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 16-SEP-2015, entry version 121. 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; OC Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Sciurognathi; OC Muroidea; Muridae; Murinae; Mus; Mus. OX NCBI_TaxID=10090; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY. RC STRAIN=BALB/c; 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 RT tissue 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., RA Davis M.J., Wilming L.G., Aidinis V., Allen J.E., RA Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., RA Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., RA Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., RA Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., RA di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., RA Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., RA Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., RA Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., RA Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., RA Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., RA Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., RA Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., RA Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., RA Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., RA Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., RA Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., RA Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., RA 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., RA Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., RA Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., RA Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., RA Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., RA Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., RA Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., RA Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., RA Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., RA Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., RA Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., RA Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., RA 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 RT project: 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., RA Mitchell J.B., Liu E.T.; RT "Characterization of mice deficient in the Src family nonreceptor RT tyrosine 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 RT cell 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 RT 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 RT 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 CC turn prevents its ubiquitination and degradation, possibly by CC reducing its binding to NEDD4. May function as a tumor suppressor CC (By similarity). {ECO:0000250}. CC -!- CATALYTIC ACTIVITY: ATP + a [protein]-L-tyrosine = ADP + a CC [protein]-L-tyrosine phosphate. {ECO:0000255|PROSITE- CC ProRule:PRU10028}. CC -!- SUBUNIT: Interacts (via the SH3-domain) with PTEN. Interacts with CC RB1 (By similarity). {ECO:0000250}. CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}. Nucleus CC {ECO:0000250}. Note=Predominantly found in the nucleus, with a CC small fraction found in 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 CC histological abnormalities in epithelial tissues or develop any CC pathological and/or metabolic disorders associated with the CC failure of epithelial organs. {ECO:0000269|PubMed:12077350}. CC -!- SIMILARITY: Belongs to the protein kinase superfamily. Tyr protein CC kinase family. SRC subfamily. {ECO:0000255|PROSITE- CC ProRule:PRU00159}. CC -!- SIMILARITY: Contains 1 protein kinase domain. CC {ECO:0000255|PROSITE-ProRule:PRU00159}. CC -!- SIMILARITY: Contains 1 SH2 domain. {ECO:0000255|PROSITE- CC ProRule:PRU00191}. CC -!- SIMILARITY: Contains 1 SH3 domain. {ECO:0000255|PROSITE- CC ProRule:PRU00192}. 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_006512534.2. DR RefSeq; XP_006512598.1; XM_006512535.2. DR RefSeq; XP_006512599.1; XM_006512536.2. DR UniGene; Mm.332432; -. DR PDB; 2D8J; NMR; -; A=52-115. DR PDB; 2DLY; NMR; -; A=113-220. DR PDBsum; 2D8J; -. DR PDBsum; 2DLY; -. DR ProteinModelPortal; Q922K9; -. DR SMR; Q922K9; 49-223, 232-498. DR STRING; 10090.ENSMUSP00000019913; -. DR PhosphoSite; Q922K9; -. DR MaxQB; Q922K9; -. DR PaxDb; Q922K9; -. DR PRIDE; Q922K9; -. DR Ensembl; ENSMUST00000019913; ENSMUSP00000019913; ENSMUSG00000019779. DR Ensembl; ENSMUST00000170771; ENSMUSP00000130289; ENSMUSG00000019779. DR GeneID; 14302; -. DR KEGG; mmu:14302; -. DR UCSC; uc007euy.2; mouse. DR CTD; 2444; -. DR MGI; MGI:103265; Frk. DR eggNOG; COG0515; -. DR GeneTree; ENSGT00760000118938; -. DR HOGENOM; HOG000233858; -. DR HOVERGEN; HBG008761; -. DR InParanoid; Q922K9; -. DR KO; K08892; -. DR OMA; PYLPCLS; -. DR OrthoDB; EOG7GTT2V; -. DR PhylomeDB; Q922K9; -. DR TreeFam; TF351634; -. DR EvolutionaryTrace; Q922K9; -. DR NextBio; 285723; -. DR PRO; PR:Q922K9; -. DR Proteomes; UP000000589; Chromosome 10. DR Bgee; Q922K9; -. DR CleanEx; MM_FRK; -. DR Genevisible; Q922K9; MM. DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell. DR GO; GO:0070062; C:extracellular exosome; ISO:MGI. DR GO; GO:0031234; C:extrinsic component of cytoplasmic side of plasma membrane; IBA:GO_Central. DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell. 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:0005102; F:receptor binding; IBA:GO_Central. DR GO; GO:0030036; P:actin cytoskeleton organization; IBA:GO_Central. DR GO; GO:0030154; P:cell differentiation; IBA:GO_Central. DR GO; GO:0016477; P:cell migration; IBA:GO_Central. DR GO; GO:0045087; P:innate immune response; IBA:GO_Central. DR GO; GO:0038083; P:peptidyl-tyrosine autophosphorylation; IBA:GO_Central. DR GO; GO:0042127; P:regulation of cell proliferation; IBA:GO_Central. DR GO; GO:0007169; P:transmembrane receptor protein tyrosine kinase signaling pathway; IBA:GO_Central. DR Gene3D; 3.30.505.10; -; 1. DR InterPro; IPR011009; Kinase-like_dom. 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; IPR001452; SH3_domain. DR InterPro; IPR008266; Tyr_kinase_AS. DR InterPro; IPR020635; Tyr_kinase_cat_dom. DR Pfam; PF07714; Pkinase_Tyr; 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 3D-structure; ATP-binding; Complete proteome; Cytoplasm; Kinase; KW Nucleotide-binding; Nucleus; Phosphoprotein; Reference proteome; KW SH2 domain; SH3 domain; Transferase; Tumor suppressor; KW Tyrosine-protein kinase. FT CHAIN 1 512 Tyrosine-protein kinase FRK. FT /FTId=PRO_0000260826. FT DOMAIN 42 117 SH3. {ECO:0000255|PROSITE- FT ProRule:PRU00192}. FT DOMAIN 123 215 SH2. {ECO:0000255|PROSITE- FT ProRule:PRU00191}. FT DOMAIN 241 498 Protein kinase. {ECO:0000255|PROSITE- FT ProRule:PRU00159}. FT NP_BIND 247 255 ATP. {ECO:0000255|PROSITE- FT ProRule:PRU00159}. FT ACT_SITE 361 361 Proton acceptor. {ECO:0000255|PROSITE- FT ProRule:PRU00159, ECO:0000255|PROSITE- FT ProRule:PRU10028}. FT BINDING 269 269 ATP. {ECO:0000255|PROSITE- FT ProRule:PRU00159}. FT MOD_RES 185 185 Phosphothreonine. FT {ECO:0000250|UniProtKB:P42685}. FT MOD_RES 394 394 Phosphotyrosine; by autocatalysis. FT {ECO:0000269|PubMed:15186217}. FT CONFLICT 154 154 S -> T (in Ref. 1; CAA88658). FT {ECO:0000305}. FT CONFLICT 237 237 D -> H (in Ref. 1; CAA88658). FT {ECO:0000305}. FT CONFLICT 335 335 L -> F (in Ref. 1; CAA88658 and 2; FT AAA65197). {ECO:0000305}. FT CONFLICT 509 509 N -> K (in Ref. 1; CAA88658 and 2; FT AAA65197). {ECO:0000305}. FT STRAND 52 58 {ECO:0000244|PDB:2D8J}. FT STRAND 63 67 {ECO:0000244|PDB:2D8J}. FT STRAND 76 80 {ECO:0000244|PDB:2D8J}. FT STRAND 83 91 {ECO:0000244|PDB:2D8J}. FT STRAND 103 108 {ECO:0000244|PDB:2D8J}. FT TURN 109 111 {ECO:0000244|PDB:2D8J}. FT STRAND 112 114 {ECO:0000244|PDB:2D8J}. FT HELIX 116 120 {ECO:0000244|PDB:2DLY}. FT STRAND 122 124 {ECO:0000244|PDB:2DLY}. FT HELIX 130 137 {ECO:0000244|PDB:2DLY}. FT STRAND 138 141 {ECO:0000244|PDB:2DLY}. FT STRAND 147 151 {ECO:0000244|PDB:2DLY}. FT STRAND 153 157 {ECO:0000244|PDB:2DLY}. FT STRAND 159 167 {ECO:0000244|PDB:2DLY}. FT STRAND 169 176 {ECO:0000244|PDB:2DLY}. FT STRAND 178 180 {ECO:0000244|PDB:2DLY}. FT STRAND 182 185 {ECO:0000244|PDB:2DLY}. FT STRAND 188 192 {ECO:0000244|PDB:2DLY}. FT HELIX 193 200 {ECO:0000244|PDB:2DLY}. FT STRAND 205 209 {ECO:0000244|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 //