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Protein

Docking protein 2

Gene

Dok2

Organism
Mus musculus (Mouse)
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.

GO - Molecular functioni

  • receptor signaling protein activity Source: MGI
  • transmembrane receptor protein tyrosine kinase adaptor activity Source: MGI

GO - Biological processi

  • MAPK cascade Source: MGI
  • Ras protein signal transduction Source: MGI
  • transmembrane receptor protein tyrosine kinase signaling pathway Source: MGI
Complete GO annotation...

Enzyme and pathway databases

ReactomeiR-MMU-210993. Tie2 Signaling.

Names & Taxonomyi

Protein namesi
Recommended name:
Docking protein 2
Alternative name(s):
Dok-related protein
Short name:
Dok-R
Downstream of tyrosine kinase 2
IL-four receptor-interacting protein
Short name:
FRIP
p56(dok-2)
Gene namesi
Name:Dok2
Synonyms:Frip
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 14

Organism-specific databases

MGIiMGI:1332623. Dok2.

Subcellular locationi

GO - Cellular componenti

  • intracellular Source: GOC
Complete GO annotation...

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi276 – 2761Y → F: No loss of binding to SH2 domain of RASGAP or NCK. Complete loss of binding to SH2 domain of RASGAP; when associated with F-304. 1 Publication
Mutagenesisi304 – 3041Y → F: No loss of binding to SH2 domain of RASGAP. Complete loss of binding to SH2 domain of RASGAP; when associated with F-276. 1 Publication
Mutagenesisi351 – 3511Y → F: No loss of binding to SH2 domain of RASGAP. Complete loss of binding to SH2 domain of NCK. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 412412Docking protein 2PRO_0000187271Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei276 – 2761Phosphotyrosine1 Publication
Modified residuei304 – 3041Phosphotyrosine1 Publication
Modified residuei351 – 3511Phosphotyrosine1 Publication

Post-translational modificationi

On immunoreceptor stimulation, phosphorylated on C-terminal tyrosine residues. Phosphorylation on Tyr-351 is required for binding to the SH2 domain of NCK. Phosphorylation on both Tyr-276 and Tyr-304 is required for interaction with RASGAP. Phosphorylated on tyrosine residues by TEK/TIE2.4 Publications

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiO70469.
PaxDbiO70469.
PRIDEiO70469.

PTM databases

iPTMnetiO70469.
PhosphoSiteiO70469.

Expressioni

Tissue specificityi

Highly expressed in spleen and lung.2 Publications

Developmental stagei

During embryonic liver development, expressed in the islands of cells, consistent with an expression in hematopoietic precursors.1 Publication

Gene expression databases

BgeeiO70469.
CleanExiMM_DOK2.
ExpressionAtlasiO70469. baseline and differential.
GenevisibleiO70469. MM.

Interactioni

Subunit structurei

Interacts with phosphorylated RASGAP and EGFR. Interacts with RET and NCK. Interacts (via PH domain) with TEK/TIE2 (tyrosine phosphorylated).3 Publications

GO - Molecular functioni

  • transmembrane receptor protein tyrosine kinase adaptor activity Source: MGI

Protein-protein interaction databases

BioGridi199268. 6 interactions.
IntActiO70469. 10 interactions.
MINTiMINT-100549.
STRINGi10090.ENSMUSP00000022698.

Structurei

3D structure databases

ProteinModelPortaliO70469.
SMRiO70469. Positions 8-123, 144-253.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini7 – 117111PHPROSITE-ProRule annotationAdd
BLAST
Domaini149 – 254106IRS-type PTBPROSITE-ProRule annotationAdd
BLAST

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi252 – 30756Pro-richAdd
BLAST
Compositional biasi326 – 36944Pro-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

eggNOGiKOG4047. Eukaryota.
ENOG410XS2S. LUCA.
HOGENOMiHOG000112245.
HOVERGENiHBG018962.
InParanoidiO70469.
OMAiRRCFSGE.
OrthoDBiEOG77WWC5.
PhylomeDBiO70469.
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.
PS50003. PH_DOMAIN. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

O70469-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MVRMEEPAVK QGFLHLQQQQ TFGKKWRRFA AVLYGESGCA LARLELQDVP
60 70 80 90 100
EKTRRGEATR KVVRLSDCLR VAEVGSEASS PRDTSAFILE TKERLYLLAA
110 120 130 140 150
PSAERSDWIQ AICLLAFPGQ RKGSPGLEEK SGSPCMEENE LYSSSTTGLC
160 170 180 190 200
KEYMVTIRPT EASERCRLRG SYTLRTGVSA LELWGGPEPG TQLYDWPYRF
210 220 230 240 250
LRRFGRDKAT FSFEAGRRCL SGEGNFEFET RHGNEIFQAL EKVIAVQKNA
260 270 280 290 300
TPSGPPSLPA TGPMMPTVLP RPESPYSRPH DSLPSPSPGT LVPGMRPGAP
310 320 330 340 350
EGEYAVPFDT VAHSLRKSFR GLLTGPPPHL PDPLYDSIQE DPGAPLPDHI
360 370 380 390 400
YDEPEGVAAL SLYDRTQRPS GETWREQATA DGGPSSLQQD SSVPDWPQAT
410
EYDNVILKKG PK
Length:412
Mass (Da):45,522
Last modified:August 1, 1998 - v1
Checksum:i02AC02530DBED053
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti245 – 2451A → T in AAH04590 (PubMed:15489334).Curated
Sequence conflicti330 – 3301L → F in AAC13266 (PubMed:9478921).Curated
Sequence conflicti347 – 3471P → T in AAC13266 (PubMed:9478921).Curated
Sequence conflicti412 – 4121Missing in AAH04590 (PubMed:15489334).Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF030627 mRNA. Translation: AAC31315.1.
AF035117 mRNA. Translation: AAC13266.1.
AF059583 mRNA. Translation: AAC78606.1.
BC004590 mRNA. Translation: AAH04590.1.
CCDSiCCDS27262.1.
RefSeqiNP_034201.1. NM_010071.2.
UniGeneiMm.243323.

Genome annotation databases

EnsembliENSMUST00000022698; ENSMUSP00000022698; ENSMUSG00000022102.
GeneIDi13449.
KEGGimmu:13449.
UCSCiuc007uoy.1. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF030627 mRNA. Translation: AAC31315.1.
AF035117 mRNA. Translation: AAC13266.1.
AF059583 mRNA. Translation: AAC78606.1.
BC004590 mRNA. Translation: AAH04590.1.
CCDSiCCDS27262.1.
RefSeqiNP_034201.1. NM_010071.2.
UniGeneiMm.243323.

3D structure databases

ProteinModelPortaliO70469.
SMRiO70469. Positions 8-123, 144-253.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi199268. 6 interactions.
IntActiO70469. 10 interactions.
MINTiMINT-100549.
STRINGi10090.ENSMUSP00000022698.

PTM databases

iPTMnetiO70469.
PhosphoSiteiO70469.

Proteomic databases

EPDiO70469.
PaxDbiO70469.
PRIDEiO70469.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000022698; ENSMUSP00000022698; ENSMUSG00000022102.
GeneIDi13449.
KEGGimmu:13449.
UCSCiuc007uoy.1. mouse.

Organism-specific databases

CTDi9046.
MGIiMGI:1332623. Dok2.

Phylogenomic databases

eggNOGiKOG4047. Eukaryota.
ENOG410XS2S. LUCA.
HOGENOMiHOG000112245.
HOVERGENiHBG018962.
InParanoidiO70469.
OMAiRRCFSGE.
OrthoDBiEOG77WWC5.
PhylomeDBiO70469.
TreeFamiTF324994.

Enzyme and pathway databases

ReactomeiR-MMU-210993. Tie2 Signaling.

Miscellaneous databases

PROiO70469.
SOURCEiSearch...

Gene expression databases

BgeeiO70469.
CleanExiMM_DOK2.
ExpressionAtlasiO70469. baseline and differential.
GenevisibleiO70469. MM.

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

Publicationsi

« Hide 'large scale' publications
  1. "FRIP, a hematopoietic cell-specific rasGAP-interacting protein phosphorylated in response to cytokine stimulation."
    Nelms K., Snow A.L., Hu-Li J., Paul W.E.
    Immunity 9:13-24(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], PHOSPHORYLATION AT TYROSINE RESIDUES.
  2. "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], TISSUE SPECIFICITY.
  3. "The Tek/Tie2 receptor signals through a novel Dok-related docking protein, Dok-R."
    Jones N., Dumont D.J.
    Oncogene 17:1097-1108(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
  4. "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].
  5. "Recruitment of Dok-R to the EGF receptor through its PTB domain is required for attenuation of Erk MAP kinase activation."
    Jones N., Dumont D.J.
    Curr. Biol. 9:1057-1060(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH EGFR; NCK AND RASGAP, PHOSPHORYLATION AT TYR-276; TYR-304 AND TYR-351, MUTAGENESIS OF TYR-276; TYR-304 AND TYR-351.
  6. "Novel p62dok family members, dok-4 and dok-5, are substrates of the c-Ret receptor tyrosine kinase and mediate neuronal differentiation."
    Grimm J., Sachs M., Britsch S., Di Cesare S., Schwarz-Romond T., Alitalo K., Birchmeier W.
    J. Cell Biol. 154:345-354(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH RET, PHOSPHORYLATION, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE.
  7. "A unique autophosphorylation site on Tie2/Tek mediates Dok-R phosphotyrosine binding domain binding and function."
    Jones N., Chen S.H., Sturk C., Master Z., Tran J., Kerbel R.S., Dumont D.J.
    Mol. Cell. Biol. 23:2658-2668(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH TEK/TIE2, PHOSPHORYLATION.

Entry informationi

Entry nameiDOK2_MOUSE
AccessioniPrimary (citable) accession number: O70469
Secondary accession number(s): O70272, Q99KL1
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 16, 2001
Last sequence update: August 1, 1998
Last modified: June 8, 2016
This is version 122 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. 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.