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Protein

Docking protein 2

Gene

DOK2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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

Enzyme and pathway databases

ReactomeiR-HSA-210993 Tie2 Signaling
R-HSA-8853659 RET signaling
SignaLinkiO60496
SIGNORiO60496

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
Proteomesi
  • UP000005640 Componenti: Chromosome 8

Organism-specific databases

EuPathDBiHostDB:ENSG00000147443.12
HGNCiHGNC:2991 DOK2
MIMi604997 gene
neXtProtiNX_O60496

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Pathology & Biotechi

Organism-specific databases

DisGeNETi9046
OpenTargetsiENSG00000147443
PharmGKBiPA27457

Polymorphism and mutation databases

BioMutaiDOK2

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001872701 – 412Docking protein 2Add BLAST412

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei271PhosphotyrosineBy similarity1
Modified residuei299PhosphotyrosineCombined sources1
Modified residuei345PhosphotyrosineBy similarity1

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
PeptideAtlasiO60496
PRIDEiO60496
ProteomicsDBi49433

2D gel databases

OGPiO60496

PTM databases

iPTMnetiO60496
PhosphoSitePlusiO60496

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

BgeeiENSG00000147443 Expressed in 156 organ(s), highest expression level in blood
CleanExiHS_DOK2
ExpressionAtlasiO60496 baseline and differential
GenevisibleiO60496 HS

Organism-specific databases

HPAiCAB004379
HPA066571

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
(Microbial infection) Interacts with Herpes simplex virus 1 (HHV-1) protein UL46; this interaction induces DOK2 phosphorylation and subsequent degradation.1 Publication

Binary interactionsi

WithEntry#Exp.IntActNotes
POT1Q9NUX52EBI-1046024,EBI-752420

GO - Molecular functioni

Protein-protein interaction databases

BioGridi114508, 37 interactors
IntActiO60496, 10 interactors
MINTiO60496
STRINGi9606.ENSP00000276420

Structurei

Secondary structure

1412
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliO60496
SMRiO60496
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiO60496

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini4 – 114PHPROSITE-ProRule annotationAdd BLAST111
Domaini147 – 252IRS-type PTBPROSITE-ProRule annotationAdd BLAST106

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi250 – 292Pro-richAdd BLAST43
Compositional biasi321 – 363Pro-richAdd BLAST43

Domaini

PTB domain mediates receptor interaction.

Sequence similaritiesi

Belongs to the DOK family. Type A subfamily.Curated

Phylogenomic databases

eggNOGiKOG4047 Eukaryota
ENOG410XS2S LUCA
GeneTreeiENSGT00730000110348
HOGENOMiHOG000112245
HOVERGENiHBG018962
InParanoidiO60496
KOiK20234
OMAiEYAVPFD
OrthoDBiEOG091G075T
PhylomeDBiO60496
TreeFamiTF324994

Family and domain databases

CDDicd01203 PTB_DOK1_DOK2_DOK3, 1 hit
Gene3Di2.30.29.30, 2 hits
InterProiView protein in InterPro
IPR037751 Dok1/2/3_PTB
IPR002404 IRS_PTB
IPR011993 PH-like_dom_sf
IPR001849 PH_domain
PfamiView protein in Pfam
PF02174 IRS, 1 hit
SMARTiView protein in SMART
SM00233 PH, 1 hit
SM00310 PTBI, 1 hit
PROSITEiView protein in PROSITE
PS51064 IRS_PTB, 1 hit
PS50003 PH_DOMAIN, 1 hit

Sequence (1+)i

Sequence statusi: Complete.

This entry has 1 described isoform and 3 potential isoforms that are computationally mapped.Show allAlign All

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

Computationally mapped potential isoform sequencesi

There are 3 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
E5RIG9E5RIG9_HUMAN
Docking protein 2
DOK2
151Annotation score:
E5RJ11E5RJ11_HUMAN
Docking protein 2
DOK2
233Annotation score:
G3V114G3V114_HUMAN
Docking protein 2
DOK2 hCG_22278
123Annotation score:

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti166L → R in AAC13265 (PubMed:9478921).Curated1
Sequence conflicti178A → S in AAC13265 (PubMed:9478921).Curated1
Sequence conflicti347E → K in AAC13265 (PubMed:9478921).Curated1
Sequence conflicti374A → R in AAC13265 (PubMed:9478921).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_030951152A → P1 PublicationCorresponds to variant dbSNP:rs1140295Ensembl.1
Natural variantiVAR_053068274P → L. Corresponds to variant dbSNP:rs34215892Ensembl.1
Natural variantiVAR_030952394S → A. Corresponds to variant dbSNP:rs2242241Ensembl.1

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_003974.3
UniGeneiHs.71215

Genome annotation databases

EnsembliENST00000276420; ENSP00000276420; ENSG00000147443
GeneIDi9046
KEGGihsa:9046
UCSCiuc003wzy.2 human

Keywords - Coding sequence diversityi

Polymorphism

Similar proteinsi

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_003974.3
UniGeneiHs.71215

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2D9WNMR-A1-114[»]
2DLWNMR-A148-247[»]
ProteinModelPortaliO60496
SMRiO60496
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi114508, 37 interactors
IntActiO60496, 10 interactors
MINTiO60496
STRINGi9606.ENSP00000276420

PTM databases

iPTMnetiO60496
PhosphoSitePlusiO60496

Polymorphism and mutation databases

BioMutaiDOK2

2D gel databases

OGPiO60496

Proteomic databases

MaxQBiO60496
PaxDbiO60496
PeptideAtlasiO60496
PRIDEiO60496
ProteomicsDBi49433

Protocols and materials databases

DNASUi9046
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000276420; ENSP00000276420; ENSG00000147443
GeneIDi9046
KEGGihsa:9046
UCSCiuc003wzy.2 human

Organism-specific databases

CTDi9046
DisGeNETi9046
EuPathDBiHostDB:ENSG00000147443.12
GeneCardsiDOK2
HGNCiHGNC:2991 DOK2
HPAiCAB004379
HPA066571
MIMi604997 gene
neXtProtiNX_O60496
OpenTargetsiENSG00000147443
PharmGKBiPA27457
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG4047 Eukaryota
ENOG410XS2S LUCA
GeneTreeiENSGT00730000110348
HOGENOMiHOG000112245
HOVERGENiHBG018962
InParanoidiO60496
KOiK20234
OMAiEYAVPFD
OrthoDBiEOG091G075T
PhylomeDBiO60496
TreeFamiTF324994

Enzyme and pathway databases

ReactomeiR-HSA-210993 Tie2 Signaling
R-HSA-8853659 RET signaling
SignaLinkiO60496
SIGNORiO60496

Miscellaneous databases

ChiTaRSiDOK2 human
EvolutionaryTraceiO60496
GeneWikiiDOK2
GenomeRNAii9046
PROiPR:O60496
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000147443 Expressed in 156 organ(s), highest expression level in blood
CleanExiHS_DOK2
ExpressionAtlasiO60496 baseline and differential
GenevisibleiO60496 HS

Family and domain databases

CDDicd01203 PTB_DOK1_DOK2_DOK3, 1 hit
Gene3Di2.30.29.30, 2 hits
InterProiView protein in InterPro
IPR037751 Dok1/2/3_PTB
IPR002404 IRS_PTB
IPR011993 PH-like_dom_sf
IPR001849 PH_domain
PfamiView protein in Pfam
PF02174 IRS, 1 hit
SMARTiView protein in SMART
SM00233 PH, 1 hit
SM00310 PTBI, 1 hit
PROSITEiView protein in PROSITE
PS51064 IRS_PTB, 1 hit
PS50003 PH_DOMAIN, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiDOK2_HUMAN
AccessioniPrimary (citable) accession number: O60496
Secondary accession number(s): Q8N5A4
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 16, 2001
Last sequence update: March 6, 2007
Last modified: September 12, 2018
This is version 157 of the entry and version 2 of the sequence. See 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. SIMILARITY comments
    Index of protein domains and families
  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. Human chromosome 8
    Human chromosome 8: entries, gene names and cross-references to MIM
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Main funding by: National Institutes of Health

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