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Protein

Non-receptor tyrosine-protein kinase TNK1

Gene

TNK1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: 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.PROSITE-ProRule annotation

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei148ATPPROSITE-ProRule annotationBy similarity1
Active sitei245Proton acceptorPROSITE-ProRule annotationBy similarity1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi122 – 130ATPPROSITE-ProRule annotationBy similarity9

GO - Molecular functioni

  • ATP binding Source: UniProtKB
  • non-membrane spanning protein tyrosine kinase activity Source: GO_Central
  • protein tyrosine kinase activity Source: UniProtKB
  • receptor binding Source: GO_Central
  • signal transducer activity Source: ProtInc

GO - Biological processi

Keywordsi

Molecular functionKinase, Transferase, Tyrosine-protein kinase
LigandATP-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:TNK1Imported
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 17

Organism-specific databases

EuPathDBiHostDB:ENSG00000174292.12.
HGNCiHGNC:11940. TNK1.

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm, Membrane

Pathology & Biotechi

Organism-specific databases

DisGeNETi8711.
OpenTargetsiENSG00000174292.
PharmGKBiPA36630.

Chemistry databases

ChEMBLiCHEMBL5334.
GuidetoPHARMACOLOGYi2245.

Polymorphism and mutation databases

BioMutaiTNK1.
DMDMi116242821.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000881731 – 666Non-receptor tyrosine-protein kinase TNK1Add BLAST666

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei60PhosphoserineCombined sources1
Modified residuei96PhosphoserineCombined sources1
Modified residuei255PhosphoserineCombined sources1
Modified residuei502PhosphoserineCombined sources1
Modified residuei514PhosphothreonineCombined sources1
Modified residuei519PhosphoserineCombined sources1
Modified residuei582PhosphoserineCombined sources1
Isoform 2Curated (identifier: Q13470-2)
Modified residuei411PhosphoserineCombined sources1

Post-translational modificationi

Autophosphorylated on tyrosine residues.1 Publication

Keywords - PTMi

Phosphoprotein

Proteomic databases

MaxQBiQ13470.
PaxDbiQ13470.
PeptideAtlasiQ13470.
PRIDEiQ13470.

PTM databases

iPTMnetiQ13470.
PhosphoSitePlusiQ13470.

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

BgeeiENSG00000174292.
CleanExiHS_TNK1.
ExpressionAtlasiQ13470. baseline and differential.
GenevisibleiQ13470. HS.

Organism-specific databases

HPAiHPA012065.
HPA056452.

Interactioni

Subunit structurei

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

Binary interactionsi

WithEntry#Exp.IntActNotes
SFNP319472EBI-1383444,EBI-476295

GO - Molecular functioni

Protein-protein interaction databases

BioGridi114253. 25 interactors.
IntActiQ13470. 32 interactors.
MINTiMINT-3975658.
STRINGi9606.ENSP00000312309.

Chemistry databases

BindingDBiQ13470.

Structurei

3D structure databases

ProteinModelPortaliQ13470.
SMRiQ13470.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini116 – 377Protein kinasePROSITE-ProRule annotationAdd BLAST262
Domaini381 – 444SH3Sequence analysisAdd BLAST64

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi511 – 573Pro-richAdd BLAST63

Sequence similaritiesi

Belongs to the protein kinase superfamily. Tyr protein kinase family.PROSITE-ProRule annotation

Keywords - Domaini

SH3 domain

Phylogenomic databases

eggNOGiKOG0199. Eukaryota.
ENOG410XPRC. LUCA.
GeneTreeiENSGT00760000118799.
HOGENOMiHOG000231055.
HOVERGENiHBG055513.
InParanoidiQ13470.
KOiK08885.
OMAiLLQEAWP.
OrthoDBiEOG091G03HT.
PhylomeDBiQ13470.
TreeFamiTF316643.

Family and domain databases

InterProiView protein in InterPro
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.
PfamiView protein in Pfam
PF07714. Pkinase_Tyr. 1 hit.
PRINTSiPR00109. TYRKINASE.
SMARTiView protein in SMART
SM00326. SH3. 1 hit.
SM00219. TyrKc. 1 hit.
SUPFAMiSSF56112. SSF56112. 1 hit.
PROSITEiView protein in PROSITE
PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00109. PROTEIN_KINASE_TYR. 1 hit.

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

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

        10         20         30         40         50
MLPEAGSLWL LKLLRDIQLA QFYWPILEEL NVTRPEHFDF VKPEDLDGIG
60 70 80 90 100
MGRPAQRRLS EALKRLRSGP KSKNWVYKIL GGFAPEHKEP TLPSDSPRHL
110 120 130 140 150
PEPEGGLKCL IPEGAVCRGE LLGSGCFGVV HRGLWTLPSG KSVPVAVKSL
160 170 180 190 200
RVGPEGPMGT ELGDFLREVS VMMNLEHPHV LRLHGLVLGQ PLQMVMELAP
210 220 230 240 250
LGSLHARLTA PAPTPPLLVA LLCLFLRQLA GAMAYLGARG LVHRDLATRN
260 270 280 290 300
LLLASPRTIK VADFGLVRPL GGARGRYVMG GPRPIPYAWC APESLRHGAF
310 320 330 340 350
SSASDVWMFG VTLWEMFSGG EEPWAGVPPY LILQRLEDRA RLPRPPLCSR
360 370 380 390 400
ALYSLALRCW APHPADRPSF SHLEGLLQEA GPSEACCVRD VTEPGALRME
410 420 430 440 450
TGDPITVIEG SSSFHSPDST IWKGQNGRTF KVGSFPASAV TLADAGGLPA
460 470 480 490 500
TRPVHRGTPA RGDQHPGSID GDRKKANLWD APPARGQRRN MPLERMKGIS
510 520 530 540 550
RSLESVLSLG PRPTGGGSSP PEIRQARAVP QGPPGLPPRP PLSSSSPQPS
560 570 580 590 600
QPSRERLPWP KRKPPHNHPM GMPGARKAAA LSGGLLSDPE LQRKIMEVEL
610 620 630 640 650
SVHGVTHQEC QTALGATGGD VVSAIRNLKV DQLFHLSSRS RADCWRILEH
660
YQWDLSAASR YVLARP
Length:666
Mass (Da):72,468
Last modified:October 17, 2006 - v3
Checksum:iAA7FBEF6CC778181
GO
Isoform 2Curated (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.Combined sources
Show »
Length:661
Mass (Da):71,922
Checksum:i73FF2816065327CB
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti36E → G in AAC50427 (PubMed:8632913).Curated1
Sequence conflicti65R → S in AAC50427 (PubMed:8632913).Curated1
Sequence conflicti94S → T in AAC50427 (PubMed:8632913).Curated1
Sequence conflicti118R → K in AAC99412 (Ref. 2) Curated1
Sequence conflicti252L → Q in AAC50427 (PubMed:8632913).Curated1
Sequence conflicti288A → T in AAC50427 (PubMed:8632913).Curated1
Sequence conflicti325A → P in AAC50427 (PubMed:8632913).Curated1
Sequence conflicti347 – 348LC → PS in AAC50427 (PubMed:8632913).Curated2
Sequence conflicti391V → A in AAC50427 (PubMed:8632913).Curated1
Sequence conflicti424G → D in AAC50427 (PubMed:8632913).Curated1
Sequence conflicti443A → T in AAC50427 (PubMed:8632913).Curated1
Sequence conflicti561K → E in AAC50427 (PubMed:8632913).Curated1
Sequence conflicti604G → W in AAC50427 (PubMed:8632913).Curated1
Sequence conflicti622V → A in AAC50427 (PubMed:8632913).Curated1
Sequence conflicti635H → L in AAC50427 (PubMed:8632913).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_041863278V → I1 PublicationCorresponds to variant dbSNP:rs55939858Ensembl.1
Natural variantiVAR_041864339R → K in a lung adenocarcinoma sample; somatic mutation. 1 Publication1
Natural variantiVAR_041865514T → K1 PublicationCorresponds to variant dbSNP:rs55641092Ensembl.1
Natural variantiVAR_041866539R → C1 PublicationCorresponds to variant dbSNP:rs36046975Ensembl.1
Natural variantiVAR_041867546S → C1 PublicationCorresponds to variant dbSNP:rs56093628Ensembl.1
Natural variantiVAR_041868598V → M3 PublicationsCorresponds to variant dbSNP:rs6503018Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_051663411 – 415Missing in isoform 2. 1 Publication5

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
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]
XP_011522347.1. XM_011524045.2. [Q13470-2]
UniGeneiHs.203420.
Hs.739114.

Genome annotation databases

EnsembliENST00000570896; ENSP00000458834; ENSG00000174292. [Q13470-2]
ENST00000576812; ENSP00000459799; ENSG00000174292. [Q13470-1]
ENST00000639010; ENSP00000491712; ENSG00000283781. [Q13470-2]
ENST00000639430; ENSP00000491136; ENSG00000283781. [Q13470-1]
GeneIDi8711.
KEGGihsa:8711.
UCSCiuc002ggi.5. human. [Q13470-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiTNK1_HUMAN
AccessioniPrimary (citable) accession number: Q13470
Secondary accession number(s): O95364, Q8IYI4
Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 15, 2005
Last sequence update: October 17, 2006
Last modified: September 27, 2017
This is version 149 of the entry and version 3 of the sequence. See 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