ID ROS1_HUMAN Reviewed; 2347 AA. AC P08922; Q15368; Q5TDB5; DT 01-NOV-1988, integrated into UniProtKB/Swiss-Prot. DT 20-FEB-2007, sequence version 3. DT 24-JAN-2024, entry version 222. DE RecName: Full=Proto-oncogene tyrosine-protein kinase ROS; DE EC=2.7.10.1 {ECO:0000269|PubMed:11094073, ECO:0000269|PubMed:16885344}; DE AltName: Full=Proto-oncogene c-Ros; DE AltName: Full=Proto-oncogene c-Ros-1; DE AltName: Full=Receptor tyrosine kinase c-ros oncogene 1; DE AltName: Full=c-Ros receptor tyrosine kinase; DE Flags: Precursor; GN Name=ROS1; Synonyms=MCF3, ROS; 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], AND VARIANTS ASN-2213; GLN-2228 AND CYS-2229. RX PubMed=2352949; DOI=10.1073/pnas.87.12.4799; RA Birchmeier C., O'Neill K., Riggs M., Wigler M.; RT "Characterization of ROS1 cDNA from a human glioblastoma cell line."; RL Proc. Natl. Acad. Sci. U.S.A. 87:4799-4803(1990). RN [2] 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 [3] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1790-2260. RX PubMed=3023956; DOI=10.1128/mcb.6.8.3000-3004.1986; RA Matsushime H., Wang L.-H., Shibuya M.; RT "Human c-ros-1 gene homologous to the v-ros sequence of UR2 sarcoma virus RT encodes for a transmembrane receptorlike molecule."; RL Mol. Cell. Biol. 6:3000-3004(1986). RN [4] RP NUCLEOTIDE SEQUENCE [MRNA] OF 1854-2347. RX PubMed=3785223; DOI=10.1128/mcb.6.9.3109-3116.1986; RA Birchmeier C., Birnbaum D., Waitches G., Fasano O., Wigler M.; RT "Characterization of an activated human ros gene."; RL Mol. Cell. Biol. 6:3109-3116(1986). RN [5] RP TISSUE SPECIFICITY. RX PubMed=8143271; DOI=10.1016/0165-4608(94)90128-7; RA Watkins D., Dion F., Poisson M., Delattre J.Y., Rouleau G.A.; RT "Analysis of oncogene expression in primary human gliomas: evidence for RT increased expression of the ros oncogene."; RL Cancer Genet. Cytogenet. 72:130-136(1994). RN [6] RP FUNCTION, INTERACTION WITH VAV3, AND CATALYTIC ACTIVITY. RX PubMed=11094073; DOI=10.1128/mcb.20.24.9212-9224.2000; RA Zeng L., Sachdev P., Yan L., Chan J.L., Trenkle T., McClelland M., RA Welsh J., Wang L.H.; RT "Vav3 mediates receptor protein tyrosine kinase signaling, regulates GTPase RT activity, modulates cell morphology, and induces cell transformation."; RL Mol. Cell. Biol. 20:9212-9224(2000). RN [7] RP DISEASE, CHROMOSOMAL TRANSLOCATION WITH GOPC, AND MUTAGENESIS OF LYS-1980. RX PubMed=12661006; DOI=10.1002/gcc.10207; RA Charest A., Lane K., McMahon K., Park J., Preisinger E., Conroy H., RA Housman D.; RT "Fusion of FIG to the receptor tyrosine kinase ROS in a glioblastoma with RT an interstitial del(6)(q21q21)."; RL Genes Chromosomes Cancer 37:58-71(2003). RN [8] RP PHOSPHORYLATION AT TYR-2274 AND TYR-2334, AND MUTAGENESIS OF TYR-2274 AND RP TYR-2334. RX PubMed=12538861; DOI=10.1073/pnas.242741799; RA Charest A., Kheifets V., Park J., Lane K., McMahon K., Nutt C.L., RA Housman D.; RT "Oncogenic targeting of an activated tyrosine kinase to the Golgi apparatus RT in a glioblastoma."; RL Proc. Natl. Acad. Sci. U.S.A. 100:916-921(2003). RN [9] RP FUNCTION, CATALYTIC ACTIVITY, AND INTERACTION WITH PTPN11. RX PubMed=16885344; DOI=10.1158/0008-5472.can-06-1193; RA Charest A., Wilker E.W., McLaughlin M.E., Lane K., Gowda R., Coven S., RA McMahon K., Kovach S., Feng Y., Yaffe M.B., Jacks T., Housman D.; RT "ROS fusion tyrosine kinase activates a SH2 domain-containing phosphatase- RT 2/phosphatidylinositol 3-kinase/mammalian target of rapamycin signaling RT axis to form glioblastoma in mice."; RL Cancer Res. 66:7473-7481(2006). RN [10] RP VARIANTS [LARGE SCALE ANALYSIS] SER-13; VAL-126; PRO-145; GLN-167; SER-224; RP CYS-338; PRO-370; HIS-419; MET-537; PHE-653; HIS-865; LEU-1109; PHE-1239; RP SER-1353; ARG-1370; GLY-1506; HIS-1776; LYS-1902; ASN-1999; ARG-2003; RP SER-2138; ASN-2203; GLU-2213; ASN-2213; GLN-2228; CYS-2229 AND LYS-2240. 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: Receptor tyrosine kinase (RTK) that plays a role in CC epithelial cell differentiation and regionalization of the proximal CC epididymal epithelium. NELL2 is an endogenous ligand for ROS1. Upon CC endogenous stimulation by NELL2, ROS1 activates the intracellular CC signaling pathway and triggers epididymal epithelial differentiation CC and subsequent sperm maturation (By similarity). May activate several CC downstream signaling pathways related to cell differentiation, CC proliferation, growth and survival including the PI3 kinase-mTOR CC signaling pathway. Mediates the phosphorylation of PTPN11, an activator CC of this pathway. May also phosphorylate and activate the transcription CC factor STAT3 to control anchorage-independent cell growth. Mediates the CC phosphorylation and the activation of VAV3, a guanine nucleotide CC exchange factor regulating cell morphology. May activate other CC downstream signaling proteins including AKT1, MAPK1, MAPK3, IRS1 and CC PLCG2. {ECO:0000250|UniProtKB:Q78DX7, ECO:0000269|PubMed:11094073, CC ECO:0000269|PubMed:16885344}. 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=2.7.10.1; CC Evidence={ECO:0000269|PubMed:11094073, ECO:0000269|PubMed:16885344}; CC -!- ACTIVITY REGULATION: Inhibited by dephosphorylation by PTPN6. CC {ECO:0000250|UniProtKB:Q78DX7}. CC -!- SUBUNIT: multimerize in the presence of ligand...Interacts with PTPN6 CC (via SH2 1 domain); the interaction is direct and promotes ROS1 CC dephosphorylation (By similarity). Interacts with PTPN11; may activate CC the PI3 kinase-mTOR signaling pathway (PubMed:16885344). Interacts with CC VAV3; constitutive interaction mediating VAV3 phosphorylation CC (PubMed:11094073). {ECO:0000250|UniProtKB:Q78DX7, CC ECO:0000269|PubMed:11094073, ECO:0000269|PubMed:16885344}. CC -!- INTERACTION: CC P08922; P18031: PTPN1; NbExp=3; IntAct=EBI-7371065, EBI-968788; CC P08922; P29350: PTPN6; NbExp=2; IntAct=EBI-7371065, EBI-78260; CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000305}; Single-pass type I CC membrane protein {ECO:0000305}. CC -!- TISSUE SPECIFICITY: Expressed in brain. Expression is increased in CC primary gliomas. {ECO:0000269|PubMed:8143271}. CC -!- PTM: Phosphorylated. Probably autophosphorylates. Phosphorylation at CC Tyr-2274 is required for the interaction with PTPN6 that mediates ROS1 CC dephosphorylation. Phosphorylation at Tyr-2274 stimulates the kinase CC activity and the activation of the ERK1 signaling cascade (By CC similarity). Phosphorylation at Tyr-2274 and/or Tyr-2334 recruits CC PTPN11 (PubMed:12538861). {ECO:0000250|UniProtKB:Q78DX7, CC ECO:0000269|PubMed:12538861}. CC -!- DISEASE: Note=A chromosomal aberration involving ROS1 is found in a CC glioblastoma multiforme sample. An intra-chromosomal deletion CC del(6)(q21q21) is responsible for the formation of GOPC-ROS1 chimeric CC protein which is localized to the Golgi and has a constitutive receptor CC tyrosine kinase activity. A SLC34A2-ROS1 chimeric protein produced in CC non-small cell lung cancer cells also retains a constitutive kinase CC activity. A third type of chimeric protein CD74-ROS1 was also CC identified in those cells. {ECO:0000269|PubMed:12661006}. CC -!- SIMILARITY: Belongs to the protein kinase superfamily. Tyr protein CC kinase family. Insulin receptor subfamily. {ECO:0000255|PROSITE- CC 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; M34353; AAA60278.1; -; mRNA. DR EMBL; Z98880; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AL132671; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; M13599; AAA60277.1; -; Genomic_DNA. DR EMBL; M13368; AAA60277.1; JOINED; Genomic_DNA. DR EMBL; M13591; AAA60277.1; JOINED; Genomic_DNA. DR EMBL; M13592; AAA60277.1; JOINED; Genomic_DNA. DR EMBL; M13593; AAA60277.1; JOINED; Genomic_DNA. DR EMBL; M13594; AAA60277.1; JOINED; Genomic_DNA. DR EMBL; M13595; AAA60277.1; JOINED; Genomic_DNA. DR EMBL; M13596; AAA60277.1; JOINED; Genomic_DNA. DR EMBL; M13597; AAA60277.1; JOINED; Genomic_DNA. DR EMBL; M13598; AAA60277.1; JOINED; Genomic_DNA. DR EMBL; M13880; AAA36580.1; -; mRNA. DR CCDS; CCDS5116.1; -. DR PIR; A35512; TVHURS. DR RefSeq; NP_002935.2; NM_002944.2. DR PDB; 3ZBF; X-ray; 2.20 A; A=1934-2232. DR PDB; 4UXL; X-ray; 2.40 A; A=1934-2232. DR PDB; 7Z5W; X-ray; 2.25 A; A/B=1930-2256. DR PDB; 7Z5X; X-ray; 2.04 A; A/B=1930-2256. DR PDBsum; 3ZBF; -. DR PDBsum; 4UXL; -. DR PDBsum; 7Z5W; -. DR PDBsum; 7Z5X; -. DR AlphaFoldDB; P08922; -. DR SMR; P08922; -. DR BioGRID; 112025; 91. DR IntAct; P08922; 99. DR MINT; P08922; -. DR STRING; 9606.ENSP00000357494; -. DR BindingDB; P08922; -. DR ChEMBL; CHEMBL5568; -. DR DrugBank; DB08865; Crizotinib. DR DrugBank; DB11986; Entrectinib. DR DrugBank; DB12010; Fostamatinib. DR DrugCentral; P08922; -. DR GuidetoPHARMACOLOGY; 1840; -. DR GlyCosmos; P08922; 33 sites, 1 glycan. DR GlyGen; P08922; 33 sites, 1 O-linked glycan (3 sites). DR iPTMnet; P08922; -. DR PhosphoSitePlus; P08922; -. DR BioMuta; ROS1; -. DR DMDM; 126302596; -. DR CPTAC; CPTAC-3062; -. DR EPD; P08922; -. DR jPOST; P08922; -. DR MassIVE; P08922; -. DR PaxDb; 9606-ENSP00000357494; -. DR PeptideAtlas; P08922; -. DR ProteomicsDB; 52177; -. DR ABCD; P08922; 2 sequenced antibodies. DR Antibodypedia; 32541; 768 antibodies from 36 providers. DR DNASU; 6098; -. DR Ensembl; ENST00000368508.7; ENSP00000357494.3; ENSG00000047936.11. DR GeneID; 6098; -. DR KEGG; hsa:6098; -. DR UCSC; uc003pxp.2; human. DR AGR; HGNC:10261; -. DR CTD; 6098; -. DR DisGeNET; 6098; -. DR GeneCards; ROS1; -. DR HGNC; HGNC:10261; ROS1. DR HPA; ENSG00000047936; Group enriched (epididymis, lung). DR MalaCards; ROS1; -. DR MIM; 165020; gene. DR neXtProt; NX_P08922; -. DR OpenTargets; ENSG00000047936; -. DR PharmGKB; PA34633; -. DR VEuPathDB; HostDB:ENSG00000047936; -. DR eggNOG; KOG1095; Eukaryota. DR GeneTree; ENSGT00940000160831; -. DR InParanoid; P08922; -. DR OrthoDB; 4577877at2759; -. DR PhylomeDB; P08922; -. DR TreeFam; TF351636; -. DR BRENDA; 2.7.10.1; 2681. DR PathwayCommons; P08922; -. DR SignaLink; P08922; -. DR SIGNOR; P08922; -. DR BioGRID-ORCS; 6098; 8 hits in 1191 CRISPR screens. DR ChiTaRS; ROS1; human. DR GeneWiki; ROS1_(gene); -. DR GenomeRNAi; 6098; -. DR Pharos; P08922; Tclin. DR PRO; PR:P08922; -. DR Proteomes; UP000005640; Chromosome 6. DR RNAct; P08922; Protein. DR Bgee; ENSG00000047936; Expressed in upper lobe of left lung and 59 other cell types or tissues. DR ExpressionAtlas; P08922; baseline and differential. DR GO; GO:0016020; C:membrane; TAS:ProtInc. DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell. DR GO; GO:0043235; C:receptor complex; IBA:GO_Central. DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW. DR GO; GO:0019903; F:protein phosphatase binding; IPI:UniProtKB. DR GO; GO:0004713; F:protein tyrosine kinase activity; IDA:UniProtKB. DR GO; GO:0004714; F:transmembrane receptor protein tyrosine kinase activity; IBA:GO_Central. DR GO; GO:0030154; P:cell differentiation; ISS:UniProtKB. DR GO; GO:0002066; P:columnar/cuboidal epithelial cell development; ISS:UniProtKB. DR GO; GO:0006468; P:protein phosphorylation; IDA:UniProtKB. DR GO; GO:0001558; P:regulation of cell growth; IDA:UniProtKB. DR GO; GO:0070372; P:regulation of ERK1 and ERK2 cascade; ISS:UniProtKB. DR GO; GO:0032006; P:regulation of TOR signaling; IDA:UniProtKB. DR GO; GO:0007283; P:spermatogenesis; ISS:UniProtKB. DR GO; GO:0007169; P:transmembrane receptor protein tyrosine kinase signaling pathway; IBA:GO_Central. DR CDD; cd00063; FN3; 7. DR CDD; cd05044; PTKc_c-ros; 1. DR Gene3D; 2.60.40.10; Immunoglobulins; 7. DR Gene3D; 2.120.10.30; TolB, C-terminal domain; 3. DR Gene3D; 1.10.510.10; Transferase(Phosphotransferase) domain 1; 1. DR InterPro; IPR011042; 6-blade_b-propeller_TolB-like. DR InterPro; IPR003961; FN3_dom. DR InterPro; IPR036116; FN3_sf. DR InterPro; IPR013783; Ig-like_fold. DR InterPro; IPR011009; Kinase-like_dom_sf. DR InterPro; IPR000033; LDLR_classB_rpt. DR InterPro; IPR000719; Prot_kinase_dom. DR InterPro; IPR017441; Protein_kinase_ATP_BS. DR InterPro; IPR001245; Ser-Thr/Tyr_kinase_cat_dom. DR InterPro; IPR008266; Tyr_kinase_AS. DR InterPro; IPR020635; Tyr_kinase_cat_dom. DR InterPro; IPR002011; Tyr_kinase_rcpt_2_CS. DR PANTHER; PTHR24416:SF527; PROTO-ONCOGENE TYROSINE-PROTEIN KINASE ROS; 1. DR PANTHER; PTHR24416; TYROSINE-PROTEIN KINASE RECEPTOR; 1. DR Pfam; PF00041; fn3; 3. DR Pfam; PF07714; PK_Tyr_Ser-Thr; 1. DR PRINTS; PR00109; TYRKINASE. DR SMART; SM00060; FN3; 9. DR SMART; SM00135; LY; 4. DR SMART; SM00219; TyrKc; 1. DR SUPFAM; SSF49265; Fibronectin type III; 5. DR SUPFAM; SSF56112; Protein kinase-like (PK-like); 1. DR SUPFAM; SSF63825; YWTD domain; 3. DR PROSITE; PS50853; FN3; 9. DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1. DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1. DR PROSITE; PS00109; PROTEIN_KINASE_TYR; 1. DR PROSITE; PS00239; RECEPTOR_TYR_KIN_II; 1. DR Genevisible; P08922; HS. PE 1: Evidence at protein level; KW 3D-structure; ATP-binding; Cell membrane; Chromosomal rearrangement; KW Glycoprotein; Kinase; Membrane; Nucleotide-binding; Phosphoprotein; KW Proto-oncogene; Receptor; Reference proteome; Repeat; Signal; Transferase; KW Transmembrane; Transmembrane helix; Tyrosine-protein kinase. FT SIGNAL 1..27 FT /evidence="ECO:0000255" FT CHAIN 28..2347 FT /note="Proto-oncogene tyrosine-protein kinase ROS" FT /id="PRO_0000016722" FT TOPO_DOM 28..1859 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 1860..1882 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 1883..2347 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT DOMAIN 101..196 FT /note="Fibronectin type-III 1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00316" FT DOMAIN 197..285 FT /note="Fibronectin type-III 2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00316" FT DOMAIN 557..671 FT /note="Fibronectin type-III 3" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00316" FT DOMAIN 947..1042 FT /note="Fibronectin type-III 4" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00316" FT DOMAIN 1043..1150 FT /note="Fibronectin type-III 5" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00316" FT DOMAIN 1450..1556 FT /note="Fibronectin type-III 6" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00316" FT DOMAIN 1557..1656 FT /note="Fibronectin type-III 7" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00316" FT DOMAIN 1658..1751 FT /note="Fibronectin type-III 8" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00316" FT DOMAIN 1752..1854 FT /note="Fibronectin type-III 9" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00316" FT DOMAIN 1945..2222 FT /note="Protein kinase" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT REGION 2284..2311 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT ACT_SITE 2079 FT /note="Proton acceptor" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159, FT ECO:0000255|PROSITE-ProRule:PRU10028" FT BINDING 1951..1959 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT BINDING 1980 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000305" FT SITE 1852..1853 FT /note="Breakpoint for translocation to form SLC34A2-ROS1 FT and CD74-ROS1 fusion proteins" FT /evidence="ECO:0000269|PubMed:12661006" FT SITE 1880..1881 FT /note="Breakpoint for translocation to form GOPC-ROS1 FT fusion protein" FT /evidence="ECO:0000269|PubMed:12661006" FT MOD_RES 2274 FT /note="Phosphotyrosine; by autocatalysis" FT /evidence="ECO:0000305|PubMed:12538861" FT MOD_RES 2334 FT /note="Phosphotyrosine; by autocatalysis" FT /evidence="ECO:0000305|PubMed:12538861" FT CARBOHYD 52 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 114 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 123 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 324 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 352 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 396 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 471 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 607 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 628 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 706 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 714 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 732 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 939 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 961 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 1015 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 1087 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 1090 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 1095 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 1211 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 1272 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 1330 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 1458 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 1461 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 1474 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 1499 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 1565 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 1669 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 1715 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 1738 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 1808 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT VARIANT 13 FT /note="N -> S (in dbSNP:rs45606237)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_041442" FT VARIANT 126 FT /note="G -> V (in dbSNP:rs34245787)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_041443" FT VARIANT 145 FT /note="T -> P (in dbSNP:rs1998206)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_030648" FT VARIANT 167 FT /note="R -> Q (in dbSNP:rs2243380)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_030649" FT VARIANT 224 FT /note="P -> S (in dbSNP:rs55959124)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_041444" FT VARIANT 338 FT /note="Y -> C (in dbSNP:rs55707658)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_041445" FT VARIANT 370 FT /note="S -> P (in dbSNP:rs56274823)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_041446" FT VARIANT 419 FT /note="Y -> H (in a gastric adenocarcinoma sample; somatic FT mutation; dbSNP:rs1444274116)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_041447" FT VARIANT 537 FT /note="I -> M (in dbSNP:rs28639589)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_041448" FT VARIANT 653 FT /note="S -> F (in dbSNP:rs34203286)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_041449" FT VARIANT 790 FT /note="N -> S (in dbSNP:rs34582164)" FT /id="VAR_049712" FT VARIANT 865 FT /note="Q -> H (in a lung large cell carcinoma sample; FT somatic mutation)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_041450" FT VARIANT 1109 FT /note="S -> L (in dbSNP:rs2229079)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_030650" FT VARIANT 1239 FT /note="Y -> F (in dbSNP:rs56192249)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_041451" FT VARIANT 1353 FT /note="Y -> S (in dbSNP:rs35269727)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_041452" FT VARIANT 1370 FT /note="C -> R (in dbSNP:rs36106063)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_041453" FT VARIANT 1439 FT /note="F -> S (in dbSNP:rs17079086)" FT /id="VAR_030651" FT VARIANT 1506 FT /note="R -> G (in dbSNP:rs35841892)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_041454" FT VARIANT 1776 FT /note="D -> H (in dbSNP:rs12664076)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_030652" FT VARIANT 1902 FT /note="E -> K (in dbSNP:rs9489124)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_030653" FT VARIANT 1999 FT /note="H -> N (in dbSNP:rs45569132)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_041455" FT VARIANT 2003 FT /note="K -> R (in a colorectal adenocarcinoma sample; FT somatic mutation)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_041456" FT VARIANT 2039 FT /note="R -> H (in dbSNP:rs3752566)" FT /id="VAR_030654" FT VARIANT 2138 FT /note="F -> S (in a gastric adenocarcinoma sample; somatic FT mutation)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_041457" FT VARIANT 2203 FT /note="D -> N (in dbSNP:rs556427413)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_041458" FT VARIANT 2213 FT /note="D -> E (in dbSNP:rs75510639)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_041459" FT VARIANT 2213 FT /note="D -> N (in dbSNP:rs529038)" FT /evidence="ECO:0000269|PubMed:17344846, FT ECO:0000269|PubMed:2352949" FT /id="VAR_030655" FT VARIANT 2228 FT /note="K -> Q (in dbSNP:rs529156)" FT /evidence="ECO:0000269|PubMed:17344846, FT ECO:0000269|PubMed:2352949" FT /id="VAR_041460" FT VARIANT 2229 FT /note="S -> C (in dbSNP:rs619203)" FT /evidence="ECO:0000269|PubMed:17344846, FT ECO:0000269|PubMed:2352949" FT /id="VAR_030656" FT VARIANT 2240 FT /note="N -> K (in dbSNP:rs210968)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_030657" FT VARIANT 2328 FT /note="K -> R (in dbSNP:rs35932630)" FT /id="VAR_049713" FT MUTAGEN 1980 FT /note="K->M: Loss of kinase activity." FT /evidence="ECO:0000269|PubMed:12661006" FT MUTAGEN 2274 FT /note="Y->F: Loss of phosphorylation at Y-2274 and loss of FT interaction with PTPN11." FT /evidence="ECO:0000269|PubMed:12538861" FT MUTAGEN 2334 FT /note="Y->F: Loss of phosphorylation at Y-2334 and loss of FT interaction with PTPN11." FT /evidence="ECO:0000269|PubMed:12538861" FT CONFLICT 2246..2260 FT /note="EDGDVICLNSDDIMP -> KFDSSEFSSFRCTVN (in Ref. 3; FT AAA60277)" FT /evidence="ECO:0000305" FT CONFLICT 2262 FT /note="A -> V (in Ref. 1; AAA60278)" FT /evidence="ECO:0000305" FT HELIX 1942..1944 FT /evidence="ECO:0007829|PDB:7Z5X" FT STRAND 1945..1952 FT /evidence="ECO:0007829|PDB:7Z5X" FT TURN 1954..1956 FT /evidence="ECO:0007829|PDB:7Z5X" FT STRAND 1959..1966 FT /evidence="ECO:0007829|PDB:7Z5X" FT STRAND 1969..1971 FT /evidence="ECO:0007829|PDB:7Z5X" FT STRAND 1974..1982 FT /evidence="ECO:0007829|PDB:7Z5X" FT HELIX 1988..2001 FT /evidence="ECO:0007829|PDB:7Z5X" FT STRAND 2012..2016 FT /evidence="ECO:0007829|PDB:7Z5X" FT STRAND 2018..2027 FT /evidence="ECO:0007829|PDB:7Z5X" FT HELIX 2034..2043 FT /evidence="ECO:0007829|PDB:7Z5X" FT HELIX 2053..2072 FT /evidence="ECO:0007829|PDB:7Z5X" FT HELIX 2082..2084 FT /evidence="ECO:0007829|PDB:7Z5X" FT STRAND 2085..2088 FT /evidence="ECO:0007829|PDB:7Z5X" FT STRAND 2090..2094 FT /evidence="ECO:0007829|PDB:7Z5X" FT STRAND 2098..2100 FT /evidence="ECO:0007829|PDB:7Z5X" FT HELIX 2125..2127 FT /evidence="ECO:0007829|PDB:7Z5X" FT HELIX 2130..2135 FT /evidence="ECO:0007829|PDB:7Z5X" FT HELIX 2140..2155 FT /evidence="ECO:0007829|PDB:7Z5X" FT STRAND 2161..2165 FT /evidence="ECO:0007829|PDB:7Z5W" FT HELIX 2167..2175 FT /evidence="ECO:0007829|PDB:7Z5X" FT HELIX 2188..2197 FT /evidence="ECO:0007829|PDB:7Z5X" FT HELIX 2202..2204 FT /evidence="ECO:0007829|PDB:7Z5X" FT HELIX 2208..2224 FT /evidence="ECO:0007829|PDB:7Z5X" SQ SEQUENCE 2347 AA; 263915 MW; 98902B9A59ACB8F5 CRC64; MKNIYCLIPK LVNFATLGCL WISVVQCTVL NSCLKSCVTN LGQQLDLGTP HNLSEPCIQG CHFWNSVDQK NCALKCRESC EVGCSSAEGA YEEEVLENAD LPTAPFASSI GSHNMTLRWK SANFSGVKYI IQWKYAQLLG SWTYTKTVSR PSYVVKPLHP FTEYIFRVVW IFTAQLQLYS PPSPSYRTHP HGVPETAPLI RNIESSSPDT VEVSWDPPQF PGGPILGYNL RLISKNQKLD AGTQRTSFQF YSTLPNTIYR FSIAAVNEVG EGPEAESSIT TSSSAVQQEE QWLFLSRKTS LRKRSLKHLV DEAHCLRLDA IYHNITGISV DVHQQIVYFS EGTLIWAKKA ANMSDVSDLR IFYRGSGLIS SISIDWLYQR MYFIMDELVC VCDLENCSNI EEITPPSISA PQKIVADSYN GYVFYLLRDG IYRADLPVPS GRCAEAVRIV ESCTLKDFAI KPQAKRIIYF NDTAQVFMST FLDGSASHLI LPRIPFADVK SFACENNDFL VTDGKVIFQQ DALSFNEFIV GCDLSHIEEF GFGNLVIFGS SSQLHPLPGR PQELSVLFGS HQALVQWKPP ALAIGANVIL ISDIIELFEL GPSAWQNWTY EVKVSTQDPP EVTHIFLNIS GTMLNVPELQ SAMKYKVSVR ASSPKRPGPW SEPSVGTTLV PASEPPFIMA VKEDGLWSKP LNSFGPGEFL SSDIGNVSDM DWYNNSLYYS DTKGDVFVWL LNGTDISENY HLPSIAGAGA LAFEWLGHFL YWAGKTYVIQ RQSVLTGHTD IVTHVKLLVN DMVVDSVGGY LYWTTLYSVE STRLNGESSL VLQTQPWFSG KKVIALTLDL SDGLLYWLVQ DSQCIHLYTA VLRGQSTGDT TITEFAAWST SEISQNALMY YSGRLFWING FRIITTQEIG QKTSVSVLEP ARFNQFTIIQ TSLKPLPGNF SFTPKVIPDS VQESSFRIEG NASSFQILWN GPPAVDWGVV FYSVEFSAHS KFLASEQHSL PVFTVEGLEP YALFNLSVTP YTYWGKGPKT SLSLRAPETV PSAPENPRIF ILPSGKCCNK NEVVVEFRWN KPKHENGVLT KFEIFYNISN QSITNKTCED WIAVNVTPSV MSFQLEGMSP RCFIAFQVRA FTSKGPGPYA DVVKSTTSEI NPFPHLITLL GNKIVFLDMD QNQVVWTFSA ERVISAVCYT ADNEMGYYAE GDSLFLLHLH NRSSSELFQD SLVFDITVIT IDWISRHLYF ALKESQNGMQ VFDVDLEHKV KYPREVKIHN RNSTIISFSV YPLLSRLYWT EVSNFGYQMF YYSIISHTLH RILQPTATNQ QNKRNQCSCN VTEFELSGAM AIDTSNLEKP LIYFAKAQEI WAMDLEGCQC WRVITVPAML AGKTLVSLTV DGDLIYWIIT AKDSTQIYQA KKGNGAIVSQ VKALRSRHIL AYSSVMQPFP DKAFLSLASD TVEPTILNAT NTSLTIRLPL AKTNLTWYGI TSPTPTYLVY YAEVNDRKNS SDLKYRILEF QDSIALIEDL QPFSTYMIQI AVKNYYSDPL EHLPPGKEIW GKTKNGVPEA VQLINTTVRS DTSLIISWRE SHKPNGPKES VRYQLAISHL ALIPETPLRQ SEFPNGRLTL LVTRLSGGNI YVLKVLACHS EEMWCTESHP VTVEMFNTPE KPYSLVPENT SLQFNWKAPL NVNLIRFWVE LQKWKYNEFY HVKTSCSQGP AYVCNITNLQ PYTSYNVRVV VVYKTGENST SLPESFKTKA GVPNKPGIPK LLEGSKNSIQ WEKAEDNGCR ITYYILEIRK STSNNLQNQN LRWKMTFNGS CSSVCTWKSK NLKGIFQFRV VAANNLGFGE YSGISENIIL VGDDFWIPET SFILTIIVGI FLVVTIPLTF VWHRRLKNQK SAKEGVTVLI NEDKELAELR GLAAGVGLAN ACYAIHTLPT QEEIENLPAF PREKLTLRLL LGSGAFGEVY EGTAVDILGV GSGEIKVAVK TLKKGSTDQE KIEFLKEAHL MSKFNHPNIL KQLGVCLLNE PQYIILELME GGDLLTYLRK ARMATFYGPL LTLVDLVDLC VDISKGCVYL ERMHFIHRDL AARNCLVSVK DYTSPRIVKI GDFGLARDIY KNDYYRKRGE GLLPVRWMAP ESLMDGIFTT QSDVWSFGIL IWEILTLGHQ PYPAHSNLDV LNYVQTGGRL EPPRNCPDDL WNLMTQCWAQ EPDQRPTFHR IQDQLQLFRN FFLNSIYKSR DEANNSGVIN ESFEGEDGDV ICLNSDDIMP VALMETKNRE GLNYMVLATE CGQGEEKSEG PLGSQESESC GLRKEEKEPH ADKDFCQEKQ VAYCPSGKPE GLNYACLTHS GYGDGSD //