ROS1_HUMAN
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 03-AUG-2022, entry version 214.
DE RecName: Full=Proto-oncogene tyrosine-protein kinase ROS;
DE EC=2.7.10.1 {ECO:0000269|PubMed:11094073};
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 IN VAV3 ACTIVATION, 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 IN CELL PROLIFERATION AND DIFFERENTIATION, FUNCTION IN
RP PHOSPHORYLATION OF PTPN11, 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: Orphan receptor tyrosine kinase (RTK) that plays a role in
CC epithelial cell differentiation and regionalization of the proximal
CC epididymal epithelium. May activate several downstream signaling
CC pathways related to cell differentiation, proliferation, growth and
CC survival including the PI3 kinase-mTOR signaling pathway. Mediates the
CC phosphorylation of PTPN11, an activator of this pathway. May also
CC phosphorylate and activate the transcription factor STAT3 to control
CC anchorage-independent cell growth. Mediates the phosphorylation and the
CC activation of VAV3, a guanine nucleotide exchange factor regulating
CC cell morphology. May activate other downstream signaling proteins
CC including AKT1, MAPK1, MAPK3, IRS1 and PLCG2.
CC {ECO:0000269|PubMed:11094073, 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:0000255|PROSITE-ProRule:PRU10028,
CC ECO:0000269|PubMed:11094073};
CC -!- ACTIVITY REGULATION: Inhibited by dephosphorylation by PTPN6.
CC {ECO:0000250}.
CC -!- SUBUNIT: Interacts with PTPN6 (via SH2 1 domain); the interaction is
CC direct and promotes ROS1 dephosphorylation (By similarity). Interacts
CC with PTPN11; may activate the PI3 kinase-mTOR signaling pathway.
CC Interacts with VAV3; constitutive interaction mediating VAV3
CC phosphorylation. {ECO:0000250, ECO:0000269|PubMed:11094073,
CC 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 (By similarity). Phosphorylation at Tyr-2274
CC stimulates the kinase activity and the activation of the ERK1 signaling
CC cascade (By similarity). Phosphorylation at Tyr-2274 and/or Tyr-2334
CC recruits PTPN11. {ECO:0000250, 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}.
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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 PDBsum; 3ZBF; -.
DR PDBsum; 4UXL; -.
DR AlphaFoldDB; P08922; -.
DR SMR; P08922; -.
DR BioGRID; 112025; 7.
DR IntAct; P08922; 17.
DR MINT; P08922; -.
DR STRING; 9606.ENSP00000357494; -.
DR BindingDB; P08922; -.
DR ChEMBL; CHEMBL5568; -.
DR DrugBank; DB11986; Entrectinib.
DR DrugBank; DB12010; Fostamatinib.
DR DrugCentral; P08922; -.
DR GuidetoPHARMACOLOGY; 1840; -.
DR GlyGen; P08922; 33 sites, 1 O-linked glycan (3 sites).
DR iPTMnet; P08922; -.
DR PhosphoSitePlus; P08922; -.
DR BioMuta; ROS1; -.
DR DMDM; 126302596; -.
DR EPD; P08922; -.
DR jPOST; P08922; -.
DR MassIVE; P08922; -.
DR PaxDb; P08922; -.
DR PeptideAtlas; P08922; -.
DR PRIDE; P08922; -.
DR ProteomicsDB; 52177; -.
DR ABCD; P08922; 2 sequenced antibodies.
DR Antibodypedia; 32541; 683 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 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 Orphanet; 357191; Selection of therapeutic option in non-small cell lung carcinoma.
DR PharmGKB; PA34633; -.
DR VEuPathDB; HostDB:ENSG00000047936; -.
DR eggNOG; KOG1095; Eukaryota.
DR GeneTree; ENSGT00940000160831; -.
DR InParanoid; P08922; -.
DR OrthoDB; 203310at2759; -.
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 1109 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 58 other tissues.
DR ExpressionAtlas; P08922; baseline and differential.
DR Genevisible; P08922; HS.
DR GO; GO:0005887; C:integral component of plasma membrane; IBA:GO_Central.
DR GO; GO:0016020; C:membrane; TAS:ProtInc.
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:0033674; P:positive regulation of kinase activity; IBA:GO_Central.
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 Gene3D; 2.120.10.30; -; 3.
DR Gene3D; 2.60.40.10; -; 7.
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 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; SSF49265; 5.
DR SUPFAM; SSF56112; SSF56112; 1.
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.
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 SITE 1880..1881
FT /note="Breakpoint for translocation to form GOPC-ROS1
FT fusion protein"
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:3ZBF"
FT STRAND 1945..1952
FT /evidence="ECO:0007829|PDB:3ZBF"
FT TURN 1955..1957
FT /evidence="ECO:0007829|PDB:4UXL"
FT STRAND 1959..1965
FT /evidence="ECO:0007829|PDB:3ZBF"
FT TURN 1966..1968
FT /evidence="ECO:0007829|PDB:4UXL"
FT STRAND 1974..1981
FT /evidence="ECO:0007829|PDB:3ZBF"
FT HELIX 1988..2002
FT /evidence="ECO:0007829|PDB:3ZBF"
FT STRAND 2012..2016
FT /evidence="ECO:0007829|PDB:3ZBF"
FT STRAND 2018..2021
FT /evidence="ECO:0007829|PDB:3ZBF"
FT STRAND 2023..2027
FT /evidence="ECO:0007829|PDB:3ZBF"
FT HELIX 2034..2043
FT /evidence="ECO:0007829|PDB:3ZBF"
FT HELIX 2053..2072
FT /evidence="ECO:0007829|PDB:3ZBF"
FT HELIX 2082..2084
FT /evidence="ECO:0007829|PDB:3ZBF"
FT STRAND 2085..2088
FT /evidence="ECO:0007829|PDB:3ZBF"
FT STRAND 2090..2094
FT /evidence="ECO:0007829|PDB:3ZBF"
FT STRAND 2098..2100
FT /evidence="ECO:0007829|PDB:3ZBF"
FT HELIX 2125..2127
FT /evidence="ECO:0007829|PDB:3ZBF"
FT HELIX 2130..2135
FT /evidence="ECO:0007829|PDB:3ZBF"
FT HELIX 2140..2155
FT /evidence="ECO:0007829|PDB:3ZBF"
FT HELIX 2167..2175
FT /evidence="ECO:0007829|PDB:3ZBF"
FT HELIX 2188..2197
FT /evidence="ECO:0007829|PDB:3ZBF"
FT HELIX 2202..2204
FT /evidence="ECO:0007829|PDB:3ZBF"
FT HELIX 2208..2227
FT /evidence="ECO:0007829|PDB:3ZBF"
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
