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Q99704 (DOK1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 132. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (4) | 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:
Docking protein 1
Alternative name(s):
Downstream of tyrosine kinase 1
p62(dok)
pp62
Gene names
Name:DOK1
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length481 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

DOK proteins are enzymatically inert adaptor or scaffolding proteins. They provide a docking platform for the assembly of multimolecular signaling complexes. DOK1 appears to be a negative regulator of the insulin signaling pathway. Modulates integrin activation by competing with talin for the same binding site on ITGB3. Ref.15

Subunit structure

Interacts with ABL1 By similarity. Interacts with RasGAP and INPP5D/SHIP1. Interacts directly with phosphorylated ITGB3. Interacts with SRMS (via the SH2 and SH3 domains). Ref.14 Ref.15

Subcellular location

Isoform 1: Cytoplasm. Nucleus Ref.11 Ref.14.

Isoform 3: Cytoplasmperinuclear region Ref.11 Ref.14.

Tissue specificity

Expressed in pancreas, heart, leukocyte and spleen. Expressed in both resting and activated peripheral blood T-cells. Expressed in breast cancer. Ref.7

Domain

The PTB domain mediates receptor interaction.

Post-translational modification

Constitutively tyrosine-phosphorylated. Phosphorylated by TEC By similarity. Phosphorylated by LYN By similarity. Phosphorylated on tyrosine residues by the insulin receptor kinase. Results in the negative regulation of the insulin signaling pathway. Phosphorylated on tyrosine residues by SRMS. Ref.1 Ref.6 Ref.14

Isoform 3 contains a N-acetylmethionine at position 1.

Sequence similarities

Belongs to the DOK family. Type A subfamily.

Contains 1 IRS-type PTB domain.

Contains 1 PH domain.

Binary interactions

With

Entry

#Exp.

IntAct

Notes

Cbll1Q9JIY22EBI-1384360,EBI-7644904From a different organism.
ERBB2P046262EBI-1384360,EBI-641062
ORFQ9Q2G42EBI-1384360,EBI-6248094From a different organism.
SRMSQ9H3Y67EBI-1384360,EBI-8541270

Alternative products

This entry describes 3 isoforms produced by alternative splicing and alternative initiation. [Align] [Select]
Isoform 1 (identifier: Q99704-1)

Also known as: p62Dok1;

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: Q99704-2)

Also known as: p22Dokdel;

The sequence of this isoform differs from the canonical sequence as follows:
     153-177: SQFWVTVQRTEAAERCGLHGSYVLR → HVLFRGRPPLPLRPWNLHLPDGTGK
     178-481: Missing.
Isoform 3 (identifier: Q99704-3)

Also known as: p44Dok;

The sequence of this isoform differs from the canonical sequence as follows:
     1-139: Missing.
Note: Produced by alternative initiation at Met-140 of isoform 1. Contains a N-acetylmethionine at position 1.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 481481Docking protein 1
PRO_0000187268

Regions

Domain4 – 119116PH
Domain151 – 259109IRS-type PTB
Compositional bias280 – 31839Pro-rich
Compositional bias356 – 43378Pro-rich

Amino acid modifications

Modified residue11N-acetylmethionine Ref.11 Ref.13
Modified residue2691Phosphoserine Ref.1 Ref.9 Ref.12
Modified residue2911Phosphoserine Ref.1 Ref.10
Modified residue2961Phosphotyrosine By similarity
Modified residue3371Phosphotyrosine By similarity
Modified residue3411Phosphotyrosine Ref.1 Ref.12
Modified residue3621Phosphotyrosine; by INSR Ref.1 Ref.6 Ref.8 Ref.12
Modified residue3771Phosphotyrosine Ref.1 Ref.8
Modified residue3981Phosphotyrosine; by INSR Ref.1 Ref.6 Ref.8
Modified residue4091Phosphotyrosine Ref.1 Ref.8
Modified residue4491Phosphotyrosine By similarity

Natural variations

Alternative sequence1 – 139139Missing in isoform 3.
VSP_038224
Alternative sequence153 – 17725SQFWV…SYVLR → HVLFRGRPPLPLRPWNLHLP DGTGK in isoform 2.
VSP_003852
Alternative sequence178 – 481304Missing in isoform 2.
VSP_003853

Experimental info

Mutagenesis3621Y → F: No association with NCK. No association with GAP; when associated with F-398. Ref.6
Mutagenesis3981Y → F: No association with GAP; when associated with F-362. Ref.6
Sequence conflict1 – 2020MDGAV…RFGTK → RLPAQASATREREPRWSPFQ in AAB88182. Ref.3

Secondary structure

................... 481
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 (p62Dok1) [UniParc].

Last modified May 1, 1997. Version 1.
Checksum: E9D947831244BA6C

FASTA48152,392
        10         20         30         40         50         60 
MDGAVMEGPL FLQSQRFGTK RWRKTWAVLY PASPHGVARL EFFDHKGSSS GGGRGSSRRL 

        70         80         90        100        110        120 
DCKVIRLAEC VSVAPVTVET PPEPGATAFR LDTAQRSHLL AADAPSSAAW VQTLCRNAFP 

       130        140        150        160        170        180 
KGSWTLAPTD NPPKLSALEM LENSLYSPTW EGSQFWVTVQ RTEAAERCGL HGSYVLRVEA 

       190        200        210        220        230        240 
ERLTLLTVGA QSQILEPLLS WPYTLLRRYG RDKVMFSFEA GRRCPSGPGT FTFQTAQGND 

       250        260        270        280        290        300 
IFQAVETAIH RQKAQGKAGQ GHDVLRADSH EGEVAEGKLP SPPGPQELLD SPPALYAEPL 

       310        320        330        340        350        360 
DSLRIAPCPS QDSLYSDPLD STSAQAGEGV QRKKPLYWDL YEHAQQQLLK AKLTDPKEDP 

       370        380        390        400        410        420 
IYDEPEGLAP VPPQGLYDLP REPKDAWWCQ ARVKEEGYEL PYNPATDDYA VPPPRSTKPL 

       430        440        450        460        470        480 
LAPKPQGPAF PEPGTATGSG IKSHNSALYS QVQKSGASGS WDCGLSRVGT DKTGVKSEGS 


T 

« Hide

Isoform 2 (p22Dokdel) [UniParc].

Checksum: 91A504A89EB6ED15
Show »

FASTA17719,370
Isoform 3 (p44Dok) [UniParc].

Checksum: DEF8E9DF694C38C9
Show »

FASTA34237,405

References

« Hide 'large scale' references
[1]"p62(dok): a constitutively tyrosine-phosphorylated, GAP-associated protein in chronic myelogenous leukemia progenitor cells."
Carpino N., Wisniewski D., Strife A., Marshak D., Kobayashi R., Stillman B., Clarkson B.
Cell 88:197-204(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), PHOSPHORYLATION AT TYROSINE RESIDUES.
[2]"Molecular cloning of a truncated p62Dok1 isoform, p22Dokdel."
Hubert P., Ferreira V., Debre P., Bismuth G.
Eur. J. Immunogenet. 27:145-148(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
[3]Yu W., Sarginson J., Gibbs R.A.
Submitted (NOV-1997) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Tissue: Brain.
[4]"Generation and annotation of the DNA sequences of human chromosomes 2 and 4."
Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H. expand/collapse author list , Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., Wilson R.K.
Nature 434:724-731(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]"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] (ISOFORM 1).
[6]"Insulin receptor-mediated p62dok tyrosine phosphorylation at residues 362 and 398 plays distinct roles for binding GTPase-activating protein and Nck and is essential for inhibiting insulin-stimulated activation of Ras and Akt."
Wick M.J., Dong L.Q., Hu D., Langlais P., Liu F.
J. Biol. Chem. 276:42843-42850(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT TYR-362 AND TYR-398, MUTAGENESIS OF TYR-362 AND TYR-398.
[7]"DOK4 and DOK5: new Dok-related genes expressed in human T cells."
Favre C., Gerard A., Clauzier E., Pontarotti P., Olive D., Nunes J.A.
Genes Immun. 4:40-45(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: TISSUE SPECIFICITY.
[8]"Immunoaffinity profiling of tyrosine phosphorylation in cancer cells."
Rush J., Moritz A., Lee K.A., Guo A., Goss V.L., Spek E.J., Zhang H., Zha X.-M., Polakiewicz R.D., Comb M.J.
Nat. Biotechnol. 23:94-101(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-362; TYR-377; TYR-398 AND TYR-409, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[9]"Phosphoproteome of resting human platelets."
Zahedi R.P., Lewandrowski U., Wiesner J., Wortelkamp S., Moebius J., Schuetz C., Walter U., Gambaryan S., Sickmann A.
J. Proteome Res. 7:526-534(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-269, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Platelet.
[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] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-291, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[11]"Targeted mass spectrometric analysis of N-terminally truncated isoforms generated via alternative translation initiation."
Kobayashi R., Patenia R., Ashizawa S., Vykoukal J.
FEBS Lett. 583:2441-2445(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION, ALTERNATIVE INITIATION (ISOFORM 3), ACETYLATION AT MET-1 (ISOFORM 3).
[12]"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-269; TYR-341 AND TYR-362, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Leukemic T-cell.
[13]"N-terminal acetylome analyses and functional insights of the N-terminal acetyltransferase NatB."
Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A., Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.
Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[14]"The unique N-terminal region of SRMS regulates enzymatic activity and phosphorylation of its novel substrate Dok1."
Goel R.K., Miah S., Black K., Kalra N., Dai C., Lukong K.E.
FEBS J. 280:4539-4559(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION, SUBCELLULAR LOCATION, INTERACTION WITH SRMS.
[15]"An integrin phosphorylation switch: the effect of beta3 integrin tail phosphorylation on Dok1 and talin binding."
Oxley C.L., Anthis N.J., Lowe E.D., Vakonakis I., Campbell I.D., Wegener K.L.
J. Biol. Chem. 283:5420-5426(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.6 ANGSTROMS) OF 152-256, FUNCTION, INTERACTION WITH ITGB3.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
U70987 mRNA. Translation: AAC51127.1.
AF180527 mRNA. Translation: AAF19167.1.
AF035299 mRNA. Translation: AAB88182.1.
AC005033 Genomic DNA. Translation: AAX93224.1.
BC114440 mRNA. Translation: AAI14441.1.
RefSeqNP_001184189.1. NM_001197260.1.
NP_001372.1. NM_001381.3.
XP_005264237.1. XM_005264180.1.
UniGeneHs.103854.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2V76X-ray1.60A/B/C/D152-256[»]
ProteinModelPortalQ99704.
SMRQ99704. Positions 4-119, 153-283.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid108131. 34 interactions.
IntActQ99704. 10 interactions.
MINTMINT-1494101.
STRING9606.ENSP00000233668.

PTM databases

PhosphoSiteQ99704.

Polymorphism databases

DMDM17366642.

Proteomic databases

PaxDbQ99704.
PRIDEQ99704.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000233668; ENSP00000233668; ENSG00000115325. [Q99704-1]
ENST00000340004; ENSP00000344330; ENSG00000115325. [Q99704-2]
ENST00000409429; ENSP00000387016; ENSG00000115325. [Q99704-3]
GeneID1796.
KEGGhsa:1796.
UCSCuc002smr.3. human. [Q99704-1]

Organism-specific databases

CTD1796.
GeneCardsGC02P074776.
HGNCHGNC:2990. DOK1.
HPACAB004224.
HPA048561.
MIM602919. gene.
neXtProtNX_Q99704.
PharmGKBPA27456.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG243145.
HOGENOMHOG000112245.
HOVERGENHBG018962.
InParanoidQ99704.
KOK14752.
OMAWPYTLLR.
OrthoDBEOG77WWC5.
PhylomeDBQ99704.
TreeFamTF324994.

Enzyme and pathway databases

ReactomeREACT_111102. Signal Transduction.
SignaLinkQ99704.

Gene expression databases

ArrayExpressQ99704.
BgeeQ99704.
CleanExHS_DOK1.
GenevestigatorQ99704.

Family and domain databases

Gene3D2.30.29.30. 2 hits.
InterProIPR002404. Insln_rcpt_S1.
IPR011993. PH_like_dom.
IPR001849. Pleckstrin_homology.
[Graphical view]
PfamPF02174. IRS. 1 hit.
[Graphical view]
SMARTSM00233. PH. 1 hit.
SM00310. PTBI. 1 hit.
[Graphical view]
PROSITEPS51064. IRS_PTB. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceQ99704.
GeneWikiDOK1.
GenomeRNAi1796.
NextBio7317.
PROQ99704.
SOURCESearch...

Entry information

Entry nameDOK1_HUMAN
AccessionPrimary (citable) accession number: Q99704
Secondary accession number(s): O43204, Q53TY2, Q9UHG6
Entry history
Integrated into UniProtKB/Swiss-Prot: November 16, 2001
Last sequence update: May 1, 1997
Last modified: April 16, 2014
This is version 132 of the entry and version 1 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 chromosome 2

Human chromosome 2: entries, gene names and cross-references to MIM