Q8TEW6 (DOK4_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Docking protein 4

Alternative name(s):
Downstream of tyrosine kinase 4
Insulin receptor substrate 5
Short name=IRS-5
Short name=IRS5

Gene names

Name:

DOK4

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	326 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. DOK4 functions in RET-mediated neurite outgrowth and plays a positive role in activation of the MAP kinase pathway By similarity. Putative link with downstream effectors of RET in neuronal differentiation. May be involved in the regulation of the immune response induced by T-cells.
Subunit structure	Interacts with RET and TEK/TIE2. Interaction with RET is mediated through the PTB domain and requires phosphorylation of RET 'Tyr-1062' By similarity.
Tissue specificity	Widely expressed. High expression in skeletal muscle, heart, kidney and liver. Weaker expression in spleen, lung and small intestine, brain, heart and. Expressed in both resting and activated peripheral blood T-cells. Ref.1 Ref.2
Domain	PTB domain mediates receptor interaction By similarity.
Post-translational modification	Phosphorylated on tyrosine residues in response to insulin, IGF1 or RET stimulation. Ref.2
Sequence similarities	Belongs to the DOK family. Type B subfamily. Contains 1 IRS-type PTB domain. Contains 1 PH domain.
Sequence caution	The sequence AAC24310.1 differs from that shown. Reason: Erroneous gene model prediction.

Ontologies

Keywords
PTM	Phosphoprotein
Technical term	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...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 326	326	Docking protein 4		PRO_0000187274
Regions
	Domain	7 – 112	106	PH
	Domain	132 – 237	106	IRS-type PTB
	Motif	265 – 275	11	DKFBH motif
Experimental info
	Sequence conflict	64	1	N → S no nucleotide entry Ref.2
	Sequence conflict	64	1	N → S in BAA91642. Ref.3
	Sequence conflict	75	1	T → A in AAL74195. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Q8TEW6 [UniParc]. Last modified May 10, 2005. Version 2. Checksum: 1595B0CEC5584816	FASTA	326	37,028
	10 20 30 40 50 60 MATNFSDIVK QGYVKMKSRK LGIYRRCWLV FRKSSSKGPQ RLEKYPDEKS VCLRGCPKVT 70 80 90 100 110 120 EISNVKCVTR LPKETKRQAV AIIFTDDSAR TFTCDSELEA EEWYKTLSVE CLGSRLNDIS 130 140 150 160 170 180 LGEPDLLAPG VQCEQTDRFN VFLLPCPNLD VYGECKLQIT HENIYLWDIH NPRVKLVSWP 190 200 210 220 230 240 LCSLRRYGRD ATRFTFEAGR MCDAGEGLYT FQTQEGEQIY QRVHSATLAI AEQHKRVLLE 250 260 270 280 290 300 MEKNVRLLNK GTEHYSYPCT PTTMLPRSAY WHHITGSQNI AEASSYAGEG YGAAQASSET 310 320 DLLNRFILLK PKPSQGDSSE AKTPSQ

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"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], TISSUE SPECIFICITY. Tissue: T-cell.
[2]	"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], TISSUE SPECIFICITY, PHOSPHORYLATION AT TYROSINE RESIDUES. Tissue: Skeletal muscle.
[3]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[4]	"Genome duplications and other features in 12 Mb of DNA sequence from human chromosome 16p and 16q." Loftus B.J., Kim U.-J., Sneddon V.P., Kalush F., Brandon R., Fuhrmann J., Mason T., Crosby M.L., Barnstead M., Cronin L., Mays A.D., Cao Y., Xu R.X., Kang H.-L., Mitchell S., Eichler E.E., Harris P.C., Venter J.C., Adams M.D. Genomics 60:295-308(1999) [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]. Tissue: Colon and Pancreas.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF466369 mRNA. Translation: AAL74195.1. AK001350 mRNA. Translation: BAA91642.1. AC004382 Genomic DNA. Translation: AAC24310.1. Sequence problems. BC001540 mRNA. Translation: AAH01540.1. BC003541 mRNA. Translation: AAH03541.1.
IPI	IPI00550728.
RefSeq	NP_060580.2. NM_018110.3.
UniGene	Hs.279832.
3D structure databases
ProteinModelPortal	Q8TEW6.
ModBase	Search...
Protein-protein interaction databases
MINT	MINT-1491631.
STRING	9606.ENSP00000344277.
PTM databases
PhosphoSite	Q8TEW6.
Polymorphism databases
DMDM	84029600.
Proteomic databases
PaxDb	Q8TEW6.
PRIDE	Q8TEW6.
Protocols and materials databases
DNASU	55715.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000340099; ENSP00000344277; ENSG00000125170. ENST00000569548; ENSP00000455128; ENSG00000125170.
GeneID	55715.
KEGG	hsa:55715.
UCSC	uc002elv.4. human.
Organism-specific databases
CTD	55715.
GeneCards	GC16M057505.
HGNC	HGNC:19868. DOK4.
MIM	608333. gene.
neXtProt	NX_Q8TEW6.
PharmGKB	PA134892921.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG256436.
HOGENOM	HOG000247025.
HOVERGEN	HBG002356.
InParanoid	Q8TEW6.
OMA	IYLWDTH.
OrthoDB	EOG470THK.
PhylomeDB	Q8TEW6.
Enzyme and pathway databases
Pathway_Interaction_DB	ret_pathway. Signaling events regulated by Ret tyrosine kinase.
SignaLink	Q8TEW6.
Gene expression databases
ArrayExpress	Q8TEW6.
Bgee	Q8TEW6.
CleanEx	HS_DOK4.
Genevestigator	Q8TEW6.
GermOnline	ENSG00000125170. 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
GenomeRNAi	55715.
NextBio	60599.
SOURCE	Search...

Entry information

Entry name

DOK4_HUMAN

Accession

Primary (citable) accession number: Q8TEW6
Secondary accession number(s): O75209, Q9BTP2, Q9NVV3

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 10, 2005
Last sequence update:	May 10, 2005
Last modified:	May 29, 2013
This is version 83 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.