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Q92608 (DOCK2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 130. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Dedicator of cytokinesis protein 2
Gene names
Name:DOCK2
Synonyms:KIAA0209
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length1830 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Involved in cytoskeletal rearrangements required for lymphocyte migration in response of chemokines. Activates RAC1 and RAC2, but not CDC42, by functioning as a guanine nucleotide exchange factor (GEF), which exchanges bound GDP for free GTP. May also participate in IL2 transcriptional activation via the activation of RAC2. Ref.14

Subunit structure

Homodimer Probable. Interacts with RAC1 and RAC2. Interacts with CRKL and VAV. Interacts with CD3Z. Ref.3 Ref.4 Ref.5 Ref.14

Subcellular location

Endomembrane system; Peripheral membrane protein. Cytoplasmcytoskeleton. Note: Colocalizes with F-actin. Ref.4

Tissue specificity

Specifically expressed in hematopoietic cells. Highly expressed in peripheral blood leukocytes, and expressed at intermediate level in thymus and spleen. Expressed at very low level in the small intestine and colon. Ref.3

Domain

The DHR-2 domain may mediate the GEF activity By similarity.

Sequence similarities

Belongs to the DOCK family.

Contains 1 DHR-1 domain.

Contains 1 DHR-2 domain.

Contains 1 SH3 domain.

Sequence caution

The sequence BAA13200.1 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
   Cellular componentCytoplasm
Cytoskeleton
Membrane
   Coding sequence diversityAlternative splicing
Polymorphism
   DomainSH3 domain
   Molecular functionGuanine-nucleotide releasing factor
   PTMAcetylation
Phosphoprotein
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processactin cytoskeleton organization

Traceable author statement Ref.5. Source: UniProtKB

alpha-beta T cell proliferation

Inferred from electronic annotation. Source: Ensembl

chemotaxis

Inferred from electronic annotation. Source: Ensembl

establishment of T cell polarity

Inferred from electronic annotation. Source: Ensembl

immunological synapse formation

Inferred from electronic annotation. Source: Ensembl

macropinocytosis

Inferred from sequence or structural similarity. Source: UniProtKB

membrane raft polarization

Inferred from electronic annotation. Source: Ensembl

myeloid dendritic cell activation involved in immune response

Inferred from sequence or structural similarity. Source: UniProtKB

negative thymic T cell selection

Inferred from electronic annotation. Source: Ensembl

positive regulation of phagocytosis

Inferred from sequence or structural similarity. Source: UniProtKB

positive thymic T cell selection

Inferred from electronic annotation. Source: Ensembl

regulation of Rac GTPase activity

Inferred from direct assay Ref.3. Source: GOC

regulation of defense response to virus by virus

Traceable author statement. Source: Reactome

small GTPase mediated signal transduction

Inferred from electronic annotation. Source: InterPro

viral process

Traceable author statement. Source: Reactome

   Cellular_componentcytoskeleton

Inferred from electronic annotation. Source: UniProtKB-SubCell

cytosol

Traceable author statement. Source: Reactome

endomembrane system

Inferred from electronic annotation. Source: UniProtKB-SubCell

extracellular vesicular exosome

Inferred from direct assay PubMed 20458337. Source: UniProt

membrane

Inferred from electronic annotation. Source: UniProtKB-KW

   Molecular_functionRac GTPase activator activity

Inferred from electronic annotation. Source: Ensembl

Rac guanyl-nucleotide exchange factor activity

Inferred from direct assay Ref.3. Source: UniProtKB

T cell receptor binding

Inferred from direct assay Ref.5. Source: UniProtKB

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

RAC1P630003EBI-448771,EBI-413628

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q92608-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform 2 (identifier: Q92608-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-449: Missing.
     462-494: Missing.
     630-766: Missing.
     934-955: SHFVACMTAILNQMGDQHYSFY → GACCNCGFPSSTPHSLIQWLWG
     956-1830: Missing.
Note: Splicing donor and acceptor sites between exon 6 and exon 7 are not canonical. No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 18301830Dedicator of cytokinesis protein 2
PRO_0000189986

Regions

Domain8 – 6962SH3
Domain423 – 607185DHR-1
Domain1211 – 1622412DHR-2
Region939 – 1476538Interaction with CRKL

Amino acid modifications

Modified residue3041N6-acetyllysine Ref.11
Modified residue5881Phosphoserine Ref.10
Modified residue5931Phosphoserine Ref.10
Modified residue7381N6-acetyllysine Ref.11
Modified residue16851Phosphoserine Ref.8 Ref.9 Ref.10
Modified residue17311Phosphoserine Ref.10

Natural variations

Alternative sequence1 – 449449Missing in isoform 2.
VSP_007696
Alternative sequence462 – 49433Missing in isoform 2.
VSP_007697
Alternative sequence630 – 766137Missing in isoform 2.
VSP_007698
Alternative sequence934 – 95522SHFVA…HYSFY → GACCNCGFPSSTPHSLIQWL WG in isoform 2.
VSP_007699
Alternative sequence956 – 1830875Missing in isoform 2.
VSP_007700
Natural variant15581D → A.
Corresponds to variant rs13179480 [ dbSNP | Ensembl ].
VAR_053064
Natural variant17461S → T.
Corresponds to variant rs2270898 [ dbSNP | Ensembl ].
VAR_015822
Natural variant17791T → S.
Corresponds to variant rs2270898 [ dbSNP | Ensembl ].
VAR_022137

Secondary structure

....................................................................... 1830
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified July 3, 2003. Version 2.
Checksum: 18568D3322DAA92A

FASTA1,830211,948
        10         20         30         40         50         60 
MAPWRKADKE RHGVAIYNFQ GSGAPQLSLQ IGDVVRIQET CGDWYRGYLI KHKMLQGIFP 

        70         80         90        100        110        120 
KSFIHIKEVT VEKRRNTENI IPAEIPLAQE VTTTLWEWGS IWKQLYVASK KERFLQVQSM 

       130        140        150        160        170        180 
MYDLMEWRSQ LLSGTLPKDE LKELKQKVTS KIDYGNKILE LDLIVRDEDG NILDPDNTSV 

       190        200        210        220        230        240 
ISLFHAHEEA TDKITERIKE EMSKDQPDYA MYSRISSSPT HSLYVFVRNF VCRIGEDAEL 

       250        260        270        280        290        300 
FMSLYDPNKQ TVISENYLVR WGSRGFPKEI EMLNNLKVVF TDLGNKDLNR DKIYLICQIV 

       310        320        330        340        350        360 
RVGKMDLKDT GAKKCTQGLR RPFGVAVMDI TDIIKGKAES DEEKQHFIPF HPVTAENDFL 

       370        380        390        400        410        420 
HSLLGKVIAS KGDSGGQGLW VTMKMLVGDI IQIRKDYPHL VDRTTVVARK LGFPEIIMPG 

       430        440        450        460        470        480 
DVRNDIYITL LQGDFDKYNK TTQRNVEVIM CVCAEDGKTL PNAICVGAGD KPMNEYRSVV 

       490        500        510        520        530        540 
YYQVKQPRWM ETVKVAVPIE DMQRIHLRFM FRHRSSLESK DKGEKNFAMS YVKLMKEDGT 

       550        560        570        580        590        600 
TLHDGFHDLV VLKGDSKKME DASAYLTLPS YRHHVENKGA TLSRSSSSVG GLSVSSRDVF 

       610        620        630        640        650        660 
SISTLVCSTK LTQNVGLLGL LKWRMKPQLL QENLEKLKIV DGEEVVKFLQ DTLDALFNIM 

       670        680        690        700        710        720 
MEHSQSDEYD ILVFDALIYI IGLIADRKFQ HFNTVLEAYI QQHFSATLAY KKLMTVLKTY 

       730        740        750        760        770        780 
LDTSSRGEQC EPILRTLKAL EYVFKFIVRS RTLFSQLYEG KEQMEFEESM RRLFESINNL 

       790        800        810        820        830        840 
MKSQYKTTIL LQVAALKYIP SVLHDVEMVF DAKLLSQLLY EFYTCIPPVK LQKQKVQSMN 

       850        860        870        880        890        900 
EIVQSNLFKK QECRDILLPV ITKELKELLE QKDDMQHQVL ERKYCVELLN SILEVLSYQD 

       910        920        930        940        950        960 
AAFTYHHIQE IMVQLLRTVN RTVITMGRDH ILISHFVACM TAILNQMGDQ HYSFYIETFQ 

       970        980        990       1000       1010       1020 
TSSELVDFLM ETFIMFKDLI GKNVYPGDWM AMSMVQNRVF LRAINKFAET MNQKFLEHTN 

      1030       1040       1050       1060       1070       1080 
FEFQLWNNYF HLAVAFITQD SLQLEQFSHA KYNKILNKYG DMRRLIGFSI RDMWYKLGQN 

      1090       1100       1110       1120       1130       1140 
KICFIPGMVG PILEMTLIPE AELRKATIPI FFDMMLCEYQ RSGDFKKFEN EIILKLDHEV 

      1150       1160       1170       1180       1190       1200 
EGGRGDEQYM QLLESILMEC AAEHPTIAKS VENFVNLVKG LLEKLLDYRG VMTDESKDNR 

      1210       1220       1230       1240       1250       1260 
MSCTVNLLNF YKDNNREEMY IRYLYKLRDL HLDCDNYTEA AYTLLLHTWL LKWSDEQCAS 

      1270       1280       1290       1300       1310       1320 
QVMQTGQQHP QTHRQLKETL YETIIGYFDK GKMWEEAISL CKELAEQYEM EIFDYELLSQ 

      1330       1340       1350       1360       1370       1380 
NLIQQAKFYE SIMKILRPKP DYFAVGYYGQ GFPSFLRNKV FIYRGKEYER REDFQMQLMT 

      1390       1400       1410       1420       1430       1440 
QFPNAEKMNT TSAPGDDVKN APGQYIQCFT VQPVLDEHPR FKNKPVPDQI INFYKSNYVQ 

      1450       1460       1470       1480       1490       1500 
RFHYSRPVRR GTVDPENEFA SMWIERTSFV TAYKLPGILR WFEVVHMSQT TISPLENAIE 

      1510       1520       1530       1540       1550       1560 
TMSTANEKIL MMINQYQSDE TLPINPLSML LNGIVDPAVM GGFAKYEKAF FTEEYVRDHP 

      1570       1580       1590       1600       1610       1620 
EDQDKLTHLK DLIAWQIPFL GAGIKIHEKR VSDNLRPFHD RMEECFKNLK MKVEKEYGVR 

      1630       1640       1650       1660       1670       1680 
EMPDFDDRRV GRPRSMLRSY RQMSIISLAS MNSDCSTPSK PTSESFDLEL ASPKTPRVEQ 

      1690       1700       1710       1720       1730       1740 
EEPISPGSTL PEVKLRRSKK RTKRSSVVFA DEKAAAESDL KRLSRKHEFM SDTNLSEHAA 

      1750       1760       1770       1780       1790       1800 
IPLKASVLSQ MSFASQSMPT IPALALSVAG IPGLDEANTS PRLSQTFLQL SDGDKKTLTR 

      1810       1820       1830 
KKVNQFFKTM LASKSAEEGK QIPDSLSTDL 

« Hide

Isoform 2 [UniParc].

Checksum: C5D6CAAB1C3A3490
Show »

FASTA33638,461

References

« Hide 'large scale' references
[1]"Prediction of the coding sequences of unidentified human genes. VI. The coding sequences of 80 new genes (KIAA0201-KIAA0280) deduced by analysis of cDNA clones from cell line KG-1 and brain."
Nagase T., Seki N., Ishikawa K., Ohira M., Kawarabayasi Y., Ohara O., Tanaka A., Kotani H., Miyajima N., Nomura N.
DNA Res. 3:321-329(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Tissue: Bone marrow.
[2]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
Tissue: Colon and Liver.
[3]"Non-adherent cell-specific expression of DOCK2, a member of the human CDM-family proteins."
Nishihara H., Kobayashi S., Hashimoto Y., Ohba F., Mochizuki N., Kurata T., Nagashima K., Matsuda M.
Biochim. Biophys. Acta 1452:179-187(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: TISSUE SPECIFICITY, RAC1 ACTIVATION, INTERACTION WITH RAC1 AND RAC2.
[4]"DOCK2 associates with CrkL and regulates Rac1 in human leukemia cell lines."
Nishihara H., Maeda M., Oda A., Tsuda M., Sawa H., Nagashima K., Tanaka S.
Blood 100:3968-3974(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION, INTERACTION WITH CRKL AND VAV.
[5]"DOCK2 mediates T cell receptor-induced activation of Rac2 and IL-2 transcription."
Nishihara H., Maeda M., Tsuda M., Makino Y., Sawa H., Nagashima K., Tanaka S.
Biochem. Biophys. Res. Commun. 296:716-720(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH CD3Z.
[6]"Identification of an evolutionarily conserved superfamily of DOCK180-related proteins with guanine nucleotide exchange activity."
Cote J.-F., Vuori K.
J. Cell Sci. 115:4901-4913(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: NOMENCLATURE.
[7]"Robust phosphoproteomic profiling of tyrosine phosphorylation sites from human T cells using immobilized metal affinity chromatography and tandem mass spectrometry."
Brill L.M., Salomon A.R., Ficarro S.B., Mukherji M., Stettler-Gill M., Peters E.C.
Anal. Chem. 76:2763-2772(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Leukemic T-cell.
[8]"Phosphorylation analysis of primary human T lymphocytes using sequential IMAC and titanium oxide enrichment."
Carrascal M., Ovelleiro D., Casas V., Gay M., Abian J.
J. Proteome Res. 7:5167-5176(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1685, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: T-cell.
[9]"Large-scale proteomics analysis of the human kinome."
Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G., Mann M., Daub H.
Mol. Cell. Proteomics 8:1751-1764(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1685, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[10]"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions."
Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K.
Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-588; SER-593; SER-1685 AND SER-1731, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Leukemic T-cell.
[11]"Lysine acetylation targets protein complexes and co-regulates major cellular functions."
Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C., Olsen J.V., Mann M.
Science 325:834-840(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-304 AND LYS-738, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[12]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[13]"The solution structure of human DOCK2 SH3 domain - ELMO1 peptide chimera complex."
RIKEN structural genomics initiative (RSGI)
Submitted (OCT-2010) to the PDB data bank
Cited for: STRUCTURE BY NMR OF 8-70.
[14]"Multiple factors confer specific Cdc42 and Rac protein activation by dedicator of cytokinesis (DOCK) nucleotide exchange factors."
Kulkarni K., Yang J., Zhang Z., Barford D.
J. Biol. Chem. 286:25341-25351(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS) OF 1192-1622 IN COMPLEX WITH RAC1, INTERACTION WITH RAC1, SUBUNIT, FUNCTION.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
D86964 mRNA. Translation: BAA13200.1. Different initiation.
BC016996 mRNA. Translation: AAH16996.1.
BC104900 mRNA. Translation: AAI04901.1.
BC113457 mRNA. Translation: AAI13458.1.
RefSeqNP_004937.1. NM_004946.2.
UniGeneHs.586174.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2RQRNMR-A8-70[»]
2YINX-ray2.70A/B1192-1622[»]
3A98X-ray2.10A/C1-177[»]
3B13X-ray3.01A/C1196-1622[»]
ProteinModelPortalQ92608.
SMRQ92608. Positions 1-167, 423-609, 1196-1622.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid108129. 10 interactions.
DIPDIP-31791N.
IntActQ92608. 3 interactions.
MINTMINT-2813049.
STRING9606.ENSP00000256935.

PTM databases

PhosphoSiteQ92608.

Polymorphism databases

DMDM32469765.

Proteomic databases

PaxDbQ92608.
PeptideAtlasQ92608.
PRIDEQ92608.

Protocols and materials databases

DNASU1794.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000256935; ENSP00000256935; ENSG00000134516. [Q92608-1]
GeneID1794.
KEGGhsa:1794.
UCSCuc003maf.3. human. [Q92608-1]

Organism-specific databases

CTD1794.
GeneCardsGC05P169064.
HGNCHGNC:2988. DOCK2.
HPAHPA036468.
HPA036469.
MIM603122. gene.
neXtProtNX_Q92608.
PharmGKBPA27454.
HUGESearch...
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG289808.
HOGENOMHOG000006631.
HOVERGENHBG051389.
InParanoidQ92608.
KOK12367.
OMAGDWMAMS.
OrthoDBEOG7QNVK8.
PhylomeDBQ92608.
TreeFamTF300423.

Enzyme and pathway databases

ReactomeREACT_116125. Disease.
REACT_604. Hemostasis.

Gene expression databases

ArrayExpressQ92608.
BgeeQ92608.
CleanExHS_DOCK2.
GenevestigatorQ92608.

Family and domain databases

InterProIPR016024. ARM-type_fold.
IPR027007. DHR-1_domain.
IPR027357. DHR-2.
IPR026791. DOCK.
IPR026799. DOCK_2.
IPR010703. DOCK_C.
IPR011511. SH3_2.
IPR001452. SH3_domain.
[Graphical view]
PANTHERPTHR23317. PTHR23317. 1 hit.
PTHR23317:SF29. PTHR23317:SF29. 1 hit.
PfamPF06920. Ded_cyto. 1 hit.
PF14429. DOCK-C2. 1 hit.
PF07653. SH3_2. 1 hit.
[Graphical view]
SMARTSM00326. SH3. 1 hit.
[Graphical view]
SUPFAMSSF48371. SSF48371. 3 hits.
SSF50044. SSF50044. 1 hit.
PROSITEPS51650. DHR_1. 1 hit.
PS51651. DHR_2. 1 hit.
PS50002. SH3. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSDOCK2. human.
GeneWikiDock2.
GenomeRNAi1794.
NextBio7309.
PROQ92608.
SOURCESearch...

Entry information

Entry nameDOCK2_HUMAN
AccessionPrimary (citable) accession number: Q92608
Secondary accession number(s): Q2M3I0, Q96AK7
Entry history
Integrated into UniProtKB/Swiss-Prot: July 3, 2003
Last sequence update: July 3, 2003
Last modified: April 16, 2014
This is version 130 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 5

Human chromosome 5: entries, gene names and cross-references to MIM