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Conserved domains on  [gi|24580520|ref|NP_608489|]
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Zizimin-related [Drosophila melanogaster]

Protein Classification

Graphical summary

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List of domain hits

Name Accession Description Interval E-value
DHR2_DOCK_C cd11695
Dock Homology Region 2, a GEF domain, of Class C Dedicator of Cytokinesis proteins; DOCK ...
1614-2035 0e+00

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


:

Pssm-ID: 212568  Cd Length: 368  Bit Score: 677.48  E-value: 0e+00
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24580520 1614 NPDLRLTWLENMAKKHRERANHTEAAMCYVHAASLvseylsmlesqkhlpvgavsfqrispntlmesavsddvlspgedg 1693
Cdd:cd11695    1 SPDLRLTWLQNMAEKHYERKNFAEAAQCLVHAAAL--------------------------------------------- 35
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24580520 1694 iclgnhftetGLKALLEEASNSFQVAGMYEAMNEVYKILIPICEANRDFQKLSKVHGKLQEAFNRISQLQ-GKRVFGTYF 1772
Cdd:cd11695   36 ----------GLVGLLEQAAESFSKAGMYEAVNEVYKLLIPILEANRDYKKLAEIHGKLQDAFTKIEKQQgGKRMFGTYF 105
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24580520 1773 RVGFYGGKFGDLDQQEFIYKEPTLTKLPEIFSRLQNFYTERFGPDSVHIIKDSNTVDINSLDPDKAYIQITYVEPYFETY 1852
Cdd:cd11695  106 RVGFYGSKFGDLDGKEFIYKEPAITKLPEISHRLETFYGERFGEERVEVIKDSNPVDTSKLDPDKAYIQITYVEPYFDEY 185
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24580520 1853 EMRHRETYFERNFNIKRFIYATPFTKNGKAHGELNEQCKRKTILTTANHFPYVKTRIMVISRQQIVLEPIEVAIEDIQKK 1932
Cdd:cd11695  186 ELKERTTYFERNYNLRRFMYATPFTPDGKAHGELAEQYKRKTILTTENSFPYVKTRLQVVNREEIVLTPIEVAIEDVQKK 265
                        330       340       350       360       370       380       390       400
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24580520 1933 TLELAAATNQEPADPKILQMVLQGCIGTTVNQGPMEMASVFLSNLSDGTTVPTKHQNKLRLCFREFSKRCADALKKNRNL 2012
Cdd:cd11695  266 TRELAAATTQEPPDPKMLQMVLQGSIGTTVNQGPLEVANVFLSDIPLDPKELDRHQNKLRLCFKEFSKKCYDALEKNKEL 345
                        410       420
                 ....*....|....*....|...
gi 24580520 2013 ILSDQKDYQRELERNNDRFIERL 2035
Cdd:cd11695  346 IGPDQKEYQKELERNYENFKEKL 368
C2_Dock-C cd08696
C2 domains found in Dedicator Of CytoKinesis (Dock) class C proteins; Dock-C is one of 4 ...
589-769 1.24e-105

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: 334.71  E-value: 1.24e-105
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24580520  589 YRNLLFVSPKELNFSSRAGSARNIAVRVQLMAGETPKDAVNAIYGKSSCPKFSTEAFTAVNYHNKCPSFYDEIKIALPAS 668
Cdd:cd08696    1 YRNLLYVYPQSLNFSNRLGSARNIAVKVQLMSGEDESQALPVIFKGSSPEEFLTEAYTAVTYHNKSPDFYDEIKIKLPAD 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24580520  669 IKQHHHLLFTIYHVSCQKKPQdlQPSVETPIGYTWLPLLEDGKLKFGEFNLPVMVESPPENYSFIPPNVHLPGIKWLDNH 748
Cdd:cd08696   81 LTDNHHLLFTFYHISCQKKQE--GGSVETPIGYTWLPLLRNGRLQSGEFNLPVSLEKPPSNYSPDSPEVKLPGTKWVDNH 158
                        170       180
                 ....*....|....*....|.
gi 24580520  749 RAVFSINVEAVTAIHTLDSFL 769
Cdd:cd08696  159 KGVFSVSVEAVSSVHTQDSYL 179
DOCK_C-D_N pfam11878
Dedicator of cytokinesis C/D, N terminal; This entry represents the N-terminal domain of the ...
46-153 7.50e-46

Dedicator of cytokinesis C/D, N terminal; This entry represents the N-terminal domain of the DOCK-C subfamily (DOCK 6, 7, 8) and DOCK-D subfamily (DOCK 9, 10, 11). DOCK family members are evolutionarily conserved guanine nucleotide exchange factors (GEFs) for Rho-family GTPases, required during several cellular processes, such as cell motility and phagocytosis. DOCK proteins are categorized into four subfamilies based on their sequence homology: DOCK-A (DOCK1/180, 2, 5), DOCK-B subfamily (DOCK3, 4), DOCK-C subfamily (DOCK6, 7, 8), DOCK-D subfamily (DOCK9, 10, 11).


:

Pssm-ID: 463380  Cd Length: 112  Bit Score: 160.90  E-value: 7.50e-46
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24580520     46 EPLDYEEFLSQHMNIINRDPLKHILDFPQGDVTVKIIPRKIRTVDHVVPNENLSDLPHHVQECVNCYTRPWKVVEYAQRH 125
Cdd:pfam11878    5 EPLDYEEFISQHLTQIENDPLRDLLLFPDDDIEVSVIPRECRTLQPTVPEEAEKEADPLVRECIKTYTSDWHVVNYKYED 84
                           90       100
                   ....*....|....*....|....*...
gi 24580520    126 LSSSCYIRERIDRGTISPSAYQQEFEID 153
Cdd:pfam11878   85 YSGDFRQLPKSKRRERPEKLPKQVFEID 112
 
Name Accession Description Interval E-value
DHR2_DOCK_C cd11695
Dock Homology Region 2, a GEF domain, of Class C Dedicator of Cytokinesis proteins; DOCK ...
1614-2035 0e+00

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


Pssm-ID: 212568  Cd Length: 368  Bit Score: 677.48  E-value: 0e+00
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24580520 1614 NPDLRLTWLENMAKKHRERANHTEAAMCYVHAASLvseylsmlesqkhlpvgavsfqrispntlmesavsddvlspgedg 1693
Cdd:cd11695    1 SPDLRLTWLQNMAEKHYERKNFAEAAQCLVHAAAL--------------------------------------------- 35
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24580520 1694 iclgnhftetGLKALLEEASNSFQVAGMYEAMNEVYKILIPICEANRDFQKLSKVHGKLQEAFNRISQLQ-GKRVFGTYF 1772
Cdd:cd11695   36 ----------GLVGLLEQAAESFSKAGMYEAVNEVYKLLIPILEANRDYKKLAEIHGKLQDAFTKIEKQQgGKRMFGTYF 105
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24580520 1773 RVGFYGGKFGDLDQQEFIYKEPTLTKLPEIFSRLQNFYTERFGPDSVHIIKDSNTVDINSLDPDKAYIQITYVEPYFETY 1852
Cdd:cd11695  106 RVGFYGSKFGDLDGKEFIYKEPAITKLPEISHRLETFYGERFGEERVEVIKDSNPVDTSKLDPDKAYIQITYVEPYFDEY 185
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24580520 1853 EMRHRETYFERNFNIKRFIYATPFTKNGKAHGELNEQCKRKTILTTANHFPYVKTRIMVISRQQIVLEPIEVAIEDIQKK 1932
Cdd:cd11695  186 ELKERTTYFERNYNLRRFMYATPFTPDGKAHGELAEQYKRKTILTTENSFPYVKTRLQVVNREEIVLTPIEVAIEDVQKK 265
                        330       340       350       360       370       380       390       400
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24580520 1933 TLELAAATNQEPADPKILQMVLQGCIGTTVNQGPMEMASVFLSNLSDGTTVPTKHQNKLRLCFREFSKRCADALKKNRNL 2012
Cdd:cd11695  266 TRELAAATTQEPPDPKMLQMVLQGSIGTTVNQGPLEVANVFLSDIPLDPKELDRHQNKLRLCFKEFSKKCYDALEKNKEL 345
                        410       420
                 ....*....|....*....|...
gi 24580520 2013 ILSDQKDYQRELERNNDRFIERL 2035
Cdd:cd11695  346 IGPDQKEYQKELERNYENFKEKL 368
C2_Dock-C cd08696
C2 domains found in Dedicator Of CytoKinesis (Dock) class C proteins; Dock-C is one of 4 ...
589-769 1.24e-105

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: 334.71  E-value: 1.24e-105
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24580520  589 YRNLLFVSPKELNFSSRAGSARNIAVRVQLMAGETPKDAVNAIYGKSSCPKFSTEAFTAVNYHNKCPSFYDEIKIALPAS 668
Cdd:cd08696    1 YRNLLYVYPQSLNFSNRLGSARNIAVKVQLMSGEDESQALPVIFKGSSPEEFLTEAYTAVTYHNKSPDFYDEIKIKLPAD 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24580520  669 IKQHHHLLFTIYHVSCQKKPQdlQPSVETPIGYTWLPLLEDGKLKFGEFNLPVMVESPPENYSFIPPNVHLPGIKWLDNH 748
Cdd:cd08696   81 LTDNHHLLFTFYHISCQKKQE--GGSVETPIGYTWLPLLRNGRLQSGEFNLPVSLEKPPSNYSPDSPEVKLPGTKWVDNH 158
                        170       180
                 ....*....|....*....|.
gi 24580520  749 RAVFSINVEAVTAIHTLDSFL 769
Cdd:cd08696  159 KGVFSVSVEAVSSVHTQDSYL 179
DHR-2_Lobe_A pfam06920
DHR-2, Lobe A; This entry represents a conserved region within a number of eukaryotic ...
1602-1761 5.90e-62

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: 208.69  E-value: 5.90e-62
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24580520   1602 DLMNRIAKGYQNNPDLRLTWLENMAKKHRERANHTEAAMCYVHAASLVSEYLSMLeSQKHLPVGAVSFQRISPNTL-MES 1680
Cdd:pfam06920    1 DLQYSLANSYKSSPDLRLTWLENLAEKHLENGNFSEAAQCLIHIAALIAEYLKLK-GKIPNPLGASAFEKISPNILrEES 79
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24580520   1681 AVSDDVlspgedGICLGNHFTETGLKALLEEASNSFQVAGMYEAMNEVYKILIPICEANRDFQKLSKVHGKLQEAFNRIS 1760
Cdd:pfam06920   80 ALKDDS------GVCDSPHFTEDGLVGLLEEAIDYLDKAERYELAIELYKLLLPIYESRRDYKKLSECHGKLAEAYEKIV 153

                   .
gi 24580520   1761 Q 1761
Cdd:pfam06920  154 E 154
DOCK-C2 pfam14429
C2 domain in Dock180 and Zizimin proteins; The Dock180/Dock1 and Zizimin proteins are atypical ...
586-767 7.82e-55

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: 189.74  E-value: 7.82e-55
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24580520    586 HYSYRNLLFVSPKELNFSSR-AGSARNIAVRVQLMAGEtpKDAV-NAIYGKSSCPkFSTEAFTAVNYHNKCPSFYDEIKI 663
Cdd:pfam14429    1 PGDYRNDLYVTPKSGNFSKQkKSSARNIEVTVEVRDSD--GEPLpNCIYGGSGGP-FVTEFKSTVYYHNKSPTWYEEIKI 77
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24580520    664 ALPASIKQHHHLLFTIYHVSCQKKPQdlqpSVETPIGYTWLPLLEDGK--LKFGEFNLPVM-VESPPENYSFIPPN---- 736
Cdd:pfam14429   78 ALPAELTPKHHLLFTFYHVSCDEKKD----KVEKPFGYAFLPLLDDDGafLRDGEHTLPVYkYDELPPGYLSLPWSsgge 153
                          170       180       190
                   ....*....|....*....|....*....|....
gi 24580520    737 ---VHLPGIKwldNHRAVFSINVEAVTAIHTLDS 767
Cdd:pfam14429  154 kesSALPGLK---GGKDLFKVRTRLCSTKYTQDE 184
DOCK_C-D_N pfam11878
Dedicator of cytokinesis C/D, N terminal; This entry represents the N-terminal domain of the ...
46-153 7.50e-46

Dedicator of cytokinesis C/D, N terminal; This entry represents the N-terminal domain of the DOCK-C subfamily (DOCK 6, 7, 8) and DOCK-D subfamily (DOCK 9, 10, 11). DOCK family members are evolutionarily conserved guanine nucleotide exchange factors (GEFs) for Rho-family GTPases, required during several cellular processes, such as cell motility and phagocytosis. DOCK proteins are categorized into four subfamilies based on their sequence homology: DOCK-A (DOCK1/180, 2, 5), DOCK-B subfamily (DOCK3, 4), DOCK-C subfamily (DOCK6, 7, 8), DOCK-D subfamily (DOCK9, 10, 11).


Pssm-ID: 463380  Cd Length: 112  Bit Score: 160.90  E-value: 7.50e-46
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24580520     46 EPLDYEEFLSQHMNIINRDPLKHILDFPQGDVTVKIIPRKIRTVDHVVPNENLSDLPHHVQECVNCYTRPWKVVEYAQRH 125
Cdd:pfam11878    5 EPLDYEEFISQHLTQIENDPLRDLLLFPDDDIEVSVIPRECRTLQPTVPEEAEKEADPLVRECIKTYTSDWHVVNYKYED 84
                           90       100
                   ....*....|....*....|....*...
gi 24580520    126 LSSSCYIRERIDRGTISPSAYQQEFEID 153
Cdd:pfam11878   85 YSGDFRQLPKSKRRERPEKLPKQVFEID 112
 
Name Accession Description Interval E-value
DHR2_DOCK_C cd11695
Dock Homology Region 2, a GEF domain, of Class C Dedicator of Cytokinesis proteins; DOCK ...
1614-2035 0e+00

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


Pssm-ID: 212568  Cd Length: 368  Bit Score: 677.48  E-value: 0e+00
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24580520 1614 NPDLRLTWLENMAKKHRERANHTEAAMCYVHAASLvseylsmlesqkhlpvgavsfqrispntlmesavsddvlspgedg 1693
Cdd:cd11695    1 SPDLRLTWLQNMAEKHYERKNFAEAAQCLVHAAAL--------------------------------------------- 35
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24580520 1694 iclgnhftetGLKALLEEASNSFQVAGMYEAMNEVYKILIPICEANRDFQKLSKVHGKLQEAFNRISQLQ-GKRVFGTYF 1772
Cdd:cd11695   36 ----------GLVGLLEQAAESFSKAGMYEAVNEVYKLLIPILEANRDYKKLAEIHGKLQDAFTKIEKQQgGKRMFGTYF 105
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24580520 1773 RVGFYGGKFGDLDQQEFIYKEPTLTKLPEIFSRLQNFYTERFGPDSVHIIKDSNTVDINSLDPDKAYIQITYVEPYFETY 1852
Cdd:cd11695  106 RVGFYGSKFGDLDGKEFIYKEPAITKLPEISHRLETFYGERFGEERVEVIKDSNPVDTSKLDPDKAYIQITYVEPYFDEY 185
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24580520 1853 EMRHRETYFERNFNIKRFIYATPFTKNGKAHGELNEQCKRKTILTTANHFPYVKTRIMVISRQQIVLEPIEVAIEDIQKK 1932
Cdd:cd11695  186 ELKERTTYFERNYNLRRFMYATPFTPDGKAHGELAEQYKRKTILTTENSFPYVKTRLQVVNREEIVLTPIEVAIEDVQKK 265
                        330       340       350       360       370       380       390       400
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24580520 1933 TLELAAATNQEPADPKILQMVLQGCIGTTVNQGPMEMASVFLSNLSDGTTVPTKHQNKLRLCFREFSKRCADALKKNRNL 2012
Cdd:cd11695  266 TRELAAATTQEPPDPKMLQMVLQGSIGTTVNQGPLEVANVFLSDIPLDPKELDRHQNKLRLCFKEFSKKCYDALEKNKEL 345
                        410       420
                 ....*....|....*....|...
gi 24580520 2013 ILSDQKDYQRELERNNDRFIERL 2035
Cdd:cd11695  346 IGPDQKEYQKELERNYENFKEKL 368
DHR2_DOCK6 cd11702
Dock Homology Region 2, a GEF domain, of Class C Dedicator of Cytokinesis 6; Dock6, also ...
1614-2035 0e+00

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


Pssm-ID: 212575  Cd Length: 423  Bit Score: 672.49  E-value: 0e+00
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24580520 1614 NPDLRLTWLENMAKKHRERANHTEAAMCYVHAASLVSEYLSMLESQKHLPVGAVSFQRISPNTLMESAVSDDVLSPGEDG 1693
Cdd:cd11702    1 SPDLRLTWLQNMAGKHSERGNHAEAAHCLVHSAALVAEYLSMLEDCRHLPVGCVSFQNISSNVLEESAVSDDILSPDEEG 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24580520 1694 ICLGNHFTETGLKALLEEASNSFQVAGMYEAMNEVYKILIPICEANRDFQKLSKVHGKLQEAFNRI-SQLQG-KRVFGTY 1771
Cdd:cd11702   81 ICSGKYFTELGLVGLLEQAAASFNMGGLYEAVNEVYKILIPIHEANRDYKKLAVVHGKLQEAFNKItNQSSGwERMFGTY 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24580520 1772 FRVGFYGGKFGDLDQQEFIYKEPTLTKLPEIFSRLQNFYTERFGPDSVHIIKDSNTVDINSLDPDKAYIQITYVEPYFET 1851
Cdd:cd11702  161 FRVGFYGCKFGDLDEQEFVYKEPSITKLAEISHRLEEFYTERFGDEVVEIIKDSNPVDKSKLDPNKAYIQITYVEPFFDT 240
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24580520 1852 YEMRHRETYFERNFNIKRFIYATPFTKNGKAHGELNEQCKRKTILTTANHFPYVKTRIMVISRQQIVLEPIEVAIEDIQK 1931
Cdd:cd11702  241 YELKDRVTYFDKNYNLRTFLFCTPFTLDGRAHGELHEQYKRKTILTTSHAFPYIKTRINVLHREEIVLIPVEVAIEDMQK 320
                        330       340       350       360       370       380       390       400
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24580520 1932 KTLELAAATNQEPADPKILQMVLQGCIGTTVNQGPMEMASVFLSNLSDGTTVpTKHQNKLRLCFREFSKRCADALKKNRN 2011
Cdd:cd11702  321 KTQELAFATHQDPADAKMLQMVLQGCVGTTVNQGPLEVAQVFLSEIPEDPKL-FRHHNKLRLCFKDFTKRCEDALRKNKA 399
                        410       420
                 ....*....|....*....|....
gi 24580520 2012 LILSDQKDYQRELERNNDRFIERL 2035
Cdd:cd11702  400 LIGPDQKEYHRELERNYQRLREAL 423
DHR2_DOCK7 cd11703
Dock Homology Region 2, a GEF domain, of Class C Dedicator of Cytokinesis 7; Dock7, also ...
1575-2039 0e+00

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


Pssm-ID: 212576  Cd Length: 473  Bit Score: 667.94  E-value: 0e+00
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24580520 1575 DLLFNLHMILSDTVKMKEYQEDPEMLLDLMNRIAKGYQNNPDLRLTWLENMAKKHRERANHTEAAMCYVHAASLVSEYLS 1654
Cdd:cd11703    1 DLVFNLHMILSDTVKMKEHQEDPEMLIDLMYRIAKGYQTSPDLRLTWLQNMAGKHSERSNHAEAAQCLVHSAALVAEYLS 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24580520 1655 MLESQKHLPVGAVSFQRISPNTLMESAVSDDVLSPGEDGICLGNHFTETGLKALLEEASNSFQVAGMYEAMNEVYKILIP 1734
Cdd:cd11703   81 MLEDRKYLPVGCVTFQNISSNVLEESAVSDDVVSPDEEGICSGKYFTEAGLVGLLEQAAASFSMAGMYEAVNEVYKVLIP 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24580520 1735 ICEANRDFQKLSKVHGKLQEAFNRISQLQGKRVFGTYFRVGFYGGKFGDLDQQEFIYKEPTLTKLPEIFSRLQNFYTERF 1814
Cdd:cd11703  161 IHEANRDAKKLATIHGKLQEAFSKIVHQDGKRMFGTYFRVGFYGTKFGDLDEQEFVYKEPAITKLAEISHRLEGFYGERF 240
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24580520 1815 GPDSVHIIKDSNTVDINSLDPDKAYIQITYVEPYFETYEMRHRETYFERNFNIKRFIYATPFTKNGKAHGELNEQCKRKT 1894
Cdd:cd11703  241 GEDVVEVIKDSNPVDKCKLDPNKAFIQITYVEPYFDTYEMKDRITYFDKNYNLRRFMYCTPFTLDGRAHGELHEQFKRKT 320
                        330       340       350       360       370       380       390       400
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24580520 1895 ILTTANHFPYVKTRIMVISRQQIVLEPIEVAIEDIQKKTLELAAATNQEPADPKILQMVLQGCIGTTVNQGPMEMASVFL 1974
Cdd:cd11703  321 ILTTSHAFPYIKTRINVIHKEEIILTPIEVAIEDMQKKTQELAFATHQDPADPKMLQMVLQGSVGTTVNQGPLEVAQVFL 400
                        410       420       430       440       450       460
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 24580520 1975 SNLSDGTTVpTKHQNKLRLCFREFSKRCADALKKNRNLILSDQKDYQRELERNNDRFIERLTPFI 2039
Cdd:cd11703  401 SEIPSDPKL-FRHHNKLRLCFKDFTKRCEDALRKNKSLIGPDQKEYQRELERNYHRLKEALQPLI 464
DHR2_DOCK8 cd11701
Dock Homology Region 2, a GEF domain, of Class C Dedicator of Cytokinesis 8; Dock8, also ...
1614-2035 0e+00

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


Pssm-ID: 212574  Cd Length: 422  Bit Score: 638.62  E-value: 0e+00
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24580520 1614 NPDLRLTWLENMAKKHRERANHTEAAMCYVHAASLVSEYLSMLESQKHLPVGAVSFQRISPNTLMESAVSDDVLSPGEDG 1693
Cdd:cd11701    2 SPDLRLTWLQNMAEKHTKRKCFTEAAMCLVHAAALVAEYLSMLEDHSYLPVGSVSFQNISSNVLEESAVSDDILSPDEDG 81
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24580520 1694 ICLGNHFTETGLKALLEEASNSFQVAGMYEAMNEVYKILIPICEANRDFQKLSKVHGKLQEAFNRISQLQGKRVFGTYFR 1773
Cdd:cd11701   82 VCSGRYFTENGLVGLLEQAAELFSTGGLYETVNEVYKIVIPILEAHRDFRKLASTHDKLQKAFDNIINKGHKRMFGTYFR 161
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24580520 1774 VGFYGGKFGDLDQQEFIYKEPTLTKLPEIFSRLQNFYTERFGPDSVHIIKDSNTVDINSLDPDKAYIQITYVEPYFETYE 1853
Cdd:cd11701  162 VGFYGSKFGDLDEQEFIYKEPAITKLPEISHRLEGFYGQCFGDDVVEVIKDSTPVDKSKLDPNKAYIQITFVEPYFDDYE 241
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24580520 1854 MRHRETYFERNFNIKRFIYATPFTKNGKAHGELNEQCKRKTILTTANHFPYVKTRIMVISRQQIVLEPIEVAIEDIQKKT 1933
Cdd:cd11701  242 MKDRVTYFEKNFNLRRFMYTTPFTLDGRPRGELSEQYKRKTILTTMHAFPYIKTRINVIQKEEFDLTPIEVAIEDMQKKT 321
                        330       340       350       360       370       380       390       400
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24580520 1934 LELAAATNQEPADPKILQMVLQGCIGTTVNQGPMEMASVFLSNLSDGTTVpTKHQNKLRLCFREFSKRCADALKKNRNLI 2013
Cdd:cd11701  322 RELAEATHQEPPDAKMLQMVLQGSVGATVNQGPLEVAQVFLAEIPADPKL-YRHHNKLRLCFKEFIMRCGEAVEKNKRLI 400
                        410       420
                 ....*....|....*....|..
gi 24580520 2014 LSDQKDYQRELERNNDRFIERL 2035
Cdd:cd11701  401 TADQREYQQELKKNYNKLRENL 422
DHR2_DOCK_D cd11694
Dock Homology Region 2, a GEF domain, of Class D Dedicator of Cytokinesis proteins; DOCK ...
1616-2035 8.12e-130

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: 412.50  E-value: 8.12e-130
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24580520 1616 DLRLTWLENMAKKHRERANHTEAAMCYVHAASLVSEYLsmlesqkhlpvgavsfQRisPNTLMEsavsddvlspgedgic 1695
Cdd:cd11694    1 ELRKTWLESMARIHEKNGNFSEAAMCYIHIAALVAEYL----------------KR--KDLLLE---------------- 46
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24580520 1696 lgnhftetglkaLLEEASNSFQVAGMYEAMNEVYKILIPICEANRDFQKLSKVHGKLQEAFNRISQLQ--GKRVFGTYFR 1773
Cdd:cd11694   47 ------------LLEACVEGLWKAERYELLGELYKLIIPIYEKRRDFEQLADCYRTLHRAYEKVVEVMesGKRLLGTYYR 114
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24580520 1774 VGFYG-GKFGDLDQQEFIYKEPTLTKLPEIFSRLQNFYTERFGPDSVHIIKDSNTVDINSLDPDKAYIQITYVEPYFETY 1852
Cdd:cd11694  115 VAFYGqAFFEEEDGKEYIYKEPKVTSLSEISERLLKLYGDKFGSENVKLIQDSGKVNPKDLDPKYAYIQVTHVTPYFDEK 194
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24580520 1853 EMRHRETYFERNFNIKRFIYATPFTKNGKAHGELNEQCKRKTILTTANHFPYVKTRIMVISRQQIVLEPIEVAIEDIQKK 1932
Cdd:cd11694  195 ELEDRKTEFERNHNIRRFVFETPFTLSGKARGAVEEQWKRRTILTTSHSFPYVKKRIPVVQREIIELSPIEVAIDEMQSK 274
                        330       340       350       360       370       380       390       400
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24580520 1933 TLELAAATNQEPADPKILQMVLQGCIGTTVNQGPMEMASVFLsnlsDGTTV---PTKHQNKLRLCFREFSKRCADALKKN 2009
Cdd:cd11694  275 VKELEELISTEPVDMKKLQLRLQGSVSVQVNAGPLAYARAFL----EPTTVknyPDDQVEDLKDVFRDFIKACGQALELN 350
                        410       420
                 ....*....|....*....|....*.
gi 24580520 2010 RNLILSDQKDYQRELERNNDRFIERL 2035
Cdd:cd11694  351 ERLIKEDQREYHEVLKENYRKMVKEL 376
DHR2_DOCK11 cd11700
Dock Homology Region 2, a GEF domain, of Class D Dedicator of Cytokinesis 11; Dock11, also ...
1615-2035 1.49e-124

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: 398.98  E-value: 1.49e-124
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24580520 1615 PDLRLTWLENMAKKHRERANHTEAAMCYVHAASLVSEYLsmlESQKHLPVGAVSFQRISPNTLMESAVSddvlspgEDGI 1694
Cdd:cd11700    1 PELRKTWLDSMAKIHVKNGDFSEAAMCYVHVAALVAEFL---HRKKLFPSGCAAFKKITPNIDEEGAMK-------EDIG 70
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24580520 1695 CLGNHFTETGLKALLEEASNSFQVAGMYEAMNEVYKILIPICEANRDFQKLSKVHGKLQEAFNRISQLQ--GKRVFGTYF 1772
Cdd:cd11700   71 MMDVHYSEEVLVELLEQCVDGLWKAERYELISEISKLIIPIYEKRREFEKLTQLYRTLHGAYAKILEVMhtGKRLLGTFF 150
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24580520 1773 RVGFYG-GKFGDLDQQEFIYKEPTLTKLPEIFSRLQNFYTERFGPDSVHIIKDSNTVDINSLDPDKAYIQITYVEPYFET 1851
Cdd:cd11700  151 RVAFYGqGFFEEEDGKEYIYKEPKLTGLSEISHRLLKLYGEKFGSENVKIIQDSNKVNQKDLDPKYAHIQVTYVKPYFDD 230
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24580520 1852 YEMRHRETYFERNFNIKRFIYATPFTKNGKAHGELNEQCKRKTILTTANHFPYVKTRIMVISRQQIVLEPIEVAIEDIQK 1931
Cdd:cd11700  231 KEMAERKTEFERNHNIQRFVFETPYTLSGKKQGGVEEQCKRRTILTTANSFPYVKKRIPVNGEKQTNLKPIDVATDEIKD 310
                        330       340       350       360       370       380       390       400
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24580520 1932 KTLELAAATNQEPADPKILQMVLQGCIGTTVNQGPMEMASVFLSNlSDGTTVPTKHQNKLRLCFREFSKRCADALKKNRN 2011
Cdd:cd11700  311 KTAELQKLCSNQDVDMIQLQLKLQGCVSVQVNAGPLAYARAFLDD-SQASKYPNKKVKELKEMFRKFIQACSIALELNER 389
                        410       420
                 ....*....|....*....|....
gi 24580520 2012 LILSDQKDYQRELERNNDRFIERL 2035
Cdd:cd11700  390 LIKEDQVEYHEGLKSNFRDMVKEL 413
DHR2_DOCK9 cd11698
Dock Homology Region 2, a GEF domain, of Class D Dedicator of Cytokinesis 9; Dock9, also ...
1616-2027 1.51e-110

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: 358.96  E-value: 1.51e-110
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24580520 1616 DLRLTWLENMAKKHRERANHTEAAMCYVHAASLVSEYLSmleSQKHLPVGAVSFQRISPNTLMESAVSDDVlspGEDGIc 1695
Cdd:cd11698    1 ELRKTWLDSMARIHVKNGDLSEAAMCYVHVAALVAEYLT---RKGMFRQGCTAFRVITPNIDEEASMMEDV---GMQDV- 73
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24580520 1696 lgnHFTETGLKALLEEASNSFQVAGMYEAMNEVYKILIPICEANRDFQKLSKVHGKLQEAFNRISQL--QGKRVFGTYFR 1773
Cdd:cd11698   74 ---HFNEDVLMELLEQCADGLWKAERYELIADIYKLIIPIYEKRRDFERLAHLYDTLHRAYSKVTEVmhSGKRLLGTYFR 150
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24580520 1774 VGFYG-GKFGDLDQQEFIYKEPTLTKLPEIFSRLQNFYTERFGPDSVHIIKDSNTVDINSLDPDKAYIQITYVEPYFETY 1852
Cdd:cd11698  151 VAFFGqGFFEDEDGKEYIYKEPKLTPLSEISQRLLKLYSDKFGSENVKMIQDSGKVNPKDLDSKYAYIQVTHVTPYFDEK 230
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24580520 1853 EMRHRETYFERNFNIKRFIYATPFTKNGKAHGELNEQCKRKTILTTANHFPYVKTRIMVISRQQIVLEPIEVAIEDIQKK 1932
Cdd:cd11698  231 ELQERKTDFERSHNIRRFMFEMPFTQSGKRQGGVEEQCKRRTILTAIHCFPYVKKRIPVMYQHHTDLNPIEVAIDEMSKK 310
                        330       340       350       360       370       380       390       400
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24580520 1933 TLELAAATNQEPADPKILQMVLQGCIGTTVNQGPMEMASVFLSNlSDGTTVPTKHQNKLRLCFREFSKRCADALKKNRNL 2012
Cdd:cd11698  311 VAELRQLCSSAEVDMIKLQLKLQGSVSVQVNAGPLAYARAFLDD-TNTKRYPDNKVKLLKEVFRQFVEACGQALAVNERL 389
                        410
                 ....*....|....*
gi 24580520 2013 ILSDQKDYQRELERN 2027
Cdd:cd11698  390 IKEDQLEYQEEMKAN 404
DHR2_DOCK cd11684
Dock Homology Region 2, a GEF domain, of Dedicator of Cytokinesis proteins; DOCK proteins ...
1616-2035 1.26e-106

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: 346.98  E-value: 1.26e-106
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24580520 1616 DLRLTWLENMAKKHRERANHTEAAMCYVHAASLVSEYLSMLESQKhlpvgavsfqrispntlmesavsddvlspgEDGIC 1695
Cdd:cd11684    1 ELYIRYLHKLADLHEERGNYVEAALCLLLHADLYAWDLKALVPAL------------------------------AESLS 50
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24580520 1696 LGNHFTETGLKALLEEASNSFQVAGMYEAMNEVYKILIPICEANRDFQKLSKVHGKLQEAFNRIsqLQGKRVFGTYFRVG 1775
Cdd:cd11684   51 FPEQTSFERKEALYKKAIDLFDKGKAWEFAIALYKELIPQYENNFDYAKLSEVHRKIAKLYEKI--AEKDRLFPTYFRVG 128
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24580520 1776 FYGGKF-GDLDQQEFIYKEPTLTKLPEIFSRLQNFYTERfgpdsvHIIKDSNTVDINSLDPDKAYIQITYVEPYFETYEM 1854
Cdd:cd11684  129 FYGKGFpESLRGKEFIYRGPEFERLGDFCERLKSLYPGA------EIIQSSEEPDDEILDSEGQYIQITSVEPYFDDEDL 202
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24580520 1855 RHRE----TYFERNFNIKRFIYATPFTKNGKA-HGELNEQCKRKTILTTANHFPYVKTRIMVISRQQIVLEPIEVAIEDI 1929
Cdd:cd11684  203 VSRAapgvRQFYRNNNINTFVYERPFTKGGKKsQNEITDQWKERTILTTEESFPTILRRSEVVSIEEIELSPIENAIEDI 282
                        330       340       350       360       370       380       390       400
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24580520 1930 QKKTLELAAATNQ----EPADPKILQMVLQGCIGTTVNQGPMEMASVFLSNLSDGTTVPTKHQNKLRLCFREFSKRCADA 2005
Cdd:cd11684  283 EKKTEELRSLINKyrsgDSPNVNPLQMLLQGTVDAAVNGGPVAYAEAFLSEEYLSNYPEAEKVKKLKEAFEEFLEILKRG 362
                        410       420       430
                 ....*....|....*....|....*....|
gi 24580520 2006 LKKNRNLILSDQKDYQRELERNNDRFIERL 2035
Cdd:cd11684  363 LALHAKLCPPEMAPLHEELEEGFEKLFKEL 392
DHR2_DOCK10 cd11699
Dock Homology Region 2, a GEF domain, of Class D Dedicator of Cytokinesis 10; Dock10, also ...
1615-2025 2.11e-106

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: 348.57  E-value: 2.11e-106
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24580520 1615 PDLRLTWLENMAKKHRERANHTEAAMCYVHAASLVSEYL--------------SMLESQKHLP----------------V 1664
Cdd:cd11699    1 PELRRTWLESMAKIHARNGDLSEAAMCYIHIAALIAEYLkrkgywkmekictsSMLPEDSQVYdsnlllttstggsmfsM 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24580520 1665 GAVSFQRISPNTLMESAVSDDvlSPGEDgiclgNHFTETGLKALLEEASNSFQVAGMYEAMNEVYKILIPICEANRDFQK 1744
Cdd:cd11699   81 GWPAFLSITPNIKEEGAMKED--SGMQD-----TPYNENTLVEQLELCVDYLWKSERYELIADVNKPVIAVFEKQRDFKR 153
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24580520 1745 LSKVHGKLQEAFNRISQL--QGKRVFGTYFRVGFYG-GKFGDLDQQEFIYKEPTLTKLPEIFSRLQNFYTERFGPDSVHI 1821
Cdd:cd11699  154 LSELYYDIHRSYLKVAEVvnSEKRLFGRYYRVAFYGqGFFEEEEGKEYIYKEPKLTGLSEISQRLLKLYADKFGADNVKI 233
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24580520 1822 IKDSNTVDINSLDPDKAYIQITYVEPYFETYEMRHRETYFERNFNIKRFIYATPFTKNGKAHGELNEQCKRKTILTTANH 1901
Cdd:cd11699  234 IQDSNKVNPKELDPKFAYIQVTYVTPYFDEKEQEDRKTDFEMHHNINRFVFETPFTLSGKKHGGVEEQCKRRTILTTSHS 313
                        330       340       350       360       370       380       390       400
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24580520 1902 FPYVKTRIMVISRQQIVLEPIEVAIEDIQKKTLELAAATNQEPADPKILQMVLQGCIGTTVNQGPMEMASVFLSNlSDGT 1981
Cdd:cd11699  314 FPYVKKRIQVVSQTSTELNPIEVAIDEMSKKVSELNQLCTMEEVDMIRLQLKLQGSVSVKVNAGPMAYARAFLEE-TNAK 392
                        410       420       430       440
                 ....*....|....*....|....*....|....*....|....
gi 24580520 1982 TVPTKHQNKLRLCFREFSKRCADALKKNRNLILSDQKDYQRELE 2025
Cdd:cd11699  393 KYPDNQVKLLKEIFRQFAEACGQALDVNERLIKEDQLEYQEEMR 436
C2_Dock-C cd08696
C2 domains found in Dedicator Of CytoKinesis (Dock) class C proteins; Dock-C is one of 4 ...
589-769 1.24e-105

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: 334.71  E-value: 1.24e-105
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24580520  589 YRNLLFVSPKELNFSSRAGSARNIAVRVQLMAGETPKDAVNAIYGKSSCPKFSTEAFTAVNYHNKCPSFYDEIKIALPAS 668
Cdd:cd08696    1 YRNLLYVYPQSLNFSNRLGSARNIAVKVQLMSGEDESQALPVIFKGSSPEEFLTEAYTAVTYHNKSPDFYDEIKIKLPAD 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24580520  669 IKQHHHLLFTIYHVSCQKKPQdlQPSVETPIGYTWLPLLEDGKLKFGEFNLPVMVESPPENYSFIPPNVHLPGIKWLDNH 748
Cdd:cd08696   81 LTDNHHLLFTFYHISCQKKQE--GGSVETPIGYTWLPLLRNGRLQSGEFNLPVSLEKPPSNYSPDSPEVKLPGTKWVDNH 158
                        170       180
                 ....*....|....*....|.
gi 24580520  749 RAVFSINVEAVTAIHTLDSFL 769
Cdd:cd08696  159 KGVFSVSVEAVSSVHTQDSYL 179
DHR-2_Lobe_A pfam06920
DHR-2, Lobe A; This entry represents a conserved region within a number of eukaryotic ...
1602-1761 5.90e-62

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: 208.69  E-value: 5.90e-62
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24580520   1602 DLMNRIAKGYQNNPDLRLTWLENMAKKHRERANHTEAAMCYVHAASLVSEYLSMLeSQKHLPVGAVSFQRISPNTL-MES 1680
Cdd:pfam06920    1 DLQYSLANSYKSSPDLRLTWLENLAEKHLENGNFSEAAQCLIHIAALIAEYLKLK-GKIPNPLGASAFEKISPNILrEES 79
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24580520   1681 AVSDDVlspgedGICLGNHFTETGLKALLEEASNSFQVAGMYEAMNEVYKILIPICEANRDFQKLSKVHGKLQEAFNRIS 1760
Cdd:pfam06920   80 ALKDDS------GVCDSPHFTEDGLVGLLEEAIDYLDKAERYELAIELYKLLLPIYESRRDYKKLSECHGKLAEAYEKIV 153

                   .
gi 24580520   1761 Q 1761
Cdd:pfam06920  154 E 154
DOCK-C2 pfam14429
C2 domain in Dock180 and Zizimin proteins; The Dock180/Dock1 and Zizimin proteins are atypical ...
586-767 7.82e-55

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: 189.74  E-value: 7.82e-55
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24580520    586 HYSYRNLLFVSPKELNFSSR-AGSARNIAVRVQLMAGEtpKDAV-NAIYGKSSCPkFSTEAFTAVNYHNKCPSFYDEIKI 663
Cdd:pfam14429    1 PGDYRNDLYVTPKSGNFSKQkKSSARNIEVTVEVRDSD--GEPLpNCIYGGSGGP-FVTEFKSTVYYHNKSPTWYEEIKI 77
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24580520    664 ALPASIKQHHHLLFTIYHVSCQKKPQdlqpSVETPIGYTWLPLLEDGK--LKFGEFNLPVM-VESPPENYSFIPPN---- 736
Cdd:pfam14429   78 ALPAELTPKHHLLFTFYHVSCDEKKD----KVEKPFGYAFLPLLDDDGafLRDGEHTLPVYkYDELPPGYLSLPWSsgge 153
                          170       180       190
                   ....*....|....*....|....*....|....
gi 24580520    737 ---VHLPGIKwldNHRAVFSINVEAVTAIHTLDS 767
Cdd:pfam14429  154 kesSALPGLK---GGKDLFKVRTRLCSTKYTQDE 184
DOCK_C-D_N pfam11878
Dedicator of cytokinesis C/D, N terminal; This entry represents the N-terminal domain of the ...
46-153 7.50e-46

Dedicator of cytokinesis C/D, N terminal; This entry represents the N-terminal domain of the DOCK-C subfamily (DOCK 6, 7, 8) and DOCK-D subfamily (DOCK 9, 10, 11). DOCK family members are evolutionarily conserved guanine nucleotide exchange factors (GEFs) for Rho-family GTPases, required during several cellular processes, such as cell motility and phagocytosis. DOCK proteins are categorized into four subfamilies based on their sequence homology: DOCK-A (DOCK1/180, 2, 5), DOCK-B subfamily (DOCK3, 4), DOCK-C subfamily (DOCK6, 7, 8), DOCK-D subfamily (DOCK9, 10, 11).


Pssm-ID: 463380  Cd Length: 112  Bit Score: 160.90  E-value: 7.50e-46
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24580520     46 EPLDYEEFLSQHMNIINRDPLKHILDFPQGDVTVKIIPRKIRTVDHVVPNENLSDLPHHVQECVNCYTRPWKVVEYAQRH 125
Cdd:pfam11878    5 EPLDYEEFISQHLTQIENDPLRDLLLFPDDDIEVSVIPRECRTLQPTVPEEAEKEADPLVRECIKTYTSDWHVVNYKYED 84
                           90       100
                   ....*....|....*....|....*...
gi 24580520    126 LSSSCYIRERIDRGTISPSAYQQEFEID 153
Cdd:pfam11878   85 YSGDFRQLPKSKRRERPEKLPKQVFEID 112
C2_Dock-D cd08697
C2 domains found in Dedicator Of CytoKinesis (Dock) class C proteins; Dock-D is one of 4 ...
589-769 1.03e-41

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: 152.09  E-value: 1.03e-41
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24580520  589 YRNLLFVSPKELNFSSRAGS--ARNIAVRVQLMAGetpkDAVNA-----IYGKSSCPkFSTEAFTAVNYHNKCPSFYDEI 661
Cdd:cd08697    1 YKNHLYVYPLHLKYDSQKTFakARNIAVCIEFRDS----DEEDAkplkcIYYGPGGG-FTTSAYAAVLHHNQNPEFYDEI 75
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24580520  662 KIALPASIKQHHHLLFTIYHVSC-QKKPQDLQPSVETPIGYTWLPLLED-GKLKFGEFNLPVMVESPPENYSFIPPNVHL 739
Cdd:cd08697   76 KIELPTQLHEKHHLLFTFYHVSCdINKKGKKKDGVETPVGYAWLPLLKDkGRLNSEEQTPPVANLLPNYPDGYLSIQPHG 155
                        170       180       190
                 ....*....|....*....|....*....|
gi 24580520  740 PGIKWLDNHRAVFSINVEAVTAIHTLDSFL 769
Cdd:cd08697  156 PEVKWVDGGKPLFKVSTHLVSTVYTQDQHL 185
DHR-2_Lobe_B pfam20422
DHR-2, Lobe B; DOCK (dedicator of cytokinesis) proteins are guanine nucleotide exchange ...
1825-1901 6.01e-40

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: 142.75  E-value: 6.01e-40
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 24580520   1825 SNTVDINSLDPDKAYIQITYVEPYFETYEMRHRETYFERNFNIKRFIYATPFTKNGKAHGELNEQCKRKTILTTANH 1901
Cdd:pfam20422    1 SNPVDESILDPDKAYIQITSVEPYFDDSELNDRVTYFERNNNVNRFVFETPFTKSGKAQGEFEEQWKRRTILTTEHS 77
DHR-2_Lobe_C pfam20421
DHR-2, Lobe C; DOCK (dedicator of cytokinesis) proteins are guanine nucleotide exchange ...
1935-2038 1.72e-39

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: 142.35  E-value: 1.72e-39
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24580520   1935 ELAAATNQEPADPKILQMVLQGCIGTTVNQGPMEMASVFLSNlSDGTTVPTKHQNKLRLCFREFSKRCADALKKNRNLIL 2014
Cdd:pfam20421    1 ELEAAINAPPPNIKTLQMVLQGSVDVQVNAGPLEYAEAFLSE-KNVDNYPAEKVEKLKEEFRDFLKVCGEALRLNKKLIS 79
                           90       100
                   ....*....|....*....|....
gi 24580520   2015 SDQKDYQRELERNNDRFIERLTPF 2038
Cdd:pfam20421   80 EDQREYQEELEEGFEKLKEKLEPY 103
C2_DOCK180_related cd08679
C2 domains found in Dedicator Of CytoKinesis 1 (DOCK 180) and related proteins; Dock180 was ...
589-769 2.39e-37

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: 139.39  E-value: 2.39e-37
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24580520  589 YRNLLFVSPKELNFSSRAGSARNIAVRVQLM--AGETPKDAVnAIYGKSScpkFSTEAFTAVNYHNKCPSFYDEIKIALP 666
Cdd:cd08679    1 LRNDLYVYPQSGELSKAKSKGRNIEITVEVRddDGDIIEPCI-SAPGSGS---ELRSEYTSVVYYHKNPVFNDEIKIQLP 76
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24580520  667 ASIKQHHHLLFTIYHVSCQKKPQDlqpSVETPIGYTWLPLLEDGK--LKFGEFNLPVMVESPPeNYSFIPPNVHLPGIKW 744
Cdd:cd08679   77 ADLTPQHHLLFTFYHVSSKKKQGD---KEETPFGYAFLPLMDKDGafIKDGDHTLPVYKYDKR-PDVGPSGYLSLPSTLA 152
                        170       180
                 ....*....|....*....|....*.
gi 24580520  745 -LDNHRAVFSINVEAVTAIHTLDSFL 769
Cdd:cd08679  153 nGKSSKDTFKIKTRLCSTILTQDKSL 178
DHR2_DOCK_B cd11696
Dock Homology Region 2, a GEF domain, of Class B Dedicator of Cytokinesis proteins; DOCK ...
1733-1965 1.90e-16

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: 83.65  E-value: 1.90e-16
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24580520 1733 IPIC-------EANRDFQKLSKVHgKLQEAF--NRISQLqgkRVFGTYFRVGFYGGKFGD-LDQQEFIYKEPTLTKLPEI 1802
Cdd:cd11696   77 IPLCrelaelyESLYDYAKLSHIL-RMEASFydNILTQL---RPEPEYFRVGFYGKGFPLfLRNKQFVYRGLDYERIGAF 152
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24580520 1803 FSRLQNFYTerfgpdSVHIIKDSNTVDINSLDPDKAYIQITYVEPYFETYEMRHRE-------TYFERNfNIKRFIYATP 1875
Cdd:cd11696  153 TQRLQSEFP------QAHILTKNTPPDDAILQADGQYIQICNVKPVPERRPVLQMVgvpdkvrSFYRVN-DVRKFQYDRP 225
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24580520 1876 FTKNGK-AHGELNEQCKRKTILTTANHFPYVKTRIMVISRQQIVLEPIEVAIEDIQKKTLELAAATNQEPADPK----IL 1950
Cdd:cd11696  226 IHKGPIdKDNEFKSLWIERTTLVTEHSLPGILRWFEVVSREVEEIPPVENACETVENKNQELRSLISQYQADPTrninPF 305
                        250
                 ....*....|....*
gi 24580520 1951 QMVLQGCIGTTVNQG 1965
Cdd:cd11696  306 SMRLQGVIDAAVNGG 320
DHR2_DOCK4 cd11705
Dock Homology Region 2, a GEF domain, of Class B Dedicator of Cytokinesis 4; Dock4 is an ...
1737-1974 6.99e-11

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: 66.59  E-value: 6.99e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24580520 1737 EANRDFQKLSKVHGKLQEAFNRISQLQgkRVFGTYFRVGFYGGKFGD-LDQQEFIYKEPTLTKLPEIFSRLQNFYterfg 1815
Cdd:cd11705   88 ESYYDYRNLSKMRMMEASLYDKIMDQQ--RLEPEFFRVGFYGKKFPFfLRNKEFVCRGHDYERLEAFQQRMLNEF----- 160
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24580520 1816 PDSVhIIKDSNTVDINSLDPDKAYIQITYVEPYFETYEMRHRE-------TYFERNfNIKRFIYATPFTKNGK-AHGELN 1887
Cdd:cd11705  161 PHAI-AMQHANQPDETIFQAEAQYLQIYAVTPIPESQEVLQRDgvpdnikSFYKVN-HIWRFRYDRPFHKGTKdKENEFK 238
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24580520 1888 EQCKRKTILTTANHFPYVKTRIMVISRQQIVLEPIEVAIEDIQKKTLELAAATNQ----EPADPKILQMVLQGCIGTTVN 1963
Cdd:cd11705  239 SLWVERTTLTLVQSLPGISRWFEVEKREVVEMSPLENAIEVLENKNQQLRTLISQcqtrQMQNINPLTMCLNGVIDAAVN 318
                        250
                 ....*....|.
gi 24580520 1964 QGPMEMASVFL 1974
Cdd:cd11705  319 GGVSRYQEAFF 329
DHR2_DOCK3 cd11704
Dock Homology Region 2, a GEF domain, of Class B Dedicator of Cytokinesis 3; Dock3, also ...
1733-1974 1.65e-10

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: 65.42  E-value: 1.65e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24580520 1733 IPIC-------EANRDFQKLSKVHGKLQEAFNRISQLQgkRVFGTYFRVGFYGGKFgdldqqEFIYKEPTLTKLPEIFSR 1805
Cdd:cd11704   77 IPLCrelafqyESLYDYQSLSWIRKMEAAYYDNIMEQQ--RLEPEFFRVGFYGRKF------PFFLRNKEYVCRGHDYER 148
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24580520 1806 LQNFYTERFG--PDSVhIIKDSNTVDINSLDPDKAYIQITYVEP---YFETYEMRH---RETYFERNFNIKRFIYATPFT 1877
Cdd:cd11704  149 LEAFQQRMLSefPQAI-AMQHPNHPDDGILQCDAQYLQIYAVTPipdNMDVLQMDRvpdRIKSFYRVNNVRKFRYDRPFH 227
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24580520 1878 KNGK-AHGELNEQCKRKTILTTANHFPYVKTRIMVISRQQIVLEPIEVAIEDIQKKTLELAAATNQEP-----ADPKILQ 1951
Cdd:cd11704  228 KGPKdKENEFKSLWIERTTLTLTHSLPGISRWFEVERRELVEVSPLENAIQVVENKNQELRTLISQYQhkqlhGNINLLS 307
                        250       260
                 ....*....|....*....|...
gi 24580520 1952 MVLQGCIGTTVNQGPMEMASVFL 1974
Cdd:cd11704  308 MCLNGVIDAAVNGGIARYQEAFF 330
DHR2_DOCK_A cd11697
Dock Homology Region 2, a GEF domain, of Class A Dedicator of Cytokinesis proteins; DOCK ...
1771-1966 7.49e-10

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: 63.50  E-value: 7.49e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24580520 1771 YFRVGFYGGKFGD-LDQQEFIYKEPTLTKLPEIFSRLQNFYterfgpdsvhiikdSNTVDINSLDP--------DKAYIQ 1841
Cdd:cd11697  125 YFRVGYYGQGFPSfLRNKVFIYRGKEYERLSDFSARLLNQF--------------PNAELMNTLTPpgdeikesPGQYLQ 190
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24580520 1842 ITYVEPyfeTYEMRHRE----------TYFERNfNIKRFIYATPFTKNGKAHG-ELNEQCKRKTILTTANHFPYVKTRIM 1910
Cdd:cd11697  191 INKVDP---VMDERPRFkgkpvsdqilNYYKVN-EVQRFTFSRPFRRGTKDPDnEFANMWLERTTLTTAYKLPGILRWFE 266
                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 24580520 1911 VISRQQIVLEPIEVAIEDIQKKTLELAAATNQEPADPKI----LQMVLQGCIGTTVNQGP 1966
Cdd:cd11697  267 VVSTSTVEISPLENAIETMEDTNKKIRDLILQHQSDPTLpinpLSMLLNGIVDAAVMGGI 326
DHR2_DOCK2 cd11706
Dock Homology Region 2, a GEF domain, of Class A Dedicator of Cytokinesis 2; Dock2 is a ...
1683-1975 3.09e-08

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: 58.46  E-value: 3.09e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24580520 1683 SDDVLSPGEDGICLGNHFTETGLK-ALLEEASNSFQVAGMYEAMNEVYKILIPICEAN-RDFQKLSKVHGKLQEAFNRIS 1760
Cdd:cd11706   55 SDEQCASQVMQTGQQHPQTQRQLKeTLYETIIGYFDKGKMWEEAISLCKELAEQYEMEiFDYELLSQNLIQQAKFYESIM 134
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24580520 1761 QLQgkRVFGTYFRVGFYGGKFGD-LDQQEFIYKEPTLTKLPEIFSRLQNFYterfgPDSVHIIKDSNTVDINSLDPDKaY 1839
Cdd:cd11706  135 KIL--RPKPDYFAVGYYGQGFPSfLRNKVFIYRGKEYERREDFQMQLMSQF-----PNAEKLNTTSAPGDDIKNSPGQ-Y 206
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24580520 1840 IQITYVEPYFETY-EMRHRE-----TYFERNFNIKRFIYATPFTKNGK-AHGELNEQCKRKTILTTANHFPYVKTRIMVI 1912
Cdd:cd11706  207 IQCFTVQPVLEEHpRLKNKPvpdqiINFYKSNYVQRFHYSRPVRKGPVdPENEFASMWIERTTFVTAYKLPGILRWFEVT 286
                        250       260       270       280       290       300
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 24580520 1913 SRQQIVLEPIEVAIEDIQKKTLELAAATNQEPADPKI----LQMVLQGCIGTTVNQGPMEMASVFLS 1975
Cdd:cd11706  287 HMSQTTISPLENAIETMSTTNEKILMMINQYQSDESLpinpLSMLLNGIVDPAVMGGFAKYEKAFFT 353
DHR2_DOCK1 cd11707
Dock Homology Region 2, a GEF domain, of Class A Dedicator of Cytokinesis 1; Dock1, also ...
1701-1965 6.09e-07

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: 54.27  E-value: 6.09e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24580520 1701 TETGLK-ALLEEASNSFQVAGMYEAMNEVYKILIPICEANR-DFQKLSKVHGKLQEAFNRISQLqgKRVFGTYFRVGFYG 1778
Cdd:cd11707   55 TQGQLKdQLYQEIIHYFDKGKMWEEAIALGKELAEQYENEMfDYEQLSELLKKQAQFYENIVKV--IRPKPDYFAVGYYG 132
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24580520 1779 GKFGD-LDQQEFIYKEPTLTKLPEIFSRLQNFYterfgPDSVHIIKDSNTVDINSLDPDKaYIQITYVEPYFETY-EMRH 1856
Cdd:cd11707  133 QGFPTfLRNKMFIYRGKEYERREDFEARLLTQF-----PNAEKMKTTSPPGDDIKNSSGQ-YIQCFTVKPLLELPpKFQN 206
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24580520 1857 RETY-----FERNFNIKRFIYATPFTKNGK-AHGELNEQCKRKTILTTANHFPYVKTRIMVISRQQIVLEPIEVAIEDIQ 1930
Cdd:cd11707  207 KPVSeqivsFYRVNEVQRFQYSRPVRKGEKdPDNEFANMWIERTTYVTAYKLPGILRWFEVKSVFMVEISPLENAIETMQ 286
                        250       260       270
                 ....*....|....*....|....*....|....*....
gi 24580520 1931 KKTLELAAATNQEPADPKI----LQMVLQGCIGTTVNQG 1965
Cdd:cd11707  287 LTNEKINNMVQQHLNDPNLpinpLSMLLNGIVDPAVMGG 325
DHR2_DOCK5 cd11708
Dock Homology Region 2, a GEF domain, of Class A Dedicator of Cytokinesis 5; Dock5 is an ...
1700-1965 4.74e-06

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: 51.10  E-value: 4.74e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24580520 1700 FTETGLKA-LLEEASNSFQVAGMYEAMNEVYKILIPICEANR-DFQKLSKVHGKLQEAFNRIsqLQGKRVFGTYFRVGFY 1777
Cdd:cd11708   54 YTQQELKErLYQEIISFFDKGKMWEKAIELSKELADMYENQVfDYEGLGNLLKKQAQFYENI--MKAMRPQPEYFAVGYY 131
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24580520 1778 GGKFGD-LDQQEFIYKEPTLTKLPEIFSRLQNFYterfgPDSVHIIKDSNTVDiNSLDPDKAYIQITYVEPYFeTYEMRH 1856
Cdd:cd11708  132 GQGFPSfLRNKIFIYRGKEYERLEDFSLKLLTQF-----PNAEKMTSTSPPGD-EIKSSTKQYVQCFTVKPVM-NLPSHY 204
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24580520 1857 RE--------TYFERNfNIKRFIYATPFTKNGK-AHGELNEQCKRKTILTTANHFPYVKTRIMV--ISRQQIvlEPIEVA 1925
Cdd:cd11708  205 KDkpvpeqilNYYRAN-EVQQFQYSRPFRKGEKdPDNEFATMWIERTTFTTAYRFPGILKWFEVkqISTEEI--SPLENA 281
                        250       260       270       280
                 ....*....|....*....|....*....|....*....|....
gi 24580520 1926 IEDIQKKTLELAAATNQEPADPKI----LQMVLQGCIGTTVNQG 1965
Cdd:cd11708  282 IETMELTNEKISNLVQQHAWDRSLpvhpLSMLLNGIVDPAVMGG 325
 
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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