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Reviewed, UniProtKB/Swiss-Prot Q13470 (TNK1_HUMAN)

Last modified November 25, 2008. Version 66. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data | Customize display text xml rdf/xml gff fasta
Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Alternative products · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents

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)
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length666 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is not processed.
Protein existenceEvidence at protein level.

General annotation (Comments)

Function

Involved in negative regulation of cell growth. May have tumor suppressor properties. May play a negative regulatory role in the Ras-MAPK pathway By similarity. 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.

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.

Subcellular location

Cytoplasm. Membrane; Peripheral membrane protein.

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.

Post-translational modification

Autophosphorylated on tyrosine residues.

Sequence similarities

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

Contains 1 protein kinase domain.

Contains 1 SH3 domain.

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 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.
Notes: No experimental confirmation available.

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
Compositional bias511 – 57363Pro-rich

Sites

Active site2451Proton acceptor By similarity
Binding site1481ATP By similarity

Amino acid modifications

Modified residue5021Phosphoserine
Modified residue5081Phosphoserine
Modified residue5141Phosphothreonine
Modified residue5191Phosphoserine
Modified residue6611Phosphotyrosine

Natural variations

Alternative sequence411 – 4155Missing in isoform 2.
VSP_051663
Natural variant2781V → I
VAR_041863
Natural variant3391R → K in a lung adenocarcinoma sample; somatic mutation.
VAR_041864
Natural variant5141T → K
VAR_041865
Natural variant5391R → C
VAR_041866
Natural variant5461S → C
VAR_041867
Natural variant5981V → M
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 »

66171,922

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: 8632913] [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: 15489334] [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: 10873601] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AUTOPHOSPHORYLATION, INTERACTION WITH PLCG1.
[5]"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: 18669648] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-502; SER-508; THR-514; SER-519 AND TYR-661, MASS SPECTROMETRY.
[6]"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: 17344846] [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

U43408 mRNA. Translation: AAC50427.1.
AF097738 Genomic DNA. Translation: AAC99412.1.
BC035782 mRNA. Translation: AAH35782.1.
RefSeqNP_003976.2.
UniGeneHs.203420

3D structure databases

HSSPHSSP built from PDB template 1LUF based on UniProtKB Q62838.
ModBaseSearch...

PTM databases

PhosphoSiteQ13470.

Genome annotation databases

EnsemblENSG00000174292. Homo sapiens. [Contig view]
GeneID8711.
KEGGhsa:8711.

Organism-specific databases

HGNCHGNC:11940. TNK1.
MIM608076. gene.
PharmGKBPA134921265.
GenAtlasSearch...
GeneCardsSearch...

Phylogenomic databases

HOGENOMQ13470.
HOVERGENQ13470.

Gene expression databases

CleanExHS_TNK1.
GermOnlineENSG00000174292. Homo sapiens.

Family and domain databases

InterProIPR000719. Prot_kinase_core.
IPR017441. Protein_kinase_ATP_bd_CS.
IPR001452. SH3.
IPR001245. Tyr_pkinase.
IPR008266. Tyr_pkinase_AS.
IPR015772. Tyrosine_kinase_TNK1.
[Graphical view]
PANTHERPTHR23256:SF130. TNK1. 1 hit.
PfamPF07714. Pkinase_Tyr. 1 hit.
[Graphical view]
PRINTSPR00109. TYRKINASE.
ProDomPD000001. Prot_kinase. 1 hit.
[Graphical view] [Entries sharing at least one domain]
SMARTSM00326. SH3. 1 hit.
SM00219. TyrKc. 1 hit.
[Graphical view]
PROSITEPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00109. PROTEIN_KINASE_TYR. 1 hit.
PS50002. SH3. False negative.
[Graphical view]
ProtoNetSearch...

Other Resources

NextBio32671.
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: November 25, 2008
This is version 66 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation projectHPI (Human Proteome Initiative)

Relevant documents

Human chromosome 17

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

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

MIM cross-references

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

Human and mouse protein kinases

Human and mouse protein kinases: classification and index

SIMILARITY comments

Index of protein domains and families

Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Alternative products · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents