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Protein

Docking protein 1

Gene

DOK1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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 ITGB3.1 Publication

GO - Molecular functioni

GO - Biological processi

  • cell surface receptor signaling pathway Source: ProtInc
  • positive regulation of epidermal growth factor receptor signaling pathway Source: Reactome
  • Ras protein signal transduction Source: Ensembl
  • signal transduction Source: ProtInc
  • transmembrane receptor protein tyrosine kinase signaling pathway Source: ProtInc
Complete GO annotation...

Enzyme and pathway databases

BioCyciZFISH:ENSG00000115325-MONOMER.
ReactomeiR-HSA-8849469. PTK6 Regulates RTKs and Their Effectors AKT1 and DOK1.
R-HSA-8853659. RET signaling.
SignaLinkiQ99704.
SIGNORiQ99704.

Names & Taxonomyi

Protein namesi
Recommended name:
Docking protein 1
Alternative name(s):
Downstream of tyrosine kinase 1
p62(dok)
pp62
Gene namesi
Name:DOK1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 2

Organism-specific databases

HGNCiHGNC:2990. DOK1.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: HPA
  • cytosol Source: Reactome
  • nucleus Source: UniProtKB
  • perinuclear region of cytoplasm Source: UniProtKB-SubCell
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi362Y → F: No association with NCK. No association with GAP; when associated with F-398. 1 Publication1
Mutagenesisi398Y → F: No association with GAP; when associated with F-362. 1 Publication1

Organism-specific databases

DisGeNETi1796.
OpenTargetsiENSG00000115325.
PharmGKBiPA27456.

Polymorphism and mutation databases

BioMutaiDOK1.
DMDMi17366642.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001872681 – 481Docking protein 1Add BLAST481

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei1N-acetylmethionineCombined sources1
Modified residuei48PhosphoserineCombined sources1
Modified residuei269PhosphoserineCombined sources1
Modified residuei291PhosphoserineCombined sources1
Modified residuei296PhosphotyrosineBy similarity1
Modified residuei337PhosphotyrosineBy similarity1
Modified residuei341PhosphotyrosineCombined sources1
Modified residuei362Phosphotyrosine; by INSRCombined sources1 Publication1
Modified residuei377PhosphotyrosineCombined sources1
Modified residuei398Phosphotyrosine; by INSRCombined sources1 Publication1
Modified residuei409PhosphotyrosineCombined sources1
Modified residuei416PhosphoserineBy similarity1
Modified residuei449PhosphotyrosineBy similarity1
Modified residuei460PhosphoserineCombined sources1
Isoform 3 (identifier: Q99704-3)
Modified residuei1N-acetylmethionine1 Publication1

Post-translational modificationi

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.By similarity3 Publications

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiQ99704.
MaxQBiQ99704.
PaxDbiQ99704.
PeptideAtlasiQ99704.
PRIDEiQ99704.

PTM databases

iPTMnetiQ99704.
PhosphoSitePlusiQ99704.

Expressioni

Tissue specificityi

Expressed in pancreas, heart, leukocyte and spleen. Expressed in both resting and activated peripheral blood T-cells. Expressed in breast cancer.1 Publication

Gene expression databases

BgeeiENSG00000115325.
CleanExiHS_DOK1.
ExpressionAtlasiQ99704. baseline and differential.
GenevisibleiQ99704. HS.

Organism-specific databases

HPAiCAB004224.
HPA048561.

Interactioni

Subunit structurei

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).By similarity2 Publications

Binary interactionsi

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

Protein-protein interaction databases

BioGridi108131. 38 interactors.
IntActiQ99704. 13 interactors.
MINTiMINT-1494101.
STRINGi9606.ENSP00000233668.

Structurei

Secondary structure

1481
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi153 – 159Combined sources7
Helixi163 – 167Combined sources5
Beta strandi172 – 178Combined sources7
Beta strandi180 – 188Combined sources9
Turni190 – 192Combined sources3
Beta strandi195 – 202Combined sources8
Helixi203 – 205Combined sources3
Beta strandi206 – 211Combined sources6
Beta strandi213 – 220Combined sources8
Beta strandi228 – 234Combined sources7
Helixi238 – 251Combined sources14

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2V76X-ray1.60A/B/C/D152-256[»]
ProteinModelPortaliQ99704.
SMRiQ99704.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ99704.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini4 – 119PHAdd BLAST116
Domaini151 – 259IRS-type PTBPROSITE-ProRule annotationAdd BLAST109

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi280 – 318Pro-richAdd BLAST39
Compositional biasi356 – 433Pro-richAdd BLAST78

Domaini

The PTB domain mediates receptor interaction.

Sequence similaritiesi

Belongs to the DOK family. Type A subfamily.Curated
Contains 1 IRS-type PTB domain.PROSITE-ProRule annotation
Contains 1 PH domain.Curated

Phylogenomic databases

eggNOGiKOG4047. Eukaryota.
ENOG410XS2S. LUCA.
GeneTreeiENSGT00730000110348.
HOGENOMiHOG000112245.
HOVERGENiHBG018962.
InParanoidiQ99704.
KOiK14752.
OMAiWPYTLLR.
OrthoDBiEOG091G075T.
PhylomeDBiQ99704.
TreeFamiTF324994.

Family and domain databases

Gene3Di2.30.29.30. 2 hits.
InterProiIPR002404. IRS_PTB.
IPR011993. PH_dom-like.
IPR001849. PH_domain.
[Graphical view]
PfamiPF02174. IRS. 1 hit.
PF00169. PH. 1 hit.
[Graphical view]
SMARTiSM00233. PH. 1 hit.
SM00310. PTBI. 1 hit.
[Graphical view]
SUPFAMiSSF50729. SSF50729. 2 hits.
PROSITEiPS51064. IRS_PTB. 1 hit.
[Graphical view]

Sequences (3)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing and alternative initiation. AlignAdd to basket

Isoform 1 (identifier: Q99704-1) [UniParc]FASTAAdd to basket
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.

« Hide

        10         20         30         40         50
MDGAVMEGPL FLQSQRFGTK RWRKTWAVLY PASPHGVARL EFFDHKGSSS
60 70 80 90 100
GGGRGSSRRL DCKVIRLAEC VSVAPVTVET PPEPGATAFR LDTAQRSHLL
110 120 130 140 150
AADAPSSAAW VQTLCRNAFP KGSWTLAPTD NPPKLSALEM LENSLYSPTW
160 170 180 190 200
EGSQFWVTVQ RTEAAERCGL HGSYVLRVEA ERLTLLTVGA QSQILEPLLS
210 220 230 240 250
WPYTLLRRYG RDKVMFSFEA GRRCPSGPGT FTFQTAQGND IFQAVETAIH
260 270 280 290 300
RQKAQGKAGQ GHDVLRADSH EGEVAEGKLP SPPGPQELLD SPPALYAEPL
310 320 330 340 350
DSLRIAPCPS QDSLYSDPLD STSAQAGEGV QRKKPLYWDL YEHAQQQLLK
360 370 380 390 400
AKLTDPKEDP IYDEPEGLAP VPPQGLYDLP REPKDAWWCQ ARVKEEGYEL
410 420 430 440 450
PYNPATDDYA VPPPRSTKPL LAPKPQGPAF PEPGTATGSG IKSHNSALYS
460 470 480
QVQKSGASGS WDCGLSRVGT DKTGVKSEGS T
Length:481
Mass (Da):52,392
Last modified:May 1, 1997 - v1
Checksum:iE9D947831244BA6C
GO
Isoform 2 (identifier: Q99704-2) [UniParc]FASTAAdd to basket
Also known as: p22Dokdel

The sequence of this isoform differs from the canonical sequence as follows:
     153-177: SQFWVTVQRTEAAERCGLHGSYVLR → HVLFRGRPPLPLRPWNLHLPDGTGK
     178-481: Missing.

Show »
Length:177
Mass (Da):19,370
Checksum:i91A504A89EB6ED15
GO
Isoform 3 (identifier: Q99704-3) [UniParc]FASTAAdd to basket
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 1.1 Publication
Show »
Length:342
Mass (Da):37,405
Checksum:iDEF8E9DF694C38C9
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti1 – 20MDGAV…RFGTK → RLPAQASATREREPRWSPFQ in AAB88182 (Ref. 3) CuratedAdd BLAST20

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0382241 – 139Missing in isoform 3. CuratedAdd BLAST139
Alternative sequenceiVSP_003852153 – 177SQFWV…SYVLR → HVLFRGRPPLPLRPWNLHLP DGTGK in isoform 2. 1 PublicationAdd BLAST25
Alternative sequenceiVSP_003853178 – 481Missing in isoform 2. 1 PublicationAdd BLAST304

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS1954.1. [Q99704-1]
CCDS56125.1. [Q99704-3]
CCDS82474.1. [Q99704-2]
RefSeqiNP_001184189.1. NM_001197260.1. [Q99704-3]
NP_001305797.1. NM_001318868.1. [Q99704-2]
NP_001372.1. NM_001381.4. [Q99704-1]
UniGeneiHs.103854.

Genome annotation databases

EnsembliENST00000233668; ENSP00000233668; ENSG00000115325. [Q99704-1]
ENST00000340004; ENSP00000344330; ENSG00000115325. [Q99704-2]
ENST00000409429; ENSP00000387016; ENSG00000115325. [Q99704-3]
GeneIDi1796.
KEGGihsa:1796.
UCSCiuc002smr.4. human. [Q99704-1]

Keywords - Coding sequence diversityi

Alternative initiation, Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS1954.1. [Q99704-1]
CCDS56125.1. [Q99704-3]
CCDS82474.1. [Q99704-2]
RefSeqiNP_001184189.1. NM_001197260.1. [Q99704-3]
NP_001305797.1. NM_001318868.1. [Q99704-2]
NP_001372.1. NM_001381.4. [Q99704-1]
UniGeneiHs.103854.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2V76X-ray1.60A/B/C/D152-256[»]
ProteinModelPortaliQ99704.
SMRiQ99704.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi108131. 38 interactors.
IntActiQ99704. 13 interactors.
MINTiMINT-1494101.
STRINGi9606.ENSP00000233668.

PTM databases

iPTMnetiQ99704.
PhosphoSitePlusiQ99704.

Polymorphism and mutation databases

BioMutaiDOK1.
DMDMi17366642.

Proteomic databases

EPDiQ99704.
MaxQBiQ99704.
PaxDbiQ99704.
PeptideAtlasiQ99704.
PRIDEiQ99704.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000233668; ENSP00000233668; ENSG00000115325. [Q99704-1]
ENST00000340004; ENSP00000344330; ENSG00000115325. [Q99704-2]
ENST00000409429; ENSP00000387016; ENSG00000115325. [Q99704-3]
GeneIDi1796.
KEGGihsa:1796.
UCSCiuc002smr.4. human. [Q99704-1]

Organism-specific databases

CTDi1796.
DisGeNETi1796.
GeneCardsiDOK1.
HGNCiHGNC:2990. DOK1.
HPAiCAB004224.
HPA048561.
MIMi602919. gene.
neXtProtiNX_Q99704.
OpenTargetsiENSG00000115325.
PharmGKBiPA27456.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG4047. Eukaryota.
ENOG410XS2S. LUCA.
GeneTreeiENSGT00730000110348.
HOGENOMiHOG000112245.
HOVERGENiHBG018962.
InParanoidiQ99704.
KOiK14752.
OMAiWPYTLLR.
OrthoDBiEOG091G075T.
PhylomeDBiQ99704.
TreeFamiTF324994.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000115325-MONOMER.
ReactomeiR-HSA-8849469. PTK6 Regulates RTKs and Their Effectors AKT1 and DOK1.
R-HSA-8853659. RET signaling.
SignaLinkiQ99704.
SIGNORiQ99704.

Miscellaneous databases

EvolutionaryTraceiQ99704.
GeneWikiiDOK1.
GenomeRNAii1796.
PROiQ99704.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000115325.
CleanExiHS_DOK1.
ExpressionAtlasiQ99704. baseline and differential.
GenevisibleiQ99704. HS.

Family and domain databases

Gene3Di2.30.29.30. 2 hits.
InterProiIPR002404. IRS_PTB.
IPR011993. PH_dom-like.
IPR001849. PH_domain.
[Graphical view]
PfamiPF02174. IRS. 1 hit.
PF00169. PH. 1 hit.
[Graphical view]
SMARTiSM00233. PH. 1 hit.
SM00310. PTBI. 1 hit.
[Graphical view]
SUPFAMiSSF50729. SSF50729. 2 hits.
PROSITEiPS51064. IRS_PTB. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiDOK1_HUMAN
AccessioniPrimary (citable) accession number: Q99704
Secondary accession number(s): O43204, Q53TY2, Q9UHG6
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 16, 2001
Last sequence update: May 1, 1997
Last modified: November 30, 2016
This is version 158 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 2
    Human chromosome 2: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  4. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.