Q99ML2 (TNK1_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Non-receptor tyrosine-protein kinase TNK1
EC=2.7.10.2

Alternative name(s):
Kinase of embryonic stem cells

Gene names

Name:	Tnk1
Synonyms:	Kos1

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	666 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	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 By similarity. Involved in negative regulation of cell growth. Has tumor suppressor properties. Plays a negative regulatory role in the Ras-MAPK pathway. Ref.1 Ref.5
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 By similarity. UniProtKB Q13470
Subcellular location	Membrane By similarity. Cytoplasm Ref.1.
Tissue specificity	Expressed in whole embryo and all adult tissues examined including liver, kidney, heart, brain, skeletal muscle and intestine. Also detected in various myeloid- and lymphoid-derived cell lines. Ref.1
Developmental stage	Expression during embryogenesis increases between E7 and E11. Levels of expression subsequently decrease and reach a steady-state level by E17. Ref.1
Post-translational modification	Autophosphorylated on tyrosine residues. Ref.1
Disruption phenotype	Mice develop spontaneous tumors, including lymphomas and carcinomas at high rates. Ref.5
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
Domain	SH3 domain
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Transferase Tyrosine-protein kinase
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	negative regulation of Ras protein signal transduction Inferred from mutant phenotype Ref.1. Source: UniProtKB negative regulation of cell growth Inferred from mutant phenotype Ref.1. Source: UniProtKB protein autophosphorylation Inferred from direct assay Ref.1. Source: UniProtKB
Cellular_component	cytosol Inferred from direct assay Ref.1. Source: UniProtKB membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	ATP binding Inferred from mutant phenotype Ref.1. Source: UniProtKB non-membrane spanning protein tyrosine kinase activity Inferred from direct assay Ref.1. Source: UniProtKB
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 Ref.2 (identifier: Q99ML2-1)

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 Ref.1 (identifier: Q99ML2-2)

The sequence of this isoform differs from the canonical sequence as follows:
     381-434: AWLSEGRCVR...TLKVGNFPAS → VRIPNSPYTH...QSLPAGSAEP
     435-666: Missing.

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_0000088174
Regions
	Domain	116 – 383	268	Protein kinase
	Domain	387 – 439	53	SH3
	Nucleotide binding	122 – 130	9	ATP By similarity UniProtKB P12931
	Compositional bias	507 – 560	54	Pro-rich
Sites
	Active site	245	1	Proton acceptor By similarity UniProtKB P12931
	Binding site	148	1	ATP By similarity UniProtKB P12931
Amino acid modifications
	Modified residue	255	1	Phosphoserine By similarity
	Modified residue	498	1	Phosphoserine By similarity
	Modified residue	510	1	Phosphothreonine By similarity
	Modified residue	515	1	Phosphoserine By similarity
	Modified residue	582	1	Phosphoserine By similarity
Natural variations
	Alternative sequence	381 – 434	54	AWLSE…NFPAS → VRIPNSPYTHIAFLPCILSP SVPCRRQTRLGAWAGIWNSA QNQVQSLPAGSAEP in isoform 2. Ref.1		VSP_051664
	Alternative sequence	435 – 666	232	Missing in isoform 2. Ref.1		VSP_051665
Experimental info
	Mutagenesis	148	1	K → A: Loss of autophosphorylation. Ref.1
	Sequence conflict	46	1	L → V in AAK35164. Ref.2
	Sequence conflict	59	1	L → I in AAK35164. Ref.2
	Sequence conflict	206	1	A → T in AAH29623. Ref.3
	Sequence conflict	206	1	A → T in AAH55303. Ref.3
	Sequence conflict	534	1	P → S in AAK35164. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified February 15, 2005. Version 2. Checksum: 5AE6A48D99BADE8B	FASTA	666	73,099
	10 20 30 40 50 60 MLPEASSLWL LRLLRDVQLA QFYRPILEEL NVTRPEHFDF VRPEDLDNIG MGRPAQRRLN 70 80 90 100 110 120 EALKRYRSGV KSKNWVYKIL GGFAPEQKEI PPRSDSPLCF HEPEGGLKCL IPEGAVRRGE 130 140 150 160 170 180 LLGSGCFGVV HRGLWTLPSG QSIPVAVKSL RVGPEGPMGT ELGDFLREVS VMMKLEHPHV 190 200 210 220 230 240 LRLHGLVLGQ PLQMVMELAP LGSLHARLTA PAPTPPLPVA LLCLFLRQLA GAMAYLGSCG 250 260 270 280 290 300 LVHRDLATRN LLLASPRMIK VADFGLVRPL GGARGRYVMG GPRPIPYAWC APESLRQGAF 310 320 330 340 350 360 SSASDVWMFG VTLWEMFSGG EEPWAGVPPY LILQRLEKDR ARLPKPPLCS RALYSLALRC 370 380 390 400 410 420 WAPHPADRPS FSNLEGLLQE AWLSEGRCVR EVTEPGALRM EPGDPITIIE GSLDTATWKG 430 440 450 460 470 480 QNGRTLKVGN FPASAVTLAD LGGSPVTHPA HRGSPAHGEK CRGGTDGDRE KATLQDLPPA 490 500 510 520 530 540 RSHRTKMPLQ RMRGISKSLE SVLSLGPRPT GGGSSPPELR RTRAMPQRLP DLPPRPPDLP 550 560 570 580 590 600 PRPPIICNSS QPTQPHKARP KRESSHNHRT GAPGASKATV PSGGPLSDPE WQRKVVEVEL 610 620 630 640 650 660 SVHGVTYQEC QVALRTTGGD VASAIRNLKV DQLFHLSNRS RADCRRILEH HQWDLSAASR YILARS
	Isoform 2 [UniParc]. Checksum: E1F1BBF451401FBC	FASTA	434	47,926
	10 20 30 40 50 60 MLPEASSLWL LRLLRDVQLA QFYRPILEEL NVTRPEHFDF VRPEDLDNIG MGRPAQRRLN 70 80 90 100 110 120 EALKRYRSGV KSKNWVYKIL GGFAPEQKEI PPRSDSPLCF HEPEGGLKCL IPEGAVRRGE 130 140 150 160 170 180 LLGSGCFGVV HRGLWTLPSG QSIPVAVKSL RVGPEGPMGT ELGDFLREVS VMMKLEHPHV 190 200 210 220 230 240 LRLHGLVLGQ PLQMVMELAP LGSLHARLTA PAPTPPLPVA LLCLFLRQLA GAMAYLGSCG 250 260 270 280 290 300 LVHRDLATRN LLLASPRMIK VADFGLVRPL GGARGRYVMG GPRPIPYAWC APESLRQGAF 310 320 330 340 350 360 SSASDVWMFG VTLWEMFSGG EEPWAGVPPY LILQRLEKDR ARLPKPPLCS RALYSLALRC 370 380 390 400 410 420 WAPHPADRPS FSNLEGLLQE VRIPNSPYTH IAFLPCILSP SVPCRRQTRL GAWAGIWNSA 430 QNQVQSLPAG SAEP

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Kos1, a nonreceptor tyrosine kinase that suppresses Ras signaling." Hoare K., Hoare S., Smith O.M., Kalmaz G., Small D., May W.S. Jr. Oncogene 22:3562-3577(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 2), FUNCTION, AUTOPHOSPHORYLATION, MUTAGENESIS OF LYS-148, SUBCELLULAR LOCATION, TISSUE SPECIFICITY. Strain: 129/Sv. Tissue: Embryonic stem cell.
[2]	"Cloning of the murine Tnk1 tyrosine kinase and evidence that it plays a role in cell adhesion." Hoehn G.T., Felschow D.M., Civin C.I. Submitted (DEC-2000) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[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 1). Strain: FVB/N-3. Tissue: Mammary gland.
[4]	"The transcriptional landscape of the mammalian genome." Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y. Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 151-666 (ISOFORM 1). Strain: C57BL/6J. Tissue: Colon.
[5]	"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, DISRUPTION PHENOTYPE.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF307745 Genomic DNA. Translation: AAL09412.1. AF307746 mRNA. Translation: AAL09413.1. AF332512 mRNA. Translation: AAK35164.1. BC029623 mRNA. Translation: AAH29623.1. BC055303 mRNA. Translation: AAH55303.1. AK033440 mRNA. Translation: BAC28288.1.
IPI	IPI00331618. IPI00471116.
RefSeq	NP_114086.3. NM_031880.3.
UniGene	Mm.28874. Mm.358793.
3D structure databases
ProteinModelPortal	Q99ML2.
SMR	Q99ML2. Positions 107-381.
ModBase	Search...
PTM databases
PhosphoSite	Q99ML2.
Proteomic databases
PRIDE	Q99ML2.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000001626; ENSMUSP00000001626; ENSMUSG00000001583. ENSMUST00000108626; ENSMUSP00000104266; ENSMUSG00000001583.
GeneID	83813.
KEGG	mmu:83813.
Organism-specific databases
CTD	8711.
MGI	MGI:1930958. Tnk1.
Phylogenomic databases
eggNOG	COG0515.
GeneTree	ENSGT00630000089536.
HOGENOM	HOG000231055.
HOVERGEN	HBG055513.
KO	K08885.
OMA	SHASDCW.
OrthoDB	EOG40CHGS.
Gene expression databases
ArrayExpress	Q99ML2.
Bgee	Q99ML2.
CleanEx	MM_TNK1.
Genevestigator	Q99ML2.
GermOnline	ENSMUSG00000001583. Mus musculus.
Family and domain databases
InterPro	IPR011009. Kinase-like_dom. IPR000719. Prot_kinase_cat_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]
Pfam	PF07714. Pkinase_Tyr. 1 hit. [Graphical view]
PRINTS	PR00109. TYRKINASE.
SMART	SM00326. SH3. 1 hit. SM00219. TyrKc. 1 hit. [Graphical view]
SUPFAM	SSF56112. Kinase_like. 1 hit.
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
NextBio	350786.
SOURCE	Search...

Entry information

Entry name

TNK1_MOUSE

Accession

Primary (citable) accession number: Q99ML2
Secondary accession number(s): Q8CCC4, Q8K0X9, Q91V11

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 15, 2005
Last sequence update:	February 15, 2005
Last modified:	May 1, 2013
This is version 96 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program