TNK1_MOUSE
ID TNK1_MOUSE Reviewed; 666 AA.
AC Q99ML2; Q8CCC4; Q8K0X9; Q91V11;
DT 15-FEB-2005, integrated into UniProtKB/Swiss-Prot.
DT 15-FEB-2005, sequence version 2.
DT 03-AUG-2022, entry version 153.
DE RecName: Full=Non-receptor tyrosine-protein kinase TNK1;
DE EC=2.7.10.2;
DE AltName: Full=Kinase of embryonic stem cells;
GN Name=Tnk1 {ECO:0000312|EMBL:AAK35164.1};
GN Synonyms=Kos1 {ECO:0000312|MGI:MGI:1930958};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1] {ECO:0000305, ECO:0000312|EMBL:AAL09413.1}
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 2), FUNCTION,
RP AUTOPHOSPHORYLATION, MUTAGENESIS OF LYS-148, SUBCELLULAR LOCATION, AND
RP TISSUE SPECIFICITY.
RC STRAIN=129/Sv {ECO:0000312|EMBL:AAL09412.1}; TISSUE=Embryonic stem cell;
RX PubMed=12789265; DOI=10.1038/sj.onc.1206480;
RA Hoare K., Hoare S., Smith O.M., Kalmaz G., Small D., May W.S. Jr.;
RT "Kos1, a nonreceptor tyrosine kinase that suppresses Ras signaling.";
RL Oncogene 22:3562-3577(2003).
RN [2] {ECO:0000305, ECO:0000312|EMBL:AAK35164.1}
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RA Hoehn G.T., Felschow D.M., Civin C.I.;
RT "Cloning of the murine Tnk1 tyrosine kinase and evidence that it plays a
RT role in cell adhesion.";
RL Submitted (DEC-2000) to the EMBL/GenBank/DDBJ databases.
RN [3] {ECO:0000305, ECO:0000312|EMBL:AAH29623.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC STRAIN=FVB/N-3 {ECO:0000312|EMBL:AAH55303.1};
RC TISSUE=Mammary gland {ECO:0000312|EMBL:AAH29623.1};
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 151-666 (ISOFORM 1).
RC STRAIN=C57BL/6J; TISSUE=Colon;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [5]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=18974114; DOI=10.1158/0008-5472.can-08-1467;
RA Hoare S., Hoare K., Reinhard M.K., Lee Y.J., Oh S.P., May W.S. Jr.;
RT "Tnk1/Kos1 knockout mice develop spontaneous tumors.";
RL Cancer Res. 68:8723-8732(2008).
RN [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-498, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Kidney;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
CC -!- FUNCTION: May function in signaling pathways utilized broadly during
CC fetal development and more selectively in adult tissues and in cells of
CC the lymphohematopoietic system. Could specifically be involved in
CC phospholipid signal transduction (By similarity). Involved in negative
CC regulation of cell growth. Has tumor suppressor properties. Plays a
CC negative regulatory role in the Ras-MAPK pathway. {ECO:0000250,
CC ECO:0000269|PubMed:12789265, ECO:0000269|PubMed:18974114}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-tyrosyl-[protein] = ADP + H(+) + O-phospho-L-tyrosyl-
CC [protein]; Xref=Rhea:RHEA:10596, Rhea:RHEA-COMP:10136, Rhea:RHEA-
CC COMP:10137, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:46858,
CC ChEBI:CHEBI:82620, ChEBI:CHEBI:456216; EC=2.7.10.2;
CC Evidence={ECO:0000255|PROSITE-ProRule:PRU10028};
CC -!- SUBUNIT: Interacts with the SH3 domain of PLCG1 via its Pro-rich
CC domain. {ECO:0000250|UniProtKB:Q13470}.
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000250}. Cytoplasm
CC {ECO:0000269|PubMed:12789265}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1 {ECO:0000269|Ref.2};
CC IsoId=Q99ML2-1; Sequence=Displayed;
CC Name=2 {ECO:0000269|PubMed:12789265};
CC IsoId=Q99ML2-2; Sequence=VSP_051664, VSP_051665;
CC -!- TISSUE SPECIFICITY: Expressed in whole embryo and all adult tissues
CC examined including liver, kidney, heart, brain, skeletal muscle and
CC intestine. Also detected in various myeloid- and lymphoid-derived cell
CC lines. {ECO:0000269|PubMed:12789265}.
CC -!- DEVELOPMENTAL STAGE: Expression during embryogenesis increases between
CC 7 dpc and 11 dpc. Levels of expression subsequently decrease and reach
CC a steady-state level by 17 dpc. {ECO:0000269|PubMed:12789265}.
CC -!- PTM: Autophosphorylated on tyrosine residues.
CC {ECO:0000269|PubMed:12789265}.
CC -!- DISRUPTION PHENOTYPE: Mice develop spontaneous tumors, including
CC lymphomas and carcinomas at high rates. {ECO:0000269|PubMed:18974114}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. Tyr protein
CC kinase family. {ECO:0000255|PROSITE-ProRule:PRU00159}.
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DR EMBL; AF307745; AAL09412.1; -; Genomic_DNA.
DR EMBL; AF307746; AAL09413.1; -; mRNA.
DR EMBL; AF332512; AAK35164.1; -; mRNA.
DR EMBL; BC029623; AAH29623.1; -; mRNA.
DR EMBL; BC055303; AAH55303.1; -; mRNA.
DR EMBL; AK033440; BAC28288.1; -; mRNA.
DR CCDS; CCDS24917.1; -. [Q99ML2-1]
DR RefSeq; NP_114086.3; NM_031880.3. [Q99ML2-1]
DR RefSeq; XP_006534617.1; XM_006534554.3. [Q99ML2-1]
DR AlphaFoldDB; Q99ML2; -.
DR SMR; Q99ML2; -.
DR STRING; 10090.ENSMUSP00000001626; -.
DR iPTMnet; Q99ML2; -.
DR PhosphoSitePlus; Q99ML2; -.
DR PaxDb; Q99ML2; -.
DR PRIDE; Q99ML2; -.
DR ProteomicsDB; 259477; -. [Q99ML2-1]
DR ProteomicsDB; 259478; -. [Q99ML2-2]
DR Antibodypedia; 6049; 358 antibodies from 34 providers.
DR DNASU; 83813; -.
DR Ensembl; ENSMUST00000001626; ENSMUSP00000001626; ENSMUSG00000001583. [Q99ML2-1]
DR Ensembl; ENSMUST00000108626; ENSMUSP00000104266; ENSMUSG00000001583. [Q99ML2-2]
DR GeneID; 83813; -.
DR KEGG; mmu:83813; -.
DR UCSC; uc007jsb.2; mouse. [Q99ML2-1]
DR UCSC; uc007jsc.2; mouse. [Q99ML2-2]
DR CTD; 8711; -.
DR MGI; MGI:1930958; Tnk1.
DR VEuPathDB; HostDB:ENSMUSG00000001583; -.
DR eggNOG; KOG0199; Eukaryota.
DR GeneTree; ENSGT00940000162159; -.
DR HOGENOM; CLU_000288_7_39_1; -.
DR InParanoid; Q99ML2; -.
DR OMA; GQMPWAG; -.
DR TreeFam; TF316643; -.
DR BioGRID-ORCS; 83813; 5 hits in 74 CRISPR screens.
DR ChiTaRS; Tnk1; mouse.
DR PRO; PR:Q99ML2; -.
DR Proteomes; UP000000589; Chromosome 11.
DR RNAct; Q99ML2; protein.
DR Bgee; ENSMUSG00000001583; Expressed in small intestine Peyer's patch and 103 other tissues.
DR ExpressionAtlas; Q99ML2; baseline and differential.
DR Genevisible; Q99ML2; MM.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR GO; GO:0031234; C:extrinsic component of cytoplasmic side of plasma membrane; IBA:GO_Central.
DR GO; GO:0016020; C:membrane; ISO:MGI.
DR GO; GO:0005524; F:ATP binding; IMP:UniProtKB.
DR GO; GO:0004715; F:non-membrane spanning protein tyrosine kinase activity; IDA:UniProtKB.
DR GO; GO:0004713; F:protein tyrosine kinase activity; ISO:MGI.
DR GO; GO:0005102; F:signaling receptor binding; IBA:GO_Central.
DR GO; GO:0030154; P:cell differentiation; IBA:GO_Central.
DR GO; GO:0045087; P:innate immune response; IBA:GO_Central.
DR GO; GO:0030308; P:negative regulation of cell growth; IMP:UniProtKB.
DR GO; GO:0046580; P:negative regulation of Ras protein signal transduction; IMP:UniProtKB.
DR GO; GO:0046777; P:protein autophosphorylation; IDA:UniProtKB.
DR GO; GO:0007169; P:transmembrane receptor protein tyrosine kinase signaling pathway; IBA:GO_Central.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR001245; Ser-Thr/Tyr_kinase_cat_dom.
DR InterPro; IPR036028; SH3-like_dom_sf.
DR InterPro; IPR001452; SH3_domain.
DR InterPro; IPR008266; Tyr_kinase_AS.
DR InterPro; IPR020635; Tyr_kinase_cat_dom.
DR Pfam; PF07714; PK_Tyr_Ser-Thr; 1.
DR PRINTS; PR00109; TYRKINASE.
DR SMART; SM00219; TyrKc; 1.
DR SUPFAM; SSF50044; SSF50044; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00109; PROTEIN_KINASE_TYR; 1.
DR PROSITE; PS50002; SH3; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; ATP-binding; Cytoplasm; Kinase; Membrane;
KW Nucleotide-binding; Phosphoprotein; Reference proteome; SH3 domain;
KW Transferase; Tyrosine-protein kinase.
FT CHAIN 1..666
FT /note="Non-receptor tyrosine-protein kinase TNK1"
FT /id="PRO_0000088174"
FT DOMAIN 116..383
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT DOMAIN 381..441
FT /note="SH3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00192"
FT REGION 442..589
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 453..477
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 529..548
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 245
FT /note="Proton acceptor"
FT /evidence="ECO:0000250|UniProtKB:P12931,
FT ECO:0000255|PROSITE-ProRule:PRU00159, ECO:0000255|PROSITE-
FT ProRule:PRU10028"
FT BINDING 122..130
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P12931,
FT ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 148
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P12931,
FT ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 96
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q13470"
FT MOD_RES 255
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q13470"
FT MOD_RES 498
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 510
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q13470"
FT MOD_RES 515
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q13470"
FT MOD_RES 582
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q13470"
FT VAR_SEQ 381..434
FT /note="AWLSEGRCVREVTEPGALRMEPGDPITIIEGSLDTATWKGQNGRTLKVGNFP
FT AS -> VRIPNSPYTHIAFLPCILSPSVPCRRQTRLGAWAGIWNSAQNQVQSLPAGSAE
FT P (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:12789265"
FT /id="VSP_051664"
FT VAR_SEQ 435..666
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:12789265"
FT /id="VSP_051665"
FT MUTAGEN 148
FT /note="K->A: Loss of autophosphorylation."
FT /evidence="ECO:0000269|PubMed:12789265"
FT CONFLICT 46
FT /note="L -> V (in Ref. 2; AAK35164)"
FT /evidence="ECO:0000305"
FT CONFLICT 59
FT /note="L -> I (in Ref. 2; AAK35164)"
FT /evidence="ECO:0000305"
FT CONFLICT 206
FT /note="A -> T (in Ref. 3; AAH29623/AAH55303)"
FT /evidence="ECO:0000305"
FT CONFLICT 534
FT /note="P -> S (in Ref. 2; AAK35164)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 666 AA; 73099 MW; 5AE6A48D99BADE8B CRC64;
MLPEASSLWL LRLLRDVQLA QFYRPILEEL NVTRPEHFDF VRPEDLDNIG MGRPAQRRLN
EALKRYRSGV KSKNWVYKIL GGFAPEQKEI PPRSDSPLCF HEPEGGLKCL IPEGAVRRGE
LLGSGCFGVV HRGLWTLPSG QSIPVAVKSL RVGPEGPMGT ELGDFLREVS VMMKLEHPHV
LRLHGLVLGQ PLQMVMELAP LGSLHARLTA PAPTPPLPVA LLCLFLRQLA GAMAYLGSCG
LVHRDLATRN LLLASPRMIK VADFGLVRPL GGARGRYVMG GPRPIPYAWC APESLRQGAF
SSASDVWMFG VTLWEMFSGG EEPWAGVPPY LILQRLEKDR ARLPKPPLCS RALYSLALRC
WAPHPADRPS FSNLEGLLQE AWLSEGRCVR EVTEPGALRM EPGDPITIIE GSLDTATWKG
QNGRTLKVGN FPASAVTLAD LGGSPVTHPA HRGSPAHGEK CRGGTDGDRE KATLQDLPPA
RSHRTKMPLQ RMRGISKSLE SVLSLGPRPT GGGSSPPELR RTRAMPQRLP DLPPRPPDLP
PRPPIICNSS QPTQPHKARP KRESSHNHRT GAPGASKATV PSGGPLSDPE WQRKVVEVEL
SVHGVTYQEC QVALRTTGGD VASAIRNLKV DQLFHLSNRS RADCRRILEH HQWDLSAASR
YILARS