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Protein

Docking protein 4

Gene

DOK4

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 4 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. 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.By similarity

GO - Molecular functioni

  1. receptor signaling protein activity Source: Ensembl

GO - Biological processi

  1. MAPK cascade Source: Ensembl
  2. nervous system development Source: Ensembl
  3. transmembrane receptor protein tyrosine kinase signaling pathway Source: Ensembl
Complete GO annotation...

Enzyme and pathway databases

SignaLinkiQ8TEW6.

Names & Taxonomyi

Protein namesi
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 namesi
Name:DOK4
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640 Componenti: Chromosome 16

Organism-specific databases

HGNCiHGNC:19868. DOK4.

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA134892921.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 326326Docking protein 4PRO_0000187274Add
BLAST

Post-translational modificationi

Phosphorylated on tyrosine residues in response to insulin, IGF1 or RET stimulation.1 Publication

Keywords - PTMi

Phosphoprotein

Proteomic databases

PaxDbiQ8TEW6.
PRIDEiQ8TEW6.

PTM databases

PhosphoSiteiQ8TEW6.

Expressioni

Tissue specificityi

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.2 Publications

Gene expression databases

BgeeiQ8TEW6.
CleanExiHS_DOK4.
ExpressionAtlasiQ8TEW6. baseline and differential.
GenevestigatoriQ8TEW6.

Organism-specific databases

HPAiHPA052844.
HPA055849.

Interactioni

Subunit structurei

Interacts with RET and TEK/TIE2. Interaction with RET is mediated through the PTB domain and requires phosphorylation of RET 'Tyr-1062' (By similarity).By similarity

Binary interactionsi

WithEntry#Exp.IntActNotes
ERBB2P046262EBI-6918542,EBI-641062
OPRM1P353724EBI-6918542,EBI-2624570

Protein-protein interaction databases

BioGridi120837. 26 interactions.
IntActiQ8TEW6. 3 interactions.
MINTiMINT-1491631.
STRINGi9606.ENSP00000344277.

Structurei

3D structure databases

ProteinModelPortaliQ8TEW6.
SMRiQ8TEW6. Positions 134-232.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini7 – 112106PHAdd
BLAST
Domaini132 – 237106IRS-type PTBPROSITE-ProRule annotationAdd
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi265 – 27511DKFBH motifAdd
BLAST

Domaini

PTB domain mediates receptor interaction.By similarity

Sequence similaritiesi

Belongs to the DOK family. Type B subfamily.Curated
Contains 1 IRS-type PTB domain.PROSITE-ProRule annotation
Contains 1 PH domain.Curated

Phylogenomic databases

eggNOGiNOG256436.
GeneTreeiENSGT00730000110348.
HOGENOMiHOG000247025.
HOVERGENiHBG002356.
InParanoidiQ8TEW6.
PhylomeDBiQ8TEW6.
TreeFamiTF324994.

Family and domain databases

Gene3Di2.30.29.30. 2 hits.
InterProiIPR002404. Insln_rcpt_S1.
IPR001849. PH_domain.
IPR011993. PH_like_dom.
[Graphical view]
PfamiPF02174. IRS. 1 hit.
PF00169. PH. 1 hit.
[Graphical view]
SMARTiSM00233. PH. 1 hit.
SM00310. PTBI. 1 hit.
[Graphical view]
PROSITEiPS51064. IRS_PTB. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Q8TEW6-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MATNFSDIVK QGYVKMKSRK LGIYRRCWLV FRKSSSKGPQ RLEKYPDEKS
60 70 80 90 100
VCLRGCPKVT EISNVKCVTR LPKETKRQAV AIIFTDDSAR TFTCDSELEA
110 120 130 140 150
EEWYKTLSVE CLGSRLNDIS LGEPDLLAPG VQCEQTDRFN VFLLPCPNLD
160 170 180 190 200
VYGECKLQIT HENIYLWDIH NPRVKLVSWP LCSLRRYGRD ATRFTFEAGR
210 220 230 240 250
MCDAGEGLYT FQTQEGEQIY QRVHSATLAI AEQHKRVLLE MEKNVRLLNK
260 270 280 290 300
GTEHYSYPCT PTTMLPRSAY WHHITGSQNI AEASSYAGEG YGAAQASSET
310 320
DLLNRFILLK PKPSQGDSSE AKTPSQ
Length:326
Mass (Da):37,028
Last modified:May 10, 2005 - v2
Checksum:i1595B0CEC5584816
GO

Sequence cautioni

The sequence AAC24310.1 differs from that shown. Reason: Erroneous gene model prediction. Curated

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti64 – 641N → S no nucleotide entry (PubMed:12730241).Curated
Sequence conflicti64 – 641N → S in BAA91642 (PubMed:14702039).Curated
Sequence conflicti75 – 751T → A in AAL74195 (PubMed:12595900).Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS10783.1.
RefSeqiNP_060580.2. NM_018110.3.
XP_005256100.1. XM_005256043.1.
UniGeneiHs.279832.

Genome annotation databases

EnsembliENST00000340099; ENSP00000344277; ENSG00000125170.
ENST00000569548; ENSP00000455128; ENSG00000125170.
GeneIDi55715.
KEGGihsa:55715.
UCSCiuc002elv.4. human.

Polymorphism databases

DMDMi84029600.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS10783.1.
RefSeqiNP_060580.2. NM_018110.3.
XP_005256100.1. XM_005256043.1.
UniGeneiHs.279832.

3D structure databases

ProteinModelPortaliQ8TEW6.
SMRiQ8TEW6. Positions 134-232.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi120837. 26 interactions.
IntActiQ8TEW6. 3 interactions.
MINTiMINT-1491631.
STRINGi9606.ENSP00000344277.

PTM databases

PhosphoSiteiQ8TEW6.

Polymorphism databases

DMDMi84029600.

Proteomic databases

PaxDbiQ8TEW6.
PRIDEiQ8TEW6.

Protocols and materials databases

DNASUi55715.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000340099; ENSP00000344277; ENSG00000125170.
ENST00000569548; ENSP00000455128; ENSG00000125170.
GeneIDi55715.
KEGGihsa:55715.
UCSCiuc002elv.4. human.

Organism-specific databases

CTDi55715.
GeneCardsiGC16M057505.
HGNCiHGNC:19868. DOK4.
HPAiHPA052844.
HPA055849.
MIMi608333. gene.
neXtProtiNX_Q8TEW6.
PharmGKBiPA134892921.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiNOG256436.
GeneTreeiENSGT00730000110348.
HOGENOMiHOG000247025.
HOVERGENiHBG002356.
InParanoidiQ8TEW6.
PhylomeDBiQ8TEW6.
TreeFamiTF324994.

Enzyme and pathway databases

SignaLinkiQ8TEW6.

Miscellaneous databases

GeneWikiiDOK4.
GenomeRNAii55715.
NextBioi60599.
PROiQ8TEW6.
SOURCEiSearch...

Gene expression databases

BgeeiQ8TEW6.
CleanExiHS_DOK4.
ExpressionAtlasiQ8TEW6. baseline and differential.
GenevestigatoriQ8TEW6.

Family and domain databases

Gene3Di2.30.29.30. 2 hits.
InterProiIPR002404. Insln_rcpt_S1.
IPR001849. PH_domain.
IPR011993. PH_like_dom.
[Graphical view]
PfamiPF02174. IRS. 1 hit.
PF00169. PH. 1 hit.
[Graphical view]
SMARTiSM00233. PH. 1 hit.
SM00310. PTBI. 1 hit.
[Graphical view]
PROSITEiPS51064. IRS_PTB. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  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(2002) [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(2002) [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(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
  4. 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(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Tissue: Colon and Pancreas.

Entry informationi

Entry nameiDOK4_HUMAN
AccessioniPrimary (citable) accession number: Q8TEW6
Secondary accession number(s): O75209, Q9BTP2, Q9NVV3
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 10, 2005
Last sequence update: May 10, 2005
Last modified: March 4, 2015
This is version 97 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 16
    Human chromosome 16: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

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 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.