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Conserved domains on  [gi|1799135512|ref|NP_001364489|]
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dedicator of cytokinesis protein 1 isoform 13 [Homo sapiens]

Protein Classification

Graphical summary

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List of domain hits

 Name Accession Description Interval E-value
DHR2_DOCK1 cd11707
Dock Homology Region 2, a GEF domain, of Class A Dedicator of Cytokinesis 1; Dock1, also ...
 950-1348 0e+00

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


:

Pssm-ID: 212580  Cd Length: 400  Bit Score: 904.79  E-value: 0e+00
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799135512  950 EMYIRYLYKLCDLHKECDNYTEAAYTLLLHAKLLKWSEDVCVAHLTQRDGYQATTQGQLKEQLYQEIIHYFDKGKMWEEA 1029
Cdd:cd11707      1 EMYIRYLYKLCDLHKECDNYTEAAYTLLLHAKLLKWSEEACAAHLTQRDGYQATTQGQLKDQLYQEIIHYFDKGKMWEEA 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799135512 1030 IALGKELAEQYENEMFDYEQLSELLKKQAQFYENIVKVIRPKPDYFAVGYYGQGFPTFLRGKVFIYRGKEYERREDFEAR 1109
Cdd:cd11707     81 IALGKELAEQYENEMFDYEQLSELLKKQAQFYENIVKVIRPKPDYFAVGYYGQGFPTFLRNKMFIYRGKEYERREDFEAR 160

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799135512 1110 LLTQFPNAEKMKTTSPPGDDIKNSPGQYIQCFTVKPKLDLPPKF-HRPVSEQIVSFYRVNEVQRFEYSRPIRKGEKNPDN 1188
Cdd:cd11707    161 LLTQFPNAEKMKTTSPPGDDIKNSSGQYIQCFTVKPLLELPPKFqNKPVSEQIVSFYRVNEVQRFQYSRPVRKGEKDPDN 240

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799135512 1189 EFANMWIERTIYTTAYKLPGILRWFEVKSVFMVEISPLENAIETMQLTNDKINSMVQQHLDDPSLPINPLSMLLNGIVDP 1268
Cdd:cd11707    241 EFANMWIERTTYVTAYKLPGILRWFEVKSVFMVEISPLENAIETMQLTNEKINNMVQQHLNDPNLPINPLSMLLNGIVDP 320

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799135512 1269 AVMGGFANYEKAFFTDRYLQEHPEAHEKIEKLKDLIAWQIPFLAEGIRIHGDKVTEALRPFHERMEACFKQLKEKVEKEY 1348
Cdd:cd11707    321 AVMGGFANYEKAFFTEKYMQEHPEDHEKIEKLKDLIAWQIPFLAEGIRIHGEKVTEALRPFHERMEACFRQLKEKVEKQY 400
C2_Dock-A cd08694
C2 domains found in Dedicator Of CytoKinesis (Dock) class A proteins; Dock-A is one of 4 ...
 160-355 1.00e-121

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


:

Pssm-ID: 176076  Cd Length: 196  Bit Score: 379.05  E-value: 1.00e-121
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799135512  160 VRNDIYVTLVQGDFDKGSKTTAKNVEVTVSVYDEDGKRLEHVIFPGAGDEAISEYKSVIYYQVKQPRWFETVKVAIPIED 239
Cdd:cd08694      1 VRNDLYLTLVQGDFDKGSKTSDKNVEVTVSVCNEDGKIIPGVISLGAGEEPIDEYKSVIYYQVDKPKWFETFKVAIPIED 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799135512  240 VNRSHLRFTFRHRSSQDSKDKSEKIFALAFVKLMRYDGTTLRDGEHDLIVYKAEAKK-LEDAATYLSLPSTKAELEEKGH 318
Cdd:cd08694     81 FKSSHLRFTFKHRSSNEAKDKSEKPFALSFVKLMQENGTTLTDGEHDLIVYKVDAKKkLEDAKAYLSLPSTRAELEARKS 160

                          170       180       190
                   ....*....|....*....|....*....|....*..
gi 1799135512  319 SATGKSMQsLGSCTISKDSFQISTLVCSTKLTQNVDL 355
Cdd:cd08694    161 SPSGSASN-LGLSLSSKDSFQISTLVCSTKLTQNVDL 196
DOCK_N super family cl24677
DOCK N-terminus; This family is found near to the N-terminus of dedicator of cytokinesis (DOCK) ...
 44-152 3.57e-20

DOCK N-terminus; This family is found near to the N-terminus of dedicator of cytokinesis (DOCK) proteins, between the variant SH3 domain (pfam07653) and the C2 domain (pfam14429).


The actual alignment was detected with superfamily member pfam16172:

Pssm-ID: 465040  Cd Length: 317  Bit Score: 93.35  E-value: 3.57e-20
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799135512   44 VMDVTDIINGKVD-DEDKQHFIPFQPlalddairhkplnmssrfsprVAGENDF--LQTVINKVIAAK-EVNHKGQGLWV 119
Cdd:pfam16172  227 VLDLTDILKGLKQsDEEVEHVVPIWS---------------------PNNESDFdeLHRDIIKSITGKyEKSPRAERLWV 285

                           90       100       110
                   ....*....|....*....|....*....|...
gi 1799135512  120 TLKLLPGDIHQIRKEFPHLVdRTTAVARKTGFP 152
Cdd:pfam16172  286 SLKLFHGDAEQLRKENPTLL-HNVAITRKLGFP 317
SH3 super family cl17036
Src Homology 3 domain superfamily; Src Homology 3 (SH3) domains are protein interaction ...
 13-43 2.28e-14

Src Homology 3 domain superfamily; Src Homology 3 (SH3) domains are protein interaction domains that bind proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. Thus, they are referred to as proline-recognition domains (PRDs). SH3 domains are less selective and show more diverse specificity compared to other PRDs. They have been shown to bind peptide sequences that lack the PxxP motif; examples include the PxxDY motif of Eps8 and the RKxxYxxY sequence in SKAP55. SH3 domain containing proteins play versatile and diverse roles in the cell, including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies, among others. Many members of this superfamily are adaptor proteins that associate with a number of protein partners, facilitating complex formation and signal transduction.


The actual alignment was detected with superfamily member cd12051:

Pssm-ID: 473055 [Multi-domain]  Cd Length: 56  Bit Score: 68.69  E-value: 2.28e-14
                           10        20        30
                   ....*....|....*....|....*....|.
gi 1799135512   13 YGVAFYNYDARGADELSLQIGDTVHILETYE 43
Cdd:cd12051      1 YGVAIYNYDARGPDELSLQIGDTVHILETYE 31
 
Name Accession Description Interval E-value
DHR2_DOCK1 cd11707
Dock Homology Region 2, a GEF domain, of Class A Dedicator of Cytokinesis 1; Dock1, also ...
 950-1348 0e+00

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


Pssm-ID: 212580  Cd Length: 400  Bit Score: 904.79  E-value: 0e+00
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799135512  950 EMYIRYLYKLCDLHKECDNYTEAAYTLLLHAKLLKWSEDVCVAHLTQRDGYQATTQGQLKEQLYQEIIHYFDKGKMWEEA 1029
Cdd:cd11707      1 EMYIRYLYKLCDLHKECDNYTEAAYTLLLHAKLLKWSEEACAAHLTQRDGYQATTQGQLKDQLYQEIIHYFDKGKMWEEA 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799135512 1030 IALGKELAEQYENEMFDYEQLSELLKKQAQFYENIVKVIRPKPDYFAVGYYGQGFPTFLRGKVFIYRGKEYERREDFEAR 1109
Cdd:cd11707     81 IALGKELAEQYENEMFDYEQLSELLKKQAQFYENIVKVIRPKPDYFAVGYYGQGFPTFLRNKMFIYRGKEYERREDFEAR 160

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799135512 1110 LLTQFPNAEKMKTTSPPGDDIKNSPGQYIQCFTVKPKLDLPPKF-HRPVSEQIVSFYRVNEVQRFEYSRPIRKGEKNPDN 1188
Cdd:cd11707    161 LLTQFPNAEKMKTTSPPGDDIKNSSGQYIQCFTVKPLLELPPKFqNKPVSEQIVSFYRVNEVQRFQYSRPVRKGEKDPDN 240

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799135512 1189 EFANMWIERTIYTTAYKLPGILRWFEVKSVFMVEISPLENAIETMQLTNDKINSMVQQHLDDPSLPINPLSMLLNGIVDP 1268
Cdd:cd11707    241 EFANMWIERTTYVTAYKLPGILRWFEVKSVFMVEISPLENAIETMQLTNEKINNMVQQHLNDPNLPINPLSMLLNGIVDP 320

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799135512 1269 AVMGGFANYEKAFFTDRYLQEHPEAHEKIEKLKDLIAWQIPFLAEGIRIHGDKVTEALRPFHERMEACFKQLKEKVEKEY 1348
Cdd:cd11707    321 AVMGGFANYEKAFFTEKYMQEHPEDHEKIEKLKDLIAWQIPFLAEGIRIHGEKVTEALRPFHERMEACFRQLKEKVEKQY 400
C2_Dock-A cd08694
C2 domains found in Dedicator Of CytoKinesis (Dock) class A proteins; Dock-A is one of 4 ...
 160-355 1.00e-121

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


Pssm-ID: 176076  Cd Length: 196  Bit Score: 379.05  E-value: 1.00e-121
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799135512  160 VRNDIYVTLVQGDFDKGSKTTAKNVEVTVSVYDEDGKRLEHVIFPGAGDEAISEYKSVIYYQVKQPRWFETVKVAIPIED 239
Cdd:cd08694      1 VRNDLYLTLVQGDFDKGSKTSDKNVEVTVSVCNEDGKIIPGVISLGAGEEPIDEYKSVIYYQVDKPKWFETFKVAIPIED 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799135512  240 VNRSHLRFTFRHRSSQDSKDKSEKIFALAFVKLMRYDGTTLRDGEHDLIVYKAEAKK-LEDAATYLSLPSTKAELEEKGH 318
Cdd:cd08694     81 FKSSHLRFTFKHRSSNEAKDKSEKPFALSFVKLMQENGTTLTDGEHDLIVYKVDAKKkLEDAKAYLSLPSTRAELEARKS 160

                          170       180       190
                   ....*....|....*....|....*....|....*..
gi 1799135512  319 SATGKSMQsLGSCTISKDSFQISTLVCSTKLTQNVDL 355
Cdd:cd08694    161 SPSGSASN-LGLSLSSKDSFQISTLVCSTKLTQNVDL 196
DOCK-C2 pfam14429
C2 domain in Dock180 and Zizimin proteins; The Dock180/Dock1 and Zizimin proteins are atypical ...
 157-354 4.89e-83

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


Pssm-ID: 464171  Cd Length: 185  Bit Score: 269.86  E-value: 4.89e-83
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799135512  157 PGDVRNDIYVTLVQGDFDKGSKTTAKNVEVTVSVYDEDGKRLEHVIFPGAGDEAISEYKSVIYYQVKQPRWFETVKVAIP 236
Cdd:pfam14429    1 PGDYRNDLYVTPKSGNFSKQKKSSARNIEVTVEVRDSDGEPLPNCIYGGSGGPFVTEFKSTVYYHNKSPTWYEEIKIALP 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799135512  237 IEDVNRSHLRFTFRHRSSQDSKDKSEKIFALAFVKLMRYDGTTLRDGEHDLIVYKAEakklEDAATYLSLPSTKAELEEK 316
Cdd:pfam14429   81 AELTPKHHLLFTFYHVSCDEKKDKVEKPFGYAFLPLLDDDGAFLRDGEHTLPVYKYD----ELPPGYLSLPWSSGGEKES 156

                          170       180       190
                   ....*....|....*....|....*....|....*...
gi 1799135512  317 ghsatgksmQSLGSCTISKDSFQISTLVCSTKLTQNVD 354
Cdd:pfam14429  157 ---------SALPGLKGGKDLFKVRTRLCSTKYTQDEH 185
DHR-2_Lobe_C pfam20421
DHR-2, Lobe C; DOCK (dedicator of cytokinesis) proteins are guanine nucleotide exchange ...
 1243-1346 1.81e-27

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


Pssm-ID: 466570 [Multi-domain]  Cd Length: 103  Bit Score: 107.68  E-value: 1.81e-27
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799135512 1243 MVQQHLDDPSLPINPLSMLLNGIVDPAVMGGFANYEKAFFTDRYLQEHPEahEKIEKLKDLIAWQIPFLAEGIRIHGDKV 1322
Cdd:pfam20421    1 ELEAAINAPPPNIKTLQMVLQGSVDVQVNAGPLEYAEAFLSEKNVDNYPA--EKVEKLKEEFRDFLKVCGEALRLNKKLI 78

                           90       100
                   ....*....|....*....|....
gi 1799135512 1323 TEALRPFHERMEACFKQLKEKVEK 1346
Cdd:pfam20421   79 SEDQREYQEELEEGFEKLKEKLEP 102
DOCK_N pfam16172
DOCK N-terminus; This family is found near to the N-terminus of dedicator of cytokinesis (DOCK) ...
 44-152 3.57e-20

DOCK N-terminus; This family is found near to the N-terminus of dedicator of cytokinesis (DOCK) proteins, between the variant SH3 domain (pfam07653) and the C2 domain (pfam14429).


Pssm-ID: 465040  Cd Length: 317  Bit Score: 93.35  E-value: 3.57e-20
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799135512   44 VMDVTDIINGKVD-DEDKQHFIPFQPlalddairhkplnmssrfsprVAGENDF--LQTVINKVIAAK-EVNHKGQGLWV 119
Cdd:pfam16172  227 VLDLTDILKGLKQsDEEVEHVVPIWS---------------------PNNESDFdeLHRDIIKSITGKyEKSPRAERLWV 285

                           90       100       110
                   ....*....|....*....|....*....|...
gi 1799135512  120 TLKLLPGDIHQIRKEFPHLVdRTTAVARKTGFP 152
Cdd:pfam16172  286 SLKLFHGDAEQLRKENPTLL-HNVAITRKLGFP 317
SH3_DOCK1_5_A cd12051
Src Homology 3 domain of Class A Dedicator of Cytokinesis proteins 1 and 5; Dock1, also called ...
 13-43 2.28e-14

Src Homology 3 domain of Class A Dedicator of Cytokinesis proteins 1 and 5; Dock1, also called Dock180, and Dock5 are class A DOCKs and are atypical guanine nucleotide exchange factors (GEFs) that lack the conventional Dbl homology (DH) domain. Dock1 interacts with the scaffold protein Elmo and the resulting complex functions upstream of Rac in many biological events including phagocytosis of apoptotic cells, cell migration and invasion. Dock5 functions upstream of Rac1 to regulate osteoclast function. All DOCKs contain two homology domains: the DHR-1 (Dock homology region-1), also called CZH1 (CED-5, Dock180, and MBC-zizimin homology 1), and DHR-2 (also called CZH2 or Docker). The DHR-1 domain binds phosphatidylinositol-3,4,5-triphosphate while DHR-2 contains the catalytic activity for Rac and/or Cdc42. Class A DOCKs also contain an SH3 domain at the N-terminal region and a PxxP motif at the C-terminus; they are specific GEFs for Rac. The SH3 domain of Dock1 binds to DHR-2 in an autoinhibitory manner; binding of Elmo to the SH3 domain of Dock1 exposes the DHR-2 domain and promotes GEF activity. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212984 [Multi-domain]  Cd Length: 56  Bit Score: 68.69  E-value: 2.28e-14
                           10        20        30
                   ....*....|....*....|....*....|.
gi 1799135512   13 YGVAFYNYDARGADELSLQIGDTVHILETYE 43
Cdd:cd12051      1 YGVAIYNYDARGPDELSLQIGDTVHILETYE 31
SH3 smart00326
Src homology 3 domains; Src homology 3 (SH3) domains bind to target proteins through sequences ...
 10-43 5.17e-06

Src homology 3 domains; Src homology 3 (SH3) domains bind to target proteins through sequences containing proline and hydrophobic amino acids. Pro-containing polypeptides may bind to SH3 domains in 2 different binding orientations.


Pssm-ID: 214620 [Multi-domain]  Cd Length: 56  Bit Score: 45.22  E-value: 5.17e-06
                            10        20        30
                    ....*....|....*....|....*....|....
gi 1799135512    10 EEKYGVAFYNYDARGADELSLQIGDTVHILETYE 43
Cdd:smart00326    1 EGPQVRALYDYTAQDPDELSFKKGDIITVLEKSD 34
SH3_1 pfam00018
SH3 domain; SH3 (Src homology 3) domains are often indicative of a protein involved in signal ...
 15-40 7.27e-04

SH3 domain; SH3 (Src homology 3) domains are often indicative of a protein involved in signal transduction related to cytoskeletal organization. First described in the Src cytoplasmic tyrosine kinase. The structure is a partly opened beta barrel.


Pssm-ID: 394975 [Multi-domain]  Cd Length: 47  Bit Score: 38.72  E-value: 7.27e-04
                           10        20
                   ....*....|....*....|....*.
gi 1799135512   15 VAFYNYDARGADELSLQIGDTVHILE 40
Cdd:pfam00018    1 VALYDYTAQEPDELSFKKGDIIIVLE 26
 
Name Accession Description Interval E-value
DHR2_DOCK1 cd11707
Dock Homology Region 2, a GEF domain, of Class A Dedicator of Cytokinesis 1; Dock1, also ...
 950-1348 0e+00

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


Pssm-ID: 212580  Cd Length: 400  Bit Score: 904.79  E-value: 0e+00
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799135512  950 EMYIRYLYKLCDLHKECDNYTEAAYTLLLHAKLLKWSEDVCVAHLTQRDGYQATTQGQLKEQLYQEIIHYFDKGKMWEEA 1029
Cdd:cd11707      1 EMYIRYLYKLCDLHKECDNYTEAAYTLLLHAKLLKWSEEACAAHLTQRDGYQATTQGQLKDQLYQEIIHYFDKGKMWEEA 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799135512 1030 IALGKELAEQYENEMFDYEQLSELLKKQAQFYENIVKVIRPKPDYFAVGYYGQGFPTFLRGKVFIYRGKEYERREDFEAR 1109
Cdd:cd11707     81 IALGKELAEQYENEMFDYEQLSELLKKQAQFYENIVKVIRPKPDYFAVGYYGQGFPTFLRNKMFIYRGKEYERREDFEAR 160

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799135512 1110 LLTQFPNAEKMKTTSPPGDDIKNSPGQYIQCFTVKPKLDLPPKF-HRPVSEQIVSFYRVNEVQRFEYSRPIRKGEKNPDN 1188
Cdd:cd11707    161 LLTQFPNAEKMKTTSPPGDDIKNSSGQYIQCFTVKPLLELPPKFqNKPVSEQIVSFYRVNEVQRFQYSRPVRKGEKDPDN 240

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799135512 1189 EFANMWIERTIYTTAYKLPGILRWFEVKSVFMVEISPLENAIETMQLTNDKINSMVQQHLDDPSLPINPLSMLLNGIVDP 1268
Cdd:cd11707    241 EFANMWIERTTYVTAYKLPGILRWFEVKSVFMVEISPLENAIETMQLTNEKINNMVQQHLNDPNLPINPLSMLLNGIVDP 320

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799135512 1269 AVMGGFANYEKAFFTDRYLQEHPEAHEKIEKLKDLIAWQIPFLAEGIRIHGDKVTEALRPFHERMEACFKQLKEKVEKEY 1348
Cdd:cd11707    321 AVMGGFANYEKAFFTEKYMQEHPEDHEKIEKLKDLIAWQIPFLAEGIRIHGEKVTEALRPFHERMEACFRQLKEKVEKQY 400
DHR2_DOCK_A cd11697
Dock Homology Region 2, a GEF domain, of Class A Dedicator of Cytokinesis proteins; DOCK ...
 950-1348 0e+00

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


Pssm-ID: 212570  Cd Length: 400  Bit Score: 795.38  E-value: 0e+00
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799135512  950 EMYIRYLYKLCDLHKECDNYTEAAYTLLLHAKLLKWSEDVCVAHLTQRDGYQATTQGQLKEQLYQEIIHYFDKGKMWEEA 1029
Cdd:cd11697      1 EMYIRYLYKLCDLHLECDNYTEAAYTLQLHAELLKWSDEPLPTLLRSRRYPEAQTHRQLKEALYYDIIDYFDKGKMWECA 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799135512 1030 IALGKELAEQYENEMFDYEQLSELLKKQAQFYENIVKVIRPKPDYFAVGYYGQGFPTFLRGKVFIYRGKEYERREDFEAR 1109
Cdd:cd11697     81 ISLCKELAEQYENETFDYLQLSELLKRMATFYDNIMKTLRPEPEYFRVGYYGQGFPSFLRNKVFIYRGKEYERLSDFSAR 160

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799135512 1110 LLTQFPNAEKMKTTSPPGDDIKNSPGQYIQCFTVKPKLDLPPKF-HRPVSEQIVSFYRVNEVQRFEYSRPIRKGEKNPDN 1188
Cdd:cd11697    161 LLNQFPNAELMNTLTPPGDEIKESPGQYLQINKVDPVMDERPRFkGKPVSDQILNYYKVNEVQRFTFSRPFRRGTKDPDN 240

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799135512 1189 EFANMWIERTIYTTAYKLPGILRWFEVKSVFMVEISPLENAIETMQLTNDKINSMVQQHLDDPSLPINPLSMLLNGIVDP 1268
Cdd:cd11697    241 EFANMWLERTTLTTAYKLPGILRWFEVVSTSTVEISPLENAIETMEDTNKKIRDLILQHQSDPTLPINPLSMLLNGIVDA 320

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799135512 1269 AVMGGFANYEKAFFTDRYLQEHPEAHEKIEKLKDLIAWQIPFLAEGIRIHGDKVTEALRPFHERMEACFKQLKEKVEKEY 1348
Cdd:cd11697    321 AVMGGIANYEKAFFTEEYLDEHPEDQELIERLKDLIAEQIPLLEAGLKIHKQKAPESLRPLHERMEECFAKMKEHVEEKY 400
DHR2_DOCK2 cd11706
Dock Homology Region 2, a GEF domain, of Class A Dedicator of Cytokinesis 2; Dock2 is a ...
 932-1351 0e+00

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


Pssm-ID: 212579  Cd Length: 421  Bit Score: 754.13  E-value: 0e+00
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799135512  932 RMSCTVNVLNFYKEIEREEMYIRYLYKLCDLHKECDNYTEAAYTLLLHAKLLKWSEDVCVAHLTQRDGYQATTQGQLKEQ 1011
Cdd:cd11706      1 RMSCTVNLLNFYKDINREAMYIRYLYKLRDLHLDCENYTEAAYTLLLHTRLLKWSDEQCASQVMQTGQQHPQTQRQLKET 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799135512 1012 LYQEIIHYFDKGKMWEEAIALGKELAEQYENEMFDYEQLSELLKKQAQFYENIVKVIRPKPDYFAVGYYGQGFPTFLRGK 1091
Cdd:cd11706     81 LYETIIGYFDKGKMWEEAISLCKELAEQYEMEIFDYELLSQNLIQQAKFYESIMKILRPKPDYFAVGYYGQGFPSFLRNK 160

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799135512 1092 VFIYRGKEYERREDFEARLLTQFPNAEKMKTTSPPGDDIKNSPGQYIQCFTVKPKLDLPPKF-HRPVSEQIVSFYRVNEV 1170
Cdd:cd11706    161 VFIYRGKEYERREDFQMQLMSQFPNAEKLNTTSAPGDDIKNSPGQYIQCFTVQPVLEEHPRLkNKPVPDQIINFYKSNYV 240

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799135512 1171 QRFEYSRPIRKGEKNPDNEFANMWIERTIYTTAYKLPGILRWFEVKSVFMVEISPLENAIETMQLTNDKINSMVQQHLDD 1250
Cdd:cd11706    241 QRFHYSRPVRKGPVDPENEFASMWIERTTFVTAYKLPGILRWFEVTHMSQTTISPLENAIETMSTTNEKILMMINQYQSD 320

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799135512 1251 PSLPINPLSMLLNGIVDPAVMGGFANYEKAFFTDRYLQEHPEAHEKIEKLKDLIAWQIPFLAEGIRIHGDKVTEALRPFH 1330
Cdd:cd11706    321 ESLPINPLSMLLNGIVDPAVMGGFAKYEKAFFTEEYVRDHPEDQDKLTRLKDLIAWQIPLLGAGIKIHGKRVTDDLRPFH 400

                          410       420
                   ....*....|....*....|.
gi 1799135512 1331 ERMEACFKQLKEKVEKEYGVR 1351
Cdd:cd11706    401 ERMEECFKQLKMKVEKEYGVR 421
DHR2_DOCK5 cd11708
Dock Homology Region 2, a GEF domain, of Class A Dedicator of Cytokinesis 5; Dock5 is an ...
 950-1348 0e+00

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


Pssm-ID: 212581  Cd Length: 400  Bit Score: 708.25  E-value: 0e+00
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799135512  950 EMYIRYLYKLCDLHKECDNYTEAAYTLLLHAKLLKWSEDVCVAHLTQRDGYQATTQGQLKEQLYQEIIHYFDKGKMWEEA 1029
Cdd:cd11708      1 DIYIRYLYKLRDLHLDCENYTEAAYTLLLHAELLQWSEKPCVPHLLQRDSYYVYTQQELKERLYQEIISFFDKGKMWEKA 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799135512 1030 IALGKELAEQYENEMFDYEQLSELLKKQAQFYENIVKVIRPKPDYFAVGYYGQGFPTFLRGKVFIYRGKEYERREDFEAR 1109
Cdd:cd11708     81 IELSKELADMYENQVFDYEGLGNLLKKQAQFYENIMKAMRPQPEYFAVGYYGQGFPSFLRNKIFIYRGKEYERLEDFSLK 160

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799135512 1110 LLTQFPNAEKMKTTSPPGDDIKNSPGQYIQCFTVKPKLDLPPKFH-RPVSEQIVSFYRVNEVQRFEYSRPIRKGEKNPDN 1188
Cdd:cd11708    161 LLTQFPNAEKMTSTSPPGDEIKSSTKQYVQCFTVKPVMNLPSHYKdKPVPEQILNYYRANEVQQFQYSRPFRKGEKDPDN 240

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799135512 1189 EFANMWIERTIYTTAYKLPGILRWFEVKSVFMVEISPLENAIETMQLTNDKINSMVQQHLDDPSLPINPLSMLLNGIVDP 1268
Cdd:cd11708    241 EFATMWIERTTFTTAYRFPGILKWFEVKQISTEEISPLENAIETMELTNEKISNLVQQHAWDRSLPVHPLSMLLNGIVDP 320

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799135512 1269 AVMGGFANYEKAFFTDRYLQEHPEAHEKIEKLKDLIAWQIPFLAEGIRIHGDKVTEALRPFHERMEACFKQLKEKVEKEY 1348
Cdd:cd11708    321 AVMGGFSNYEKAFFTEKYLQEHPEDQEKIELLKQLIALQMPLLAEGIRIHGEKLTEQLKPLHERLVSCFKDLRAKVEKLY 400
DHR2_DOCK_B cd11696
Dock Homology Region 2, a GEF domain, of Class B Dedicator of Cytokinesis proteins; DOCK ...
 950-1344 1.58e-147

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


Pssm-ID: 212569  Cd Length: 391  Bit Score: 457.29  E-value: 1.58e-147
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799135512  950 EMYIRYLYKLCDLHKECDNYTEAAYTLLLHAKLLKWSEDVCVAHLTQRDgyqaTTQGQLKEQLYQEIIHYFDKGKMWEEA 1029
Cdd:cd11696      1 EMYLRYIYKLHDLHLQAENYTEAAFTLLLYAELLSWSSDPLPADLHHPS----QPEWQRKEALYLKILQYFDRGKCWEKG 76

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799135512 1030 IALGKELAEQYENeMFDYEQLSELLKKQAQFYENIVKVIRPKPDYFAVGYYGQGFPTFLRGKVFIYRGKEYERREDFEAR 1109
Cdd:cd11696     77 IPLCRELAELYES-LYDYAKLSHILRMEASFYDNILTQLRPEPEYFRVGFYGKGFPLFLRNKQFVYRGLDYERIGAFTQR 155

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799135512 1110 LLTQFPNAEKMKTTSPPGDDIKNSPGQYIQCFTVKPKLDLPPKFHRP-VSEQIVSFYRVNEVQRFEYSRPIRKGEKNPDN 1188
Cdd:cd11696    156 LQSEFPQAHILTKNTPPDDAILQADGQYIQICNVKPVPERRPVLQMVgVPDKVRSFYRVNDVRKFQYDRPIHKGPIDKDN 235

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799135512 1189 EFANMWIERTIYTTAYKLPGILRWFEVKSVFMVEISPLENAIETMQLTNDKINSMVQQHLDDPSLPINPLSMLLNGIVDP 1268
Cdd:cd11696    236 EFKSLWIERTTLVTEHSLPGILRWFEVVSREVEEIPPVENACETVENKNQELRSLISQYQADPTRNINPFSMRLQGVIDA 315

                          330       340       350       360       370       380       390
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1799135512 1269 AVMGGFANYEKAFFTDRYLQEHPEAHEKIEKLKDLIAWQIPFLAEGIRIHGDKVTEALRPFHERMEACFKQLKEKV 1344
Cdd:cd11696    316 AVNGGIAKYQEAFFTPEFILSHPEDAEHIARLRELILEQVQILEAGLALHGKLAPPEVRPLHKRLVERFTQMKQSL 391
DHR2_DOCK cd11684
Dock Homology Region 2, a GEF domain, of Dedicator of Cytokinesis proteins; DOCK proteins ...
 950-1344 2.41e-145

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


Pssm-ID: 212566 [Multi-domain]  Cd Length: 392  Bit Score: 451.37  E-value: 2.41e-145
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799135512  950 EMYIRYLYKLCDLHKECDNYTEAAYTLLLHAKLLKWSEDVCVAHLTQRDGYQATTQGQLKEQLYQEIIHYFDKGKMWEEA 1029
Cdd:cd11684      1 ELYIRYLHKLADLHEERGNYVEAALCLLLHADLYAWDLKALVPALAESLSFPEQTSFERKEALYKKAIDLFDKGKAWEFA 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799135512 1030 IALGKELAEQYENEmFDYEQLSELLKKQAQFYENIVKVIRPKPDYFAVGYYGQGFPTFLRGKVFIYRGKEYERREDFEAR 1109
Cdd:cd11684     81 IALYKELIPQYENN-FDYAKLSEVHRKIAKLYEKIAEKDRLFPTYFRVGFYGKGFPESLRGKEFIYRGPEFERLGDFCER 159

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799135512 1110 LLTQFPNAEKMKTTSPPGDDIKNSPGQYIQCFTVKPKLDLPPKFHRPvSEQIVSFYRVNEVQRFEYSRPIRKGEKNPDNE 1189
Cdd:cd11684    160 LKSLYPGAEIIQSSEEPDDEILDSEGQYIQITSVEPYFDDEDLVSRA-APGVRQFYRNNNINTFVYERPFTKGGKKSQNE 238

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799135512 1190 FANMWIERTIYTTAYKLPGILRWFEVKSVFMVEISPLENAIETMQLTNDKINSMVQQHLDDPSLPINPLSMLLNGIVDPA 1269
Cdd:cd11684    239 ITDQWKERTILTTEESFPTILRRSEVVSIEEIELSPIENAIEDIEKKTEELRSLINKYRSGDSPNVNPLQMLLQGTVDAA 318

                          330       340       350       360       370       380       390
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1799135512 1270 VMGGFANYEKAFFTDRYLQEHPEAhEKIEKLKDLIAWQIPFLAEGIRIHGDKVTEALRPFHERMEACFKQLKEKV 1344
Cdd:cd11684    319 VNGGPVAYAEAFLSEEYLSNYPEA-EKVKKLKEAFEEFLEILKRGLALHAKLCPPEMAPLHEELEEGFEKLFKEL 392
C2_Dock-A cd08694
C2 domains found in Dedicator Of CytoKinesis (Dock) class A proteins; Dock-A is one of 4 ...
 160-355 1.00e-121

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


Pssm-ID: 176076  Cd Length: 196  Bit Score: 379.05  E-value: 1.00e-121
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799135512  160 VRNDIYVTLVQGDFDKGSKTTAKNVEVTVSVYDEDGKRLEHVIFPGAGDEAISEYKSVIYYQVKQPRWFETVKVAIPIED 239
Cdd:cd08694      1 VRNDLYLTLVQGDFDKGSKTSDKNVEVTVSVCNEDGKIIPGVISLGAGEEPIDEYKSVIYYQVDKPKWFETFKVAIPIED 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799135512  240 VNRSHLRFTFRHRSSQDSKDKSEKIFALAFVKLMRYDGTTLRDGEHDLIVYKAEAKK-LEDAATYLSLPSTKAELEEKGH 318
Cdd:cd08694     81 FKSSHLRFTFKHRSSNEAKDKSEKPFALSFVKLMQENGTTLTDGEHDLIVYKVDAKKkLEDAKAYLSLPSTRAELEARKS 160

                          170       180       190
                   ....*....|....*....|....*....|....*..
gi 1799135512  319 SATGKSMQsLGSCTISKDSFQISTLVCSTKLTQNVDL 355
Cdd:cd08694    161 SPSGSASN-LGLSLSSKDSFQISTLVCSTKLTQNVDL 196
DHR2_DOCK3 cd11704
Dock Homology Region 2, a GEF domain, of Class B Dedicator of Cytokinesis 3; Dock3, also ...
 950-1341 4.68e-102

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


Pssm-ID: 212577  Cd Length: 392  Bit Score: 332.74  E-value: 4.68e-102
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799135512  950 EMYIRYLYKLCDLHKECDNYTEAAYTLLLHAKLLKWSEdvcvAHLTQRDGYQATTQGQLKEQLYQEIIHYFDKGKMWEEA 1029
Cdd:cd11704      1 EMYIRYIHKLCDMHLQAENYTEAAFTLLLYCELLQWED----RPLREFLHYPSQSEWQRKEGLCRKIIHYFNKGKSWEFG 76

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799135512 1030 IALGKELAEQYENeMFDYEQLSELLKKQAQFYENIVKVIRPKPDYFAVGYYGQGFPTFLRGKVFIYRGKEYERREDFEAR 1109
Cdd:cd11704     77 IPLCRELAFQYES-LYDYQSLSWIRKMEAAYYDNIMEQQRLEPEFFRVGFYGRKFPFFLRNKEYVCRGHDYERLEAFQQR 155

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799135512 1110 LLTQFPNAEKMKTTSPPGDDIKNSPGQYIQCFTVKPKLDLPPKFHRP-VSEQIVSFYRVNEVQRFEYSRPIRKGEKNPDN 1188
Cdd:cd11704    156 MLSEFPQAIAMQHPNHPDDGILQCDAQYLQIYAVTPIPDNMDVLQMDrVPDRIKSFYRVNNVRKFRYDRPFHKGPKDKEN 235

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799135512 1189 EFANMWIERTIYTTAYKLPGILRWFEVKSVFMVEISPLENAIETMQLTNDKINSMVQQHLDDP-SLPINPLSMLLNGIVD 1267
Cdd:cd11704    236 EFKSLWIERTTLTLTHSLPGISRWFEVERRELVEVSPLENAIQVVENKNQELRTLISQYQHKQlHGNINLLSMCLNGVID 315

                          330       340       350       360       370       380       390
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1799135512 1268 PAVMGGFANYEKAFFTDRYLQEHPEAHEKIEKLKDLIAWQIPFLAEGIRIHGDKVTEALRPFHERMEACFKQLK 1341
Cdd:cd11704    316 AAVNGGIARYQEAFFDKDYISKHPGDAEKITQLKELMQEQVHVLGVGLAVHEKFVHPEMRPLHKKLIDQFQMMR 389
DHR2_DOCK4 cd11705
Dock Homology Region 2, a GEF domain, of Class B Dedicator of Cytokinesis 4; Dock4 is an ...
 950-1344 3.68e-99

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


Pssm-ID: 212578  Cd Length: 391  Bit Score: 324.29  E-value: 3.68e-99
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799135512  950 EMYIRYLYKLCDLHKECDNYTEAAYTLLLHAKLLKWSEDVCVAHLTqrdgYQATTQGQLKEQLYQEIIHYFDKGKMWEEA 1029
Cdd:cd11705      1 EMYIRYIHKLYDLHLKAQNFTEAAYTLLLYDELLEWSDRPLREFLS----YPMQTEWQRKEYLHLTIIQNFDRGKCWENG 76

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799135512 1030 IALGKELAEQYENeMFDYEQLSELLKKQAQFYENIVKVIRPKPDYFAVGYYGQGFPTFLRGKVFIYRGKEYERREDFEAR 1109
Cdd:cd11705     77 IILCRKLAEQYES-YYDYRNLSKMRMMEASLYDKIMDQQRLEPEFFRVGFYGKKFPFFLRNKEFVCRGHDYERLEAFQQR 155

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799135512 1110 LLTQFPNAEKMKTTSPPGDDIKNSPGQYIQCFTVKPKLDLPPKFHRP-VSEQIVSFYRVNEVQRFEYSRPIRKGEKNPDN 1188
Cdd:cd11705    156 MLNEFPHAIAMQHANQPDETIFQAEAQYLQIYAVTPIPESQEVLQRDgVPDNIKSFYKVNHIWRFRYDRPFHKGTKDKEN 235

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799135512 1189 EFANMWIERTIYTTAYKLPGILRWFEVKSVFMVEISPLENAIETMQLTNDKINSMVQQHLDDPSLPINPLSMLLNGIVDP 1268
Cdd:cd11705    236 EFKSLWVERTTLTLVQSLPGISRWFEVEKREVVEMSPLENAIEVLENKNQQLRTLISQCQTRQMQNINPLTMCLNGVIDA 315

                          330       340       350       360       370       380       390
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1799135512 1269 AVMGGFANYEKAFFTDRYLQEHPEAHEKIEKLKDLIAWQIPFLAEGIRIHGDKVTEALRPFHERMEACFKQLKEKV 1344
Cdd:cd11705    316 AVNGGVSRYQEAFFVKEYILNHPEDGDKITRLRELMLEQAQILEFGLAVHEKFVPQDMRPLHKKLVDQFFVMKSSL 391
DOCK-C2 pfam14429
C2 domain in Dock180 and Zizimin proteins; The Dock180/Dock1 and Zizimin proteins are atypical ...
 157-354 4.89e-83

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


Pssm-ID: 464171  Cd Length: 185  Bit Score: 269.86  E-value: 4.89e-83
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799135512  157 PGDVRNDIYVTLVQGDFDKGSKTTAKNVEVTVSVYDEDGKRLEHVIFPGAGDEAISEYKSVIYYQVKQPRWFETVKVAIP 236
Cdd:pfam14429    1 PGDYRNDLYVTPKSGNFSKQKKSSARNIEVTVEVRDSDGEPLPNCIYGGSGGPFVTEFKSTVYYHNKSPTWYEEIKIALP 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799135512  237 IEDVNRSHLRFTFRHRSSQDSKDKSEKIFALAFVKLMRYDGTTLRDGEHDLIVYKAEakklEDAATYLSLPSTKAELEEK 316
Cdd:pfam14429   81 AELTPKHHLLFTFYHVSCDEKKDKVEKPFGYAFLPLLDDDGAFLRDGEHTLPVYKYD----ELPPGYLSLPWSSGGEKES 156

                          170       180       190
                   ....*....|....*....|....*....|....*...
gi 1799135512  317 ghsatgksmQSLGSCTISKDSFQISTLVCSTKLTQNVD 354
Cdd:pfam14429  157 ---------SALPGLKGGKDLFKVRTRLCSTKYTQDEH 185
C2_Dock-B cd08695
C2 domains found in Dedicator Of CytoKinesis (Dock) class B proteins; Dock-B is one of 4 ...
 160-355 2.54e-71

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


Pssm-ID: 176077  Cd Length: 189  Bit Score: 236.89  E-value: 2.54e-71
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799135512  160 VRNDIYVTLVQGDFDKGSKTTAKNVEVTVSVYDEDGKRLEHVIFPGAGDEAISEYKSVIYYQVKQPRWFETVKVAIPIED 239
Cdd:cd08695      1 VRNDLYLTLERGEFEKGGKSTAKNIEVTMVVLDADGQVLKDCISLGSGEPPCSEYRSFVLYHNNSPRWNETIKLPIPIDK 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799135512  240 VNRSHLRFTFRHRSSQDSKDKseKIFALAFVKLMRYDGTTLRDGEHDLIVYKA-EAKKLEDAATYLSLPSTKAELeekgh 318
Cdd:cd08695     81 FRGSHLRFEFRHCSTKDKGEK--KLFGFSFVPLMREDGTTLPDGSHELYVYKCdENATFLDPALYLGLPCSKEDF----- 153

                          170       180       190
                   ....*....|....*....|....*....|....*..
gi 1799135512  319 SATGKSMQSLGSCTiSKDSFQISTLVCSTKLTQNVDL 355
Cdd:cd08695    154 QGCPNSPSPLFSRS-SKESFWIRTLLCSTKLTQNVDL 189
C2_DOCK180_related cd08679
C2 domains found in Dedicator Of CytoKinesis 1 (DOCK 180) and related proteins; Dock180 was ...
 161-355 3.44e-58

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


Pssm-ID: 176061  Cd Length: 178  Bit Score: 198.71  E-value: 3.44e-58
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799135512  161 RNDIYVTLVQGDFDKGsKTTAKNVEVTVSVYDEDGKRLEHVIF-PGAGDEAISEYKSVIYYQvKQPRWFETVKVAIPIED 239
Cdd:cd08679      2 RNDLYVYPQSGELSKA-KSKGRNIEITVEVRDDDGDIIEPCISaPGSGSELRSEYTSVVYYH-KNPVFNDEIKIQLPADL 79

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799135512  240 VNRSHLRFTFRHRSSQDS-KDKSEKIFALAFVKLMRYDGTTLRDGEHDLIVYKAEAKKLEDAATYLSLPSTKAELEEKgh 318
Cdd:cd08679     80 TPQHHLLFTFYHVSSKKKqGDKEETPFGYAFLPLMDKDGAFIKDGDHTLPVYKYDKRPDVGPSGYLSLPSTLANGKSS-- 157

                          170       180       190
                   ....*....|....*....|....*....|....*..
gi 1799135512  319 satgksmqslgsctisKDSFQISTLVCSTKLTQNVDL 355
Cdd:cd08679    158 ----------------KDTFKIKTRLCSTILTQDKSL 178
DHR-2_Lobe_C pfam20421
DHR-2, Lobe C; DOCK (dedicator of cytokinesis) proteins are guanine nucleotide exchange ...
 1243-1346 1.81e-27

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


Pssm-ID: 466570 [Multi-domain]  Cd Length: 103  Bit Score: 107.68  E-value: 1.81e-27
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799135512 1243 MVQQHLDDPSLPINPLSMLLNGIVDPAVMGGFANYEKAFFTDRYLQEHPEahEKIEKLKDLIAWQIPFLAEGIRIHGDKV 1322
Cdd:pfam20421    1 ELEAAINAPPPNIKTLQMVLQGSVDVQVNAGPLEYAEAFLSEKNVDNYPA--EKVEKLKEEFRDFLKVCGEALRLNKKLI 78

                           90       100
                   ....*....|....*....|....
gi 1799135512 1323 TEALRPFHERMEACFKQLKEKVEK 1346
Cdd:pfam20421   79 SEDQREYQEELEEGFEKLKEKLEP 102
DHR-2_Lobe_A pfam06920
DHR-2, Lobe A; This entry represents a conserved region within a number of eukaryotic ...
 938-1066 3.93e-24

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


Pssm-ID: 462040 [Multi-domain]  Cd Length: 154  Bit Score: 100.06  E-value: 3.93e-24
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799135512  938 NVLNFYKEieREEMYIRYLYKLCDLHKECDNYTEAAYTLLLHAKLL---------KWSEDVCVA----------HLTQR- 997
Cdd:pfam06920    5 SLANSYKS--SPDLRLTWLENLAEKHLENGNFSEAAQCLIHIAALIaeylklkgkIPNPLGASAfekispnilrEESALk 82

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1799135512  998 ------DGYQATTQGQLKeqLYQEIIHYFDKGKMWEEAIALGKELAEQYENEmFDYEQLSELLKKQAQFYENIVK 1066
Cdd:pfam06920   83 ddsgvcDSPHFTEDGLVG--LLEEAIDYLDKAERYELAIELYKLLLPIYESR-RDYKKLSECHGKLAEAYEKIVE 154
DOCK_N pfam16172
DOCK N-terminus; This family is found near to the N-terminus of dedicator of cytokinesis (DOCK) ...
 44-152 3.57e-20

DOCK N-terminus; This family is found near to the N-terminus of dedicator of cytokinesis (DOCK) proteins, between the variant SH3 domain (pfam07653) and the C2 domain (pfam14429).


Pssm-ID: 465040  Cd Length: 317  Bit Score: 93.35  E-value: 3.57e-20
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799135512   44 VMDVTDIINGKVD-DEDKQHFIPFQPlalddairhkplnmssrfsprVAGENDF--LQTVINKVIAAK-EVNHKGQGLWV 119
Cdd:pfam16172  227 VLDLTDILKGLKQsDEEVEHVVPIWS---------------------PNNESDFdeLHRDIIKSITGKyEKSPRAERLWV 285

                           90       100       110
                   ....*....|....*....|....*....|...
gi 1799135512  120 TLKLLPGDIHQIRKEFPHLVdRTTAVARKTGFP 152
Cdd:pfam16172  286 SLKLFHGDAEQLRKENPTLL-HNVAITRKLGFP 317
DHR-2_Lobe_B pfam20422
DHR-2, Lobe B; DOCK (dedicator of cytokinesis) proteins are guanine nucleotide exchange ...
 1123-1205 7.75e-20

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


Pssm-ID: 466571 [Multi-domain]  Cd Length: 77  Bit Score: 84.97  E-value: 7.75e-20
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799135512 1123 TSPPGDDIKNSPGQYIQCFTVKPKLDLPPKFHRpvseqIVSFYRVNEVQRFEYSRPIRKGEKnPDNEFANMWIERTIYTT 1202
Cdd:pfam20422    1 SNPVDESILDPDKAYIQITSVEPYFDDSELNDR-----VTYFERNNNVNRFVFETPFTKSGK-AQGEFEEQWKRRTILTT 74


                   ...
gi 1799135512 1203 AYK 1205
Cdd:pfam20422   75 EHS 77
DHR2_DOCK_D cd11694
Dock Homology Region 2, a GEF domain, of Class D Dedicator of Cytokinesis proteins; DOCK ...
 955-1344 1.49e-18

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


Pssm-ID: 212567  Cd Length: 376  Bit Score: 89.71  E-value: 1.49e-18
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799135512  955 YLYKLCDLHKECDNYTEAAYTLL---------LHAK-LLKWSEDVCVAHLTQRDGYQattqgqLKEQLYQEIIHYfdkgk 1024
Cdd:cd11694      6 WLESMARIHEKNGNFSEAAMCYIhiaalvaeyLKRKdLLLELLEACVEGLWKAERYE------LLGELYKLIIPI----- 74

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799135512 1025 mweeaialgkelaeqYENEMfDYEQLSELLKKQAQFYENIVKVIRPK----PDYFAVGYYGQGFPTFLRGKVFIYRGKEY 1100
Cdd:cd11694     75 ---------------YEKRR-DFEQLADCYRTLHRAYEKVVEVMESGkrllGTYYRVAFYGQAFFEEEDGKEYIYKEPKV 138

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799135512 1101 ERREDFEARLLTQF------PNAEKMKTTSPPGDDIKNSPGQYIQCFTVKPKLDlppkfHRPVSEQIVSFYRVNEVQRFE 1174
Cdd:cd11694    139 TSLSEISERLLKLYgdkfgsENVKLIQDSGKVNPKDLDPKYAYIQVTHVTPYFD-----EKELEDRKTEFERNHNIRRFV 213

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799135512 1175 YSRPIRKGEKNpDNEFANMWIERTIYTTAYKLPGILRWFEVKSVFMVEISPLENAIETMQltnDKINSMvQQHLDDPSLP 1254
Cdd:cd11694    214 FETPFTLSGKA-RGAVEEQWKRRTILTTSHSFPYVKKRIPVVQREIIELSPIEVAIDEMQ---SKVKEL-EELISTEPVD 288

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799135512 1255 INPLSMLLNGIVDPAVMGGFANYEKAFFTDRYLQEHPEahEKIEKLKDLIAWQIPFLAEGIRIHGDKVTEALRPFHERME 1334
Cdd:cd11694    289 MKKLQLRLQGSVSVQVNAGPLAYARAFLEPTTVKNYPD--DQVEDLKDVFRDFIKACGQALELNERLIKEDQREYHEVLK 366

                          410
                   ....*....|
gi 1799135512 1335 ACFKQLKEKV 1344
Cdd:cd11694    367 ENYRKMVKEL 376
DHR2_DOCK_C cd11695
Dock Homology Region 2, a GEF domain, of Class C Dedicator of Cytokinesis proteins; DOCK ...
 963-1270 1.47e-15

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


Pssm-ID: 212568  Cd Length: 368  Bit Score: 80.42  E-value: 1.47e-15
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799135512  963 HKECDNYTEAAYTLLlHAKLLKWsedvcVAHLTQRdgyqattqgqlkeqlyqeiIHYFDKGKMWEEAIALGKELAEQYEN 1042
Cdd:cd11695     16 HYERKNFAEAAQCLV-HAAALGL-----VGLLEQA-------------------AESFSKAGMYEAVNEVYKLLIPILEA 70

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799135512 1043 EMfDYEQLSELLKKQAQFYENIVKVIRPK---PDYFAVGYYGQGFPTfLRGKVFIYRGKEYERREDFEARLLT----QF- 1114
Cdd:cd11695     71 NR-DYKKLAEIHGKLQDAFTKIEKQQGGKrmfGTYFRVGFYGSKFGD-LDGKEFIYKEPAITKLPEISHRLETfygeRFg 148

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799135512 1115 -PNAEKMKTTSPPGDDIKNSPGQYIQCFTVKPKLDLPPKFHRpvseqIVSFYRVNEVQRFEYSRPIRKGEKnPDNEFANM 1193
Cdd:cd11695    149 eERVEVIKDSNPVDTSKLDPDKAYIQITYVEPYFDEYELKER-----TTYFERNYNLRRFMYATPFTPDGK-AHGELAEQ 222

                          250       260       270       280       290       300       310
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1799135512 1194 WIERTIYTTAYKLPGILRWFEVKSVFMVEISPLENAIETMQLTNDKINSMVQQHLDDPSLpinpLSMLLNGIVDPAV 1270
Cdd:cd11695    223 YKRKTILTTENSFPYVKTRLQVVNREEIVLTPIEVAIEDVQKKTRELAAATTQEPPDPKM----LQMVLQGSIGTTV 295
DHR2_DOCK9 cd11698
Dock Homology Region 2, a GEF domain, of Class D Dedicator of Cytokinesis 9; Dock9, also ...
 1046-1344 1.97e-14

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


Pssm-ID: 212571  Cd Length: 415  Bit Score: 77.38  E-value: 1.97e-14
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799135512 1046 DYEQLSELLKKQAQFYENIVKVI----RPKPDYFAVGYYGQGFPTFLRGKVFIYRGKEYERREDFEARLLTQFPN---AE 1118
Cdd:cd11698    116 DFERLAHLYDTLHRAYSKVTEVMhsgkRLLGTYFRVAFFGQGFFEDEDGKEYIYKEPKLTPLSEISQRLLKLYSDkfgSE 195

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799135512 1119 KMKTTSPPG----DDIkNSPGQYIQCFTVKPKLDlppkfHRPVSEQIVSFYRVNEVQRFEYSRPI-RKGEKNPDNEfaNM 1193
Cdd:cd11698    196 NVKMIQDSGkvnpKDL-DSKYAYIQVTHVTPYFD-----EKELQERKTDFERSHNIRRFMFEMPFtQSGKRQGGVE--EQ 267

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799135512 1194 WIERTIYTTAYKLPGILRWFEVKSVFMVEISPLENAIETMqltNDKINSMvQQHLDDPSLPINPLSMLLNGIVDPAVMGG 1273
Cdd:cd11698    268 CKRRTILTAIHCFPYVKKRIPVMYQHHTDLNPIEVAIDEM---SKKVAEL-RQLCSSAEVDMIKLQLKLQGSVSVQVNAG 343

                          250       260       270       280       290       300       310
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1799135512 1274 FANYEKAFFTDRYLQEHPEahEKIEKLKDLIAWQIPFLAEGIRIHGDKVTEALRPFHERMEACFKQLKEKV 1344
Cdd:cd11698    344 PLAYARAFLDDTNTKRYPD--NKVKLLKEVFRQFVEACGQALAVNERLIKEDQLEYQEEMKANYREMAKEL 412
SH3_DOCK1_5_A cd12051
Src Homology 3 domain of Class A Dedicator of Cytokinesis proteins 1 and 5; Dock1, also called ...
 13-43 2.28e-14

Src Homology 3 domain of Class A Dedicator of Cytokinesis proteins 1 and 5; Dock1, also called Dock180, and Dock5 are class A DOCKs and are atypical guanine nucleotide exchange factors (GEFs) that lack the conventional Dbl homology (DH) domain. Dock1 interacts with the scaffold protein Elmo and the resulting complex functions upstream of Rac in many biological events including phagocytosis of apoptotic cells, cell migration and invasion. Dock5 functions upstream of Rac1 to regulate osteoclast function. All DOCKs contain two homology domains: the DHR-1 (Dock homology region-1), also called CZH1 (CED-5, Dock180, and MBC-zizimin homology 1), and DHR-2 (also called CZH2 or Docker). The DHR-1 domain binds phosphatidylinositol-3,4,5-triphosphate while DHR-2 contains the catalytic activity for Rac and/or Cdc42. Class A DOCKs also contain an SH3 domain at the N-terminal region and a PxxP motif at the C-terminus; they are specific GEFs for Rac. The SH3 domain of Dock1 binds to DHR-2 in an autoinhibitory manner; binding of Elmo to the SH3 domain of Dock1 exposes the DHR-2 domain and promotes GEF activity. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212984 [Multi-domain]  Cd Length: 56  Bit Score: 68.69  E-value: 2.28e-14
                           10        20        30
                   ....*....|....*....|....*....|.
gi 1799135512   13 YGVAFYNYDARGADELSLQIGDTVHILETYE 43
Cdd:cd12051      1 YGVAIYNYDARGPDELSLQIGDTVHILETYE 31
DHR2_DOCK10 cd11699
Dock Homology Region 2, a GEF domain, of Class D Dedicator of Cytokinesis 10; Dock10, also ...
 994-1299 1.65e-13

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


Pssm-ID: 212572  Cd Length: 446  Bit Score: 74.70  E-value: 1.65e-13
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799135512  994 LTQRDGYQAT--TQGQLKEQLYQeIIHYFDKGKMWEEAIALGKELAEQYENEMfDYEQLSELLKKQAQFYENIVKVIRPK 1071
Cdd:cd11699     98 MKEDSGMQDTpyNENTLVEQLEL-CVDYLWKSERYELIADVNKPVIAVFEKQR-DFKRLSELYYDIHRSYLKVAEVVNSE 175

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799135512 1072 PD----YFAVGYYGQGFPTFLRGKVFIYRGKEYERREDFEARLLTQFPNAEKMKTTSPPGDDIKNSPGQ------YIQCF 1141
Cdd:cd11699    176 KRlfgrYYRVAFYGQGFFEEEEGKEYIYKEPKLTGLSEISQRLLKLYADKFGADNVKIIQDSNKVNPKEldpkfaYIQVT 255

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799135512 1142 TVKPKLDlppkfHRPVSEQIVSFYRVNEVQRFEYSRPIR-KGEKNPDNEfaNMWIERTIYTTAYKLPGILRWFEVKSVFM 1220
Cdd:cd11699    256 YVTPYFD-----EKEQEDRKTDFEMHHNINRFVFETPFTlSGKKHGGVE--EQCKRRTILTTSHSFPYVKKRIQVVSQTS 328

                          250       260       270       280       290       300       310
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1799135512 1221 VEISPLENAIETMQLTNDKINSMVQQHLDDpslpINPLSMLLNGIVDPAVMGGFANYEKAFFTDRYLQEHPEAHEKIEK 1299
Cdd:cd11699    329 TELNPIEVAIDEMSKKVSELNQLCTMEEVD----MIRLQLKLQGSVSVKVNAGPMAYARAFLEETNAKKYPDNQVKLLK 403
DHR2_DOCK11 cd11700
Dock Homology Region 2, a GEF domain, of Class D Dedicator of Cytokinesis 11; Dock11, also ...
 985-1340 2.08e-13

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


Pssm-ID: 212573  Cd Length: 413  Bit Score: 74.26  E-value: 2.08e-13
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799135512  985 WSEDVCVAHLTQrdgyqaTTQGQLKEQLYQEIIHyfdkgkmweeaiaLGKELAEQYENEMfDYEQLSELLKKQAQFYENI 1064
Cdd:cd11700     76 YSEEVLVELLEQ------CVDGLWKAERYELISE-------------ISKLIIPIYEKRR-EFEKLTQLYRTLHGAYAKI 135

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799135512 1065 VKVIRPKP----DYFAVGYYGQGFPTFLRGKVFIYRGKEYERREDFEARLLTQFPNAEKMKTTSPPGDDIK------NSP 1134
Cdd:cd11700    136 LEVMHTGKrllgTFFRVAFYGQGFFEEEDGKEYIYKEPKLTGLSEISHRLLKLYGEKFGSENVKIIQDSNKvnqkdlDPK 215

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799135512 1135 GQYIQCFTVKPKLDlppkfHRPVSEQIVSFYRVNEVQRFEYSRPIR-KGEKNPDNEfaNMWIERTIYTTAYKLPGILRWF 1213
Cdd:cd11700    216 YAHIQVTYVKPYFD-----DKEMAERKTEFERNHNIQRFVFETPYTlSGKKQGGVE--EQCKRRTILTTANSFPYVKKRI 288

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799135512 1214 EVKSVFMVEISPLENAIETMQltnDKiNSMVQQHLDDPSLPINPLSMLLNGIVDPAVMGGFANYEKAFFTDRYLQEHPEa 1293
Cdd:cd11700    289 PVNGEKQTNLKPIDVATDEIK---DK-TAELQKLCSNQDVDMIQLQLKLQGCVSVQVNAGPLAYARAFLDDSQASKYPN- 363

                          330       340       350       360
                   ....*....|....*....|....*....|....*....|....*..
gi 1799135512 1294 hEKIEKLKDLIAWQIPFLAEGIRIHGDKVTEALRPFHERMEACFKQL 1340
Cdd:cd11700    364 -KKVKELKEMFRKFIQACSIALELNERLIKEDQVEYHEGLKSNFRDM 409
DHR2_DOCK8 cd11701
Dock Homology Region 2, a GEF domain, of Class C Dedicator of Cytokinesis 8; Dock8, also ...
 1046-1344 3.41e-11

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


Pssm-ID: 212574  Cd Length: 422  Bit Score: 67.37  E-value: 3.41e-11
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799135512 1046 DYEQLSELLKKQAQFYENIVKVIRPK--PDYFAVGYYGQGFPTfLRGKVFIYRGKEYERREDFEARLLTQF-----PNAE 1118
Cdd:cd11701    129 DFRKLASTHDKLQKAFDNIINKGHKRmfGTYFRVGFYGSKFGD-LDEQEFIYKEPAITKLPEISHRLEGFYgqcfgDDVV 207

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799135512 1119 KMKTTSPPGDDIKNSPGQ-YIQCFTVKPKLDlppkfHRPVSEQIVSFYRVNEVQRFEYSRPIRKgEKNPDNEFANMWIER 1197
Cdd:cd11701    208 EVIKDSTPVDKSKLDPNKaYIQITFVEPYFD-----DYEMKDRVTYFEKNFNLRRFMYTTPFTL-DGRPRGELSEQYKRK 281

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799135512 1198 TIYTTAYKLPGILRWFEVKSVFMVEISPLENAIETMQLTNDKINSMVQQHLDDPSLpinpLSMLLNGIVDPAVMGGFANY 1277
Cdd:cd11701    282 TILTTMHAFPYIKTRINVIQKEEFDLTPIEVAIEDMQKKTRELAEATHQEPPDAKM----LQMVLQGSVGATVNQGPLEV 357

                          250       260       270       280       290       300
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1799135512 1278 EKAFFTDryLQEHPEAHEKIEKLKDLIAWQIPFLAEGIRIHGDKVTEALRPFHERMEACFKQLKEKV 1344
Cdd:cd11701    358 AQVFLAE--IPADPKLYRHHNKLRLCFKEFIMRCGEAVEKNKRLITADQREYQQELKKNYNKLRENL 422
SH3_DOCK_AB cd11872
Src Homology 3 domain of Class A and B Dedicator of Cytokinesis proteins; DOCK proteins are ...
 13-43 1.45e-07

Src Homology 3 domain of Class A and B Dedicator of Cytokinesis proteins; DOCK proteins are atypical guanine nucleotide exchange factors (GEFs) that lack the conventional Dbl homology (DH) domain. They are divided into four classes (A-D) based on sequence similarity and domain architecture: class A includes Dock1, 2 and 5; class B includes Dock3 and 4; class C includes Dock6, 7, and 8; and class D includes Dock9, 10 and 11. All DOCKs contain two homology domains: the DHR-1 (Dock homology region-1), also called CZH1 (CED-5, Dock180, and MBC-zizimin homology 1), and DHR-2 (also called CZH2 or Docker). The DHR-1 domain binds phosphatidylinositol-3,4,5-triphosphate while DHR-2 contains the catalytic activity for Rac and/or Cdc42. This subfamily includes only Class A and B DOCKs, which also contain an SH3 domain at the N-terminal region and a PxxP motif at the C-terminus. Class A/B DOCKs are mostly specific GEFs for Rac, except Dock4 which activates the Ras family GTPase Rap1, probably indirectly through interaction with Rap regulatory proteins. The SH3 domain of class A/B DOCKs have been shown to bind Elmo, a scaffold protein that promotes GEF activity of DOCKs by releasing DHR-2 autoinhibition by the intramolecular SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212805 [Multi-domain]  Cd Length: 56  Bit Score: 49.50  E-value: 1.45e-07
                           10        20        30
                   ....*....|....*....|....*....|.
gi 1799135512   13 YGVAFYNYDARGADELSLQIGDTVHILETYE 43
Cdd:cd11872      1 YGVAIYNFQGDGEHQLSLQVGDTVQILEECE 31
DHR2_DOCK6 cd11702
Dock Homology Region 2, a GEF domain, of Class C Dedicator of Cytokinesis 6; Dock6, also ...
 1012-1342 2.26e-07

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


Pssm-ID: 212575  Cd Length: 423  Bit Score: 55.01  E-value: 2.26e-07
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799135512 1012 LYQEIIHYFDKGKMWEEAIALGKELAEQYENEMfDYEQLSELLKKQAQFYENIVKVI----RPKPDYFAVGYYGQGFPTf 1087
Cdd:cd11702     95 LLEQAAASFNMGGLYEAVNEVYKILIPIHEANR-DYKKLAVVHGKLQEAFNKITNQSsgweRMFGTYFRVGFYGCKFGD- 172

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799135512 1088 LRGKVFIYRGKEYERREDFEARLLTQFPN------AEKMKTTSPPGDDIKNSPGQYIQCFTVKPKLDLppkfhRPVSEQI 1161
Cdd:cd11702    173 LDEQEFVYKEPSITKLAEISHRLEEFYTErfgdevVEIIKDSNPVDKSKLDPNKAYIQITYVEPFFDT-----YELKDRV 247

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799135512 1162 VSFYRVNEVQRFEYSRPIRKgEKNPDNEFANMWIERTIYTTAYKLPGILRWFEVKSVFMVEISPLENAIETMQLTNDKIN 1241
Cdd:cd11702    248 TYFDKNYNLRTFLFCTPFTL-DGRAHGELHEQYKRKTILTTSHAFPYIKTRINVLHREEIVLIPVEVAIEDMQKKTQELA 326

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799135512 1242 SMVQQHLDDPSLpinpLSMLLNGIVDPAVMGGFANYEKAFFTDryLQEHPEAHEKIEKLKDLIAWQIPFLAEGIRIHGDK 1321
Cdd:cd11702    327 FATHQDPADAKM----LQMVLQGCVGTTVNQGPLEVAQVFLSE--IPEDPKLFRHHNKLRLCFKDFTKRCEDALRKNKAL 400

                          330       340
                   ....*....|....*....|.
gi 1799135512 1322 VTEALRPFHERMEACFKQLKE 1342
Cdd:cd11702    401 IGPDQKEYHRELERNYQRLRE 421
SH3_DOCK2_A cd12050
Src Homology 3 domain of Class A Dedicator of Cytokinesis protein 2; Dock2 is a hematopoietic ...
 13-43 4.00e-06

Src Homology 3 domain of Class A Dedicator of Cytokinesis protein 2; Dock2 is a hematopoietic cell-specific, class A DOCK and is an atypical guanine nucleotide exchange factor (GEF) that lacks the conventional Dbl homology (DH) domain. It plays an important role in lymphocyte migration and activation, T-cell differentiation, neutrophil chemotaxis, and type I interferon induction. All DOCKs contain two homology domains: the DHR-1 (Dock homology region-1), also called CZH1 (CED-5, Dock180, and MBC-zizimin homology 1), and DHR-2 (also called CZH2 or Docker). The DHR-1 domain binds phosphatidylinositol-3,4,5-triphosphate while DHR-2 contains the catalytic activity for Rac and/or Cdc42. Class A DOCKs also contain an SH3 domain at the N-terminal region and a PxxP motif at the C-terminus; they are specific GEFs for Rac. The SH3 domain of Dock2 binds to DHR-2 in an autoinhibitory manner; binding of the scaffold protein Elmo to the SH3 domain of Dock2 exposes the DHR-2 domain and promotes GEF activity. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212983  Cd Length: 56  Bit Score: 45.61  E-value: 4.00e-06
                           10        20        30
                   ....*....|....*....|....*....|.
gi 1799135512   13 YGVAFYNYDARGADELSLQIGDTVHILETYE 43
Cdd:cd12050      1 YGVAIYNFKGSGVPQLSLQIGDVVHIQETCE 31
SH3 smart00326
Src homology 3 domains; Src homology 3 (SH3) domains bind to target proteins through sequences ...
 10-43 5.17e-06

Src homology 3 domains; Src homology 3 (SH3) domains bind to target proteins through sequences containing proline and hydrophobic amino acids. Pro-containing polypeptides may bind to SH3 domains in 2 different binding orientations.


Pssm-ID: 214620 [Multi-domain]  Cd Length: 56  Bit Score: 45.22  E-value: 5.17e-06
                            10        20        30
                    ....*....|....*....|....*....|....
gi 1799135512    10 EEKYGVAFYNYDARGADELSLQIGDTVHILETYE 43
Cdd:smart00326    1 EGPQVRALYDYTAQDPDELSFKKGDIITVLEKSD 34
C2_Dock-D cd08697
C2 domains found in Dedicator Of CytoKinesis (Dock) class C proteins; Dock-D is one of 4 ...
 161-355 5.27e-06

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


Pssm-ID: 176079  Cd Length: 185  Bit Score: 48.86  E-value: 5.27e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799135512  161 RNDIYVTLVQGDFDkGSKTTAK--NVEVTVSVYD---EDGKRLEHVIFPGAGDEAISEYKSVIYYQVkQPRWFETVKVAI 235
Cdd:cd08697      2 KNHLYVYPLHLKYD-SQKTFAKarNIAVCIEFRDsdeEDAKPLKCIYYGPGGGFTTSAYAAVLHHNQ-NPEFYDEIKIEL 79

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799135512  236 PIEDVNRSHLRFTFRHRS-----SQDSKDKSEKIFALAFVKLMRYDGtTLRDGEHDLIVykaeakkledAATYLSLPStk 310
Cdd:cd08697     80 PTQLHEKHHLLFTFYHVScdinkKGKKKDGVETPVGYAWLPLLKDKG-RLNSEEQTPPV----------ANLLPNYPD-- 146

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|....*....
gi 1799135512  311 aeleekghsaTGKSMQSLGSCTISKDS----FQISTLVCSTKLTQNVDL 355
Cdd:cd08697    147 ----------GYLSIQPHGPEVKWVDGgkplFKVSTHLVSTVYTQDQHL 185
DHR2_DOCK7 cd11703
Dock Homology Region 2, a GEF domain, of Class C Dedicator of Cytokinesis 7; Dock7, also ...
 1012-1345 5.37e-06

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


Pssm-ID: 212576  Cd Length: 473  Bit Score: 50.85  E-value: 5.37e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799135512 1012 LYQEIIHYFDKGKMWEEAIALGKELAEQYENEMfDYEQLSELLKKQAQFYENIV--KVIRPKPDYFAVGYYGQGFPTfLR 1089
Cdd:cd11703    134 LLEQAAASFSMAGMYEAVNEVYKVLIPIHEANR-DAKKLATIHGKLQEAFSKIVhqDGKRMFGTYFRVGFYGTKFGD-LD 211

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799135512 1090 GKVFIYRGKEYERREDFEARLLTQF-----PNAEKMKTTSPPGDDIKNSPGQ-YIQCFTVKPKLDLppkfhRPVSEQIVS 1163
Cdd:cd11703    212 EQEFVYKEPAITKLAEISHRLEGFYgerfgEDVVEVIKDSNPVDKCKLDPNKaFIQITYVEPYFDT-----YEMKDRITY 286

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799135512 1164 FYRVNEVQRFEYSRPIRKgEKNPDNEFANMWIERTIYTTAYKLPGILRWFEVKSVFMVEISPLENAIETMQLTNDKINSM 1243
Cdd:cd11703    287 FDKNYNLRRFMYCTPFTL-DGRAHGELHEQFKRKTILTTSHAFPYIKTRINVIHKEEIILTPIEVAIEDMQKKTQELAFA 365

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799135512 1244 VQQHLDDPSLpinpLSMLLNGIVDPAVMGGFANYEKAFFTDryLQEHPEAHEKIEKLKDLIAWQIPFLAEGIRIHGDKVT 1323
Cdd:cd11703    366 THQDPADPKM----LQMVLQGSVGTTVNQGPLEVAQVFLSE--IPSDPKLFRHHNKLRLCFKDFTKRCEDALRKNKSLIG 439

                          330       340
                   ....*....|....*....|..
gi 1799135512 1324 EALRPFHERMEACFKQLKEKVE 1345
Cdd:cd11703    440 PDQKEYQRELERNYHRLKEALQ 461
C2_Dock-C cd08696
C2 domains found in Dedicator Of CytoKinesis (Dock) class C proteins; Dock-C is one of 4 ...
 177-317 2.20e-05

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


Pssm-ID: 176078  Cd Length: 179  Bit Score: 46.58  E-value: 2.20e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799135512  177 SKTTAKNVEVTVSV-YDEDGKRLEHVIFPGAGDEAISE--YKSVIYYQvKQPRWFETVKVAIPIEDVNRSHLRFTFRHRS 253
Cdd:cd08696     17 RLGSARNIAVKVQLmSGEDESQALPVIFKGSSPEEFLTeaYTAVTYHN-KSPDFYDEIKIKLPADLTDNHHLLFTFYHIS 95

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1799135512  254 SQDSKDKSEKIFALAFVKLMRYDGTTLRDGEHDLIVykaeakKLEDAATYLS-------LPSTKAELEEKG 317
Cdd:cd08696     96 CQKKQEGGSVETPIGYTWLPLLRNGRLQSGEFNLPV------SLEKPPSNYSpdspevkLPGTKWVDNHKG 160
SH3 cd00174
Src Homology 3 domain superfamily; Src Homology 3 (SH3) domains are protein interaction ...
 13-43 3.69e-04

Src Homology 3 domain superfamily; Src Homology 3 (SH3) domains are protein interaction domains that bind proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. Thus, they are referred to as proline-recognition domains (PRDs). SH3 domains are less selective and show more diverse specificity compared to other PRDs. They have been shown to bind peptide sequences that lack the PxxP motif; examples include the PxxDY motif of Eps8 and the RKxxYxxY sequence in SKAP55. SH3 domain containing proteins play versatile and diverse roles in the cell, including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies, among others. Many members of this superfamily are adaptor proteins that associate with a number of protein partners, facilitating complex formation and signal transduction.


Pssm-ID: 212690 [Multi-domain]  Cd Length: 51  Bit Score: 39.75  E-value: 3.69e-04
                           10        20        30
                   ....*....|....*....|....*....|.
gi 1799135512   13 YGVAFYNYDARGADELSLQIGDTVHILETYE 43
Cdd:cd00174      1 YARALYDYEAQDDDELSFKKGDIITVLEKDD 31
SH3_1 pfam00018
SH3 domain; SH3 (Src homology 3) domains are often indicative of a protein involved in signal ...
 15-40 7.27e-04

SH3 domain; SH3 (Src homology 3) domains are often indicative of a protein involved in signal transduction related to cytoskeletal organization. First described in the Src cytoplasmic tyrosine kinase. The structure is a partly opened beta barrel.


Pssm-ID: 394975 [Multi-domain]  Cd Length: 47  Bit Score: 38.72  E-value: 7.27e-04
                           10        20
                   ....*....|....*....|....*.
gi 1799135512   15 VAFYNYDARGADELSLQIGDTVHILE 40
Cdd:pfam00018    1 VALYDYTAQEPDELSFKKGDIIIVLE 26
SH3_Src_like cd11845
Src homology 3 domain of Src kinase-like Protein Tyrosine Kinases; Src subfamily members ...
 15-41 1.08e-03

Src homology 3 domain of Src kinase-like Protein Tyrosine Kinases; Src subfamily members include Src, Lck, Hck, Blk, Lyn, Fgr, Fyn, Yrk, Yes, and Brk. Src (or c-Src) proteins are cytoplasmic (or non-receptor) PTKs which are anchored to the plasma membrane. They contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr. They are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). However, Brk lacks the N-terminal myristoylation sites. Src proteins are involved in signaling pathways that regulate cytokine and growth factor responses, cytoskeleton dynamics, cell proliferation, survival, and differentiation. They were identified as the first proto-oncogene products, and they regulate cell adhesion, invasion, and motility in cancer cells, and tumor vasculature, contributing to cancer progression and metastasis. Src kinases are overexpressed in a variety of human cancers, making them attractive targets for therapy. They are also implicated in acute inflammatory responses and osteoclast function. Src, Fyn, Yes, and Yrk are widely expressed, while Blk, Lck, Hck, Fgr, Lyn, and Brk show a limited expression pattern. This subfamily also includes Drosophila Src42A, Src oncogene at 42A (also known as Dsrc41) which accumulates at sites of cell-cell or cell-matrix adhesion, and participates in Drosphila development and wound healing. It has been shown to promote tube elongation in the tracheal system, is essential for proper cell-cell matching during dorsal closure, and regulates cell-cell contacts in developing Drosophila eyes. The SH3 domain of Src kinases contributes to substrate recruitment by binding adaptor proteins/substrates, and regulation of kinase activity through an intramolecular interaction. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212779 [Multi-domain]  Cd Length: 52  Bit Score: 38.33  E-value: 1.08e-03
                           10        20
                   ....*....|....*....|....*..
gi 1799135512   15 VAFYNYDARGADELSLQIGDTVHILET 41
Cdd:cd11845      3 VALYDYEARTDDDLSFKKGDRLQILDD 29
SH3_Sla1p_3 cd11775
Third Src Homology 3 domain of the fungal endocytic adaptor protein Sla1p; Sla1p facilitates ...
 12-55 1.52e-03

Third Src Homology 3 domain of the fungal endocytic adaptor protein Sla1p; Sla1p facilitates endocytosis by playing a role as an adaptor protein in coupling components of the actin cytoskeleton to the endocytic machinery. It interacts with Abp1p, Las17p and Pan1p, which are activator proteins of actin-related protein 2/3 (Arp2/3). Sla1p contains multiple domains including three SH3 domains, a SAM (sterile alpha motif) domain, and a Sla1 homology domain 1 (SHD1), which binds to the NPFXD motif that is found in many integral membrane proteins such as the Golgi-localized Arf-binding protein Lsb5p and the P4-ATPases, Drs2p and Dnf1p. The third SH3 domain of Sla1p can bind ubiquitin while retaining the ability to bind proline-rich ligands; monoubiquitination of target proteins signals internalization and sorting through the endocytic pathway. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212709 [Multi-domain]  Cd Length: 57  Bit Score: 38.07  E-value: 1.52e-03
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*..
gi 1799135512   12 KYGVAFYNYDARGADELSLQIGDTVHILETYEVMD---VTDIINGKV 55
Cdd:cd11775      1 KRGKVLYDFDAQSDDELTVKEGDVVYILDDKKSKDwwmVENVSTGKE 47
SH3_MLK cd11876
Src Homology 3 domain of Mixed Lineage Kinases; MLKs are Serine/Threonine Kinases (STKs), ...
 15-41 2.82e-03

Src Homology 3 domain of Mixed Lineage Kinases; MLKs are Serine/Threonine Kinases (STKs), catalyzing the transfer of the gamma-phosphoryl group from ATP to S/T residues on protein substrates. MLKs act as mitogen-activated protein kinase kinase kinases (MAP3Ks, MKKKs, MAPKKKs), which phosphorylate and activate MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. MLKs play roles in immunity and inflammation, as well as in cell death, proliferation, and cell cycle regulation. Mammals have four MLKs (MLK1-4), mostly conserved in vertebrates, which contain an SH3 domain, a catalytic kinase domain, a leucine zipper, a proline-rich region, and a CRIB domain that mediates binding to GTP-bound Cdc42 and Rac. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212809 [Multi-domain]  Cd Length: 58  Bit Score: 37.49  E-value: 2.82e-03
                           10        20
                   ....*....|....*....|....*..
gi 1799135512   15 VAFYNYDARGADELSLQIGDTVHILET 41
Cdd:cd11876      3 TALFDYDARGEDELTLRRGQPVEVLSK 29
SH3_p47phox_like cd11856
Src homology 3 domains of the p47phox subunit of NADPH oxidase and similar domains; This ...
 15-41 5.69e-03

Src homology 3 domains of the p47phox subunit of NADPH oxidase and similar domains; This family is composed of the tandem SH3 domains of p47phox subunit of NADPH oxidase and Nox Organizing protein 1 (NoxO1), the four SH3 domains of Tks4 (Tyr kinase substrate with four SH3 domains), the five SH3 domains of Tks5, the SH3 domain of obscurin, Myosin-I, and similar domains. Most members of this group also contain Phox homology (PX) domains, except for obscurin and Myosin-I. p47phox and NoxO1 are regulators of the phagocytic NADPH oxidase complex (also called Nox2 or gp91phox) and nonphagocytic NADPH oxidase Nox1, respectively. They play roles in the activation of their respective NADPH oxidase, which catalyzes the transfer of electrons from NADPH to molecular oxygen to form superoxide. Tks proteins are Src substrates and scaffolding proteins that play important roles in the formation of podosomes and invadopodia, the dynamic actin-rich structures that are related to cell migration and cancer cell invasion. Obscurin is a giant muscle protein that plays important roles in the organization and assembly of the myofibril and the sarcoplasmic reticulum. Type I myosins (Myosin-I) are actin-dependent motors in endocytic actin structures and actin patches. They play roles in membrane traffic in endocytic and secretory pathways, cell motility, and mechanosensing. Myosin-I contains an N-terminal actin-activated ATPase, a phospholipid-binding TH1 (tail homology 1) domain, and a C-terminal extension which includes an F-actin-binding TH2 domain, an SH3 domain, and an acidic peptide that participates in activating the Arp2/3complex. The SH3 domain of myosin-I is required for myosin-I-induced actin polymerization. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212790 [Multi-domain]  Cd Length: 53  Bit Score: 36.46  E-value: 5.69e-03
                           10        20
                   ....*....|....*....|....*..
gi 1799135512   15 VAFYNYDARGADELSLQIGDTVHILET 41
Cdd:cd11856      3 VAIADYEAQGDDEISLQEGEVVEVLEK 29
 
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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