Reviewed, UniProtKB/Swiss-Prot Q14185 (DOCK1_HUMAN)

Names and origin

Protein names

Recommended name:
    Dedicator of cytokinesis protein 1
Alternative name(s):
    180 kDa protein downstream of CRK
    DOCK180

Gene names

Name:

DOCK1

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	1865 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence 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-triphosphate 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 (CZH-1) domain. Contains 1 DHR-2 (CZH-2) domain. Contains 1 SH3 domain.

Ontologies

Keywords
Biological process	Apoptosis Phagocytosis
Cellular component	Cytoplasm Membrane
Domain	SH3 domain SH3-binding
Molecular function	Guanine-nucleotide releasing factor
PTM	Phosphoprotein
Technical term	Complete proteome
Gene Ontology (GO)
Biological process	apoptosis Traceable author statement. Source: ProtInc integrin-mediated signaling pathway Ref.4 Traceable author statement. Source: ProtInc phagocytosis, engulfment Traceable author statement. Source: ProtInc small GTPase mediated signal transduction Ref.4 Traceable author statement. Source: ProtInc
Cellular component	cytoplasm Traceable author statement. Source: ProtInc membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	GTPase activator activity Ref.4 Traceable author statement. Source: ProtInc SH3 domain binding Inferred from electronic annotation. Source: UniProtKB-KW guanyl-nucleotide exchange factor activity Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
CRK	P46108	1	EBI-446740,EBI-886
ELMO1	Q92556	2	EBI-446740,EBI-346417
FYN	P06241	1	EBI-446740,EBI-515315
GRB2	P62993	1	EBI-446740,EBI-401755
NCK1	P16333	1	EBI-446740,EBI-389883
RAC1	P63000	3	EBI-446740,EBI-413628
SRC	P12931	1	EBI-446740,EBI-621482

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 1865	1865	Dedicator of cytokinesis protein 1		PRO_0000189984
Regions
	Domain	9 – 70	62	SH3
	Domain	422 – 664	243	DHR-1
	Domain	1111 – 1616	506	DHR-2
	Region	1687 – 1695	9	Phosphoinositide-binding Potential
	Region	1793 – 1819	27	Interaction with NCK2 second and third SH3 domain (minor)
	Region	1820 – 1836	17	Interaction with NCK2 third SH3 domain (major)
	Region	1837 – 1852	16	Interaction with NCK2 (minor)
	Motif	1799 – 1805	7	SH3-binding; interaction with CRK Potential
	Motif	1838 – 1843	6	SH3-binding; interaction with CRK Potential
Amino acid modifications
	Modified residue	1751	1	Phosphoserine Ref.10
	Modified residue	1858	1	Phosphoserine Ref.9
Experimental info
	Mutagenesis	1401 – 1402	2	YI → AA: Abolishes Rac GEF activity.
	Mutagenesis	1487 – 1489	3	ISP → AAA: Abolishes Rac GEF activity. Ref.7
	Sequence conflict	1857	1	A → T in BAA09454. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Q14185-1 [UniParc]. Last modified October 14, 2008. Version 2. Checksum: 940C5AFD047EBEDE	FASTA	1,865	215,346
	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

References

	« Hide 'large scale' referencesShow '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: 8657152] [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. , 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: 15164054] [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: 8662907] [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: 9808620] [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: 11240126] [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: 11171081] [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: 12134158] [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: 12432077] [Abstract] Cited for: NOMENCLATURE, GEF ACTIVITY.
[9]	"A probability-based approach for high-throughput protein phosphorylation analysis and site localization." Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P. Nat. Biotechnol. 24:1285-1292(2006) [PubMed: 16964243] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1858, MASS SPECTROMETRY. Tissue: Epithelium.
[10]	"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: 18669648] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1751, MASS SPECTROMETRY.
[11]	Colinge J., Superti-Furga G., Bennett K.L. Submitted (OCT-2008) to UniProtKB Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBLGenBankDDBJ	D50857 mRNA. Translation: BAA09454.1. AL157711 , AL355316, AL359094, AL390920, AL607029, BX470155, BX470201 Genomic DNA. Translation: CAH71463.2. AL359094 , AL157711, AL355316, AL390920, AL607029, BX470155, BX470201 Genomic DNA. Translation: CAH71477.2. BX470201 , AL157711, AL355316, AL359094, AL390920, AL607029, BX470155 Genomic DNA. Translation: CAH72560.2. AL390920 , AL157711, AL355316, AL359094, AL607029, BX470155, BX470201 Genomic DNA. Translation: CAH73231.2. AL607029 , AL157711, AL355316, AL359094, AL390920, BX470155, BX470201 Genomic DNA. Translation: CAI15329.2. AL355316 , AL157711, AL359094, AL390920, AL607029, BX470155, BX470201 Genomic DNA. Translation: CAI16871.2. BX470155 , AL157711, AL355316, AL359094, AL390920, AL607029, BX470201 Genomic DNA. Translation: CAI22477.2.
IPI	IPI00015286.
RefSeq	NP_001371.1.
UniGene	Hs.159195 Hs.645702
3D structure databases
ModBase	Search...
Protein-protein interaction databases
IntAct	Q14185. 8 interactions.
PTM databases
PhosphoSite	Q14185.
Proteomic databases
PRIDE	Q14185.
Genome annotation databases
Ensembl	ENSG00000150760. Homo sapiens. [Contig view]
GeneID	1793.
KEGG	hsa:1793.
UCSC	uc001ljt.1. human.
Organism-specific databases
GeneCards	GC10P128584.
H-InvDB	HIX0009304.
HGNC	HGNC:2987. DOCK1.
HPA	CAB004378.
MIM	601403. gene.
PharmGKB	PA27453.
GenAtlas	Search...
Phylogenomic databases
HOGENOM	Q14185.
HOVERGEN	Q14185.
Enzyme and pathway databases
Pathway_Interaction_DB	trkrpathway. Neurotrophic factor-mediated Trk receptor signaling. a4b1_paxdep_pathway. Paxillin-dependent events mediated by a4b1. a4b1_paxindep_pathway. Paxillin-independent events mediated by a4b1 and a4b7. met_pathway. Signaling events activated by Hepatocyte Growth Factor Receptor (c-Met).
Gene expression databases
ArrayExpress	Q14185.
Bgee	Q14185.
CleanEx	HS_DOCK1.
Family and domain databases
InterPro	IPR001452. SH3_domain. [Graphical view]
Pfam	PF00018. SH3_1. 1 hit. [Graphical view]
ProDom	PD000066. SH3. 1 hit. [Graphical view] [Entries sharing at least one domain]
SMART	SM00326. SH3. 1 hit. [Graphical view]
PROSITE	PS50002. SH3. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	7305.
SOURCE	Search...

Entry information

Entry name

DOCK1_HUMAN

Accession

Primary (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:	July 7, 2009
This is version 81 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)