Docking protein 1 - Homo sapiens (Human)

Preferred order of sections

Names and origin

Protein names

Recommended name:
Docking protein 1

Alternative name(s):
Downstream of tyrosine kinase 1
p62(dok)
pp62

Gene names

Name:

DOK1

Organism

Homo sapiens (Human) [Reference 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	481 AA.
Sequence status	Complete.
Protein existence	Evidence 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.13
Subunit structure	Interacts with ABL1 By similarity. Interacts with RasGAP and INPP5D/SHIP1. Interacts directly with phosphorylated ITGB3. Ref.13
Subcellular location	Isoform 1: Cytoplasm Ref.11. Isoform 3: Cytoplasm › perinuclear region Ref.11.
Tissue specificity	Expressed in pancreas, heart, leukocyte and spleen. Expressed in both resting and activated peripheral blood T-cells. 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. Ref.1 Ref.6 Phosphorylated on tyrosine residues by the insulin receptor kinase. Results in the negative regulation of the insulin signaling pathway. Ref.1 Ref.6 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.

Ontologies

Keywords
Cellular component	Cytoplasm
Coding sequence diversity	Alternative initiation Alternative splicing
PTM	Acetylation Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	Ras protein signal transduction Inferred from electronic annotation. Source: Compara insulin receptor signaling pathway Traceable author statement. Source: Reactome intracellular protein kinase cascade Inferred from electronic annotation. Source: Compara
Cellular_component	cytosol Traceable author statement. Source: Reactome perinuclear region of cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	phospholipid binding Inferred from electronic annotation. Source: InterPro receptor signaling protein activity Inferred from electronic annotation. Source: Compara
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
ORF	Q9Q2G4	2	EBI-1384360,EBI-6248094	From a different organism.

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 key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 481

481

Docking protein 1

PRO_0000187268

Regions

Domain

4 – 119

116

PH

Domain

151 – 259

109

IRS-type PTB

Compositional bias

280 – 318

39

Pro-rich

Compositional bias

356 – 433

78

Pro-rich

Amino acid modifications

Modified residue

269

1

Phosphoserine Ref.1 Ref.9 Ref.12

Modified residue

291

1

Phosphoserine Ref.1 Ref.10

Modified residue

296

1

Phosphotyrosine By similarity

Modified residue

315

1

Phosphotyrosine By similarity

Modified residue

337

1

Phosphotyrosine By similarity

Modified residue

341

1

Phosphotyrosine Ref.1 Ref.12

Modified residue

362

1

Phosphotyrosine; by INSR Ref.1 Ref.6 Ref.8 Ref.12

Modified residue

377

1

Phosphotyrosine Ref.1 Ref.8

Modified residue

398

1

Phosphotyrosine; by INSR Ref.1 Ref.6 Ref.8

Modified residue

409

1

Phosphotyrosine Ref.1 Ref.8

Modified residue

449

1

Phosphotyrosine By similarity

Natural variations

Alternative sequence

1 – 139

139

Missing in isoform 3.

VSP_038224

Alternative sequence

153 – 177

25

SQFWV…SYVLR → HVLFRGRPPLPLRPWNLHLP DGTGK in isoform 2.

VSP_003852

Alternative sequence

178 – 481

304

Missing in isoform 2.

VSP_003853

Experimental info

Mutagenesis

362

1

Y → F: No association with NCK. No association with GAP; when associated with F-398. Ref.6

Mutagenesis

398

1

Y → F: No association with GAP; when associated with F-362. Ref.6

Sequence conflict

1 – 20

20

MDGAV…RFGTK → RLPAQASATREREPRWSPFQ in AAB88182. Ref.3

Secondary structure

1

.

481

Helix Strand Turn

Details...

Sequences

Sequence		Length	Mass (Da)
Isoform 1 (p62Dok1) [UniParc]. Last modified May 1, 1997. Version 1. Checksum: E9D947831244BA6C Show »	FASTA	481	52,392
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 »	FASTA	177	19,370
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 KGSWTLAPTD NPPKLSALEM LENSLYSPTW EGHVLFRGRP PLPLRPWNLH LPDGTGK « Hide
Isoform 3 (p44Dok) [UniParc]. Checksum: DEF8E9DF694C38C9 Show »	FASTA	342	37,405
10 20 30 40 50 60 MLENSLYSPT WEGSQFWVTV QRTEAAERCG LHGSYVLRVE AERLTLLTVG AQSQILEPLL 70 80 90 100 110 120 SWPYTLLRRY GRDKVMFSFE AGRRCPSGPG TFTFQTAQGN DIFQAVETAI HRQKAQGKAG 130 140 150 160 170 180 QGHDVLRADS HEGEVAEGKL PSPPGPQELL DSPPALYAEP LDSLRIAPCP SQDSLYSDPL 190 200 210 220 230 240 DSTSAQAGEG VQRKKPLYWD LYEHAQQQLL KAKLTDPKED PIYDEPEGLA PVPPQGLYDL 250 260 270 280 290 300 PREPKDAWWC QARVKEEGYE LPYNPATDDY AVPPPRSTKP LLAPKPQGPA FPEPGTATGS 310 320 330 340 GIKSHNSALY SQVQKSGASG SWDCGLSRVG TDKTGVKSEG ST « Hide

References

	« Hide 'large scale' referencesShow '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. 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, MASS SPECTROMETRY.
[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, MASS SPECTROMETRY. 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, MASS SPECTROMETRY. 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, MASS SPECTROMETRY. Tissue: Leukemic T-cell.
[13]	"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.

IPI

IPI00015287.
IPI00218542.
IPI00917613.

RefSeq

NP_001184189.1. NM_001197260.1.
NP_001372.1. NM_001381.3.

UniGene

Hs.103854.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2V76	X-ray	1.60	A/B/C/D	152-256	[»]

ProteinModelPortal

Q99704.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q99704. 4 interactions.

MINT

MINT-1494101.

STRING

9606.ENSP00000233668.

PTM databases

PhosphoSite

Q99704.

Polymorphism databases

DMDM

17366642.

Proteomic databases

PaxDb

Q99704.

PRIDE

Q99704.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000233668; ENSP00000233668; ENSG00000115325.
ENST00000340004; ENSP00000344330; ENSG00000115325.
ENST00000409429; ENSP00000387016; ENSG00000115325.

GeneID

1796.

KEGG

hsa:1796.

UCSC

uc002smr.3. human.

Organism-specific databases

CTD

1796.

GeneCards

GC02P074776.

HGNC

HGNC:2990. DOK1.

HPA

CAB004224.

MIM

602919. gene.

neXtProt

NX_Q99704.

PharmGKB

PA27456.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG243145.

HOGENOM

HOG000112245.

HOVERGEN

HBG018962.

InParanoid

Q99704.

KO

K14752.

OMA

WPYTLLR.

PhylomeDB

Q99704.

Enzyme and pathway databases

Pathway_Interaction_DB

bcr_5pathway. BCR signaling pathway.
fcer1pathway. Fc-epsilon receptor I signaling in mast cells.
insulin_pathway. Insulin Pathway.
pdgfrbpathway. PDGFR-beta signaling pathway.
ptp1bpathway. Signaling events mediated by PTP1B.
kitpathway. Signaling events mediated by Stem cell factor receptor (c-Kit).
ret_pathway. Signaling events regulated by Ret tyrosine kinase.

Reactome

REACT_111102. Signal Transduction.

Gene expression databases

ArrayExpress

Q99704.

Bgee

Q99704.

CleanEx

HS_DOK1.

Genevestigator

Q99704.

GermOnline

ENSG00000115325. Homo sapiens.

Family and domain databases

Gene3D

2.30.29.30. 2 hits.

InterPro

IPR002404. Insln_rcpt_S1.
IPR011993. PH_like_dom.
IPR001849. Pleckstrin_homology.
[Graphical view]

Pfam

PF02174. IRS. 1 hit.
[Graphical view]

SMART

SM00233. PH. 1 hit.
SM00310. PTBI. 1 hit.
[Graphical view]

PROSITE

PS51064. IRS_PTB. 1 hit.
PS50003. PH_DOMAIN. False negative.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

Q99704.

GenomeRNAi

1796.

NextBio

7317.

SOURCE

Search...

Entry information

Entry name

DOK1_HUMAN

Accession

Primary (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:	May 1, 2013
This is version 123 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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

Human chromosome 2

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

MIM cross-references

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

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

SIMILARITY comments

Index of protein domains and families

Preferred order of sections

Names and origin

Protein attributes

General annotation (Comments)

Ontologies

Binary interactions

With

Entry

#Exp.

IntAct

Notes

Alternative products

Sequence annotation (Features)

Molecule processing

Regions

Amino acid modifications

Natural variations

Experimental info

Secondary structure

Sequences

References

Cross-references

Sequence databases

3D structure databases

Protein-protein interaction databases

PTM databases

Polymorphism databases

Proteomic databases

Protocols and materials databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Enzyme and pathway databases

Gene expression databases

Family and domain databases

Other

Entry information

Relevant documents