Q9P104 (DOK5_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Docking protein 5

Alternative name(s):
Downstream of tyrosine kinase 5
Insulin receptor substrate 6
Short name=IRS-6
Short name=IRS6

Gene names

Name:	DOK5
Synonyms:	C20orf180

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	306 AA.
Sequence status	Complete.
Protein existence	Evidence 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. DOK5 functions in RET-mediated neurite outgrowth and plays a positive role in activation of the MAP kinase pathway. Putative link with downstream effectors of RET in neuronal differentiation.
Subunit structure	Interacts with phosphorylated RET. In contrast to other DOK proteins, it does not interact with RASGAP By similarity.
Tissue specificity	Highest expression in skeletal muscle, lower in brain, heart and kidney. Also detected in activated peripheral blood T-lymphocytes. Ref.2 Ref.3
Domain	PTB domain mediates receptor interaction By similarity.
Post-translational modification	Phosphorylated on tyrosine residues in response to insulin, IGF1 and GDNF. Ref.3
Sequence similarities	Belongs to the DOK family. Type B subfamily. Contains 1 IRS-type PTB domain. Contains 1 PH domain.

Ontologies

Keywords
Coding sequence diversity	Alternative splicing
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	MAPK cascade Inferred from electronic annotation. Source: Compara nervous system development Inferred from electronic annotation. Source: Compara transmembrane receptor protein tyrosine kinase signaling pathway Inferred from electronic annotation. Source: Compara
Molecular_function	phospholipid binding Inferred from electronic annotation. Source: InterPro receptor signaling protein activity Inferred from electronic annotation. Source: Compara
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q9P104-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: Q9P104-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-108: Missing.

Note: No experimental confirmation available.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 306

306

Docking protein 5

PRO_0000187277

Regions

Domain

8 – 112

105

PH

Domain

132 – 237

106

IRS-type PTB

Motif

263 – 273

11

DKFBH motif

Natural variations

Alternative sequence

1 – 108

108

Missing in isoform 2.

VSP_003854

Experimental info

Sequence conflict

225 – 234

10

SAALAIAEQH → LLQMKMSERA in AAF66443. Ref.1

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

306

Helix Strand Turn

Details...

Beta strand

137 – 143

7

Beta strand

153 – 159

7

Beta strand

161 – 171

11

Beta strand

174 – 180

7

Helix

181 – 183

3

Beta strand

184 – 189

6

Beta strand

191 – 198

8

Beta strand

200 – 204

5

Beta strand

206 – 212

7

Helix

216 – 229

14

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified December 6, 2002. Version 2. Checksum: 2F259529E8B068DB	FASTA	306	35,464
	10 20 30 40 50 60 MASNFNDIVK QGYVRIRSRR LGIYQRCWLV FKKASSKGPK RLEKFSDERA AYFRCYHKVT 70 80 90 100 110 120 ELNNVKNVAR LPKSTKKHAI GIYFNDDTSK TFACESDLEA DEWCKVLQME CVGTRINDIS 130 140 150 160 170 180 LGEPDLLATG VEREQSERFN VYLMPSPNLD VHGECALQIT YEYICLWDVQ NPRVKLISWP 190 200 210 220 230 240 LSALRRYGRD TTWFTFEAGR MCETGEGLFI FQTRDGEAIY QKVHSAALAI AEQHERLLQS 250 260 270 280 290 300 VKNSMLQMKM SERAASLSTM VPLPRSAYWQ HITRQHSTGQ LYRLQDVSSP LKLHRTETFP AYRSEH
	Isoform 2 [UniParc]. Checksum: 291F9F2A419FE062	FASTA	198	22,824
	10 20 30 40 50 60 MECVGTRIND ISLGEPDLLA TGVEREQSER FNVYLMPSPN LDVHGECALQ ITYEYICLWD 70 80 90 100 110 120 VQNPRVKLIS WPLSALRRYG RDTTWFTFEA GRMCETGEGL FIFQTRDGEA IYQKVHSAAL 130 140 150 160 170 180 AIAEQHERLL QSVKNSMLQM KMSERAASLS TMVPLPRSAY WQHITRQHST GQLYRLQDVS 190 SPLKLHRTET FPAYRSEH

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	Luo W.Q., Chen J.H., Huang X.W., Zhou Y., Zhou H.J., Hu S.N., Yuan J.G. Submitted (MAR-1999) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[2]	"DOK4 and DOK5: new Dok-related genes expressed in human T cells." Favre C., Gerard A., Clauzier E., Pontarotti P., Olive D., Nunes J.A. Genes Immun. 4:40-45(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY.
[3]	"Two new substrates in insulin signaling, IRS5/DOK4 and IRS6/DOK5." Cai D., Dhe-Paganon S., Melendez P.A., Lee J., Shoelson S.E. J. Biol. Chem. 278:25323-25330(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY, PHOSPHORYLATION AT TYROSINE RESIDUES. Tissue: Skeletal muscle.
[4]	"The DNA sequence and comparative analysis of human chromosome 20." Deloukas P., Matthews L.H., Ashurst J.L., Burton J., Gilbert J.G.R., Jones M., Stavrides G., Almeida J.P., Babbage A.K., Bagguley C.L., Bailey J., Barlow K.F., Bates K.N., Beard L.M., Beare D.M., Beasley O.P., Bird C.P., Blakey S.E. , Bridgeman A.M., Brown A.J., Buck D., Burrill W.D., Butler A.P., Carder C., Carter N.P., Chapman J.C., Clamp M., Clark G., Clark L.N., Clark S.Y., Clee C.M., Clegg S., Cobley V.E., Collier R.E., Connor R.E., Corby N.R., Coulson A., Coville G.J., Deadman R., Dhami P.D., Dunn M., Ellington A.G., Frankland J.A., Fraser A., French L., Garner P., Grafham D.V., Griffiths C., Griffiths M.N.D., Gwilliam R., Hall R.E., Hammond S., Harley J.L., Heath P.D., Ho S., Holden J.L., Howden P.J., Huckle E., Hunt A.R., Hunt S.E., Jekosch K., Johnson C.M., Johnson D., Kay M.P., Kimberley A.M., King A., Knights A., Laird G.K., Lawlor S., Lehvaeslaiho M.H., Leversha M.A., Lloyd C., Lloyd D.M., Lovell J.D., Marsh V.L., Martin S.L., McConnachie L.J., McLay K., McMurray A.A., Milne S.A., Mistry D., Moore M.J.F., Mullikin J.C., Nickerson T., Oliver K., Parker A., Patel R., Pearce T.A.V., Peck A.I., Phillimore B.J.C.T., Prathalingam S.R., Plumb R.W., Ramsay H., Rice C.M., Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S., Skuce C.D., Smith M.L., Soderlund C., Steward C.A., Sulston J.E., Swann R.M., Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A., Tracey A., Tromans A.C., Vaudin M., Wall M., Wallis J.M., Whitehead S.L., Whittaker P., Willey D.L., Williams L., Williams S.A., Wilming L., Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S., Rogers J. Nature 414:865-871(2001) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	"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] (ISOFORM 2). Tissue: Brain.
[6]	"The full-ORF clone resource of the German cDNA consortium." Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., Wiemann S., Schupp I. BMC Genomics 8:399-399(2007) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 42-306 (ISOFORM 1). Tissue: Kidney.
[7]	"Expression, crystallization and preliminary X-ray studies of the recombinant PTB domain of human dok-5 protein." Shi N., Zhou W., Tang K., Gao Y., Jin J., Gao F., Peng X., Bartlam M., Qiang B., Yuan J., Rao Z. Acta Crystallogr. D 58:2170-2172(2002) [PubMed] [Europe PMC] [Abstract] Cited for: CRYSTALLIZATION.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AF132732 mRNA. Translation: AAF66443.1.
AF466368 mRNA. Translation: AAL74194.1.
AL118501, AL162292 Genomic DNA. Translation: CAI19415.1.
AL118501 Genomic DNA. Translation: CAI19416.1.
AL162292, AL118501 Genomic DNA. Translation: CAI16465.1.
BC008992 mRNA. Translation: AAH08992.1.
AL050069 mRNA. Translation: CAB43255.3.

IPI

IPI00020443.
IPI00219471.

PIR

T08731.

RefSeq

NP_060901.2. NM_018431.3.

UniGene

Hs.656582.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1J0W	X-ray	2.50	A/B	133-232	[»]

ProteinModelPortal

Q9P104.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q9P104. 2 interactions.

MINT

MINT-1435904.

STRING

9606.ENSP00000262593.

PTM databases

PhosphoSite

Q9P104.

Polymorphism databases

DMDM

26393190.

Proteomic databases

PaxDb

Q9P104.

PRIDE

Q9P104.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000262593; ENSP00000262593; ENSG00000101134.
ENST00000395939; ENSP00000379270; ENSG00000101134.

GeneID

55816.

KEGG

hsa:55816.

UCSC

uc002xwy.3. human.

Organism-specific databases

CTD

55816.

GeneCards

GC20P053092.

HGNC

HGNC:16173. DOK5.

MIM

608334. gene.

neXtProt

NX_Q9P104.

PharmGKB

PA25724.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG256436.

HOVERGEN

HBG002356.

InParanoid

Q9P104.

OMA

HAVGIYF.

OrthoDB

EOG47PX68.

PhylomeDB

Q9P104.

Enzyme and pathway databases

Pathway_Interaction_DB

ret_pathway. Signaling events regulated by Ret tyrosine kinase.

Gene expression databases

Bgee

Q9P104.

CleanEx

HS_DOK5.

Genevestigator

Q9P104.

GermOnline

ENSG00000101134. Homo sapiens.

Family and domain databases

Gene3D

2.30.29.30. 2 hits.

InterPro

IPR002404. Insln_rcpt_S1.
IPR011993. PH_like_dom.
IPR001849. Pleckstrin_homology.
[Graphical view]

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. False negative.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

Q9P104.

GenomeRNAi

55816.

NextBio

60998.

SOURCE

Search...

Entry information

Entry name

DOK5_HUMAN

Accession

Primary (citable) accession number: Q9P104
Secondary accession number(s): Q5T7Y0 , Q5TE53, Q8TEW7, Q96H13, Q9BZ24, Q9NQF4, Q9Y411

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 6, 2002
Last sequence update:	December 6, 2002
Last modified:	May 1, 2013
This is version 109 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.