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Protein

Docking protein 2

Gene

DOK2

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. DOK2 may modulate the cellular proliferation induced by IL-4, as well as IL-2 and IL-3. May be involved in modulating Bcr-Abl signaling. Attenuates EGF-stimulated MAP kinase activation (By similarity).By similarity

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Enzyme and pathway databases

ReactomeiREACT_12621. Tie2 Signaling.
SignaLinkiO60496.

Names & Taxonomyi

Protein namesi
Recommended name:
Docking protein 2
Alternative name(s):
Downstream of tyrosine kinase 2
p56(dok-2)
Gene namesi
Name:DOK2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640 Componenti: Chromosome 8

Organism-specific databases

HGNCiHGNC:2991. DOK2.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA27457.

Polymorphism and mutation databases

BioMutaiDOK2.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 412412Docking protein 2PRO_0000187270Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei271 – 2711PhosphotyrosineBy similarity
Modified residuei299 – 2991Phosphotyrosine3 Publications
Modified residuei345 – 3451PhosphotyrosineBy similarity

Post-translational modificationi

On immunoreceptor stimulation, phosphorylated on C-terminal tyrosine residues. Phosphorylation on Tyr-345 is required for binding to the SH2 domain of NCK. Phosphorylation on both Tyr-271 and Tyr-299 is required for interaction with RASGAP. Phosphorylated on tyrosine residues by TEK/TIE2 (By similarity).By similarity

Keywords - PTMi

Phosphoprotein

Proteomic databases

MaxQBiO60496.
PaxDbiO60496.
PRIDEiO60496.

2D gel databases

OGPiO60496.

PTM databases

PhosphoSiteiO60496.

Expressioni

Tissue specificityi

Highly expressed in peripheral blood leukocytes, lymph nodes and spleen. Lower expression in thymus, bone marrow and fetal liver.1 Publication

Gene expression databases

BgeeiO60496.
CleanExiHS_DOK2.
ExpressionAtlasiO60496. baseline and differential.
GenevisibleiO60496. HS.

Organism-specific databases

HPAiCAB004379.

Interactioni

Subunit structurei

Interacts with phosphorylated RASGAP and EGFR. Interacts with RET and NCK. Interacts (via PH domain) with TEK/TIE2 (tyrosine phosphorylated) (By similarity).By similarity

Protein-protein interaction databases

BioGridi114508. 25 interactions.
IntActiO60496. 7 interactions.
MINTiMINT-1452945.
STRINGi9606.ENSP00000276420.

Structurei

Secondary structure

1
412
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi5 – 139Combined sources
Beta strandi17 – 204Combined sources
Beta strandi25 – 317Combined sources
Beta strandi34 – 374Combined sources
Beta strandi40 – 445Combined sources
Beta strandi50 – 523Combined sources
Beta strandi57 – 604Combined sources
Helixi62 – 643Combined sources
Beta strandi65 – 706Combined sources
Beta strandi75 – 773Combined sources
Beta strandi82 – 909Combined sources
Beta strandi92 – 976Combined sources
Helixi99 – 11315Combined sources
Beta strandi151 – 1555Combined sources
Helixi159 – 1646Combined sources
Beta strandi168 – 1747Combined sources
Beta strandi176 – 1805Combined sources
Beta strandi184 – 1874Combined sources
Helixi196 – 1983Combined sources
Beta strandi202 – 2054Combined sources
Beta strandi208 – 2136Combined sources
Beta strandi221 – 2266Combined sources
Helixi231 – 24717Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
2D9WNMR-A1-114[»]
2DLWNMR-A148-247[»]
ProteinModelPortaliO60496.
SMRiO60496. Positions 5-116, 148-252.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiO60496.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini4 – 114111PHPROSITE-ProRule annotationAdd
BLAST
Domaini147 – 252106IRS-type PTBPROSITE-ProRule annotationAdd
BLAST

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi250 – 29243Pro-richAdd
BLAST
Compositional biasi321 – 36343Pro-richAdd
BLAST

Domaini

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.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiNOG319058.
GeneTreeiENSGT00730000110348.
HOGENOMiHOG000112245.
HOVERGENiHBG018962.
InParanoidiO60496.
OMAiDWVQAIC.
OrthoDBiEOG77WWC5.
PhylomeDBiO60496.
TreeFamiTF324994.

Family and domain databases

Gene3Di2.30.29.30. 2 hits.
InterProiIPR002404. Insln_rcpt_S1.
IPR011993. PH-like_dom.
IPR001849. PH_domain.
[Graphical view]
PfamiPF02174. IRS. 1 hit.
[Graphical view]
SMARTiSM00233. PH. 1 hit.
SM00310. PTBI. 1 hit.
[Graphical view]
PROSITEiPS51064. IRS_PTB. 1 hit.
PS50003. PH_DOMAIN. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

O60496-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MGDGAVKQGF LYLQQQQTFG KKWRRFGASL YGGSDCALAR LELQEGPEKP
60 70 80 90 100
RRCEAARKVI RLSDCLRVAE AGGEASSPRD TSAFFLETKE RLYLLAAPAA
110 120 130 140 150
ERGDWVQAIC LLAFPGQRKE LSGPEGKQSR PCMEENELYS SAVTVGPHKE
160 170 180 190 200
FAVTMRPTEA SERCHLRGSY TLRAGESALE LWGGPEPGTQ LYDWPYRFLR
210 220 230 240 250
RFGRDKVTFS FEAGRRCVSG EGNFEFETRQ GNEIFLALEE AISAQKNAAP
260 270 280 290 300
ATPQPQPATI PASLPRPDSP YSRPHDSLPP PSPTTPVPAP RPRGQEGEYA
310 320 330 340 350
VPFDAVARSL GKNFRGILAV PPQLLADPLY DSIEETLPPR PDHIYDEPEG
360 370 380 390 400
VAALSLYDSP QEPRGEAWRR QATADRDPAG LQHVQPAGQD FSASGWQPGT
410
EYDNVVLKKG PK
Length:412
Mass (Da):45,379
Last modified:March 6, 2007 - v2
Checksum:iEFAEDBA68439757F
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti166 – 1661L → R in AAC13265 (PubMed:9478921).Curated
Sequence conflicti178 – 1781A → S in AAC13265 (PubMed:9478921).Curated
Sequence conflicti347 – 3471E → K in AAC13265 (PubMed:9478921).Curated
Sequence conflicti374 – 3741A → R in AAC13265 (PubMed:9478921).Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti152 – 1521A → P.1 Publication
Corresponds to variant rs1140295 [ dbSNP | Ensembl ].
VAR_030951
Natural varianti274 – 2741P → L.
Corresponds to variant rs34215892 [ dbSNP | Ensembl ].
VAR_053068
Natural varianti394 – 3941S → A.
Corresponds to variant rs2242241 [ dbSNP | Ensembl ].
VAR_030952

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF034970 mRNA. Translation: AAC13265.1.
BC032623 mRNA. Translation: AAH32623.1.
CCDSiCCDS6016.1.
RefSeqiNP_003965.2. NM_003974.2.
UniGeneiHs.71215.

Genome annotation databases

EnsembliENST00000276420; ENSP00000276420; ENSG00000147443.
GeneIDi9046.
KEGGihsa:9046.
UCSCiuc003wzx.1. human.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF034970 mRNA. Translation: AAC13265.1.
BC032623 mRNA. Translation: AAH32623.1.
CCDSiCCDS6016.1.
RefSeqiNP_003965.2. NM_003974.2.
UniGeneiHs.71215.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
2D9WNMR-A1-114[»]
2DLWNMR-A148-247[»]
ProteinModelPortaliO60496.
SMRiO60496. Positions 5-116, 148-252.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi114508. 25 interactions.
IntActiO60496. 7 interactions.
MINTiMINT-1452945.
STRINGi9606.ENSP00000276420.

PTM databases

PhosphoSiteiO60496.

Polymorphism and mutation databases

BioMutaiDOK2.

2D gel databases

OGPiO60496.

Proteomic databases

MaxQBiO60496.
PaxDbiO60496.
PRIDEiO60496.

Protocols and materials databases

DNASUi9046.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000276420; ENSP00000276420; ENSG00000147443.
GeneIDi9046.
KEGGihsa:9046.
UCSCiuc003wzx.1. human.

Organism-specific databases

CTDi9046.
GeneCardsiGC08M021766.
HGNCiHGNC:2991. DOK2.
HPAiCAB004379.
MIMi604997. gene.
neXtProtiNX_O60496.
PharmGKBiPA27457.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiNOG319058.
GeneTreeiENSGT00730000110348.
HOGENOMiHOG000112245.
HOVERGENiHBG018962.
InParanoidiO60496.
OMAiDWVQAIC.
OrthoDBiEOG77WWC5.
PhylomeDBiO60496.
TreeFamiTF324994.

Enzyme and pathway databases

ReactomeiREACT_12621. Tie2 Signaling.
SignaLinkiO60496.

Miscellaneous databases

ChiTaRSiDOK2. human.
EvolutionaryTraceiO60496.
GeneWikiiDOK2.
GenomeRNAii9046.
NextBioi33885.
PROiO60496.
SOURCEiSearch...

Gene expression databases

BgeeiO60496.
CleanExiHS_DOK2.
ExpressionAtlasiO60496. baseline and differential.
GenevisibleiO60496. HS.

Family and domain databases

Gene3Di2.30.29.30. 2 hits.
InterProiIPR002404. Insln_rcpt_S1.
IPR011993. PH-like_dom.
IPR001849. PH_domain.
[Graphical view]
PfamiPF02174. IRS. 1 hit.
[Graphical view]
SMARTiSM00233. PH. 1 hit.
SM00310. PTBI. 1 hit.
[Graphical view]
PROSITEiPS51064. IRS_PTB. 1 hit.
PS50003. PH_DOMAIN. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Molecular cloning and characterization of p56dok-2 defines a new family of RasGAP-binding proteins."
    Di Cristofano A., Carpino N., Dunant N., Friedland G., Kobayashi R., Strife A., Wisniewski D., Clarkson B., Pandolfi P.P., Resh M.D.
    J. Biol. Chem. 273:4827-4830(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 8-21; 30-49; 59-89 AND 128-149, TISSUE SPECIFICITY, INTERACTION WITH RASGAP, VARIANT PRO-152.
  2. "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].
    Tissue: Brain.
  3. "Robust phosphoproteomic profiling of tyrosine phosphorylation sites from human T cells using immobilized metal affinity chromatography and tandem mass spectrometry."
    Brill L.M., Salomon A.R., Ficarro S.B., Mukherji M., Stettler-Gill M., Peters E.C.
    Anal. Chem. 76:2763-2772(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-299, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Leukemic T-cell.
  4. "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-299, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
  5. "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 TYR-299, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Leukemic T-cell.
  6. "Solution structure of the PH and IRS domains of human docking protein 2, isoform A."
    RIKEN structural genomics initiative (RSGI)
    Submitted (OCT-2006) to the PDB data bank
    Cited for: STRUCTURE BY NMR OF 1-247.

Entry informationi

Entry nameiDOK2_HUMAN
AccessioniPrimary (citable) accession number: O60496
Secondary accession number(s): Q8N5A4
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 16, 2001
Last sequence update: March 6, 2007
Last modified: July 22, 2015
This is version 128 of the entry and version 2 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, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 8
    Human chromosome 8: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

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 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.