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 01-MAY-2013, entry version 140.
DE RecName: Full=Proto-oncogene tyrosine-protein kinase ROS;
DE EC=2.7.10.1;
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;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANTS ASN-2213; GLN-2228 AND
RP 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.,
RA Gilbert J.G.R., Clamp M.E., Bethel G., Milne S., Ainscough R.,
RA Almeida J.P., Ambrose K.D., Andrews T.D., Ashwell R.I.S.,
RA Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Barker D.J.,
RA Barlow K.F., Bates K., Beare D.M., Beasley H., Beasley O., Bird C.P.,
RA Blakey S.E., Bray-Allen S., Brook J., Brown A.J., Brown J.Y.,
RA 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.,
RA Ellington A.E., Evans K.A., Faulkner L., Francis M.D., Frankish A.,
RA Frankland J., French L., Garner P., Garnett J., Ghori M.J.,
RA Gilby L.M., Gillson C.J., Glithero R.J., Grafham D.V., Grant M.,
RA Gribble S., Griffiths C., Griffiths M.N.D., Hall R., Halls K.S.,
RA Hammond S., Harley J.L., Hart E.A., Heath P.D., Heathcott R.,
RA Holmes S.J., Howden P.J., Howe K.L., Howell G.R., Huckle E.,
RA Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M., Joy A.A.,
RA Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K., Langford C.,
RA Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R., Lloyd D.M.,
RA Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M.,
RA Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K.,
RA McMurray A., Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T.,
RA Novik K.L., Oliver K., Overton-Larty E.K., Parker A., Patel R.,
RA Pearce A.V., Peck A.I., Phillimore B.J.C.T., Phillips S., Plumb R.W.,
RA Porter K.M., Ramsey Y., Ranby S.A., Rice C.M., Ross M.T., Searle S.M.,
RA Sehra H.K., Sheridan E., Skuce C.D., Smith S., Smith M., Spraggon L.,
RA Squares S.L., Steward C.A., Sycamore N., Tamlyn-Hall G., Tester J.,
RA Theaker A.J., Thomas D.W., Thorpe A., Tracey A., Tromans A., Tubby B.,
RA Wall M., Wallis J.M., West A.P., White S.S., Whitehead S.L.,
RA Whittaker H., Wild A., Willey D.J., Wilmer T.E., Wood J.M., Wray P.W.,
RA Wyatt J.C., Young L., Younger R.M., Bentley D.R., Coulson A.,
RA Durbin R.M., Hubbard T., Sulston J.E., Dunham I., 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;
RA Matsushime H., Wang L.-H., Shibuya M.;
RT "Human c-ros-1 gene homologous to the v-ros sequence of UR2 sarcoma
RT virus 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;
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
RT for increased expression of the ros oncogene.";
RL Cancer Genet. Cytogenet. 72:130-136(1994).
RN [6]
RP FUNCTION IN VAV3 ACTIVATION, AND INTERACTION WITH VAV3.
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
RT GTPase activity, modulates cell morphology, and induces cell
RT transformation.";
RL Mol. Cell. Biol. 20:9212-9224(2000).
RN [7]
RP DISEASE, CHROMOSOMAL TRANSLOCATION WITH GOPC, AND MUTAGENESIS OF
RP 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
RT with 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
RP AND 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
RT apparatus in a glioblastoma.";
RL Proc. Natl. Acad. Sci. U.S.A. 100:916-921(2003).
RN [9]
RP FUNCTION IN CELL PROLIFERATION AND DIFFERENTATION, 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
RT phosphatase-2/phosphatidylinositol 3-kinase/mammalian target of
RT rapamycin signaling axis to form glioblastoma in mice.";
RL Cancer Res. 66:7473-7481(2006).
RN [10]
RP CHROMOSOMAL TRANSLOCATION WITH CD74 AND SLC34A2.
RX PubMed=18083107; DOI=10.1016/j.cell.2007.11.025;
RA Rikova K., Guo A., Zeng Q., Possemato A., Yu J., Haack H., Nardone J.,
RA Lee K., Reeves C., Li Y., Hu Y., Tan Z., Stokes M., Sullivan L.,
RA Mitchell J., Wetzel R., Macneill J., Ren J.M., Yuan J.,
RA Bakalarski C.E., Villen J., Kornhauser J.M., Smith B., Li D., Zhou X.,
RA Gygi S.P., Gu T.-L., Polakiewicz R.D., Rush J., Comb M.J.;
RT "Global survey of phosphotyrosine signaling identifies oncogenic
RT kinases in lung cancer.";
RL Cell 131:1190-1203(2007).
RN [11]
RP VARIANTS [LARGE SCALE ANALYSIS] SER-13; VAL-126; PRO-145; GLN-167;
RP SER-224; CYS-338; PRO-370; HIS-419; MET-537; PHE-653; HIS-865;
RP LEU-1109; PHE-1239; SER-1353; ARG-1370; GLY-1506; HIS-1776; LYS-1902;
RP ASN-1999; ARG-2003; SER-2138; ASN-2203; GLU-2213; ASN-2213; GLN-2228;
RP CYS-2229 AND LYS-2240.
RX PubMed=17344846; DOI=10.1038/nature05610;
RA Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C.,
RA Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S.,
RA O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S.,
RA Bhamra G., Buck G., Choudhury B., Clements J., Cole J., Dicks E.,
RA Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J.,
RA Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K.,
RA Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T.,
RA West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P.,
RA Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E.,
RA DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E.,
RA Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T.,
RA Yuen S.T., Leung S.Y., Wooster R., 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
CC in epithelial cell differentiation and regionalization of the
CC proximal epididymal epithelium. May activate several downstream
CC signaling pathways related to cell differentiation, proliferation,
CC growth and survival including the PI3 kinase-mTOR signaling
CC pathway. Mediates the phosphorylation of PTPN11, an activator of
CC this pathway. May also phosphorylate and activate the
CC transcription factor STAT3 to control anchorage-independent cell
CC growth. Mediates the phosphorylation and the activation of VAV3, a
CC guanine nucleotide exchange factor regulating cell morphology. May
CC activate other downstream signaling proteins including AKT1,
CC MAPK1, MAPK3, IRS1 and PLCG2.
CC -!- CATALYTIC ACTIVITY: ATP + a [protein]-L-tyrosine = ADP + a
CC [protein]-L-tyrosine phosphate.
CC -!- ENZYME REGULATION: Inhibited by dephosphorylation by PTPN6 (By
CC similarity).
CC -!- SUBUNIT: Interacts with PTPN6 (via SH2 1 domain); the interaction
CC is direct and promotes ROS1 dephosphorylation (By similarity).
CC Interacts with PTPN11; may activate the PI3 kinase-mTOR signaling
CC pathway. Interacts with VAV3; constitutive interaction mediating
CC VAV3 phosphorylation.
CC -!- SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane
CC protein (Probable).
CC -!- TISSUE SPECIFICITY: Expressed in brain. Expression is increased in
CC primary gliomas.
CC -!- PTM: Phosphorylated. Probably autophosphorylates. Phosphorylation
CC at Tyr-2274 is required for the interaction with PTPN6 that
CC mediates ROS1 dephosphorylation (By similarity). Phosphorylation
CC at Tyr-2274 stimulates the kinase activity and the activation of
CC the ERK1 signaling cascade (By similarity). Phosphorylation at
CC Tyr-2274 and/or Tyr-2334 recruits PTPN11.
CC -!- DISEASE: Note=A chromosomal aberration involving ROS1 is found in
CC a glioblastoma multiforme sample. An intra-chromosomal deletion
CC del(6)(q21q21) is responsible for the formation of GOPC-ROS1
CC chimeric protein which is localized to the Golgi and has a
CC constitutive receptor tyrosine kinase activity. A SLC34A2-ROS1
CC chimeric protein produced in non-small cell lung cancer cells also
CC retains a constitutive kinase activity. A third type of chimeric
CC protein CD74-ROS1 was also identified in those cells.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. Tyr protein
CC kinase family. Insulin receptor subfamily.
CC -!- SIMILARITY: Contains 9 fibronectin type-III domains.
CC -!- SIMILARITY: Contains 1 protein kinase domain.
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DR EMBL; M34353; AAA60278.1; -; mRNA.
DR EMBL; Z98880; CAI42374.1; -; Genomic_DNA.
DR EMBL; AL132671; CAI42374.1; JOINED; Genomic_DNA.
DR EMBL; AL132671; CAI23378.1; -; Genomic_DNA.
DR EMBL; Z98880; CAI23378.1; JOINED; 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 IPI; IPI00288965; -.
DR PIR; A35512; TVHURS.
DR RefSeq; NP_002935.2; NM_002944.2.
DR UniGene; Hs.1041; -.
DR ProteinModelPortal; P08922; -.
DR MINT; MINT-2800684; -.
DR STRING; 9606.ENSP00000357494; -.
DR PhosphoSite; P08922; -.
DR DMDM; 126302596; -.
DR PaxDb; P08922; -.
DR PRIDE; P08922; -.
DR DNASU; 6098; -.
DR Ensembl; ENST00000368508; ENSP00000357494; ENSG00000047936.
DR GeneID; 6098; -.
DR KEGG; hsa:6098; -.
DR UCSC; uc003pxp.1; human.
DR CTD; 6098; -.
DR GeneCards; GC06M117609; -.
DR H-InvDB; HIX0207391; -.
DR HGNC; HGNC:10261; ROS1.
DR HPA; HPA049098; -.
DR MIM; 165020; gene.
DR neXtProt; NX_P08922; -.
DR PharmGKB; PA34633; -.
DR eggNOG; COG0515; -.
DR HOGENOM; HOG000137937; -.
DR HOVERGEN; HBG058631; -.
DR InParanoid; P08922; -.
DR KO; K05088; -.
DR OMA; EQWLFLS; -.
DR OrthoDB; EOG4PK26W; -.
DR BRENDA; 2.7.10.1; 2681.
DR BindingDB; P08922; -.
DR ChEMBL; CHEMBL5568; -.
DR ChiTaRS; ROS1; human.
DR GenomeRNAi; 6098; -.
DR NextBio; 23723; -.
DR ArrayExpress; P08922; -.
DR Bgee; P08922; -.
DR CleanEx; HS_ROS1; -.
DR Genevestigator; P08922; -.
DR GermOnline; ENSG00000047936; Homo sapiens.
DR GO; GO:0016021; C:integral to membrane; IEA:UniProtKB-KW.
DR GO; GO:0016020; C:membrane; TAS:ProtInc.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0004713; F:protein tyrosine kinase activity; IDA:UniProtKB.
DR GO; GO:0004714; F:transmembrane receptor protein tyrosine kinase activity; IEA:EC.
DR GO; GO:0016049; P:cell growth; IDA:UniProtKB.
DR GO; GO:0008283; P:cell proliferation; ISS:UniProtKB.
DR GO; GO:0002066; P:columnar/cuboidal epithelial cell development; ISS:UniProtKB.
DR GO; GO:0010629; P:negative regulation of gene expression; IEA:Compara.
DR GO; GO:0070372; P:regulation of ERK1 and ERK2 cascade; ISS:UniProtKB.
DR GO; GO:0010966; P:regulation of phosphate transport; IEA:Compara.
DR GO; GO:0032006; P:regulation of TOR signaling cascade; IDA:UniProtKB.
DR GO; GO:0007283; P:spermatogenesis; ISS:UniProtKB.
DR GO; GO:0007169; P:transmembrane receptor protein tyrosine kinase signaling pathway; IEA:InterPro.
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; Fibronectin_type3.
DR InterPro; IPR013783; Ig-like_fold.
DR InterPro; IPR011009; Kinase-like_dom.
DR InterPro; IPR000033; LDLR_classB_rpt.
DR InterPro; IPR000719; Prot_kinase_cat_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; 4.
DR Pfam; PF07714; Pkinase_Tyr; 1.
DR PRINTS; PR00109; TYRKINASE.
DR SMART; SM00060; FN3; 9.
DR SMART; SM00135; LY; 4.
DR SMART; SM00219; TyrKc; 1.
DR SUPFAM; SSF49265; FN_III-like; 8.
DR SUPFAM; SSF56112; Kinase_like; 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 ATP-binding; Cell membrane; Chromosomal rearrangement;
KW Complete proteome; Glycoprotein; Kinase; Membrane; Nucleotide-binding;
KW Phosphoprotein; Polymorphism; Proto-oncogene; Receptor;
KW Reference proteome; Repeat; Signal; Transferase; Transmembrane;
KW Transmembrane helix; Tyrosine-protein kinase.
FT SIGNAL 1 27 Potential.
FT CHAIN 28 2347 Proto-oncogene tyrosine-protein kinase
FT ROS.
FT /FTId=PRO_0000016722.
FT TOPO_DOM 28 1859 Extracellular (Potential).
FT TRANSMEM 1860 1882 Helical; (Potential).
FT TOPO_DOM 1883 2347 Cytoplasmic (Potential).
FT DOMAIN 98 188 Fibronectin type-III 1.
FT DOMAIN 194 281 Fibronectin type-III 2.
FT DOMAIN 558 668 Fibronectin type-III 3.
FT DOMAIN 944 1036 Fibronectin type-III 4.
FT DOMAIN 1041 1147 Fibronectin type-III 5.
FT DOMAIN 1450 1548 Fibronectin type-III 6.
FT DOMAIN 1558 1653 Fibronectin type-III 7.
FT DOMAIN 1655 1748 Fibronectin type-III 8.
FT DOMAIN 1749 1851 Fibronectin type-III 9.
FT DOMAIN 1945 2222 Protein kinase.
FT NP_BIND 1951 1959 ATP (By similarity).
FT ACT_SITE 2079 2079 Proton acceptor (By similarity).
FT BINDING 1980 1980 ATP (Probable).
FT SITE 1852 1853 Breakpoint for translocation to form
FT SLC34A2-ROS1 and CD74-ROS1 fusion
FT proteins.
FT SITE 1880 1881 Breakpoint for translocation to form
FT GOPC-ROS1 fusion protein.
FT MOD_RES 2274 2274 Phosphotyrosine; by autocatalysis
FT (Probable).
FT MOD_RES 2334 2334 Phosphotyrosine; by autocatalysis
FT (Probable).
FT CARBOHYD 52 52 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 114 114 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 123 123 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 324 324 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 352 352 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 396 396 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 471 471 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 607 607 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 628 628 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 706 706 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 714 714 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 732 732 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 939 939 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 961 961 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 1015 1015 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 1087 1087 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 1090 1090 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 1095 1095 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 1211 1211 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 1272 1272 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 1330 1330 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 1458 1458 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 1461 1461 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 1474 1474 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 1499 1499 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 1565 1565 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 1669 1669 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 1715 1715 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 1738 1738 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 1808 1808 N-linked (GlcNAc...) (Potential).
FT VARIANT 13 13 N -> S (in dbSNP:rs45606237).
FT /FTId=VAR_041442.
FT VARIANT 126 126 G -> V (in dbSNP:rs34245787).
FT /FTId=VAR_041443.
FT VARIANT 145 145 T -> P (in dbSNP:rs1998206).
FT /FTId=VAR_030648.
FT VARIANT 167 167 R -> Q (in dbSNP:rs2243380).
FT /FTId=VAR_030649.
FT VARIANT 224 224 P -> S (in dbSNP:rs55959124).
FT /FTId=VAR_041444.
FT VARIANT 338 338 Y -> C (in dbSNP:rs55707658).
FT /FTId=VAR_041445.
FT VARIANT 370 370 S -> P (in dbSNP:rs56274823).
FT /FTId=VAR_041446.
FT VARIANT 419 419 Y -> H (in a gastric adenocarcinoma
FT sample; somatic mutation).
FT /FTId=VAR_041447.
FT VARIANT 537 537 I -> M (in dbSNP:rs28639589).
FT /FTId=VAR_041448.
FT VARIANT 653 653 S -> F (in dbSNP:rs34203286).
FT /FTId=VAR_041449.
FT VARIANT 790 790 N -> S (in dbSNP:rs34582164).
FT /FTId=VAR_049712.
FT VARIANT 865 865 Q -> H (in a lung large cell carcinoma
FT sample; somatic mutation).
FT /FTId=VAR_041450.
FT VARIANT 1109 1109 S -> L (in dbSNP:rs2229079).
FT /FTId=VAR_030650.
FT VARIANT 1239 1239 Y -> F (in dbSNP:rs56192249).
FT /FTId=VAR_041451.
FT VARIANT 1353 1353 Y -> S (in dbSNP:rs35269727).
FT /FTId=VAR_041452.
FT VARIANT 1370 1370 C -> R (in dbSNP:rs36106063).
FT /FTId=VAR_041453.
FT VARIANT 1439 1439 F -> S (in dbSNP:rs17079086).
FT /FTId=VAR_030651.
FT VARIANT 1506 1506 R -> G (in dbSNP:rs35841892).
FT /FTId=VAR_041454.
FT VARIANT 1776 1776 D -> H (in dbSNP:rs12664076).
FT /FTId=VAR_030652.
FT VARIANT 1902 1902 E -> K (in dbSNP:rs9489124).
FT /FTId=VAR_030653.
FT VARIANT 1999 1999 H -> N (in dbSNP:rs45569132).
FT /FTId=VAR_041455.
FT VARIANT 2003 2003 K -> R (in a colorectal adenocarcinoma
FT sample; somatic mutation).
FT /FTId=VAR_041456.
FT VARIANT 2039 2039 R -> H (in dbSNP:rs3752566).
FT /FTId=VAR_030654.
FT VARIANT 2138 2138 F -> S (in a gastric adenocarcinoma
FT sample; somatic mutation).
FT /FTId=VAR_041457.
FT VARIANT 2203 2203 D -> N.
FT /FTId=VAR_041458.
FT VARIANT 2213 2213 D -> E.
FT /FTId=VAR_041459.
FT VARIANT 2213 2213 D -> N (in dbSNP:rs529038).
FT /FTId=VAR_030655.
FT VARIANT 2228 2228 K -> Q (in dbSNP:rs529156).
FT /FTId=VAR_041460.
FT VARIANT 2229 2229 S -> C (in dbSNP:rs619203).
FT /FTId=VAR_030656.
FT VARIANT 2240 2240 N -> K (in dbSNP:rs210968).
FT /FTId=VAR_030657.
FT VARIANT 2328 2328 K -> R (in dbSNP:rs35932630).
FT /FTId=VAR_049713.
FT MUTAGEN 1980 1980 K->M: Loss of kinase activity.
FT MUTAGEN 2274 2274 Y->F: Loss of phosphorylation at Y-2274
FT and loss of interaction with PTPN11.
FT MUTAGEN 2334 2334 Y->F: Loss of phosphorylation at Y-2334
FT and loss of interaction with PTPN11.
FT CONFLICT 2246 2260 EDGDVICLNSDDIMP -> KFDSSEFSSFRCTVN (in
FT Ref. 3; AAA60277).
FT CONFLICT 2262 2262 A -> V (in Ref. 1; AAA60278).
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
//
