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O60496 (DOK2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 118. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Docking protein 2
Alternative name(s):
Downstream of tyrosine kinase 2
p56(dok-2)
Gene names
Name:DOK2
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length412 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. 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.

Subunit structure

Interacts with phosphorylated RASGAP and EGFR. Interacts with RET and NCK. Interacts (via PH domain) with TEK/TIE2 (tyrosine phosphorylated) By similarity. Ref.1

Tissue specificity

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

Domain

PTB domain mediates receptor interaction.

Post-translational modification

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.

Sequence similarities

Belongs to the DOK family. Type A subfamily.

Contains 1 IRS-type PTB domain.

Contains 1 PH domain.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 412412Docking protein 2
PRO_0000187270

Regions

Domain4 – 114111PH
Domain147 – 252106IRS-type PTB
Compositional bias250 – 29243Pro-rich
Compositional bias321 – 36343Pro-rich

Amino acid modifications

Modified residue2711Phosphotyrosine By similarity
Modified residue2991Phosphotyrosine Ref.3 Ref.4 Ref.5
Modified residue3451Phosphotyrosine By similarity

Natural variations

Natural variant1521A → P. Ref.1
Corresponds to variant rs1140295 [ dbSNP | Ensembl ].
VAR_030951
Natural variant2741P → L.
Corresponds to variant rs34215892 [ dbSNP | Ensembl ].
VAR_053068
Natural variant3941S → A.
Corresponds to variant rs2242241 [ dbSNP | Ensembl ].
VAR_030952

Experimental info

Sequence conflict1661L → R in AAC13265. Ref.1
Sequence conflict1781A → S in AAC13265. Ref.1
Sequence conflict3471E → K in AAC13265. Ref.1
Sequence conflict3741A → R in AAC13265. Ref.1

Secondary structure

.............................................. 412
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
O60496 [UniParc].

Last modified March 6, 2007. Version 2.
Checksum: EFAEDBA68439757F

FASTA41245,379
        10         20         30         40         50         60 
MGDGAVKQGF LYLQQQQTFG KKWRRFGASL YGGSDCALAR LELQEGPEKP RRCEAARKVI 

        70         80         90        100        110        120 
RLSDCLRVAE AGGEASSPRD TSAFFLETKE RLYLLAAPAA ERGDWVQAIC LLAFPGQRKE 

       130        140        150        160        170        180 
LSGPEGKQSR PCMEENELYS SAVTVGPHKE FAVTMRPTEA SERCHLRGSY TLRAGESALE 

       190        200        210        220        230        240 
LWGGPEPGTQ LYDWPYRFLR RFGRDKVTFS FEAGRRCVSG EGNFEFETRQ GNEIFLALEE 

       250        260        270        280        290        300 
AISAQKNAAP ATPQPQPATI PASLPRPDSP YSRPHDSLPP PSPTTPVPAP RPRGQEGEYA 

       310        320        330        340        350        360 
VPFDAVARSL GKNFRGILAV PPQLLADPLY DSIEETLPPR PDHIYDEPEG VAALSLYDSP 

       370        380        390        400        410 
QEPRGEAWRR QATADRDPAG LQHVQPAGQD FSASGWQPGT EYDNVVLKKG PK 

« Hide

References

« Hide 'large scale' references
[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.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF034970 mRNA. Translation: AAC13265.1.
BC032623 mRNA. Translation: AAH32623.1.
CCDSCCDS6016.1.
RefSeqNP_003965.2. NM_003974.2.
UniGeneHs.71215.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2D9WNMR-A1-114[»]
2DLWNMR-A148-247[»]
ProteinModelPortalO60496.
SMRO60496. Positions 5-116, 148-252, 301-333.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid114508. 20 interactions.
IntActO60496. 1 interaction.
MINTMINT-1452945.
STRING9606.ENSP00000276420.

PTM databases

PhosphoSiteO60496.

2D gel databases

OGPO60496.

Proteomic databases

MaxQBO60496.
PaxDbO60496.
PRIDEO60496.

Protocols and materials databases

DNASU9046.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000276420; ENSP00000276420; ENSG00000147443.
GeneID9046.
KEGGhsa:9046.
UCSCuc003wzx.1. human.

Organism-specific databases

CTD9046.
GeneCardsGC08M021822.
HGNCHGNC:2991. DOK2.
HPACAB004379.
MIM604997. gene.
neXtProtNX_O60496.
PharmGKBPA27457.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG319058.
HOGENOMHOG000112245.
HOVERGENHBG018962.
InParanoidO60496.
OMAGKKWRRF.
OrthoDBEOG77WWC5.
PhylomeDBO60496.
TreeFamTF324994.

Enzyme and pathway databases

ReactomeREACT_604. Hemostasis.
SignaLinkO60496.

Gene expression databases

ArrayExpressO60496.
BgeeO60496.
CleanExHS_DOK2.
GenevestigatorO60496.

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.
PS50003. PH_DOMAIN. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceO60496.
GeneWikiDOK2.
GenomeRNAi9046.
NextBio33885.
PROO60496.
SOURCESearch...

Entry information

Entry nameDOK2_HUMAN
AccessionPrimary (citable) accession number: O60496
Secondary accession number(s): Q8N5A4
Entry history
Integrated into UniProtKB/Swiss-Prot: November 16, 2001
Last sequence update: March 6, 2007
Last modified: July 9, 2014
This is version 118 of the entry and version 2 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 polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 8

Human chromosome 8: entries, gene names and cross-references to MIM