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Protein

Docking protein 3

Gene

DOK3

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. DOK3 is a negative regulator of JNK signaling in B-cells through interaction with INPP5D/SHIP1. May modulate ABL1 function (By similarity).By similarity

GO - Biological processi

Complete GO annotation...

Enzyme and pathway databases

SignaLinkiQ7L591.

Names & Taxonomyi

Protein namesi
Recommended name:
Docking protein 3
Alternative name(s):
Downstream of tyrosine kinase 3
Gene namesi
Name:DOK3
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 5

Organism-specific databases

HGNCiHGNC:24583. DOK3.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Membrane

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA128394725.

Polymorphism and mutation databases

BioMutaiDOK3.
DMDMi84029599.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 496496Docking protein 3PRO_0000187272Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei330 – 3301PhosphoserineBy similarity
Modified residuei364 – 3641PhosphoserineBy similarity
Modified residuei381 – 3811PhosphotyrosineBy similarity
Modified residuei425 – 4251PhosphoserineBy similarity

Post-translational modificationi

Constitutively tyrosine-phosphorylated.By similarity
On IL2 stimulation, phosphorylated on C-terminal tyrosine residues possibly by Src kinases. Can also be phosphorylated by ABL1 kinase (By similarity).By similarity

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiQ7L591.
MaxQBiQ7L591.
PaxDbiQ7L591.
PeptideAtlasiQ7L591.
PRIDEiQ7L591.

PTM databases

iPTMnetiQ7L591.
PhosphoSiteiQ7L591.

Expressioni

Tissue specificityi

Expressed in spleen.1 Publication

Gene expression databases

BgeeiQ7L591.
CleanExiHS_DOK3.
ExpressionAtlasiQ7L591. baseline and differential.
GenevisibleiQ7L591. HS.

Interactioni

Subunit structurei

On tyrosine phosphorylation, interacts with CSK and INPP5D/SHIP1 via their SH2 domains. Both Tyr-381 and Tyr-398 are required for interaction with INPP5D. Only Tyr-381 is required for interaction with CSK. Binds ABL1 through the PTB domain and in a kinase-dependent manner. Does not interact with RasGAP (By similarity).By similarity

Binary interactionsi

WithEntry#Exp.IntActNotes
DOK4Q8TEW63EBI-10694655,EBI-6918542
GRB2Q078833EBI-2834978,EBI-7061573From a different organism.
RBPMSQ930623EBI-2834978,EBI-740322
TRAF1Q130773EBI-2834978,EBI-359224

Protein-protein interaction databases

BioGridi123005. 26 interactions.
IntActiQ7L591. 21 interactions.
MINTiMINT-3068370.
STRINGi9606.ENSP00000349727.

Structurei

3D structure databases

ProteinModelPortaliQ7L591.
SMRiQ7L591. Positions 64-181, 216-352.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini63 – 179117PHAdd
BLAST
Domaini213 – 317105IRS-type PTBPROSITE-ProRule annotationAdd
BLAST

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi320 – 37354Pro-richAdd
BLAST
Compositional biasi391 – 496106Pro-richAdd
BLAST

Domaini

PTB domain mediates receptor interaction.By similarity

Sequence similaritiesi

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

Phylogenomic databases

eggNOGiKOG4047. Eukaryota.
ENOG410XS2S. LUCA.
GeneTreeiENSGT00730000110348.
HOGENOMiHOG000112245.
HOVERGENiHBG051391.
InParanoidiQ7L591.
OMAiKGPAPCD.
OrthoDBiEOG77WWC5.
PhylomeDBiQ7L591.
TreeFamiTF324994.

Family and domain databases

Gene3Di2.30.29.30. 1 hit.
InterProiIPR002404. IRS_PTB.
IPR011993. PH_dom-like.
IPR001849. PH_domain.
[Graphical view]
PfamiPF02174. IRS. 1 hit.
[Graphical view]
SMARTiSM00233. PH. 1 hit.
SM00310. PTBI. 1 hit.
[Graphical view]
SUPFAMiSSF50729. SSF50729. 2 hits.
PROSITEiPS51064. IRS_PTB. 1 hit.
[Graphical view]

Sequences (4)i

Sequence statusi: Complete.

This entry describes 4 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q7L591-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MTRGARLRSD ARAQLNQLSL DGGTGSGQKG KCEEFPSSLS SVSPGLEAAA
60 70 80 90 100
LLLAVTMDPL ETPIKDGILY QQHVKFGKKC WRKVWALLYA GGPSGVARLE
110 120 130 140 150
SWEVRDGGLG AAGDRSAGPG RRGERRVIRL ADCVSVLPAD GESCPRDTGA
160 170 180 190 200
FLLTTTERSH LLAAQHRQAW MGPICQLAFP GTGEASSGST DAQSPKRGLV
210 220 230 240 250
PMEENSIYSS WQEVGEFPVV VQRTEAATRC QLKGPALLVL GPDAIQLREA
260 270 280 290 300
KGTQALYSWP YHFLRKFGSD KGVFSFEAGR RCHSGEGLFA FSTPCAPDLC
310 320 330 340 350
RAVAGAIARQ RERLPELTRP QPCPLPRATS LPSLDTPGEL REMPPGPEPP
360 370 380 390 400
TSRKMHLAEP GPQSLPLLLG PEPNDLASGL YASVCKRASG PPGNEHLYEN
410 420 430 440 450
LCVLEASPTL HGGEPEPHEG PGSRSPTTSP IYHNGQDLSW PGPANDSTLE
460 470 480 490
AQYRRLLELD QVEGTGRPDP QAGFKAKLVT LLSRERRKGP APCDRP
Note: No experimental confirmation available.
Length:496
Mass (Da):53,288
Last modified:May 10, 2005 - v2
Checksum:i7E186B998F9F1E24
GO
Isoform 2 (identifier: Q7L591-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-170: Missing.
     272-386: GVFSFEAGRR...ASGLYASVCK → ILLGTPGVSL...TSAAHTLGTS
     387-496: Missing.

Note: No experimental confirmation available.Curated
Show »
Length:216
Mass (Da):23,255
Checksum:i3276F905C619BC3D
GO
Isoform 3 (identifier: Q7L591-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-56: Missing.
     272-386: GVFSFEAGRR...ASGLYASVCK → ILLGTPGVSL...TSAAHTLGTS
     387-496: Missing.

Note: No experimental confirmation available.Curated
Show »
Length:330
Mass (Da):35,735
Checksum:iE4D842CAE0D6D8C3
GO
Isoform 4 (identifier: Q7L591-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-56: Missing.
     79-180: Missing.
     272-386: GVFSFEAGRR...ASGLYASVCK → ILLGTPGVSL...TSAAHTLGTS
     387-496: Missing.

Note: No experimental confirmation available.Curated
Show »
Length:228
Mass (Da):24,737
Checksum:i09009F00CD8DF2F9
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti267 – 2671F → L in BAB15399 (PubMed:14702039).Curated
Isoform 2 (identifier: Q7L591-2)
Sequence conflicti188 – 1881R → C in AAH04867 (PubMed:15372022).Curated
Isoform 4 (identifier: Q7L591-4)
Sequence conflicti200 – 2001R → C in BAC04986 (PubMed:14702039).Curated
Isoform 3 (identifier: Q7L591-3)
Sequence conflicti302 – 3021R → C in AAH04564 (PubMed:15489334).Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti12 – 121R → P.
Corresponds to variant rs3749728 [ dbSNP | Ensembl ].
VAR_057525
Natural varianti22 – 221G → R.
Corresponds to variant rs41275297 [ dbSNP | Ensembl ].
VAR_062002

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 170170Missing in isoform 2. 1 PublicationVSP_013713Add
BLAST
Alternative sequencei1 – 5656Missing in isoform 3 and isoform 4. 2 PublicationsVSP_013712Add
BLAST
Alternative sequencei79 – 180102Missing in isoform 4. 1 PublicationVSP_013714Add
BLAST
Alternative sequencei272 – 386115GVFSF…ASVCK → ILLGTPGVSLLICKGERTDD VSGIILDESLLRAYSVPGAG GHSRVQDSLGPVLREPTFQG ERSFLKTSMLRSLLCSCSWR HPRSQPRTQASCLQGSDCPA PHRNSTSAAHTLGTS in isoform 2, isoform 3 and isoform 4. 2 PublicationsVSP_013715Add
BLAST
Alternative sequencei387 – 496110Missing in isoform 2, isoform 3 and isoform 4. 2 PublicationsVSP_013716Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK026223 mRNA. Translation: BAB15399.1.
AK097258 mRNA. Translation: BAC04986.1.
AC145098 Genomic DNA. No translation available.
BC004564 mRNA. Translation: AAH04564.2.
BC004867 mRNA. Translation: AAH04867.1.
CCDSiCCDS4426.1. [Q7L591-1]
CCDS47349.1. [Q7L591-4]
CCDS47350.1. [Q7L591-3]
RefSeqiNP_001138347.1. NM_001144875.1. [Q7L591-3]
NP_001138348.1. NM_001144876.1. [Q7L591-4]
NP_001295164.1. NM_001308235.1.
NP_001295165.1. NM_001308236.1.
NP_079148.2. NM_024872.2. [Q7L591-1]
XP_005266044.1. XM_005265987.1. [Q7L591-3]
UniGeneiHs.720849.

Genome annotation databases

EnsembliENST00000312943; ENSP00000325174; ENSG00000146094. [Q7L591-3]
ENST00000357198; ENSP00000349727; ENSG00000146094. [Q7L591-1]
ENST00000377112; ENSP00000366316; ENSG00000146094. [Q7L591-4]
GeneIDi79930.
KEGGihsa:79930.
UCSCiuc003mhi.5. human. [Q7L591-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK026223 mRNA. Translation: BAB15399.1.
AK097258 mRNA. Translation: BAC04986.1.
AC145098 Genomic DNA. No translation available.
BC004564 mRNA. Translation: AAH04564.2.
BC004867 mRNA. Translation: AAH04867.1.
CCDSiCCDS4426.1. [Q7L591-1]
CCDS47349.1. [Q7L591-4]
CCDS47350.1. [Q7L591-3]
RefSeqiNP_001138347.1. NM_001144875.1. [Q7L591-3]
NP_001138348.1. NM_001144876.1. [Q7L591-4]
NP_001295164.1. NM_001308235.1.
NP_001295165.1. NM_001308236.1.
NP_079148.2. NM_024872.2. [Q7L591-1]
XP_005266044.1. XM_005265987.1. [Q7L591-3]
UniGeneiHs.720849.

3D structure databases

ProteinModelPortaliQ7L591.
SMRiQ7L591. Positions 64-181, 216-352.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi123005. 26 interactions.
IntActiQ7L591. 21 interactions.
MINTiMINT-3068370.
STRINGi9606.ENSP00000349727.

PTM databases

iPTMnetiQ7L591.
PhosphoSiteiQ7L591.

Polymorphism and mutation databases

BioMutaiDOK3.
DMDMi84029599.

Proteomic databases

EPDiQ7L591.
MaxQBiQ7L591.
PaxDbiQ7L591.
PeptideAtlasiQ7L591.
PRIDEiQ7L591.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000312943; ENSP00000325174; ENSG00000146094. [Q7L591-3]
ENST00000357198; ENSP00000349727; ENSG00000146094. [Q7L591-1]
ENST00000377112; ENSP00000366316; ENSG00000146094. [Q7L591-4]
GeneIDi79930.
KEGGihsa:79930.
UCSCiuc003mhi.5. human. [Q7L591-1]

Organism-specific databases

CTDi79930.
GeneCardsiDOK3.
H-InvDBHIX0200730.
HGNCiHGNC:24583. DOK3.
MIMi611435. gene.
neXtProtiNX_Q7L591.
PharmGKBiPA128394725.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG4047. Eukaryota.
ENOG410XS2S. LUCA.
GeneTreeiENSGT00730000110348.
HOGENOMiHOG000112245.
HOVERGENiHBG051391.
InParanoidiQ7L591.
OMAiKGPAPCD.
OrthoDBiEOG77WWC5.
PhylomeDBiQ7L591.
TreeFamiTF324994.

Enzyme and pathway databases

SignaLinkiQ7L591.

Miscellaneous databases

ChiTaRSiDOK3. human.
GeneWikiiDOK3.
GenomeRNAii79930.
NextBioi69852.
PROiQ7L591.
SOURCEiSearch...

Gene expression databases

BgeeiQ7L591.
CleanExiHS_DOK3.
ExpressionAtlasiQ7L591. baseline and differential.
GenevisibleiQ7L591. HS.

Family and domain databases

Gene3Di2.30.29.30. 1 hit.
InterProiIPR002404. IRS_PTB.
IPR011993. PH_dom-like.
IPR001849. PH_domain.
[Graphical view]
PfamiPF02174. IRS. 1 hit.
[Graphical view]
SMARTiSM00233. PH. 1 hit.
SM00310. PTBI. 1 hit.
[Graphical view]
SUPFAMiSSF50729. SSF50729. 2 hits.
PROSITEiPS51064. IRS_PTB. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "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] (ISOFORMS 1 AND 4).
    Tissue: Small intestine.
  2. "The DNA sequence and comparative analysis of human chromosome 5."
    Schmutz J., Martin J., Terry A., Couronne O., Grimwood J., Lowry S., Gordon L.A., Scott D., Xie G., Huang W., Hellsten U., Tran-Gyamfi M., She X., Prabhakar S., Aerts A., Altherr M., Bajorek E., Black S.
    , Branscomb E., Caoile C., Challacombe J.F., Chan Y.M., Denys M., Detter J.C., Escobar J., Flowers D., Fotopulos D., Glavina T., Gomez M., Gonzales E., Goodstein D., Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Lopez F., Lou Y., Martinez D., Medina C., Morgan J., Nandkeshwar R., Noonan J.P., Pitluck S., Pollard M., Predki P., Priest J., Ramirez L., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., Thayer N., Tice H., Tsai M., Ustaszewska A., Vo N., Wheeler J., Wu K., Yang J., Dickson M., Cheng J.-F., Eichler E.E., Olsen A., Pennacchio L.A., Rokhsar D.S., Richardson P., Lucas S.M., Myers R.M., Rubin E.M.
    Nature 431:268-274(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  3. "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] (ISOFORMS 2 AND 3).
    Tissue: B-cell and Lymph.
  4. "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: TISSUE SPECIFICITY.
  5. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Platelet.
  6. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
  7. "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome."
    Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., Ye M., Zou H.
    J. Proteomics 96:253-262(2014) [PubMed] [Europe PMC] [Abstract]
    Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Liver.

Entry informationi

Entry nameiDOK3_HUMAN
AccessioniPrimary (citable) accession number: Q7L591
Secondary accession number(s): E9PAT0
, H7BXS0, Q8N864, Q9BQB3, Q9H666
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 10, 2005
Last sequence update: May 10, 2005
Last modified: March 16, 2016
This is version 115 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 5
    Human chromosome 5: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. 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.