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Q13470 (TNK1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 120. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Non-receptor tyrosine-protein kinase TNK1

EC=2.7.10.2
Alternative name(s):
CD38 negative kinase 1
Gene names
Name:TNK1
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length666 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Involved in negative regulation of cell growth. Has tumor suppressor properties. Plays a negative regulatory role in the Ras-MAPK pathway. May function in signaling pathways utilized broadly during fetal development and more selectively in adult tissues and in cells of the lymphohematopoietic system. Could specifically be involved in phospholipid signal transduction. Ref.4 Ref.6

Catalytic activity

ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.

Subunit structure

Interacts with the SH3 domain of PLCG1 via its Pro-rich domain. Ref.4

Subcellular location

Cytoplasm. Membrane; Peripheral membrane protein Ref.4.

Tissue specificity

Expressed in all umbilical cord blood, bone marrow and adult blood cell sub-populations and in several leukemia cell lines. Highly expressed in fetal blood, brain, lung, liver and kidney. Detected at lower levels in adult prostate, testis, ovary, small intestine and colon. Not expressed in adult lung, liver, kidney or brain. Ref.1 Ref.4

Post-translational modification

Autophosphorylated on tyrosine residues. Ref.4

Sequence similarities

Belongs to the protein kinase superfamily. Tyr protein kinase family.

Contains 1 protein kinase domain.

Contains 1 SH3 domain.

Ontologies

Keywords
   Cellular componentCytoplasm
Membrane
   Coding sequence diversityAlternative splicing
Polymorphism
   DomainSH3 domain
   LigandATP-binding
Nucleotide-binding
   Molecular functionKinase
Transferase
Tyrosine-protein kinase
   PTMPhosphoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processnegative regulation of Ras protein signal transduction

Inferred from electronic annotation. Source: Ensembl

negative regulation of cell growth

Inferred from electronic annotation. Source: Ensembl

peptidyl-tyrosine phosphorylation

Inferred from direct assay Ref.4. Source: GOC

protein autophosphorylation

Inferred from direct assay Ref.4. Source: UniProtKB

protein phosphorylation

Traceable author statement Ref.1. Source: ProtInc

signal transduction

Traceable author statement Ref.1. Source: GOC

   Cellular_componentcell junction

Inferred from direct assay. Source: HPA

cytoplasm

Inferred from direct assay Ref.4. Source: UniProtKB

cytosol

Inferred from electronic annotation. Source: Ensembl

membrane

Inferred from direct assay Ref.4. Source: UniProtKB

   Molecular_functionATP binding

Inferred from direct assay Ref.4. Source: UniProtKB

non-membrane spanning protein tyrosine kinase activity

Non-traceable author statement Ref.4. Source: UniProtKB

protein binding

Inferred from physical interaction Ref.4. Source: UniProtKB

protein tyrosine kinase activity

Inferred from direct assay Ref.4. Source: UniProtKB

signal transducer activity

Traceable author statement Ref.1. Source: ProtInc

Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 Ref.1 (identifier: Q13470-1)

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: Q13470-2)

The sequence of this isoform differs from the canonical sequence as follows:
     411-415: Missing.
Note: No experimental confirmation available. Contains a phosphoserine at position 411.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 666666Non-receptor tyrosine-protein kinase TNK1
PRO_0000088173

Regions

Domain116 – 377262Protein kinase
Domain381 – 44464SH3
Nucleotide binding122 – 1309ATP By similarity UniProtKB P12931
Compositional bias511 – 57363Pro-rich

Sites

Active site2451Proton acceptor By similarity UniProtKB P12931
Binding site1481ATP By similarity UniProtKB P12931

Amino acid modifications

Modified residue601Phosphoserine Ref.7
Modified residue2551Phosphoserine Ref.7 Ref.9
Modified residue5021Phosphoserine Ref.7 Ref.8 Ref.9 Ref.10 Ref.11
Modified residue5141Phosphothreonine Ref.7 Ref.10
Modified residue5191Phosphoserine Ref.8
Modified residue5821Phosphoserine Ref.7

Natural variations

Alternative sequence411 – 4155Missing in isoform 2.
VSP_051663
Natural variant2781V → I. Ref.12
Corresponds to variant rs55939858 [ dbSNP | Ensembl ].
VAR_041863
Natural variant3391R → K in a lung adenocarcinoma sample; somatic mutation. Ref.12
VAR_041864
Natural variant5141T → K. Ref.12
Corresponds to variant rs55641092 [ dbSNP | Ensembl ].
VAR_041865
Natural variant5391R → C. Ref.12
Corresponds to variant rs36046975 [ dbSNP | Ensembl ].
VAR_041866
Natural variant5461S → C. Ref.12
Corresponds to variant rs56093628 [ dbSNP | Ensembl ].
VAR_041867
Natural variant5981V → M. Ref.1 Ref.2 Ref.12
Corresponds to variant rs6503018 [ dbSNP | Ensembl ].
VAR_041868

Experimental info

Sequence conflict361E → G in AAC50427. Ref.1
Sequence conflict651R → S in AAC50427. Ref.1
Sequence conflict941S → T in AAC50427. Ref.1
Sequence conflict1181R → K in AAC99412. Ref.2
Sequence conflict2521L → Q in AAC50427. Ref.1
Sequence conflict2881A → T in AAC50427. Ref.1
Sequence conflict3251A → P in AAC50427. Ref.1
Sequence conflict347 – 3482LC → PS in AAC50427. Ref.1
Sequence conflict3911V → A in AAC50427. Ref.1
Sequence conflict4241G → D in AAC50427. Ref.1
Sequence conflict4431A → T in AAC50427. Ref.1
Sequence conflict5611K → E in AAC50427. Ref.1
Sequence conflict6041G → W in AAC50427. Ref.1
Sequence conflict6221V → A in AAC50427. Ref.1
Sequence conflict6351H → L in AAC50427. Ref.1

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified October 17, 2006. Version 3.
Checksum: AA7FBEF6CC778181

FASTA66672,468
        10         20         30         40         50         60 
MLPEAGSLWL LKLLRDIQLA QFYWPILEEL NVTRPEHFDF VKPEDLDGIG MGRPAQRRLS 

        70         80         90        100        110        120 
EALKRLRSGP KSKNWVYKIL GGFAPEHKEP TLPSDSPRHL PEPEGGLKCL IPEGAVCRGE 

       130        140        150        160        170        180 
LLGSGCFGVV HRGLWTLPSG KSVPVAVKSL RVGPEGPMGT ELGDFLREVS VMMNLEHPHV 

       190        200        210        220        230        240 
LRLHGLVLGQ PLQMVMELAP LGSLHARLTA PAPTPPLLVA LLCLFLRQLA GAMAYLGARG 

       250        260        270        280        290        300 
LVHRDLATRN LLLASPRTIK VADFGLVRPL GGARGRYVMG GPRPIPYAWC APESLRHGAF 

       310        320        330        340        350        360 
SSASDVWMFG VTLWEMFSGG EEPWAGVPPY LILQRLEDRA RLPRPPLCSR ALYSLALRCW 

       370        380        390        400        410        420 
APHPADRPSF SHLEGLLQEA GPSEACCVRD VTEPGALRME TGDPITVIEG SSSFHSPDST 

       430        440        450        460        470        480 
IWKGQNGRTF KVGSFPASAV TLADAGGLPA TRPVHRGTPA RGDQHPGSID GDRKKANLWD 

       490        500        510        520        530        540 
APPARGQRRN MPLERMKGIS RSLESVLSLG PRPTGGGSSP PEIRQARAVP QGPPGLPPRP 

       550        560        570        580        590        600 
PLSSSSPQPS QPSRERLPWP KRKPPHNHPM GMPGARKAAA LSGGLLSDPE LQRKIMEVEL 

       610        620        630        640        650        660 
SVHGVTHQEC QTALGATGGD VVSAIRNLKV DQLFHLSSRS RADCWRILEH YQWDLSAASR 


YVLARP 

« Hide

Isoform 2 [UniParc].

Checksum: 73FF2816065327CB
Show »

FASTA66171,922

References

« Hide 'large scale' references
[1]"Tnk1: a novel intracellular tyrosine kinase gene isolated from human umbilical cord blood CD34+/Lin-/CD38- stem/progenitor cells."
Hoehn G.T., Stokland T., Amin S., Ramirez M., Hawkins A.L., Griffin C.A., Small D., Civin C.I.
Oncogene 12:903-913(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANT MET-598, TISSUE SPECIFICITY, CHROMOSOMAL LOCATION.
Tissue: Umbilical cord blood.
[2]"Genomic structure and chromosomal mapping of the human non-receptor tyrosine kinase gene, Tnk1."
Hoehn G.T., Felschow D.M., Civin C.I.
Submitted (OCT-1998) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT MET-598.
[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] (ISOFORM 2).
Tissue: Ovary.
[4]"Characterization of the tyrosine kinase Tnk1 and its binding with phospholipase C-gamma1."
Felschow D.M., Civin C.I., Hoehn G.T.
Biochem. Biophys. Res. Commun. 273:294-301(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AUTOPHOSPHORYLATION, INTERACTION WITH PLCG1.
[5]"Global, in vivo, and site-specific phosphorylation dynamics in signaling networks."
Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.
Cell 127:635-648(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[6]"Tnk1/Kos1 knockout mice develop spontaneous tumors."
Hoare S., Hoare K., Reinhard M.K., Lee Y.J., Oh S.P., May W.S. Jr.
Cancer Res. 68:8723-8732(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[7]"Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle."
Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., Greff Z., Keri G., Stemmann O., Mann M.
Mol. Cell 31:438-448(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-60; SER-255; SER-502; THR-514 AND SER-582, PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-411 (ISOFORM 2), IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[8]"A quantitative atlas of mitotic phosphorylation."
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-502 AND SER-519, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[9]"Large-scale proteomics analysis of the human kinome."
Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G., Mann M., Daub H.
Mol. Cell. Proteomics 8:1751-1764(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-255 AND SER-502, PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-411 (ISOFORM 2), IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[10]"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis."
Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.
Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-502 AND THR-514, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[11]"System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation."
Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.
Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-502, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[12]"Patterns of somatic mutation in human cancer genomes."
Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G. expand/collapse author list , Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R.
Nature 446:153-158(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS [LARGE SCALE ANALYSIS] ILE-278; LYS-339; LYS-514; CYS-539; CYS-546 AND MET-598.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
U43408 mRNA. Translation: AAC50427.1.
AF097738 Genomic DNA. Translation: AAC99412.1.
BC035782 mRNA. Translation: AAH35782.1.
CCDSCCDS45602.1. [Q13470-2]
CCDS58510.1. [Q13470-1]
RefSeqNP_001238831.1. NM_001251902.1. [Q13470-1]
NP_003976.2. NM_003985.4. [Q13470-2]
UniGeneHs.203420.
Hs.739114.

3D structure databases

ProteinModelPortalQ13470.
SMRQ13470. Positions 107-441.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid114253. 5 interactions.
IntActQ13470. 2 interactions.
MINTMINT-3975658.
STRING9606.ENSP00000312309.

Chemistry

BindingDBQ13470.
ChEMBLCHEMBL5334.
GuidetoPHARMACOLOGY2245.

PTM databases

PhosphoSiteQ13470.

Polymorphism databases

DMDM116242821.

Proteomic databases

MaxQBQ13470.
PaxDbQ13470.
PRIDEQ13470.

Protocols and materials databases

DNASU8711.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000311668; ENSP00000312309; ENSG00000174292. [Q13470-2]
ENST00000570896; ENSP00000458834; ENSG00000174292. [Q13470-2]
ENST00000576812; ENSP00000459799; ENSG00000174292. [Q13470-1]
GeneID8711.
KEGGhsa:8711.
UCSCuc002ggi.4. human. [Q13470-1]
uc002ggj.4. human. [Q13470-2]

Organism-specific databases

CTD8711.
GeneCardsGC17P007284.
HGNCHGNC:11940. TNK1.
HPAHPA012065.
HPA056452.
MIM608076. gene.
neXtProtNX_Q13470.
PharmGKBPA36630.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0515.
HOGENOMHOG000231055.
HOVERGENHBG055513.
InParanoidQ13470.
KOK08885.
OMAVRDVTEP.
OrthoDBEOG71G9T3.
PhylomeDBQ13470.
TreeFamTF316643.

Gene expression databases

ArrayExpressQ13470.
BgeeQ13470.
CleanExHS_TNK1.
GenevestigatorQ13470.

Family and domain databases

InterProIPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR001245. Ser-Thr/Tyr_kinase_cat_dom.
IPR001452. SH3_domain.
IPR008266. Tyr_kinase_AS.
IPR020635. Tyr_kinase_cat_dom.
[Graphical view]
PfamPF07714. Pkinase_Tyr. 1 hit.
[Graphical view]
PRINTSPR00109. TYRKINASE.
SMARTSM00326. SH3. 1 hit.
SM00219. TyrKc. 1 hit.
[Graphical view]
SUPFAMSSF56112. SSF56112. 1 hit.
PROSITEPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00109. PROTEIN_KINASE_TYR. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GenomeRNAi8711.
NextBio32671.
PROQ13470.
SOURCESearch...

Entry information

Entry nameTNK1_HUMAN
AccessionPrimary (citable) accession number: Q13470
Secondary accession number(s): O95364, Q8IYI4
Entry history
Integrated into UniProtKB/Swiss-Prot: February 15, 2005
Last sequence update: October 17, 2006
Last modified: July 9, 2014
This is version 120 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

Human and mouse protein kinases

Human and mouse protein kinases: classification and index

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 17

Human chromosome 17: entries, gene names and cross-references to MIM