Reviewed, UniProtKB/Swiss-Prot O60496 (DOK2_HUMAN)

Names and origin

Protein names

Recommended name:
    Docking protein 2
Alternative name(s):
    Downstream of tyrosine kinase 2
    p56(dok-2)

Gene names

Name:

DOK2

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	412 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Docking proteins interact with receptor tyrosine kinases and mediate particular biological responses. 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 By similarity.
Tissue specificity	Highly expressed in peripheral blood leukocytes, lymph nodes and spleen. Lower expression in thymus, bone marrow and fetal liver.
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 By similarity.
Sequence similarities	Belongs to the DOK family. Type A subfamily. Contains 1 IRS-type PTB domain. Contains 1 PH domain.

Ontologies

Keywords
Coding sequence diversity	Polymorphism
PTM	Phosphoprotein
Technical term	3D-structure Direct protein sequencing
Gene Ontology (GO)
Biological process	cell surface receptor linked signal transduction Traceable author statement. Source: ProtInc
Molecular function	identical protein binding Inferred from physical interaction. Source: IntAct
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
itself		1	EBI-1046024,EBI-1046024
ASF1B	Q9NVP2	1	EBI-1046024,EBI-1055650
CFLAR	O15519	1	EBI-1046024,EBI-514941
DNAJB11	Q9UBS4	1	EBI-1046024,EBI-713113
EPO	P01588	1	EBI-1046024,EBI-1027362
HSPA4L	O95757	1	EBI-1046024,EBI-358652
PSMD10	O75832	1	EBI-1046024,EBI-752185
RAB10	P61026	1	EBI-1046024,EBI-726075
SPOP	O43791	1	EBI-1046024,EBI-743549
SSSCA1	O60232	1	EBI-1046024,EBI-741415

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Molecule processing

Chain

1 – 412

412

Docking protein 2

Regions

Domain

4 – 114

111

PH

Domain

147 – 252

106

IRS-type PTB

Compositional bias

250 – 292

43

Pro-rich

Compositional bias

321 – 363

43

Pro-rich

Amino acid modifications

Modified residue

271

1

Phosphotyrosine By similarity

Modified residue

299

1

Phosphotyrosine

Modified residue

345

1

Phosphotyrosine By similarity

Natural variations

Natural variant

152

1

A → P: dbSNP rs1140295.

Natural variant

394

1

S → A: dbSNP rs2242241.

Experimental info

Sequence conflict

166

1

L → R in AAC13265. Ref.1

Sequence conflict

178

1

A → S in AAC13265. Ref.1

Sequence conflict

347

1

E → K in AAC13265. Ref.1

Sequence conflict

374

1

A → R in AAC13265. Ref.1

Secondary structure

1

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412

Helix Strand Turn

Details...

Beta strand

5 – 13

9

Beta strand

17 – 20

4

Beta strand

25 – 31

7

Beta strand

34 – 37

4

Beta strand

40 – 44

5

Beta strand

50 – 52

3

Beta strand

57 – 60

4

Helix

62 – 64

3

Beta strand

65 – 70

6

Beta strand

75 – 77

3

Beta strand

82 – 90

9

Beta strand

92 – 97

6

Helix

99 – 113

15

Beta strand

151 – 155

5

Helix

159 – 164

6

Beta strand

168 – 174

7

Beta strand

176 – 180

5

Beta strand

184 – 187

4

Helix

196 – 198

3

Beta strand

202 – 205

4

Beta strand

208 – 213

6

Beta strand

221 – 226

6

Sequences

	Sequence		Length	Mass (Da)
	O60496-1 [UniParc]. Last modified March 6, 2007. Version 2. Checksum: EFAEDBA68439757F	FASTA	412	45,379
	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

References

	« Hide 'large scale' referencesShow '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: 9478921] [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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Brain.
[3]	"Profiling of tyrosine phosphorylation pathways in human cells using mass spectrometry." Salomon A.R., Ficarro S.B., Brill L.M., Brinker A., Phung Q.T., Ericson C., Sauer K., Brock A., Horn D.M., Schultz P.G., Peters E.C. Proc. Natl. Acad. Sci. U.S.A. 100:443-448(2003) [PubMed: 12522270] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-299, MASS SPECTROMETRY.
[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: 15592455] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-299, MASS SPECTROMETRY.
[5]	"Quantitative phosphoproteome analysis using a dendrimer conjugation chemistry and tandem mass spectrometry." Tao W.A., Wollscheid B., O'Brien R., Eng J.K., Li X.-J., Bodenmiller B., Watts J.D., Hood L., Aebersold R. Nat. Methods 2:591-598(2005) [PubMed: 16094384] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-299, MASS SPECTROMETRY. Tissue: T-cell.
[6]	"Global survey of phosphotyrosine signaling identifies oncogenic kinases in lung cancer." Rikova K., Guo A., Zeng Q., Possemato A., Yu J., Haack H., Nardone J., Lee K., Reeves C., Li Y., Hu Y., Tan Z., Stokes M., Sullivan L., Mitchell J., Wetzel R., Macneill J., Ren J.M. , Yuan J., Bakalarski C.E., Villen J., Kornhauser J.M., Smith B., Li D., Zhou X., Gygi S.P., Gu T.-L., Polakiewicz R.D., Rush J., Comb M.J. Cell 131:1190-1203(2007) [PubMed: 18083107] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-299, MASS SPECTROMETRY.
[7]	"Solution structure of the IRS domain 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 153-247.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBLGenBankDDBJ

AF034970 mRNA. Translation: AAC13265.1.
BC032623 mRNA. Translation: AAH32623.1.

RefSeq

NP_003965.2.

UniGene

Hs.71215

3D structure databases

PDBMSD

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2D9W	NMR	-	A	1-116	[»]
2DLW	NMR	-	A	153-247	[»]

ModBase

Search...

Protein-protein interaction databases

IntAct

O60496.

PTM databases

PhosphoSite

O60496.

2-D gel databases

OGP

O60496.

Genome annotation databases

Ensembl

ENSG00000147443. Homo sapiens. [Contig view]

GeneID

9046.

KEGG

hsa:9046.

Organism-specific databases

HGNC

HGNC:2991. DOK2.

HPA

CAB004379.

MIM

604997. gene.

PharmGKB

PA27457.

GenAtlas

Search...

GeneCards

Search...

Phylogenomic databases

HOGENOM

O60496.

HOVERGEN

O60496.

Gene expression databases

ArrayExpress

O60496.

CleanEx

HS_DOK2.

GermOnline

ENSG00000147443. Homo sapiens.

Family and domain databases

InterPro

IPR002404. Insln_rcpt_S1.
IPR001849. PH.
IPR011993. PH_type.
[Graphical view]

Gene3D

G3DSA:2.30.29.30. PH_type. 1 hit.

Pfam

PF02174. IRS. 1 hit.
PF00169. PH. 1 hit.
[Graphical view]

SMART

SM00233. PH. 1 hit.
SM00310. PTBI. 1 hit.
[Graphical view]

PROSITE

PS51064. IRS_PTB. 1 hit.
PS50003. PH_DOMAIN. 1 hit.
[Graphical view]

ProDom

O60496.
[Graphical view] [Entries sharing at least one domain]

BLOCKS

Search...

Other Resources

SOURCE

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ProtoNet

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Entry information

Entry name

DOK2_HUMAN

Accession

Primary (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:	September 2, 2008
This is version 64 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)