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Conserved domains on  [gi|1060604597|ref|NP_001317543|]
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dedicator of cytokinesis protein 7 isoform 6 [Homo sapiens]

Protein Classification

dedicator of cytokinesis protein 7( domain architecture ID 10570938)

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_DOCK7 cd11703
Dock Homology Region 2, a GEF domain, of Class C Dedicator of Cytokinesis 7; Dock7, also ...
 1635-2109 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: 962.62  E-value: 0e+00
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1060604597 1635 DLVFNLHMILSDTVKMKEHQEDPEMLIDLMYRIAKGYQTSPDLRLTWLQNMAGKHSERSNHAEAAQCLVHSAALVAEYLS 1714
Cdd:cd11703      1 DLVFNLHMILSDTVKMKEHQEDPEMLIDLMYRIAKGYQTSPDLRLTWLQNMAGKHSERSNHAEAAQCLVHSAALVAEYLS 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1060604597 1715 MLEDRKYLPVGCVTFQNISSNVLEESAVSDDVVSPDEEGICSGKYFTESGLVGLLEQAAASFSMAGMYEAVNEVYKVLIP 1794
Cdd:cd11703     81 MLEDRKYLPVGCVTFQNISSNVLEESAVSDDVVSPDEEGICSGKYFTEAGLVGLLEQAAASFSMAGMYEAVNEVYKVLIP 160

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1060604597 1795 IHEANRDAKKLSTIHGKLQEAFSKIVHQSTGweRMFGTYFRVGFYGTKFGDLDEQEFVYKEPAITKLAEISHRLEGFYGE 1874
Cdd:cd11703    161 IHEANRDAKKLATIHGKLQEAFSKIVHQDGK--RMFGTYFRVGFYGTKFGDLDEQEFVYKEPAITKLAEISHRLEGFYGE 238

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1060604597 1875 RFGEDVVEVIKDSNPVDKCKLDPNKAYIQITYVEPYFDTYEMKDRITYFDKNYNLRRFMYCTPFTLDGRAHGELHEQFKR 1954
Cdd:cd11703    239 RFGEDVVEVIKDSNPVDKCKLDPNKAFIQITYVEPYFDTYEMKDRITYFDKNYNLRRFMYCTPFTLDGRAHGELHEQFKR 318

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1060604597 1955 KTILTTSHAFPYIKTRVNVTHKEEIILTPIEVAIEDMQKKTQELAFATHQDPADPKMLQMVLQGSVGTTVNQGPLEVAQV 2034
Cdd:cd11703    319 KTILTTSHAFPYIKTRINVIHKEEIILTPIEVAIEDMQKKTQELAFATHQDPADPKMLQMVLQGSVGTTVNQGPLEVAQV 398

                          410       420       430       440       450       460       470
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1060604597 2035 FLSEIPSDPKLFRHHNKLRLCFKDFTKRCEDALRKNKSLIGPDQKEYQRELERNYHRLKEALQPLINRKIPQLYK 2109
Cdd:cd11703    399 FLSEIPSDPKLFRHHNKLRLCFKDFTKRCEDALRKNKSLIGPDQKEYQRELERNYHRLKEALQPLINRKIPQLYK 473
C2_Dock-C cd08696
C2 domains found in Dedicator Of CytoKinesis (Dock) class C proteins; Dock-C is one of 4 ...
 560-737 2.15e-115

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: 362.83  E-value: 2.15e-115
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1060604597  560 YRNLLYIYPQSLNFANRQGSARNITVKVQFMYGEDPSNAMPVIFGKSSCSEFSKEAYTAVVYHNRSPDFHEEIKVKLPAT 639
Cdd:cd08696      1 YRNLLYVYPQSLNFSNRLGSARNIAVKVQLMSGEDESQALPVIFKGSSPEEFLTEAYTAVTYHNKSPDFYDEIKIKLPAD 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1060604597  640 LTDHHHLLFTFYHVSCQQKQ-NTPLETPVGYTWIPMLQNGRLKTGQFCLPVSLEKPPQAYSVLSPEVPLPGMKWVDNHKG 718
Cdd:cd08696     81 LTDNHHLLFTFYHISCQKKQeGGSVETPIGYTWLPLLRNGRLQSGEFNLPVSLEKPPSNYSPDSPEVKLPGTKWVDNHKG 160

                          170
                   ....*....|....*....
gi 1060604597  719 VFNVEVVAVSSIHTQDPYL 737
Cdd:cd08696    161 VFSVSVEAVSSVHTQDSYL 179
DOCK_C-D_N pfam11878
Dedicator of cytokinesis C/D, N terminal; This entry represents the N-terminal domain of the ...
 52-161 4.12e-50

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: 173.22  E-value: 4.12e-50
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1060604597   52 TEAVDPVDLEDYLITHPLAVDSGPLRDLIEFPPDDIEVVYSPRDCRTLVSAVPEE--SEMDPHVRDCIRSYTEDWAIVIR 129
Cdd:pfam11878    1 PKVVEPLDYEEFISQHLTQIENDPLRDLLLFPDDDIEVSVIPRECRTLQPTVPEEaeKEADPLVRECIKTYTSDWHVVNY 80

                           90       100       110
                   ....*....|....*....|....*....|..
gi 1060604597  130 KYHKLGTGFNPNTLDKQKERQKGLPKQVFESD 161
Cdd:pfam11878   81 KYEDYSGDFRQLPKSKRRERPEKLPKQVFEID 112
 
Name Accession Description Interval E-value
DHR2_DOCK7 cd11703
Dock Homology Region 2, a GEF domain, of Class C Dedicator of Cytokinesis 7; Dock7, also ...
 1635-2109 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: 962.62  E-value: 0e+00
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1060604597 1635 DLVFNLHMILSDTVKMKEHQEDPEMLIDLMYRIAKGYQTSPDLRLTWLQNMAGKHSERSNHAEAAQCLVHSAALVAEYLS 1714
Cdd:cd11703      1 DLVFNLHMILSDTVKMKEHQEDPEMLIDLMYRIAKGYQTSPDLRLTWLQNMAGKHSERSNHAEAAQCLVHSAALVAEYLS 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1060604597 1715 MLEDRKYLPVGCVTFQNISSNVLEESAVSDDVVSPDEEGICSGKYFTESGLVGLLEQAAASFSMAGMYEAVNEVYKVLIP 1794
Cdd:cd11703     81 MLEDRKYLPVGCVTFQNISSNVLEESAVSDDVVSPDEEGICSGKYFTEAGLVGLLEQAAASFSMAGMYEAVNEVYKVLIP 160

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1060604597 1795 IHEANRDAKKLSTIHGKLQEAFSKIVHQSTGweRMFGTYFRVGFYGTKFGDLDEQEFVYKEPAITKLAEISHRLEGFYGE 1874
Cdd:cd11703    161 IHEANRDAKKLATIHGKLQEAFSKIVHQDGK--RMFGTYFRVGFYGTKFGDLDEQEFVYKEPAITKLAEISHRLEGFYGE 238

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1060604597 1875 RFGEDVVEVIKDSNPVDKCKLDPNKAYIQITYVEPYFDTYEMKDRITYFDKNYNLRRFMYCTPFTLDGRAHGELHEQFKR 1954
Cdd:cd11703    239 RFGEDVVEVIKDSNPVDKCKLDPNKAFIQITYVEPYFDTYEMKDRITYFDKNYNLRRFMYCTPFTLDGRAHGELHEQFKR 318

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1060604597 1955 KTILTTSHAFPYIKTRVNVTHKEEIILTPIEVAIEDMQKKTQELAFATHQDPADPKMLQMVLQGSVGTTVNQGPLEVAQV 2034
Cdd:cd11703    319 KTILTTSHAFPYIKTRINVIHKEEIILTPIEVAIEDMQKKTQELAFATHQDPADPKMLQMVLQGSVGTTVNQGPLEVAQV 398

                          410       420       430       440       450       460       470
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1060604597 2035 FLSEIPSDPKLFRHHNKLRLCFKDFTKRCEDALRKNKSLIGPDQKEYQRELERNYHRLKEALQPLINRKIPQLYK 2109
Cdd:cd11703    399 FLSEIPSDPKLFRHHNKLRLCFKDFTKRCEDALRKNKSLIGPDQKEYQRELERNYHRLKEALQPLINRKIPQLYK 473
C2_Dock-C cd08696
C2 domains found in Dedicator Of CytoKinesis (Dock) class C proteins; Dock-C is one of 4 ...
 560-737 2.15e-115

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: 362.83  E-value: 2.15e-115
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1060604597  560 YRNLLYIYPQSLNFANRQGSARNITVKVQFMYGEDPSNAMPVIFGKSSCSEFSKEAYTAVVYHNRSPDFHEEIKVKLPAT 639
Cdd:cd08696      1 YRNLLYVYPQSLNFSNRLGSARNIAVKVQLMSGEDESQALPVIFKGSSPEEFLTEAYTAVTYHNKSPDFYDEIKIKLPAD 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1060604597  640 LTDHHHLLFTFYHVSCQQKQ-NTPLETPVGYTWIPMLQNGRLKTGQFCLPVSLEKPPQAYSVLSPEVPLPGMKWVDNHKG 718
Cdd:cd08696     81 LTDNHHLLFTFYHISCQKKQeGGSVETPIGYTWLPLLRNGRLQSGEFNLPVSLEKPPSNYSPDSPEVKLPGTKWVDNHKG 160

                          170
                   ....*....|....*....
gi 1060604597  719 VFNVEVVAVSSIHTQDPYL 737
Cdd:cd08696    161 VFSVSVEAVSSVHTQDSYL 179
DHR-2_Lobe_A pfam06920
DHR-2, Lobe A; This entry represents a conserved region within a number of eukaryotic ...
 1662-1821 4.12e-69

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: 229.10  E-value: 4.12e-69
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1060604597 1662 DLMYRIAKGYQTSPDLRLTWLQNMAGKHSERSNHAEAAQCLVHSAALVAEYLSMLeDRKYLPVGCVTFQNISSNVL-EES 1740
Cdd:pfam06920    1 DLQYSLANSYKSSPDLRLTWLENLAEKHLENGNFSEAAQCLIHIAALIAEYLKLK-GKIPNPLGASAFEKISPNILrEES 79

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1060604597 1741 AVSDDVvspdeeGICSGKYFTESGLVGLLEQAAASFSMAGMYEAVNEVYKVLIPIHEANRDAKKLSTIHGKLQEAFSKIV 1820
Cdd:pfam06920   80 ALKDDS------GVCDSPHFTEDGLVGLLEEAIDYLDKAERYELAIELYKLLLPIYESRRDYKKLSECHGKLAEAYEKIV 153


                   .
gi 1060604597 1821 H 1821
Cdd:pfam06920  154 E 154
DOCK-C2 pfam14429
C2 domain in Dock180 and Zizimin proteins; The Dock180/Dock1 and Zizimin proteins are atypical ...
 557-736 9.08e-62

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: 209.38  E-value: 9.08e-62
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1060604597  557 NTTYRNLLYIYPQSLNFANR-QGSARNITVKVQFMYGEdpSNAMP-VIFGKSSCsEFSKEAYTAVVYHNRSPDFHEEIKV 634
Cdd:pfam14429    1 PGDYRNDLYVTPKSGNFSKQkKSSARNIEVTVEVRDSD--GEPLPnCIYGGSGG-PFVTEFKSTVYYHNKSPTWYEEIKI 77

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1060604597  635 KLPATLTDHHHLLFTFYHVSCQQKqNTPLETPVGYTWIPMLQNGR--LKTGQFCLPVSL-EKPPQAYSVLS-------PE 704
Cdd:pfam14429   78 ALPAELTPKHHLLFTFYHVSCDEK-KDKVEKPFGYAFLPLLDDDGafLRDGEHTLPVYKyDELPPGYLSLPwssggekES 156

                          170       180       190
                   ....*....|....*....|....*....|..
gi 1060604597  705 VPLPGMKwvdNHKGVFNVEVVAVSSIHTQDPY 736
Cdd:pfam14429  157 SALPGLK---GGKDLFKVRTRLCSTKYTQDEH 185
DOCK_C-D_N pfam11878
Dedicator of cytokinesis C/D, N terminal; This entry represents the N-terminal domain of the ...
 52-161 4.12e-50

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: 173.22  E-value: 4.12e-50
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1060604597   52 TEAVDPVDLEDYLITHPLAVDSGPLRDLIEFPPDDIEVVYSPRDCRTLVSAVPEE--SEMDPHVRDCIRSYTEDWAIVIR 129
Cdd:pfam11878    1 PKVVEPLDYEEFISQHLTQIENDPLRDLLLFPDDDIEVSVIPRECRTLQPTVPEEaeKEADPLVRECIKTYTSDWHVVNY 80

                           90       100       110
                   ....*....|....*....|....*....|..
gi 1060604597  130 KYHKLGTGFNPNTLDKQKERQKGLPKQVFESD 161
Cdd:pfam11878   81 KYEDYSGDFRQLPKSKRRERPEKLPKQVFEID 112
 
Name Accession Description Interval E-value
DHR2_DOCK7 cd11703
Dock Homology Region 2, a GEF domain, of Class C Dedicator of Cytokinesis 7; Dock7, also ...
 1635-2109 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: 962.62  E-value: 0e+00
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1060604597 1635 DLVFNLHMILSDTVKMKEHQEDPEMLIDLMYRIAKGYQTSPDLRLTWLQNMAGKHSERSNHAEAAQCLVHSAALVAEYLS 1714
Cdd:cd11703      1 DLVFNLHMILSDTVKMKEHQEDPEMLIDLMYRIAKGYQTSPDLRLTWLQNMAGKHSERSNHAEAAQCLVHSAALVAEYLS 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1060604597 1715 MLEDRKYLPVGCVTFQNISSNVLEESAVSDDVVSPDEEGICSGKYFTESGLVGLLEQAAASFSMAGMYEAVNEVYKVLIP 1794
Cdd:cd11703     81 MLEDRKYLPVGCVTFQNISSNVLEESAVSDDVVSPDEEGICSGKYFTEAGLVGLLEQAAASFSMAGMYEAVNEVYKVLIP 160

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1060604597 1795 IHEANRDAKKLSTIHGKLQEAFSKIVHQSTGweRMFGTYFRVGFYGTKFGDLDEQEFVYKEPAITKLAEISHRLEGFYGE 1874
Cdd:cd11703    161 IHEANRDAKKLATIHGKLQEAFSKIVHQDGK--RMFGTYFRVGFYGTKFGDLDEQEFVYKEPAITKLAEISHRLEGFYGE 238

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1060604597 1875 RFGEDVVEVIKDSNPVDKCKLDPNKAYIQITYVEPYFDTYEMKDRITYFDKNYNLRRFMYCTPFTLDGRAHGELHEQFKR 1954
Cdd:cd11703    239 RFGEDVVEVIKDSNPVDKCKLDPNKAFIQITYVEPYFDTYEMKDRITYFDKNYNLRRFMYCTPFTLDGRAHGELHEQFKR 318

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1060604597 1955 KTILTTSHAFPYIKTRVNVTHKEEIILTPIEVAIEDMQKKTQELAFATHQDPADPKMLQMVLQGSVGTTVNQGPLEVAQV 2034
Cdd:cd11703    319 KTILTTSHAFPYIKTRINVIHKEEIILTPIEVAIEDMQKKTQELAFATHQDPADPKMLQMVLQGSVGTTVNQGPLEVAQV 398

                          410       420       430       440       450       460       470
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1060604597 2035 FLSEIPSDPKLFRHHNKLRLCFKDFTKRCEDALRKNKSLIGPDQKEYQRELERNYHRLKEALQPLINRKIPQLYK 2109
Cdd:cd11703    399 FLSEIPSDPKLFRHHNKLRLCFKDFTKRCEDALRKNKSLIGPDQKEYQRELERNYHRLKEALQPLINRKIPQLYK 473
DHR2_DOCK6 cd11702
Dock Homology Region 2, a GEF domain, of Class C Dedicator of Cytokinesis 6; Dock6, also ...
 1674-2096 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: 914.01  E-value: 0e+00
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1060604597 1674 SPDLRLTWLQNMAGKHSERSNHAEAAQCLVHSAALVAEYLSMLEDRKYLPVGCVTFQNISSNVLEESAVSDDVVSPDEEG 1753
Cdd:cd11702      1 SPDLRLTWLQNMAGKHSERGNHAEAAHCLVHSAALVAEYLSMLEDCRHLPVGCVSFQNISSNVLEESAVSDDILSPDEEG 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1060604597 1754 ICSGKYFTESGLVGLLEQAAASFSMAGMYEAVNEVYKVLIPIHEANRDAKKLSTIHGKLQEAFSKIVHQSTGWERMFGTY 1833
Cdd:cd11702     81 ICSGKYFTELGLVGLLEQAAASFNMGGLYEAVNEVYKILIPIHEANRDYKKLAVVHGKLQEAFNKITNQSSGWERMFGTY 160

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1060604597 1834 FRVGFYGTKFGDLDEQEFVYKEPAITKLAEISHRLEGFYGERFGEDVVEVIKDSNPVDKCKLDPNKAYIQITYVEPYFDT 1913
Cdd:cd11702    161 FRVGFYGCKFGDLDEQEFVYKEPSITKLAEISHRLEEFYTERFGDEVVEIIKDSNPVDKSKLDPNKAYIQITYVEPFFDT 240

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1060604597 1914 YEMKDRITYFDKNYNLRRFMYCTPFTLDGRAHGELHEQFKRKTILTTSHAFPYIKTRVNVTHKEEIILTPIEVAIEDMQK 1993
Cdd:cd11702    241 YELKDRVTYFDKNYNLRTFLFCTPFTLDGRAHGELHEQYKRKTILTTSHAFPYIKTRINVLHREEIVLIPVEVAIEDMQK 320

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1060604597 1994 KTQELAFATHQDPADPKMLQMVLQGSVGTTVNQGPLEVAQVFLSEIPSDPKLFRHHNKLRLCFKDFTKRCEDALRKNKSL 2073
Cdd:cd11702    321 KTQELAFATHQDPADAKMLQMVLQGCVGTTVNQGPLEVAQVFLSEIPEDPKLFRHHNKLRLCFKDFTKRCEDALRKNKAL 400

                          410       420
                   ....*....|....*....|...
gi 1060604597 2074 IGPDQKEYQRELERNYHRLKEAL 2096
Cdd:cd11702    401 IGPDQKEYHRELERNYQRLREAL 423
DHR2_DOCK8 cd11701
Dock Homology Region 2, a GEF domain, of Class C Dedicator of Cytokinesis 8; Dock8, also ...
 1673-2096 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: 781.53  E-value: 0e+00
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1060604597 1673 TSPDLRLTWLQNMAGKHSERSNHAEAAQCLVHSAALVAEYLSMLEDRKYLPVGCVTFQNISSNVLEESAVSDDVVSPDEE 1752
Cdd:cd11701      1 TSPDLRLTWLQNMAEKHTKRKCFTEAAMCLVHAAALVAEYLSMLEDHSYLPVGSVSFQNISSNVLEESAVSDDILSPDED 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1060604597 1753 GICSGKYFTESGLVGLLEQAAASFSMAGMYEAVNEVYKVLIPIHEANRDAKKLSTIHGKLQEAFSKIVHQstGWERMFGT 1832
Cdd:cd11701     81 GVCSGRYFTENGLVGLLEQAAELFSTGGLYETVNEVYKIVIPILEAHRDFRKLASTHDKLQKAFDNIINK--GHKRMFGT 158

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1060604597 1833 YFRVGFYGTKFGDLDEQEFVYKEPAITKLAEISHRLEGFYGERFGEDVVEVIKDSNPVDKCKLDPNKAYIQITYVEPYFD 1912
Cdd:cd11701    159 YFRVGFYGSKFGDLDEQEFIYKEPAITKLPEISHRLEGFYGQCFGDDVVEVIKDSTPVDKSKLDPNKAYIQITFVEPYFD 238

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1060604597 1913 TYEMKDRITYFDKNYNLRRFMYCTPFTLDGRAHGELHEQFKRKTILTTSHAFPYIKTRVNVTHKEEIILTPIEVAIEDMQ 1992
Cdd:cd11701    239 DYEMKDRVTYFEKNFNLRRFMYTTPFTLDGRPRGELSEQYKRKTILTTMHAFPYIKTRINVIQKEEFDLTPIEVAIEDMQ 318

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1060604597 1993 KKTQELAFATHQDPADPKMLQMVLQGSVGTTVNQGPLEVAQVFLSEIPSDPKLFRHHNKLRLCFKDFTKRCEDALRKNKS 2072
Cdd:cd11701    319 KKTRELAEATHQEPPDAKMLQMVLQGSVGATVNQGPLEVAQVFLAEIPADPKLYRHHNKLRLCFKEFIMRCGEAVEKNKR 398

                          410       420
                   ....*....|....*....|....
gi 1060604597 2073 LIGPDQKEYQRELERNYHRLKEAL 2096
Cdd:cd11701    399 LITADQREYQQELKKNYNKLRENL 422
DHR2_DOCK_C cd11695
Dock Homology Region 2, a GEF domain, of Class C Dedicator of Cytokinesis proteins; DOCK ...
 1674-2096 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: 750.28  E-value: 0e+00
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1060604597 1674 SPDLRLTWLQNMAGKHSERSNHAEAAQCLVHSAALvaeylsmledrkylpvgcvtfqnissnvleesavsddvvspdeeg 1753
Cdd:cd11695      1 SPDLRLTWLQNMAEKHYERKNFAEAAQCLVHAAAL--------------------------------------------- 35

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1060604597 1754 icsgkyftesGLVGLLEQAAASFSMAGMYEAVNEVYKVLIPIHEANRDAKKLSTIHGKLQEAFSKIVHQStGWERMFGTY 1833
Cdd:cd11695     36 ----------GLVGLLEQAAESFSKAGMYEAVNEVYKLLIPILEANRDYKKLAEIHGKLQDAFTKIEKQQ-GGKRMFGTY 104

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1060604597 1834 FRVGFYGTKFGDLDEQEFVYKEPAITKLAEISHRLEGFYGERFGEDVVEVIKDSNPVDKCKLDPNKAYIQITYVEPYFDT 1913
Cdd:cd11695    105 FRVGFYGSKFGDLDGKEFIYKEPAITKLPEISHRLETFYGERFGEERVEVIKDSNPVDTSKLDPDKAYIQITYVEPYFDE 184

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1060604597 1914 YEMKDRITYFDKNYNLRRFMYCTPFTLDGRAHGELHEQFKRKTILTTSHAFPYIKTRVNVTHKEEIILTPIEVAIEDMQK 1993
Cdd:cd11695    185 YELKERTTYFERNYNLRRFMYATPFTPDGKAHGELAEQYKRKTILTTENSFPYVKTRLQVVNREEIVLTPIEVAIEDVQK 264

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1060604597 1994 KTQELAFATHQDPADPKMLQMVLQGSVGTTVNQGPLEVAQVFLSEIPSDPK-LFRHHNKLRLCFKDFTKRCEDALRKNKS 2072
Cdd:cd11695    265 KTRELAAATTQEPPDPKMLQMVLQGSIGTTVNQGPLEVANVFLSDIPLDPKeLDRHQNKLRLCFKEFSKKCYDALEKNKE 344

                          410       420
                   ....*....|....*....|....
gi 1060604597 2073 LIGPDQKEYQRELERNYHRLKEAL 2096
Cdd:cd11695    345 LIGPDQKEYQKELERNYENFKEKL 368
DHR2_DOCK_D cd11694
Dock Homology Region 2, a GEF domain, of Class D Dedicator of Cytokinesis proteins; DOCK ...
 1676-2096 9.79e-130

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


Pssm-ID: 212567  Cd Length: 376  Bit Score: 412.50  E-value: 9.79e-130
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1060604597 1676 DLRLTWLQNMAGKHSERSNHAEAAQCLVHSAALVAEYLSmledRKYLpvgcvtfqnissnvleesavsddvvspdeegic 1755
Cdd:cd11694      1 ELRKTWLESMARIHEKNGNFSEAAMCYIHIAALVAEYLK----RKDL--------------------------------- 43

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1060604597 1756 sgkyftesgLVGLLEQAAASFSMAGMYEAVNEVYKVLIPIHEANRDAKKLSTIHGKLQEAFSKIVHQSTGWERMFGTYFR 1835
Cdd:cd11694     44 ---------LLELLEACVEGLWKAERYELLGELYKLIIPIYEKRRDFEQLADCYRTLHRAYEKVVEVMESGKRLLGTYYR 114

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1060604597 1836 VGFYGTK-FGDLDEQEFVYKEPAITKLAEISHRLEGFYGERFGEDVVEVIKDSNPVDKCKLDPNKAYIQITYVEPYFDTY 1914
Cdd:cd11694    115 VAFYGQAfFEEEDGKEYIYKEPKVTSLSEISERLLKLYGDKFGSENVKLIQDSGKVNPKDLDPKYAYIQVTHVTPYFDEK 194

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1060604597 1915 EMKDRITYFDKNYNLRRFMYCTPFTLDGRAHGELHEQFKRKTILTTSHAFPYIKTRVNVTHKEEIILTPIEVAIEDMQKK 1994
Cdd:cd11694    195 ELEDRKTEFERNHNIRRFVFETPFTLSGKARGAVEEQWKRRTILTTSHSFPYVKKRIPVVQREIIELSPIEVAIDEMQSK 274

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1060604597 1995 TQELAFATHQDPADPKMLQMVLQGSVGTTVNQGPLEVAQVFLSEIPSdPKLFRHH-NKLRLCFKDFTKRCEDALRKNKSL 2073
Cdd:cd11694    275 VKELEELISTEPVDMKKLQLRLQGSVSVQVNAGPLAYARAFLEPTTV-KNYPDDQvEDLKDVFRDFIKACGQALELNERL 353

                          410       420
                   ....*....|....*....|...
gi 1060604597 2074 IGPDQKEYQRELERNYHRLKEAL 2096
Cdd:cd11694    354 IKEDQREYHEVLKENYRKMVKEL 376
DHR2_DOCK11 cd11700
Dock Homology Region 2, a GEF domain, of Class D Dedicator of Cytokinesis 11; Dock11, also ...
 1675-2096 1.79e-116

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: 376.26  E-value: 1.79e-116
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1060604597 1675 PDLRLTWLQNMAGKHSERSNHAEAAQCLVHSAALVAEYLsmlEDRKYLPVGCVTFQNISSNVLEESAVSDDVVSPDeegi 1754
Cdd:cd11700      1 PELRKTWLDSMAKIHVKNGDFSEAAMCYVHVAALVAEFL---HRKKLFPSGCAAFKKITPNIDEEGAMKEDIGMMD---- 73

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1060604597 1755 csgKYFTESGLVGLLEQAAASFSMAGMYEAVNEVYKVLIPIHEANRDAKKLSTIHGKLQEAFSKIVHQSTGWERMFGTYF 1834
Cdd:cd11700     74 ---VHYSEEVLVELLEQCVDGLWKAERYELISEISKLIIPIYEKRREFEKLTQLYRTLHGAYAKILEVMHTGKRLLGTFF 150

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1060604597 1835 RVGFYG-TKFGDLDEQEFVYKEPAITKLAEISHRLEGFYGERFGEDVVEVIKDSNPVDKCKLDPNKAYIQITYVEPYFDT 1913
Cdd:cd11700    151 RVAFYGqGFFEEEDGKEYIYKEPKLTGLSEISHRLLKLYGEKFGSENVKIIQDSNKVNQKDLDPKYAHIQVTYVKPYFDD 230

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1060604597 1914 YEMKDRITYFDKNYNLRRFMYCTPFTLDGRAHGELHEQFKRKTILTTSHAFPYIKTRVNVTHKEEIILTPIEVAIEDMQK 1993
Cdd:cd11700    231 KEMAERKTEFERNHNIQRFVFETPYTLSGKKQGGVEEQCKRRTILTTANSFPYVKKRIPVNGEKQTNLKPIDVATDEIKD 310

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1060604597 1994 KTQELAFATHQDPADPKMLQMVLQGSVGTTVNQGPLEVAQVFLSEIPSDPKLFRHHNKLRLCFKDFTKRCEDALRKNKSL 2073
Cdd:cd11700    311 KTAELQKLCSNQDVDMIQLQLKLQGCVSVQVNAGPLAYARAFLDDSQASKYPNKKVKELKEMFRKFIQACSIALELNERL 390

                          410       420
                   ....*....|....*....|...
gi 1060604597 2074 IGPDQKEYQRELERNYHRLKEAL 2096
Cdd:cd11700    391 IKEDQVEYHEGLKSNFRDMVKEL 413
C2_Dock-C cd08696
C2 domains found in Dedicator Of CytoKinesis (Dock) class C proteins; Dock-C is one of 4 ...
 560-737 2.15e-115

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: 362.83  E-value: 2.15e-115
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1060604597  560 YRNLLYIYPQSLNFANRQGSARNITVKVQFMYGEDPSNAMPVIFGKSSCSEFSKEAYTAVVYHNRSPDFHEEIKVKLPAT 639
Cdd:cd08696      1 YRNLLYVYPQSLNFSNRLGSARNIAVKVQLMSGEDESQALPVIFKGSSPEEFLTEAYTAVTYHNKSPDFYDEIKIKLPAD 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1060604597  640 LTDHHHLLFTFYHVSCQQKQ-NTPLETPVGYTWIPMLQNGRLKTGQFCLPVSLEKPPQAYSVLSPEVPLPGMKWVDNHKG 718
Cdd:cd08696     81 LTDNHHLLFTFYHISCQKKQeGGSVETPIGYTWLPLLRNGRLQSGEFNLPVSLEKPPSNYSPDSPEVKLPGTKWVDNHKG 160

                          170
                   ....*....|....*....
gi 1060604597  719 VFNVEVVAVSSIHTQDPYL 737
Cdd:cd08696    161 VFSVSVEAVSSVHTQDSYL 179
DHR2_DOCK cd11684
Dock Homology Region 2, a GEF domain, of Dedicator of Cytokinesis proteins; DOCK proteins ...
 1676-2096 1.28e-114

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: 369.70  E-value: 1.28e-114
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1060604597 1676 DLRLTWLQNMAGKHSERSNHAEAAQCLVHSAALVAEYLsmledrkylpvgcvtfqnissnvleesavsDDVVSPDEEGIC 1755
Cdd:cd11684      1 ELYIRYLHKLADLHEERGNYVEAALCLLLHADLYAWDL------------------------------KALVPALAESLS 50

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1060604597 1756 SGKYFTESGLVGLLEQAAASFSMAGMYEAVNEVYKVLIPIHEANRDAKKLSTIHGKLQEAFSKIVHQstgwERMFGTYFR 1835
Cdd:cd11684     51 FPEQTSFERKEALYKKAIDLFDKGKAWEFAIALYKELIPQYENNFDYAKLSEVHRKIAKLYEKIAEK----DRLFPTYFR 126

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1060604597 1836 VGFYGTKF-GDLDEQEFVYKEPAITKLAEISHRLEGFYGERfgedvvEVIKDSNPVDKCKLDPNKAYIQITYVEPYFDTY 1914
Cdd:cd11684    127 VGFYGKGFpESLRGKEFIYRGPEFERLGDFCERLKSLYPGA------EIIQSSEEPDDEILDSEGQYIQITSVEPYFDDE 200

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1060604597 1915 EMK----DRITYFDKNYNLRRFMYCTPFTLDGRA-HGELHEQFKRKTILTTSHAFPYIKTRVNVTHKEEIILTPIEVAIE 1989
Cdd:cd11684    201 DLVsraaPGVRQFYRNNNINTFVYERPFTKGGKKsQNEITDQWKERTILTTEESFPTILRRSEVVSIEEIELSPIENAIE 280

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1060604597 1990 DMQKKTQELAFATHQ----DPADPKMLQMVLQGSVGTTVNQGPLEVAQVFLS-EIPSDPKLFRHHNKLRLCFKDFTKRCE 2064
Cdd:cd11684    281 DIEKKTEELRSLINKyrsgDSPNVNPLQMLLQGTVDAAVNGGPVAYAEAFLSeEYLSNYPEAEKVKKLKEAFEEFLEILK 360

                          410       420       430
                   ....*....|....*....|....*....|..
gi 1060604597 2065 DALRKNKSLIGPDQKEYQRELERNYHRLKEAL 2096
Cdd:cd11684    361 RGLALHAKLCPPEMAPLHEELEEGFEKLFKEL 392
DHR2_DOCK9 cd11698
Dock Homology Region 2, a GEF domain, of Class D Dedicator of Cytokinesis 9; Dock9, also ...
 1676-2096 4.44e-108

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: 352.02  E-value: 4.44e-108
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1060604597 1676 DLRLTWLQNMAGKHSERSNHAEAAQCLVHSAALVAEYLSmledRK-YLPVGCVTFQNISSNVLEESAVSDDVVSPDeegi 1754
Cdd:cd11698      1 ELRKTWLDSMARIHVKNGDLSEAAMCYVHVAALVAEYLT----RKgMFRQGCTAFRVITPNIDEEASMMEDVGMQD---- 72

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1060604597 1755 csgKYFTESGLVGLLEQAAASFSMAGMYEAVNEVYKVLIPIHEANRDAKKLSTIHGKLQEAFSKIVHQSTGWERMFGTYF 1834
Cdd:cd11698     73 ---VHFNEDVLMELLEQCADGLWKAERYELIADIYKLIIPIYEKRRDFERLAHLYDTLHRAYSKVTEVMHSGKRLLGTYF 149

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1060604597 1835 RVGFYGTKF-GDLDEQEFVYKEPAITKLAEISHRLEGFYGERFGEDVVEVIKDSNPVDKCKLDPNKAYIQITYVEPYFDT 1913
Cdd:cd11698    150 RVAFFGQGFfEDEDGKEYIYKEPKLTPLSEISQRLLKLYSDKFGSENVKMIQDSGKVNPKDLDSKYAYIQVTHVTPYFDE 229

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1060604597 1914 YEMKDRITYFDKNYNLRRFMYCTPFTLDGRAHGELHEQFKRKTILTTSHAFPYIKTRVNVTHKEEIILTPIEVAIEDMQK 1993
Cdd:cd11698    230 KELQERKTDFERSHNIRRFMFEMPFTQSGKRQGGVEEQCKRRTILTAIHCFPYVKKRIPVMYQHHTDLNPIEVAIDEMSK 309

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1060604597 1994 KTQELAFATHQDPADPKMLQMVLQGSVGTTVNQGPLEVAQVFLSEIPSDPKLFRHHNKLRLCFKDFTKRCEDALRKNKSL 2073
Cdd:cd11698    310 KVAELRQLCSSAEVDMIKLQLKLQGSVSVQVNAGPLAYARAFLDDTNTKRYPDNKVKLLKEVFRQFVEACGQALAVNERL 389

                          410       420
                   ....*....|....*....|...
gi 1060604597 2074 IGPDQKEYQRELERNYHRLKEAL 2096
Cdd:cd11698    390 IKEDQLEYQEEMKANYREMAKEL 412
DHR2_DOCK10 cd11699
Dock Homology Region 2, a GEF domain, of Class D Dedicator of Cytokinesis 10; Dock10, also ...
 1675-2089 1.75e-102

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: 337.02  E-value: 1.75e-102
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1060604597 1675 PDLRLTWLQNMAGKHSERSNHAEAAQCLVHSAALVAEYL--------------SMLEDRKYLP----------------V 1724
Cdd:cd11699      1 PELRRTWLESMAKIHARNGDLSEAAMCYIHIAALIAEYLkrkgywkmekictsSMLPEDSQVYdsnlllttstggsmfsM 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1060604597 1725 GCVTFQNISSNVLEESAVSDDVVSPDEEgicsgkyFTESGLVGLLEQAAASFSMAGMYEAVNEVYKVLIPIHEANRDAKK 1804
Cdd:cd11699     81 GWPAFLSITPNIKEEGAMKEDSGMQDTP-------YNENTLVEQLELCVDYLWKSERYELIADVNKPVIAVFEKQRDFKR 153

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1060604597 1805 LSTIHGKLQEAFSKIVHQSTGWERMFGTYFRVGFYGTKFGDLDE-QEFVYKEPAITKLAEISHRLEGFYGERFGEDVVEV 1883
Cdd:cd11699    154 LSELYYDIHRSYLKVAEVVNSEKRLFGRYYRVAFYGQGFFEEEEgKEYIYKEPKLTGLSEISQRLLKLYADKFGADNVKI 233

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1060604597 1884 IKDSNPVDKCKLDPNKAYIQITYVEPYFDTYEMKDRITYFDKNYNLRRFMYCTPFTLDGRAHGELHEQFKRKTILTTSHA 1963
Cdd:cd11699    234 IQDSNKVNPKELDPKFAYIQVTYVTPYFDEKEQEDRKTDFEMHHNINRFVFETPFTLSGKKHGGVEEQCKRRTILTTSHS 313

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1060604597 1964 FPYIKTRVNVTHKEEIILTPIEVAIEDMQKKTQELAFATHQDPADPKMLQMVLQGSVGTTVNQGPLEVAQVFLSEIPSDP 2043
Cdd:cd11699    314 FPYVKKRIQVVSQTSTELNPIEVAIDEMSKKVSELNQLCTMEEVDMIRLQLKLQGSVSVKVNAGPMAYARAFLEETNAKK 393

                          410       420       430       440
                   ....*....|....*....|....*....|....*....|....*.
gi 1060604597 2044 KLFRHHNKLRLCFKDFTKRCEDALRKNKSLIGPDQKEYQRELERNY 2089
Cdd:cd11699    394 YPDNQVKLLKEIFRQFAEACGQALDVNERLIKEDQLEYQEEMRSHY 439
DHR-2_Lobe_A pfam06920
DHR-2, Lobe A; This entry represents a conserved region within a number of eukaryotic ...
 1662-1821 4.12e-69

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: 229.10  E-value: 4.12e-69
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1060604597 1662 DLMYRIAKGYQTSPDLRLTWLQNMAGKHSERSNHAEAAQCLVHSAALVAEYLSMLeDRKYLPVGCVTFQNISSNVL-EES 1740
Cdd:pfam06920    1 DLQYSLANSYKSSPDLRLTWLENLAEKHLENGNFSEAAQCLIHIAALIAEYLKLK-GKIPNPLGASAFEKISPNILrEES 79

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1060604597 1741 AVSDDVvspdeeGICSGKYFTESGLVGLLEQAAASFSMAGMYEAVNEVYKVLIPIHEANRDAKKLSTIHGKLQEAFSKIV 1820
Cdd:pfam06920   80 ALKDDS------GVCDSPHFTEDGLVGLLEEAIDYLDKAERYELAIELYKLLLPIYESRRDYKKLSECHGKLAEAYEKIV 153


                   .
gi 1060604597 1821 H 1821
Cdd:pfam06920  154 E 154
DOCK-C2 pfam14429
C2 domain in Dock180 and Zizimin proteins; The Dock180/Dock1 and Zizimin proteins are atypical ...
 557-736 9.08e-62

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: 209.38  E-value: 9.08e-62
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1060604597  557 NTTYRNLLYIYPQSLNFANR-QGSARNITVKVQFMYGEdpSNAMP-VIFGKSSCsEFSKEAYTAVVYHNRSPDFHEEIKV 634
Cdd:pfam14429    1 PGDYRNDLYVTPKSGNFSKQkKSSARNIEVTVEVRDSD--GEPLPnCIYGGSGG-PFVTEFKSTVYYHNKSPTWYEEIKI 77

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1060604597  635 KLPATLTDHHHLLFTFYHVSCQQKqNTPLETPVGYTWIPMLQNGR--LKTGQFCLPVSL-EKPPQAYSVLS-------PE 704
Cdd:pfam14429   78 ALPAELTPKHHLLFTFYHVSCDEK-KDKVEKPFGYAFLPLLDDDGafLRDGEHTLPVYKyDELPPGYLSLPwssggekES 156

                          170       180       190
                   ....*....|....*....|....*....|..
gi 1060604597  705 VPLPGMKwvdNHKGVFNVEVVAVSSIHTQDPY 736
Cdd:pfam14429  157 SALPGLK---GGKDLFKVRTRLCSTKYTQDEH 185
C2_Dock-D cd08697
C2 domains found in Dedicator Of CytoKinesis (Dock) class C proteins; Dock-D is one of 4 ...
 560-737 6.82e-53

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: 184.06  E-value: 6.82e-53
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1060604597  560 YRNLLYIYPQSLNFANRQGS--ARNITVKVQFMYGeDPSNAMPV--IFGKSSCSeFSKEAYTAVVYHNRSPDFHEEIKVK 635
Cdd:cd08697      1 YKNHLYVYPLHLKYDSQKTFakARNIAVCIEFRDS-DEEDAKPLkcIYYGPGGG-FTTSAYAAVLHHNQNPEFYDEIKIE 78

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1060604597  636 LPATLTDHHHLLFTFYHVSCQQ----KQNTPLETPVGYTWIPMLQ-NGRLKTGQFCLPVSLEKPPQAYSVLSPEVPLPGM 710
Cdd:cd08697     79 LPTQLHEKHHLLFTFYHVSCDInkkgKKKDGVETPVGYAWLPLLKdKGRLNSEEQTPPVANLLPNYPDGYLSIQPHGPEV 158

                          170       180
                   ....*....|....*....|....*..
gi 1060604597  711 KWVDNHKGVFNVEVVAVSSIHTQDPYL 737
Cdd:cd08697    159 KWVDGGKPLFKVSTHLVSTVYTQDQHL 185
C2_DOCK180_related cd08679
C2 domains found in Dedicator Of CytoKinesis 1 (DOCK 180) and related proteins; Dock180 was ...
 560-737 8.27e-52

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: 180.60  E-value: 8.27e-52
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1060604597  560 YRNLLYIYPQSLNFANRQGSARNITVKVQFMYGEDPSNAMPVIFgkSSCSEFSKEAYTAVVYHNRSPDFHEEIKVKLPAT 639
Cdd:cd08679      1 LRNDLYVYPQSGELSKAKSKGRNIEITVEVRDDDGDIIEPCISA--PGSGSELRSEYTSVVYYHKNPVFNDEIKIQLPAD 78

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1060604597  640 LTDHHHLLFTFYHVSCQQKQNTPLETPVGYTWIPML--QNGRLKTGQFCLPVSLEkPPQAYSVLSPEVPLPGMKWVDNHK 717
Cdd:cd08679     79 LTPQHHLLFTFYHVSSKKKQGDKEETPFGYAFLPLMdkDGAFIKDGDHTLPVYKY-DKRPDVGPSGYLSLPSTLANGKSS 157

                          170       180
                   ....*....|....*....|.
gi 1060604597  718 G-VFNVEVVAVSSIHTQDPYL 737
Cdd:cd08679    158 KdTFKIKTRLCSTILTQDKSL 178
DOCK_C-D_N pfam11878
Dedicator of cytokinesis C/D, N terminal; This entry represents the N-terminal domain of the ...
 52-161 4.12e-50

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: 173.22  E-value: 4.12e-50
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1060604597   52 TEAVDPVDLEDYLITHPLAVDSGPLRDLIEFPPDDIEVVYSPRDCRTLVSAVPEE--SEMDPHVRDCIRSYTEDWAIVIR 129
Cdd:pfam11878    1 PKVVEPLDYEEFISQHLTQIENDPLRDLLLFPDDDIEVSVIPRECRTLQPTVPEEaeKEADPLVRECIKTYTSDWHVVNY 80

                           90       100       110
                   ....*....|....*....|....*....|..
gi 1060604597  130 KYHKLGTGFNPNTLDKQKERQKGLPKQVFESD 161
Cdd:pfam11878   81 KYEDYSGDFRQLPKSKRRERPEKLPKQVFEID 112
DHR-2_Lobe_C pfam20421
DHR-2, Lobe C; DOCK (dedicator of cytokinesis) proteins are guanine nucleotide exchange ...
 1997-2099 5.47e-47

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: 163.92  E-value: 5.47e-47
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1060604597 1997 ELAFATHQDPADPKMLQMVLQGSVGTTVNQGPLEVAQVFLSEIPSDPKLFRHHNKLRLCFKDFTKRCEDALRKNKSLIGP 2076
Cdd:pfam20421    1 ELEAAINAPPPNIKTLQMVLQGSVDVQVNAGPLEYAEAFLSEKNVDNYPAEKVEKLKEEFRDFLKVCGEALRLNKKLISE 80

                           90       100
                   ....*....|....*....|...
gi 1060604597 2077 DQKEYQRELERNYHRLKEALQPL 2099
Cdd:pfam20421   81 DQREYQEELEEGFEKLKEKLEPY 103
DHR-2_Lobe_B pfam20422
DHR-2, Lobe B; DOCK (dedicator of cytokinesis) proteins are guanine nucleotide exchange ...
 1887-1963 2.44e-39

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: 141.21  E-value: 2.44e-39
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1060604597 1887 SNPVDKCKLDPNKAYIQITYVEPYFDTYEMKDRITYFDKNYNLRRFMYCTPFTLDGRAHGELHEQFKRKTILTTSHA 1963
Cdd:pfam20422    1 SNPVDESILDPDKAYIQITSVEPYFDDSELNDRVTYFERNNNVNRFVFETPFTKSGKAQGEFEEQWKRRTILTTEHS 77
DHR2_DOCK_B cd11696
Dock Homology Region 2, a GEF domain, of Class B Dedicator of Cytokinesis proteins; DOCK ...
 1790-2096 1.74e-17

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: 87.12  E-value: 1.74e-17
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1060604597 1790 KVLIPIHEANRDAKKLSTIHGKLQEAFSKIVHQstgwERMFGTYFRVGFYGTKFGD-LDEQEFVYKEPAITKLAEISHRL 1868
Cdd:cd11696     81 RELAELYESLYDYAKLSHILRMEASFYDNILTQ----LRPEPEYFRVGFYGKGFPLfLRNKQFVYRGLDYERIGAFTQRL 156

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1060604597 1869 EGFYGErfgedvVEVIKDSNPVDKCKLDPNKAYIQITYVEP------YFDTYEMKDRITYFDKNYNLRRFMYCTPF---T 1939
Cdd:cd11696    157 QSEFPQ------AHILTKNTPPDDAILQADGQYIQICNVKPvperrpVLQMVGVPDKVRSFYRVNDVRKFQYDRPIhkgP 230

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1060604597 1940 LDgrAHGELHEQFKRKTILTTSHAFPYIKTRVNVTHKEEIILTPIEVAIEDMQKKTQELAFATHQDPADPK----MLQMV 2015
Cdd:cd11696    231 ID--KDNEFKSLWIERTTLVTEHSLPGILRWFEVVSREVEEIPPVENACETVENKNQELRSLISQYQADPTrninPFSMR 308

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1060604597 2016 LQGSVGTTVNQGPLEVAQVFLSE--IPSDPKLFRHHNKLRLCFKDFTKRCEDALRKNKSLIGPDQKEYQRELERNYHRLK 2093
Cdd:cd11696    309 LQGVIDAAVNGGIAKYQEAFFTPefILSHPEDAEHIARLRELILEQVQILEAGLALHGKLAPPEVRPLHKRLVERFTQMK 388


                   ...
gi 1060604597 2094 EAL 2096
Cdd:cd11696    389 QSL 391
DHR2_DOCK3 cd11704
Dock Homology Region 2, a GEF domain, of Class B Dedicator of Cytokinesis 3; Dock3, also ...
 1796-2096 4.22e-14

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: 76.59  E-value: 4.22e-14
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1060604597 1796 HEANRDAKKLSTIHGKLQEAFSKIVHQstgwERMFGTYFRVGFYGTKFGD-LDEQEFVYKepaitklAEISHRLEGFYGE 1874
Cdd:cd11704     87 YESLYDYQSLSWIRKMEAAYYDNIMEQ----QRLEPEFFRVGFYGRKFPFfLRNKEYVCR-------GHDYERLEAFQQR 155

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1060604597 1875 RFGEDVVEV-IKDSNPVDKCKLDPNKAYIQITYVEP---YFDTYEMK---DRITYFDKNYNLRRFMYCTPFTLDGR-AHG 1946
Cdd:cd11704    156 MLSEFPQAIaMQHPNHPDDGILQCDAQYLQIYAVTPipdNMDVLQMDrvpDRIKSFYRVNNVRKFRYDRPFHKGPKdKEN 235

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1060604597 1947 ELHEQFKRKTILTTSHAFPYIKTRVNVTHKEEIILTPIEVAIEDMQKKTQEL-----AFATHQDPADPKMLQMVLQGSVG 2021
Cdd:cd11704    236 EFKSLWIERTTLTLTHSLPGISRWFEVERRELVEVSPLENAIQVVENKNQELrtlisQYQHKQLHGNINLLSMCLNGVID 315

                          250       260       270       280       290       300       310
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1060604597 2022 TTVNQGPLEVAQVFLSE--IPSDPKLFRHHNKLRLCFKDFTKRCEDALRKNKSLIGPDQKEYQRELERNYHRLKEAL 2096
Cdd:cd11704    316 AAVNGGIARYQEAFFDKdyISKHPGDAEKITQLKELMQEQVHVLGVGLAVHEKFVHPEMRPLHKKLIDQFQMMRSSL 392
DHR2_DOCK_A cd11697
Dock Homology Region 2, a GEF domain, of Class A Dedicator of Cytokinesis proteins; DOCK ...
 1801-2038 1.22e-13

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: 75.44  E-value: 1.22e-13
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1060604597 1801 DAKKLSTIHGKLQEAFSKIVHQStgweRMFGTYFRVGFYGTKFGD-LDEQEFVYKEPAITKLAEISHRLEGFYGErfged 1879
Cdd:cd11697     97 DYLQLSELLKRMATFYDNIMKTL----RPEPEYFRVGYYGQGFPSfLRNKVFIYRGKEYERLSDFSARLLNQFPN----- 167

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1060604597 1880 vVEVIKDSNPVDKCKLDPNKAYIQITYVEPYFDTYE------MKDRITYFDKNYNLRRFMYCTPF---TLDGRahGELHE 1950
Cdd:cd11697    168 -AELMNTLTPPGDEIKESPGQYLQINKVDPVMDERPrfkgkpVSDQILNYYKVNEVQRFTFSRPFrrgTKDPD--NEFAN 244

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1060604597 1951 QFKRKTILTTSHAFPYIKTRVNVTHKEEIILTPIEVAIEDMQKKTQELAFATHQDPADPKM----LQMVLQGSVGTTVNQ 2026
Cdd:cd11697    245 MWLERTTLTTAYKLPGILRWFEVVSTSTVEISPLENAIETMEDTNKKIRDLILQHQSDPTLpinpLSMLLNGIVDAAVMG 324

                          250
                   ....*....|..
gi 1060604597 2027 GPLEVAQVFLSE 2038
Cdd:cd11697    325 GIANYEKAFFTE 336
DHR2_DOCK2 cd11706
Dock Homology Region 2, a GEF domain, of Class A Dedicator of Cytokinesis 2; Dock2 is a ...
 1707-2038 9.44e-12

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: 69.63  E-value: 9.44e-12
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1060604597 1707 ALVAEYLSMLEDrkyLPVGCVTFQNISSNVLEESAV---SDDVVSPDEEGICSGKYFTESGLV-GLLEQAAASFSMAGMY 1782
Cdd:cd11706     19 AMYIRYLYKLRD---LHLDCENYTEAAYTLLLHTRLlkwSDEQCASQVMQTGQQHPQTQRQLKeTLYETIIGYFDKGKMW 95

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1060604597 1783 EAVNEVYKVLIPIHEAN-RDAKKLSTI---HGKLQEAFSKIVHQSTgwermfgTYFRVGFYGTKFGD-LDEQEFVYKEPA 1857
Cdd:cd11706     96 EEAISLCKELAEQYEMEiFDYELLSQNliqQAKFYESIMKILRPKP-------DYFAVGYYGQGFPSfLRNKVFIYRGKE 168

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1060604597 1858 ITKLAEISHRLEGFYgerfgEDVVEVIKDSNPVDKCKLDPNKaYIQITYVEPYFDTY------EMKDRITYFDKNYNLRR 1931
Cdd:cd11706    169 YERREDFQMQLMSQF-----PNAEKLNTTSAPGDDIKNSPGQ-YIQCFTVQPVLEEHprlknkPVPDQIINFYKSNYVQR 242

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1060604597 1932 FMYCTPF---TLDgrAHGELHEQFKRKTILTTSHAFPYIKTRVNVTHKEEIILTPIEVAIEDMQKKTQELAFATHQDPAD 2008
Cdd:cd11706    243 FHYSRPVrkgPVD--PENEFASMWIERTTFVTAYKLPGILRWFEVTHMSQTTISPLENAIETMSTTNEKILMMINQYQSD 320

                          330       340       350
                   ....*....|....*....|....*....|....
gi 1060604597 2009 PKM----LQMVLQGSVGTTVNQGPLEVAQVFLSE 2038
Cdd:cd11706    321 ESLpinpLSMLLNGIVDPAVMGGFAKYEKAFFTE 354
DHR2_DOCK4 cd11705
Dock Homology Region 2, a GEF domain, of Class B Dedicator of Cytokinesis 4; Dock4 is an ...
 1796-2096 1.09e-10

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: 65.82  E-value: 1.09e-10
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1060604597 1796 HEANRDAKKLSTIHGKLQEAFSKIVHQstgwERMFGTYFRVGFYGTKFGD-LDEQEFVYKEPAITKLAEISHRLEGFYGE 1874
Cdd:cd11705     87 YESYYDYRNLSKMRMMEASLYDKIMDQ----QRLEPEFFRVGFYGKKFPFfLRNKEFVCRGHDYERLEAFQQRMLNEFPH 162

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1060604597 1875 RFGedvvevIKDSNPVDKCKLDPNKAYIQITYVEPYFDTYEM------KDRITYFDKNYNLRRFMYCTPFTLDGR-AHGE 1947
Cdd:cd11705    163 AIA------MQHANQPDETIFQAEAQYLQIYAVTPIPESQEVlqrdgvPDNIKSFYKVNHIWRFRYDRPFHKGTKdKENE 236

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1060604597 1948 LHEQFKRKTILTTSHAFPYIKTRVNVTHKEEIILTPIEVAIEDMQKKTQELAFATHQ----DPADPKMLQMVLQGSVGTT 2023
Cdd:cd11705    237 FKSLWVERTTLTLVQSLPGISRWFEVEKREVVEMSPLENAIEVLENKNQQLRTLISQcqtrQMQNINPLTMCLNGVIDAA 316

                          250       260       270       280       290       300       310
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1060604597 2024 VNQGPLEVAQVFLSE--IPSDPKLFRHHNKLRLCFKDFTKRCEDALRKNKSLIGPDQKEYQRELERNYHRLKEAL 2096
Cdd:cd11705    317 VNGGVSRYQEAFFVKeyILNHPEDGDKITRLRELMLEQAQILEFGLAVHEKFVPQDMRPLHKKLVDQFFVMKSSL 391
DHR2_DOCK5 cd11708
Dock Homology Region 2, a GEF domain, of Class A Dedicator of Cytokinesis 5; Dock5 is an ...
 1768-2064 5.78e-10

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: 63.81  E-value: 5.78e-10
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1060604597 1768 LLEQAAASFSMAGMYEAVNEVYKVLIPIHEANR-DAKKLSTIHGKLQEAFSKIVHQStgweRMFGTYFRVGFYGTKFGD- 1845
Cdd:cd11708     63 LYQEIISFFDKGKMWEKAIELSKELADMYENQVfDYEGLGNLLKKQAQFYENIMKAM----RPQPEYFAVGYYGQGFPSf 138

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1060604597 1846 LDEQEFVYKEPAITKLAEISHRLEGFYgerfgEDVVEVIKDSNPVDKCKLDPnKAYIQITYVEPYFD-TYEMKDR----- 1919
Cdd:cd11708    139 LRNKIFIYRGKEYERLEDFSLKLLTQF-----PNAEKMTSTSPPGDEIKSST-KQYVQCFTVKPVMNlPSHYKDKpvpeq 212

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1060604597 1920 -ITYFDKNyNLRRFMYCTPFTLDGR-AHGELHEQFKRKTILTTSHAFPYIKTRVNVTH--KEEIilTPIEVAIEDMQKKT 1995
Cdd:cd11708    213 iLNYYRAN-EVQQFQYSRPFRKGEKdPDNEFATMWIERTTFTTAYRFPGILKWFEVKQisTEEI--SPLENAIETMELTN 289

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1060604597 1996 QELAFATHQDPADPKM----LQMVLQGSVGTTVNQGPLEVAQVF-----LSEIPSDP---KLFRH--------------- 2048
Cdd:cd11708    290 EKISNLVQQHAWDRSLpvhpLSMLLNGIVDPAVMGGFSNYEKAFftekyLQEHPEDQekiELLKQlialqmpllaegiri 369

                          330       340
                   ....*....|....*....|....*...
gi 1060604597 2049 ------------HNKLRLCFKDFTKRCE 2064
Cdd:cd11708    370 hgeklteqlkplHERLVSCFKDLRAKVE 397
DHR2_DOCK1 cd11707
Dock Homology Region 2, a GEF domain, of Class A Dedicator of Cytokinesis 1; Dock1, also ...
 1676-2038 2.11e-08

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: 58.90  E-value: 2.11e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1060604597 1676 DLRLTWLQNMAGKHSERSNHAEAAQCLVHSAALVaeylsmledrKYLPVGCVT-------FQNISSNVLEESAVSDDVVS 1748
Cdd:cd11707      1 EMYIRYLYKLCDLHKECDNYTEAAYTLLLHAKLL----------KWSEEACAAhltqrdgYQATTQGQLKDQLYQEIIHY 70

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1060604597 1749 PDEegicsGKYFTESGLVGLleqaaasfSMAGMYEavNEVYkvlipiheanrDAKKLSTIHGKLQEAFSKIVHQStgweR 1828
Cdd:cd11707     71 FDK-----GKMWEEAIALGK--------ELAEQYE--NEMF-----------DYEQLSELLKKQAQFYENIVKVI----R 120

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1060604597 1829 MFGTYFRVGFYGTKFGD-LDEQEFVYKEPAITKLAEISHRLEGFYGErfgedvVEVIKDSNPV-DKCKLDPNKaYIQITY 1906
Cdd:cd11707    121 PKPDYFAVGYYGQGFPTfLRNKMFIYRGKEYERREDFEARLLTQFPN------AEKMKTTSPPgDDIKNSSGQ-YIQCFT 193

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1060604597 1907 VEPYFDTYEMK------DRITYFDKNYNLRRFMYCTPFTL-DGRAHGELHEQFKRKTILTTSHAFPYIKTRVNVTHKEEI 1979
Cdd:cd11707    194 VKPLLELPPKFqnkpvsEQIVSFYRVNEVQRFQYSRPVRKgEKDPDNEFANMWIERTTYVTAYKLPGILRWFEVKSVFMV 273

                          330       340       350       360       370       380
                   ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1060604597 1980 ILTPIEVAIEDMQKKTQELAFATHQDPADPKM----LQMVLQGSVGTTVNQGPLEVAQVFLSE 2038
Cdd:cd11707    274 EISPLENAIETMQLTNEKINNMVQQHLNDPNLpinpLSMLLNGIVDPAVMGGFANYEKAFFTE 336
C2_Dock-A cd08694
C2 domains found in Dedicator Of CytoKinesis (Dock) class A proteins; Dock-A is one of 4 ...
 561-678 3.07e-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: 47.01  E-value: 3.07e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1060604597  561 RNLLYIYPQSLNFAN-RQGSARNITVKVQfMYGEDpSNAMPVIFGKSSCSEFSKEAYTAVVYHNRSPDFHEEIKVKLPAT 639
Cdd:cd08694      2 RNDLYLTLVQGDFDKgSKTSDKNVEVTVS-VCNED-GKIIPGVISLGAGEEPIDEYKSVIYYQVDKPKWFETFKVAIPIE 79

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|
gi 1060604597  640 LTDHHHLLFTFYHVSCQQKQNTPlETPVGYTWIPMLQ-NG 678
Cdd:cd08694     80 DFKSSHLRFTFKHRSSNEAKDKS-EKPFALSFVKLMQeNG 118
C2_Dock-B cd08695
C2 domains found in Dedicator Of CytoKinesis (Dock) class B proteins; Dock-B is one of 4 ...
 561-678 9.12e-05

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: 45.45  E-value: 9.12e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1060604597  561 RNLLYIYPQSLNFaNRQG--SARNITVKVQFMY--GEDPSNAMPVIFGKSSCSEFskeaYTAVVYHNRSPDFHEEIKVKL 636
Cdd:cd08695      2 RNDLYLTLERGEF-EKGGksTAKNIEVTMVVLDadGQVLKDCISLGSGEPPCSEY----RSFVLYHNNSPRWNETIKLPI 76

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|..
gi 1060604597  637 PATLTDHHHLLFTFYHVSCQQKQNTPLetpVGYTWIPMLQNG 678
Cdd:cd08695     77 PIDKFRGSHLRFEFRHCSTKDKGEKKL---FGFSFVPLMRED 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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