ID FRK_MOUSE Reviewed; 512 AA. AC Q922K9; Q61364; Q61745; DT 28-NOV-2006, integrated into UniProtKB/Swiss-Prot. DT 23-JAN-2007, sequence version 3. DT 27-MAR-2024, entry version 174. DE RecName: Full=Tyrosine-protein kinase FRK; DE EC=2.7.10.2; DE AltName: Full=Beta-cell Src-homology tyrosine kinase; DE Short=BSK; DE AltName: Full=FYN-related kinase; DE AltName: Full=Intestine tyrosine kinase; GN Name=Frk; Synonyms=Bsk, Iyk; 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] RP NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY. RC STRAIN=BALB/cJ; TISSUE=Mammary gland; RX PubMed=7733928; DOI=10.1006/bbrc.1995.1540; RA Thuveson M., Albrecht D., Zuercher G., Andres A., Ziemiecki A.; RT "iyk, a novel intracellular protein tyrosine kinase differentially RT expressed in the mouse mammary gland and intestine."; RL Biochem. Biophys. Res. Commun. 209:582-589(1995). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY. RX PubMed=7835707; DOI=10.1016/0378-1119(94)00718-8; RA Oberg-Welsh C., Welsh M.; RT "Cloning of BSK, a murine FRK homologue with a specific pattern of tissue RT distribution."; RL Gene 152:239-242(1995). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC STRAIN=C57BL/6J; TISSUE=Kidney, Mammary gland, and Skin; 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 [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC STRAIN=FVB/N; TISSUE=Mammary tumor; 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 [5] RP DISRUPTION PHENOTYPE. RX PubMed=12077350; DOI=10.1128/mcb.22.14.5235-5247.2002; RA Chandrasekharan S., Qiu T.H., Alkharouf N., Brantley K., Mitchell J.B., RA Liu E.T.; RT "Characterization of mice deficient in the Src family nonreceptor tyrosine RT kinase Frk/rak."; RL Mol. Cell. Biol. 22:5235-5247(2002). RN [6] RP PHOSPHORYLATION AT TYR-394. RX PubMed=15186217; DOI=10.1042/bj20040285; RA Welsh M., Welsh C., Ekman M., Dixelius J., Hagerkvist R., Anneren C., RA Akerblom B., Mahboobi S., Chandrasekharan S., Liu E.T.; RT "The tyrosine kinase FRK/RAK participates in cytokine-induced islet cell RT cytotoxicity."; RL Biochem. J. 382:261-268(2004). RN [7] RP IDENTIFICATION BY 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). RN [8] RP STRUCTURE BY NMR OF 50-220. RG RIKEN structural genomics initiative (RSGI); RT "Solution structure of the SH3 and SH2 domains of FYN-related kinase."; RL Submitted (OCT-2006) to the PDB data bank. 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 (By similarity). CC {ECO:0000250}. 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 (By similarity). {ECO:0000250}. CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}. Nucleus {ECO:0000250}. CC Note=Predominantly found in the nucleus, with a small fraction found in CC the cell periphery. {ECO:0000250}. CC -!- TISSUE SPECIFICITY: Expressed in intestinal tract, fetal and adult CC islets of Langerhans, kidney, liver and lung. CC {ECO:0000269|PubMed:7733928, ECO:0000269|PubMed:7835707}. CC -!- DISRUPTION PHENOTYPE: Mice are viable and do not show any histological CC abnormalities in epithelial tissues or develop any pathological and/or CC metabolic disorders associated with the failure of epithelial organs. CC {ECO:0000269|PubMed:12077350}. CC -!- SIMILARITY: Belongs to the protein kinase superfamily. Tyr protein CC kinase family. SRC subfamily. {ECO:0000255|PROSITE-ProRule:PRU00159}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; Z48757; CAA88658.1; -; mRNA. DR EMBL; L36132; AAA65197.1; -; mRNA. DR EMBL; AK028855; BAC26155.1; -; mRNA. DR EMBL; AK052614; BAC35063.1; -; mRNA. DR EMBL; AK166379; BAE38741.1; -; mRNA. DR EMBL; BC007137; AAH07137.1; -; mRNA. DR CCDS; CCDS23781.1; -. DR PIR; I49552; I49552. DR RefSeq; NP_001153016.1; NM_001159544.1. DR RefSeq; NP_034367.2; NM_010237.3. DR RefSeq; XP_006512597.1; XM_006512534.3. DR RefSeq; XP_006512598.1; XM_006512535.3. DR RefSeq; XP_006512599.1; XM_006512536.3. DR PDB; 2D8J; NMR; -; A=52-115. DR PDB; 2DLY; NMR; -; A=113-220. DR PDBsum; 2D8J; -. DR PDBsum; 2DLY; -. DR AlphaFoldDB; Q922K9; -. DR BMRB; Q922K9; -. DR SMR; Q922K9; -. DR STRING; 10090.ENSMUSP00000019913; -. DR iPTMnet; Q922K9; -. DR PhosphoSitePlus; Q922K9; -. DR MaxQB; Q922K9; -. DR PaxDb; 10090-ENSMUSP00000130289; -. DR PeptideAtlas; Q922K9; -. DR ProteomicsDB; 267502; -. DR Pumba; Q922K9; -. DR Antibodypedia; 32472; 648 antibodies from 35 providers. DR DNASU; 14302; -. DR Ensembl; ENSMUST00000019913.15; ENSMUSP00000019913.8; ENSMUSG00000019779.16. DR Ensembl; ENSMUST00000170771.3; ENSMUSP00000130289.2; ENSMUSG00000019779.16. DR GeneID; 14302; -. DR KEGG; mmu:14302; -. DR UCSC; uc007euy.2; mouse. DR AGR; MGI:103265; -. DR CTD; 2444; -. DR MGI; MGI:103265; Frk. DR VEuPathDB; HostDB:ENSMUSG00000019779; -. DR eggNOG; KOG0197; Eukaryota. DR GeneTree; ENSGT00940000156987; -. DR HOGENOM; CLU_000288_7_2_1; -. DR InParanoid; Q922K9; -. DR OMA; SSHEGWW; -. DR OrthoDB; 1614410at2759; -. DR PhylomeDB; Q922K9; -. DR TreeFam; TF351634; -. DR Reactome; R-MMU-6798695; Neutrophil degranulation. DR Reactome; R-MMU-8948751; Regulation of PTEN stability and activity. DR BioGRID-ORCS; 14302; 3 hits in 78 CRISPR screens. DR ChiTaRS; Frk; mouse. DR EvolutionaryTrace; Q922K9; -. DR PRO; PR:Q922K9; -. DR Proteomes; UP000000589; Chromosome 10. DR RNAct; Q922K9; Protein. DR Bgee; ENSMUSG00000019779; Expressed in seminal vesicle and 185 other cell types or tissues. DR GO; GO:0005829; C:cytosol; ISO:MGI. DR GO; GO:0031234; C:extrinsic component of cytoplasmic side of plasma membrane; IBA:GO_Central. DR GO; GO:0005654; C:nucleoplasm; ISO:MGI. 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; 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:0000122; P:negative regulation of transcription by RNA polymerase II; ISO:MGI. DR GO; GO:0016310; P:phosphorylation; IEA:UniProtKB-KW. DR GO; GO:0007169; P:transmembrane receptor protein tyrosine kinase signaling pathway; IBA:GO_Central. DR CDD; cd05068; PTKc_Frk_like; 1. DR CDD; cd10369; SH2_Src_Frk; 1. DR CDD; cd11845; SH3_Src_like; 1. DR Gene3D; 3.30.505.10; SH2 domain; 1. DR Gene3D; 2.30.30.40; SH3 Domains; 1. DR Gene3D; 1.10.510.10; Transferase(Phosphotransferase) domain 1; 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 PANTHER; PTHR24418; TYROSINE-PROTEIN KINASE; 1. DR PANTHER; PTHR24418:SF465; TYROSINE-PROTEIN KINASE FRK; 1. 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; SSF56112; Protein kinase-like (PK-like); 1. DR SUPFAM; SSF55550; SH2 domain; 1. DR SUPFAM; SSF50044; SH3-domain; 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. DR Genevisible; Q922K9; MM. PE 1: Evidence at protein level; KW 3D-structure; ATP-binding; Cytoplasm; Kinase; Nucleotide-binding; Nucleus; KW Phosphoprotein; Reference proteome; SH2 domain; SH3 domain; Transferase; KW Tumor suppressor; Tyrosine-protein kinase. FT CHAIN 1..512 FT /note="Tyrosine-protein kinase FRK" FT /id="PRO_0000260826" FT DOMAIN 49..117 FT /note="SH3" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00192" FT DOMAIN 123..215 FT /note="SH2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00191" FT DOMAIN 241..498 FT /note="Protein kinase" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT ACT_SITE 361 FT /note="Proton acceptor" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159, FT ECO:0000255|PROSITE-ProRule:PRU10028" FT BINDING 247..255 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT BINDING 269 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT MOD_RES 185 FT /note="Phosphothreonine" FT /evidence="ECO:0000250|UniProtKB:P42685" FT MOD_RES 394 FT /note="Phosphotyrosine; by autocatalysis" FT /evidence="ECO:0000269|PubMed:15186217" FT CONFLICT 154 FT /note="S -> T (in Ref. 1; CAA88658)" FT /evidence="ECO:0000305" FT CONFLICT 237 FT /note="D -> H (in Ref. 1; CAA88658)" FT /evidence="ECO:0000305" FT CONFLICT 335 FT /note="L -> F (in Ref. 1; CAA88658 and 2; AAA65197)" FT /evidence="ECO:0000305" FT CONFLICT 509 FT /note="N -> K (in Ref. 1; CAA88658 and 2; AAA65197)" FT /evidence="ECO:0000305" FT STRAND 52..58 FT /evidence="ECO:0007829|PDB:2D8J" FT STRAND 63..67 FT /evidence="ECO:0007829|PDB:2D8J" FT STRAND 76..80 FT /evidence="ECO:0007829|PDB:2D8J" FT STRAND 83..91 FT /evidence="ECO:0007829|PDB:2D8J" FT STRAND 103..108 FT /evidence="ECO:0007829|PDB:2D8J" FT TURN 109..111 FT /evidence="ECO:0007829|PDB:2D8J" FT STRAND 112..114 FT /evidence="ECO:0007829|PDB:2D8J" FT HELIX 116..120 FT /evidence="ECO:0007829|PDB:2DLY" FT STRAND 122..124 FT /evidence="ECO:0007829|PDB:2DLY" FT HELIX 130..137 FT /evidence="ECO:0007829|PDB:2DLY" FT STRAND 138..141 FT /evidence="ECO:0007829|PDB:2DLY" FT STRAND 147..151 FT /evidence="ECO:0007829|PDB:2DLY" FT STRAND 153..157 FT /evidence="ECO:0007829|PDB:2DLY" FT STRAND 159..167 FT /evidence="ECO:0007829|PDB:2DLY" FT STRAND 169..176 FT /evidence="ECO:0007829|PDB:2DLY" FT STRAND 178..180 FT /evidence="ECO:0007829|PDB:2DLY" FT STRAND 182..185 FT /evidence="ECO:0007829|PDB:2DLY" FT STRAND 188..192 FT /evidence="ECO:0007829|PDB:2DLY" FT HELIX 193..200 FT /evidence="ECO:0007829|PDB:2DLY" FT STRAND 205..209 FT /evidence="ECO:0007829|PDB:2DLY" SQ SEQUENCE 512 AA; 58844 MW; B79A0BC07B9EC5F8 CRC64; MGSVCVRLWA YLQPFLPCWS QEADKSVVIE NPGAFCPPEA PRSQEPERSH GQYFVALFDY QARTAEDLSF RAGDKLQVLD TSHEGWWLAR HLEKKGTGLG QQLQGYIPSN YVAEDRSLQA EPWFFGAIKR ADAEKQLLYS ENQTGAFLIR ESESQKGDFS LSVLDEGVVK HYRIRRLDEG GFFLTRRKVF STLNEFVNYY TTTSDGLCVK LEKPCLKIQV PTPFDLSYKT ADQWEIDRNS IQLLKRLGSG QFGEVWEGLW NNTTPVAVKT LKPGSMDPND FLREAQIMKS LRHPKLIQLY AVCTLEDPIY IITELMRHGS LQEYLQNDGG SKIHLIQQVD MAAQVASGMA YLESQNYIHR DLAARNVLVG EHNIYKVADF GLARVFKVDN EDIYESKHEI KLPVKWTAPE AIRTNKFSIK SDVWSFGILL YEIITYGKMP YSGMTGAQVI QMLSQNYRLP QPSNCPQQFY SIMLECWNVE PKQRPTFETL HWKLEDYFET DCSYSDTNNF IN //