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Q13470

- TNK1_HUMAN

UniProt

Q13470 - TNK1_HUMAN

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Protein
Non-receptor tyrosine-protein kinase TNK1
Gene
TNK1
Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5 - Experimental evidence at protein leveli

Functioni

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.2 Publications

Catalytic activityi

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

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei148 – 1481ATP By similarityBy similarity
Active sitei245 – 2451Proton acceptor By similarityBy similarity

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi122 – 1309ATP By similarityBy similarity

GO - Molecular functioni

  1. ATP binding Source: UniProtKB
  2. non-membrane spanning protein tyrosine kinase activity Source: UniProtKB
  3. protein binding Source: UniProtKB
  4. protein tyrosine kinase activity Source: UniProtKB
  5. signal transducer activity Source: ProtInc

GO - Biological processi

  1. negative regulation of Ras protein signal transduction Source: Ensembl
  2. negative regulation of cell growth Source: Ensembl
  3. peptidyl-tyrosine phosphorylation Source: GOC
  4. protein autophosphorylation Source: UniProtKB
  5. protein phosphorylation Source: ProtInc
  6. signal transduction Source: GOC
Complete GO annotation...

Keywords - Molecular functioni

Kinase, Transferase, Tyrosine-protein kinase

Keywords - Ligandi

ATP-binding, Nucleotide-binding

Names & Taxonomyi

Protein namesi
Recommended name:
Non-receptor tyrosine-protein kinase TNK1 (EC:2.7.10.2)
Alternative name(s):
CD38 negative kinase 1
Gene namesi
Name:TNK1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 17

Organism-specific databases

HGNCiHGNC:11940. TNK1.

Subcellular locationi

Cytoplasm. Membrane; Peripheral membrane protein 1 Publication

GO - Cellular componenti

  1. cell junction Source: HPA
  2. cytoplasm Source: UniProtKB
  3. cytosol Source: Ensembl
  4. membrane Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Membrane

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA36630.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 666666Non-receptor tyrosine-protein kinase TNK1
PRO_0000088173Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei60 – 601Phosphoserine1 Publication
Modified residuei255 – 2551Phosphoserine2 Publications
Modified residuei502 – 5021Phosphoserine5 Publications
Modified residuei514 – 5141Phosphothreonine2 Publications
Modified residuei519 – 5191Phosphoserine1 Publication
Modified residuei582 – 5821Phosphoserine1 Publication

Post-translational modificationi

Autophosphorylated on tyrosine residues.1 Publication

Keywords - PTMi

Phosphoprotein

Proteomic databases

MaxQBiQ13470.
PaxDbiQ13470.
PRIDEiQ13470.

PTM databases

PhosphoSiteiQ13470.

Expressioni

Tissue specificityi

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.2 Publications

Gene expression databases

ArrayExpressiQ13470.
BgeeiQ13470.
CleanExiHS_TNK1.
GenevestigatoriQ13470.

Organism-specific databases

HPAiHPA012065.
HPA056452.

Interactioni

Subunit structurei

Interacts with the SH3 domain of PLCG1 via its Pro-rich domain.1 Publication

Protein-protein interaction databases

BioGridi114253. 5 interactions.
IntActiQ13470. 2 interactions.
MINTiMINT-3975658.
STRINGi9606.ENSP00000312309.

Structurei

3D structure databases

ProteinModelPortaliQ13470.
SMRiQ13470. Positions 107-441.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini116 – 377262Protein kinase
Add
BLAST
Domaini381 – 44464SH3
Add
BLAST

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi511 – 57363Pro-rich
Add
BLAST

Sequence similaritiesi

Contains 1 SH3 domain.

Keywords - Domaini

SH3 domain

Phylogenomic databases

eggNOGiCOG0515.
HOGENOMiHOG000231055.
HOVERGENiHBG055513.
InParanoidiQ13470.
KOiK08885.
OMAiVRDVTEP.
OrthoDBiEOG71G9T3.
PhylomeDBiQ13470.
TreeFamiTF316643.

Family and domain databases

InterProiIPR011009. 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]
PfamiPF07714. Pkinase_Tyr. 1 hit.
[Graphical view]
PRINTSiPR00109. TYRKINASE.
SMARTiSM00326. SH3. 1 hit.
SM00219. TyrKc. 1 hit.
[Graphical view]
SUPFAMiSSF56112. SSF56112. 1 hit.
PROSITEiPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00109. PROTEIN_KINASE_TYR. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. Align

Isoform 11 Publication (identifier: Q13470-1) [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

MLPEAGSLWL LKLLRDIQLA QFYWPILEEL NVTRPEHFDF VKPEDLDGIG    50
MGRPAQRRLS EALKRLRSGP KSKNWVYKIL GGFAPEHKEP TLPSDSPRHL 100
PEPEGGLKCL IPEGAVCRGE LLGSGCFGVV HRGLWTLPSG KSVPVAVKSL 150
RVGPEGPMGT ELGDFLREVS VMMNLEHPHV LRLHGLVLGQ PLQMVMELAP 200
LGSLHARLTA PAPTPPLLVA LLCLFLRQLA GAMAYLGARG LVHRDLATRN 250
LLLASPRTIK VADFGLVRPL GGARGRYVMG GPRPIPYAWC APESLRHGAF 300
SSASDVWMFG VTLWEMFSGG EEPWAGVPPY LILQRLEDRA RLPRPPLCSR 350
ALYSLALRCW APHPADRPSF SHLEGLLQEA GPSEACCVRD VTEPGALRME 400
TGDPITVIEG SSSFHSPDST IWKGQNGRTF KVGSFPASAV TLADAGGLPA 450
TRPVHRGTPA RGDQHPGSID GDRKKANLWD APPARGQRRN MPLERMKGIS 500
RSLESVLSLG PRPTGGGSSP PEIRQARAVP QGPPGLPPRP PLSSSSPQPS 550
QPSRERLPWP KRKPPHNHPM GMPGARKAAA LSGGLLSDPE LQRKIMEVEL 600
SVHGVTHQEC QTALGATGGD VVSAIRNLKV DQLFHLSSRS RADCWRILEH 650
YQWDLSAASR YVLARP 666
Length:666
Mass (Da):72,468
Last modified:October 17, 2006 - v3
Checksum:iAA7FBEF6CC778181
GO
Isoform 2 (identifier: Q13470-2) [UniParc]FASTAAdd to Basket

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.

Show »
Length:661
Mass (Da):71,922
Checksum:i73FF2816065327CB
GO

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti278 – 2781V → I.1 Publication
Corresponds to variant rs55939858 [ dbSNP | Ensembl ].
VAR_041863
Natural varianti339 – 3391R → K in a lung adenocarcinoma sample; somatic mutation. 1 Publication
VAR_041864
Natural varianti514 – 5141T → K.1 Publication
Corresponds to variant rs55641092 [ dbSNP | Ensembl ].
VAR_041865
Natural varianti539 – 5391R → C.1 Publication
Corresponds to variant rs36046975 [ dbSNP | Ensembl ].
VAR_041866
Natural varianti546 – 5461S → C.1 Publication
Corresponds to variant rs56093628 [ dbSNP | Ensembl ].
VAR_041867
Natural varianti598 – 5981V → M.3 Publications
Corresponds to variant rs6503018 [ dbSNP | Ensembl ].
VAR_041868

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei411 – 4155Missing in isoform 2.
VSP_051663

Sequence conflict

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti36 – 361E → G in AAC50427. 1 Publication
Sequence conflicti65 – 651R → S in AAC50427. 1 Publication
Sequence conflicti94 – 941S → T in AAC50427. 1 Publication
Sequence conflicti118 – 1181R → K in AAC99412. 1 Publication
Sequence conflicti252 – 2521L → Q in AAC50427. 1 Publication
Sequence conflicti288 – 2881A → T in AAC50427. 1 Publication
Sequence conflicti325 – 3251A → P in AAC50427. 1 Publication
Sequence conflicti347 – 3482LC → PS in AAC50427. 1 Publication
Sequence conflicti391 – 3911V → A in AAC50427. 1 Publication
Sequence conflicti424 – 4241G → D in AAC50427. 1 Publication
Sequence conflicti443 – 4431A → T in AAC50427. 1 Publication
Sequence conflicti561 – 5611K → E in AAC50427. 1 Publication
Sequence conflicti604 – 6041G → W in AAC50427. 1 Publication
Sequence conflicti622 – 6221V → A in AAC50427. 1 Publication
Sequence conflicti635 – 6351H → L in AAC50427. 1 Publication

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
U43408 mRNA. Translation: AAC50427.1.
AF097738 Genomic DNA. Translation: AAC99412.1.
BC035782 mRNA. Translation: AAH35782.1.
CCDSiCCDS45602.1. [Q13470-2]
CCDS58510.1. [Q13470-1]
RefSeqiNP_001238831.1. NM_001251902.1. [Q13470-1]
NP_003976.2. NM_003985.4. [Q13470-2]
UniGeneiHs.203420.
Hs.739114.

Genome annotation databases

EnsembliENST00000311668; ENSP00000312309; ENSG00000174292. [Q13470-2]
ENST00000570896; ENSP00000458834; ENSG00000174292. [Q13470-2]
ENST00000576812; ENSP00000459799; ENSG00000174292. [Q13470-1]
GeneIDi8711.
KEGGihsa:8711.
UCSCiuc002ggi.4. human. [Q13470-1]
uc002ggj.4. human. [Q13470-2]

Polymorphism databases

DMDMi116242821.

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
U43408 mRNA. Translation: AAC50427.1 .
AF097738 Genomic DNA. Translation: AAC99412.1 .
BC035782 mRNA. Translation: AAH35782.1 .
CCDSi CCDS45602.1. [Q13470-2 ]
CCDS58510.1. [Q13470-1 ]
RefSeqi NP_001238831.1. NM_001251902.1. [Q13470-1 ]
NP_003976.2. NM_003985.4. [Q13470-2 ]
UniGenei Hs.203420.
Hs.739114.

3D structure databases

ProteinModelPortali Q13470.
SMRi Q13470. Positions 107-441.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 114253. 5 interactions.
IntActi Q13470. 2 interactions.
MINTi MINT-3975658.
STRINGi 9606.ENSP00000312309.

Chemistry

BindingDBi Q13470.
ChEMBLi CHEMBL5334.
GuidetoPHARMACOLOGYi 2245.

PTM databases

PhosphoSitei Q13470.

Polymorphism databases

DMDMi 116242821.

Proteomic databases

MaxQBi Q13470.
PaxDbi Q13470.
PRIDEi Q13470.

Protocols and materials databases

DNASUi 8711.
Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000311668 ; ENSP00000312309 ; ENSG00000174292 . [Q13470-2 ]
ENST00000570896 ; ENSP00000458834 ; ENSG00000174292 . [Q13470-2 ]
ENST00000576812 ; ENSP00000459799 ; ENSG00000174292 . [Q13470-1 ]
GeneIDi 8711.
KEGGi hsa:8711.
UCSCi uc002ggi.4. human. [Q13470-1 ]
uc002ggj.4. human. [Q13470-2 ]

Organism-specific databases

CTDi 8711.
GeneCardsi GC17P007284.
HGNCi HGNC:11940. TNK1.
HPAi HPA012065.
HPA056452.
MIMi 608076. gene.
neXtProti NX_Q13470.
PharmGKBi PA36630.
GenAtlasi Search...

Phylogenomic databases

eggNOGi COG0515.
HOGENOMi HOG000231055.
HOVERGENi HBG055513.
InParanoidi Q13470.
KOi K08885.
OMAi VRDVTEP.
OrthoDBi EOG71G9T3.
PhylomeDBi Q13470.
TreeFami TF316643.

Miscellaneous databases

GenomeRNAii 8711.
NextBioi 32671.
PROi Q13470.
SOURCEi Search...

Gene expression databases

ArrayExpressi Q13470.
Bgeei Q13470.
CleanExi HS_TNK1.
Genevestigatori Q13470.

Family and domain databases

InterProi IPR011009. 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 ]
Pfami PF07714. Pkinase_Tyr. 1 hit.
[Graphical view ]
PRINTSi PR00109. TYRKINASE.
SMARTi SM00326. SH3. 1 hit.
SM00219. TyrKc. 1 hit.
[Graphical view ]
SUPFAMi SSF56112. SSF56112. 1 hit.
PROSITEi PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00109. PROTEIN_KINASE_TYR. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  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. 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. Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-502 AND SER-519, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Cervix carcinoma.
  9. 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.
    , 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.

Entry informationi

Entry nameiTNK1_HUMAN
AccessioniPrimary (citable) accession number: Q13470
Secondary accession number(s): O95364, Q8IYI4
Entry historyi
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 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 17
    Human chromosome 17: 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. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  6. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

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