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Q14185 (DOCK1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 127. 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·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Dedicator of cytokinesis protein 1
Alternative name(s):
180 kDa protein downstream of CRK
Short name=DOCK180
Gene names
Name:DOCK1
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length1865 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Involved in cytoskeletal rearrangements required for phagocytosis of apoptotic cells and cell motility. Functions as a guanine nucleotide exchange factor (GEF), which activates Rac Rho small GTPases by exchanging bound GDP for free GTP. Its GEF activity may be enhanced by ELMO1. Ref.1

Subunit structure

Interacts with the SH3 domains of CRK and NCK2 via multiple sites. Interacts with nucleotide-free RAC1 via its DHR-2 domain. Interacts with ELMO1, ELMO2 and probably ELMO3 via its SH3 domain. Interacts with RAC1 and BAI1. Ref.1 Ref.3 Ref.4 Ref.5 Ref.6 Ref.7

Subcellular location

Cytoplasm Probable. Membrane Probable. Note: Recruited to membranes via its interaction with phosphatidylinositol 3,4,5-trisphosphate Probable.

Tissue specificity

Highly expressed in placenta, lung, kidney, pancreas and ovary. Expressed at intermediate level in thymus, testes and colon.

Domain

The DHR-2 domain is necessary and sufficient for the GEF activity.

Sequence similarities

Belongs to the DOCK family.

Contains 1 DHR-1 domain.

Contains 1 DHR-2 domain.

Contains 1 SH3 domain.

Ontologies

Keywords
   Biological processApoptosis
Phagocytosis
   Cellular componentCytoplasm
Membrane
   Coding sequence diversityPolymorphism
   DomainSH3 domain
SH3-binding
   Molecular functionGuanine-nucleotide releasing factor
   PTMPhosphoprotein
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processFc-gamma receptor signaling pathway involved in phagocytosis

Traceable author statement. Source: Reactome

apoptotic process

Traceable author statement PubMed 9548255. Source: ProtInc

axon guidance

Traceable author statement. Source: Reactome

blood coagulation

Traceable author statement. Source: Reactome

cell migration

Inferred from electronic annotation. Source: Ensembl

innate immune response

Traceable author statement. Source: Reactome

integrin-mediated signaling pathway

Traceable author statement Ref.4. Source: ProtInc

phagocytosis, engulfment

Traceable author statement PubMed 9548255. Source: ProtInc

positive regulation of GTPase activity

Traceable author statement Ref.4. Source: GOC

signal transduction

Traceable author statement PubMed 8661160. Source: ProtInc

small GTPase mediated signal transduction

Traceable author statement Ref.4. Source: ProtInc

   Cellular_componentcytoplasm

Inferred from direct assay. Source: HPA

cytosol

Traceable author statement. Source: Reactome

membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

nucleus

Inferred from direct assay. Source: HPA

   Molecular_functionGTPase activator activity

Traceable author statement Ref.4. Source: ProtInc

guanyl-nucleotide exchange factor activity

Inferred from electronic annotation. Source: UniProtKB-KW

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 18651865Dedicator of cytokinesis protein 1
PRO_0000189984

Regions

Domain9 – 7062SH3
Domain425 – 609185DHR-1
Domain1207 – 1617411DHR-2
Region1687 – 16959Phosphoinositide-binding Potential
Region1793 – 181927Interaction with NCK2 second and third SH3 domain (minor)
Region1820 – 183617Interaction with NCK2 third SH3 domain (major)
Region1837 – 185216Interaction with NCK2 (minor)
Motif1799 – 18057SH3-binding; interaction with CRK Potential
Motif1838 – 18436SH3-binding; interaction with CRK Potential

Amino acid modifications

Modified residue17511Phosphoserine Ref.9
Modified residue17561Phosphoserine By similarity

Natural variations

Natural variant17931A → T.
Corresponds to variant rs869801 [ dbSNP | Ensembl ].
VAR_059971

Experimental info

Mutagenesis1401 – 14022YI → AA: Abolishes Rac GEF activity.
Mutagenesis1487 – 14893ISP → AAA: Abolishes Rac GEF activity. Ref.7
Sequence conflict18571A → T in BAA09454. Ref.1

Secondary structure

....................... 1865
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Q14185 [UniParc].

Last modified October 14, 2008. Version 2.
Checksum: 940C5AFD047EBEDE

FASTA1,865215,346
        10         20         30         40         50         60 
MTRWVPTKRE EKYGVAFYNY DARGADELSL QIGDTVHILE TYEGWYRGYT LRKKSKKGIF 

        70         80         90        100        110        120 
PASYIHLKEA IVEGKGQHET VIPGDLPLIQ EVTTTLREWS TIWRQLYVQD NREMFRSVRH 

       130        140        150        160        170        180 
MIYDLIEWRS QILSGTLPQD ELKELKKKVT AKIDYGNRIL DLDLVVRDED GNILDPELTS 

       190        200        210        220        230        240 
TISLFRAHEI ASKQVEERLQ EEKSQKQNID INRQAKFAAT PSLALFVNLK NVVCKIGEDA 

       250        260        270        280        290        300 
EVLMSLYDPV ESKFISENYL VRWSSSGLPK DIDRLHNLRA VFTDLGSKDL KREKISFVCQ 

       310        320        330        340        350        360 
IVRVGRMELR DNNTRKLTSG LRRPFGVAVM DVTDIINGKV DDEDKQHFIP FQPVAGENDF 

       370        380        390        400        410        420 
LQTVINKVIA AKEVNHKGQG LWVTLKLLPG DIHQIRKEFP HLVDRTTAVA RKTGFPEIIM 

       430        440        450        460        470        480 
PGDVRNDIYV TLVQGDFDKG SKTTAKNVEV TVSVYDEDGK RLEHVIFPGA GDEAISEYKS 

       490        500        510        520        530        540 
VIYYQVKQPR WFETVKVAIP IEDVNRSHLR FTFRHRSSQD SKDKSEKIFA LAFVKLMRYD 

       550        560        570        580        590        600 
GTTLRDGEHD LIVYKAEAKK LEDAATYLSL PSTKAELEEK GHSATGKSMQ SLGSCTISKD 

       610        620        630        640        650        660 
SFQISTLVCS TKLTQNVDLL GLLKWRSNTS LLQQNLRQLM KVDGGEVVKF LQDTLDALFN 

       670        680        690        700        710        720 
IMMENSESET FDTLVFDALV FIIGLIADRK FQHFNPVLET YIKKHFSATL AYTKLTKVLK 

       730        740        750        760        770        780 
NYVDGAEKPG VNEQLYKAMK ALESIFKFIV RSRILFNQLY ENKGEADFVE SLLQLFRSIN 

       790        800        810        820        830        840 
DMMSSMSDQT VRVKGAALKY LPTIVNDVKL VFDPKELSKM FTEFILNVPM GLLTIQKLYC 

       850        860        870        880        890        900 
LIEIVHSDLF TQHDCREILL PMMTDQLKYH LERQEDLEAC CQLLSHILEV LYRKDVGPTQ 

       910        920        930        940        950        960 
RHVQIIMEKL LRTVNRTVIS MGRDSELIGN FVACMTAILR QMEDYHYAHL IKTFGKMRTD 

       970        980        990       1000       1010       1020 
VVDFLMETFI MFKNLIGKNV YPFDWVIMNM VQNKVFLRAI NQYADMLNKK FLDQANFELQ 

      1030       1040       1050       1060       1070       1080 
LWNNYFHLAV AFLTQESLQL ENFSSAKRAK ILNKYGDMRR QIGFEIRDMW YNLGQHKIKF 

      1090       1100       1110       1120       1130       1140 
IPEMVGPILE MTLIPETELR KATIPIFFDM MQCEFHSTRS FQMFENEIIT KLDHEVEGGR 

      1150       1160       1170       1180       1190       1200 
GDEQYKVLFD KILLEHCRKH KYLAKTGETF VKLVVRLMER LLDYRTIMHD ENKENRMSCT 

      1210       1220       1230       1240       1250       1260 
VNVLNFYKEI EREEMYIRYL YKLCDLHKEC DNYTEAAYTL LLHAKLLKWS EDVCVAHLTQ 

      1270       1280       1290       1300       1310       1320 
RDGYQATTQG QLKEQLYQEI IHYFDKGKMW EEAIALGKEL AEQYENEMFD YEQLSELLKK 

      1330       1340       1350       1360       1370       1380 
QAQFYENIVK VIRPKPDYFA VGYYGQGFPT FLRGKVFIYR GKEYERREDF EARLLTQFPN 

      1390       1400       1410       1420       1430       1440 
AEKMKTTSPP GDDIKNSPGQ YIQCFTVKPK LDLPPKFHRP VSEQIVSFYR VNEVQRFEYS 

      1450       1460       1470       1480       1490       1500 
RPIRKGEKNP DNEFANMWIE RTIYTTAYKL PGILRWFEVK SVFMVEISPL ENAIETMQLT 

      1510       1520       1530       1540       1550       1560 
NDKINSMVQQ HLDDPSLPIN PLSMLLNGIV DPAVMGGFAN YEKAFFTDRY LQEHPEAHEK 

      1570       1580       1590       1600       1610       1620 
IEKLKDLIAW QIPFLAEGIR IHGDKVTEAL RPFHERMEAC FKQLKEKVEK EYGVRIMPSS 

      1630       1640       1650       1660       1670       1680 
LDDRRGSRPR SMVRSFTMPS SSRPLSVASV SSLSSDSTPS RPGSDGFALE PLLPKKMHSR 

      1690       1700       1710       1720       1730       1740 
SQDKLDKDDL EKEKKDKKKE KRNSKHQEIF EKEFKPTDIS LQQSEAVILS ETISPLRPQR 

      1750       1760       1770       1780       1790       1800 
PKSQVMNVIG SERRFSVSPS SPSSQQTPPP VTPRAKLSFS MQSSLELNGM TGADVADVPP 

      1810       1820       1830       1840       1850       1860 
PLPLKGSVAD YGNLMENQDL LGSPTPPPPP PHQRHLPPPL PSKTPPPPPP KTTRKQASVD 


SGIVQ 

« Hide

References

« Hide 'large scale' references
[1]"DOCK180, a major CRK-binding protein, alters cell morphology upon translocation to the cell membrane."
Hasegawa H., Kiyokawa E., Tanaka S., Nagashima K., Gotoh N., Shibuya M., Kurata T., Matsuda M.
Mol. Cell. Biol. 16:1770-1776(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, INTERACTION WITH CRK.
Tissue: Placenta.
[2]"The DNA sequence and comparative analysis of human chromosome 10."
Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L., Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K., Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L., Taylor A., Battles J. expand/collapse author list , Bird C.P., Ainscough R., Almeida J.P., Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P., Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N., Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A., Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C., Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D., Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C., Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K., Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A., Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S., McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S., Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V., Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A., Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M., Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A., Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P., Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y., Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D., Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J.
Nature 429:375-381(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]"Interaction between the amino-terminal SH3 domain of CRK and its natural target proteins."
Matsuda M., Ota S., Tanimura R., Nakamura H., Matuoka K., Takenawa T., Nagashima K., Kurata T.
J. Biol. Chem. 271:14468-14472(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH CRK.
[4]"Activation of Rac1 by a Crk SH3-binding protein, DOCK180."
Kiyokawa E., Hashimoto Y., Kobayashi S., Sugimura H., Kurata T., Matsuda M.
Genes Dev. 12:3331-3336(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: GEF ACTIVITY, INTERACTION WITH RAC1.
[5]"Identification and kinetic analysis of the interaction between Nck-2 and DOCK180."
Tu Y., Kucik D.F., Wu C.
FEBS Lett. 491:193-199(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH NCK2.
[6]"Membrane recruitment of DOCK180 by binding to PtdIns(3,4,5)P3."
Kobayashi S., Shirai T., Kiyokawa E., Mochizuki N., Matsuda M., Fukui Y.
Biochem. J. 354:73-78(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH PTDINS(3,4,5)P3.
[7]"Unconventional Rac-GEF activity is mediated through the Dock180-ELMO complex."
Brugnera E., Haney L., Grimsley C., Lu M., Walk S.F., Tosello-Trampont A.-C., Macara I.G., Madhani H., Fink G.R., Ravichandran K.S.
Nat. Cell Biol. 4:574-582(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: GEF ACTIVITY, INTERACTION WITH RAC1; ELMO1 AND ELMO2, SUBUNIT OF A COMPLEX CONTAINING ELMO1 AND DOCK1, MUTAGENESIS OF 1401-TYR-ILE-1402 AND 1487-ILE--PRO-1489.
[8]"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, GEF ACTIVITY.
[9]"A quantitative atlas of mitotic phosphorylation."
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1751, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[10]"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].
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
D50857 mRNA. Translation: BAA09454.1.
AL157711 expand/collapse EMBL AC list , AL355316, AL359094, AL390920, AL607029, BX470155, BX470201 Genomic DNA. Translation: CAH71463.2.
AL359094 expand/collapse EMBL AC list , AL157711, AL355316, AL390920, AL607029, BX470155, BX470201 Genomic DNA. Translation: CAH71477.2.
BX470201 expand/collapse EMBL AC list , AL157711, AL355316, AL359094, AL390920, AL607029, BX470155 Genomic DNA. Translation: CAH72560.2.
AL390920 expand/collapse EMBL AC list , AL157711, AL355316, AL359094, AL607029, BX470155, BX470201 Genomic DNA. Translation: CAH73231.2.
AL607029 expand/collapse EMBL AC list , AL157711, AL355316, AL359094, AL390920, BX470155, BX470201 Genomic DNA. Translation: CAI15329.2.
AL355316 expand/collapse EMBL AC list , AL157711, AL359094, AL390920, AL607029, BX470155, BX470201 Genomic DNA. Translation: CAI16871.2.
BX470155 expand/collapse EMBL AC list , AL157711, AL355316, AL359094, AL390920, AL607029, BX470201 Genomic DNA. Translation: CAI22477.2.
RefSeqNP_001371.1. NM_001380.3.
UniGeneHs.159195.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
3L4CX-ray2.37A/B420-619[»]
ProteinModelPortalQ14185.
SMRQ14185. Positions 1-168, 425-611, 1192-1617.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid108128. 13 interactions.
DIPDIP-29391N.
IntActQ14185. 13 interactions.
MINTMINT-190985.
STRING9606.ENSP00000381107.

PTM databases

PhosphoSiteQ14185.

Polymorphism databases

DMDM209572608.

Proteomic databases

PaxDbQ14185.
PRIDEQ14185.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000280333; ENSP00000280333; ENSG00000150760.
GeneID1793.
KEGGhsa:1793.
UCSCuc001ljt.3. human.

Organism-specific databases

CTD1793.
GeneCardsGC10P128584.
HGNCHGNC:2987. DOCK1.
HPACAB004378.
HPA048692.
HPA053277.
MIM601403. gene.
neXtProtNX_Q14185.
PharmGKBPA27453.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG289808.
HOGENOMHOG000006631.
HOVERGENHBG051389.
KOK13708.
OMAAEKPGVN.
OrthoDBEOG7QNVK8.
PhylomeDBQ14185.
TreeFamTF300423.

Enzyme and pathway databases

ReactomeREACT_111045. Developmental Biology.
REACT_604. Hemostasis.
REACT_6900. Immune System.

Gene expression databases

BgeeQ14185.
CleanExHS_DOCK1.
GenevestigatorQ14185.

Family and domain databases

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

Other

ChiTaRSDOCK1. human.
EvolutionaryTraceQ14185.
GeneWikiDock180.
GenomeRNAi1793.
NextBio7305.
PROQ14185.
SOURCESearch...

Entry information

Entry nameDOCK1_HUMAN
AccessionPrimary (citable) accession number: Q14185
Secondary accession number(s): A9Z1Z5
Entry history
Integrated into UniProtKB/Swiss-Prot: July 3, 2003
Last sequence update: October 14, 2008
Last modified: April 16, 2014
This is version 127 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 10

Human chromosome 10: entries, gene names and cross-references to MIM