWEQDFMFEINRLDLG-LTVEVWNKGLIWDTMVGTVW-----IPLR 86
Cdd:cd08378  19 PVVEVKLGNYKGSTKAIeRTSNPEWNQVFAFSKDRLQGStLEVSVWDKDKAKDDFLGGVCfdlseVPTR 87
C2A_RasGAP cd08383
C2 domain (first repeat) of Ras GTPase activating proteins (GAPs); RasGAPs suppress Ras ...
 24-115 6.54e-05

C2 domain (first repeat) of Ras GTPase activating proteins (GAPs); RasGAPs suppress 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. The proteins here all contain either a single C2 domain or two tandem C2 domains, a Ras-GAP domain, and a pleckstrin homology (PH)-like 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. Members here have a type-I topology.


Pssm-ID: 176029 [Multi-domain]  Cd Length: 117  Bit Score: 39.55  E-value: 6.54e-05
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
2CJT_A       24 NTYVTLKVQNVK-STTIAVRGSQPSWEQDFMFEINRLDLG-LTVEVWNKGliWDTM---VGTVWIPLRtiRQSNEEGPGE 98
Cdd:cd08383  19 DPYCTVSLDQVEvARTKTVEKLNPFWGEEFVFDDPPPDVTfFTLSFYNKD--KRSKdrdIVIGKVALS--KLDLGQGKDE 94

                        90
                ....*....|....*..
2CJT_A       99 WLTLdsQAIMADSEICG 115
Cdd:cd08383  95 WFPL--TPVDPDSEVQG 109
C2_PLC_like cd00275
C2 domain present in Phosphoinositide-specific phospholipases C (PLC); PLCs are involved in ...
 16-90 1.86e-04

C2 domain present in Phosphoinositide-specific phospholipases C (PLC); PLCs are involved in the hydrolysis of phosphatidylinositol-4,5-bisphosphate (PIP2) to d-myo-inositol-1,4,5-trisphosphate (1,4,5-IP3) and sn-1,2-diacylglycerol (DAG). 1,4,5-IP3 and DAG are second messengers in eukaryotic signal transduction cascades. PLC is composed of a N-terminal PH domain followed by a series of EF hands, a catalytic TIM barrel and a C-terminal C2 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. Members here have a type-II topology.


Pssm-ID: 175974 [Multi-domain]  Cd Length: 128  Bit Score: 38.68  E-value: 1.86e-04
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
2CJT_A       16 FDGAQEKFNTYVTLKV------QNVKSTTIAVR--GSQPSWEQDFMFEINRLDLG-LTVEVWNKGLIWDTMVGTVWIPLR 86
Cdd:cd00275  18 KGDKGSIVDPYVEVEIhglpadDSAKFKTKVVKnnGFNPVWNETFEFDVTVPELAfLRFVVYDEDSGDDDFLGQACLPLD 97


                ....
2CJT_A       87 TIRQ 90
Cdd:cd00275  98 SLRQ 101
C2B_Tricalbin-like cd04052
C2 domain second repeat present in Tricalbin-like proteins; 5 to 6 copies of the C2 domain are ...
 17-104 1.01e-03

C2 domain second repeat present in Tricalbin-like proteins; 5 to 6 copies of the C2 domain are present in Tricalbin, a yeast homolog of Synaptotagmin, which is involved in membrane trafficking and sorting. 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-II topology.


Pssm-ID: 176017 [Multi-domain]  Cd Length: 111  Bit Score: 36.43  E-value: 1.01e-03
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
2CJT_A       17 DGAQEKFNTYVTLKVQN--VKSTTIAVRGSQPSWEQDFMFEI-NRLDLGLTVEVWNKGLIWDTMVGTVWIPLRTIRQSNE 93
Cdd:cd04052   7 ESKTGLLSPYAELYLNGklVYTTRVKKKTNNPSWNASTEFLVtDRRKSRVTVVVKDDRDRHDPVLGSVSISLNDLIDATS 86

                        90
                ....*....|.
2CJT_A       94 EGpGEWLTLDS 104
Cdd:cd04052  87 VG-QQWFPLSG 96
C2B_Synaptotagmin-like cd04050
C2 domain second repeat present in Synaptotagmin-like proteins; Synaptotagmin is a ...
 24-104 1.23e-03

C2 domain second repeat present in Synaptotagmin-like proteins; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. 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: 176015 [Multi-domain]  Cd Length: 105  Bit Score: 36.00  E-value: 1.23e-03
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
2CJT_A       24 NTYVTLKVQNV-KSTTIAVRGSQPSWEQDFMFEINRLDLG-LTVEVWNKGLiwDTMVGTVWIPLRTIRQSNEEGPGEWLT 101
Cdd:cd04050  22 SPYVELTVGKTtQKSKVKERTNNPVWEEGFTFLVRNPENQeLEIEVKDDKT--GKSLGSLTLPLSELLKEPDLTLDQPFP 99


                ...
2CJT_A      102 LDS 104
Cdd:cd04050 100 LDN 102
C2C_MCTP_PRT_plant cd04019
C2 domain third repeat found in Multiple C2 domain and Transmembrane region Proteins (MCTP); ...
 27-131 1.74e-03

C2 domain third repeat found in Multiple C2 domain and Transmembrane region Proteins (MCTP); plant subset; MCTPs are involved in Ca2+ signaling at the membrane. Plant-MCTPs are composed of a variable N-terminal sequence, four C2 domains, two transmembrane regions (TMRs), and a short C-terminal sequence. It is one of four protein classes that are anchored to membranes via a transmembrane region; the others being synaptotagmins, extended synaptotagmins, and ferlins. MCTPs are the only membrane-bound C2 domain proteins that contain two functional TMRs. MCTPs are unique in that they bind Ca2+ but not phospholipids. 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 third C2 repeat, C2C, and has a type-II topology.


Pssm-ID: 175986 [Multi-domain]  Cd Length: 150  Bit Score: 36.11  E-value: 1.74e-03
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
2CJT_A       27 VTLKVQNVKSTTIAVRGSQPSWEQDFMF---EINRLDLGLTVEVwNKGLIWDTMVGTVWIPLRTI--RQSNEEGPGEWLT 101
Cdd:cd04019  27 AQLGNQVLRTRPSQTRNGNPSWNEELMFvaaEPFEDHLILSVED-RVGPNKDEPLGRAVIPLNDIerRVDDRPVPSRWFS 105

                        90       100       110
                ....*....|....*....|....*....|
2CJT_A      102 LdSQAIMADSEicGTKDPTFHRILLDAHFE 131
Cdd:cd04019 106 L-ERPGGAMEQ--KKKRKFASRIHLRLCLD 132
C2A_Munc13-like cd08676
C2 domain first repeat in Munc13 (mammalian uncoordinated)-like proteins; C2-like domains are ...
 29-102 3.84e-03

C2 domain first repeat in Munc13 (mammalian uncoordinated)-like proteins; C2-like domains are thought to be involved in phospholipid binding in a Ca2+ independent manner in both Unc13 and Munc13. Caenorabditis elegans Unc13 has a central domain with sequence similarity to PKC, which includes C1 and C2-related domains. Unc13 binds phorbol esters and DAG with high affinity in a phospholipid manner. Mutations in Unc13 results in abnormal neuronal connections and impairment in cholinergic neurotransmission in the nematode. Munc13 is the mammalian homolog which are expressed in the brain. There are 3 isoforms (Munc13-1, -2, -3) and are thought to play a role in neurotransmitter release and are hypothesized to be high-affinity receptors for phorbol esters. Unc13 and Munc13 contain both C1 and C2 domains. There are two C2 related domains present, one central and one at the carboxyl end. Munc13-1 contains a third C2-like domain. Munc13 interacts with syntaxin, synaptobrevin, and synaptotagmin suggesting a role for these as scaffolding proteins. 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-II topology.


Pssm-ID: 176058 [Multi-domain]  Cd Length: 153  Bit Score: 35.42  E-value: 3.84e-03
                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
2CJT_A       29 LKVQNVKSTTIavrgsQPSWEQDFMFEINRLDLG-LTVEVWNKGliwDTMVGTVWIPLRTIRQSNEEgpgEWLTL 102
Cdd:cd08676  90 IKVTEVKPQTL-----NPVWNETFRFEVEDVSNDqLHLDIWDHD---DDFLGCVNIPLKDLPSCGLD---SWFKL 153
C2A_RasA2_RasA3 cd08401
C2 domain first repeat present in RasA2 and RasA3; RasA2 and RasA3 are GAP1s (GTPase ...
 18-115 4.63e-03

C2 domain first repeat present in RasA2 and RasA3; RasA2 and RasA3 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. RasA2 and RasA3 are both inositol 1,3,4,5-tetrakisphosphate-binding proteins and contain an N-terminal C2 domain, a Ras-GAP domain, a pleckstrin-homology (PH) domain which localizes it to the plasma membrane, and Bruton's Tyrosine Kinase (BTK) a 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 first C2 repeat, C2A, and has a type-I topology.


Pssm-ID: 176046 [Multi-domain]  Cd Length: 121  Bit Score: 34.72  E-value: 4.63e-03
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
2CJT_A       18 GAQEKFNTYVTLKV--QNVKSTTIAVRGSQPSWEQDFMFEINRLDLGLTVEVWNKGLIW-DTMVGTVWIPLRTIRQSNee 94
Cdd:cd08401  17 GPNKMRDCYCTVNLdqEEVFRTKTVEKSLCPFFGEDFYFEIPRTFRHLSFYIYDRDVLRrDSVIGKVAIKKEDLHKYY-- 94

                        90       100
                ....*....|....*....|.
2CJT_A       95 GPGEWLTLdsQAIMADSEICG 115
Cdd:cd08401  95 GKDTWFPL--QPVDADSEVQG 113
C2_Calpain cd04046
C2 domain present in Calpain proteins; A single C2 domain is found in calpains (EC 3.4.22.52, ...
 9-81 5.16e-03

C2 domain present in Calpain proteins; A single C2 domain is found in calpains (EC 3.4.22.52, EC 3.4.22.53), calcium-dependent, non-lysosomal cysteine proteases. Caplains are classified as belonging to Clan CA by MEROPS and include six families: C1, C2, C10, C12, C28, and C47. 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: 176011 [Multi-domain]  Cd Length: 126  Bit Score: 34.56  E-value: 5.16e-03
                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
2CJT_A        9 VGVKKAKFDGAQEKF---NTYVTLKVQNVKSTTIAVRG-SQPSWEQDFMFEINRLDLGLTVEVWNKGLIWDTMVGTV 81
Cdd:cd04046   7 VHVHSAEGLSKQDSGggaDPYVIIKCEGESVRSPVQKDtLSPEFDTQAIFYRKKPRSPIKIQVWNSNLLCDEFLGQA 83
C2B_RasGAP cd08675
C2 domain second repeat of Ras GTPase activating proteins (GAPs); RasGAPs suppress Ras ...
 25-92 8.10e-03

C2 domain second repeat of Ras GTPase activating proteins (GAPs); RasGAPs suppress 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. The proteins here all contain two tandem C2 domains, a Ras-GAP domain, and a pleckstrin homology (PH)-like 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. Members here have a type-I topology.


Pssm-ID: 176057 [Multi-domain]  Cd Length: 137  Bit Score: 34.27  E-value: 8.10e-03
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
2CJT_A       25 TYVTLKVQNVKSTTIAVRGSQPSWEQDFMFEINRL----------------DLGLTVEVWNKGLIW-DTMVGTVWIPLRT 87
Cdd:cd08675  26 TLNYSSKTDTKRTKVKKKTNNPRFDEAFYFELTIGfsyekksfkveeedleKSELRVELWHASMVSgDDFLGEVRIPLQG 105


                ....*
2CJT_A       88 IRQSN 92
Cdd:cd08675 106 LQQAG 110
 
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