Reviewed, UniProtKB/Swiss-Prot Q13470 (TNK1_HUMAN)

Names and origin

Protein names

Recommended name:
    Non-receptor tyrosine-protein kinase TNK1
    EC=2.7.10.2
Alternative name(s):
    CD38 negative kinase 1

Gene names

Name:

TNK1

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	666 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence 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.

Ontologies

Keywords
Cellular component	Cytoplasm Membrane
Coding sequence diversity	Alternative splicing Polymorphism
Domain	SH3 domain
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Transferase Tyrosine-protein kinase
PTM	Phosphoprotein
Gene Ontology (GO)
Biological process	protein amino acid autophosphorylation Ref.4 Inferred from direct assay. Source: UniProtKB
Cellular component	cytoplasm Ref.4 Inferred from direct assay. Source: UniProtKB membrane Ref.4 Inferred from direct assay. Source: UniProtKB
Molecular function	ATP binding Ref.4 Inferred from direct assay. Source: UniProtKB non-membrane spanning protein tyrosine kinase activity Ref.1 Ref.4 Non-traceable author statement. Source: UniProtKB protein binding Ref.4 Inferred from physical interaction. Source: UniProtKB signal transducer activity Ref.1 Traceable author statement. Source: ProtInc
Complete GO annotation...

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 key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 666	666	Non-receptor tyrosine-protein kinase TNK1		PRO_0000088173
Regions
	Domain	116 – 377	262	Protein kinase
	Domain	381 – 444	64	SH3
	Nucleotide binding	122 – 130	9	ATP By similarity
	Compositional bias	511 – 573	63	Pro-rich
Sites
	Active site	245	1	Proton acceptor By similarity
	Binding site	148	1	ATP By similarity
Amino acid modifications
	Modified residue	502	1	Phosphoserine
	Modified residue	508	1	Phosphoserine
	Modified residue	514	1	Phosphothreonine
	Modified residue	519	1	Phosphoserine
	Modified residue	661	1	Phosphotyrosine
Natural variations
	Alternative sequence	411 – 415	5	Missing in isoform 2.		VSP_051663
	Natural variant	278	1	V → I		VAR_041863
	Natural variant	339	1	R → K in a lung adenocarcinoma sample; somatic mutation.		VAR_041864
	Natural variant	514	1	T → K		VAR_041865
	Natural variant	539	1	R → C		VAR_041866
	Natural variant	546	1	S → C		VAR_041867
	Natural variant	598	1	V → M		VAR_041868
Experimental info
	Sequence conflict	36	1	E → G in AAC50427. Ref.1
	Sequence conflict	65	1	R → S in AAC50427. Ref.1
	Sequence conflict	94	1	S → T in AAC50427. Ref.1
	Sequence conflict	118	1	R → K in AAC99412. Ref.2
	Sequence conflict	252	1	L → Q in AAC50427. Ref.1
	Sequence conflict	288	1	A → T in AAC50427. Ref.1
	Sequence conflict	325	1	A → P in AAC50427. Ref.1
	Sequence conflict	347 – 348	2	LC → PS in AAC50427. Ref.1
	Sequence conflict	391	1	V → A in AAC50427. Ref.1
	Sequence conflict	424	1	G → D in AAC50427. Ref.1
	Sequence conflict	443	1	A → T in AAC50427. Ref.1
	Sequence conflict	561	1	K → E in AAC50427. Ref.1
	Sequence conflict	604	1	G → W in AAC50427. Ref.1
	Sequence conflict	622	1	V → A in AAC50427. Ref.1
	Sequence conflict	635	1	H → L in AAC50427. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified October 17, 2006. Version 3. Checksum: AA7FBEF6CC778181	FASTA	666	72,468
	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
	Isoform 2 [UniParc]. Checksum: 73FF2816065327CB		661	71,922
	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 SPDSTIWKGQ 430 440 450 460 470 480 NGRTFKVGSF PASAVTLADA GGLPATRPVH RGTPARGDQH PGSIDGDRKK ANLWDAPPAR 490 500 510 520 530 540 GQRRNMPLER MKGISRSLES VLSLGPRPTG GGSSPPEIRQ ARAVPQGPPG LPPRPPLSSS 550 560 570 580 590 600 SPQPSQPSRE RLPWPKRKPP HNHPMGMPGA RKAAALSGGL LSDPELQRKI MEVELSVHGV 610 620 630 640 650 660 THQECQTALG ATGGDVVSAI RNLKVDQLFH LSSRSRADCW RILEHYQWDL SAASRYVLAR P

References

	« Hide 'large scale' referencesShow '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. , 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
EMBLGenBankDDBJ	U43408 mRNA. Translation: AAC50427.1. AF097738 Genomic DNA. Translation: AAC99412.1. BC035782 mRNA. Translation: AAH35782.1.
RefSeq	NP_003976.2.
UniGene	Hs.203420
3D structure databases
HSSP	HSSP built from PDB template 1LUF based on UniProtKB Q62838.
ModBase	Search...
PTM databases
PhosphoSite	Q13470.
Genome annotation databases
Ensembl	ENSG00000174292. Homo sapiens. [Contig view]
GeneID	8711.
KEGG	hsa:8711.
Organism-specific databases
HGNC	HGNC:11940. TNK1.
MIM	608076. gene.
PharmGKB	PA134921265.
GenAtlas	Search...
GeneCards	Search...
Phylogenomic databases
HOGENOM	Q13470.
HOVERGEN	Q13470.
Gene expression databases
CleanEx	HS_TNK1.
GermOnline	ENSG00000174292. Homo sapiens.
Family and domain databases
InterPro	IPR000719. Prot_kinase_core. IPR017441. Protein_kinase_ATP_bd_CS. IPR001452. SH3. IPR001245. Tyr_pkinase. IPR008266. Tyr_pkinase_AS. IPR015772. Tyrosine_kinase_TNK1. [Graphical view]
PANTHER	PTHR23256:SF130. TNK1. 1 hit.
Pfam	PF07714. Pkinase_Tyr. 1 hit. [Graphical view]
PRINTS	PR00109. TYRKINASE.
ProDom	PD000001. Prot_kinase. 1 hit. [Graphical view] [Entries sharing at least one domain]
SMART	SM00326. SH3. 1 hit. SM00219. TyrKc. 1 hit. [Graphical view]
PROSITE	PS00107. PROTEIN_KINASE_ATP. 1 hit. PS50011. PROTEIN_KINASE_DOM. 1 hit. PS00109. PROTEIN_KINASE_TYR. 1 hit. PS50002. SH3. False negative. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	32671.
SOURCE	Search...

Entry information

Entry name

TNK1_HUMAN

Accession

Primary (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 status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)