FRK_HUMAN
ID FRK_HUMAN Reviewed; 505 AA.
AC P42685; B4DY49; Q13128; Q9NTR5;
DT 01-NOV-1995, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1995, sequence version 1.
DT 03-AUG-2022, entry version 211.
DE RecName: Full=Tyrosine-protein kinase FRK;
DE EC=2.7.10.2;
DE AltName: Full=FYN-related kinase;
DE AltName: Full=Nuclear tyrosine protein kinase RAK;
DE AltName: Full=Protein-tyrosine kinase 5;
GN Name=FRK; Synonyms=PTK5, RAK;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY, AND SUBCELLULAR
RP LOCATION.
RX PubMed=7696183;
RA Cance W.G., Craven R.J., Bergman M., Xu L.H., Alitalo K., Liu E.T.;
RT "Rak, a novel nuclear tyrosine kinase expressed in epithelial cells.";
RL Cell Growth Differ. 5:1347-1355(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Lymphoid tissue;
RX PubMed=7510261; DOI=10.1016/0378-1119(94)90817-6;
RA Lee J., Wang Z., Luoh S.-M., Wood W.I., Scadden D.T.;
RT "Cloning of FRK, a novel human intracellular SRC-like tyrosine kinase-
RT encoding gene.";
RL Gene 138:247-251(1994).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Testis;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=14574404; DOI=10.1038/nature02055;
RA Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L.,
RA Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R.,
RA Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D.,
RA Andrews T.D., Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H.,
RA Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J.,
RA Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V.,
RA Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J.,
RA Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E.,
RA Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J.,
RA French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J.,
RA Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C.,
RA Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A.,
RA Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R.,
RA Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M.,
RA Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K.,
RA Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R.,
RA Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M.,
RA Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A.,
RA Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L.,
RA Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I.,
RA Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y.,
RA Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E.,
RA Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A.,
RA Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W.,
RA Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M.,
RA West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J.,
RA Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M.,
RA Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I.,
RA Rogers J., Beck S.;
RT "The DNA sequence and analysis of human chromosome 6.";
RL Nature 425:805-811(2003).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Urinary bladder;
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 [7]
RP PARTIAL NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=8099900; DOI=10.1002/ijc.2910540409;
RA Cance W.G., Craven R.J., Weiner T.M., Liu E.T.;
RT "Novel protein kinases expressed in human breast cancer.";
RL Int. J. Cancer 54:571-577(1993).
RN [8]
RP INTERACTION WITH RB1.
RX PubMed=7664264;
RA Craven R.J., Cance W.G., Liu E.T.;
RT "The nuclear tyrosine kinase Rak associates with the retinoblastoma protein
RT pRb.";
RL Cancer Res. 55:3969-3972(1995).
RN [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-37, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007;
RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,
RA Greff Z., Keri G., Stemmann O., Mann M.;
RT "Kinase-selective enrichment enables quantitative phosphoproteomics of the
RT kinome across the cell cycle.";
RL Mol. Cell 31:438-448(2008).
RN [10]
RP FUNCTION, INTERACTION WITH PTEN, AND MUTAGENESIS OF LYS-262.
RX PubMed=19345329; DOI=10.1016/j.ccr.2009.02.012;
RA Yim E.-K., Peng G., Dai H., Hu R., Li K., Lu Y., Mills G.B.,
RA Meric-Bernstam F., Hennessy B.T., Craven R.J., Lin S.-Y.;
RT "Rak functions as a tumor suppressor by regulating PTEN protein stability
RT and function.";
RL Cancer Cell 15:304-314(2009).
RN [11]
RP REVIEW ON FUNCTION.
RX PubMed=19652529; DOI=10.4161/cc.8.17.9389;
RA Brauer P.M., Tyner A.L.;
RT "RAKing in AKT: a tumor suppressor function for the intracellular tyrosine
RT kinase FRK.";
RL Cell Cycle 8:2728-2732(2009).
RN [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-40 AND THR-178, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [13]
RP VARIANTS [LARGE SCALE ANALYSIS] VAL-100; ARG-122 AND LEU-133.
RX PubMed=17344846; DOI=10.1038/nature05610;
RA Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G.,
RA Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S.,
RA Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G.,
RA Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K.,
RA Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D.,
RA Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R.,
RA Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A.,
RA Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F.,
RA Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F.,
RA Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G.,
RA Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R.,
RA Futreal P.A., Stratton M.R.;
RT "Patterns of somatic mutation in human cancer genomes.";
RL Nature 446:153-158(2007).
CC -!- FUNCTION: Non-receptor tyrosine-protein kinase that negatively
CC regulates cell proliferation. Positively regulates PTEN protein
CC stability through phosphorylation of PTEN on 'Tyr-336', which in turn
CC prevents its ubiquitination and degradation, possibly by reducing its
CC binding to NEDD4. May function as a tumor suppressor.
CC {ECO:0000269|PubMed:19345329}.
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 (via the SH3-domain) with PTEN. Interacts with RB1.
CC {ECO:0000269|PubMed:19345329, ECO:0000269|PubMed:7664264}.
CC -!- INTERACTION:
CC P42685; Q12982: BNIP2; NbExp=8; IntAct=EBI-1383583, EBI-752094;
CC P42685; P60484: PTEN; NbExp=7; IntAct=EBI-1383583, EBI-696162;
CC P42685; P06400: RB1; NbExp=3; IntAct=EBI-1383583, EBI-491274;
CC P42685; Q15427: SF3B4; NbExp=4; IntAct=EBI-1383583, EBI-348469;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:7696183}. Nucleus
CC {ECO:0000269|PubMed:7696183}. Note=Predominantly found in the nucleus,
CC with a small fraction found in the cell periphery.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P42685-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P42685-2; Sequence=VSP_056496, VSP_056497;
CC -!- TISSUE SPECIFICITY: Predominantly expressed in epithelial derived cell
CC lines and tissues, especially normal liver, kidney, breast and colon.
CC {ECO:0000269|PubMed:7696183}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. Tyr protein
CC kinase family. SRC subfamily. {ECO:0000255|PROSITE-ProRule:PRU00159}.
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DR EMBL; U22322; AAC50116.1; -; mRNA.
DR EMBL; U00803; AAA18284.1; -; mRNA.
DR EMBL; AK302264; BAG63611.1; -; mRNA.
DR EMBL; AL021451; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL121963; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL357141; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471051; EAW48241.1; -; Genomic_DNA.
DR EMBL; BC012916; AAH12916.1; -; mRNA.
DR CCDS; CCDS5103.1; -. [P42685-1]
DR PIR; I38396; I38396.
DR RefSeq; NP_002022.1; NM_002031.2. [P42685-1]
DR RefSeq; XP_005266937.1; XM_005266880.4. [P42685-1]
DR RefSeq; XP_005266938.1; XM_005266881.2. [P42685-1]
DR RefSeq; XP_005266939.1; XM_005266882.4. [P42685-1]
DR RefSeq; XP_011533955.1; XM_011535653.2. [P42685-1]
DR RefSeq; XP_011533956.1; XM_011535654.2. [P42685-1]
DR RefSeq; XP_011533957.1; XM_011535655.2. [P42685-1]
DR RefSeq; XP_016866134.1; XM_017010645.1. [P42685-1]
DR AlphaFoldDB; P42685; -.
DR SMR; P42685; -.
DR BioGRID; 108726; 11.
DR IntAct; P42685; 44.
DR MINT; P42685; -.
DR STRING; 9606.ENSP00000476145; -.
DR BindingDB; P42685; -.
DR ChEMBL; CHEMBL4223; -.
DR DrugBank; DB01254; Dasatinib.
DR DrugBank; DB12010; Fostamatinib.
DR DrugBank; DB08896; Regorafenib.
DR DrugBank; DB15035; Zanubrutinib.
DR DrugCentral; P42685; -.
DR GuidetoPHARMACOLOGY; 2025; -.
DR iPTMnet; P42685; -.
DR PhosphoSitePlus; P42685; -.
DR BioMuta; FRK; -.
DR DMDM; 1169745; -.
DR CPTAC; CPTAC-2793; -.
DR EPD; P42685; -.
DR jPOST; P42685; -.
DR MassIVE; P42685; -.
DR MaxQB; P42685; -.
DR PaxDb; P42685; -.
DR PeptideAtlas; P42685; -.
DR PRIDE; P42685; -.
DR ProteomicsDB; 5498; -.
DR ProteomicsDB; 55538; -. [P42685-1]
DR TopDownProteomics; P42685-1; -. [P42685-1]
DR Antibodypedia; 32472; 583 antibodies from 35 providers.
DR DNASU; 2444; -.
DR Ensembl; ENST00000606080.2; ENSP00000476145.1; ENSG00000111816.8. [P42685-1]
DR GeneID; 2444; -.
DR KEGG; hsa:2444; -.
DR MANE-Select; ENST00000606080.2; ENSP00000476145.1; NM_002031.3; NP_002022.1.
DR UCSC; uc003pwi.2; human. [P42685-1]
DR CTD; 2444; -.
DR DisGeNET; 2444; -.
DR GeneCards; FRK; -.
DR HGNC; HGNC:3955; FRK.
DR HPA; ENSG00000111816; Tissue enhanced (choroid).
DR MIM; 606573; gene.
DR neXtProt; NX_P42685; -.
DR OpenTargets; ENSG00000111816; -.
DR PharmGKB; PA28373; -.
DR VEuPathDB; HostDB:ENSG00000111816; -.
DR eggNOG; KOG0197; Eukaryota.
DR GeneTree; ENSGT00940000156987; -.
DR HOGENOM; CLU_000288_7_2_1; -.
DR InParanoid; P42685; -.
DR OMA; SSHEGWW; -.
DR OrthoDB; 539311at2759; -.
DR PhylomeDB; P42685; -.
DR TreeFam; TF351634; -.
DR BRENDA; 2.7.10.2; 2681.
DR PathwayCommons; P42685; -.
DR Reactome; R-HSA-6798695; Neutrophil degranulation.
DR Reactome; R-HSA-8948751; Regulation of PTEN stability and activity.
DR SignaLink; P42685; -.
DR SIGNOR; P42685; -.
DR BioGRID-ORCS; 2444; 6 hits in 1103 CRISPR screens.
DR ChiTaRS; FRK; human.
DR GeneWiki; Fyn-related_kinase; -.
DR GenomeRNAi; 2444; -.
DR Pharos; P42685; Tchem.
DR PRO; PR:P42685; -.
DR Proteomes; UP000005640; Chromosome 6.
DR RNAct; P42685; protein.
DR Bgee; ENSG00000111816; Expressed in jejunal mucosa and 157 other tissues.
DR Genevisible; P42685; HS.
DR GO; GO:0035578; C:azurophil granule lumen; TAS:Reactome.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:0031234; C:extrinsic component of cytoplasmic side of plasma membrane; IBA:GO_Central.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; TAS:ProtInc.
DR GO; GO:0035580; C:specific granule lumen; TAS:Reactome.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0004715; F:non-membrane spanning protein tyrosine kinase activity; IBA:GO_Central.
DR GO; GO:0004713; F:protein tyrosine kinase activity; EXP:Reactome.
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:0000122; P:negative regulation of transcription by RNA polymerase II; IDA:BHF-UCL.
DR GO; GO:0007169; P:transmembrane receptor protein tyrosine kinase signaling pathway; IBA:GO_Central.
DR CDD; cd10369; SH2_Src_Frk; 1.
DR Gene3D; 3.30.505.10; -; 1.
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; IPR000980; SH2.
DR InterPro; IPR036860; SH2_dom_sf.
DR InterPro; IPR035805; SH2_Frk.
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 Pfam; PF00017; SH2; 1.
DR Pfam; PF00018; SH3_1; 1.
DR PRINTS; PR00401; SH2DOMAIN.
DR PRINTS; PR00452; SH3DOMAIN.
DR PRINTS; PR00109; TYRKINASE.
DR SMART; SM00252; SH2; 1.
DR SMART; SM00326; SH3; 1.
DR SMART; SM00219; TyrKc; 1.
DR SUPFAM; SSF50044; SSF50044; 1.
DR SUPFAM; SSF55550; SSF55550; 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; PS50001; SH2; 1.
DR PROSITE; PS50002; SH3; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; ATP-binding; Cytoplasm; Kinase; Nucleotide-binding;
KW Nucleus; Phosphoprotein; Reference proteome; SH2 domain; SH3 domain;
KW Transferase; Tumor suppressor; Tyrosine-protein kinase.
FT CHAIN 1..505
FT /note="Tyrosine-protein kinase FRK"
FT /id="PRO_0000088097"
FT DOMAIN 42..110
FT /note="SH3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00192"
FT DOMAIN 116..208
FT /note="SH2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00191"
FT DOMAIN 234..491
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT ACT_SITE 354
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10028"
FT BINDING 240..248
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 262
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 37
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18691976"
FT MOD_RES 40
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 178
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 387
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:Q922K9"
FT VAR_SEQ 1..13
FT /note="MSNICQRLWEYLE -> MDSTSLLPNPWIR (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_056496"
FT VAR_SEQ 14..155
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_056497"
FT VARIANT 100
FT /note="I -> V (in dbSNP:rs34704018)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041702"
FT VARIANT 122
FT /note="G -> R (in dbSNP:rs3756772)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_006283"
FT VARIANT 133
FT /note="S -> L (in dbSNP:rs34064900)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041703"
FT MUTAGEN 262
FT /note="K->R: Loss of ability to phosphorylate PTEN."
FT /evidence="ECO:0000269|PubMed:19345329"
FT CONFLICT 115
FT /note="P -> A (in Ref. 1; AAC50116)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 505 AA; 58254 MW; 06EC050DDBCD930B CRC64;
MSNICQRLWE YLEPYLPCLS TEADKSTVIE NPGALCSPQS QRHGHYFVAL FDYQARTAED
LSFRAGDKLQ VLDTLHEGWW FARHLEKRRD GSSQQLQGYI PSNYVAEDRS LQAEPWFFGA
IGRSDAEKQL LYSENKTGSF LIRESESQKG EFSLSVLDGA VVKHYRIKRL DEGGFFLTRR
RIFSTLNEFV SHYTKTSDGL CVKLGKPCLK IQVPAPFDLS YKTVDQWEID RNSIQLLKRL
GSGQFGEVWE GLWNNTTPVA VKTLKPGSMD PNDFLREAQI MKNLRHPKLI QLYAVCTLED
PIYIITELMR HGSLQEYLQN DTGSKIHLTQ QVDMAAQVAS GMAYLESRNY IHRDLAARNV
LVGEHNIYKV ADFGLARVFK VDNEDIYESR HEIKLPVKWT APEAIRSNKF SIKSDVWSFG
ILLYEIITYG KMPYSGMTGA QVIQMLAQNY RLPQPSNCPQ QFYNIMLECW NAEPKERPTF
ETLRWKLEDY FETDSSYSDA NNFIR
