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Conserved domains on  [gi|528488072|ref|XP_001920107|]
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dedicator of cytokinesis protein 8 isoform X1 [Danio rerio]

Protein Classification

dedicator of cytokinesis protein 7( domain architecture ID 10570936)

dedicator of cytokinesis protein 7 functions as a guanine nucleotide exchange factor (GEF), which activates Rac1 and Rac3 Rho small GTPases by exchanging bound GDP for free GTP

Graphical summary

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List of domain hits

 Name Accession Description Interval E-value
DHR2_DOCK8 cd11701
Dock Homology Region 2, a GEF domain, of Class C Dedicator of Cytokinesis 8; Dock8, also ...
 1630-2051 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: 937.92  E-value: 0e+00
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528488072 1630 TSPDLRLTWLQNMAEKHNGRKCFTESAMCLVHAAALVAEYLSMLEDHKYLPVGSVTFQNISPNVLEESAVSDDILSPDED 1709
Cdd:cd11701     1 TSPDLRLTWLQNMAEKHTKRKCFTEAAMCLVHAAALVAEYLSMLEDHSYLPVGSVSFQNISSNVLEESAVSDDILSPDED 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528488072 1710 GVCSGRYFTENGLVGLLEQAAELFSNGGLFEAVNEVYKVIVPILEAHRDFRKLASTHDKLQRAFDNIIQKGHKRMFGTYF 1789
Cdd:cd11701    81 GVCSGRYFTENGLVGLLEQAAELFSTGGLYETVNEVYKIVIPILEAHRDFRKLASTHDKLQKAFDNIINKGHKRMFGTYF 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528488072 1790 RVGFYGSKFGDLDEQEFIYKEPGITHLPEISHRLENFYSQCFGDGVLEMIKDSTPVDRNKLSPNKAYIQITFVEPYFDDY 1869
Cdd:cd11701   161 RVGFYGSKFGDLDEQEFIYKEPAITKLPEISHRLEGFYGQCFGDDVVEVIKDSTPVDKSKLDPNKAYIQITFVEPYFDDY 240

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528488072 1870 EMKDRLTNFEKNFNLRRFMYTTPFTKSGRPRGELNEQYKRKTILTTMHAFPYIKTRINVIQKEEFDLTPIEVAIEDMQKK 1949
Cdd:cd11701   241 EMKDRVTYFEKNFNLRRFMYTTPFTLDGRPRGELSEQYKRKTILTTMHAFPYIKTRINVIQKEEFDLTPIEVAIEDMQKK 320

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528488072 1950 TRELAEATHREKPDAVMLQMVLQGSVTATVNQGPLEVAQVFLNEIPADPKLFRHHNKLRLCFKEFILRCGEAIEKNKQLI 2029
Cdd:cd11701   321 TRELAEATHQEPPDAKMLQMVLQGSVGATVNQGPLEVAQVFLAEIPADPKLYRHHNKLRLCFKEFIMRCGEAVEKNKRLI 400

                         410       420
                  ....*....|....*....|..
gi 528488072 2030 TPDQKEYQQEMKKNYNKLRENL 2051
Cdd:cd11701   401 TADQREYQQELKKNYNKLRENL 422
C2_Dock-C cd08696
C2 domains found in Dedicator Of CytoKinesis (Dock) class C proteins; Dock-C is one of 4 ...
 549-731 2.03e-107

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: 340.10  E-value: 2.03e-107
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528488072  549 YRNLLYVYPLRLNLTNRLTSARNITVKIQFMSGEDSSCAMPVIFGKSSGPEFLTEVYTPVTYHNRSPDFYDEIKILLPAR 628
Cdd:cd08696     1 YRNLLYVYPQSLNFSNRLGSARNIAVKVQLMSGEDESQALPVIFKGSSPEEFLTEAYTAVTYHNKSPDFYDEIKIKLPAD 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528488072  629 LTDKHHLLFTFFHISCQQKQnQTGSVEALIGYSWLPMLNNDRLQTSQQCLPIVLDKLPINYSLHTPEklpAQVPPVKWLE 708
Cdd:cd08696    81 LTDNHHLLFTFYHISCQKKQ-EGGSVETPIGYTWLPLLRNGRLQSGEFNLPVSLEKPPSNYSPDSPE---VKLPGTKWVD 156

                         170       180
                  ....*....|....*....|...
gi 528488072  709 NHKGLFNLELQAVSSVQTQDSHL 731
Cdd:cd08696   157 NHKGVFSVSVEAVSSVHTQDSYL 179
DOCK_C-D_N pfam11878
Dedicator of cytokinesis C/D, N terminal; This entry represents the N-terminal domain of the ...
 57-163 1.90e-38

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: 139.71  E-value: 1.90e-38
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528488072    57 YEAVEPVDLDEFLMSQLRSGDAEVMQELGEFPDDDLDVELVERECRTIRPTIAEEG-VELDSHVRDCVQSYTQPWLVVSR 135
Cdd:pfam11878    1 PKVVEPLDYEEFISQHLTQIENDPLRDLLLFPDDDIEVSVIPRECRTLQPTVPEEAeKEADPLVRECIKTYTSDWHVVNY 80

                           90       100       110
                   ....*....|....*....|....*....|..
gi 528488072   136 RSQGYGW----ISYSDRTDSNKILQRQTFESD 163
Cdd:pfam11878   81 KYEDYSGdfrqLPKSKRRERPEKLPKQVFEID 112
 
Name Accession Description Interval E-value
DHR2_DOCK8 cd11701
Dock Homology Region 2, a GEF domain, of Class C Dedicator of Cytokinesis 8; Dock8, also ...
 1630-2051 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: 937.92  E-value: 0e+00
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528488072 1630 TSPDLRLTWLQNMAEKHNGRKCFTESAMCLVHAAALVAEYLSMLEDHKYLPVGSVTFQNISPNVLEESAVSDDILSPDED 1709
Cdd:cd11701     1 TSPDLRLTWLQNMAEKHTKRKCFTEAAMCLVHAAALVAEYLSMLEDHSYLPVGSVSFQNISSNVLEESAVSDDILSPDED 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528488072 1710 GVCSGRYFTENGLVGLLEQAAELFSNGGLFEAVNEVYKVIVPILEAHRDFRKLASTHDKLQRAFDNIIQKGHKRMFGTYF 1789
Cdd:cd11701    81 GVCSGRYFTENGLVGLLEQAAELFSTGGLYETVNEVYKIVIPILEAHRDFRKLASTHDKLQKAFDNIINKGHKRMFGTYF 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528488072 1790 RVGFYGSKFGDLDEQEFIYKEPGITHLPEISHRLENFYSQCFGDGVLEMIKDSTPVDRNKLSPNKAYIQITFVEPYFDDY 1869
Cdd:cd11701   161 RVGFYGSKFGDLDEQEFIYKEPAITKLPEISHRLEGFYGQCFGDDVVEVIKDSTPVDKSKLDPNKAYIQITFVEPYFDDY 240

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528488072 1870 EMKDRLTNFEKNFNLRRFMYTTPFTKSGRPRGELNEQYKRKTILTTMHAFPYIKTRINVIQKEEFDLTPIEVAIEDMQKK 1949
Cdd:cd11701   241 EMKDRVTYFEKNFNLRRFMYTTPFTLDGRPRGELSEQYKRKTILTTMHAFPYIKTRINVIQKEEFDLTPIEVAIEDMQKK 320

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528488072 1950 TRELAEATHREKPDAVMLQMVLQGSVTATVNQGPLEVAQVFLNEIPADPKLFRHHNKLRLCFKEFILRCGEAIEKNKQLI 2029
Cdd:cd11701   321 TRELAEATHQEPPDAKMLQMVLQGSVGATVNQGPLEVAQVFLAEIPADPKLYRHHNKLRLCFKEFIMRCGEAVEKNKRLI 400

                         410       420
                  ....*....|....*....|..
gi 528488072 2030 TPDQKEYQQEMKKNYNKLRENL 2051
Cdd:cd11701   401 TADQREYQQELKKNYNKLRENL 422
C2_Dock-C cd08696
C2 domains found in Dedicator Of CytoKinesis (Dock) class C proteins; Dock-C is one of 4 ...
 549-731 2.03e-107

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: 340.10  E-value: 2.03e-107
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528488072  549 YRNLLYVYPLRLNLTNRLTSARNITVKIQFMSGEDSSCAMPVIFGKSSGPEFLTEVYTPVTYHNRSPDFYDEIKILLPAR 628
Cdd:cd08696     1 YRNLLYVYPQSLNFSNRLGSARNIAVKVQLMSGEDESQALPVIFKGSSPEEFLTEAYTAVTYHNKSPDFYDEIKIKLPAD 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528488072  629 LTDKHHLLFTFFHISCQQKQnQTGSVEALIGYSWLPMLNNDRLQTSQQCLPIVLDKLPINYSLHTPEklpAQVPPVKWLE 708
Cdd:cd08696    81 LTDNHHLLFTFYHISCQKKQ-EGGSVETPIGYTWLPLLRNGRLQSGEFNLPVSLEKPPSNYSPDSPE---VKLPGTKWVD 156

                         170       180
                  ....*....|....*....|...
gi 528488072  709 NHKGLFNLELQAVSSVQTQDSHL 731
Cdd:cd08696   157 NHKGVFSVSVEAVSSVHTQDSYL 179
DHR-2_Lobe_A pfam06920
DHR-2, Lobe A; This entry represents a conserved region within a number of eukaryotic ...
 1619-1778 9.52e-66

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: 219.47  E-value: 9.52e-66
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528488072  1619 DLMYRIAKGYQTSPDLRLTWLQNMAEKHNGRKCFTESAMCLVHAAALVAEYLSMLeDHKYLPVGSVTFQNISPNVL-EES 1697
Cdd:pfam06920    1 DLQYSLANSYKSSPDLRLTWLENLAEKHLENGNFSEAAQCLIHIAALIAEYLKLK-GKIPNPLGASAFEKISPNILrEES 79

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528488072  1698 AVSDDilspdeDGVCSGRYFTENGLVGLLEQAAELFSNGGLFEAVNEVYKVIVPILEAHRDFRKLASTHDKLQRAFDNII 1777
Cdd:pfam06920   80 ALKDD------SGVCDSPHFTEDGLVGLLEEAIDYLDKAERYELAIELYKLLLPIYESRRDYKKLSECHGKLAEAYEKIV 153


                   .
gi 528488072  1778 Q 1778
Cdd:pfam06920  154 E 154
DOCK-C2 pfam14429
C2 domain in Dock180 and Zizimin proteins; The Dock180/Dock1 and Zizimin proteins are atypical ...
 546-730 1.38e-59

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: 203.22  E-value: 1.38e-59
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528488072   546 HNIYRNLLYVYPLRLNLTNRL-TSARNITVKIQFMsgEDSSCAMP-VIFGKSSGPeFLTEVYTPVTYHNRSPDFYDEIKI 623
Cdd:pfam14429    1 PGDYRNDLYVTPKSGNFSKQKkSSARNIEVTVEVR--DSDGEPLPnCIYGGSGGP-FVTEFKSTVYYHNKSPTWYEEIKI 77

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528488072   624 LLPARLTDKHHLLFTFFHISCQQKQNqtgSVEALIGYSWLPMLNNDR--LQTSQQCLPI-VLDKLPINYsLHTPEKLPAQ 700
Cdd:pfam14429   78 ALPAELTPKHHLLFTFYHVSCDEKKD---KVEKPFGYAFLPLLDDDGafLRDGEHTLPVyKYDELPPGY-LSLPWSSGGE 153

                          170       180       190
                   ....*....|....*....|....*....|..
gi 528488072   701 VPPVKW--LENHKGLFNLELQAVSSVQTQDSH 730
Cdd:pfam14429  154 KESSALpgLKGGKDLFKVRTRLCSTKYTQDEH 185
DOCK_C-D_N pfam11878
Dedicator of cytokinesis C/D, N terminal; This entry represents the N-terminal domain of the ...
 57-163 1.90e-38

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: 139.71  E-value: 1.90e-38
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528488072    57 YEAVEPVDLDEFLMSQLRSGDAEVMQELGEFPDDDLDVELVERECRTIRPTIAEEG-VELDSHVRDCVQSYTQPWLVVSR 135
Cdd:pfam11878    1 PKVVEPLDYEEFISQHLTQIENDPLRDLLLFPDDDIEVSVIPRECRTLQPTVPEEAeKEADPLVRECIKTYTSDWHVVNY 80

                           90       100       110
                   ....*....|....*....|....*....|..
gi 528488072   136 RSQGYGW----ISYSDRTDSNKILQRQTFESD 163
Cdd:pfam11878   81 KYEDYSGdfrqLPKSKRRERPEKLPKQVFEID 112
 
Name Accession Description Interval E-value
DHR2_DOCK8 cd11701
Dock Homology Region 2, a GEF domain, of Class C Dedicator of Cytokinesis 8; Dock8, also ...
 1630-2051 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: 937.92  E-value: 0e+00
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528488072 1630 TSPDLRLTWLQNMAEKHNGRKCFTESAMCLVHAAALVAEYLSMLEDHKYLPVGSVTFQNISPNVLEESAVSDDILSPDED 1709
Cdd:cd11701     1 TSPDLRLTWLQNMAEKHTKRKCFTEAAMCLVHAAALVAEYLSMLEDHSYLPVGSVSFQNISSNVLEESAVSDDILSPDED 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528488072 1710 GVCSGRYFTENGLVGLLEQAAELFSNGGLFEAVNEVYKVIVPILEAHRDFRKLASTHDKLQRAFDNIIQKGHKRMFGTYF 1789
Cdd:cd11701    81 GVCSGRYFTENGLVGLLEQAAELFSTGGLYETVNEVYKIVIPILEAHRDFRKLASTHDKLQKAFDNIINKGHKRMFGTYF 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528488072 1790 RVGFYGSKFGDLDEQEFIYKEPGITHLPEISHRLENFYSQCFGDGVLEMIKDSTPVDRNKLSPNKAYIQITFVEPYFDDY 1869
Cdd:cd11701   161 RVGFYGSKFGDLDEQEFIYKEPAITKLPEISHRLEGFYGQCFGDDVVEVIKDSTPVDKSKLDPNKAYIQITFVEPYFDDY 240

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528488072 1870 EMKDRLTNFEKNFNLRRFMYTTPFTKSGRPRGELNEQYKRKTILTTMHAFPYIKTRINVIQKEEFDLTPIEVAIEDMQKK 1949
Cdd:cd11701   241 EMKDRVTYFEKNFNLRRFMYTTPFTLDGRPRGELSEQYKRKTILTTMHAFPYIKTRINVIQKEEFDLTPIEVAIEDMQKK 320

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528488072 1950 TRELAEATHREKPDAVMLQMVLQGSVTATVNQGPLEVAQVFLNEIPADPKLFRHHNKLRLCFKEFILRCGEAIEKNKQLI 2029
Cdd:cd11701   321 TRELAEATHQEPPDAKMLQMVLQGSVGATVNQGPLEVAQVFLAEIPADPKLYRHHNKLRLCFKEFIMRCGEAVEKNKRLI 400

                         410       420
                  ....*....|....*....|..
gi 528488072 2030 TPDQKEYQQEMKKNYNKLRENL 2051
Cdd:cd11701   401 TADQREYQQELKKNYNKLRENL 422
DHR2_DOCK6 cd11702
Dock Homology Region 2, a GEF domain, of Class C Dedicator of Cytokinesis 6; Dock6, also ...
 1631-2051 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: 738.74  E-value: 0e+00
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528488072 1631 SPDLRLTWLQNMAEKHNGRKCFTESAMCLVHAAALVAEYLSMLEDHKYLPVGSVTFQNISPNVLEESAVSDDILSPDEDG 1710
Cdd:cd11702     1 SPDLRLTWLQNMAGKHSERGNHAEAAHCLVHSAALVAEYLSMLEDCRHLPVGCVSFQNISSNVLEESAVSDDILSPDEEG 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528488072 1711 VCSGRYFTENGLVGLLEQAAELFSNGGLFEAVNEVYKVIVPILEAHRDFRKLASTHDKLQRAFDNIIQK--GHKRMFGTY 1788
Cdd:cd11702    81 ICSGKYFTELGLVGLLEQAAASFNMGGLYEAVNEVYKILIPIHEANRDYKKLAVVHGKLQEAFNKITNQssGWERMFGTY 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528488072 1789 FRVGFYGSKFGDLDEQEFIYKEPGITHLPEISHRLENFYSQCFGDGVLEMIKDSTPVDRNKLSPNKAYIQITFVEPYFDD 1868
Cdd:cd11702   161 FRVGFYGCKFGDLDEQEFVYKEPSITKLAEISHRLEEFYTERFGDEVVEIIKDSNPVDKSKLDPNKAYIQITYVEPFFDT 240

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528488072 1869 YEMKDRLTNFEKNFNLRRFMYTTPFTKSGRPRGELNEQYKRKTILTTMHAFPYIKTRINVIQKEEFDLTPIEVAIEDMQK 1948
Cdd:cd11702   241 YELKDRVTYFDKNYNLRTFLFCTPFTLDGRAHGELHEQYKRKTILTTSHAFPYIKTRINVLHREEIVLIPVEVAIEDMQK 320

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528488072 1949 KTRELAEATHREKPDAVMLQMVLQGSVTATVNQGPLEVAQVFLNEIPADPKLFRHHNKLRLCFKEFILRCGEAIEKNKQL 2028
Cdd:cd11702   321 KTQELAFATHQDPADAKMLQMVLQGCVGTTVNQGPLEVAQVFLSEIPEDPKLFRHHNKLRLCFKDFTKRCEDALRKNKAL 400

                         410       420
                  ....*....|....*....|...
gi 528488072 2029 ITPDQKEYQQEMKKNYNKLRENL 2051
Cdd:cd11702   401 IGPDQKEYHRELERNYQRLREAL 423
DHR2_DOCK7 cd11703
Dock Homology Region 2, a GEF domain, of Class C Dedicator of Cytokinesis 7; Dock7, also ...
 1592-2064 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: 731.11  E-value: 0e+00
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528488072 1592 ELLRNLNSILSDTVKMKEFQKDPEMLMDLMYRIAKGYQTSPDLRLTWLQNMAEKHNGRKCFTESAMCLVHAAALVAEYLS 1671
Cdd:cd11703     1 DLVFNLHMILSDTVKMKEHQEDPEMLIDLMYRIAKGYQTSPDLRLTWLQNMAGKHSERSNHAEAAQCLVHSAALVAEYLS 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528488072 1672 MLEDHKYLPVGSVTFQNISPNVLEESAVSDDILSPDEDGVCSGRYFTENGLVGLLEQAAELFSNGGLFEAVNEVYKVIVP 1751
Cdd:cd11703    81 MLEDRKYLPVGCVTFQNISSNVLEESAVSDDVVSPDEEGICSGKYFTEAGLVGLLEQAAASFSMAGMYEAVNEVYKVLIP 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528488072 1752 ILEAHRDFRKLASTHDKLQRAFDNIIQKGHKRMFGTYFRVGFYGSKFGDLDEQEFIYKEPGITHLPEISHRLENFYSQCF 1831
Cdd:cd11703   161 IHEANRDAKKLATIHGKLQEAFSKIVHQDGKRMFGTYFRVGFYGTKFGDLDEQEFVYKEPAITKLAEISHRLEGFYGERF 240

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528488072 1832 GDGVLEMIKDSTPVDRNKLSPNKAYIQITFVEPYFDDYEMKDRLTNFEKNFNLRRFMYTTPFTKSGRPRGELNEQYKRKT 1911
Cdd:cd11703   241 GEDVVEVIKDSNPVDKCKLDPNKAFIQITYVEPYFDTYEMKDRITYFDKNYNLRRFMYCTPFTLDGRAHGELHEQFKRKT 320

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528488072 1912 ILTTMHAFPYIKTRINVIQKEEFDLTPIEVAIEDMQKKTRELAEATHREKPDAVMLQMVLQGSVTATVNQGPLEVAQVFL 1991
Cdd:cd11703   321 ILTTSHAFPYIKTRINVIHKEEIILTPIEVAIEDMQKKTQELAFATHQDPADPKMLQMVLQGSVGTTVNQGPLEVAQVFL 400

                         410       420       430       440       450       460       470
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 528488072 1992 NEIPADPKLFRHHNKLRLCFKEFILRCGEAIEKNKQLITPDQKEYQQEMKKNYNKLRENLRPMLERKIPELYK 2064
Cdd:cd11703   401 SEIPSDPKLFRHHNKLRLCFKDFTKRCEDALRKNKSLIGPDQKEYQRELERNYHRLKEALQPLINRKIPQLYK 473
DHR2_DOCK_C cd11695
Dock Homology Region 2, a GEF domain, of Class C Dedicator of Cytokinesis proteins; DOCK ...
 1631-2051 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: 679.41  E-value: 0e+00
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528488072 1631 SPDLRLTWLQNMAEKHNGRKCFTESAMCLVHAAALvaeylsmledhkylpvgsvtfqnispnvleesavsddilspdedg 1710
Cdd:cd11695     1 SPDLRLTWLQNMAEKHYERKNFAEAAQCLVHAAAL--------------------------------------------- 35

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528488072 1711 vcsgryftenGLVGLLEQAAELFSNGGLFEAVNEVYKVIVPILEAHRDFRKLASTHDKLQRAFDNIIQK-GHKRMFGTYF 1789
Cdd:cd11695    36 ----------GLVGLLEQAAESFSKAGMYEAVNEVYKLLIPILEANRDYKKLAEIHGKLQDAFTKIEKQqGGKRMFGTYF 105

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528488072 1790 RVGFYGSKFGDLDEQEFIYKEPGITHLPEISHRLENFYSQCFGDGVLEMIKDSTPVDRNKLSPNKAYIQITFVEPYFDDY 1869
Cdd:cd11695   106 RVGFYGSKFGDLDGKEFIYKEPAITKLPEISHRLETFYGERFGEERVEVIKDSNPVDTSKLDPDKAYIQITYVEPYFDEY 185

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528488072 1870 EMKDRLTNFEKNFNLRRFMYTTPFTKSGRPRGELNEQYKRKTILTTMHAFPYIKTRINVIQKEEFDLTPIEVAIEDMQKK 1949
Cdd:cd11695   186 ELKERTTYFERNYNLRRFMYATPFTPDGKAHGELAEQYKRKTILTTENSFPYVKTRLQVVNREEIVLTPIEVAIEDVQKK 265

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528488072 1950 TRELAEATHREKPDAVMLQMVLQGSVTATVNQGPLEVAQVFLNEIPADPK-LFRHHNKLRLCFKEFILRCGEAIEKNKQL 2028
Cdd:cd11695   266 TRELAAATTQEPPDPKMLQMVLQGSIGTTVNQGPLEVANVFLSDIPLDPKeLDRHQNKLRLCFKEFSKKCYDALEKNKEL 345

                         410       420
                  ....*....|....*....|...
gi 528488072 2029 ITPDQKEYQQEMKKNYNKLRENL 2051
Cdd:cd11695   346 IGPDQKEYQKELERNYENFKEKL 368
DHR2_DOCK_D cd11694
Dock Homology Region 2, a GEF domain, of Class D Dedicator of Cytokinesis proteins; DOCK ...
 1633-2051 4.08e-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: 413.27  E-value: 4.08e-130
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528488072 1633 DLRLTWLQNMAEKHNGRKCFTESAMCLVHAAALVAEYLSMledhkylpvgsvtfqnispnvleesavsddilspdedgvc 1712
Cdd:cd11694     1 ELRKTWLESMARIHEKNGNFSEAAMCYIHIAALVAEYLKR---------------------------------------- 40

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528488072 1713 sgryftENGLVGLLEQAAELFSNGGLFEAVNEVYKVIVPILEAHRDFRKLASTHDKLQRAFDNIIQKGH--KRMFGTYFR 1790
Cdd:cd11694    41 ------KDLLLELLEACVEGLWKAERYELLGELYKLIIPIYEKRRDFEQLADCYRTLHRAYEKVVEVMEsgKRLLGTYYR 114

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528488072 1791 VGFYG-SKFGDLDEQEFIYKEPGITHLPEISHRLENFYSQCFGDGVLEMIKDSTPVDRNKLSPNKAYIQITFVEPYFDDY 1869
Cdd:cd11694   115 VAFYGqAFFEEEDGKEYIYKEPKVTSLSEISERLLKLYGDKFGSENVKLIQDSGKVNPKDLDPKYAYIQVTHVTPYFDEK 194

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528488072 1870 EMKDRLTNFEKNFNLRRFMYTTPFTKSGRPRGELNEQYKRKTILTTMHAFPYIKTRINVIQKEEFDLTPIEVAIEDMQKK 1949
Cdd:cd11694   195 ELEDRKTEFERNHNIRRFVFETPFTLSGKARGAVEEQWKRRTILTTSHSFPYVKKRIPVVQREIIELSPIEVAIDEMQSK 274

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528488072 1950 TRELAEATHREKPDAVMLQMVLQGSVTATVNQGPLEVAQVFLNEiPADPKLFRHH-NKLRLCFKEFILRCGEAIEKNKQL 2028
Cdd:cd11694   275 VKELEELISTEPVDMKKLQLRLQGSVSVQVNAGPLAYARAFLEP-TTVKNYPDDQvEDLKDVFRDFIKACGQALELNERL 353

                         410       420
                  ....*....|....*....|...
gi 528488072 2029 ITPDQKEYQQEMKKNYNKLRENL 2051
Cdd:cd11694   354 IKEDQREYHEVLKENYRKMVKEL 376
DHR2_DOCK11 cd11700
Dock Homology Region 2, a GEF domain, of Class D Dedicator of Cytokinesis 11; Dock11, also ...
 1632-2051 5.46e-117

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: 377.41  E-value: 5.46e-117
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528488072 1632 PDLRLTWLQNMAEKHNGRKCFTESAMCLVHAAALVAEYLsmlEDHKYLPVGSVTFQNISPNVLEESAVSDDILSPDEdgv 1711
Cdd:cd11700     1 PELRKTWLDSMAKIHVKNGDFSEAAMCYVHVAALVAEFL---HRKKLFPSGCAAFKKITPNIDEEGAMKEDIGMMDV--- 74

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528488072 1712 csgrYFTENGLVGLLEQAAELFSNGGLFEAVNEVYKVIVPILEAHRDFRKLASTHDKLQRAFDNIIQKGH--KRMFGTYF 1789
Cdd:cd11700    75 ----HYSEEVLVELLEQCVDGLWKAERYELISEISKLIIPIYEKRREFEKLTQLYRTLHGAYAKILEVMHtgKRLLGTFF 150

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528488072 1790 RVGFYG-SKFGDLDEQEFIYKEPGITHLPEISHRLENFYSQCFGDGVLEMIKDSTPVDRNKLSPNKAYIQITFVEPYFDD 1868
Cdd:cd11700   151 RVAFYGqGFFEEEDGKEYIYKEPKLTGLSEISHRLLKLYGEKFGSENVKIIQDSNKVNQKDLDPKYAHIQVTYVKPYFDD 230

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528488072 1869 YEMKDRLTNFEKNFNLRRFMYTTPFTKSGRPRGELNEQYKRKTILTTMHAFPYIKTRINVIQKEEFDLTPIEVAIEDMQK 1948
Cdd:cd11700   231 KEMAERKTEFERNHNIQRFVFETPYTLSGKKQGGVEEQCKRRTILTTANSFPYVKKRIPVNGEKQTNLKPIDVATDEIKD 310

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528488072 1949 KTRELAEATHREKPDAVMLQMVLQGSVTATVNQGPLEVAQVFLNEIPADPKLFRHHNKLRLCFKEFILRCGEAIEKNKQL 2028
Cdd:cd11700   311 KTAELQKLCSNQDVDMIQLQLKLQGCVSVQVNAGPLAYARAFLDDSQASKYPNKKVKELKEMFRKFIQACSIALELNERL 390

                         410       420
                  ....*....|....*....|...
gi 528488072 2029 ITPDQKEYQQEMKKNYNKLRENL 2051
Cdd:cd11700   391 IKEDQVEYHEGLKSNFRDMVKEL 413
DHR2_DOCK9 cd11698
Dock Homology Region 2, a GEF domain, of Class D Dedicator of Cytokinesis 9; Dock9, also ...
 1633-2051 1.96e-114

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: 370.13  E-value: 1.96e-114
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528488072 1633 DLRLTWLQNMAEKHNGRKCFTESAMCLVHAAALVAEYLSMledHKYLPVGSVTFQNISPNVLEESAVSDDILSPDEdgvc 1712
Cdd:cd11698     1 ELRKTWLDSMARIHVKNGDLSEAAMCYVHVAALVAEYLTR---KGMFRQGCTAFRVITPNIDEEASMMEDVGMQDV---- 73

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528488072 1713 sgrYFTENGLVGLLEQAAELFSNGGLFEAVNEVYKVIVPILEAHRDFRKLASTHDKLQRAFDNIIQKGH--KRMFGTYFR 1790
Cdd:cd11698    74 ---HFNEDVLMELLEQCADGLWKAERYELIADIYKLIIPIYEKRRDFERLAHLYDTLHRAYSKVTEVMHsgKRLLGTYFR 150

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528488072 1791 VGFYGSKF-GDLDEQEFIYKEPGITHLPEISHRLENFYSQCFGDGVLEMIKDSTPVDRNKLSPNKAYIQITFVEPYFDDY 1869
Cdd:cd11698   151 VAFFGQGFfEDEDGKEYIYKEPKLTPLSEISQRLLKLYSDKFGSENVKMIQDSGKVNPKDLDSKYAYIQVTHVTPYFDEK 230

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528488072 1870 EMKDRLTNFEKNFNLRRFMYTTPFTKSGRPRGELNEQYKRKTILTTMHAFPYIKTRINVIQKEEFDLTPIEVAIEDMQKK 1949
Cdd:cd11698   231 ELQERKTDFERSHNIRRFMFEMPFTQSGKRQGGVEEQCKRRTILTAIHCFPYVKKRIPVMYQHHTDLNPIEVAIDEMSKK 310

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528488072 1950 TRELAEATHREKPDAVMLQMVLQGSVTATVNQGPLEVAQVFLNEIPADPKLFRHHNKLRLCFKEFILRCGEAIEKNKQLI 2029
Cdd:cd11698   311 VAELRQLCSSAEVDMIKLQLKLQGSVSVQVNAGPLAYARAFLDDTNTKRYPDNKVKLLKEVFRQFVEACGQALAVNERLI 390

                         410       420
                  ....*....|....*....|..
gi 528488072 2030 TPDQKEYQQEMKKNYNKLRENL 2051
Cdd:cd11698   391 KEDQLEYQEEMKANYREMAKEL 412
DHR2_DOCK cd11684
Dock Homology Region 2, a GEF domain, of Dedicator of Cytokinesis proteins; DOCK proteins ...
 1633-2051 2.34e-113

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: 366.24  E-value: 2.34e-113
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528488072 1633 DLRLTWLQNMAEKHNGRKCFTESAMCLVHAAALVAEYLSMLEDHKylpvgsvtfqnispnvleesavsddilspdEDGVC 1712
Cdd:cd11684     1 ELYIRYLHKLADLHEERGNYVEAALCLLLHADLYAWDLKALVPAL------------------------------AESLS 50

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528488072 1713 SGRYFTENGLVGLLEQAAELFSNGGLFEAVNEVYKVIVPILEAHRDFRKLASTHDKLQRAFDNIIQKghKRMFGTYFRVG 1792
Cdd:cd11684    51 FPEQTSFERKEALYKKAIDLFDKGKAWEFAIALYKELIPQYENNFDYAKLSEVHRKIAKLYEKIAEK--DRLFPTYFRVG 128

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528488072 1793 FYGSKF-GDLDEQEFIYKEPGITHLPEISHRLENFYSQCfgdgvlEMIKDSTPVDRNKLSPNKAYIQITFVEPYFDDYEM 1871
Cdd:cd11684   129 FYGKGFpESLRGKEFIYRGPEFERLGDFCERLKSLYPGA------EIIQSSEEPDDEILDSEGQYIQITSVEPYFDDEDL 202

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528488072 1872 K----DRLTNFEKNFNLRRFMYTTPFTKSGRPR-GELNEQYKRKTILTTMHAFPYIKTRINVIQKEEFDLTPIEVAIEDM 1946
Cdd:cd11684   203 VsraaPGVRQFYRNNNINTFVYERPFTKGGKKSqNEITDQWKERTILTTEESFPTILRRSEVVSIEEIELSPIENAIEDI 282

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528488072 1947 QKKTRELAEATHR----EKPDAVMLQMVLQGSVTATVNQGPLEVAQVFLNEIPADPKLFRHH-NKLRLCFKEFILRCGEA 2021
Cdd:cd11684   283 EKKTEELRSLINKyrsgDSPNVNPLQMLLQGTVDAAVNGGPVAYAEAFLSEEYLSNYPEAEKvKKLKEAFEEFLEILKRG 362

                         410       420       430
                  ....*....|....*....|....*....|
gi 528488072 2022 IEKNKQLITPDQKEYQQEMKKNYNKLRENL 2051
Cdd:cd11684   363 LALHAKLCPPEMAPLHEELEEGFEKLFKEL 392
C2_Dock-C cd08696
C2 domains found in Dedicator Of CytoKinesis (Dock) class C proteins; Dock-C is one of 4 ...
 549-731 2.03e-107

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: 340.10  E-value: 2.03e-107
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528488072  549 YRNLLYVYPLRLNLTNRLTSARNITVKIQFMSGEDSSCAMPVIFGKSSGPEFLTEVYTPVTYHNRSPDFYDEIKILLPAR 628
Cdd:cd08696     1 YRNLLYVYPQSLNFSNRLGSARNIAVKVQLMSGEDESQALPVIFKGSSPEEFLTEAYTAVTYHNKSPDFYDEIKIKLPAD 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528488072  629 LTDKHHLLFTFFHISCQQKQnQTGSVEALIGYSWLPMLNNDRLQTSQQCLPIVLDKLPINYSLHTPEklpAQVPPVKWLE 708
Cdd:cd08696    81 LTDNHHLLFTFYHISCQKKQ-EGGSVETPIGYTWLPLLRNGRLQSGEFNLPVSLEKPPSNYSPDSPE---VKLPGTKWVD 156

                         170       180
                  ....*....|....*....|...
gi 528488072  709 NHKGLFNLELQAVSSVQTQDSHL 731
Cdd:cd08696   157 NHKGVFSVSVEAVSSVHTQDSYL 179
DHR2_DOCK10 cd11699
Dock Homology Region 2, a GEF domain, of Class D Dedicator of Cytokinesis 10; Dock10, also ...
 1632-2051 3.87e-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: 347.80  E-value: 3.87e-106
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528488072 1632 PDLRLTWLQNMAEKHNGRKCFTESAMCLVHAAALVAEYL--------------SMLEDHKYLP----------------V 1681
Cdd:cd11699     1 PELRRTWLESMAKIHARNGDLSEAAMCYIHIAALIAEYLkrkgywkmekictsSMLPEDSQVYdsnlllttstggsmfsM 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528488072 1682 GSVTFQNISPNVLEESAVSDDILSPDEDgvcsgryFTENGLVGLLEQAAELFSNGGLFEAVNEVYKVIVPILEAHRDFRK 1761
Cdd:cd11699    81 GWPAFLSITPNIKEEGAMKEDSGMQDTP-------YNENTLVEQLELCVDYLWKSERYELIADVNKPVIAVFEKQRDFKR 153

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528488072 1762 LASTHDKLQRAFDNIIQ--KGHKRMFGTYFRVGFYGSKFGDLDE-QEFIYKEPGITHLPEISHRLENFYSQCFGDGVLEM 1838
Cdd:cd11699   154 LSELYYDIHRSYLKVAEvvNSEKRLFGRYYRVAFYGQGFFEEEEgKEYIYKEPKLTGLSEISQRLLKLYADKFGADNVKI 233

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528488072 1839 IKDSTPVDRNKLSPNKAYIQITFVEPYFDDYEMKDRLTNFEKNFNLRRFMYTTPFTKSGRPRGELNEQYKRKTILTTMHA 1918
Cdd:cd11699   234 IQDSNKVNPKELDPKFAYIQVTYVTPYFDEKEQEDRKTDFEMHHNINRFVFETPFTLSGKKHGGVEEQCKRRTILTTSHS 313

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528488072 1919 FPYIKTRINVIQKEEFDLTPIEVAIEDMQKKTRELAEATHREKPDAVMLQMVLQGSVTATVNQGPLEVAQVFLNEIPADP 1998
Cdd:cd11699   314 FPYVKKRIQVVSQTSTELNPIEVAIDEMSKKVSELNQLCTMEEVDMIRLQLKLQGSVSVKVNAGPMAYARAFLEETNAKK 393

                         410       420       430       440       450
                  ....*....|....*....|....*....|....*....|....*....|...
gi 528488072 1999 KLFRHHNKLRLCFKEFILRCGEAIEKNKQLITPDQKEYQQEMKKNYNKLRENL 2051
Cdd:cd11699   394 YPDNQVKLLKEIFRQFAEACGQALDVNERLIKEDQLEYQEEMRSHYRDMLSEL 446
DHR-2_Lobe_A pfam06920
DHR-2, Lobe A; This entry represents a conserved region within a number of eukaryotic ...
 1619-1778 9.52e-66

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: 219.47  E-value: 9.52e-66
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528488072  1619 DLMYRIAKGYQTSPDLRLTWLQNMAEKHNGRKCFTESAMCLVHAAALVAEYLSMLeDHKYLPVGSVTFQNISPNVL-EES 1697
Cdd:pfam06920    1 DLQYSLANSYKSSPDLRLTWLENLAEKHLENGNFSEAAQCLIHIAALIAEYLKLK-GKIPNPLGASAFEKISPNILrEES 79

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528488072  1698 AVSDDilspdeDGVCSGRYFTENGLVGLLEQAAELFSNGGLFEAVNEVYKVIVPILEAHRDFRKLASTHDKLQRAFDNII 1777
Cdd:pfam06920   80 ALKDD------SGVCDSPHFTEDGLVGLLEEAIDYLDKAERYELAIELYKLLLPIYESRRDYKKLSECHGKLAEAYEKIV 153


                   .
gi 528488072  1778 Q 1778
Cdd:pfam06920  154 E 154
DOCK-C2 pfam14429
C2 domain in Dock180 and Zizimin proteins; The Dock180/Dock1 and Zizimin proteins are atypical ...
 546-730 1.38e-59

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: 203.22  E-value: 1.38e-59
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528488072   546 HNIYRNLLYVYPLRLNLTNRL-TSARNITVKIQFMsgEDSSCAMP-VIFGKSSGPeFLTEVYTPVTYHNRSPDFYDEIKI 623
Cdd:pfam14429    1 PGDYRNDLYVTPKSGNFSKQKkSSARNIEVTVEVR--DSDGEPLPnCIYGGSGGP-FVTEFKSTVYYHNKSPTWYEEIKI 77

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528488072   624 LLPARLTDKHHLLFTFFHISCQQKQNqtgSVEALIGYSWLPMLNNDR--LQTSQQCLPI-VLDKLPINYsLHTPEKLPAQ 700
Cdd:pfam14429   78 ALPAELTPKHHLLFTFYHVSCDEKKD---KVEKPFGYAFLPLLDDDGafLRDGEHTLPVyKYDELPPGY-LSLPWSSGGE 153

                          170       180       190
                   ....*....|....*....|....*....|..
gi 528488072   701 VPPVKW--LENHKGLFNLELQAVSSVQTQDSH 730
Cdd:pfam14429  154 KESSALpgLKGGKDLFKVRTRLCSTKYTQDEH 185
C2_Dock-D cd08697
C2 domains found in Dedicator Of CytoKinesis (Dock) class C proteins; Dock-D is one of 4 ...
 549-731 7.87e-50

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: 175.20  E-value: 7.87e-50
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528488072  549 YRNLLYVYPLRLNLTNR--LTSARNITVKIQFMSGEDSScAMPV--IFGKSSGPeFLTEVYTPVTYHNRSPDFYDEIKIL 624
Cdd:cd08697     1 YKNHLYVYPLHLKYDSQktFAKARNIAVCIEFRDSDEED-AKPLkcIYYGPGGG-FTTSAYAAVLHHNQNPEFYDEIKIE 78

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528488072  625 LPARLTDKHHLLFTFFHISCQQ--KQNQTGSVEALIGYSWLPML-NNDRLQTSQQCLPIVLdkLPINYSLHTPEKLPaQV 701
Cdd:cd08697    79 LPTQLHEKHHLLFTFYHVSCDInkKGKKKDGVETPVGYAWLPLLkDKGRLNSEEQTPPVAN--LLPNYPDGYLSIQP-HG 155

                         170       180       190
                  ....*....|....*....|....*....|
gi 528488072  702 PPVKWLENHKGLFNLELQAVSSVQTQDSHL 731
Cdd:cd08697   156 PEVKWVDGGKPLFKVSTHLVSTVYTQDQHL 185
DHR-2_Lobe_C pfam20421
DHR-2, Lobe C; DOCK (dedicator of cytokinesis) proteins are guanine nucleotide exchange ...
 1952-2054 9.46e-43

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: 151.59  E-value: 9.46e-43
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528488072  1952 ELAEATHREKPDAVMLQMVLQGSVTATVNQGPLEVAQVFLNEIPADPKLFRHHNKLRLCFKEFILRCGEAIEKNKQLITP 2031
Cdd:pfam20421    1 ELEAAINAPPPNIKTLQMVLQGSVDVQVNAGPLEYAEAFLSEKNVDNYPAEKVEKLKEEFRDFLKVCGEALRLNKKLISE 80

                           90       100
                   ....*....|....*....|...
gi 528488072  2032 DQKEYQQEMKKNYNKLRENLRPM 2054
Cdd:pfam20421   81 DQREYQEELEEGFEKLKEKLEPY 103
C2_DOCK180_related cd08679
C2 domains found in Dedicator Of CytoKinesis 1 (DOCK 180) and related proteins; Dock180 was ...
 549-731 8.66e-42

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: 152.10  E-value: 8.66e-42
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528488072  549 YRNLLYVYPLRLNLTNRLTSARNITVKIQFMSGEDSSCAmPVIFGKSSGPEFLTEvYTPVTYHNRSPDFYDEIKILLPAR 628
Cdd:cd08679     1 LRNDLYVYPQSGELSKAKSKGRNIEITVEVRDDDGDIIE-PCISAPGSGSELRSE-YTSVVYYHKNPVFNDEIKIQLPAD 78

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528488072  629 LTDKHHLLFTFFHISCQQKQNQtgSVEALIGYSWLPMLNNDR--LQTSQQCLPI--VLDKLPINYSLHTPeklpaQVPPV 704
Cdd:cd08679    79 LTPQHHLLFTFYHVSSKKKQGD--KEETPFGYAFLPLMDKDGafIKDGDHTLPVykYDKRPDVGPSGYLS-----LPSTL 151

                         170       180
                  ....*....|....*....|....*..
gi 528488072  705 KWLENHKGLFNLELQAVSSVQTQDSHL 731
Cdd:cd08679   152 ANGKSSKDTFKIKTRLCSTILTQDKSL 178
DOCK_C-D_N pfam11878
Dedicator of cytokinesis C/D, N terminal; This entry represents the N-terminal domain of the ...
 57-163 1.90e-38

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: 139.71  E-value: 1.90e-38
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528488072    57 YEAVEPVDLDEFLMSQLRSGDAEVMQELGEFPDDDLDVELVERECRTIRPTIAEEG-VELDSHVRDCVQSYTQPWLVVSR 135
Cdd:pfam11878    1 PKVVEPLDYEEFISQHLTQIENDPLRDLLLFPDDDIEVSVIPRECRTLQPTVPEEAeKEADPLVRECIKTYTSDWHVVNY 80

                           90       100       110
                   ....*....|....*....|....*....|..
gi 528488072   136 RSQGYGW----ISYSDRTDSNKILQRQTFESD 163
Cdd:pfam11878   81 KYEDYSGdfrqLPKSKRRERPEKLPKQVFEID 112
DHR-2_Lobe_B pfam20422
DHR-2, Lobe B; DOCK (dedicator of cytokinesis) proteins are guanine nucleotide exchange ...
 1842-1918 6.25e-37

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: 134.27  E-value: 6.25e-37
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 528488072  1842 STPVDRNKLSPNKAYIQITFVEPYFDDYEMKDRLTNFEKNFNLRRFMYTTPFTKSGRPRGELNEQYKRKTILTTMHA 1918
Cdd:pfam20422    1 SNPVDESILDPDKAYIQITSVEPYFDDSELNDRVTYFERNNNVNRFVFETPFTKSGKAQGEFEEQWKRRTILTTEHS 77
DHR2_DOCK_A cd11697
Dock Homology Region 2, a GEF domain, of Class A Dedicator of Cytokinesis proteins; DOCK ...
 1731-2050 8.13e-21

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: 97.40  E-value: 8.13e-21
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528488072 1731 ELFSNGGLFEAVNEVYKVIVPILEAHR-DFRKLASTHDKLQRAFDNIIQKGhkRMFGTYFRVGFYGSKFGD-LDEQEFIY 1808
Cdd:cd11697    69 DYFDKGKMWECAISLCKELAEQYENETfDYLQLSELLKRMATFYDNIMKTL--RPEPEYFRVGYYGQGFPSfLRNKVFIY 146

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528488072 1809 KEPGITHLPEISHRLENFYSQCfgdgvlEMIKDSTPVDRNKLSPNKAYIQITFVEPYFDDYE------MKDRLTNFEKNF 1882
Cdd:cd11697   147 RGKEYERLSDFSARLLNQFPNA------ELMNTLTPPGDEIKESPGQYLQINKVDPVMDERPrfkgkpVSDQILNYYKVN 220

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528488072 1883 NLRRFMYTTPFTKSGR-PRGELNEQYKRKTILTTMHAFPYIKTRINVIQKEEFDLTPIEVAIEDMQKKTRELAEATHREK 1961
Cdd:cd11697   221 EVQRFTFSRPFRRGTKdPDNEFANMWLERTTLTTAYKLPGILRWFEVVSTSTVEISPLENAIETMEDTNKKIRDLILQHQ 300

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528488072 1962 PDAVM----LQMVLQGSVTATVNQGPLEVAQVFLNEipadpKLFRHH-------NKLRLCFKEFILRCGEAIEKNKQLIT 2030
Cdd:cd11697   301 SDPTLpinpLSMLLNGIVDAAVMGGIANYEKAFFTE-----EYLDEHpedqeliERLKDLIAEQIPLLEAGLKIHKQKAP 375

                         330       340
                  ....*....|....*....|
gi 528488072 2031 PDQKEYQQEMKKNYNKLREN 2050
Cdd:cd11697   376 ESLRPLHERMEECFAKMKEH 395
DHR2_DOCK_B cd11696
Dock Homology Region 2, a GEF domain, of Class B Dedicator of Cytokinesis proteins; DOCK ...
 1754-2051 1.88e-20

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: 95.97  E-value: 1.88e-20
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528488072 1754 EAHRDFRKLASTHDKLQRAFDNIIQKghKRMFGTYFRVGFYGSKFGD-LDEQEFIYKEPGITHLPEISHRLENFYSQCfg 1832
Cdd:cd11696    88 ESLYDYAKLSHILRMEASFYDNILTQ--LRPEPEYFRVGFYGKGFPLfLRNKQFVYRGLDYERIGAFTQRLQSEFPQA-- 163

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528488072 1833 dgvlEMIKDSTPVDRNKLSPNKAYIQITFVEPYFDDYEM------KDRLTNFEKNFNLRRFMYTTPFTKSGRPR-GELNE 1905
Cdd:cd11696   164 ----HILTKNTPPDDAILQADGQYIQICNVKPVPERRPVlqmvgvPDKVRSFYRVNDVRKFQYDRPIHKGPIDKdNEFKS 239

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528488072 1906 QYKRKTILTTMHAFPYIKTRINVIQKEEFDLTPIEVAIEDMQKKTREL----AEATHREKPDAVMLQMVLQGSVTATVNQ 1981
Cdd:cd11696   240 LWIERTTLVTEHSLPGILRWFEVVSREVEEIPPVENACETVENKNQELrsliSQYQADPTRNINPFSMRLQGVIDAAVNG 319

                         250       260       270       280       290       300       310
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 528488072 1982 GPLEVAQVFLNE--IPADPKLFRHHNKLRLCFKEFILRCGEAIEKNKQLITPDQKEYQQEMKKNYNKLRENL 2051
Cdd:cd11696   320 GIAKYQEAFFTPefILSHPEDAEHIARLRELILEQVQILEAGLALHGKLAPPEVRPLHKRLVERFTQMKQSL 391
DHR2_DOCK3 cd11704
Dock Homology Region 2, a GEF domain, of Class B Dedicator of Cytokinesis 3; Dock3, also ...
 1724-2051 1.50e-17

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: 87.37  E-value: 1.50e-17
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528488072 1724 GLLEQAAELFSNGGLFEAVNEVYKVIVPILEAHRDFRKLASTHDKLQRAFDNIIQKghKRMFGTYFRVGFYGSKFGD-LD 1802
Cdd:cd11704    58 GLCRKIIHYFNKGKSWEFGIPLCRELAFQYESLYDYQSLSWIRKMEAAYYDNIMEQ--QRLEPEFFRVGFYGRKFPFfLR 135

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528488072 1803 EQEFIYKEPGITHLPEISHRLENFYSQcfgdgVLEMIKDSTPvDRNKLSPNKAYIQITFVEP---YFDDYEMK---DRLT 1876
Cdd:cd11704   136 NKEYVCRGHDYERLEAFQQRMLSEFPQ-----AIAMQHPNHP-DDGILQCDAQYLQIYAVTPipdNMDVLQMDrvpDRIK 209

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528488072 1877 NFEKNFNLRRFMYTTPFTKSGRPR-GELNEQYKRKTILTTMHAFPYIKTRINVIQKEEFDLTPIEVAIEDMQKKTREL-- 1953
Cdd:cd11704   210 SFYRVNNVRKFRYDRPFHKGPKDKeNEFKSLWIERTTLTLTHSLPGISRWFEVERRELVEVSPLENAIQVVENKNQELrt 289

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528488072 1954 --AEATHREKPDAV-MLQMVLQGSVTATVNQGPLEVAQVFLNE--IPADPKLFRHHNKLRLCFKEFILRCGEAIEKNKQL 2028
Cdd:cd11704   290 liSQYQHKQLHGNInLLSMCLNGVIDAAVNGGIARYQEAFFDKdyISKHPGDAEKITQLKELMQEQVHVLGVGLAVHEKF 369

                         330       340
                  ....*....|....*....|...
gi 528488072 2029 ITPDQKEYQQEMKKNYNKLRENL 2051
Cdd:cd11704   370 VHPEMRPLHKKLIDQFQMMRSSL 392
DHR2_DOCK5 cd11708
Dock Homology Region 2, a GEF domain, of Class A Dedicator of Cytokinesis 5; Dock5 is an ...
 1725-2057 1.28e-16

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: 84.61  E-value: 1.28e-16
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528488072 1725 LLEQAAELFSNGGLFEAVNEVYKVIVPILEAHR-DFRKLASTHDKLQRAFDNIIQKghKRMFGTYFRVGFYGSKFGD-LD 1802
Cdd:cd11708    63 LYQEIISFFDKGKMWEKAIELSKELADMYENQVfDYEGLGNLLKKQAQFYENIMKA--MRPQPEYFAVGYYGQGFPSfLR 140

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528488072 1803 EQEFIYKEPGITHLPEISHRLenfYSQcFGDGVlEMIKDSTPVDRNKLSPnKAYIQITFVEP------YFDDYEMKDRLT 1876
Cdd:cd11708   141 NKIFIYRGKEYERLEDFSLKL---LTQ-FPNAE-KMTSTSPPGDEIKSST-KQYVQCFTVKPvmnlpsHYKDKPVPEQIL 214

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528488072 1877 NFEKNFNLRRFMYTTPFTKSGR-PRGELNEQYKRKTILTTMHAFPYIKTRINVIQKEEFDLTPIEVAIEDMQKKTRELAE 1955
Cdd:cd11708   215 NYYRANEVQQFQYSRPFRKGEKdPDNEFATMWIERTTFTTAYRFPGILKWFEVKQISTEEISPLENAIETMELTNEKISN 294

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528488072 1956 ATHREKPDAVM----LQMVLQGSVTATVNQGPLEVAQVFLNEipadpKLFRHHNKLRlcfkefilrcgEAIEKNKQLITP 2031
Cdd:cd11708   295 LVQQHAWDRSLpvhpLSMLLNGIVDPAVMGGFSNYEKAFFTE-----KYLQEHPEDQ-----------EKIELLKQLIAL 358

                         330       340
                  ....*....|....*....|....*.
gi 528488072 2032 DQKEYQQEMKKNYNKLRENLRPMLER 2057
Cdd:cd11708   359 QMPLLAEGIRIHGEKLTEQLKPLHER 384
DHR2_DOCK1 cd11707
Dock Homology Region 2, a GEF domain, of Class A Dedicator of Cytokinesis 1; Dock1, also ...
 1758-2057 4.26e-14

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: 76.61  E-value: 4.26e-14
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528488072 1758 DFRKLASTHDKLQRAFDNIIQKghKRMFGTYFRVGFYGSKFGD-LDEQEFIYKEPGITHLPEISHRLENFYSQCfgdgvl 1836
Cdd:cd11707    97 DYEQLSELLKKQAQFYENIVKV--IRPKPDYFAVGYYGQGFPTfLRNKMFIYRGKEYERREDFEARLLTQFPNA------ 168

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528488072 1837 EMIKDSTPVDRNKLSPNKAYIQITFVEPYFD------DYEMKDRLTNFEKNFNLRRFMYTTPFTKSGR-PRGELNEQYKR 1909
Cdd:cd11707   169 EKMKTTSPPGDDIKNSSGQYIQCFTVKPLLElppkfqNKPVSEQIVSFYRVNEVQRFQYSRPVRKGEKdPDNEFANMWIE 248

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528488072 1910 KTILTTMHAFPYIKTRINVIQKEEFDLTPIEVAIEDMQKKTRELAEATHREKPDAVM----LQMVLQGSVTATVNQGPLE 1985
Cdd:cd11707   249 RTTYVTAYKLPGILRWFEVKSVFMVEISPLENAIETMQLTNEKINNMVQQHLNDPNLpinpLSMLLNGIVDPAVMGGFAN 328

                         250       260       270       280       290       300       310
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 528488072 1986 VAQVFLNEipadpKLFRHHNKLRlcfkefilrcgEAIEKNKQLITPDQKEYQQEMKKNYNKLRENLRPMLER 2057
Cdd:cd11707   329 YEKAFFTE-----KYMQEHPEDH-----------EKIEKLKDLIAWQIPFLAEGIRIHGEKVTEALRPFHER 384
DHR2_DOCK2 cd11706
Dock Homology Region 2, a GEF domain, of Class A Dedicator of Cytokinesis 2; Dock2 is a ...
 1700-2048 4.70e-14

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: 76.57  E-value: 4.70e-14
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528488072 1700 SDDILSPDEDGVCSGRYFTENGLV-GLLEQAAELFSNGGLFEAVNEVYKVIVPILEAH-RDFRKLASTHDKLQRAFDNII 1777
Cdd:cd11706    55 SDEQCASQVMQTGQQHPQTQRQLKeTLYETIIGYFDKGKMWEEAISLCKELAEQYEMEiFDYELLSQNLIQQAKFYESIM 134

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528488072 1778 QKghKRMFGTYFRVGFYGSKFGD-LDEQEFIYKepGITHlpeisHRLENFYSQCFGD--GVLEMIKDSTPVDRNKLSPNK 1854
Cdd:cd11706   135 KI--LRPKPDYFAVGYYGQGFPSfLRNKVFIYR--GKEY-----ERREDFQMQLMSQfpNAEKLNTTSAPGDDIKNSPGQ 205

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528488072 1855 aYIQITFVEPYFD------DYEMKDRLTNFEKNFNLRRFMYTTPFTKSGR-PRGELNEQYKRKTILTTMHAFPYIKTRIN 1927
Cdd:cd11706   206 -YIQCFTVQPVLEehprlkNKPVPDQIINFYKSNYVQRFHYSRPVRKGPVdPENEFASMWIERTTFVTAYKLPGILRWFE 284

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528488072 1928 VIQKEEFDLTPIEVAIEDMQKKTRELAEATHREKPDAVM----LQMVLQGSVTATVNQGPLEVAQVFLNEipadPKLFRH 2003
Cdd:cd11706   285 VTHMSQTTISPLENAIETMSTTNEKILMMINQYQSDESLpinpLSMLLNGIVDPAVMGGFAKYEKAFFTE----EYVRDH 360

                         330       340       350       360       370
                  ....*....|....*....|....*....|....*....|....*....|...
gi 528488072 2004 H----NKLRLcfKEFIL----RCGEAIEKNKQLITPDQKEYQQEMKKNYNKLR 2048
Cdd:cd11706   361 PedqdKLTRL--KDLIAwqipLLGAGIKIHGKRVTDDLRPFHERMEECFKQLK 411
DHR2_DOCK4 cd11705
Dock Homology Region 2, a GEF domain, of Class B Dedicator of Cytokinesis 4; Dock4 is an ...
 1754-1991 9.03e-13

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: 72.37  E-value: 9.03e-13
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528488072 1754 EAHRDFRKLASTHDKLQRAFDNIIQKghKRMFGTYFRVGFYGSKFGD-LDEQEFIYKEPGITHLPEISHRLENFYSQCFG 1832
Cdd:cd11705    88 ESYYDYRNLSKMRMMEASLYDKIMDQ--QRLEPEFFRVGFYGKKFPFfLRNKEFVCRGHDYERLEAFQQRMLNEFPHAIA 165

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528488072 1833 dgvlemIKDSTPVDRNKLSPNKAYIQITFVEPYFDDYEM------KDRLTNFEKNFNLRRFMYTTPFTKSGRPR-GELNE 1905
Cdd:cd11705   166 ------MQHANQPDETIFQAEAQYLQIYAVTPIPESQEVlqrdgvPDNIKSFYKVNHIWRFRYDRPFHKGTKDKeNEFKS 239

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528488072 1906 QYKRKTILTTMHAFPYIKTRINVIQKEEFDLTPIEVAIEDMQKKTREL----AEATHREKPDAVMLQMVLQGSVTATVNQ 1981
Cdd:cd11705   240 LWVERTTLTLVQSLPGISRWFEVEKREVVEMSPLENAIEVLENKNQQLrtliSQCQTRQMQNINPLTMCLNGVIDAAVNG 319

                         250
                  ....*....|
gi 528488072 1982 GPLEVAQVFL 1991
Cdd:cd11705   320 GVSRYQEAFF 329
C2_Dock-A cd08694
C2 domains found in Dedicator Of CytoKinesis (Dock) class A proteins; Dock-A is one of 4 ...
 567-669 8.31e-05

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: 45.86  E-value: 8.31e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528488072  567 TSARNITVKIQfMSGEDSScAMPVIFGKSSGPEFLTEVYTPVTYHNRSPDFYDEIKILLPARLTDKHHLLFTFFHISCQQ 646
Cdd:cd08694    20 TSDKNVEVTVS-VCNEDGK-IIPGVISLGAGEEPIDEYKSVIYYQVDKPKWFETFKVAIPIEDFKSSHLRFTFKHRSSNE 97

                          90       100
                  ....*....|....*....|...
gi 528488072  647 KQNQTgsvEALIGYSWLPMLNND 669
Cdd:cd08694    98 AKDKS---EKPFALSFVKLMQEN 117
C2_Dock-B cd08695
C2 domains found in Dedicator Of CytoKinesis (Dock) class B proteins; Dock-B is one of 4 ...
 567-669 1.87e-03

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: 41.60  E-value: 1.87e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528488072  567 TSARNITVKIqFMSGEDSSCAMPVIFGkSSGPEFLTEVYTPVTYHNRSPDFYDEIKILLPARLTDKHHLLFTFFHISCQQ 646
Cdd:cd08695    20 STAKNIEVTM-VVLDADGQVLKDCISL-GSGEPPCSEYRSFVLYHNNSPRWNETIKLPIPIDKFRGSHLRFEFRHCSTKD 97

                          90       100
                  ....*....|....*....|...
gi 528488072  647 KQNQTgsveaLIGYSWLPMLNND 669
Cdd:cd08695    98 KGEKK-----LFGFSFVPLMRED 115
 
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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