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Conserved domains on  [gi|2102677298|ref|XP_043800793|]
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ras GTPase-activating protein 3 isoform X3 [Apis laboriosa]

Protein Classification

synaptotagmin family protein; RIM/PCLO family C2 domain-containing protein( domain architecture ID 10325932)

synaptotagmin family protein is a membrane-trafficking protein characterized by an N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains; similar to synaptotagmins 4 and 11, which do not bind calcium| RIM (Rab-3-interacting molecule)/PCLO (protein piccolo) family C2 domain-containing protein

Graphical summary

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List of domain hits

 Name Accession Description Interval E-value
RasGAP_GAP1_like cd05128
Ras-GTPase Activating Domain of GAP1 and similar proteins; The GAP1 family of Ras ...
 311-579 5.79e-149

Ras-GTPase Activating Domain of GAP1 and similar proteins; The GAP1 family of Ras GTPase-activating proteins includes GAP1(m) (or RASA2), GAP1_IP4BP (or RASA3), Ca2+ -promoted Ras inactivator (CAPRI, or RASAL4), and Ras GTPase activating-like proteins (RASAL) or RASAL1. The members are characterized by a conserved domain structure comprising N-terminal tandem C2 domains, a highly conserved central RasGAP domain, and a C-terminal pleckstrin homology domain that is associated with a Bruton's tyrosine kinase motif. While this domain structure is conserved, a small change in the function of each individual domain and the interaction between domains has a marked effect on the regulation of each protein.


:

Pssm-ID: 213330  Cd Length: 269  Bit Score: 443.23  E-value: 5.79e-149
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2102677298  311 MYDRLRNLLLQSVNIQPITSSAVYILGEIVS-SKMEAAQPLVRVLVHYGQLVSVMRALASHEISKLTDPTTIFRGNTLVS 389
Cdd:cd05128      2 YYEPLLNLLLESLDVPPFTASAVYLLEELVKvDKDDVARPLVRIFLHHGQIVPLLRALASREISKTQDPNTLFRGNSLAS 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2102677298  390 KMMDEGMRLAGLHYLHSTLRPAMKQVFLEKKSCEIDPTRVKDANTIQTNLTNLKEYVERVFIAITTSGVRCPSLMCEMFW 469
Cdd:cd05128     82 KCMDEFMKLVGMQYLHETLKPVIDEIFSEKKSCEIDPSKLKDGEVLETNLANLRGYVERVFKAITSSARRCPTLMCEIFS 161

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2102677298  470 CLKELAATHFPKNKEVRYSVISGFIFLRFFAPAILGPRLFDITTEQIDSQTNRTLTLISKTIQSLGNLVSCRGgaGSVCK 549
Cdd:cd05128    162 DLRESAAQRFPDNEDVPYTAVSGFIFLRFFAPAILNPKLFGLREEHPDPQTARTLTLISKTIQTLGNLGSSSS--GLGVK 239

                          250       260       270
                   ....*....|....*....|....*....|
gi 2102677298  550 EEYMECVYREFYTEKHIQAVKQFLELISTS 579
Cdd:cd05128    240 EAYMSPLYERFTDEQHVDAVKKFLDRISSV 269
C2B_RasA3 cd04010
C2 domain second repeat present in RAS p21 protein activator 3 (RasA3); RasA3 are members of ...
 145-300 1.91e-69

C2 domain second repeat present in RAS p21 protein activator 3 (RasA3); RasA3 are members of GTPase activating protein 1 (GAP1), a Ras-specific GAP, 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. RasA3 contains an N-terminal C2 domain, 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: 175977 [Multi-domain]  Cd Length: 148  Bit Score: 228.05  E-value: 1.91e-69
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2102677298  145 KLTVRVIECSELTIKNGGCDPFAIVTVIYSNGKQVLKRTKIKKKTVSPYFNETFIFEPEITESKEKDISHYSLEHGEVNE 224
Cdd:cd04010      1 KLSVRVIECSDLALKNGTCDPYASVTLIYSNKKQDTKRTKVKKKTNNPQFDEAFYFDVTIDSSPEKKQFEMPEEDAEKLE 80

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 2102677298  225 VIVGLWHASsgMGEQPAFLGEVRVTLRGLQkQSTNSTTAWYFLQPRAVKHRPNkisnsSTSPGVLPGLGSLRLKIH 300
Cdd:cd04010     81 LRVDLWHAS--MGGGDVFLGEVRIPLRGLD-LQAGSHQAWYFLQPREEKSTPP-----GTRSSKDNSLGSLRLKIN 148
C2 super family cl14603
C2 domain; The C2 domain was first identified in PKC. C2 domains fold into an 8-standed ...
 14-135 6.77e-63

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 cd08401:

Pssm-ID: 472691 [Multi-domain]  Cd Length: 121  Bit Score: 208.44  E-value: 6.77e-63
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2102677298   14 LKIKIGEVKNLQSRNHgSPGARDVYCVLSLDQEEIFRTTTMERTLNPFFGEEFQFEVPRKFRYLGIYVYDRDRhLKQDKI 93
Cdd:cd08401      2 LKIKIGEAKNLPPRSG-PNKMRDCYCTVNLDQEEVFRTKTVEKSLCPFFGEDFYFEIPRTFRHLSFYIYDRDV-LRRDSV 79

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|..
gi 2102677298   94 LGKVAIKREDLTTYHNKEHWFPLRPVDADSEVQGKAHLEISL 135
Cdd:cd08401     80 IGKVAIKKEDLHKYYGKDTWFPLQPVDADSEVQGKVHLELRL 121
PH_GAP1-like cd01244
RAS p21 protein activator (GTPase activating protein) family pleckstrin homology (PH) domain; ...
 600-705 1.33e-56

RAS p21 protein activator (GTPase activating protein) family pleckstrin homology (PH) domain; RASAL1, GAP1(m), GAP1(IP4BP), and CAPRI are all members of the GAP1 family of GTPase-activating proteins. They contain N-terminal SH2-SH3-SH2 domains, followed by two C2 domains, a PH domain, a RasGAP domain, and a BTK domain. With the notable exception of GAP1(m), they all possess an arginine finger-dependent GAP activity on the Ras-related protein Rap1. They act as a suppressor of RAS enhancing the weak intrinsic GTPase activity of RAS proteins resulting in the inactive GDP-bound form of RAS, allowing control of cellular proliferation and differentiation. PH domains share little sequence conservation, but all have a common fold, which is electrostatically polarized. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


:

Pssm-ID: 269950  Cd Length: 107  Bit Score: 190.58  E-value: 1.33e-56
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2102677298  600 KEGVMIKRAQGRK-RFGRKNFKQRYFKLTTQDLSYSKTKGKEPLCKIPLEEILAVEKLHEDSFKMKNIFQIIQSQRALYV 678
Cdd:cd01244      1 KEGYLIKRAQGRKkKFGRKNFKKRYFRLTNEALSYSKSKGKQPLCSIPLEDILAVERVEEESFKMKNMFQIVQPDRTLYL 80

                           90       100
                   ....*....|....*....|....*..
gi 2102677298  679 QAGNCVEEKEWIDILTKICRTNSNRLE 705
Cdd:cd01244     81 QAKNVVELNEWLSALRKVCLCNPNRLP 107
BTK smart00107
Bruton's tyrosine kinase Cys-rich motif; Zinc-binding motif containing conserved cysteines and ...
 700-735 1.83e-13

Bruton's tyrosine kinase Cys-rich motif; Zinc-binding motif containing conserved cysteines and a histidine. Always found C-terminal to PH domains (but not all PH domains are followed by BTK motifs). The crystal structure shows this motif packs against the PH domain. The PH+Btk module pair has been called the Tec homology (TH) region.


:

Pssm-ID: 128417  Cd Length: 36  Bit Score: 65.10  E-value: 1.83e-13
                            10        20        30
                    ....*....|....*....|....*....|....*.
gi 2102677298   700 NSNRLEKYHPSAYINGHWLCCKAIAEIAPGCSEVSP 735
Cdd:smart00107    1 NNNLLQKYHPSFWVDGKWLCCQQSEKNAPGCTPYEA 36
 
Name Accession Description Interval E-value
RasGAP_GAP1_like cd05128
Ras-GTPase Activating Domain of GAP1 and similar proteins; The GAP1 family of Ras ...
 311-579 5.79e-149

Ras-GTPase Activating Domain of GAP1 and similar proteins; The GAP1 family of Ras GTPase-activating proteins includes GAP1(m) (or RASA2), GAP1_IP4BP (or RASA3), Ca2+ -promoted Ras inactivator (CAPRI, or RASAL4), and Ras GTPase activating-like proteins (RASAL) or RASAL1. The members are characterized by a conserved domain structure comprising N-terminal tandem C2 domains, a highly conserved central RasGAP domain, and a C-terminal pleckstrin homology domain that is associated with a Bruton's tyrosine kinase motif. While this domain structure is conserved, a small change in the function of each individual domain and the interaction between domains has a marked effect on the regulation of each protein.


Pssm-ID: 213330  Cd Length: 269  Bit Score: 443.23  E-value: 5.79e-149
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2102677298  311 MYDRLRNLLLQSVNIQPITSSAVYILGEIVS-SKMEAAQPLVRVLVHYGQLVSVMRALASHEISKLTDPTTIFRGNTLVS 389
Cdd:cd05128      2 YYEPLLNLLLESLDVPPFTASAVYLLEELVKvDKDDVARPLVRIFLHHGQIVPLLRALASREISKTQDPNTLFRGNSLAS 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2102677298  390 KMMDEGMRLAGLHYLHSTLRPAMKQVFLEKKSCEIDPTRVKDANTIQTNLTNLKEYVERVFIAITTSGVRCPSLMCEMFW 469
Cdd:cd05128     82 KCMDEFMKLVGMQYLHETLKPVIDEIFSEKKSCEIDPSKLKDGEVLETNLANLRGYVERVFKAITSSARRCPTLMCEIFS 161

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2102677298  470 CLKELAATHFPKNKEVRYSVISGFIFLRFFAPAILGPRLFDITTEQIDSQTNRTLTLISKTIQSLGNLVSCRGgaGSVCK 549
Cdd:cd05128    162 DLRESAAQRFPDNEDVPYTAVSGFIFLRFFAPAILNPKLFGLREEHPDPQTARTLTLISKTIQTLGNLGSSSS--GLGVK 239

                          250       260       270
                   ....*....|....*....|....*....|
gi 2102677298  550 EEYMECVYREFYTEKHIQAVKQFLELISTS 579
Cdd:cd05128    240 EAYMSPLYERFTDEQHVDAVKKFLDRISSV 269
RasGAP smart00323
GTPase-activator protein for Ras-like GTPases; All alpha-helical domain that accelerates the ...
 292-635 1.52e-103

GTPase-activator protein for Ras-like GTPases; All alpha-helical domain that accelerates the GTPase activity of Ras, thereby "switching" it into an "off" position. Improved domain limits from structure.


Pssm-ID: 214617  Cd Length: 344  Bit Score: 327.34  E-value: 1.52e-103
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2102677298   292 LGSLRLKIHYTADHVFPSAMYDRLRNLLLQSVNiqpitSSAVYILGEIVS--SKMEAAQPLVRVLVHYGQLVSVMRALAS 369
Cdd:smart00323    6 LGSLRLKTVYTTDFILPSEYYEELLELLLFSLD-----LSLASALSEVCSglDKDELATKLVRLFLRRGRGHPFLRALID 80

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2102677298   370 HEISKLTDPTTIFRGNTLVSKMMDEGMRLAGLHYLHSTLRPAMKQVFLEKKSCEIDPTRVKDANtIQTNLTNLKEYVERV 449
Cdd:smart00323   81 PEVERTDDPNTIFRGNSLATKSMEVYMKLVGNQYLHTTLKPVLKKIVESKKSCEVDPAKLEGED-LETNLENLLQYVERL 159

                           170       180       190       200       210       220       230       240
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2102677298   450 FIAITTSGVRCPSLMCEMFWCLKELAATHFPkNKEVRYSVISGFIFLRFFAPAILGPRLFDITTEQIDSQTNRTLTLISK 529
Cdd:smart00323  160 FDAIINSSDRLPYGLRDICKQLRQAAEKRFP-DADVIYKAVSSFVFLRFFCPAIVSPKLFNLVDEHPDPTTRRTLTLIAK 238

                           250       260       270       280       290       300       310       320
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2102677298   530 TIQSLGNLVScrggagSVCKEEYMECVyrEFYTEKHIQAVKQFLELISTSSNSNIAKQRTSTQ-------QEQPIVLKEG 602
Cdd:smart00323  239 VLQNLANLSE------FGSKEPWMEPL--NDFLLSHKDRVKDFLDELSSVPEILVDKVSDSTTisgrelsLLHSLLLENG 310

                           330       340       350
                    ....*....|....*....|....*....|....
gi 2102677298   603 VMIKRAQG-RKRFGRKNFKQRYFKLTTQDLSYSK 635
Cdd:smart00323  311 DALKRELNnEDPLGKLLFKLRYFGLTTHELTYGK 344
C2B_RasA3 cd04010
C2 domain second repeat present in RAS p21 protein activator 3 (RasA3); RasA3 are members of ...
 145-300 1.91e-69

C2 domain second repeat present in RAS p21 protein activator 3 (RasA3); RasA3 are members of GTPase activating protein 1 (GAP1), a Ras-specific GAP, 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. RasA3 contains an N-terminal C2 domain, 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: 175977 [Multi-domain]  Cd Length: 148  Bit Score: 228.05  E-value: 1.91e-69
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2102677298  145 KLTVRVIECSELTIKNGGCDPFAIVTVIYSNGKQVLKRTKIKKKTVSPYFNETFIFEPEITESKEKDISHYSLEHGEVNE 224
Cdd:cd04010      1 KLSVRVIECSDLALKNGTCDPYASVTLIYSNKKQDTKRTKVKKKTNNPQFDEAFYFDVTIDSSPEKKQFEMPEEDAEKLE 80

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 2102677298  225 VIVGLWHASsgMGEQPAFLGEVRVTLRGLQkQSTNSTTAWYFLQPRAVKHRPNkisnsSTSPGVLPGLGSLRLKIH 300
Cdd:cd04010     81 LRVDLWHAS--MGGGDVFLGEVRIPLRGLD-LQAGSHQAWYFLQPREEKSTPP-----GTRSSKDNSLGSLRLKIN 148
C2A_RasA2_RasA3 cd08401
C2 domain first repeat present in RasA2 and RasA3; RasA2 and RasA3 are GAP1s (GTPase ...
 14-135 6.77e-63

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: 208.44  E-value: 6.77e-63
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2102677298   14 LKIKIGEVKNLQSRNHgSPGARDVYCVLSLDQEEIFRTTTMERTLNPFFGEEFQFEVPRKFRYLGIYVYDRDRhLKQDKI 93
Cdd:cd08401      2 LKIKIGEAKNLPPRSG-PNKMRDCYCTVNLDQEEVFRTKTVEKSLCPFFGEDFYFEIPRTFRHLSFYIYDRDV-LRRDSV 79

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|..
gi 2102677298   94 LGKVAIKREDLTTYHNKEHWFPLRPVDADSEVQGKAHLEISL 135
Cdd:cd08401     80 IGKVAIKKEDLHKYYGKDTWFPLQPVDADSEVQGKVHLELRL 121
PH_GAP1-like cd01244
RAS p21 protein activator (GTPase activating protein) family pleckstrin homology (PH) domain; ...
 600-705 1.33e-56

RAS p21 protein activator (GTPase activating protein) family pleckstrin homology (PH) domain; RASAL1, GAP1(m), GAP1(IP4BP), and CAPRI are all members of the GAP1 family of GTPase-activating proteins. They contain N-terminal SH2-SH3-SH2 domains, followed by two C2 domains, a PH domain, a RasGAP domain, and a BTK domain. With the notable exception of GAP1(m), they all possess an arginine finger-dependent GAP activity on the Ras-related protein Rap1. They act as a suppressor of RAS enhancing the weak intrinsic GTPase activity of RAS proteins resulting in the inactive GDP-bound form of RAS, allowing control of cellular proliferation and differentiation. PH domains share little sequence conservation, but all have a common fold, which is electrostatically polarized. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 269950  Cd Length: 107  Bit Score: 190.58  E-value: 1.33e-56
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2102677298  600 KEGVMIKRAQGRK-RFGRKNFKQRYFKLTTQDLSYSKTKGKEPLCKIPLEEILAVEKLHEDSFKMKNIFQIIQSQRALYV 678
Cdd:cd01244      1 KEGYLIKRAQGRKkKFGRKNFKKRYFRLTNEALSYSKSKGKQPLCSIPLEDILAVERVEEESFKMKNMFQIVQPDRTLYL 80

                           90       100
                   ....*....|....*....|....*..
gi 2102677298  679 QAGNCVEEKEWIDILTKICRTNSNRLE 705
Cdd:cd01244     81 QAKNVVELNEWLSALRKVCLCNPNRLP 107
RasGAP pfam00616
GTPase-activator protein for Ras-like GTPase; All alpha-helical domain that accelerates the ...
 363-536 4.41e-34

GTPase-activator protein for Ras-like GTPase; All alpha-helical domain that accelerates the GTPase activity of Ras, thereby "switching" it into an "off" position.


Pssm-ID: 459871  Cd Length: 207  Bit Score: 130.10  E-value: 4.41e-34
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2102677298  363 VMRALASHEISKLTDPTTIFRGNTLVSKMMDEGMRLA-GLHYLHSTLRPAMKQVFL-EKKSCEIDPTRVKDA-------- 432
Cdd:pfam00616    1 LISELIEEEIESSDNPNDLLRGNSLVSKLLETYNRRPrGQEYLKKVLGPLVRKIIEdEDLDLESDPRKIYESlinqeelk 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2102677298  433 ----------------------NTIQTNLTNLKEYVERVFIAITTSGVRCPSLMCEMFWCLKELAATHFP-KNKEVRYSV 489
Cdd:pfam00616   81 tgrsdlprdvspeeaiedpevrQIFEDNLQKLRELADEFLDAIYSSLNQLPYGIRYICKQLYELLEEKFPdASEEEILNA 160

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|....*..
gi 2102677298  490 ISGFIFLRFFAPAILGPRLFDITTEQIDSQTNRTLTLISKTIQSLGN 536
Cdd:pfam00616  161 IGGFLFLRFFCPAIVNPDLFGLVDHQISPKQRRNLTLIAKVLQNLAN 207
C2 pfam00168
C2 domain;
13-116 2.85e-19

C2 domain;


Pssm-ID: 425499 [Multi-domain]  Cd Length: 104  Bit Score: 83.91  E-value: 2.85e-19
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2102677298   13 RLKIKIGEVKNLQSRNhgSPGARDVYCVLSL-DQEEIFRTTTMERTLNPFFGEEFQFEVP-RKFRYLGIYVYDRDRhLKQ 90
Cdd:pfam00168    2 RLTVTVIEAKNLPPKD--GNGTSDPYVKVYLlDGKQKKKTKVVKNTLNPVWNETFTFSVPdPENAVLEIEVYDYDR-FGR 78

                           90       100
                   ....*....|....*....|....*.
gi 2102677298   91 DKILGKVAIKREDLTTYHNKEHWFPL 116
Cdd:pfam00168   79 DDFIGEVRIPLSELDSGEGLDGWYPL 104
C2 smart00239
Protein kinase C conserved region 2 (CalB); Ca2+-binding motif present in phospholipases, ...
 13-113 1.64e-16

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: 75.99  E-value: 1.64e-16
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2102677298    13 RLKIKIGEVKNLQSRNhgSPGARDVYCVLSLDQE--EIFRTTTMERTLNPFFGEEFQFEV-PRKFRYLGIYVYDRDRhLK 89
Cdd:smart00239    1 TLTVKIISARNLPPKD--KGGKSDPYVKVSLDGDpkEKKKTKVVKNTLNPVWNETFEFEVpPPELAELEIEVYDKDR-FG 77

                            90       100
                    ....*....|....*....|....
gi 2102677298    90 QDKILGKVAIKREDLTTYHNKEHW 113
Cdd:smart00239   78 RDDFIGQVTIPLSDLLLGGRHEKL 101
C2 pfam00168
C2 domain;
145-265 6.46e-14

C2 domain;


Pssm-ID: 425499 [Multi-domain]  Cd Length: 104  Bit Score: 68.50  E-value: 6.46e-14
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2102677298  145 KLTVRVIECSELTIK--NGGCDPFAIVTVIYSNGKqvlKRTKIKKKTVSPYFNETFIFEpeiteskekdishysLEHGEV 222
Cdd:pfam00168    2 RLTVTVIEAKNLPPKdgNGTSDPYVKVYLLDGKQK---KKTKVVKNTLNPVWNETFTFS---------------VPDPEN 63

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|...
gi 2102677298  223 NEVIVGLWHASSGMGEQpaFLGEVRVTLRGLQKQSTNSTtaWY 265
Cdd:pfam00168   64 AVLEIEVYDYDRFGRDD--FIGEVRIPLSELDSGEGLDG--WY 102
BTK smart00107
Bruton's tyrosine kinase Cys-rich motif; Zinc-binding motif containing conserved cysteines and ...
 700-735 1.83e-13

Bruton's tyrosine kinase Cys-rich motif; Zinc-binding motif containing conserved cysteines and a histidine. Always found C-terminal to PH domains (but not all PH domains are followed by BTK motifs). The crystal structure shows this motif packs against the PH domain. The PH+Btk module pair has been called the Tec homology (TH) region.


Pssm-ID: 128417  Cd Length: 36  Bit Score: 65.10  E-value: 1.83e-13
                            10        20        30
                    ....*....|....*....|....*....|....*.
gi 2102677298   700 NSNRLEKYHPSAYINGHWLCCKAIAEIAPGCSEVSP 735
Cdd:smart00107    1 NNNLLQKYHPSFWVDGKWLCCQQSEKNAPGCTPYEA 36
BTK pfam00779
BTK motif; Zinc-binding motif containing conserved cysteines and a histidine. Always found ...
 706-735 2.96e-13

BTK motif; Zinc-binding motif containing conserved cysteines and a histidine. Always found C-terminal to PH domains. The crystal structure shows this motif packs against the PH domain. The PH+Btk module pair has been called the Tec homology (TH) region.


Pssm-ID: 459937  Cd Length: 30  Bit Score: 64.47  E-value: 2.96e-13
                           10        20        30
                   ....*....|....*....|....*....|
gi 2102677298  706 KYHPSAYINGHWLCCKAIAEIAPGCSEVSP 735
Cdd:pfam00779    1 KYHPGAFVDGKWLCCKQTDKNAPGCSPVTS 30
PH smart00233
Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The ...
 598-698 3.55e-13

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


Pssm-ID: 214574 [Multi-domain]  Cd Length: 102  Bit Score: 66.42  E-value: 3.55e-13
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2102677298   598 VLKEGVMIKRAQGrkrfGRKNFKQRYFKLTTQDLSYSKTK----GKEPLCKIPLEEILAVEKLHEDSFKMKNIFQIIQSQ 673
Cdd:smart00233    1 VIKEGWLYKKSGG----GKKSWKKRYFVLFNSTLLYYKSKkdkkSYKPKGSIDLSGCTVREAPDPDSSKKPHCFEIKTSD 76

                            90       100
                    ....*....|....*....|....*.
gi 2102677298   674 RA-LYVQAGNCVEEKEWIDILTKICR 698
Cdd:smart00233   77 RKtLLLQAESEEEREKWVEALRKAIA 102
PH pfam00169
PH domain; PH stands for pleckstrin homology.
 598-698 8.33e-12

PH domain; PH stands for pleckstrin homology.


Pssm-ID: 459697 [Multi-domain]  Cd Length: 105  Bit Score: 62.58  E-value: 8.33e-12
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2102677298  598 VLKEGVMIKRAQGRKrfgrKNFKQRYFKLTTQDLSYSK----TKGKEPLCKIPLEEILAVEKLHEDSFKMKNIFQIIQSQ 673
Cdd:pfam00169    1 VVKEGWLLKKGGGKK----KSWKKRYFVLFDGSLLYYKddksGKSKEPKGSISLSGCEVVEVVASDSPKRKFCFELRTGE 76

                           90       100
                   ....*....|....*....|....*....
gi 2102677298  674 ----RALYVQAGNCVEEKEWIDILTKICR 698
Cdd:pfam00169   77 rtgkRTYLLQAESEEERKDWIKAIQSAIR 105
C2 smart00239
Protein kinase C conserved region 2 (CalB); Ca2+-binding motif present in phospholipases, ...
 145-256 1.13e-11

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: 62.12  E-value: 1.13e-11
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2102677298   145 KLTVRVIECSELTIKNGG--CDPFAIVTVIYSNGKQvlKRTKIKKKTVSPYFNETFIFEpeiteskekdishysLEHGEV 222
Cdd:smart00239    1 TLTVKIISARNLPPKDKGgkSDPYVKVSLDGDPKEK--KKTKVVKNTLNPVWNETFEFE---------------VPPPEL 63

                            90       100       110
                    ....*....|....*....|....*....|....
gi 2102677298   223 NEVIVGLWHASSGMGEQpaFLGEVRVTLRGLQKQ 256
Cdd:smart00239   64 AELEIEVYDKDRFGRDD--FIGQVTIPLSDLLLG 95
COG5038 COG5038
Ca2+-dependent lipid-binding protein, contains C2 domain [General function prediction only];
14-99 9.18e-06

Ca2+-dependent lipid-binding protein, contains C2 domain [General function prediction only];


Pssm-ID: 227371 [Multi-domain]  Cd Length: 1227  Bit Score: 49.76  E-value: 9.18e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2102677298   14 LKIKIGEVKNLQSRNhgSPGARDVYCVLSLDQEEIFRTTTMERTLNPFFGEEFQFEVPRKFR-YLGIYVYDRDRHLKqDK 92
Cdd:COG5038   1042 LTIMLRSGENLPSSD--ENGYSDPFVKLFLNEKSVYKTKVVKKTLNPVWNEEFTIEVLNRVKdVLTINVNDWDSGEK-ND 1118


                   ....*..
gi 2102677298   93 ILGKVAI 99
Cdd:COG5038   1119 LLGTAEI 1125
IQG1 COG5261
Protein involved in regulation of cellular morphogenesis/cytokinesis [Cell division and ...
 318-558 4.03e-04

Protein involved in regulation of cellular morphogenesis/cytokinesis [Cell division and chromosome partitioning / Signal transduction mechanisms];


Pssm-ID: 227586 [Multi-domain]  Cd Length: 1054  Bit Score: 44.49  E-value: 4.03e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2102677298  318 LLLQSVniQPITSSAVYI----------LGEIVSSKMEAAQPLVRVLVHYGQ-------LVSVMRALASHEISKLTDPTT 380
Cdd:COG5261    380 FLLQSS--IPLFSIAICVgrvkrfsidaLLNIVKLQILGNGYEIRKLYSLGKsnceehlSVSLFQMLLRTEVEATSLVQS 457

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2102677298  381 IFRGNTLVSKMMDEGMRLA-GLHYLHSTLRPAMKQVF-LEKKSCEIDPTRVKDANTIQT--------NLTNLKEYVE--- 447
Cdd:COG5261    458 LLRGNLPVHRNMTNYFRRSqGQAALREIRYQIINDVAiHEDLEVDINPLLVYRALLNKGqlspdkdlELLTSNEEVSefl 537

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2102677298  448 -------------------------RVFIAITTSGVRcpsLMCEMFWCLKELAA-THFPKNKEVR------------YSV 489
Cdd:COG5261    538 avmnavqessakllelsterildavYNSLDEIGYGIR---FVCELIRVVFELTPnRLFPSISDSRclrticfaeidsLGL 614

                          250       260       270       280       290       300       310
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 2102677298  490 ISGFIFLRFFAPAILGPRLFDITTEQIDSqTNRTLTLISKTIQSLGNLVSCRGGAGS------VCKEEYMECVYR 558
Cdd:COG5261    615 IGGFFFLRFVNEALVSPQTSMLKDSCPSD-NVRKLATLSKILQSVFEITSSDKFDVPlqpflkEYKEKVHNLLRK 688
PLN03008 PLN03008
Phospholipase D delta
 19-125 8.16e-04

Phospholipase D delta


Pssm-ID: 178585 [Multi-domain]  Cd Length: 868  Bit Score: 43.54  E-value: 8.16e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2102677298   19 GEVKNLQSRNHGSPGARDVYCVLSLDQEEIFRTTTMERTLNPFFGEEFQFEVPRKFRYLGIYVYDRDRHLKQdkILGKVA 98
Cdd:PLN03008    61 GEFGDKNIRSHRKVITSDPYVTVVVPQATLARTRVLKNSQEPLWDEKFNISIAHPFAYLEFQVKDDDVFGAQ--IIGTAK 138

                           90       100       110
                   ....*....|....*....|....*....|..
gi 2102677298   99 IKREDLTTYHNKEHWFPL-----RPVDADSEV 125
Cdd:PLN03008   139 IPVRDIASGERISGWFPVlgasgKPPKAETAI 170
COG5038 COG5038
Ca2+-dependent lipid-binding protein, contains C2 domain [General function prediction only];
146-289 4.05e-03

Ca2+-dependent lipid-binding protein, contains C2 domain [General function prediction only];


Pssm-ID: 227371 [Multi-domain]  Cd Length: 1227  Bit Score: 41.28  E-value: 4.05e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2102677298  146 LTVRVIECSELTI--KNGGCDPFaivTVIYSNGKQVLKrTKIKKKTVSPYFNETFIFEpeiTESKEKDIShyslehgevn 223
Cdd:COG5038   1042 LTIMLRSGENLPSsdENGYSDPF---VKLFLNEKSVYK-TKVVKKTLNPVWNEEFTIE---VLNRVKDVL---------- 1104

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 2102677298  224 EVIVGLWHassgMGEQPAFLGEVRVTLRGLQ-KQSTNS----TTAWyFLQPRAVKH-----RPNKISNSSTSPGVL 289
Cdd:COG5038   1105 TINVNDWD----SGEKNDLLGTAEIDLSKLEpGGTTNSniplDGKT-FIVLDGTLHpgfnfRSKYALNVSRKEGIL 1175
 
Name Accession Description Interval E-value
RasGAP_GAP1_like cd05128
Ras-GTPase Activating Domain of GAP1 and similar proteins; The GAP1 family of Ras ...
 311-579 5.79e-149

Ras-GTPase Activating Domain of GAP1 and similar proteins; The GAP1 family of Ras GTPase-activating proteins includes GAP1(m) (or RASA2), GAP1_IP4BP (or RASA3), Ca2+ -promoted Ras inactivator (CAPRI, or RASAL4), and Ras GTPase activating-like proteins (RASAL) or RASAL1. The members are characterized by a conserved domain structure comprising N-terminal tandem C2 domains, a highly conserved central RasGAP domain, and a C-terminal pleckstrin homology domain that is associated with a Bruton's tyrosine kinase motif. While this domain structure is conserved, a small change in the function of each individual domain and the interaction between domains has a marked effect on the regulation of each protein.


Pssm-ID: 213330  Cd Length: 269  Bit Score: 443.23  E-value: 5.79e-149
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2102677298  311 MYDRLRNLLLQSVNIQPITSSAVYILGEIVS-SKMEAAQPLVRVLVHYGQLVSVMRALASHEISKLTDPTTIFRGNTLVS 389
Cdd:cd05128      2 YYEPLLNLLLESLDVPPFTASAVYLLEELVKvDKDDVARPLVRIFLHHGQIVPLLRALASREISKTQDPNTLFRGNSLAS 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2102677298  390 KMMDEGMRLAGLHYLHSTLRPAMKQVFLEKKSCEIDPTRVKDANTIQTNLTNLKEYVERVFIAITTSGVRCPSLMCEMFW 469
Cdd:cd05128     82 KCMDEFMKLVGMQYLHETLKPVIDEIFSEKKSCEIDPSKLKDGEVLETNLANLRGYVERVFKAITSSARRCPTLMCEIFS 161

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2102677298  470 CLKELAATHFPKNKEVRYSVISGFIFLRFFAPAILGPRLFDITTEQIDSQTNRTLTLISKTIQSLGNLVSCRGgaGSVCK 549
Cdd:cd05128    162 DLRESAAQRFPDNEDVPYTAVSGFIFLRFFAPAILNPKLFGLREEHPDPQTARTLTLISKTIQTLGNLGSSSS--GLGVK 239

                          250       260       270
                   ....*....|....*....|....*....|
gi 2102677298  550 EEYMECVYREFYTEKHIQAVKQFLELISTS 579
Cdd:cd05128    240 EAYMSPLYERFTDEQHVDAVKKFLDRISSV 269
RasGAP_RASA3 cd05134
Ras-GTPase Activating Domain of RASA3; RASA3 (or GAP1_IP4BP) is a member of the GAP1 family ...
 309-579 4.64e-105

Ras-GTPase Activating Domain of RASA3; RASA3 (or GAP1_IP4BP) is a member of the GAP1 family and has been shown to specifically bind 1,3,4,5-tetrakisphosphate (IP4). Thus, RASA3 may function as an IP4 receptor. The members of GAP1 family are characterized by a conserved domain structure comprising N-terminal tandem C2 domains, a highly conserved central RasGAP domain, and a C-terminal pleckstrin-homology domain that is associated with a Bruton's tyrosine kinase motif. Purified RASA3 stimulates GAP activity on Ras with about a five-fold lower potency than p120RasGAP, but shows no GAP-stimulating activity at all against Rac or Rab3A.


Pssm-ID: 213336  Cd Length: 269  Bit Score: 328.52  E-value: 4.64e-105
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2102677298  309 SAMYDRLRNLLLQSVNIQPITSSAVYILGEIVSSKMEAAQPLVRVLVHYGQLVSVMRALASHEISKLTDPTTIFRGNTLV 388
Cdd:cd05134      1 SEYYSPLRDLLLKSADVEPVSASAAHILGEVCREKQEAAIPLVRLFLHYGKIVPFISAIASAEVNRTQDPNTIFRGNSLT 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2102677298  389 SKMMDEGMRLAGLHYLHSTLRPAMKQVFLEKKSCEIDPTRVKDANTIQTNLTNLKEYVERVFIAITTSGVRCPSLMCEMF 468
Cdd:cd05134     81 SKCIDETMKLAGMHYLQVTLKPIIDEICQEHKPCEIDPVKLKDGENLENNRENLRQYVDRIFRVITKSGVSCPTVMCDIF 160

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2102677298  469 WCLKELAATHFPKNKEVRYSVISGFIFLRFFAPAILGPRLFDITTEQIDSQTNRTLTLISKTIQSLGNLVSCRGGAgsvC 548
Cdd:cd05134    161 FSLRESAAKRFQVDPDVRYTAVSSFIFLRFFAPAILSPNLFQLTPHHPDPQTSRTLTLISKTIQTLGSLSKSKSAN---F 237

                          250       260       270
                   ....*....|....*....|....*....|.
gi 2102677298  549 KEEYMECVYREFYTEKHIQAVKQFLELISTS 579
Cdd:cd05134    238 KESYMAAFYDYFNEQKYADAVKNFLDLISSS 268
RasGAP smart00323
GTPase-activator protein for Ras-like GTPases; All alpha-helical domain that accelerates the ...
 292-635 1.52e-103

GTPase-activator protein for Ras-like GTPases; All alpha-helical domain that accelerates the GTPase activity of Ras, thereby "switching" it into an "off" position. Improved domain limits from structure.


Pssm-ID: 214617  Cd Length: 344  Bit Score: 327.34  E-value: 1.52e-103
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2102677298   292 LGSLRLKIHYTADHVFPSAMYDRLRNLLLQSVNiqpitSSAVYILGEIVS--SKMEAAQPLVRVLVHYGQLVSVMRALAS 369
Cdd:smart00323    6 LGSLRLKTVYTTDFILPSEYYEELLELLLFSLD-----LSLASALSEVCSglDKDELATKLVRLFLRRGRGHPFLRALID 80

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2102677298   370 HEISKLTDPTTIFRGNTLVSKMMDEGMRLAGLHYLHSTLRPAMKQVFLEKKSCEIDPTRVKDANtIQTNLTNLKEYVERV 449
Cdd:smart00323   81 PEVERTDDPNTIFRGNSLATKSMEVYMKLVGNQYLHTTLKPVLKKIVESKKSCEVDPAKLEGED-LETNLENLLQYVERL 159

                           170       180       190       200       210       220       230       240
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2102677298   450 FIAITTSGVRCPSLMCEMFWCLKELAATHFPkNKEVRYSVISGFIFLRFFAPAILGPRLFDITTEQIDSQTNRTLTLISK 529
Cdd:smart00323  160 FDAIINSSDRLPYGLRDICKQLRQAAEKRFP-DADVIYKAVSSFVFLRFFCPAIVSPKLFNLVDEHPDPTTRRTLTLIAK 238

                           250       260       270       280       290       300       310       320
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2102677298   530 TIQSLGNLVScrggagSVCKEEYMECVyrEFYTEKHIQAVKQFLELISTSSNSNIAKQRTSTQ-------QEQPIVLKEG 602
Cdd:smart00323  239 VLQNLANLSE------FGSKEPWMEPL--NDFLLSHKDRVKDFLDELSSVPEILVDKVSDSTTisgrelsLLHSLLLENG 310

                           330       340       350
                    ....*....|....*....|....*....|....
gi 2102677298   603 VMIKRAQG-RKRFGRKNFKQRYFKLTTQDLSYSK 635
Cdd:smart00323  311 DALKRELNnEDPLGKLLFKLRYFGLTTHELTYGK 344
RasGAP_RASA2 cd05394
Ras-GTPase Activating Domain of RASA2; RASA2 (or GAP1(m)) is a member of the GAP1 family of ...
 309-579 6.63e-83

Ras-GTPase Activating Domain of RASA2; RASA2 (or GAP1(m)) is a member of the GAP1 family of Ras GTPase-activating proteins that includes GAP1_IP4BP (or RASA3), CAPRI, and RASAL. In vitro, RASA2 has been shown to bind inositol 1,3,4,5-tetrakisphosphate (IP4), the water soluble inositol head group of the lipid second messenger phosphatidylinositol 3,4,5-trisphosphate (PIP3). In vivo studies also demonstrated that RASA2 binds PIP3, and it is recruited to the plasma membrane following agonist stimulation of PI 3-kinase. Furthermore, the membrane translocation is a consequence of the ability of its pleckstrin homology (PH) domain to bind PIP3.


Pssm-ID: 213342  Cd Length: 272  Bit Score: 269.46  E-value: 6.63e-83
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2102677298  309 SAMYDRLRNLLLQSVNIQPITSSAVYILGEIVSSKMEAAQPLVRVLVHYGQLVSVMRALASHEISKLTDPTTIFRGNTLV 388
Cdd:cd05394      1 SACYTSLRNLLLKSPDVKPISASAAHILGEICRDKYDAVLPLVRLLLHHNKLVPFVAAVAALDLKDTQEANTIFRGNSLA 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2102677298  389 SKMMDEGMRLAGLHYLHSTLRPAMKQVFLEKKSCEIDPTRVKDANTIQTNLTNLKEYVERVFIAITTSGVRCPSLMCEMF 468
Cdd:cd05394     81 TRCLDEMMKIVGKHYLKVTLKPVLDEICESPKPCEIDPIKLKEGDNVENNKENLRYYVDKVFFSIVKSSMSCPTLMCDVF 160

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2102677298  469 WCLKELAATHFPKNKEVRYSVISGFIFLRFFAPAILGPRLFDITTEQIDSQTNRTLTLISKTIQSLGNLVSCRGGAGSVC 548
Cdd:cd05394    161 RSLRHLAVKRFPNDPHVQYSAVSSFVFLRFFAVAVVSPHTFQLRPHHPDAQTSRTLTLISKTIQTLGSWGSLSKSKLSSF 240

                          250       260       270
                   ....*....|....*....|....*....|.
gi 2102677298  549 KEEYMECVYREFYTEKHIQAVKQFLELISTS 579
Cdd:cd05394    241 KETFMCDFFKMFQEEKYIEKVKKFLDEISST 271
C2B_RasA3 cd04010
C2 domain second repeat present in RAS p21 protein activator 3 (RasA3); RasA3 are members of ...
 145-300 1.91e-69

C2 domain second repeat present in RAS p21 protein activator 3 (RasA3); RasA3 are members of GTPase activating protein 1 (GAP1), a Ras-specific GAP, 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. RasA3 contains an N-terminal C2 domain, 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: 175977 [Multi-domain]  Cd Length: 148  Bit Score: 228.05  E-value: 1.91e-69
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2102677298  145 KLTVRVIECSELTIKNGGCDPFAIVTVIYSNGKQVLKRTKIKKKTVSPYFNETFIFEPEITESKEKDISHYSLEHGEVNE 224
Cdd:cd04010      1 KLSVRVIECSDLALKNGTCDPYASVTLIYSNKKQDTKRTKVKKKTNNPQFDEAFYFDVTIDSSPEKKQFEMPEEDAEKLE 80

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 2102677298  225 VIVGLWHASsgMGEQPAFLGEVRVTLRGLQkQSTNSTTAWYFLQPRAVKHRPNkisnsSTSPGVLPGLGSLRLKIH 300
Cdd:cd04010     81 LRVDLWHAS--MGGGDVFLGEVRIPLRGLD-LQAGSHQAWYFLQPREEKSTPP-----GTRSSKDNSLGSLRLKIN 148
C2A_RasA2_RasA3 cd08401
C2 domain first repeat present in RasA2 and RasA3; RasA2 and RasA3 are GAP1s (GTPase ...
 14-135 6.77e-63

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: 208.44  E-value: 6.77e-63
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2102677298   14 LKIKIGEVKNLQSRNHgSPGARDVYCVLSLDQEEIFRTTTMERTLNPFFGEEFQFEVPRKFRYLGIYVYDRDRhLKQDKI 93
Cdd:cd08401      2 LKIKIGEAKNLPPRSG-PNKMRDCYCTVNLDQEEVFRTKTVEKSLCPFFGEDFYFEIPRTFRHLSFYIYDRDV-LRRDSV 79

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|..
gi 2102677298   94 LGKVAIKREDLTTYHNKEHWFPLRPVDADSEVQGKAHLEISL 135
Cdd:cd08401     80 IGKVAIKKEDLHKYYGKDTWFPLQPVDADSEVQGKVHLELRL 121
PH_GAP1-like cd01244
RAS p21 protein activator (GTPase activating protein) family pleckstrin homology (PH) domain; ...
 600-705 1.33e-56

RAS p21 protein activator (GTPase activating protein) family pleckstrin homology (PH) domain; RASAL1, GAP1(m), GAP1(IP4BP), and CAPRI are all members of the GAP1 family of GTPase-activating proteins. They contain N-terminal SH2-SH3-SH2 domains, followed by two C2 domains, a PH domain, a RasGAP domain, and a BTK domain. With the notable exception of GAP1(m), they all possess an arginine finger-dependent GAP activity on the Ras-related protein Rap1. They act as a suppressor of RAS enhancing the weak intrinsic GTPase activity of RAS proteins resulting in the inactive GDP-bound form of RAS, allowing control of cellular proliferation and differentiation. PH domains share little sequence conservation, but all have a common fold, which is electrostatically polarized. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 269950  Cd Length: 107  Bit Score: 190.58  E-value: 1.33e-56
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2102677298  600 KEGVMIKRAQGRK-RFGRKNFKQRYFKLTTQDLSYSKTKGKEPLCKIPLEEILAVEKLHEDSFKMKNIFQIIQSQRALYV 678
Cdd:cd01244      1 KEGYLIKRAQGRKkKFGRKNFKKRYFRLTNEALSYSKSKGKQPLCSIPLEDILAVERVEEESFKMKNMFQIVQPDRTLYL 80

                           90       100
                   ....*....|....*....|....*..
gi 2102677298  679 QAGNCVEEKEWIDILTKICRTNSNRLE 705
Cdd:cd01244     81 QAKNVVELNEWLSALRKVCLCNPNRLP 107
RasGAP_RASAL cd05135
Ras-GTPase Activating Domain of RASAL1 and similar proteins; Ras GTPase activating-like ...
 308-574 3.11e-54

Ras-GTPase Activating Domain of RASAL1 and similar proteins; Ras GTPase activating-like protein (RASAL) or RASAL1 is a member of the GAP1 family, and a Ca2+ sensor responding in-phase to repetitive Ca2+ signals by associating with the plasma membrane and deactivating Ras. It contains a conserved domain structure comprising N-terminal tandem C2 domains, a highly conserved central RasGAP domain, and a C-terminal pleckstrin-homology domain that is associated with a Bruton's tyrosine kinase motif. RASAL, like Ca2+ -promoted Ras inactivator (CAPRI, or RASAL4), is a cytosolic protein that undergoes a rapid translocation to the plasma membrane in response to receptor-mediated elevation in the concentration of intracellular free Ca2+, a translocation that activates its ability to function as a RasGAP. However, unlike RASAL4, RASAL undergoes an oscillatory translocation to the plasma membrane that occurs in synchrony with repetitive Ca2+ spikes.


Pssm-ID: 213337  Cd Length: 287  Bit Score: 190.79  E-value: 3.11e-54
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2102677298  308 PSAMYDRLRNLLLQSVN--IQPITSSAVYILGEIVS--SKMEAAQPLVRVLVHYGQLVSVMRALASHEISKLTDPTTIFR 383
Cdd:cd05135      1 PSQYYQPLIDLLVESVQspAEAEDSTPLAMLEEVTTgeSRQDVATKLVKIFLGQGLVVPFLDYLNTREVGRTTDPNTLFR 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2102677298  384 GNTLVSKMMDEGMRLAGLHYLHSTLRPAMKQVFLEKKSCEIDPTR--------------VKDANTIQTNLTNLKEYVERV 449
Cdd:cd05135     81 SNSLASKSMEQFMKVVGMPYLHEVLKPVINRIFEEKKYVELDPCKidlnrtrrisfkgsLSEAQVRESSLELLQGYLGSI 160

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2102677298  450 FIAITTSGVRCPSLMCEMFWCLKELAATHFPK--NKEVRYSVISGFIFLRFFAPAILGPRLFDITTEQIDSQTNRTLTLI 527
Cdd:cd05135    161 IDAIVGSVDQCPPVMRVAFKQLHKRVEERFPEaeHQDVKYLAISGFLFLRFFAPAILTPKLFQLREQHADPRTSRTLLLL 240

                          250       260       270       280
                   ....*....|....*....|....*....|....*....|....*..
gi 2102677298  528 SKTIQSLGNLvSCRGGAGsvcKEEYMECVYRefYTEKHIQAVKQFLE 574
Cdd:cd05135    241 AKAVQSIGNL-GLQLGQG---KEQWMAPLHP--FILQSVARVKDFLD 281
PH_GAP1_mammal-like cd13371
GAP1(IP4BP) pleckstrin homology (PH) domain; GAP1 (also called IP4BP, RASA3/Ras ...
 594-707 3.35e-54

GAP1(IP4BP) pleckstrin homology (PH) domain; GAP1 (also called IP4BP, RASA3/Ras GTPase-activating protein 3, and RAS p21 protein activator (GTPase activating protein) 3/GAPIII/MGC46517/MGC47588)) is a member of the GAP1 family of GTPase-activating proteins, along with RASAL1, GAP1(m), and CAPRI. With the notable exception of GAP1(m), they all possess an arginine finger-dependent GAP activity on the Ras-related protein Rap1. GAP1(IP4BP) contains two C2 domains, a PH domain, a RasGAP domain, and a BTK domain. Its C2 domains, like those of GAP1M, do not contain the C2 motif that is known to be required for calcium-dependent phospholipid binding. GAP1(IP4BP) is regulated by the binding of its PH domains to phophoinositides, PIP3 (phosphatidylinositol 3,4,5-trisphosphate) and PIP2 (phosphatidylinositol 4,5-bisphosphate). It suppresses RAS, enhancing the weak intrinsic GTPase activity of RAS proteins resulting in the inactive GDP-bound form of RAS, allowing control of cellular proliferation and differentiation. GAP1(IP4BP) binds tyrosine-protein kinase, HCK. Members here include humans, chickens, frogs, and fish. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 241522  Cd Length: 125  Bit Score: 184.47  E-value: 3.35e-54
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2102677298  594 EQPIVLKEGVMIKRAQGRKRFGRKNFKQRYFKLTTQDLSYSKTKGKEPLCKIPLEEILAVEKLHEDSFKMKNIFQIIQSQ 673
Cdd:cd13371     12 EQPILLKEGFMIKRAQGRKRFGMKNFKKRWFRLTNHEFTYHKSKGDHPLCSIPIENILAVERLEEESFKMKNMFQVIQPE 91

                           90       100       110
                   ....*....|....*....|....*....|....
gi 2102677298  674 RALYVQAGNCVEEKEWIDILTKICRTNSNRLEKY 707
Cdd:cd13371     92 RALYIQANNCVEAKDWIDILTKVSQCNKKRLTVY 125
C2B_RasGAP cd08675
C2 domain second repeat of Ras GTPase activating proteins (GAPs); RasGAPs suppress Ras ...
 146-295 4.03e-54

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: 184.50  E-value: 4.03e-54
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2102677298  146 LTVRVIECSELTIK-NGGCDPFAIVTVIYSnGKQVLKRTKIKKKTVSPYFNETFIFEPEITESKEKDISHYSLEHGEVNE 224
Cdd:cd08675      1 LSVRVLECRDLALKsNGTCDPFARVTLNYS-SKTDTKRTKVKKKTNNPRFDEAFYFELTIGFSYEKKSFKVEEEDLEKSE 79

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 2102677298  225 VIVGLWHASsgMGEQPAFLGEVRVTLRGLQKQstNSTTAWYFLQPRavkhrpnkiSNSSTSPGVLPGLGSL 295
Cdd:cd08675     80 LRVELWHAS--MVSGDDFLGEVRIPLQGLQQA--GSHQAWYFLQPR---------EAPGTRSSNDGSLGSL 137
PH_GAP1m_mammal-like cd13370
GTPase activating protein 1 m pleckstrin homology (PH) domain; GAP1(m) (also called RASA2/RAS ...
 581-715 6.61e-53

GTPase activating protein 1 m pleckstrin homology (PH) domain; GAP1(m) (also called RASA2/RAS p21 protein activator (GTPase activating protein) 2) is a member of the GAP1 family of GTPase-activating proteins, along with RASAL1, GAP1(IP4BP), and CAPRI. With the notable exception of GAP1(m), they all possess an arginine finger-dependent GAP activity on the Ras-related protein Rap1. GAP1(m) contains two C2 domains, a PH domain, a RasGAP domain, and a BTK domain. Its C2 domains, like those of GAP1IP4BP, do not contain the C2 motif that is known to be required for calcium-dependent phospholipid binding. GAP1(m) is regulated by the binding of its PH domains to phophoinositides, PIP3 (phosphatidylinositol 3,4,5-trisphosphate). It suppresses RAS, enhancing the weak intrinsic GTPase activity of RAS proteins resulting in the inactive GDP-bound form of RAS, allowing control of cellular proliferation and differentiation. GAP1(m) binds inositol tetrakisphosphate (IP4). PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 241521  Cd Length: 133  Bit Score: 180.91  E-value: 6.61e-53
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2102677298  581 NSNIAKQRTSTqqEQPIVLKEGVMIKRAQGRKRFGRKNFKQRYFKLTTQDLSYSKTKGKEPLCKIPLEEILAVEKLHEDS 660
Cdd:cd13370      1 SSTESKESSGV--SESVHLKEGEMHKRAQGRTRIGKKNFKKRWFCLTSRELTYHKQKGKEAIFTIPVKNILAVEKLEESA 78

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 2102677298  661 FKMKNIFQIIQSQRALYVQAGNCVEEKEWIDILTKICRTNSNRLEKYHPSAYING 715
Cdd:cd13370     79 FNKKNMFQVIHSEKPLYVQANNCVEANEWIEVLSRVSRCNQKRLSFYHPSAYLGG 133
RasGAP cd04519
Ras GTPase Activating Domain; RasGAP functions as an enhancer of the hydrolysis of GTP that is ...
 312-577 6.58e-52

Ras GTPase Activating Domain; RasGAP functions as an enhancer of the hydrolysis of GTP that is bound to Ras-GTPases. Proteins having a RasGAP domain include p120GAP, IQGAP, Rab5-activating protein 6, and Neurofibromin, among others. Although the Rho (Ras homolog) GTPases are most closely related to members of the Ras family, RhoGAP and RasGAP exhibit no similarity at their amino acid sequence level. RasGTPases function as molecular switches in a large number of signaling pathways. They are in the on state when bound to GTP, and in the off state when bound to GDP. The RasGAP domain speeds up the hydrolysis of GTP in Ras-like proteins acting as a negative regulator.


Pssm-ID: 213328  Cd Length: 256  Bit Score: 183.08  E-value: 6.58e-52
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2102677298  312 YDRLRNLLLQSVN---IQPITSSAVYILGEIVsskmeaAQPLVRVLVHYGQLVSVMRALASHEISKLTDPTTIFRGNTLV 388
Cdd:cd04519      2 EYRLLSLLLTESPlalLRELSQVLPVKDKEEV------ATALLRIFESRGLALEFLRYLVRSEVKNTKNPNTLFRGNSLA 75

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2102677298  389 SKMMDEGMRLAGLHYLHSTLRPAMKQVFLEKKSCEIDpTRVKDANTIQTNLTNLKEYVERVFIAITTSGVRCPSLMCEMF 468
Cdd:cd04519     76 TKLLDQYMKLVGQEYLKETLSPLIREILESKESCEID-TKLPVGEDLEENLENLLELVNKLVDRILSSLDRLPPELRYVF 154

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2102677298  469 WCLKELAATHFPKNKEVRYSVISGFIFLRFFAPAILGPRLFDITTEQIDSQTNRTLTLISKTIQSLGNLVSCRGgagsvc 548
Cdd:cd04519    155 KILREFLAERFPEEPDEAYQAVSGFLFLRFICPAIVSPELFGLVPDEPSEQARRNLTLISKVLQSLANGVEFGD------ 228

                          250       260
                   ....*....|....*....|....*....
gi 2102677298  549 KEEYMecVYREFYTEKHIQAVKQFLELIS 577
Cdd:cd04519    229 KEPFM--KPLNDFIKSNKPKLKQFLDELS 255
RasGAP_DAB2IP cd05136
Ras-GTPase Activating Domain of DAB2IP and similar proteins; The DAB2IP family of Ras ...
 300-584 2.83e-48

Ras-GTPase Activating Domain of DAB2IP and similar proteins; The DAB2IP family of Ras GTPase-activating proteins includes DAB2IP, nGAP, and Syn GAP. Disabled 2 interactive protein, (DAB2IP; also known as ASK-interacting protein 1 (AIP1)), is a member of the GTPase-activating proteins, down-regulates Ras-mediated signal pathways, and mediates TNF-induced activation of ASK1-JNK signaling pathways. The mechanism by which TNF signaling is coupled to DAB2IP is not known.


Pssm-ID: 213338  Cd Length: 324  Bit Score: 174.69  E-value: 2.83e-48
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2102677298  300 HYTADHVFPSAMYDRLRNLLLQ-----SVNIQPITSsavyilgeiVSSKMEAAQPLVRVLVHYGQLVSVMRALASHEISK 374
Cdd:cd05136      1 RYQSVDILPLEVYKEFLEYLTNnyldlCEVLEPVLS---------VKAKEELATALVHILQSTGKAKEFLTDLVMAEVDR 71

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2102677298  375 LTDPTTIFRGNTLVSKMMDEGMRLAGLHYLHSTLRPAMKQVFLEKKSCEIDPTRVKDANTIQTNLTNLKEYVERVFIAIT 454
Cdd:cd05136     72 LDDEHLIFRGNTLATKAMEAYLKLVGQKYLQETLGEFIRALYESEEDCEVDPSKCPPSASLSRNQANLRRSVELAWCKIL 151

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2102677298  455 TSGVRCPSLMCEMFWCLKE-LAATHFPknkEVRYSVISGFIFLRFFAPAILGPRLFDITTEQIDSQTNRTLTLISKTIQS 533
Cdd:cd05136    152 SSHCVFPRELREVFSSWRErLEERGRE---DIADRLISASLFLRFLCPAILSPSLFNLTQEYPSERAARNLTLIAKVIQN 228

                          250       260       270       280       290
                   ....*....|....*....|....*....|....*....|....*....|....
gi 2102677298  534 LGNLvSCRGGagsvcKEEYMecvyrEF---YTEKHIQAVKQFLELISTSSNSNI 584
Cdd:cd05136    229 LANF-TRFGG-----KEEYM-----EFmndFVEQEWPNMKQFLQEISSPSPSSN 271
C2A_RasGAP cd08383
C2 domain (first repeat) of Ras GTPase activating proteins (GAPs); RasGAPs suppress Ras ...
 14-135 1.87e-43

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: 153.57  E-value: 1.87e-43
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2102677298   14 LKIKIGEVKNLQSRnhgspGARDVYCVLSLDQEEIFRTTTMERtLNPFFGEEFQFEVPR---KFRYLGIYVYDRDRhLKQ 90
Cdd:cd08383      2 LRLRILEAKNLPSK-----GTRDPYCTVSLDQVEVARTKTVEK-LNPFWGEEFVFDDPPpdvTFFTLSFYNKDKRS-KDR 74

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*
gi 2102677298   91 DKILGKVAIKREDLttYHNKEHWFPLRPVDADSEVQGKAHLEISL 135
Cdd:cd08383     75 DIVIGKVALSKLDL--GQGKDEWFPLTPVDPDSEVQGSVRLRARY 117
RasGAP_p120GAP cd05391
Ras-GTPase Activating Domain of p120; p120GAP is a negative regulator of Ras that stimulates ...
 304-583 9.37e-43

Ras-GTPase Activating Domain of p120; p120GAP is a negative regulator of Ras that stimulates hydrolysis of bound GTP to GDP. Once the Ras regulator p120GAP, a member of the GAP protein family, is recruited to the membrane, it is transiently immobilized to interact with Ras-GTP. The down-regulation of Ras by p120GAP is a critical step in the regulation of many cellular processes, which is disrupted in approximately 30% of human cancers. p120GAP contains SH2, SH3, PH, calcium- and lipid-binding domains, suggesting its involvement in a complex network of cellular interactions in vivo.


Pssm-ID: 213340  Cd Length: 328  Bit Score: 159.19  E-value: 9.37e-43
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2102677298  304 DHVFPSAMYDRLRNLLLQSvniqpiTSSAVYILGEIV-SSKMEAAQPLVRVLVHYGQLVSVMRALASHEISKLTDPTTIF 382
Cdd:cd05391      2 EKIMPEEEYSELKELILQK------ELHVVYALAHVCgQDRTLLASILLRIFRHEKLESLLLRTLNDREISMEDEATTLF 75

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2102677298  383 RGNTLVSKMMDEGMRLAGLHYLHSTLRPAMKQVFLEKKSCEIDPTRVKDANTIQTNLTNLKEYVERVFIAITTSGVRCPS 462
Cdd:cd05391     76 RATTLASTLMEQYMKATATPFVHHALKDTILKILESKQSCELNPSKLEKNEDVNTNLEHLLNILSELVEKIFMAAEILPP 155

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2102677298  463 LMCEMFWCLKELAATHFPKNKEVRYSVISGFIFLRFFAPAILGPRLFDITTEQIDSQTNRTLTLISKTIQSLGNLVSCrg 542
Cdd:cd05391    156 TLRYIYGCLQKSVQQKWPTNTTVRTRVVSGFVFLRLICPAILNPRMFNIISETPSPTAARTLTLVAKSLQNLANLVEF-- 233

                          250       260       270       280
                   ....*....|....*....|....*....|....*....|.
gi 2102677298  543 GAgsvcKEEYMECVyrEFYTEKHIQAVKQFLELISTSSNSN 583
Cdd:cd05391    234 GA----KEPYMEGV--NPFIKKNKERMIMFLDELGNVPELP 268
RasGAP_CLA2_BUD2 cd05137
Ras-GTPase Activating Domain of CLA2/BUD2; CLA2/BUD2 functions as a GTPase-activating protein ...
 298-581 1.17e-42

Ras-GTPase Activating Domain of CLA2/BUD2; CLA2/BUD2 functions as a GTPase-activating protein (GAP) for BUD1/RSR1 and is necessary for proper bud-site selection in yeast. BUD2 has sequence similarity to the catalytic domain of RasGAPs, and stimulates the hydrolysis of BUD1-GTP to BUD1-GDP. Elimination of Bud2p activity by mutation causes a random budding pattern with no growth defect. Overproduction of Bud2p also alters the budding pattern.


Pssm-ID: 213339 [Multi-domain]  Cd Length: 356  Bit Score: 159.65  E-value: 1.17e-42
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2102677298  298 KIHYTADHVFPSAMYDRLRNLLLQSVNIQPItssavYILGEIVSSKME-AAQPLVRVLVHYGQLVSVMRALASHEISKLT 376
Cdd:cd05137      1 KVRLDENVVLPSKNYKPLEELLHNFDLGLTL-----QIAELVPGDKLErLSEILLDIFQASGREDEWFMALVEDEIDGID 75

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2102677298  377 DPT---------------TIFRGNTLVSKMMDEGMRLAGLHYLHSTLRPAMKQVFLEKKSCEIDPTRVKDA------NTI 435
Cdd:cd05137     76 KSTsknkdmgkssnneanLLFRGNSLLTKSLEKYMRRIGKEYLEKSIGDVIRKICEENKDCEVDPSRVKESdsiekeEDL 155

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2102677298  436 QTNLTNLKEYVERVFIAITTSGVRCPSLMCEMFWCLKELAATHF-PKNKEVRYSVISGFIFLRFFAPAILGPRLFDITTE 514
Cdd:cd05137    156 EENWENLISLTEEIWNSIYITSNDCPPELRKILKHIRAKVEDRYgDFLRTVTLNSVSGFLFLRFFCPAILNPKLFGLLKD 235

                          250       260       270       280       290       300
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 2102677298  515 QIDSQTNRTLTLISKTIQSLGNLVScrggagSVCKEEYMEcVYREFYTeKHIQAVKQFLELISTSSN 581
Cdd:cd05137    236 HPRPRAQRTLTLIAKVLQNLANLTT------FGQKEPWME-PMNEFLT-THREELKDYIDKITGIKL 294
PH_Btk cd01238
Bruton's tyrosine kinase pleckstrin homology (PH) domain; Btk is a member of the Tec family of ...
 600-735 8.08e-40

Bruton's tyrosine kinase pleckstrin homology (PH) domain; Btk is a member of the Tec family of cytoplasmic protein tyrosine kinases that includes BMX, IL2-inducible T-cell kinase (Itk) and Tec. Btk plays a role in the maturation of B cells. Tec proteins general have an N-terminal PH domain, followed by a Tek homology (TH) domain, a SH3 domain, a SH2 domain and a kinase domain. The Btk PH domain binds phosphatidylinositol 3,4,5-trisphosphate and responds to signalling via phosphatidylinositol 3-kinase. The PH domain is also involved in membrane anchoring which is confirmed by the discovery of a mutation of a critical arginine residue in the BTK PH domain. This results in severe human immunodeficiency known as X-linked agammaglobulinemia (XLA) in humans and a related disorder is mice.PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 269944 [Multi-domain]  Cd Length: 140  Bit Score: 143.91  E-value: 8.08e-40
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2102677298  600 KEGVMIKRAQGRKRFGRKNFKQRYFKLTTQDLSY----SKTKGKEPLCkIPLEEILAVEKLH-EDSFKMKNIFQIIQSQR 674
Cdd:cd01238      1 LEGLLVKRSQGKKRFGPVNYKERWFVLTKSSLSYyegdGEKRGKEKGS-IDLSKVRCVEEVKdEAFFERKYPFQVVYDDY 79

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 2102677298  675 ALYVQAGNCVEEKEWIDILTKICRTNSNRLEKYHPSAYINGHWLCCKAIAEIAPGCSEVSP 735
Cdd:cd01238     80 TLYVFAPSEEDRDEWIAALRKVCRNNSNLHDKYHPGFWTGGKWSCCGQTSKSAPGCQPAFD 140
RasGAP_RASA4 cd05395
Ras-GTPase Activating Domain of RASA4; Ras GTPase activating-like 4 protein (RASAL4), also ...
 308-554 2.53e-39

Ras-GTPase Activating Domain of RASA4; Ras GTPase activating-like 4 protein (RASAL4), also known as Ca2+ -promoted Ras inactivator (CAPRI), is a member of the GAP1 family. Members of the GAP1 family are characterized by a conserved domain structure comprising N-terminal tandem C2 domains, a highly conserved central RasGAP domain, and a C-terminal pleckstrin-homology domain that is associated with a Bruton's tyrosine kinase motif. RASAL4, like RASAL, is a cytosolic protein that undergoes a rapid translocation to the plasma membrane in response to a receptor-mediated elevation in the concentration of intracellular free Ca2+ ([Ca2+]i). However, unlike RASAL, RASAL4 does not sense oscillations in [Ca2+]i.


Pssm-ID: 213343 [Multi-domain]  Cd Length: 287  Bit Score: 147.71  E-value: 2.53e-39
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2102677298  308 PSAMYDRLRNLLLQSVNIQPITSSA--VYILGEIVS--SKMEAAQPLVRVLVHYGQLVSVMRALASHEISKLTDPTTIFR 383
Cdd:cd05395      1 PSSHYQPLVQLLCQEVKLGHQAGPVqlISLIDETTTaeCRQEVATNLVKLFLGQGLAKEFLDLLFQLELDKTTEPNTLFR 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2102677298  384 GNTLVSKMMDEGMRLAGLHYLHSTLRPAMKQVFLEKKSCEIDPTRVK--------------DANTIQTNLTNLKEYVERV 449
Cdd:cd05395     81 SNSLASKSMESFLKVAGMQYLHSVLGPTINRVFEEKKYVELDPSKVEikdvgcsglhriqtESEVIEQSAQLLQSYLGEL 160

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2102677298  450 FIAITTSGVRCPSLMCEMFWCLKELAATHFPKNK--EVRYSVISGFIFLRFFAPAILGPRLFDITTEQIDSQTNRTLTLI 527
Cdd:cd05395    161 LSAISKSVKYCPAVIRATFRQLFKRVQERFPENQhqNVKFIAVTSFLCLRFFSPAIMSPKLFHLREKHADARTSRTLLLL 240

                          250       260
                   ....*....|....*....|....*..
gi 2102677298  528 SKTIQSLGNLVScrggAGSVCKEEYME 554
Cdd:cd05395    241 AKAVQNVGNMDT----LASRAKEAWMA 263
RasGAP_Neurofibromin_like cd05392
Ras-GTPase Activating Domain of proteins similar to neurofibromin; Neurofibromin-like proteins ...
 347-592 2.56e-35

Ras-GTPase Activating Domain of proteins similar to neurofibromin; Neurofibromin-like proteins include the Saccharomyces cerevisiae RasGAP proteins Ira1 and Ira2, the closest homolog of neurofibromin, which is responsible for the human autosomal dominant disease neurofibromatosis type I (NF1). The RasGAP Ira1/2 proteins are negative regulators of the Ras-cAMP signaling pathway and conserved from yeast to human. In yeast Ras proteins are activated by GEFs, and inhibited by two GAPs, Ira1 and Ira2. Ras proteins activate the cAMP/protein kinase A (PKA) pathway, which controls metabolism, stress resistance, growth, and meiosis. Recent studies showed that the kelch proteins Gpb1 and Gpb2 inhibit Ras activity via association with Ira1 and Ira2. Gpb1/2 bind to a conserved C-terminal domain of Ira1/2, and loss of Gpb1/2 results in a destabilization of Ira1 and Ira2, leading to elevated levels of Ras2-GTP and uninhibited cAMP-PKA signaling. Since the Gpb1/2 binding domain on Ira1/2 is conserved in the human neurofibromin protein, the studies suggest that an analogous signaling mechanism may contribute to the neoplastic development of NF1.


Pssm-ID: 213341  Cd Length: 317  Bit Score: 137.03  E-value: 2.56e-35
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2102677298  347 AQPLVRVLVHYGQLVSVMRALASHEISKLTDPTTIFRGNTLVSKMMDEGMRLAGLHYLHSTLRPAMKQVFLEKKSCEIDP 426
Cdd:cd05392     36 AQSLLNLFETRNRLLPLISWLIEDEISHTSRAADLFRRNSVATRLLTLYAKSVGNKYLRKVLRPLLTEIVDNKDYFEVEK 115

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2102677298  427 TRVKDANtIQTNLTNLKEYVERVFIAITTSGVRCPSLMCEMFWCLKELAATHFPKNKevrYSVISGFIFLRFFAPAILGP 506
Cdd:cd05392    116 IKPDDEN-LEENADLLMKYAQMLLDSITDSVDQLPPSFRYICNTIYESVSKKFPDAA---LIAVGGFLFLRFICPAIVSP 191

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2102677298  507 RLFDITTEQIDSQTNRTLTLISKTIQSLGNlvscrgGAGSVCKEEYMECvYREFyTEKHIQAVKQFLELISTSSNSNIAK 586
Cdd:cd05392    192 ESENLLDPPPTPEARRSLILIAKVLQNIAN------GVLFSLKEPYLES-LNEF-LKKNSDRIQQFLSEVSTIPPTDPIF 263


                   ....*.
gi 2102677298  587 QRTSTQ 592
Cdd:cd05392    264 DESDEE 269
RasGAP pfam00616
GTPase-activator protein for Ras-like GTPase; All alpha-helical domain that accelerates the ...
 363-536 4.41e-34

GTPase-activator protein for Ras-like GTPase; All alpha-helical domain that accelerates the GTPase activity of Ras, thereby "switching" it into an "off" position.


Pssm-ID: 459871  Cd Length: 207  Bit Score: 130.10  E-value: 4.41e-34
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2102677298  363 VMRALASHEISKLTDPTTIFRGNTLVSKMMDEGMRLA-GLHYLHSTLRPAMKQVFL-EKKSCEIDPTRVKDA-------- 432
Cdd:pfam00616    1 LISELIEEEIESSDNPNDLLRGNSLVSKLLETYNRRPrGQEYLKKVLGPLVRKIIEdEDLDLESDPRKIYESlinqeelk 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2102677298  433 ----------------------NTIQTNLTNLKEYVERVFIAITTSGVRCPSLMCEMFWCLKELAATHFP-KNKEVRYSV 489
Cdd:pfam00616   81 tgrsdlprdvspeeaiedpevrQIFEDNLQKLRELADEFLDAIYSSLNQLPYGIRYICKQLYELLEEKFPdASEEEILNA 160

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|....*..
gi 2102677298  490 ISGFIFLRFFAPAILGPRLFDITTEQIDSQTNRTLTLISKTIQSLGN 536
Cdd:pfam00616  161 IGGFLFLRFFCPAIVNPDLFGLVDHQISPKQRRNLTLIAKVLQNLAN 207
RasGAP_Neurofibromin cd05130
Ras-GTPase Activating Domain of neurofibromin; Neurofibromin is the product of the ...
 369-578 8.20e-32

Ras-GTPase Activating Domain of neurofibromin; Neurofibromin is the product of the neurofibromatosis type 1 gene (NF1) and shares a region of similarity with catalytic domain of the mammalian p120RasGAP protein and an extended similarity with the Saccharomyces cerevisiae RasGAP proteins Ira1 and Ira2. Neurofibromin has been shown to function as a GAP (GTPase-activating protein) which inhibits low molecular weight G proteins such as Ras by stimulating their intrinsic GTPase activity. NF1 is a common genetic disorder characterized by various symptoms ranging from predisposition for the development of tumors to learning disability or mental retardation. Loss of neurofibromin activity can be correlated to the increase in Ras-GTP concentration in neurofibromas of NF1 of patients, supporting the notion that unregulated Ras signaling may contribute to their development.


Pssm-ID: 213332 [Multi-domain]  Cd Length: 332  Bit Score: 127.44  E-value: 8.20e-32
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2102677298  369 SHEISKLTDPTTIFRGNTLVSKMMDEGMRLAGLHYLHSTLRPAMKQVFL--EKKSCEIDPTRVKDANTIQTNLTNLKEYV 446
Cdd:cd05130     65 SKEVELADSMQTLFRGNSLASKIMTFCFKVYGATYLQSLLEPLLRTMITssEWVSYEVDPTRLEGNENLEENQRNLLQLT 144

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2102677298  447 ERVFIAITTSGVRCPSLMCEMFWCLKELAATHFPKNKevrYSVISGFIFLRFFAPAILGPRLFDITTEQIDSQTNRTLTL 526
Cdd:cd05130    145 EKFFHAIISSSDEFPPQLRSVCHCLYQVVSHRFPNSG---LGAVGSAIFLRFINPAIVSPYEYGILDREPPPRVKRGLKL 221

                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|..
gi 2102677298  527 ISKTIQSLGNLVscrggagSVCKEEYMEcVYREFyTEKHIQAVKQFLELIST 578
Cdd:cd05130    222 MSKILQNIANHV-------LFTKEAHML-PFNDF-LRNHFEAGRRFFSSIAS 264
C2A_Rasal1_RasA4 cd04054
C2 domain first repeat present in RasA1 and RasA4; Rasal1 and RasA4 are both members of GAP1 ...
 14-135 3.26e-26

C2 domain first repeat present in RasA1 and RasA4; Rasal1 and RasA4 are both members of GAP1 (GTPase activating protein 1). Rasal1 responds to repetitive Ca2+ signals by associating with the plasma membrane and deactivating Ras. RasA4 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 of these proteins contains 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 first C2 repeat, C2A, and has a type-I topology.


Pssm-ID: 176018 [Multi-domain]  Cd Length: 121  Bit Score: 104.52  E-value: 3.26e-26
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2102677298   14 LKIKIGEVKNLQSRNhgSPGARDVYCVLSLDQEEIFRTTTMERTLNPFFGEEFQFEVPRKFRYLGIYVYDRDRhLKQDKI 93
Cdd:cd04054      2 LYIRIVEGKNLPAKD--ITGSSDPYCIVKVDNEVIIRTATVWKTLNPFWGEEYTVHLPPGFHTVSFYVLDEDT-LSRDDV 78

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|...
gi 2102677298   94 LGKVAIKREDLTTY-HNKEHWFPLRPVDADSEVQGKAHLEISL 135
Cdd:cd04054     79 IGKVSLTREVISAHpRGIDGWMNLTEVDPDEEVQGEIHLELSV 121
RasGAP_GAPA cd05132
Ras-GTPase Activating Domain of GAPA; GAPA is an IQGAP-related protein and is predicted to ...
 360-576 9.48e-20

Ras-GTPase Activating Domain of GAPA; GAPA is an IQGAP-related protein and is predicted to bind to small GTPases, which are yet to be identified. IQGAP proteins are integral components of cytoskeletal regulation. Results from truncated GAPAs indicated that almost the entire region of GAPA homologous to IQGAP is required for cytokinesis in Dictyostelium. More members of the IQGAP family are emerging, and evidence suggests that there are both similarities and differences in their function.


Pssm-ID: 213334  Cd Length: 352  Bit Score: 92.03  E-value: 9.48e-20
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2102677298  360 LVSVMRALASHEISKLTDPTTIFRGNTLVSKMMDEGMRLA-GLHYLHSTLRPAMKQVFLEKK-SCEIDPTRV-------- 429
Cdd:cd05132     26 LLSMFQSVLTYEFDETTEFGSLLRANTAVSRMMTTYTRRGpGQSYLKTVLADRINDLISLKDlNLEINPLKVyeqmindi 105

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2102677298  430 -----------------------KDANTIQTNLTNLKEYVERVFIAITTS------GVRcpslmcemfW-C--LKELAAT 477
Cdd:cd05132    106 eldtglpsnlprgitpeeaaenpAVQNIIEPRLEMLEEITNSFLEAIINSldevpyGIR---------WiCkqIRSLTRR 176

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2102677298  478 HFPK-NKEVRYSVISGFIFLRFFAPAILGPRLFDITTEQIDSQTNRTLTLISKTIQSLGNlvscrggAGSVCKEEYMECV 556
Cdd:cd05132    177 KFPDaSDETICSLIGGFFLLRFINPAIVSPQAYMLVDGKPSDNTRRTLTLIAKLLQNLAN-------KPSYSKEPYMAPL 249

                          250       260
                   ....*....|....*....|
gi 2102677298  557 yrEFYTEKHIQAVKQFLELI 576
Cdd:cd05132    250 --QPFVEENKERLNKFLNDL 267
C2 pfam00168
C2 domain;
13-116 2.85e-19

C2 domain;


Pssm-ID: 425499 [Multi-domain]  Cd Length: 104  Bit Score: 83.91  E-value: 2.85e-19
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2102677298   13 RLKIKIGEVKNLQSRNhgSPGARDVYCVLSL-DQEEIFRTTTMERTLNPFFGEEFQFEVP-RKFRYLGIYVYDRDRhLKQ 90
Cdd:pfam00168    2 RLTVTVIEAKNLPPKD--GNGTSDPYVKVYLlDGKQKKKTKVVKNTLNPVWNETFTFSVPdPENAVLEIEVYDYDR-FGR 78

                           90       100
                   ....*....|....*....|....*.
gi 2102677298   91 DKILGKVAIKREDLTTYHNKEHWFPL 116
Cdd:pfam00168   79 DDFIGEVRIPLSELDSGEGLDGWYPL 104
C2 cd00030
C2 domain; The C2 domain was first identified in PKC. C2 domains fold into an 8-standed ...
 14-116 1.80e-18

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: 81.73  E-value: 1.80e-18
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2102677298   14 LKIKIGEVKNLQSRNhgSPGARDVYCVLSLDQEEIFRTTTMERTLNPFFGEEFQFEV-PRKFRYLGIYVYDRDRhLKQDK 92
Cdd:cd00030      1 LRVTVIEARNLPAKD--LNGKSDPYVKVSLGGKQKFKTKVVKNTLNPVWNETFEFPVlDPESDTLTVEVWDKDR-FSKDD 77

                           90       100
                   ....*....|....*....|....*
gi 2102677298   93 ILGKVAIK-REDLTTYHNKEHWFPL 116
Cdd:cd00030     78 FLGEVEIPlSELLDSGKEGELWLPL 102
PH_RASAL1 cd13369
Ras-GTPase-activating-like protein pleckstrin homology (PH) domain; RASAL1 is a member of the ...
 597-715 1.94e-18

Ras-GTPase-activating-like protein pleckstrin homology (PH) domain; RASAL1 is a member of the GAP1 family of GTPase-activating proteins, along with GAP1(m), GAP1(IP4BP) and CAPRI. RASAL1 contains two C2 domains, a PH domain, a RasGAP domain, and a BTK domain. RASAL1 contains two fully conserved C2 domains, a PH domain, a RasGAP domain, and a BTK domain. Its catalytic GAP domain has dual RasGAP and RapGAP activities, while its C2 domains bind phospholipids in the presence of Ca2+. Both CAPRI and RASAL1 are calcium-activated RasGAPs that inactivate Ras at the plasma membrane. Thereby enhancing the weak intrinsic GTPase activity of RAS proteins resulting in the inactive GDP-bound form of RAS and allowing control of cellular proliferation and differentiation. CAPRI and RASAL1 differ in that CAPRI is an amplitude sensor while RASAL1 senses calcium oscillations. This difference between them resides not in their C2 domains, but in their PH domains leading to speculation that this might reflect an association with either phosphoinositides and/or proteins. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270175  Cd Length: 138  Bit Score: 82.60  E-value: 1.94e-18
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2102677298  597 IVLKEGVMIKR-AQGRKRFGRKNFKQRYFKLTTQDLSYSKTKGKEPLCKIPLEEILAVEKLHEDSFKMKNIFQIIQSQ-- 673
Cdd:cd13369     14 VTVKEGYLHKRkAEGVGLVTRFTFKKRYFWLSSETLSYSKSPDWQVRSSIPVQRICAVERVDENAFQQPNVMQVVTQDge 93

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*
gi 2102677298  674 ---RALYVQAGNCVEEKEWIDILTKICRTNSNRLEKYHPSAYING 715
Cdd:cd13369     94 gqvHTTYIQCKNVNELNQWLSALRKVSLSNERMLPACHPGAFRSA 138
C2 smart00239
Protein kinase C conserved region 2 (CalB); Ca2+-binding motif present in phospholipases, ...
 13-113 1.64e-16

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: 75.99  E-value: 1.64e-16
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2102677298    13 RLKIKIGEVKNLQSRNhgSPGARDVYCVLSLDQE--EIFRTTTMERTLNPFFGEEFQFEV-PRKFRYLGIYVYDRDRhLK 89
Cdd:smart00239    1 TLTVKIISARNLPPKD--KGGKSDPYVKVSLDGDpkEKKKTKVVKNTLNPVWNETFEFEVpPPELAELEIEVYDKDR-FG 77

                            90       100
                    ....*....|....*....|....
gi 2102677298    90 QDKILGKVAIKREDLTTYHNKEHW 113
Cdd:smart00239   78 RDDFIGQVTIPLSDLLLGGRHEKL 101
PH_CAPRI cd13372
Ca2+ promoted Ras inactivator pleckstrin homology (PH) domain; CAPRI (also called RASA4/RAS ...
 575-704 2.50e-16

Ca2+ promoted Ras inactivator pleckstrin homology (PH) domain; CAPRI (also called RASA4/RAS p21 protein activator (GTPase activating protein) 4/GAPL/FLJ59070/KIAA0538/MGC131890) is a member of the GAP1 family of GTPase-activating proteins. CAPRI contains two fully conserved C2 domains, a PH domain, a RasGAP domain, and a BTK domain. Its catalytic GAP domain has dual RasGAP and RapGAP activities, while its C2 domains bind phospholipids in the presence of Ca2+. Both CAPRI and RASAL are calcium-activated RasGAPs that inactivate Ras at the plasma membrane. Thereby enhancing the weak intrinsic GTPase activity of RAS proteins resulting in the inactive GDP-bound form of RAS and allowing control of cellular proliferation and differentiation. CAPRI and RASAL differ in that CAPRI is an amplitude sensor while RASAL senses calcium oscillations. This difference between them resides not in their C2 domains, but in their PH domains leading to speculation that this might reflect an association with either phosphoinositides and/or proteins. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 241523  Cd Length: 140  Bit Score: 76.83  E-value: 2.50e-16
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2102677298  575 LISTSSNSNIAKQRTSTQQEQPIvlKEG-VMIKRAQGRKRFGRKNFKQRYFKLTTQDLSYSKTKGKEPLCKIPLEEILAV 653
Cdd:cd13372      5 LVDIEEEDELDLTRMLLLQAPMV--KEGfLFIHRTKGKGPLMASSFKKLYFTLTKDALSFAKTPHSKKSSSISLAKIRAA 82

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 2102677298  654 EKLHEDSFKMKNIFQIIQS-----QRALYVQAGNCVEEKEWIDILTKICRTNSNRL 704
Cdd:cd13372     83 EKVEEKCFGSSNVMQIIYTddagqQETLYLQCKSVNELNQWLSALRKVCSNNTNLL 138
PH2_TAPP1_2 cd13271
Tandem PH-domain-containing proteins 1 and 2 Pleckstrin homology (PH) domain, C-terminal ...
 592-690 1.33e-14

Tandem PH-domain-containing proteins 1 and 2 Pleckstrin homology (PH) domain, C-terminal repeat; The binding of TAPP1 (also called PLEKHA1/pleckstrin homology domain containing, family A (phosphoinositide binding specific) member 1) and TAPP2 (also called PLEKHA2) adaptors to PtdIns(3,4)P(2), but not PI(3,4, 5)P3, function as negative regulators of insulin and PI3K signalling pathways (i.e. TAPP/utrophin/syntrophin complex). TAPP1 and TAPP2 contain two sequential PH domains in which the C-terminal PH domain specifically binds PtdIns(3,4)P2 with high affinity. The N-terminal PH domain does not interact with any phosphoinositide tested. They also contain a C-terminal PDZ-binding motif that interacts with several PDZ-binding proteins, including PTPN13 (known previously as PTPL1 or FAP-1) as well as the scaffolding proteins MUPP1 (multiple PDZ-domain-containing protein 1), syntrophin and utrophin. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270090  Cd Length: 114  Bit Score: 70.85  E-value: 1.33e-14
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2102677298  592 QQEQPIVLKEGVMIKraQGRKRfgrKNFKQRYFKLTTQDLSYSKTK-GKEPLCKIPLEEILAV-EKLHEDSFKMKNIFQI 669
Cdd:cd13271      2 QRAGRNVIKSGYCVK--QGAVR---KNWKRRFFILDDNTISYYKSEtDKEPLRTIPLREVLKVhECLVKSLLMRDNLFEI 76

                           90       100
                   ....*....|....*....|.
gi 2102677298  670 IQSQRALYVQAGNCVEEKEWI 690
Cdd:cd13271     77 ITTSRTFYIQADSPEEMHSWI 97
C2 pfam00168
C2 domain;
145-265 6.46e-14

C2 domain;


Pssm-ID: 425499 [Multi-domain]  Cd Length: 104  Bit Score: 68.50  E-value: 6.46e-14
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2102677298  145 KLTVRVIECSELTIK--NGGCDPFAIVTVIYSNGKqvlKRTKIKKKTVSPYFNETFIFEpeiteskekdishysLEHGEV 222
Cdd:pfam00168    2 RLTVTVIEAKNLPPKdgNGTSDPYVKVYLLDGKQK---KKTKVVKNTLNPVWNETFTFS---------------VPDPEN 63

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|...
gi 2102677298  223 NEVIVGLWHASSGMGEQpaFLGEVRVTLRGLQKQSTNSTtaWY 265
Cdd:pfam00168   64 AVLEIEVYDYDRFGRDD--FIGEVRIPLSELDSGEGLDG--WY 102
BTK smart00107
Bruton's tyrosine kinase Cys-rich motif; Zinc-binding motif containing conserved cysteines and ...
 700-735 1.83e-13

Bruton's tyrosine kinase Cys-rich motif; Zinc-binding motif containing conserved cysteines and a histidine. Always found C-terminal to PH domains (but not all PH domains are followed by BTK motifs). The crystal structure shows this motif packs against the PH domain. The PH+Btk module pair has been called the Tec homology (TH) region.


Pssm-ID: 128417  Cd Length: 36  Bit Score: 65.10  E-value: 1.83e-13
                            10        20        30
                    ....*....|....*....|....*....|....*.
gi 2102677298   700 NSNRLEKYHPSAYINGHWLCCKAIAEIAPGCSEVSP 735
Cdd:smart00107    1 NNNLLQKYHPSFWVDGKWLCCQQSEKNAPGCTPYEA 36
BTK pfam00779
BTK motif; Zinc-binding motif containing conserved cysteines and a histidine. Always found ...
 706-735 2.96e-13

BTK motif; Zinc-binding motif containing conserved cysteines and a histidine. Always found C-terminal to PH domains. The crystal structure shows this motif packs against the PH domain. The PH+Btk module pair has been called the Tec homology (TH) region.


Pssm-ID: 459937  Cd Length: 30  Bit Score: 64.47  E-value: 2.96e-13
                           10        20        30
                   ....*....|....*....|....*....|
gi 2102677298  706 KYHPSAYINGHWLCCKAIAEIAPGCSEVSP 735
Cdd:pfam00779    1 KYHPGAFVDGKWLCCKQTDKNAPGCSPVTS 30
PH smart00233
Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The ...
 598-698 3.55e-13

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


Pssm-ID: 214574 [Multi-domain]  Cd Length: 102  Bit Score: 66.42  E-value: 3.55e-13
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2102677298   598 VLKEGVMIKRAQGrkrfGRKNFKQRYFKLTTQDLSYSKTK----GKEPLCKIPLEEILAVEKLHEDSFKMKNIFQIIQSQ 673
Cdd:smart00233    1 VIKEGWLYKKSGG----GKKSWKKRYFVLFNSTLLYYKSKkdkkSYKPKGSIDLSGCTVREAPDPDSSKKPHCFEIKTSD 76

                            90       100
                    ....*....|....*....|....*.
gi 2102677298   674 RA-LYVQAGNCVEEKEWIDILTKICR 698
Cdd:smart00233   77 RKtLLLQAESEEEREKWVEALRKAIA 102
C2 cd00030
C2 domain; The C2 domain was first identified in PKC. C2 domains fold into an 8-standed ...
 146-267 5.46e-12

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: 63.24  E-value: 5.46e-12
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2102677298  146 LTVRVIECSELTIK--NGGCDPFAIVTViysnGKQVLKRTKIKKKTVSPYFNETFIFEpeiteskekdishysLEHGEVN 223
Cdd:cd00030      1 LRVTVIEARNLPAKdlNGKSDPYVKVSL----GGKQKFKTKVVKNTLNPVWNETFEFP---------------VLDPESD 61

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....
gi 2102677298  224 EVIVGLWHASSGMGEQpaFLGEVRVTLRGLqKQSTNSTTAWYFL 267
Cdd:cd00030     62 TLTVEVWDKDRFSKDD--FLGEVEIPLSEL-LDSGKEGELWLPL 102
C2D_Tricalbin-like cd04040
C2 domain fourth repeat present in Tricalbin-like proteins; 5 to 6 copies of the C2 domain are ...
 14-129 6.36e-12

C2 domain fourth 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 fifth C2 repeat, C2E, and has a type-II topology.


Pssm-ID: 176005 [Multi-domain]  Cd Length: 115  Bit Score: 63.36  E-value: 6.36e-12
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2102677298   14 LKIKIGEVKNLQS--RNhgspGARDVYCVLSLDQEEIFRTTTMERTLNPFFGEEFQFEVP-RKFRYLGIYVYDRDRhLKQ 90
Cdd:cd04040      1 LTVDVISAENLPSadRN----GKSDPFVKFYLNGEKVFKTKTIKKTLNPVWNESFEVPVPsRVRAVLKVEVYDWDR-GGK 75

                           90       100       110
                   ....*....|....*....|....*....|....*....
gi 2102677298   91 DKILGKVAIKREDLTTYHNKEhwFPLrPVDADSEVQGKA 129
Cdd:cd04040     76 DDLLGSAYIDLSDLEPEETTE--LTL-PLDGQGGGKLGA 111
PH pfam00169
PH domain; PH stands for pleckstrin homology.
 598-698 8.33e-12

PH domain; PH stands for pleckstrin homology.


Pssm-ID: 459697 [Multi-domain]  Cd Length: 105  Bit Score: 62.58  E-value: 8.33e-12
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2102677298  598 VLKEGVMIKRAQGRKrfgrKNFKQRYFKLTTQDLSYSK----TKGKEPLCKIPLEEILAVEKLHEDSFKMKNIFQIIQSQ 673
Cdd:pfam00169    1 VVKEGWLLKKGGGKK----KSWKKRYFVLFDGSLLYYKddksGKSKEPKGSISLSGCEVVEVVASDSPKRKFCFELRTGE 76

                           90       100
                   ....*....|....*....|....*....
gi 2102677298  674 ----RALYVQAGNCVEEKEWIDILTKICR 698
Cdd:pfam00169   77 rtgkRTYLLQAESEEERKDWIKAIQSAIR 105
C2 smart00239
Protein kinase C conserved region 2 (CalB); Ca2+-binding motif present in phospholipases, ...
 145-256 1.13e-11

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: 62.12  E-value: 1.13e-11
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2102677298   145 KLTVRVIECSELTIKNGG--CDPFAIVTVIYSNGKQvlKRTKIKKKTVSPYFNETFIFEpeiteskekdishysLEHGEV 222
Cdd:smart00239    1 TLTVKIISARNLPPKDKGgkSDPYVKVSLDGDPKEK--KKTKVVKNTLNPVWNETFEFE---------------VPPPEL 63

                            90       100       110
                    ....*....|....*....|....*....|....
gi 2102677298   223 NEVIVGLWHASSGMGEQpaFLGEVRVTLRGLQKQ 256
Cdd:smart00239   64 AELEIEVYDKDRFGRDD--FIGQVTIPLSDLLLG 95
C2A_Synaptotagmin-8 cd08387
C2A domain first repeat present in Synaptotagmin 8; Synaptotagmin is a membrane-trafficking ...
 14-118 4.98e-11

C2A domain first repeat present in Synaptotagmin 8; 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 first C2 repeat, C2A, and has a type-I topology.


Pssm-ID: 176033 [Multi-domain]  Cd Length: 124  Bit Score: 60.88  E-value: 4.98e-11
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2102677298   14 LKIKIGEVKNLQSRNHGspGARDVYCVLSL--DQEEIFRTTTMERTLNPFFGEEFQFEVPRKF---RYLGIYVYDRDRHL 88
Cdd:cd08387     18 LNVKLIQARNLQPRDFS--GTADPYCKVRLlpDRSNTKQSKIHKKTLNPEFDESFVFEVPPQElpkRTLEVLLYDFDQFS 95

                           90       100       110
                   ....*....|....*....|....*....|
gi 2102677298   89 KqDKILGKVAIKREDLTTYHNKEHWFPLRP 118
Cdd:cd08387     96 R-DECIGVVELPLAEVDLSEKLDLWRKIQS 124
C2_NEDD4_NEDD4L cd04033
C2 domain present in the Human neural precursor cell-expressed, developmentally down-regulated ...
 33-135 1.96e-10

C2 domain present in the Human neural precursor cell-expressed, developmentally down-regulated 4 (NEDD4) and NEDD4-like (NEDD4L/NEDD42); Nedd4 and Nedd4-2 are two of the nine members of the Human Nedd4 family. All vertebrates appear to have both Nedd4 and Nedd4-2 genes. They are thought to participate in the regulation of epithelial Na+ channel (ENaC) activity. They also have identical specificity for ubiquitin conjugating enzymes (E2). Nedd4 and Nedd4-2 are composed of a C2 domain, 2-4 WW domains, and a ubiquitin ligase Hect domain. Their WW domains can bind PPxY (PY) or LPSY motifs, and in vitro studies suggest that WW3 and WW4 of both proteins bind PY motifs in the key substrates, with WW3 generally exhibiting higher affinity. Most Nedd4 family members, especially Nedd4-2, also have multiple splice variants, which might play different roles in regulating their substrates. 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: 175999 [Multi-domain]  Cd Length: 133  Bit Score: 59.67  E-value: 1.96e-10
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2102677298   33 GARDVYCVLSL------DQEEIFRTTTMERTLNPFFGEEFQFEV-PRKFRYLgIYVYDRDRhLKQDKILGKVAIKREDLT 105
Cdd:cd04033     19 GASDPYVKISLydpdgnGEIDSVQTKTIKKTLNPKWNEEFFFRVnPREHRLL-FEVFDENR-LTRDDFLGQVEVPLNNLP 96

                           90       100       110
                   ....*....|....*....|....*....|....*.
gi 2102677298  106 TYHNKEHW------FPLRPVDADSEVqgKAHLEISL 135
Cdd:cd04033     97 TETPGNERrytfkdYLLRPRSSKSRV--KGHLRLYM 130
C2B_Synaptotagmin cd00276
C2 domain second repeat present in Synaptotagmin; Synaptotagmin is a membrane-trafficking ...
 144-213 2.90e-10

C2 domain second repeat present in Synaptotagmin; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. There are several classes of Synaptotagmins. 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: 175975 [Multi-domain]  Cd Length: 134  Bit Score: 59.13  E-value: 2.90e-10
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 2102677298  144 SKLTVRVIECSELTIKNGGC--DPFAIVTVIYSNGKQVLKRTKIKKKTVSPYFNETFIFepEITESKEKDIS 213
Cdd:cd00276     14 ERLTVVVLKARNLPPSDGKGlsDPYVKVSLLQGGKKLKKKKTSVKKGTLNPVFNEAFSF--DVPAEQLEEVS 83
C2B_Tricalbin-like cd04052
C2 domain second repeat present in Tricalbin-like proteins; 5 to 6 copies of the C2 domain are ...
 29-136 5.03e-10

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: 57.61  E-value: 5.03e-10
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2102677298   29 HGSPGARDVYCVLSLDQEEIFRTTTMERTLNPFFGEEFQFEVPRKFR-YLGIYVYD-RDRHlkqDKILGKVAIKREDL-T 105
Cdd:cd04052      7 ESKTGLLSPYAELYLNGKLVYTTRVKKKTNNPSWNASTEFLVTDRRKsRVTVVVKDdRDRH---DPVLGSVSISLNDLiD 83

                           90       100       110
                   ....*....|....*....|....*....|.
gi 2102677298  106 TYHNKEHWFPLRPVdadsevqGKAHLEISLQ 136
Cdd:cd04052     84 ATSVGQQWFPLSGN-------GQGRIRISAL 107
PH cd00821
Pleckstrin homology (PH) domain; PH domains have diverse functions, but in general are ...
 600-693 6.04e-10

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


Pssm-ID: 275388 [Multi-domain]  Cd Length: 92  Bit Score: 56.78  E-value: 6.04e-10
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2102677298  600 KEGVMIKRaqgrKRFGRKNFKQRYFKLTTQDLSYSKTK---GKEPLCKIPLEEILAVEKLHEDsfKMKNIFQII-QSQRA 675
Cdd:cd00821      1 KEGYLLKR----GGGGLKSWKKRWFVLFEGVLLYYKSKkdsSYKPKGSIPLSGILEVEEVSPK--ERPHCFELVtPDGRT 74

                           90
                   ....*....|....*...
gi 2102677298  676 LYVQAGNCVEEKEWIDIL 693
Cdd:cd00821     75 YYLQADSEEERQEWLKAL 92
C2B_Rabphilin_Doc2 cd08384
C2 domain second repeat present in Rabphilin and Double C2 domain; Rabphilin is found neurons ...
 131-239 9.59e-10

C2 domain second repeat present in Rabphilin and Double C2 domain; Rabphilin is found neurons and in neuroendrocrine cells, while Doc2 is found not only in the brain but in tissues, including mast cells, chromaffin cells, and osteoblasts. Rabphilin and Doc2s share highly homologous tandem C2 domains, although their N-terminal structures are completely different: rabphilin contains an N-terminal Rab-binding domain (RBD),7 whereas Doc2 contains an N-terminal Munc13-1-interacting domain (MID). 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: 176030 [Multi-domain]  Cd Length: 133  Bit Score: 57.74  E-value: 9.59e-10
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2102677298  131 LEISLQSQIghAQSKLTVRVIECSELTI--KNGGCDPFAIVTVIYSNGKQVLKRTKIKKKTVSPYFNETFIFEPEITE-- 206
Cdd:cd08384      2 ILVSLMYNT--QRRGLIVGIIRCVNLAAmdANGYSDPFVKLYLKPDAGKKSKHKTQVKKKTLNPEFNEEFFYDIKHSDla 79

                           90       100       110
                   ....*....|....*....|....*....|...
gi 2102677298  207 SKEKDISHYSLEHGEVNEVIVGLWHASSGMGEQ 239
Cdd:cd08384     80 KKTLEITVWDKDIGKSNDYIGGLQLGINAKGER 112
C2C_MCTP_PRT cd08377
C2 domain third repeat found in Multiple C2 domain and Transmembrane region Proteins (MCTP); ...
 14-136 1.01e-09

C2 domain third repeat found in Multiple C2 domain and Transmembrane region Proteins (MCTP); MCTPs are involved in Ca2+ signaling at the membrane. The cds in this family contain multiple C2 domains as well as a C-terminal PRT domain. 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: 176023 [Multi-domain]  Cd Length: 119  Bit Score: 57.31  E-value: 1.01e-09
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2102677298   14 LKIKIGEVKNLQSRNHGspGARDVYCVLSLDQEEIfRTTTMERTLNPFFGEEFQFEVPRKFRYLGIYVYDRDRHLKQDkI 93
Cdd:cd08377      3 LQVKVIRASGLAAADIG--GKSDPFCVLELVNARL-QTHTIYKTLNPEWNKIFTFPIKDIHDVLEVTVYDEDKDKKPE-F 78

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....
gi 2102677298   94 LGKVAIKredLTTYHNKE-HWFPLRPVDADSEVQGKAHLEISLQ 136
Cdd:cd08377     79 LGKVAIP---LLSIKNGErKWYALKDKKLRTRAKGSILLEMDVI 119
C2A_Synaptotagmin-like cd04024
C2 domain first repeat present in Synaptotagmin-like proteins; Synaptotagmin is a ...
 14-135 1.30e-09

C2 domain first 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 first C2 repeat, C2A, and has a type-I topology.


Pssm-ID: 175990 [Multi-domain]  Cd Length: 128  Bit Score: 57.05  E-value: 1.30e-09
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2102677298   14 LKIKIGEVKNLQSRNHGSPGARDVYCVLSL-DQEeiFRTTTMERTLNPFFGEEFQFEV-PRKFRYLGIYVYDRDRHLKQD 91
Cdd:cd04024      3 LRVHVVEAKDLAAKDRSGKGKSDPYAILSVgAQR--FKTQTIPNTLNPKWNYWCEFPIfSAQNQLLKLILWDKDRFAGKD 80

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*....
gi 2102677298   92 KiLGKVAIKREDLTTYHNKEH---WFPLRPVDA--DSEVQGKAHLEISL 135
Cdd:cd04024     81 Y-LGEFDIALEEVFADGKTGQsdkWITLKSTRPgkTSVVSGEIHLQFSW 128
PH1_PH_fungal cd13298
Fungal proteins Pleckstrin homology (PH) domain, repeat 1; The functions of these fungal ...
 598-702 1.82e-09

Fungal proteins Pleckstrin homology (PH) domain, repeat 1; The functions of these fungal proteins are unknown, but they all contain 2 PH domains. This cd represents the first PH repeat. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270110  Cd Length: 106  Bit Score: 56.09  E-value: 1.82e-09
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2102677298  598 VLKEGVMIKRaqGRKRfgrKNFKQRYFKLTTQDLSYSK-TKGKEPLCKIPLEEILAVEKLHEDsfKMKNIFQIIQSQRAL 676
Cdd:cd13298      6 VLKSGYLLKR--SRKT---KNWKKRWVVLRPCQLSYYKdEKEYKLRRVINLSELLAVAPLKDK--KRKNVFGIYTPSKNL 78

                           90       100
                   ....*....|....*....|....*.
gi 2102677298  677 YVQAGNCVEEKEWIDILTKICRTNSN 702
Cdd:cd13298     79 HFRATSEKDANEWVEALREEFRLDDE 104
C2_SynGAP_like cd04013
C2 domain present in Ras GTPase activating protein (GAP) family; SynGAP, GAP1, RasGAP, and ...
 9-139 3.95e-09

C2 domain present in Ras GTPase activating protein (GAP) family; SynGAP, GAP1, RasGAP, and neurofibromin are all members of the Ras-specific GAP (GTPase-activating protein) family. SynGAP regulates the MAP kinase signaling pathway and is critical for cognition and synapse function. Mutations in this gene causes mental retardation in humans. SynGAP contains a PH-like domain, a C2 domain, and a Ras-GAP 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.


Pssm-ID: 175980 [Multi-domain]  Cd Length: 146  Bit Score: 56.16  E-value: 3.95e-09
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2102677298    9 RVEERLKIKIGEVKNLqsrnhgsPGARDVYCVLSLDQEEIFRTTTMERTLNPFFGEEFQFEVPRKFRYLGIYVY-DRDRH 87
Cdd:cd04013      8 RTENSLKLWIIEAKGL-------PPKKRYYCELCLDKTLYARTTSKLKTDTLFWGEHFEFSNLPPVSVITVNLYrESDKK 80

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....
gi 2102677298   88 LKQDK--ILGKVAIKREDLTTYHNKEHWFPLRPVDADSEVQGKAHLEISLQSQI 139
Cdd:cd04013     81 KKKDKsqLIGTVNIPVTDVSSRQFVEKWYPVSTPKGNGKSGGKEGKGESPSIRI 134
C2A_SLP-1_2 cd08393
C2 domain first repeat present in Synaptotagmin-like proteins 1 and 2; All Slp members ...
 146-268 1.08e-08

C2 domain first repeat present in Synaptotagmin-like proteins 1 and 2; All Slp members basically share an N-terminal Slp homology domain (SHD) and C-terminal tandem C2 domains (named the C2A domain and the C2B domain) with the SHD and C2 domains being separated by a linker sequence of various length. Slp1/JFC1 and Slp2/exophilin 4 promote granule docking to the plasma membrane. Additionally, their C2A domains are both Ca2+ independent, unlike Slp3 and Slp4/granuphilin which are Ca2+ dependent. It is thought that SHD (except for the Slp4-SHD) functions as a specific Rab27A/B-binding domain. In addition to Slps, rabphilin, Noc2, and Munc13-4 also function as Rab27-binding 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-I topology.


Pssm-ID: 176039 [Multi-domain]  Cd Length: 125  Bit Score: 54.36  E-value: 1.08e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2102677298  146 LTVRVIECSELTI---KNGGCDPFAIVTVIYSNGKQVLKRTKIKKKTVSPYFNETFIFEPEITESKEKDIShyslehgev 222
Cdd:cd08393     17 LHVHVIQCQDLAAadpKKQRSDPYVKTYLLPDKSNRGKRKTSVKKKTLNPVFNETLRYKVEREELPTRVLN--------- 87

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*.
gi 2102677298  223 neviVGLWHASSgMGEQpAFLGEVRVTLRglQKQSTNSTTAWYFLQ 268
Cdd:cd08393     88 ----LSVWHRDS-LGRN-SFLGEVEVDLG--SWDWSNTQPTWYPLQ 125
C2A_MCTP_PRT cd04042
C2 domain first repeat found in Multiple C2 domain and Transmembrane region Proteins (MCTP); ...
 13-117 1.41e-08

C2 domain first repeat found in Multiple C2 domain and Transmembrane region Proteins (MCTP); MCTPs are involved in Ca2+ signaling at the membrane. MCTP is composed of a variable N-terminal sequence, three 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 first C2 repeat, C2A, and has a type-II topology.


Pssm-ID: 176007 [Multi-domain]  Cd Length: 121  Bit Score: 53.82  E-value: 1.41e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2102677298   13 RLKIKIGEVKNLQSRNHGspGARDVYCVLSLDQEEIFRTTTMERTLNPFFGEEFQFEVPRKFRYLGIYVYDRDRHLkQDK 92
Cdd:cd04042      1 QLDIHLKEGRNLAARDRG--GTSDPYVKFKYGGKTVYKSKTIYKNLNPVWDEKFTLPIEDVTQPLYIKVFDYDRGL-TDD 77

                           90       100
                   ....*....|....*....|....*
gi 2102677298   93 ILGKVAIKREDLTTYHNKEHWFPLR 117
Cdd:cd04042     78 FMGSAFVDLSTLELNKPTEVKLKLE 102
C2C_KIAA1228 cd04030
C2 domain third repeat present in uncharacterized human KIAA1228-like proteins; KIAA proteins ...
 127-268 1.61e-08

C2 domain third repeat present in uncharacterized human KIAA1228-like proteins; KIAA proteins are uncharacterized human proteins. They were compiled by the Kazusa mammalian cDNA project which identified more than 2000 human genes. They are identified by 4 digit codes that precede the KIAA designation. Many KIAA genes are still functionally uncharacterized including KIAA1228. 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: 175996 [Multi-domain]  Cd Length: 127  Bit Score: 53.82  E-value: 1.61e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2102677298  127 GKAHLEISLQSQighaQSKLTVRVIECSELTIKN--GGCDPFAIVTVIYSNGKQVLKRTKIKKKTVSPYFNETFIFEPEI 204
Cdd:cd04030      3 GRIQLTIRYSSQ----RQKLIVTVHKCRNLPPCDssDIPDPYVRLYLLPDKSKSTRRKTSVKKDNLNPVFDETFEFPVSL 78

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 2102677298  205 TESKEKdishySLEhgevneviVGLWHASSGMGEQPAFLGEVRVTLRglQKQSTNSTTAWYFLQ 268
Cdd:cd04030     79 EELKRR-----TLD--------VAVKNSKSFLSREKKLLGQVLIDLS--DLDLSKGFTQWYDLT 127
C2A_RIM1alpha cd04031
C2 domain first repeat contained in Rab3-interacting molecule (RIM) proteins; RIMs are ...
 9-117 1.71e-08

C2 domain first repeat contained in Rab3-interacting molecule (RIM) proteins; RIMs are believed to organize specialized sites of the plasma membrane called active zones. They also play a role in controlling neurotransmitter release, plasticity processes, as well as memory and learning. RIM contains an N-terminal zinc finger domain, a PDZ domain, and two C-terminal C2 domains (C2A, C2B). 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 and do not bind Ca2+.


Pssm-ID: 175997 [Multi-domain]  Cd Length: 125  Bit Score: 53.79  E-value: 1.71e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2102677298    9 RVEERLKIKIGEVKNLQSRNHGSPgaRDVY--CVLSLDQEEIF--RTTTMERTLNPFFGEEFQFEVPR----KFRYLGIY 80
Cdd:cd04031     13 KVTSQLIVTVLQARDLPPRDDGSL--RNPYvkVYLLPDRSEKSkrRTKTVKKTLNPEWNQTFEYSNVRretlKERTLEVT 90

                           90       100       110
                   ....*....|....*....|....*....|....*....
gi 2102677298   81 VYDRDRHlKQDKILGKVAIkreDLTTY--HNKEHWFPLR 117
Cdd:cd04031     91 VWDYDRD-GENDFLGEVVI---DLADAllDDEPHWYPLQ 125
C2A_Synaptotagmin-15-17 cd08390
C2A domain first repeat present in Synaptotagmins 15 and 17; Synaptotagmin is a ...
 11-118 2.04e-08

C2A domain first repeat present in Synaptotagmins 15 and 17; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. It is thought to be involved in the trafficking and exocytosis of secretory vesicles in non-neuronal tissues and is Ca2+ independent. Human synaptotagmin 15 has 2 alternatively spliced forms that encode proteins with different C-termini. The larger, SYT15a, contains a N-terminal TM region, a putative fatty-acylation site, and 2 tandem C terminal C2 domains. The smaller, SYT15b, lacks the C-terminal portion of the second C2 domain. Unlike most other synaptotagmins it is nearly absent in the brain and rather is found in the heart, lungs, skeletal muscle, and testis. Synaptotagmin 17 is located in the brain, kidney, and prostate and is thought to be a peripheral membrane protein. 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 first C2 repeat, C2A, and has a type-I topology.


Pssm-ID: 176036 [Multi-domain]  Cd Length: 123  Bit Score: 53.41  E-value: 2.04e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2102677298   11 EERLKIKIGEVKNLQSRNHGSPGaRDVYCVLSL--DQEEIFRTTTMERTLNPFFGEEFQFEVPRKF---RYLGIYVYDRD 85
Cdd:cd08390     13 EEQLTVSLIKARNLPPRTKDVAH-CDPFVKVCLlpDERRSLQSKVKRKTQNPNFDETFVFQVSFKElqrRTLRLSVYDVD 91

                           90       100       110
                   ....*....|....*....|....*....|...
gi 2102677298   86 RHLKQDkILGKVAIKREDLTTYHNKEHWFPLRP 118
Cdd:cd08390     92 RFSRHC-IIGHVLFPLKDLDLVKGGVVWRDLEP 123
C2B_Munc13-like cd04009
C2 domain second repeat in Munc13 (mammalian uncoordinated)-like proteins; C2-like domains are ...
 141-201 3.04e-08

C2 domain second 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 third C2 repeat, C2C, and has a type-II topology.


Pssm-ID: 175976 [Multi-domain]  Cd Length: 133  Bit Score: 53.40  E-value: 3.04e-08
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 2102677298  141 HAQSKLTVRVIECSELTIK--NGGCDPFAIVTVI----YSngKQVLKRTKIKKKTVSPYFNETFIFE 201
Cdd:cd04009     13 ASEQSLRVEILNARNLLPLdsNGSSDPFVKVELLprhlFP--DVPTPKTQVKKKTLFPLFDESFEFN 77
C2_PKC_epsilon cd04014
C2 domain in Protein Kinase C (PKC) epsilon; A single C2 domain is found in PKC epsilon. The ...
 14-137 3.88e-08

C2 domain in Protein Kinase C (PKC) epsilon; A single C2 domain is found in PKC epsilon. The PKC family of serine/threonine kinases regulates apoptosis, proliferation, migration, motility, chemo-resistance, and differentiation. There are 3 groups: group 1 (alpha, betaI, beta II, gamma) which require phospholipids and calcium, group 2 (delta, epsilon, theta, eta) which do not require calcium for activation, and group 3 (xi, iota/lambda) which are atypical and can be activated in the absence of diacylglycerol and calcium. 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: 175981 [Multi-domain]  Cd Length: 132  Bit Score: 53.05  E-value: 3.88e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2102677298   14 LKIKIGEVKNLQ----SRNHGSPGAR----DVYCVLSLDQEEIFRTTTMERTLNPFFGEEFQFEVpRKFRYLGIYVYdrd 85
Cdd:cd04014      6 LKIKICEAVDLKptdwSTRHAVPKKGsqllDPYVSIDVDDTHIGKTSTKPKTNSPVWNEEFTTEV-HNGRNLELTVF--- 81

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|
gi 2102677298   86 rHlkqDKILGK---VA---IKREDLTTY--HNKEHWFPLRPvdadsevQGKAHLEISLQS 137
Cdd:cd04014     82 -H---DAAIGPddfVAnctISFEDLIQRgsGSFDLWVDLEP-------QGKLHVKIELKG 130
C2_ArfGAP cd04038
C2 domain present in Arf GTPase Activating Proteins (GAP); ArfGAP is a GTPase activating ...
 14-112 4.38e-08

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: 53.10  E-value: 4.38e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2102677298   14 LKIKIGEVKNLQSRNhgsPGARDVYCVLSLDQEEIfRTTTMERTLNPFFGEEFQFEVPRKFRYLGIYVYDRDRHLKQDKi 93
Cdd:cd04038      4 LKVRVVRGTNLAVRD---FTSSDPYVVLTLGNQKV-KTRVIKKNLNPVWNEELTLSVPNPMAPLKLEVFDKDTFSKDDS- 78

                           90
                   ....*....|....*....
gi 2102677298   94 LGKVAIKREDLTTYHNKEH 112
Cdd:cd04038     79 MGEAEIDLEPLVEAAKLDH 97
C2A_Synaptotagmin-15-17 cd08390
C2A domain first repeat present in Synaptotagmins 15 and 17; Synaptotagmin is a ...
 134-201 6.16e-08

C2A domain first repeat present in Synaptotagmins 15 and 17; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. It is thought to be involved in the trafficking and exocytosis of secretory vesicles in non-neuronal tissues and is Ca2+ independent. Human synaptotagmin 15 has 2 alternatively spliced forms that encode proteins with different C-termini. The larger, SYT15a, contains a N-terminal TM region, a putative fatty-acylation site, and 2 tandem C terminal C2 domains. The smaller, SYT15b, lacks the C-terminal portion of the second C2 domain. Unlike most other synaptotagmins it is nearly absent in the brain and rather is found in the heart, lungs, skeletal muscle, and testis. Synaptotagmin 17 is located in the brain, kidney, and prostate and is thought to be a peripheral membrane protein. 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 first C2 repeat, C2A, and has a type-I topology.


Pssm-ID: 176036 [Multi-domain]  Cd Length: 123  Bit Score: 52.26  E-value: 6.16e-08
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 2102677298  134 SLQSQIGHAQskLTVRVIECSEL---TIKNGGCDPFAIVTVIYSNGKQvlKRTKIKKKTVSPYFNETFIFE 201
Cdd:cd08390      6 SVQYDLEEEQ--LTVSLIKARNLpprTKDVAHCDPFVKVCLLPDERRS--LQSKVKRKTQNPNFDETFVFQ 72
PH_DAPP1 cd10573
Dual Adaptor for Phosphotyrosine and 3-Phosphoinositides Pleckstrin homology (PH) domain; ...
 596-693 9.55e-08

Dual Adaptor for Phosphotyrosine and 3-Phosphoinositides Pleckstrin homology (PH) domain; DAPP1 (also known as PHISH/3' phosphoinositide-interacting SH2 domain-containing protein or Bam32) plays a role in B-cell activation and has potential roles in T-cell and mast cell function. DAPP1 promotes B cell receptor (BCR) induced activation of Rho GTPases Rac1 and Cdc42, which feed into mitogen-activated protein kinases (MAPK) activation pathways and affect cytoskeletal rearrangement. DAPP1can also regulate BCR-induced activation of extracellular signal-regulated kinase (ERK), and c-jun NH2-terminal kinase (JNK). DAPP1 contains an N-terminal SH2 domain and a C-terminal pleckstrin homology (PH) domain with a single tyrosine phosphorylation site located centrally. DAPP1 binds strongly to both PtdIns(3,4,5)P3 and PtdIns(3,4)P2. The PH domain is essential for plasma membrane recruitment of PI3K upon cell activation. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 269977 [Multi-domain]  Cd Length: 96  Bit Score: 50.79  E-value: 9.55e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2102677298  596 PIVLKEGVMIKRAqgrkrFGRKNFKQRYFKLTTQDLSYSKTKG-KEPLCKIPLEEILAVEKlhEDSFKMKNIFQIIQSQR 674
Cdd:cd10573      1 SLGSKEGYLTKLG-----GIVKNWKTRWFVLRRNELKYFKTRGdTKPIRVLDLRECSSVQR--DYSQGKVNCFCLVFPER 73

                           90
                   ....*....|....*....
gi 2102677298  675 ALYVQAGNCVEEKEWIDIL 693
Cdd:cd10573     74 TFYMYANTEEEADEWVKLL 92
C2A_Rabphilin_Doc2 cd04035
C2 domain first repeat present in Rabphilin and Double C2 domain; Rabphilin is found neurons ...
 131-260 2.01e-07

C2 domain first repeat present in Rabphilin and Double C2 domain; Rabphilin is found neurons and in neuroendrocrine cells, while Doc2 is found not only in the brain but in tissues, including mast cells, chromaffin cells, and osteoblasts. Rabphilin and Doc2s share highly homologous tandem C2 domains, although their N-terminal structures are completely different: rabphilin contains an N-terminal Rab-binding domain (RBD),7 whereas Doc2 contains an N-terminal Munc13-1-interacting domain (MID). 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: 176000 [Multi-domain]  Cd Length: 123  Bit Score: 50.74  E-value: 2.01e-07
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2102677298  131 LEISLQSQIghAQSKLTVRVIECSEL--TIKNGGCDPFAIVTVIYSNGKQVLKRTKIKKKTVSPYFNETFIFEPeITesk 208
Cdd:cd04035      4 LEFTLLYDP--ANSALHCTIIRAKGLkaMDANGLSDPYVKLNLLPGASKATKLRTKTVHKTRNPEFNETLTYYG-IT--- 77

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 2102677298  209 EKDISHYSLehgevnEVIVglwhassgMGEQPA---FLGEVRVTLRGLQKQSTNS 260
Cdd:cd04035     78 EEDIQRKTL------RLLV--------LDEDRFgndFLGETRIPLKKLKPNQTKQ 118
C2D_Tricalbin-like cd04040
C2 domain fourth repeat present in Tricalbin-like proteins; 5 to 6 copies of the C2 domain are ...
 146-201 2.03e-07

C2 domain fourth 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 fifth C2 repeat, C2E, and has a type-II topology.


Pssm-ID: 176005 [Multi-domain]  Cd Length: 115  Bit Score: 50.26  E-value: 2.03e-07
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*...
gi 2102677298  146 LTVRVIECSELTI--KNGGCDPFAivtVIYSNGKQVLKrTKIKKKTVSPYFNETFIFE 201
Cdd:cd04040      1 LTVDVISAENLPSadRNGKSDPFV---KFYLNGEKVFK-TKTIKKTLNPVWNESFEVP 54
C2_C21orf25-like cd08678
C2 domain found in the Human chromosome 21 open reading frame 25 (C21orf25) protein; The ...
 21-124 2.41e-07

C2 domain found in the Human chromosome 21 open reading frame 25 (C21orf25) protein; The members in this cd are named after the Human C21orf25 which contains a single C2 domain. Several other members contain a C1 domain downstream of the C2 domain. 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: 176060 [Multi-domain]  Cd Length: 126  Bit Score: 50.44  E-value: 2.41e-07
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2102677298   21 VKNLQS--RNHGSpGARDVYCVLSLD---QEeiFRTTTMERTLNPFFGEEFQFEVPRKFRYLGIYVYDRDRhLKQDKILG 95
Cdd:cd08678      3 VKNIKAngLSEAA-GSSNPYCVLEMDeppQK--YQSSTQKNTSNPFWDEHFLFELSPNSKELLFEVYDNGK-KSDSKFLG 78

                           90       100
                   ....*....|....*....|....*....
gi 2102677298   96 KVAIKREDLTTYHNKEHWFPLRPVDADSE 124
Cdd:cd08678     79 LAIVPFDELRKNPSGRQIFPLQGRPYEGD 107
C2_Munc13_fungal cd04043
C2 domain in Munc13 (mammalian uncoordinated) proteins; fungal group; C2-like domains are ...
 16-141 2.86e-07

C2 domain in Munc13 (mammalian uncoordinated) proteins; fungal group; 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: 176008 [Multi-domain]  Cd Length: 126  Bit Score: 50.34  E-value: 2.86e-07
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2102677298   16 IKIGEVKNLQSRnhGSPGARDVYCVLSLD--QEEIFRTTTMERTLNPFFGEEFQFEVPRKF-RYLGIYVYDRdRHLKQDK 92
Cdd:cd04043      5 IRIVRAENLKAD--SSNGLSDPYVTLVDTngKRRIAKTRTIYDTLNPRWDEEFELEVPAGEpLWISATVWDR-SFVGKHD 81

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|..
gi 2102677298   93 ILGKVAIK---REDLTTYHNKEHWFPLRPvdadsevQGKAHLEISLQSQIGH 141
Cdd:cd04043     82 LCGRASLKldpKRFGDDGLPREIWLDLDT-------QGRLLLRVSMEGERDD 126
C2A_Synaptotagmin-1-5-6-9-10 cd08385
C2A domain first repeat present in Synaptotagmins 1, 5, 6, 9, and 10; Synaptotagmin is a ...
 11-113 3.37e-07

C2A domain first repeat present in Synaptotagmins 1, 5, 6, 9, and 10; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. Synaptotagmin 1, a member of class 1 synaptotagmins, is located in the brain and endocranium and localized to the synaptic vesicles and secretory granules. It functions as a Ca2+ sensor for fast exocytosis as do synaptotagmins 5, 6, and 10. It is distinguished from the other synaptotagmins by having an N-glycosylated N-terminus. Synaptotagmins 5, 6, and 10, members of class 3 synaptotagmins, are located primarily in the brain and localized to the active zone and plasma membrane. They is distinguished from the other synaptotagmins by having disulfide bonds at its N-terminus. Synaptotagmin 6 also regulates the acrosome reaction, a unique Ca2+-regulated exocytosis, in sperm. Synaptotagmin 9, a class 5 synaptotagmins, is located in the brain and localized to the synaptic vesicles. It is thought to be a Ca2+-sensor for dense-core vesicle exocytosis. 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 first C2 repeat, C2A, and has a type-I topology.


Pssm-ID: 176031 [Multi-domain]  Cd Length: 124  Bit Score: 49.96  E-value: 3.37e-07
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2102677298   11 EERLKIKIGEVKNLQSRNHGspGARDVYCVLSL--DQEEIFRTTTMERTLNPFFGEEFQFEVPRK---FRYLGIYVYDRD 85
Cdd:cd08385     15 SNQLTVGIIQAADLPAMDMG--GTSDPYVKVYLlpDKKKKFETKVHRKTLNPVFNETFTFKVPYSelgNKTLVFSVYDFD 92

                           90       100
                   ....*....|....*....|....*...
gi 2102677298   86 RHLKQDKIlGKVAIKREDLTTYHNKEHW 113
Cdd:cd08385     93 RFSKHDLI-GEVRVPLLTVDLGHVTEEW 119
RasGAP_IQGAP_like cd05127
Ras-GTPase Activating Domain of IQ motif containing GTPase activating proteins; This family ...
 366-532 3.57e-07

Ras-GTPase Activating Domain of IQ motif containing GTPase activating proteins; This family represents IQ motif containing GTPase activating protein (IQGAP) which associated with the Ras GTP-binding protein. A primary function of IQGAP proteins is to modulate cytoskeletal architecture. There are three known IQGAP family members: IQGAP1, IQGAP2 and IQGAP3. Human IQGAP1 and IQGAP2 share 62% identity. IQGAPs are multi-domain molecules having a calponin-homology (CH) domain which binds F-actin, IQGAP-specific repeats, a single WW domain, four IQ motifs that mediate interactions with calmodulin, and a RasGAP related domain that binds active Rho family GTPases. IQGAP is an essential regulator of cytoskeletal function. IQGAP1 negatively regulates Ras family GTPases by stimulating their intrinsic GTPase activity, the protein actually lacks GAP activity. Both IQGAP1 and IQGAP2 specifically bind to Cdc42 and Rac1, but not to RhoA. Despite of their similarities to part of the sequence of RasGAP, neither IQGAP1 nor IQGAP2 interacts with Ras. IQGAP3, only present in mammals, regulates the organization of the cytoskeleton under the regulation of Rac1 and Cdc42 in neuronal cells. The depletion of IQGAP3 is shown to impair neurite or axon outgrowth in neuronal cells with disorganized cytoskeleton.


Pssm-ID: 213329 [Multi-domain]  Cd Length: 331  Bit Score: 53.36  E-value: 3.57e-07
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2102677298  366 ALASHE--ISKLTDPTTIFRGNTLVSKMMDEGMRLA-GLHYLHSTLRPAMKQVfLEKKSCEI--DP-------------- 426
Cdd:cd05127     15 KTALREeiESKVSLPEDIVTGNPTVIKLVVNYNRGPrGQKYLRELLGPVVKEI-LDDDDLDLetDPvdiykawinqeesr 93

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2102677298  427 -----TRVKDANTIQ------------TNLTNLKEYVERVFIAITTS------GVRCpslMC-EMFWCLKElaatHFPKN 482
Cdd:cd05127     94 tgepsKLPYDVTREQalkdpevrkrliEHLEKLRAITDKFLTAITESldkmpyGMRY---IAkVLKEALRE----KFPDA 166

                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 2102677298  483 KEVRY-SVISGFIFLRFFAPAILGPRLFDIT----TEQIDSQTNRTLTLISKTIQ 532
Cdd:cd05127    167 PEEEIlKIVGNLLYYRYMNPAIVAPEAFDIIdlsvGGQLSPLQRRNLGSIAKVLQ 221
C2B_RasA1_RasA4 cd04025
C2 domain second repeat present in RasA1 and RasA4; RasA1 and RasA4 are GAP1s (GTPase ...
 145-299 4.29e-07

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: 49.79  E-value: 4.29e-07
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2102677298  145 KLTVRVIECSELTIK--NGGCDPFaiVTVIYsNGKQvlKRTKIKKKTVSPYFNETFIFEpeiteskekdishysLEHGEV 222
Cdd:cd04025      1 RLRCHVLEARDLAPKdrNGTSDPF--VRVFY-NGQT--LETSVVKKSCYPRWNEVFEFE---------------LMEGAD 60

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 2102677298  223 NEVIVGLWHASsgMGEQPAFLGEVRVTLRGLQKQStnSTTAWYFLQPRAVKHRPNKISnsstspgvlpgLGSLRLKI 299
Cdd:cd04025     61 SPLSVEVWDWD--LVSKNDFLGKVVFSIQTLQQAK--QEEGWFRLLPDPRAEEESGGN-----------LGSLRLKV 122
C2B_Synaptotagmin-1 cd08402
C2 domain second repeat present in Synaptotagmin 1; Synaptotagmin is a membrane-trafficking ...
 145-201 4.76e-07

C2 domain second repeat present in Synaptotagmin 1; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. Synaptotagmin 1, a member of the class 1 synaptotagmins, is located in the brain and endocranium and localized to the synaptic vesicles and secretory granules. It functions as a Ca2+ sensor for fast exocytosis. It, like synaptotagmin-2, has an N-glycosylated N-terminus. Synaptotagmin 4, a member of class 4 synaptotagmins, is located in the brain. It functions are unknown. It, like synaptotagmin-11, has an Asp to Ser substitution in its C2A domain. 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: 176047 [Multi-domain]  Cd Length: 136  Bit Score: 50.09  E-value: 4.76e-07
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|
gi 2102677298  145 KLTVRVIECSELTIKN--GGCDPFAIVTvIYSNGKQV-LKRTKIKKKTVSPYFNETFIFE 201
Cdd:cd08402     16 KLTVVILEAKNLKKMDvgGLSDPYVKIH-LMQNGKRLkKKKTTIKKRTLNPYYNESFSFE 74
C2A_Synaptotagmin-8 cd08387
C2A domain first repeat present in Synaptotagmin 8; Synaptotagmin is a membrane-trafficking ...
 146-212 5.92e-07

C2A domain first repeat present in Synaptotagmin 8; 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 first C2 repeat, C2A, and has a type-I topology.


Pssm-ID: 176033 [Multi-domain]  Cd Length: 124  Bit Score: 49.32  E-value: 5.92e-07
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 2102677298  146 LTVRVIECSELTIKN--GGCDPFAIVTVIysNGKQVLKRTKIKKKTVSPYFNETFIFEPEITESKEKDI 212
Cdd:cd08387     18 LNVKLIQARNLQPRDfsGTADPYCKVRLL--PDRSNTKQSKIHKKTLNPEFDESFVFEVPPQELPKRTL 84
C2A_SLP cd08521
C2 domain first repeat present in Synaptotagmin-like proteins; All Slp members basically share ...
 132-267 6.29e-07

C2 domain first repeat present in Synaptotagmin-like proteins; All Slp members basically share an N-terminal Slp homology domain (SHD) and C-terminal tandem C2 domains (named the C2A domain and the C2B domain) with the SHD and C2 domains being separated by a linker sequence of various length. Slp1/JFC1 and Slp2/exophilin 4 promote granule docking to the plasma membrane. Additionally, their C2A domains are both Ca2+ independent, unlike the case in Slp3 and Slp4/granuphilin in which their C2A domains are Ca2+ dependent. It is thought that SHD (except for the Slp4-SHD) functions as a specific Rab27A/B-binding domain. In addition to Slps, rabphilin, Noc2, and Munc13-4 also function as Rab27-binding proteins. It has been demonstrated that Slp3 and Slp4/granuphilin promote dense-core vesicle exocytosis. Slp5 mRNA has been shown to be restricted to human placenta and liver suggesting a role in Rab27A-dependent membrane trafficking in specific tissues. 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: 176056 [Multi-domain]  Cd Length: 123  Bit Score: 49.18  E-value: 6.29e-07
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2102677298  132 EISLQSQIGHAQSKLTVRVIECSELTI---KNGGCDPFAIVTVIYSNGKQVLKRTKIKKKTVSPYFNETFIFEpeitesk 208
Cdd:cd08521      2 EIEFSLSYNYKTGSLEVHIKECRNLAYadeKKKRSNPYVKVYLLPDKSKQSKRKTSVKKNTTNPVFNETLKYH------- 74

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....*....
gi 2102677298  209 ekdISHYSLEHGEVNeviVGLWHasSGMGEQPAFLGEVRVTLRGLQKQSTNSTtaWYFL 267
Cdd:cd08521     75 ---ISKSQLETRTLQ---LSVWH--HDRFGRNTFLGEVEIPLDSWDLDSQQSE--WYPL 123
C2B_Synaptotagmin-1 cd08402
C2 domain second repeat present in Synaptotagmin 1; Synaptotagmin is a membrane-trafficking ...
 5-119 6.66e-07

C2 domain second repeat present in Synaptotagmin 1; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. Synaptotagmin 1, a member of the class 1 synaptotagmins, is located in the brain and endocranium and localized to the synaptic vesicles and secretory granules. It functions as a Ca2+ sensor for fast exocytosis. It, like synaptotagmin-2, has an N-glycosylated N-terminus. Synaptotagmin 4, a member of class 4 synaptotagmins, is located in the brain. It functions are unknown. It, like synaptotagmin-11, has an Asp to Ser substitution in its C2A domain. 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: 176047 [Multi-domain]  Cd Length: 136  Bit Score: 49.71  E-value: 6.66e-07
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2102677298    5 TRLVRVEERLKIKIGEVKNLQSRNHGspGARDVYCVLSLDQE----EIFRTTTMERTLNPFFGEEFQFEVPR---KFRYL 77
Cdd:cd08402      8 LRYVPTAGKLTVVILEAKNLKKMDVG--GLSDPYVKIHLMQNgkrlKKKKTTIKKRTLNPYYNESFSFEVPFeqiQKVHL 85

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*..
gi 2102677298   78 GIYVYDRDRHLKQDKIlGKVAIKreDLTTYHNKEHWF-----PLRPV 119
Cdd:cd08402     86 IVTVLDYDRIGKNDPI-GKVVLG--CNATGAELRHWSdmlasPRRPI 129
C2_Rab11-FIP_classI cd08682
C2 domain found in Rab11-family interacting proteins (FIP) class I; Rab GTPases recruit ...
 21-136 6.85e-07

C2 domain found in Rab11-family interacting proteins (FIP) class I; Rab GTPases recruit various effector proteins to organelles and vesicles. Rab11-family interacting proteins (FIPs) are involved in mediating the role of Rab11. FIPs can be divided into three classes: class I FIPs (Rip11a, Rip11b, RCP, and FIP2) which contain a C2 domain after N-terminus of the protein, class II FIPs (FIP3 and FIP4) which contain two EF-hands and a proline rich region, and class III FIPs (FIP1) which exhibits no homology to known protein domains. All FIP proteins contain a highly conserved, 20-amino acid motif at the C-terminus of the protein, known as Rab11/25 binding domain (RBD). Class I FIPs are thought to bind to endocytic membranes via their C2 domain, which interacts directly with phospholipids. Class II FIPs do not have any membrane binding domains leaving much to speculate about the mechanism involving FIP3 and FIP4 interactions with endocytic membranes. The members in this CD are class I FIPs. The exact function of the Rab11 and FIP interaction is unknown, but there is speculation that it involves the role of forming a targeting complex that recruits a group of proteins involved in membrane transport to organelles. 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: 176064 [Multi-domain]  Cd Length: 126  Bit Score: 49.37  E-value: 6.85e-07
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2102677298   21 VKNLQSRN---HGSPGARDVYCVLSLDQEeIFRTTTMERTLNPFFGEEFQFEVPrkfrylGIYVYDRDRHLKQ------- 90
Cdd:cd08682      3 VTVLQARGllcKGKSGTNDAYVIIQLGKE-KYSTSVKEKTTSPVWKEECSFELP------GLLSGNGNRATLQltvmhrn 75

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....
gi 2102677298   91 ----DKILGKVAIKREDLTTYHNKE--HWFPL--RPVDADSEvqgKAHLEISLQ 136
Cdd:cd08682     76 llglDKFLGQVSIPLNDLDEDKGRRrtRWFKLesKPGKDDKE---RGEIEVDIQ 126
C2A_MCTP_PRT_plant cd04022
C2 domain first repeat found in Multiple C2 domain and Transmembrane region Proteins (MCTP); ...
 145-272 1.23e-06

C2 domain first 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 first C2 repeat, C2A, and has a type-II topology.


Pssm-ID: 175989 [Multi-domain]  Cd Length: 127  Bit Score: 48.49  E-value: 1.23e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2102677298  145 KLTVRVIECSELTIKN--GGCDPFaiVTVIYSNGKQvlkRTKIKKKTVSPYFNETFIF---EPEITESKEKDISHYSleh 219
Cdd:cd04022      1 KLVVEVVDAQDLMPKDgqGSSSAY--VELDFDGQKK---RTRTKPKDLNPVWNEKLVFnvsDPSRLSNLVLEVYVYN--- 72

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|...
gi 2102677298  220 gevnevivglwHASSGMGEqpAFLGEVRVTLRGLQKQStNSTTAWYFLQPRAV 272
Cdd:cd04022     73 -----------DRRSGRRR--SFLGRVRISGTSFVPPS-EAVVQRYPLEKRGL 111
C2A_Synaptotagmin-1-5-6-9-10 cd08385
C2A domain first repeat present in Synaptotagmins 1, 5, 6, 9, and 10; Synaptotagmin is a ...
 141-200 1.63e-06

C2A domain first repeat present in Synaptotagmins 1, 5, 6, 9, and 10; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. Synaptotagmin 1, a member of class 1 synaptotagmins, is located in the brain and endocranium and localized to the synaptic vesicles and secretory granules. It functions as a Ca2+ sensor for fast exocytosis as do synaptotagmins 5, 6, and 10. It is distinguished from the other synaptotagmins by having an N-glycosylated N-terminus. Synaptotagmins 5, 6, and 10, members of class 3 synaptotagmins, are located primarily in the brain and localized to the active zone and plasma membrane. They is distinguished from the other synaptotagmins by having disulfide bonds at its N-terminus. Synaptotagmin 6 also regulates the acrosome reaction, a unique Ca2+-regulated exocytosis, in sperm. Synaptotagmin 9, a class 5 synaptotagmins, is located in the brain and localized to the synaptic vesicles. It is thought to be a Ca2+-sensor for dense-core vesicle exocytosis. 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 first C2 repeat, C2A, and has a type-I topology.


Pssm-ID: 176031 [Multi-domain]  Cd Length: 124  Bit Score: 48.03  E-value: 1.63e-06
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 2102677298  141 HAQSKLTVRVIECSELTIK--NGGCDPFAIVTVIYSNGKQVlkRTKIKKKTVSPYFNETFIF 200
Cdd:cd08385     13 FQSNQLTVGIIQAADLPAMdmGGTSDPYVKVYLLPDKKKKF--ETKVHRKTLNPVFNETFTF 72
C2_PKC_alpha_gamma cd04026
C2 domain in Protein Kinase C (PKC) alpha and gamma; A single C2 domain is found in PKC alpha ...
 127-201 1.94e-06

C2 domain in Protein Kinase C (PKC) alpha and gamma; A single C2 domain is found in PKC alpha and gamma. The PKC family of serine/threonine kinases regulates apoptosis, proliferation, migration, motility, chemo-resistance, and differentiation. There are 3 groups: group 1(alpha, betaI, beta II, gamma) which require phospholipids and calcium, group 2 (delta, epsilon, theta, eta) which do not require calcium for activation, and group 3 (xi, iota/lambda) which are atypical and can be activated in the absence of diacylglycerol and calcium. 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: 175992 [Multi-domain]  Cd Length: 131  Bit Score: 48.03  E-value: 1.94e-06
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 2102677298  127 GKAHLEISLQsqighaQSKLTVRVIECSELtIK---NGGCDPFAIVTVIYSNGKQVLKRTKIKKKTVSPYFNETFIFE 201
Cdd:cd04026      2 GRIYLKISVK------DNKLTVEVREAKNL-IPmdpNGLSDPYVKLKLIPDPKNETKQKTKTIKKTLNPVWNETFTFD 72
C2_Ras_p21A1 cd08400
C2 domain present in RAS p21 protein activator 1 (RasA1); RasA1 is a GAP1 (GTPase activating ...
 14-118 3.61e-06

C2 domain present in RAS p21 protein activator 1 (RasA1); RasA1 is a GAP1 (GTPase activating protein 1), a Ras-specific GAP member, 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. RasA1 contains a C2 domain, a Ras-GAP domain, a pleckstrin homology (PH)-like domain, a SH3 domain, and 2 SH2 domains. 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: 176045 [Multi-domain]  Cd Length: 126  Bit Score: 47.36  E-value: 3.61e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2102677298   14 LKIKIGEVKNLQSRNHGSPgardvYCVLSLDQEEIFRTTTMErTLNPFFGEEFQFE-VPRKFRYLGIYVYDRDRHLKqDK 92
Cdd:cd08400      6 LQLNVLEAHKLPVKHVPHP-----YCVISLNEVKVARTKVRE-GPNPVWSEEFVFDdLPPDVNSFTISLSNKAKRSK-DS 78

                           90       100
                   ....*....|....*....|....*.
gi 2102677298   93 ILGKVAIKREDLTTYHNKEHWFPLRP 118
Cdd:cd08400     79 EIAEVTVQLSKLQNGQETDEWYPLSS 104
C2B_SLP_1-2-3-4 cd04020
C2 domain second repeat present in Synaptotagmin-like proteins 1-4; All Slp members basically ...
 145-278 4.44e-06

C2 domain second repeat present in Synaptotagmin-like proteins 1-4; All Slp members basically share an N-terminal Slp homology domain (SHD) and C-terminal tandem C2 domains (named the C2A domain and the C2B domain) with the SHD and C2 domains being separated by a linker sequence of various length. Slp1/JFC1 and Slp2/exophilin 4 promote granule docking to the plasma membrane. Additionally, their C2A domains are both Ca2+ independent, unlike the case in Slp3 and Slp4/granuphilin in which their C2A domains are Ca2+ dependent. It is thought that SHD (except for the Slp4-SHD) functions as a specific Rab27A/B-binding domain. In addition to Slps, rabphilin, Noc2, and Munc13-4 also function as Rab27-binding proteins. It has been demonstrated that Slp3 and Slp4/granuphilin promote dense-core vesicle exocytosis. 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: 175987 [Multi-domain]  Cd Length: 162  Bit Score: 47.70  E-value: 4.44e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2102677298  145 KLTVRVIECSELTIK--NGGCDPFAIVTVIYSNGKQVLKRTKIKKKTVSPYFNETFIFEPEITEskekDISHYSLEhgev 222
Cdd:cd04020     28 ELHVWVKEAKNLPALksGGTSDSFVKCYLLPDKSKKSKQKTPVVKKSVNPVWNHTFVYDGVSPE----DLSQACLE---- 99

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 2102677298  223 neviVGLW-HASSGMGEqpaFLGEVRVTLRGLQKQSTN-----ST----TAWyflqpRAVKHRPNK 278
Cdd:cd04020    100 ----LTVWdHDKLSSND---FLGGVRLGLGTGKSYGQAvdwmdSTgeeiLLW-----QKMLDNPNS 153
C2B_Synaptotagmin-4 cd08404
C2 domain second repeat present in Synaptotagmin 4; Synaptotagmin is a membrane-trafficking ...
 131-213 4.57e-06

C2 domain second repeat present in Synaptotagmin 4; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. Synaptotagmin 4, a member of class 4 synaptotagmins, is located in the brain. It functions are unknown. It, like synaptotagmin-11, has an Asp to Ser substitution in its C2A domain. 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: 176049 [Multi-domain]  Cd Length: 136  Bit Score: 47.04  E-value: 4.57e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2102677298  131 LEISLQSQigHAQSKLTVRVIECSEL--TIKNGGCDPFAIVTVIYSNGKQVLKRTKIKKKTVSPYFNETFIFepEITESK 208
Cdd:cd08404      4 LLLSLCYQ--PTTNRLTVVVLKARHLpkMDVSGLADPYVKVNLYYGKKRISKKKTHVKKCTLNPVFNESFVF--DIPSEE 79


                   ....*
gi 2102677298  209 EKDIS 213
Cdd:cd08404     80 LEDIS 84
C2B_Synaptotagmin-7 cd08405
C2 domain second repeat present in Synaptotagmin 7; Synaptotagmin is a membrane-trafficking ...
 144-200 4.88e-06

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: 47.03  E-value: 4.88e-06
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*....
gi 2102677298  144 SKLTVRVIECSELTIK--NGGCDPFAIVTVIYSNGKQVLKRTKIKKKTVSPYFNETFIF 200
Cdd:cd08405     15 NRITVNIIKARNLKAMdiNGTSDPYVKVWLMYKDKRVEKKKTVIKKRTLNPVFNESFIF 73
PH_TAAP2-like cd13255
Tandem PH-domain-containing protein 2 Pleckstrin homology (PH) domain; The binding of TAPP2 ...
 594-696 5.10e-06

Tandem PH-domain-containing protein 2 Pleckstrin homology (PH) domain; The binding of TAPP2 (also called PLEKHA2) adaptors to PtdIns(3,4)P(2), but not PI(3,4, 5)P3, function as negative regulators of insulin and PI3K signalling pathways (i.e. TAPP/utrophin/syntrophin complex). TAPP2 contains two sequential PH domains in which the C-terminal PH domain specifically binds PtdIns(3,4)P2 with high affinity. The N-terminal PH domain does not interact with any phosphoinositide tested. They also contain a C-terminal PDZ-binding motif that interacts with several PDZ-binding proteins, including PTPN13 (known previously as PTPL1 or FAP-1) as well as the scaffolding proteins MUPP1 (multiple PDZ-domain-containing protein 1), syntrophin and utrophin. The members here are most sequence similar to TAPP2 proteins, but may not be actual TAPP2 proteins. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270075  Cd Length: 110  Bit Score: 46.25  E-value: 5.10e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2102677298  594 EQPIVLKEGVMIKRAQGRKRFgrknfKQRYFKLTTQDLSYSKTKGKEPLCK-IPLEEILAVE----KLHEdsfkmkNIFQ 668
Cdd:cd13255      2 ISEAVLKAGYLEKKGERRKTW-----KKRWFVLRPTKLAYYKNDKEYRLLRlIDLTDIHTCTevqlKKHD------NTFG 70

                           90       100
                   ....*....|....*....|....*...
gi 2102677298  669 IIQSQRALYVQAGNCVEEKEWIDILTKI 696
Cdd:cd13255     71 IVTPARTFYVQADSKAEMESWISAINLA 98
C2A_Synaptotagmin-7 cd08386
C2A domain first repeat present in Synaptotagmin 7; Synaptotagmin is a membrane-trafficking ...
 127-201 5.94e-06

C2A domain first 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 first C2 repeat, C2A, and has a type-I topology.


Pssm-ID: 176032 [Multi-domain]  Cd Length: 125  Bit Score: 46.55  E-value: 5.94e-06
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 2102677298  127 GKAHLEISLQSQighaQSKLTVRVIECSELTIKN--GGCDPFaiVTVIYSNGKQVLKRTKIKKKTVSPYFNETFIFE 201
Cdd:cd08386      3 GRIQFSVSYDFQ----ESTLTLKILKAVELPAKDfsGTSDPF--VKIYLLPDKKHKLETKVKRKNLNPHWNETFLFE 73
C2B_Rabphilin_Doc2 cd08384
C2 domain second repeat present in Rabphilin and Double C2 domain; Rabphilin is found neurons ...
 50-114 7.14e-06

C2 domain second repeat present in Rabphilin and Double C2 domain; Rabphilin is found neurons and in neuroendrocrine cells, while Doc2 is found not only in the brain but in tissues, including mast cells, chromaffin cells, and osteoblasts. Rabphilin and Doc2s share highly homologous tandem C2 domains, although their N-terminal structures are completely different: rabphilin contains an N-terminal Rab-binding domain (RBD),7 whereas Doc2 contains an N-terminal Munc13-1-interacting domain (MID). 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: 176030 [Multi-domain]  Cd Length: 133  Bit Score: 46.57  E-value: 7.14e-06
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 2102677298   50 RTTTMERTLNPFFGEEFQFEVPRK---FRYLGIYVYDRDRHLKQDKI----LGKVAiKREDLttyhnkEHWF 114
Cdd:cd08384     53 KTQVKKKTLNPEFNEEFFYDIKHSdlaKKTLEITVWDKDIGKSNDYIgglqLGINA-KGERL------RHWL 117
C2B_Synaptotagmin-3-5-6-9-10 cd08403
C2 domain second repeat present in Synaptotagmins 3, 5, 6, 9, and 10; Synaptotagmin is a ...
 145-203 7.61e-06

C2 domain second repeat present in Synaptotagmins 3, 5, 6, 9, and 10; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. Synaptotagmin 3, a member of class 3 synaptotagmins, is located in the brain and localized to the active zone and plasma membrane. It functions as a Ca2+ sensor for fast exocytosis. It, along with synaptotagmins 5,6, and 10, has disulfide bonds at its N-terminus. Synaptotagmin 9, a class 5 synaptotagmins, is located in the brain and localized to the synaptic vesicles. It is thought to be a Ca2+-sensor for dense-core vesicle exocytosis. 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: 176048 [Multi-domain]  Cd Length: 134  Bit Score: 46.35  E-value: 7.61e-06
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 2102677298  145 KLTVRVIECSELTIKN--GGCDPFAIVTVIySNGKQVLKR-TKIKKKTVSPYFNETFIFE--PE 203
Cdd:cd08403     15 RLTLTIIKARNLKAMDitGFSDPYVKVSLM-CEGRRLKKKkTSVKKNTLNPTYNEALVFDvpPE 77
C2B_Ferlin cd04011
C2 domain second repeat in Ferlin; Ferlins are involved in vesicle fusion events. Ferlins and ...
 148-201 8.90e-06

C2 domain second 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 second C2 repeat, C2B, and has a type-II topology.


Pssm-ID: 175978 [Multi-domain]  Cd Length: 111  Bit Score: 45.64  E-value: 8.90e-06
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 2102677298  148 VRVIECSELtiKNGGCDPFAIVTViysnGKQVlKRTKIKKKTVSPYFNETFIFE 201
Cdd:cd04011      8 VRVIEARQL--VGGNIDPVVKVEV----GGQK-KYTSVKKGTNCPFYNEYFFFN 54
COG5038 COG5038
Ca2+-dependent lipid-binding protein, contains C2 domain [General function prediction only];
14-99 9.18e-06

Ca2+-dependent lipid-binding protein, contains C2 domain [General function prediction only];


Pssm-ID: 227371 [Multi-domain]  Cd Length: 1227  Bit Score: 49.76  E-value: 9.18e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2102677298   14 LKIKIGEVKNLQSRNhgSPGARDVYCVLSLDQEEIFRTTTMERTLNPFFGEEFQFEVPRKFR-YLGIYVYDRDRHLKqDK 92
Cdd:COG5038   1042 LTIMLRSGENLPSSD--ENGYSDPFVKLFLNEKSVYKTKVVKKTLNPVWNEEFTIEVLNRVKdVLTINVNDWDSGEK-ND 1118


                   ....*..
gi 2102677298   93 ILGKVAI 99
Cdd:COG5038   1119 LLGTAEI 1125
PH2_MyoX cd13296
Myosin X Pleckstrin homology (PH) domain, repeat 2; MyoX, a MyTH-FERM myosin, is a molecular ...
 600-704 1.07e-05

Myosin X Pleckstrin homology (PH) domain, repeat 2; MyoX, a MyTH-FERM myosin, is a molecular motor that has crucial functions in the transport and/or tethering of integrins in the actin-based extensions known as filopodia, microtubule binding, and in netrin-mediated axon guidance. It functions as a dimer. MyoX walks on bundles of actin, rather than single filaments, unlike the other unconventional myosins. MyoX is present in organisms ranging from humans to choanoflagellates, but not in Drosophila and Caenorhabditis elegans.MyoX consists of a N-terminal motor/head region, a neck made of 3 IQ motifs, and a tail consisting of a coiled-coil domain, a PEST region, 3 PH domains, a myosin tail homology 4 (MyTH4), and a FERM domain at its very C-terminus. The first PH domain in the MyoX tail is a split-PH domain, interupted by the second PH domain such that PH 1a and PH 1b flanks PH 2. The third PH domain (PH 3) follows the PH 1b domain. This cd contains the second PH repeat. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270108  Cd Length: 103  Bit Score: 45.15  E-value: 1.07e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2102677298  600 KEGVMIKRAQGRKRFGRKNFKQRYFKLTTQDLSYSKT--KGKEPLCKIPLEEILAVEKLHEDSfkmkNIFQIIQSQRALY 677
Cdd:cd13296      1 KSGWLTKKGGGSSTLSRRNWKSRWFVLRDTVLKYYENdqEGEKLLGTIDIRSAKEIVDNDPKE----NRLSITTEERTYH 76

                           90       100
                   ....*....|....*....|....*..
gi 2102677298  678 VQAGNCVEEKEWIDILTKICRTNSNRL 704
Cdd:cd13296     77 LVAESPEDASQWVNVLTRVISATDLEL 103
PH_MELT_VEPH1 cd01264
Melted pleckstrin homology (PH) domain; The melted protein (also called Ventricular zone ...
 595-693 1.09e-05

Melted pleckstrin homology (PH) domain; The melted protein (also called Ventricular zone expressed PH domain-containing protein homolog 1) is expressed in the developing central nervous system of vertebrates. It contains a single C-terminal PH domain that is required for membrane targeting. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 269965  Cd Length: 105  Bit Score: 45.14  E-value: 1.09e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2102677298  595 QPIVlkEGvMIKRAQGRKRFGRKnFKQRYFKLTTQDLSYSKTKGKEPLCKIPLEEILAVEKLHEDSFKMKNIFQIIQSQR 674
Cdd:cd01264      1 QPVI--EG-QLKEKKGRWKFFKR-WRTRYFTLSGAQLSYRGGKSKPDAPPIELSKIRSVKVVRKKDRSIPKAFEIFTDDK 76

                           90
                   ....*....|....*....
gi 2102677298  675 ALYVQAGNCVEEKEWIDIL 693
Cdd:cd01264     77 TYVLKAKDEKNAEEWLQCL 95
C2B_Synaptotagmin-7 cd08405
C2 domain second repeat present in Synaptotagmin 7; Synaptotagmin is a membrane-trafficking ...
 13-111 1.49e-05

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: 45.49  E-value: 1.49e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2102677298   13 RLKIKIGEVKNLQSRNHGspGARDVYCVLSL---DQE-EIFRTTTMERTLNPFFGEEFQFEVP-RKFR--YLGIYVYDRD 85
Cdd:cd08405     16 RITVNIIKARNLKAMDIN--GTSDPYVKVWLmykDKRvEKKKTVIKKRTLNPVFNESFIFNIPlERLRetTLIITVMDKD 93

                           90       100
                   ....*....|....*....|....*...
gi 2102677298   86 RhLKQDKILGKV--AIKREDLTTYHNKE 111
Cdd:cd08405     94 R-LSRNDLIGKIylGWKSGGLELKHWKD 120
C2B_RIM1alpha cd04028
C2 domain second repeat contained in Rab3-interacting molecule (RIM) proteins; RIMs are ...
 131-269 2.16e-05

C2 domain second repeat contained in Rab3-interacting molecule (RIM) proteins; RIMs are believed to organize specialized sites of the plasma membrane called active zones. They also play a role in controlling neurotransmitter release, plasticity processes, as well as memory and learning. RIM contains an N-terminal zinc finger domain, a PDZ domain, and two C-terminal C2 domains (C2A, C2B). 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 and do not bind Ca2+.


Pssm-ID: 175994 [Multi-domain]  Cd Length: 146  Bit Score: 45.46  E-value: 2.16e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2102677298  131 LEISLQSQIGHaqskLTVRVIECSELTIKNGGCDPFA-IVTVIYSNGKQVL--KRTKIKKKTVSPYFNETFIFEPEItes 207
Cdd:cd04028     20 IQLGLYDKKGQ----LEVEVIRARGLVQKPGSKVLPApYVKVYLLEGKKCIakKKTKIARKTLDPLYQQQLVFDVSP--- 92

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 2102677298  208 kekdishysleHGEVNEVIVglWhASSGMGEQPAFLGEVRVTLRGLqkQSTNSTTAWYFLQP 269
Cdd:cd04028     93 -----------TGKTLQVIV--W-GDYGRMDKKVFMGVAQILLDDL--DLSNLVIGWYKLFP 138
RasGAP_IQGAP3 cd12207
Ras-GTPase Activating Domain of IQ motif containing GTPase activating protein 3; This family ...
 360-532 2.91e-05

Ras-GTPase Activating Domain of IQ motif containing GTPase activating protein 3; This family represents the IQ motif containing GTPase activating protein 3 (IQGAP3), which associates with Ras GTP-binding proteins. A primary function of IQGAP proteins is to modulate cytoskeletal architecture. There are three known IQGAP family members: IQGAP1, IQGAP2 and IQGAP3. Human IQGAP1 and IQGAP2 share 62% identity. IQGAPs are multi-domain molecules having a calponin-homology (CH) domain which binds F-actin, IQGAP-specific repeats, a single WW domain, four IQ motifs that mediate interactions with calmodulin, and a RasGAP related domain that binds active Rho family GTPases. IQGAP is an essential regulator of cytoskeletal function. IQGAP1 negatively regulates Ras family GTPases by stimulating their intrinsic GTPase activity, the protein actually lacks GAP activity. Both IQGAP1 and IQGAP2 specifically bind to Cdc42 and Rac1, but not to RhoA. Despite of their similarities to part of the sequence of RasGAP, neither IQGAP1 nor IQGAP2 interacts with Ras. IQGAP3, only present in mammals, regulates the organization of the cytoskeleton under the regulation of Rac1 and Cdc42 in neuronal cells. The depletion of IQGAP3 is shown to impair neurite or axon outgrowth in neuronal cells with disorganized cytoskeleton.


Pssm-ID: 213346 [Multi-domain]  Cd Length: 350  Bit Score: 47.52  E-value: 2.91e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2102677298  360 LVSVMRALASHEI-SKLTDPTTIFRGNTLVSKMMDEGMRLA-GLHYLHSTLRPAMKQVFLEKK-SCEIDPTRVKDA--NT 434
Cdd:cd12207     20 LLQLFKTALQEEIsSKVEKPQDVITGNPTVIRLLVSFYRSArGQNALRHILGPVVQDVLQDKGlSIRTDPVQIYKAwiNQ 99

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2102677298  435 IQTN-----------------------------LTNLKEYVERVFIAITTSGVRCPSLMCEMFWCLKELAATHFPKNKEV 485
Cdd:cd12207    100 TETQsgcrsslpyevspeqalshpevqrrldiaIRNLLAVTDKFLSAITSSVDKIPYGMRYVAKVLRDSLQEKFPGASED 179

                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|..
gi 2102677298  486 R-YSVISGFIFLRFFAPAILGPRLFDI----TTEQIDSQTNRTLTLISKTIQ 532
Cdd:cd12207    180 EvYKVVGNLLYYRFMNPAVVAPDGFDIvdcsAGGALQPEQRRMLGSVAKVLQ 231
C2B_Synaptotagmin cd00276
C2 domain second repeat present in Synaptotagmin; Synaptotagmin is a membrane-trafficking ...
 12-113 3.11e-05

C2 domain second repeat present in Synaptotagmin; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. There are several classes of Synaptotagmins. 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: 175975 [Multi-domain]  Cd Length: 134  Bit Score: 44.50  E-value: 3.11e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2102677298   12 ERLKIKIGEVKNLQSRNHgsPGARDVYCVLSL--DQEEIF--RTTTMERTLNPFFGEEFQFEVPRKFR---YLGIYVYDR 84
Cdd:cd00276     14 ERLTVVVLKARNLPPSDG--KGLSDPYVKVSLlqGGKKLKkkKTSVKKGTLNPVFNEAFSFDVPAEQLeevSLVITVVDK 91

                           90       100
                   ....*....|....*....|....*....
gi 2102677298   85 DRHLKqDKILGKVAIKREDLTTYHnkEHW 113
Cdd:cd00276     92 DSVGR-NEVIGQVVLGPDSGGEEL--EHW 117
PH_Phafin2-like cd01218
Phafin2 (also called EAPF, FLJ13187, ZFYVE18 or PLEKHF2) Pleckstrin Homology (PH) domain; ...
 599-695 3.51e-05

Phafin2 (also called EAPF, FLJ13187, ZFYVE18 or PLEKHF2) Pleckstrin Homology (PH) domain; Phafin2 is differentially expressed in the liver cancer cell and regulates the structure and function of the endosomes through Rab5-dependent processes. Phafin2 modulates the cell's response to extracellular stimulation by modulating the receptor density on the cell surface. Phafin2 contains a PH domain and a FYVE domain. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 269927 [Multi-domain]  Cd Length: 123  Bit Score: 44.17  E-value: 3.51e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2102677298  599 LKEGVMIKRAqgrkrfgRKNFKQRYFKLTTQDLSY-SKTKGKEPLCK---IPLEEIlAVEKLhEDSFKMKNIFQIIQSQR 674
Cdd:cd01218     31 VGEGVLTKVC-------RKKPKPRQFFLFNDILVYgSIVINKKKYNKqriIPLEDV-KIEDL-EDTGELKNGWQIISPKK 101

                           90       100
                   ....*....|....*....|.
gi 2102677298  675 ALYVQAGNCVEEKEWIDILTK 695
Cdd:cd01218    102 SFVVYAATATEKSEWMDHINK 122
C2B_Synaptotagmin-12 cd08406
C2 domain second repeat present in Synaptotagmin 12; Synaptotagmin is a membrane-trafficking ...
 145-237 4.81e-05

C2 domain second repeat present in Synaptotagmin 12; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. Synaptotagmin 12, a member of class 6 synaptotagmins, is located in the brain. It functions are unknown. It, like synaptotagmins 8 and 13, do not have any consensus Ca2+ binding sites. 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: 176051 [Multi-domain]  Cd Length: 136  Bit Score: 44.40  E-value: 4.81e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2102677298  145 KLTVRVIECSELTIKNGGC--DPFAIVTVIySNGKQVLK-RTKIKKKTVSPYFNETFIFEPEITESKEKDISHYSLEHGE 221
Cdd:cd08406     16 RLTVVVVKARNLVWDNGKTtaDPFVKVYLL-QDGRKISKkKTSVKRDDTNPIFNEAMIFSVPAIVLQDLSLRVTVAESTE 94

                           90       100
                   ....*....|....*....|..
gi 2102677298  222 ------VNEVIVGlwHASSGMG 237
Cdd:cd08406     95 dgktpnVGHVIIG--PAASGMG 114
C2_Calpain cd04046
C2 domain present in Calpain proteins; A single C2 domain is found in calpains (EC 3.4.22.52, ...
 159-200 5.95e-05

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: 43.81  E-value: 5.95e-05
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|..
gi 2102677298  159 KNGGCDPFAIvtvIYSNGKQVlkRTKIKKKTVSPYFNETFIF 200
Cdd:cd04046     20 SGGGADPYVI---IKCEGESV--RSPVQKDTLSPEFDTQAIF 56
C2_Rab11-FIP_classI cd08682
C2 domain found in Rab11-family interacting proteins (FIP) class I; Rab GTPases recruit ...
 148-267 6.16e-05

C2 domain found in Rab11-family interacting proteins (FIP) class I; Rab GTPases recruit various effector proteins to organelles and vesicles. Rab11-family interacting proteins (FIPs) are involved in mediating the role of Rab11. FIPs can be divided into three classes: class I FIPs (Rip11a, Rip11b, RCP, and FIP2) which contain a C2 domain after N-terminus of the protein, class II FIPs (FIP3 and FIP4) which contain two EF-hands and a proline rich region, and class III FIPs (FIP1) which exhibits no homology to known protein domains. All FIP proteins contain a highly conserved, 20-amino acid motif at the C-terminus of the protein, known as Rab11/25 binding domain (RBD). Class I FIPs are thought to bind to endocytic membranes via their C2 domain, which interacts directly with phospholipids. Class II FIPs do not have any membrane binding domains leaving much to speculate about the mechanism involving FIP3 and FIP4 interactions with endocytic membranes. The members in this CD are class I FIPs. The exact function of the Rab11 and FIP interaction is unknown, but there is speculation that it involves the role of forming a targeting complex that recruits a group of proteins involved in membrane transport to organelles. 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: 176064 [Multi-domain]  Cd Length: 126  Bit Score: 43.60  E-value: 6.16e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2102677298  148 VRVIECSELTIK--NGGCDPFAIVTViysnGKQVLkRTKIKKKTVSPYFNETFIFEpeiteskekdISHYSLEHGEVNEV 225
Cdd:cd08682      3 VTVLQARGLLCKgkSGTNDAYVIIQL----GKEKY-STSVKEKTTSPVWKEECSFE----------LPGLLSGNGNRATL 67

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|..
gi 2102677298  226 IVGLWHASSGMGEQpaFLGEVRVTLRGLQKQSTNSTTAWYFL 267
Cdd:cd08682     68 QLTVMHRNLLGLDK--FLGQVSIPLNDLDEDKGRRRTRWFKL 107
C2A_MCTP_PRT_plant cd04022
C2 domain first repeat found in Multiple C2 domain and Transmembrane region Proteins (MCTP); ...
 13-99 6.62e-05

C2 domain first 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 first C2 repeat, C2A, and has a type-II topology.


Pssm-ID: 175989 [Multi-domain]  Cd Length: 127  Bit Score: 43.48  E-value: 6.62e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2102677298   13 RLKIKIGEVKNLQSRN-HGSPGArdvYCVLSLDqEEIFRTTTMERTLNPFFGEEFQFEV--PRKFRY--LGIYVYDRDRH 87
Cdd:cd04022      1 KLVVEVVDAQDLMPKDgQGSSSA---YVELDFD-GQKKRTRTKPKDLNPVWNEKLVFNVsdPSRLSNlvLEVYVYNDRRS 76

                           90
                   ....*....|..
gi 2102677298   88 LKQDKILGKVAI 99
Cdd:cd04022     77 GRRRSFLGRVRI 88
C2_NEDD4_NEDD4L cd04033
C2 domain present in the Human neural precursor cell-expressed, developmentally down-regulated ...
 146-301 7.02e-05

C2 domain present in the Human neural precursor cell-expressed, developmentally down-regulated 4 (NEDD4) and NEDD4-like (NEDD4L/NEDD42); Nedd4 and Nedd4-2 are two of the nine members of the Human Nedd4 family. All vertebrates appear to have both Nedd4 and Nedd4-2 genes. They are thought to participate in the regulation of epithelial Na+ channel (ENaC) activity. They also have identical specificity for ubiquitin conjugating enzymes (E2). Nedd4 and Nedd4-2 are composed of a C2 domain, 2-4 WW domains, and a ubiquitin ligase Hect domain. Their WW domains can bind PPxY (PY) or LPSY motifs, and in vitro studies suggest that WW3 and WW4 of both proteins bind PY motifs in the key substrates, with WW3 generally exhibiting higher affinity. Most Nedd4 family members, especially Nedd4-2, also have multiple splice variants, which might play different roles in regulating their substrates. 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: 175999 [Multi-domain]  Cd Length: 133  Bit Score: 43.50  E-value: 7.02e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2102677298  146 LTVRVIECSELTIKN--GGCDPFAIVTVIYSNGKQVLK--RTKIKKKTVSPYFNETFIFepEITESKEKDIshysLEHGE 221
Cdd:cd04033      2 LRVKVLAGIDLAKKDifGASDPYVKISLYDPDGNGEIDsvQTKTIKKTLNPKWNEEFFF--RVNPREHRLL----FEVFD 75

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2102677298  222 VNEVIVGLwhassgmgeqpaFLGEVRVTLRGL----QKQSTNSTTAWYFLQPRAVKHRPNkisnsstspgvlpglGSLRL 297
Cdd:cd04033     76 ENRLTRDD------------FLGQVEVPLNNLptetPGNERRYTFKDYLLRPRSSKSRVK---------------GHLRL 128


                   ....
gi 2102677298  298 KIHY 301
Cdd:cd04033    129 YMAY 132
C2A_Ferlin cd08373
C2 domain first repeat in Ferlin; Ferlins are involved in vesicle fusion events. Ferlins and ...
 150-255 1.44e-04

C2 domain first 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 first C2 repeat, C2A, and has a type-II topology.


Pssm-ID: 176019 [Multi-domain]  Cd Length: 127  Bit Score: 42.63  E-value: 1.44e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2102677298  150 VIECSELTIKNGGCDPFAIVTViysngKQVLKRTKIKKKTVSPYFNETFIFepeiteskekDISHySLEHGEVNEVIVGL 229
Cdd:cd08373      2 VVSLKNLPGLKGKGDRIAKVTF-----RGVKKKTRVLENELNPVWNETFEW----------PLAG-SPDPDESLEIVVKD 65

                           90       100
                   ....*....|....*....|....*.
gi 2102677298  230 WhassGMGEQPAFLGEVRVTLRGLQK 255
Cdd:cd08373     66 Y----EKVGRNRLIGSATVSLQDLVS 87
C2A_C2C_Synaptotagmin_like cd08391
C2 domain first and third repeat in Synaptotagmin-like proteins; Synaptotagmin is a ...
 14-131 1.52e-04

C2 domain first and third repeat 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 either the first or third repeat in Synaptotagmin-like proteins with a type-I topology.


Pssm-ID: 176037 [Multi-domain]  Cd Length: 121  Bit Score: 42.28  E-value: 1.52e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2102677298   14 LKIKIGEVKNLQSRNHG----SPGARDVYCVLSLDqEEIFRTTTMERTLNPFFGEEFQF---EVPRKfrYLGIYVYDRDR 86
Cdd:cd08391      3 LRIHVIEAQDLVAKDKFvgglVKGKSDPYVIVRVG-AQTFKSKVIKENLNPKWNEVYEAvvdEVPGQ--ELEIELFDEDP 79

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*...
gi 2102677298   87 hlKQDKILGKVAIkreDLTTYHNK---EHWFPLRPVDadsevQGKAHL 131
Cdd:cd08391     80 --DKDDFLGRLSI---DLGSVEKKgfiDEWLPLEDVK-----SGRLHL 117
C2A_SLP-1_2 cd08393
C2 domain first repeat present in Synaptotagmin-like proteins 1 and 2; All Slp members ...
 50-117 1.84e-04

C2 domain first repeat present in Synaptotagmin-like proteins 1 and 2; All Slp members basically share an N-terminal Slp homology domain (SHD) and C-terminal tandem C2 domains (named the C2A domain and the C2B domain) with the SHD and C2 domains being separated by a linker sequence of various length. Slp1/JFC1 and Slp2/exophilin 4 promote granule docking to the plasma membrane. Additionally, their C2A domains are both Ca2+ independent, unlike Slp3 and Slp4/granuphilin which are Ca2+ dependent. It is thought that SHD (except for the Slp4-SHD) functions as a specific Rab27A/B-binding domain. In addition to Slps, rabphilin, Noc2, and Munc13-4 also function as Rab27-binding 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-I topology.


Pssm-ID: 176039 [Multi-domain]  Cd Length: 125  Bit Score: 42.42  E-value: 1.84e-04
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 2102677298   50 RTTTMERTLNPFFGEEFQFEVPRKF---RYLGIYVYDRDRhLKQDKILGKVAIkreDLTTY---HNKEHWFPLR 117
Cdd:cd08393     56 KTSVKKKTLNPVFNETLRYKVEREElptRVLNLSVWHRDS-LGRNSFLGEVEV---DLGSWdwsNTQPTWYPLQ 125
C2A_Munc13-like cd08676
C2 domain first repeat in Munc13 (mammalian uncoordinated)-like proteins; C2-like domains are ...
 14-116 2.53e-04

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: 42.36  E-value: 2.53e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2102677298   14 LKIKIGEVKNLQSRNhgSPGARDVYCVLSLDQ----------------------------EEIFRTTTMERTLNPFFGEE 65
Cdd:cd08676     30 LKVTVIEAKGLLAKD--VNGFSDPYCMLGIVPasrernsekskkrkshrkkavlkdtvpaKSIKVTEVKPQTLNPVWNET 107

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 2102677298   66 FQFEVPR----KFRylgIYVYDRDrhlkqDKILGKVAIKREDLTTyHNKEHWFPL 116
Cdd:cd08676    108 FRFEVEDvsndQLH---LDIWDHD-----DDFLGCVNIPLKDLPS-CGLDSWFKL 153
PH_DGK_type2 cd13274
Type 2 Diacylglycerol kinase Pleckstrin homology (PH) domain; DGK (also called DAGK) catalyzes ...
 599-703 3.02e-04

Type 2 Diacylglycerol kinase Pleckstrin homology (PH) domain; DGK (also called DAGK) catalyzes the conversion of diacylglycerol (DAG) to phosphatidic acid (PA) utilizing ATP as a source of the phosphate. In non-stimulated cells, DGK activity is low and DAG is used for glycerophospholipid biosynthesis. Upon receptor activation of the phosphoinositide pathway, DGK activity increases which drives the conversion of DAG to PA. DGK acts as a switch by terminating the signalling of one lipid while simultaneously activating signalling by another. There are 9 mammalian DGK isoforms all with conserved catalytic domains and two cysteine rich domains. These are further classified into 5 groups according to the presence of additional functional domains and substrate specificity: Type 1 - DGK-alpha, DGK-beta, DGK-gamma - contain EF-hand motifs and a recoverin homology domain; Type 2 - DGK-delta, DGK-eta, and DGK-kappa- contain a pleckstrin homology domain, two cysteine-rich zinc finger-like structures, and a separated catalytic region; Type 3 - DGK-epsilon - has specificity for arachidonate-containing DAG; Type 4 - DGK-zeta, DGK-iota- contain a MARCKS homology domain, ankyrin repeats, a C-terminal nuclear localization signal, and a PDZ-binding motif; Type 5 - DGK-theta - contains a third cysteine-rich domain, a pleckstrin homology domain and a proline rich region. The type 2 DGKs are present as part of this Metazoan DGK hierarchy. They have a N-terminal PH domain, two cysteine rich domains, followed by bipartite catalytic domains, and a C-terminal SAM domain. Their catalytic domains and perhaps other DGK catalytic domains may function as two independent units in a coordinated fashion. They may also require other motifs for maximal activity because several DGK catalytic domains have very little DAG kinase activity when expressed as isolated subunits. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270093  Cd Length: 97  Bit Score: 40.84  E-value: 3.02e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2102677298  599 LKEGVMIKRAqgrKRFGRknFKQRYFKLTTQDLSYSKTKGkeplCKIpLEEILAVE-KLHEDSFK-MKNIFQIIQSQRAL 676
Cdd:cd13274      1 IKEGPLLKQT---SSFQR--WKRRYFKLKGRKLYYAKDSK----SLI-FEEIDLSDaSVAECSTKnVNNSFTVITPFRKL 70

                           90       100
                   ....*....|....*....|....*..
gi 2102677298  677 YVQAGNCVEEKEWIDILtkicRTNSNR 703
Cdd:cd13274     71 ILCAESRKEMEEWISAL----KTVQQR 93
C2_Smurf-like cd08382
C2 domain present in Smad ubiquitination-related factor (Smurf)-like proteins; A single C2 ...
 35-99 3.37e-04

C2 domain present in Smad ubiquitination-related factor (Smurf)-like proteins; A single C2 domain is found in Smurf proteins, C2-WW-HECT-domain E3s, which play an important role in the downregulation of the TGF-beta signaling pathway. Smurf proteins also regulate cell shape, motility, and polarity by degrading small guanosine triphosphatases (GTPases). 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 type-II topology.


Pssm-ID: 176028 [Multi-domain]  Cd Length: 123  Bit Score: 41.52  E-value: 3.37e-04
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 2102677298   35 RDVYCVLSLDQEEIFRTTTMERTLNPFFGEEFQFEVpRKFRYLGIYVYDRDR-HLKQDKILGKVAI 99
Cdd:cd08382     21 PDPFAVITVDGGQTHSTDVAKKTLDPKWNEHFDLTV-GPSSIITIQVFDQKKfKKKDQGFLGCVRI 85
IQG1 COG5261
Protein involved in regulation of cellular morphogenesis/cytokinesis [Cell division and ...
 318-558 4.03e-04

Protein involved in regulation of cellular morphogenesis/cytokinesis [Cell division and chromosome partitioning / Signal transduction mechanisms];


Pssm-ID: 227586 [Multi-domain]  Cd Length: 1054  Bit Score: 44.49  E-value: 4.03e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2102677298  318 LLLQSVniQPITSSAVYI----------LGEIVSSKMEAAQPLVRVLVHYGQ-------LVSVMRALASHEISKLTDPTT 380
Cdd:COG5261    380 FLLQSS--IPLFSIAICVgrvkrfsidaLLNIVKLQILGNGYEIRKLYSLGKsnceehlSVSLFQMLLRTEVEATSLVQS 457

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2102677298  381 IFRGNTLVSKMMDEGMRLA-GLHYLHSTLRPAMKQVF-LEKKSCEIDPTRVKDANTIQT--------NLTNLKEYVE--- 447
Cdd:COG5261    458 LLRGNLPVHRNMTNYFRRSqGQAALREIRYQIINDVAiHEDLEVDINPLLVYRALLNKGqlspdkdlELLTSNEEVSefl 537

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2102677298  448 -------------------------RVFIAITTSGVRcpsLMCEMFWCLKELAA-THFPKNKEVR------------YSV 489
Cdd:COG5261    538 avmnavqessakllelsterildavYNSLDEIGYGIR---FVCELIRVVFELTPnRLFPSISDSRclrticfaeidsLGL 614

                          250       260       270       280       290       300       310
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 2102677298  490 ISGFIFLRFFAPAILGPRLFDITTEQIDSqTNRTLTLISKTIQSLGNLVSCRGGAGS------VCKEEYMECVYR 558
Cdd:COG5261    615 IGGFFFLRFVNEALVSPQTSMLKDSCPSD-NVRKLATLSKILQSVFEITSSDKFDVPlqpflkEYKEKVHNLLRK 688
C2A_SLP-4_5 cd04029
C2 domain first repeat present in Synaptotagmin-like proteins 4 and 5; All Slp members ...
 146-250 4.98e-04

C2 domain first repeat present in Synaptotagmin-like proteins 4 and 5; All Slp members basically share an N-terminal Slp homology domain (SHD) and C-terminal tandem C2 domains (named the C2A domain and the C2B domain) with the SHD and C2 domains being separated by a linker sequence of various length. SHD of Slp (except for the Slp4-SHD) function as a specific Rab27A/B-binding domain. In addition to Slp, rabphilin, Noc2, and Munc13-4 also function as Rab27-binding proteins. It has been demonstrated that Slp4/granuphilin promotes dense-core vesicle exocytosis. The C2A domain of Slp4 is Ca2+ dependent. Slp5 mRNA has been shown to be restricted to human placenta and liver suggesting a role in Rab27A-dependent membrane trafficking in specific tissues. 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: 175995 [Multi-domain]  Cd Length: 125  Bit Score: 40.89  E-value: 4.98e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2102677298  146 LTVRVIECSELTIKNGG---CDPFAIVTVIYSNGKQVLKRTKIKKKTVSPYFNETFIFEpeiteskekdISHYSLehgEV 222
Cdd:cd04029     17 LNVHVKECRNLAYGDEAkkrSNPYVKTYLLPDKSRQSKRKTSIKRNTTNPVYNETLKYS----------ISHSQL---ET 83

                           90       100
                   ....*....|....*....|....*...
gi 2102677298  223 NEVIVGLWHasSGMGEQPAFLGEVRVTL 250
Cdd:cd04029     84 RTLQLSVWH--YDRFGRNTFLGEVEIPL 109
C2A_Synaptotagmin-14_16 cd08389
C2A domain first repeat present in Synaptotagmins 14 and 16; Synaptotagmin 14 and 16 are ...
 131-204 5.09e-04

C2A domain first repeat present in Synaptotagmins 14 and 16; Synaptotagmin 14 and 16 are membrane-trafficking proteins in specific tissues outside the brain. Both of these contain C-terminal tandem C2 repeats, but only Synaptotagmin 14 has an N-terminal transmembrane domain and a putative fatty-acylation site. 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 and this is indeed the case here. 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 first C2 repeat, C2A, and has a type-I topology.


Pssm-ID: 176035 [Multi-domain]  Cd Length: 124  Bit Score: 41.07  E-value: 5.09e-04
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 2102677298  131 LEISLQSQIghAQSKLTVRVIECSELTIKN-GGCDPFAIVTVIYSNGKQVLKrTKIKKKTvSPYFNETFIF---EPEI 204
Cdd:cd08389      5 LDVAFEYDP--SARKLTVTVIRAQDIPTKDrGGASSWQVHLVLLPSKKQRAK-TKVQRGP-NPVFNETFTFsrvEPEE 78
C2D_Ferlin cd04017
C2 domain fourth repeat in Ferlin; Ferlins are involved in vesicle fusion events. Ferlins and ...
 159-209 5.37e-04

C2 domain fourth 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 fourth C2 repeat, C2D, and has a type-II topology.


Pssm-ID: 175984 [Multi-domain]  Cd Length: 135  Bit Score: 40.99  E-value: 5.37e-04
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 2102677298  159 KNGGCDPFAIVtvIYSNgkQVlKRTKIKKKTVSPYFNETFIFEP-EITESKE 209
Cdd:cd04017     18 KSGLSDPFARV--SFLN--QS-QETEVIKETLSPTWDQTLIFDEvELYGSPE 64
C2E_Ferlin cd04037
C2 domain fifth repeat in Ferlin; Ferlins are involved in vesicle fusion events. Ferlins and ...
 7-139 5.91e-04

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: 40.61  E-value: 5.91e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2102677298    7 LVRVeerlkiKIGEVKNLQSRNhgSPGARDVYCVLSLDQEEI-FRTTTMERTLNPFFGEEFQFE--VPRKfRYLGIYVYD 83
Cdd:cd04037      1 LVRV------YVVRARNLQPKD--PNGKSDPYLKIKLGKKKInDRDNYIPNTLNPVFGKMFELEatLPGN-SILKISVMD 71

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 2102677298   84 RDRhLKQDKILGKVAIKREDltTYHNKEHWFPLRPVdaDSEVQGKAHLEISLQSQI 139
Cdd:cd04037     72 YDL-LGSDDLIGETVIDLED--RFFSKHRATCGLPP--TYEESGPNQWRDSLKPSG 122
C2_Intersectin cd08375
C2 domain present in Intersectin; A single instance of the C2 domain is located C terminally ...
 13-104 7.48e-04

C2 domain present in Intersectin; A single instance of the C2 domain is located C terminally in the intersectin protein. Intersectin functions as a scaffolding protein, providing a link between the actin cytoskeleton and the components of endocytosis and plays a role in signal transduction. In addition to C2, intersectin contains several additional domains including: Eps15 homology domains, SH3 domains, a RhoGEF domain, and a PH 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. The members here have topology I.


Pssm-ID: 176021 [Multi-domain]  Cd Length: 136  Bit Score: 40.83  E-value: 7.48e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2102677298   13 RLKIKIGEVKNLQSRNhgSPGARDVYCVLSLDQEEiFRTTTMERTLNPFFGEEFQFEVpRKFR--YLGIYVYDRDrHLKQ 90
Cdd:cd08375     16 RLMVVIVEGRDLKPCN--SNGKSDPYCEVSMGSQE-HKTKVVSDTLNPKWNSSMQFFV-KDLEqdVLCITVFDRD-FFSP 90

                           90
                   ....*....|....
gi 2102677298   91 DKILGKVAIKREDL 104
Cdd:cd08375     91 DDFLGRTEIRVADI 104
C2_PKC_alpha_gamma cd04026
C2 domain in Protein Kinase C (PKC) alpha and gamma; A single C2 domain is found in PKC alpha ...
 11-91 8.10e-04

C2 domain in Protein Kinase C (PKC) alpha and gamma; A single C2 domain is found in PKC alpha and gamma. The PKC family of serine/threonine kinases regulates apoptosis, proliferation, migration, motility, chemo-resistance, and differentiation. There are 3 groups: group 1(alpha, betaI, beta II, gamma) which require phospholipids and calcium, group 2 (delta, epsilon, theta, eta) which do not require calcium for activation, and group 3 (xi, iota/lambda) which are atypical and can be activated in the absence of diacylglycerol and calcium. 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: 175992 [Multi-domain]  Cd Length: 131  Bit Score: 40.71  E-value: 8.10e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2102677298   11 EERLKIKIGEVKNLqsrnhgSP----GARDVYCVLSL---DQEEI-FRTTTMERTLNPFFGEEFQFEVPR--KFRYLGIY 80
Cdd:cd04026     12 DNKLTVEVREAKNL------IPmdpnGLSDPYVKLKLipdPKNETkQKTKTIKKTLNPVWNETFTFDLKPadKDRRLSIE 85

                           90
                   ....*....|.
gi 2102677298   81 VYDRDRHLKQD 91
Cdd:cd04026     86 VWDWDRTTRND 96
PLN03008 PLN03008
Phospholipase D delta
 19-125 8.16e-04

Phospholipase D delta


Pssm-ID: 178585 [Multi-domain]  Cd Length: 868  Bit Score: 43.54  E-value: 8.16e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2102677298   19 GEVKNLQSRNHGSPGARDVYCVLSLDQEEIFRTTTMERTLNPFFGEEFQFEVPRKFRYLGIYVYDRDRHLKQdkILGKVA 98
Cdd:PLN03008    61 GEFGDKNIRSHRKVITSDPYVTVVVPQATLARTRVLKNSQEPLWDEKFNISIAHPFAYLEFQVKDDDVFGAQ--IIGTAK 138

                           90       100       110
                   ....*....|....*....|....*....|..
gi 2102677298   99 IKREDLTTYHNKEHWFPL-----RPVDADSEV 125
Cdd:PLN03008   139 IPVRDIASGERISGWFPVlgasgKPPKAETAI 170
PH_Bem3 cd13277
Bud emergence protein 3 (Bem3) Pleckstrin homology (PH) domain; Bud emergence in Saccharomyces ...
 599-697 1.13e-03

Bud emergence protein 3 (Bem3) Pleckstrin homology (PH) domain; Bud emergence in Saccharomyces cerevisiae involves cell cycle-regulated reorganizations of cortical cytoskeletal elements and requires the action of the Rho-type GTPase Cdc42. Bem3 contains a RhoGAP domain and a PH domain. Though Bem3 and Bem2 both contain a RhoGAP, but only Bem3 is able to stimulate the hydrolysis of GTP on Cdc42. Bem3 is thought to be the GAP for Cdc42. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270096  Cd Length: 111  Bit Score: 39.58  E-value: 1.13e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2102677298  599 LKEGVMIKRaqgRKRFGRK--NFKQRYFKLTTQDLSYSKTKGKEPLCKIPLEE--ILAVEKLHEDSFKMKNIFQIIQSQR 674
Cdd:cd13277      4 VKEGYLLKR---RKKTLGStgGWKLRYGVLDGNILELYESRGGQLLESIKLRNaqIERQPNLPDDKYGTRHGFLINEHKK 80

                           90       100       110
                   ....*....|....*....|....*....|
gi 2102677298  675 AL-------YVQAGNCVEEKEWIDILTKIC 697
Cdd:cd13277     81 SGlssttkyYLCAETDKERDEWVSALSEYI 110
C2_Smurf-like cd08382
C2 domain present in Smad ubiquitination-related factor (Smurf)-like proteins; A single C2 ...
 164-198 1.20e-03

C2 domain present in Smad ubiquitination-related factor (Smurf)-like proteins; A single C2 domain is found in Smurf proteins, C2-WW-HECT-domain E3s, which play an important role in the downregulation of the TGF-beta signaling pathway. Smurf proteins also regulate cell shape, motility, and polarity by degrading small guanosine triphosphatases (GTPases). 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 type-II topology.


Pssm-ID: 176028 [Multi-domain]  Cd Length: 123  Bit Score: 39.98  E-value: 1.20e-03
                           10        20        30
                   ....*....|....*....|....*....|....*
gi 2102677298  164 DPFAIVTViysNGKQVlKRTKIKKKTVSPYFNETF 198
Cdd:cd08382     22 DPFAVITV---DGGQT-HSTDVAKKTLDPKWNEHF 52
PH1_FGD5_FGD6 cd13389
FYVE, RhoGEF and PH domain containing/faciogenital dysplasia proteins 5 and 6, N-terminal ...
 599-695 1.23e-03

FYVE, RhoGEF and PH domain containing/faciogenital dysplasia proteins 5 and 6, N-terminal Pleckstrin Homology (PH) domain; FGD5 regulates promotes angiogenesis of vascular endothelial growth factor (VEGF) in vascular endothelial cells, including network formation, permeability, directional movement, and proliferation. The specific function of FGD6 is unknown. In general, FGDs have a RhoGEF (DH) domain, followed by a PH domain, a FYVE domain and a C-terminal PH domain. All FGDs are guanine nucleotide exchange factors that activate the Rho GTPase Cdc42, an important regulator of membrane trafficking. The RhoGEF domain is responsible for GEF catalytic activity, while the PH domain is involved in intracellular targeting of the DH domain. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 275424  Cd Length: 124  Bit Score: 39.95  E-value: 1.23e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2102677298  599 LKEGVMIKRAqgrkrfgRKNFKQRYFKLTTQDLSYskTKGKEPLCKIPLEEILAVE----KLHEDSfKMKNIFQIIQSQR 674
Cdd:cd13389     15 IKEGELMKVS-------RKEMQPRYFFLFNDCLLY--TTPVQSSGMLKLNNELPLSgmkvKLPEDE-EYSNEFQIISTKR 84

                           90       100
                   ....*....|....*....|.
gi 2102677298  675 ALYVQAGNCVEEKEWIDILTK 695
Cdd:cd13389     85 SFTLIASSEEERDEWVKALSR 105
PH1_ARAP cd13253
ArfGAP with RhoGAP domain, ankyrin repeat and PH domain Pleckstrin homology (PH) domain, ...
 617-695 1.37e-03

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


Pssm-ID: 270073  Cd Length: 94  Bit Score: 38.91  E-value: 1.37e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2102677298  617 KNFKQRYFKLTTQDLSYSKTKgKEPLCK--IPLEEIlAVEKLHEDsfkmkNIFQIIQSQRALYVQAGNCVEEKEWIDILT 694
Cdd:cd13253     16 KGFQKRWVVFDGLSLRYFDSE-KDAYSKriIPLSAI-STVRAVGD-----NKFELVTTNRTFVFRAESDDERNLWCSTLQ 88


                   .
gi 2102677298  695 K 695
Cdd:cd13253     89 A 89
C2C_Munc13 cd08395
C2 domain third repeat in Munc13 (mammalian uncoordinated) proteins; C2-like domains are ...
 145-217 1.45e-03

C2 domain third 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 third C2 repeat, C2C, and has a type-II topology.


Pssm-ID: 176041 [Multi-domain]  Cd Length: 120  Bit Score: 39.69  E-value: 1.45e-03
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 2102677298  145 KLTVRVIECSELTIKNGGC-DPFAIVTVIYSNGKQVLKR--TKIKKKTVSPYFNETFIFepeiTESKEKDISHYSL 217
Cdd:cd08395      1 KVTVKVVAANDLKWQTTGMfRPFVEVNLIGPHLSDKKRKfaTKSKNNNWSPKYNETFQF----ILGNEDDPESYEL 72
C2B_Synaptotagmin-14_16 cd08408
C2 domain second repeat present in Synaptotagmins 14 and 16; Synaptotagmin 14 and 16 are ...
 145-200 1.56e-03

C2 domain second repeat present in Synaptotagmins 14 and 16; Synaptotagmin 14 and 16 are membrane-trafficking proteins in specific tissues outside the brain. Both of these contain C-terminal tandem C2 repeats, but only Synaptotagmin 14 has an N-terminal transmembrane domain and a putative fatty-acylation site. 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 and this is indeed the case here. 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: 176053 [Multi-domain]  Cd Length: 138  Bit Score: 40.04  E-value: 1.56e-03
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*....
gi 2102677298  145 KLTVRVIECSEL--TIKNGGCDPFAIVTVIYSNGKQVLK-RTKIKKKTVSPYFNETFIF 200
Cdd:cd08408     16 RLSVEVIKGSNFknLAMNKAPDTYVKLTLLNSDGQEISKsKTSIRRGQPDPEFKETFVF 74
PH1_PLEKHH1_PLEKHH2 cd13282
Pleckstrin homology (PH) domain containing, family H (with MyTH4 domain) members 1 and 2 ...
 617-700 1.97e-03

Pleckstrin homology (PH) domain containing, family H (with MyTH4 domain) members 1 and 2 (PLEKHH1) PH domain, repeat 1; PLEKHH1 and PLEKHH2 (also called PLEKHH1L) are thought to function in phospholipid binding and signal transduction. There are 3 Human PLEKHH genes: PLEKHH1, PLEKHH2, and PLEKHH3. There are many isoforms, the longest of which contain a FERM domain, a MyTH4 domain, two PH domains, a peroximal domain, a vacuolar domain, and a coiled coil stretch. The FERM domain has a cloverleaf tripart structure (FERM_N, FERM_M, FERM_C/N, alpha-, and C-lobe/A-lobe, B-lobe, C-lobe/F1, F2, F3). The C-lobe/F3 within the FERM domain is part of the PH domain family. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 241436  Cd Length: 96  Bit Score: 38.43  E-value: 1.97e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2102677298  617 KNFKQRYFKLTTQDLSYSKTK---GKEPLCKIPLEEILAVEKLHEDSfkmknIFQIIQSQRALYVQAGNCVEEKEWIDIL 693
Cdd:cd13282     13 KTWKRRWFVLKNGELFYYKSPndvIRKPQGQIALDGSCEIARAEGAQ-----TFEIVTEKRTYYLTADSENDLDEWIRVI 87


                   ....*..
gi 2102677298  694 TKICRTN 700
Cdd:cd13282     88 QNVLRRQ 94
C2B_Munc13-like cd04009
C2 domain second repeat in Munc13 (mammalian uncoordinated)-like proteins; C2-like domains are ...
 11-73 2.34e-03

C2 domain second 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 third C2 repeat, C2C, and has a type-II topology.


Pssm-ID: 175976 [Multi-domain]  Cd Length: 133  Bit Score: 39.14  E-value: 2.34e-03
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 2102677298   11 EERLKIKIGEVKNLQSRNhgSPGARDVYCVLSLDQEEIF------RTTTMERTLNPFFGEEFQFEVPRK 73
Cdd:cd04009     15 EQSLRVEILNARNLLPLD--SNGSSDPFVKVELLPRHLFpdvptpKTQVKKKTLFPLFDESFEFNVPPE 81
PH2_Pleckstrin_2 cd13302
Pleckstrin 2 Pleckstrin homology (PH) domain, repeat 2; Pleckstrin is a protein found in ...
 597-690 2.37e-03

Pleckstrin 2 Pleckstrin homology (PH) domain, repeat 2; Pleckstrin is a protein found in platelets. This name is derived from platelet and leukocyte C kinase substrate and the KSTR string of amino acids. Pleckstrin 2 contains two PH domains and a DEP (dishvelled, egl-10, and pleckstrin) domain. Unlike pleckstrin 1, pleckstrin 2 does not contain obvious sites of PKC phosphorylation. Pleckstrin 2 plays a role in actin rearrangement, large lamellipodia and peripheral ruffle formation, and may help orchestrate cytoskeletal arrangement. The PH domains of pleckstrin 2 are thought to contribute to lamellipodia formation. This cd contains the second PH domain repeat. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270114  Cd Length: 109  Bit Score: 38.65  E-value: 2.37e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2102677298  597 IVLKEGVMIKraQGRKRfgrKNFKQRYFKLTTQDL---SYSKTKGKEPLCKIPLEEILaVEKLHEDSFKMK-----NIFQ 668
Cdd:cd13302      6 IIVKQGCLLK--QGHRR---KNWKVRKFVLRDDPAylhYYDPAKGEDPLGAIHLRGCV-VTAVEDNSNPRKgsvegNLFE 79

                           90       100
                   ....*....|....*....|...
gi 2102677298  669 II-QSQRALYVQAGNCVEEKEWI 690
Cdd:cd13302     80 IItADEVHYYLQAATPAERTEWI 102
YPK1_N_like cd11651
Fungal protein kinase domain similar to the N-terminus of YPK1; This fungal domain family ...
 21-134 2.48e-03

Fungal protein kinase domain similar to the N-terminus of YPK1; This fungal domain family includes the N-terminal region of the Saccharomyces cerevisiae AGC kinases YPK1 and YPK2, which were found to be essential for the proliferation of yeast. YPK1 is required for cell growth and acts as a downstream kinase in the sphingolipid-mediated signaling pathway of yeast. It also plays a role in efficient endocytosis and in the maintenance of cell wall integrity.


Pssm-ID: 212165  Cd Length: 174  Bit Score: 40.10  E-value: 2.48e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2102677298   21 VKNLQSRNHGSPgarDVYCVLSLDQEEIFRTTTMERTLNPFFGEEFQFEVPRKFRyLGIYVYDRDRHL------KQDKIL 94
Cdd:cd11651     56 VQRSPSTSGPRP---LPYAVLEFDKNEVLIDALGGTVTNPVWNYEATFDVSRPSE-LTISVYLRNPDAlglggeRDDLNG 131

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|
gi 2102677298   95 GKVAIKREDLTTYHNKEHWFPLrpvdadSEVQGKAHLEIS 134
Cdd:cd11651    132 LVNDMSPSIQVPEYLSDQWIDL------QGGTGEIRVQID 165
C2B_Synaptotagmin-17 cd08410
C2 domain second repeat present in Synaptotagmin 17; Synaptotagmin is a membrane-trafficking ...
 145-213 2.54e-03

C2 domain second repeat present in Synaptotagmin 17; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. Synaptotagmin 17 is located in the brain, kidney, and prostate and is thought to be a peripheral membrane protein. 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: 176055 [Multi-domain]  Cd Length: 135  Bit Score: 39.10  E-value: 2.54e-03
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 2102677298  145 KLTVRVIECSEL--TIKNGGCDPFAIVTVIYSNGKQVLKRTKIKKKTVSPYFNETFIFepEITESKEKDIS 213
Cdd:cd08410     15 RLNVDIIRAKQLlqTDMSQGSDPFVKIQLVHGLKLIKTKKTSCMRGTIDPFYNESFSF--KVPQEELENVS 83
COG5038 COG5038
Ca2+-dependent lipid-binding protein, contains C2 domain [General function prediction only];
146-289 4.05e-03

Ca2+-dependent lipid-binding protein, contains C2 domain [General function prediction only];


Pssm-ID: 227371 [Multi-domain]  Cd Length: 1227  Bit Score: 41.28  E-value: 4.05e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2102677298  146 LTVRVIECSELTI--KNGGCDPFaivTVIYSNGKQVLKrTKIKKKTVSPYFNETFIFEpeiTESKEKDIShyslehgevn 223
Cdd:COG5038   1042 LTIMLRSGENLPSsdENGYSDPF---VKLFLNEKSVYK-TKVVKKTLNPVWNEEFTIE---VLNRVKDVL---------- 1104

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 2102677298  224 EVIVGLWHassgMGEQPAFLGEVRVTLRGLQ-KQSTNS----TTAWyFLQPRAVKH-----RPNKISNSSTSPGVL 289
Cdd:COG5038   1105 TINVNDWD----SGEKNDLLGTAEIDLSKLEpGGTTNSniplDGKT-FIVLDGTLHpgfnfRSKYALNVSRKEGIL 1175
C2_PSD cd04039
C2 domain present in Phosphatidylserine decarboxylase (PSD); PSD is involved in the ...
 164-201 4.05e-03

C2 domain present in Phosphatidylserine decarboxylase (PSD); PSD is involved in the biosynthesis of aminophospholipid by converting phosphatidylserine (PtdSer) to phosphatidylethanolamine (PtdEtn). There is a single C2 domain present and it is thought to confer PtdSer binding motif that is common to PKC and synaptotagmin. 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: 176004 [Multi-domain]  Cd Length: 108  Bit Score: 38.00  E-value: 4.05e-03
                           10        20        30
                   ....*....|....*....|....*....|....*...
gi 2102677298  164 DPFAIVTViysnGKQVLkRTKIKKKTVSPYFNETFIFE 201
Cdd:cd04039     27 DPFVIISF----GRRVF-RTSWRRHTLNPVFNERLAFE 59
C2A_Rabphilin_Doc2 cd04035
C2 domain first repeat present in Rabphilin and Double C2 domain; Rabphilin is found neurons ...
 12-86 4.66e-03

C2 domain first repeat present in Rabphilin and Double C2 domain; Rabphilin is found neurons and in neuroendrocrine cells, while Doc2 is found not only in the brain but in tissues, including mast cells, chromaffin cells, and osteoblasts. Rabphilin and Doc2s share highly homologous tandem C2 domains, although their N-terminal structures are completely different: rabphilin contains an N-terminal Rab-binding domain (RBD),7 whereas Doc2 contains an N-terminal Munc13-1-interacting domain (MID). 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: 176000 [Multi-domain]  Cd Length: 123  Bit Score: 38.03  E-value: 4.66e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2102677298   12 ERLKIKIGEVKNLQSRNHGspGARDVYCVLSLDQEEI----FRTTTMERTLNPFFGEEFQF------EVPRKfrYLGIYV 81
Cdd:cd04035     15 SALHCTIIRAKGLKAMDAN--GLSDPYVKLNLLPGASkatkLRTKTVHKTRNPEFNETLTYygiteeDIQRK--TLRLLV 90


                   ....*
gi 2102677298   82 YDRDR 86
Cdd:cd04035     91 LDEDR 95
RasGAP_RAP6 cd05129
Ras-GTPase Activating Domain of Rab5-activating protein 6; Rab5-activating protein 6 (RAP6) is ...
 345-534 5.04e-03

Ras-GTPase Activating Domain of Rab5-activating protein 6; Rab5-activating protein 6 (RAP6) is an endosomal protein with a role in the regulation of receptor-mediated endocytosis. RAP6 contains a Vps9 domain, which is involved in the activation of Rab5, and a Ras GAP domain (RGD). Rab5 is a small GTPase required for the control of the endocytic route, and its activity is regulated by guanine nucleotide exchange factor, such as Rabex5, and GAPs, such as RN-tre. Human Rap6 protein is localized on the plasma membrane and on the endosome. RAP6 binds to Rab5 and Ras through the Vps9 and RGD domains, respectively.


Pssm-ID: 213331  Cd Length: 365  Bit Score: 40.40  E-value: 5.04e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2102677298  345 EAAQPLVRVLVH--YG---------QLVSVMRALASHEISKLTDPTTIFRGNTLVS----KMMDEGMRLAGLhYLHSTLR 409
Cdd:cd05129     40 EQTQNVIQTIVTslYGncimpederLLLQLLRELMELQLKKSDNPRRLLRKGSCAFsrvfKLFTELLFSAKL-YLTAALH 118

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2102677298  410 PAMKQV------FLE----KKSCEIDP----TRVKDANTIQTNLtNLKEYVERV---FIAITTSGVRCPSLMCEMF---- 468
Cdd:cd05129    119 KPIMQVlvddeiFLEtdpqKALCRFSPaeqeKRFGEEGTPEQQR-KLQQYRAEFlsrLVALVNKFISSLRQSVYCFpqsl 197

                          170       180       190       200       210       220       230
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 2102677298  469 -WCLKELAATHFPKNK---EVRYSVISGFIFLRFFAPAILGPRLFDITTEQIDSQTNR-TLTLISKTIQSL 534
Cdd:cd05129    198 rWIVRQLRKILTRSGDdeeAEARALCTDLLFTNFICPAIVNPEQYGIISDAPISEVARhNLMQVAQILQVL 268
C2A_fungal cd04041
C2 domain first repeat; fungal group; C2 domains were first identified in Protein Kinase C ...
 33-112 6.82e-03

C2 domain first repeat; fungal group; 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: 176006 [Multi-domain]  Cd Length: 111  Bit Score: 37.24  E-value: 6.82e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2102677298   33 GARDVYCVLSL--DQEEIFRTTTMERTLNPFFgEEFQF------EVPRKFRyLGIYVYDRDRHlKQDKILGKVAIKREDL 104
Cdd:cd04041     21 GSSDPYVTASFakFGKPLYSTRIIRKDLNPVW-EETWFvlvtpdEVKAGER-LSCRLWDSDRF-TADDRLGRVEIDLKEL 97


                   ....*...
gi 2102677298  105 TTYHNKEH 112
Cdd:cd04041     98 IEDRNWMG 105
C2A_Tricalbin-like cd04044
C2 domain first repeat present in Tricalbin-like proteins; 5 to 6 copies of the C2 domain are ...
 157-198 7.76e-03

C2 domain first 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 first C2 repeat, C2A, and has a type-II topology.


Pssm-ID: 176009 [Multi-domain]  Cd Length: 124  Bit Score: 37.53  E-value: 7.76e-03
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|..
gi 2102677298  157 TIKNGGCDPFAIVTViysNGKQVLKRTKIKKKTVSPYFNETF 198
Cdd:cd04044     18 DIIGGTVDPYVTFSI---SNRRELARTKVKKDTSNPVWNETK 56
C2B_PI3K_class_II cd08381
C2 domain second repeat present in class II phosphatidylinositol 3-kinases (PI3Ks); There are ...
 14-117 9.00e-03

C2 domain second repeat present in class II phosphatidylinositol 3-kinases (PI3Ks); There are 3 classes of PI3Ks based on structure, regulation, and specificity. All classes contain a N-terminal C2 domain, a PIK domain, and a kinase catalytic domain. Unlike class I and class III, class II PI3Ks have additionally a PX domain and a C-terminal C2 domain containing a nuclear localization signal both of which bind phospholipids though in a slightly different fashion. PI3Ks (AKA phosphatidylinositol (PtdIns) 3-kinases) regulate cell processes such as cell growth, differentiation, proliferation, and motility. PI3Ks work on phosphorylation of phosphatidylinositol, phosphatidylinositide (4)P (PtdIns (4)P),2 or PtdIns(4,5)P2. Specifically they phosphorylate the D3 hydroxyl group of phosphoinositol lipids on the inositol ring. 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: 176027 [Multi-domain]  Cd Length: 122  Bit Score: 37.27  E-value: 9.00e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2102677298   14 LKIKIGEVKNLQSRNHGSPGARdVYCVLSLD-QEEIFRTT-TMERTLNPFFGEEFQFE-VPR---KFRYLGIYVYDRDRH 87
Cdd:cd08381     15 LFVMVMHAKNLPLLDGSDPDPY-VKTYLLPDpQKTTKRKTkVVRKTRNPTFNEMLVYDgLPVedlQQRVLQVSVWSHDSL 93

                           90       100       110
                   ....*....|....*....|....*....|
gi 2102677298   88 LKQDKiLGKVAIKREDLTTYHNKEHWFPLR 117
Cdd:cd08381     94 VENEF-LGGVCIPLKKLDLSQETEKWYPLG 122
PH_SWAP-70 cd13273
Switch-associated protein-70 Pleckstrin homology (PH) domain; SWAP-70 (also called ...
 598-690 9.34e-03

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


Pssm-ID: 270092  Cd Length: 110  Bit Score: 36.89  E-value: 9.34e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2102677298  598 VLKEGVMIKRAqgrkrFGRKNFKQRYFKLTTQDLSYSKTK-GKEPLCKIPLEEILAVEKLhEDSFKMKNIFQIIQSQRAL 676
Cdd:cd13273      8 VIKKGYLWKKG-----HLLPTWTERWFVLKPNSLSYYKSEdLKEKKGEIALDSNCCVESL-PDREGKKCRFLVKTPDKTY 81

                           90
                   ....*....|....
gi 2102677298  677 YVQAGNCVEEKEWI 690
Cdd:cd13273     82 ELSASDHKTRQEWI 95
C2_Freud-1 cd08690
C2 domain found in 5' repressor element under dual repression binding protein-1 (Freud-1); ...
 50-106 9.85e-03

C2 domain found in 5' repressor element under dual repression binding protein-1 (Freud-1); Freud-1 is a novel calcium-regulated repressor that negatively regulates basal 5-HT1A receptor expression in neurons. It may also play a role in the altered regulation of 5-HT1A receptors associated with anxiety or major depression. Freud-1 contains two DM-14 basic repeats, a helix-loop-helix DNA binding domain, and a C2 domain. The Freud-1 C2 domain is thought to be calcium insensitive and it lacks several acidic residues that mediate calcium binding of the PKC C2 domain. In addition, it contains a poly-basic insert that is not present in calcium-dependent C2 domains and may function as a nuclear localization signal. 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: 176072 [Multi-domain]  Cd Length: 155  Bit Score: 37.67  E-value: 9.85e-03
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 2102677298   50 RTTTMERTLNPFFGEEFQFEVPRKFRYL-------GIY--VYDRDRHLKQDKILGKVAIKREDLTT 106
Cdd:cd08690     44 KTSTIKDTNSPEYNESFKLNINRKHRSFqrvfkrhGLKfeVYHKGGFLRSDKLLGTAQVKLEPLET 109
 
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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