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P08922

- ROS1_HUMAN

UniProt

P08922 - ROS1_HUMAN

Protein

Proto-oncogene tyrosine-protein kinase ROS

Gene

ROS1

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 154 (01 Oct 2014)
      Sequence version 3 (20 Feb 2007)
      Previous versions | rss
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    Functioni

    Orphan receptor tyrosine kinase (RTK) that plays a role in epithelial cell differentiation and regionalization of the proximal epididymal epithelium. May activate several downstream signaling pathways related to cell differentiation, proliferation, growth and survival including the PI3 kinase-mTOR signaling pathway. Mediates the phosphorylation of PTPN11, an activator of this pathway. May also phosphorylate and activate the transcription factor STAT3 to control anchorage-independent cell growth. Mediates the phosphorylation and the activation of VAV3, a guanine nucleotide exchange factor regulating cell morphology. May activate other downstream signaling proteins including AKT1, MAPK1, MAPK3, IRS1 and PLCG2.2 Publications

    Catalytic activityi

    ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.PROSITE-ProRule annotation

    Enzyme regulationi

    Inhibited by dephosphorylation by PTPN6.By similarity

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sitei1852 – 18532Breakpoint for translocation to form SLC34A2-ROS1 and CD74-ROS1 fusion proteins
    Sitei1880 – 18812Breakpoint for translocation to form GOPC-ROS1 fusion protein
    Binding sitei1980 – 19801ATPCurated
    Active sitei2079 – 20791Proton acceptorPROSITE-ProRule annotation

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Nucleotide bindingi1951 – 19599ATPPROSITE-ProRule annotation

    GO - Molecular functioni

    1. ATP binding Source: UniProtKB-KW
    2. protein binding Source: IntAct
    3. protein phosphatase binding Source: UniProtKB
    4. protein tyrosine kinase activity Source: UniProtKB
    5. transmembrane receptor protein tyrosine kinase activity Source: UniProtKB-EC

    GO - Biological processi

    1. cell differentiation Source: UniProtKB
    2. cell growth Source: UniProtKB
    3. cell proliferation Source: UniProtKB
    4. columnar/cuboidal epithelial cell development Source: UniProtKB
    5. negative regulation of gene expression Source: Ensembl
    6. peptidyl-tyrosine phosphorylation Source: GOC
    7. protein phosphorylation Source: UniProtKB
    8. regulation of ERK1 and ERK2 cascade Source: UniProtKB
    9. regulation of phosphate transport Source: Ensembl
    10. regulation of TOR signaling Source: UniProtKB
    11. spermatogenesis Source: UniProtKB
    12. transmembrane receptor protein tyrosine kinase signaling pathway Source: InterPro

    Keywords - Molecular functioni

    Kinase, Receptor, Transferase, Tyrosine-protein kinase

    Keywords - Ligandi

    ATP-binding, Nucleotide-binding

    Enzyme and pathway databases

    BRENDAi2.7.10.1. 2681.
    SignaLinkiP08922.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Proto-oncogene tyrosine-protein kinase ROS (EC:2.7.10.1)
    Alternative name(s):
    Proto-oncogene c-Ros
    Proto-oncogene c-Ros-1
    Receptor tyrosine kinase c-ros oncogene 1
    c-Ros receptor tyrosine kinase
    Gene namesi
    Name:ROS1
    Synonyms:MCF3, ROS
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 6

    Organism-specific databases

    HGNCiHGNC:10261. ROS1.

    Subcellular locationi

    GO - Cellular componenti

    1. integral component of membrane Source: UniProtKB-KW
    2. membrane Source: ProtInc
    3. plasma membrane Source: UniProtKB-SubCell

    Keywords - Cellular componenti

    Cell membrane, Membrane

    Pathology & Biotechi

    Involvement in diseasei

    A chromosomal aberration involving ROS1 is found in a glioblastoma multiforme sample. An intra-chromosomal deletion del6(q21q21) is responsible for the formation of GOPC-ROS1 chimeric protein which is localized to the Golgi and has a constitutive receptor tyrosine kinase activity. A SLC34A2-ROS1 chimeric protein produced in non-small cell lung cancer cells also retains a constitutive kinase activity. A third type of chimeric protein CD74-ROS1 was also identified in those cells.1 Publication

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi1980 – 19801K → M: Loss of kinase activity. 1 Publication
    Mutagenesisi2274 – 22741Y → F: Loss of phosphorylation at Y-2274 and loss of interaction with PTPN11. 1 Publication
    Mutagenesisi2334 – 23341Y → F: Loss of phosphorylation at Y-2334 and loss of interaction with PTPN11. 1 Publication

    Keywords - Diseasei

    Proto-oncogene

    Organism-specific databases

    PharmGKBiPA34633.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Signal peptidei1 – 2727Sequence AnalysisAdd
    BLAST
    Chaini28 – 23472320Proto-oncogene tyrosine-protein kinase ROSPRO_0000016722Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Glycosylationi52 – 521N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi114 – 1141N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi123 – 1231N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi324 – 3241N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi352 – 3521N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi396 – 3961N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi471 – 4711N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi607 – 6071N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi628 – 6281N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi706 – 7061N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi714 – 7141N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi732 – 7321N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi939 – 9391N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi961 – 9611N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi1015 – 10151N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi1087 – 10871N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi1090 – 10901N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi1095 – 10951N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi1211 – 12111N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi1272 – 12721N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi1330 – 13301N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi1458 – 14581N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi1461 – 14611N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi1474 – 14741N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi1499 – 14991N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi1565 – 15651N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi1669 – 16691N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi1715 – 17151N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi1738 – 17381N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi1808 – 18081N-linked (GlcNAc...)Sequence Analysis
    Modified residuei2274 – 22741Phosphotyrosine; by autocatalysis1 Publication
    Modified residuei2334 – 23341Phosphotyrosine; by autocatalysis1 Publication

    Post-translational modificationi

    Phosphorylated. Probably autophosphorylates. Phosphorylation at Tyr-2274 is required for the interaction with PTPN6 that mediates ROS1 dephosphorylation By similarity. Phosphorylation at Tyr-2274 stimulates the kinase activity and the activation of the ERK1 signaling cascade By similarity. Phosphorylation at Tyr-2274 and/or Tyr-2334 recruits PTPN11.By similarity1 Publication

    Keywords - PTMi

    Glycoprotein, Phosphoprotein

    Proteomic databases

    PaxDbiP08922.
    PRIDEiP08922.

    PTM databases

    PhosphoSiteiP08922.

    Expressioni

    Tissue specificityi

    Expressed in brain. Expression is increased in primary gliomas.1 Publication

    Gene expression databases

    ArrayExpressiP08922.
    BgeeiP08922.
    CleanExiHS_ROS1.
    GenevestigatoriP08922.

    Organism-specific databases

    HPAiHPA049098.

    Interactioni

    Subunit structurei

    Interacts with PTPN6 (via SH2 1 domain); the interaction is direct and promotes ROS1 dephosphorylation By similarity. Interacts with PTPN11; may activate the PI3 kinase-mTOR signaling pathway. Interacts with VAV3; constitutive interaction mediating VAV3 phosphorylation.By similarity2 Publications

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    PTPN1P180313EBI-7371065,EBI-968788
    PTPN6P293502EBI-7371065,EBI-78260

    Protein-protein interaction databases

    BioGridi112025. 5 interactions.
    IntActiP08922. 3 interactions.
    MINTiMINT-2800684.
    STRINGi9606.ENSP00000357494.

    Structurei

    Secondary structure

    1
    2347
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Helixi1942 – 19443
    Beta strandi1945 – 19528
    Beta strandi1959 – 19657
    Beta strandi1974 – 19818
    Helixi1988 – 200215
    Beta strandi2012 – 20165
    Beta strandi2018 – 20214
    Beta strandi2023 – 20275
    Helixi2034 – 204310
    Helixi2053 – 207220
    Helixi2082 – 20843
    Beta strandi2085 – 20884
    Beta strandi2090 – 20945
    Beta strandi2098 – 21003
    Helixi2125 – 21273
    Helixi2130 – 21356
    Helixi2140 – 215516
    Helixi2167 – 21759
    Helixi2188 – 219710
    Helixi2202 – 22043
    Helixi2208 – 222720

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    3ZBFX-ray2.20A1934-2232[»]
    ProteinModelPortaliP08922.
    SMRiP08922. Positions 99-185, 191-279, 632-668, 943-1147, 1484-1537, 1657-1849, 1881-2229.
    ModBaseiSearch...
    MobiDBiSearch...

    Topological domain

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Topological domaini28 – 18591832ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini1883 – 2347465CytoplasmicSequence AnalysisAdd
    BLAST

    Transmembrane

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transmembranei1860 – 188223HelicalSequence AnalysisAdd
    BLAST

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini101 – 19696Fibronectin type-III 1PROSITE-ProRule annotationAdd
    BLAST
    Domaini197 – 28589Fibronectin type-III 2PROSITE-ProRule annotationAdd
    BLAST
    Domaini557 – 671115Fibronectin type-III 3PROSITE-ProRule annotationAdd
    BLAST
    Domaini947 – 104296Fibronectin type-III 4PROSITE-ProRule annotationAdd
    BLAST
    Domaini1043 – 1150108Fibronectin type-III 5PROSITE-ProRule annotationAdd
    BLAST
    Domaini1450 – 1556107Fibronectin type-III 6PROSITE-ProRule annotationAdd
    BLAST
    Domaini1557 – 1656100Fibronectin type-III 7PROSITE-ProRule annotationAdd
    BLAST
    Domaini1658 – 175194Fibronectin type-III 8PROSITE-ProRule annotationAdd
    BLAST
    Domaini1752 – 1854103Fibronectin type-III 9PROSITE-ProRule annotationAdd
    BLAST
    Domaini1945 – 2222278Protein kinasePROSITE-ProRule annotationAdd
    BLAST

    Sequence similaritiesi

    Belongs to the protein kinase superfamily. Tyr protein kinase family. Insulin receptor subfamily.PROSITE-ProRule annotation
    Contains 9 fibronectin type-III domains.PROSITE-ProRule annotation
    Contains 1 protein kinase domain.PROSITE-ProRule annotation

    Keywords - Domaini

    Repeat, Signal, Transmembrane, Transmembrane helix

    Phylogenomic databases

    eggNOGiCOG0515.
    HOGENOMiHOG000137937.
    HOVERGENiHBG058631.
    InParanoidiP08922.
    KOiK05088.
    OMAiYWLVQDS.
    OrthoDBiEOG7GN2KT.
    PhylomeDBiP08922.
    TreeFamiTF351636.

    Family and domain databases

    Gene3Di2.120.10.30. 3 hits.
    2.60.40.10. 7 hits.
    InterProiIPR011042. 6-blade_b-propeller_TolB-like.
    IPR003961. Fibronectin_type3.
    IPR013783. Ig-like_fold.
    IPR011009. Kinase-like_dom.
    IPR000033. LDLR_classB_rpt.
    IPR000719. Prot_kinase_dom.
    IPR017441. Protein_kinase_ATP_BS.
    IPR001245. Ser-Thr/Tyr_kinase_cat_dom.
    IPR008266. Tyr_kinase_AS.
    IPR020635. Tyr_kinase_cat_dom.
    IPR002011. Tyr_kinase_rcpt_2_CS.
    [Graphical view]
    PfamiPF00041. fn3. 4 hits.
    PF07714. Pkinase_Tyr. 1 hit.
    [Graphical view]
    PRINTSiPR00109. TYRKINASE.
    SMARTiSM00060. FN3. 9 hits.
    SM00135. LY. 4 hits.
    SM00219. TyrKc. 1 hit.
    [Graphical view]
    SUPFAMiSSF49265. SSF49265. 5 hits.
    SSF56112. SSF56112. 1 hit.
    PROSITEiPS50853. FN3. 9 hits.
    PS00107. PROTEIN_KINASE_ATP. 1 hit.
    PS50011. PROTEIN_KINASE_DOM. 1 hit.
    PS00109. PROTEIN_KINASE_TYR. 1 hit.
    PS00239. RECEPTOR_TYR_KIN_II. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    Sequence processingi: The displayed sequence is further processed into a mature form.

    P08922-1 [UniParc]FASTAAdd to Basket

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    MKNIYCLIPK LVNFATLGCL WISVVQCTVL NSCLKSCVTN LGQQLDLGTP     50
    HNLSEPCIQG CHFWNSVDQK NCALKCRESC EVGCSSAEGA YEEEVLENAD 100
    LPTAPFASSI GSHNMTLRWK SANFSGVKYI IQWKYAQLLG SWTYTKTVSR 150
    PSYVVKPLHP FTEYIFRVVW IFTAQLQLYS PPSPSYRTHP HGVPETAPLI 200
    RNIESSSPDT VEVSWDPPQF PGGPILGYNL RLISKNQKLD AGTQRTSFQF 250
    YSTLPNTIYR FSIAAVNEVG EGPEAESSIT TSSSAVQQEE QWLFLSRKTS 300
    LRKRSLKHLV DEAHCLRLDA IYHNITGISV DVHQQIVYFS EGTLIWAKKA 350
    ANMSDVSDLR IFYRGSGLIS SISIDWLYQR MYFIMDELVC VCDLENCSNI 400
    EEITPPSISA PQKIVADSYN GYVFYLLRDG IYRADLPVPS GRCAEAVRIV 450
    ESCTLKDFAI KPQAKRIIYF NDTAQVFMST FLDGSASHLI LPRIPFADVK 500
    SFACENNDFL VTDGKVIFQQ DALSFNEFIV GCDLSHIEEF GFGNLVIFGS 550
    SSQLHPLPGR PQELSVLFGS HQALVQWKPP ALAIGANVIL ISDIIELFEL 600
    GPSAWQNWTY EVKVSTQDPP EVTHIFLNIS GTMLNVPELQ SAMKYKVSVR 650
    ASSPKRPGPW SEPSVGTTLV PASEPPFIMA VKEDGLWSKP LNSFGPGEFL 700
    SSDIGNVSDM DWYNNSLYYS DTKGDVFVWL LNGTDISENY HLPSIAGAGA 750
    LAFEWLGHFL YWAGKTYVIQ RQSVLTGHTD IVTHVKLLVN DMVVDSVGGY 800
    LYWTTLYSVE STRLNGESSL VLQTQPWFSG KKVIALTLDL SDGLLYWLVQ 850
    DSQCIHLYTA VLRGQSTGDT TITEFAAWST SEISQNALMY YSGRLFWING 900
    FRIITTQEIG QKTSVSVLEP ARFNQFTIIQ TSLKPLPGNF SFTPKVIPDS 950
    VQESSFRIEG NASSFQILWN GPPAVDWGVV FYSVEFSAHS KFLASEQHSL 1000
    PVFTVEGLEP YALFNLSVTP YTYWGKGPKT SLSLRAPETV PSAPENPRIF 1050
    ILPSGKCCNK NEVVVEFRWN KPKHENGVLT KFEIFYNISN QSITNKTCED 1100
    WIAVNVTPSV MSFQLEGMSP RCFIAFQVRA FTSKGPGPYA DVVKSTTSEI 1150
    NPFPHLITLL GNKIVFLDMD QNQVVWTFSA ERVISAVCYT ADNEMGYYAE 1200
    GDSLFLLHLH NRSSSELFQD SLVFDITVIT IDWISRHLYF ALKESQNGMQ 1250
    VFDVDLEHKV KYPREVKIHN RNSTIISFSV YPLLSRLYWT EVSNFGYQMF 1300
    YYSIISHTLH RILQPTATNQ QNKRNQCSCN VTEFELSGAM AIDTSNLEKP 1350
    LIYFAKAQEI WAMDLEGCQC WRVITVPAML AGKTLVSLTV DGDLIYWIIT 1400
    AKDSTQIYQA KKGNGAIVSQ VKALRSRHIL AYSSVMQPFP DKAFLSLASD 1450
    TVEPTILNAT NTSLTIRLPL AKTNLTWYGI TSPTPTYLVY YAEVNDRKNS 1500
    SDLKYRILEF QDSIALIEDL QPFSTYMIQI AVKNYYSDPL EHLPPGKEIW 1550
    GKTKNGVPEA VQLINTTVRS DTSLIISWRE SHKPNGPKES VRYQLAISHL 1600
    ALIPETPLRQ SEFPNGRLTL LVTRLSGGNI YVLKVLACHS EEMWCTESHP 1650
    VTVEMFNTPE KPYSLVPENT SLQFNWKAPL NVNLIRFWVE LQKWKYNEFY 1700
    HVKTSCSQGP AYVCNITNLQ PYTSYNVRVV VVYKTGENST SLPESFKTKA 1750
    GVPNKPGIPK LLEGSKNSIQ WEKAEDNGCR ITYYILEIRK STSNNLQNQN 1800
    LRWKMTFNGS CSSVCTWKSK NLKGIFQFRV VAANNLGFGE YSGISENIIL 1850
    VGDDFWIPET SFILTIIVGI FLVVTIPLTF VWHRRLKNQK SAKEGVTVLI 1900
    NEDKELAELR GLAAGVGLAN ACYAIHTLPT QEEIENLPAF PREKLTLRLL 1950
    LGSGAFGEVY EGTAVDILGV GSGEIKVAVK TLKKGSTDQE KIEFLKEAHL 2000
    MSKFNHPNIL KQLGVCLLNE PQYIILELME GGDLLTYLRK ARMATFYGPL 2050
    LTLVDLVDLC VDISKGCVYL ERMHFIHRDL AARNCLVSVK DYTSPRIVKI 2100
    GDFGLARDIY KNDYYRKRGE GLLPVRWMAP ESLMDGIFTT QSDVWSFGIL 2150
    IWEILTLGHQ PYPAHSNLDV LNYVQTGGRL EPPRNCPDDL WNLMTQCWAQ 2200
    EPDQRPTFHR IQDQLQLFRN FFLNSIYKSR DEANNSGVIN ESFEGEDGDV 2250
    ICLNSDDIMP VALMETKNRE GLNYMVLATE CGQGEEKSEG PLGSQESESC 2300
    GLRKEEKEPH ADKDFCQEKQ VAYCPSGKPE GLNYACLTHS GYGDGSD 2347
    Length:2,347
    Mass (Da):263,915
    Last modified:February 20, 2007 - v3
    Checksum:i98902B9A59ACB8F5
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti2246 – 226015EDGDV…DDIMP → KFDSSEFSSFRCTVN in AAA60277. (PubMed:3023956)CuratedAdd
    BLAST
    Sequence conflicti2262 – 22621A → V in AAA60278. (PubMed:2352949)Curated

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti13 – 131N → S.1 Publication
    Corresponds to variant rs45606237 [ dbSNP | Ensembl ].
    VAR_041442
    Natural varianti126 – 1261G → V.1 Publication
    Corresponds to variant rs34245787 [ dbSNP | Ensembl ].
    VAR_041443
    Natural varianti145 – 1451T → P.1 Publication
    Corresponds to variant rs1998206 [ dbSNP | Ensembl ].
    VAR_030648
    Natural varianti167 – 1671R → Q.1 Publication
    Corresponds to variant rs2243380 [ dbSNP | Ensembl ].
    VAR_030649
    Natural varianti224 – 2241P → S.1 Publication
    Corresponds to variant rs55959124 [ dbSNP | Ensembl ].
    VAR_041444
    Natural varianti338 – 3381Y → C.1 Publication
    Corresponds to variant rs55707658 [ dbSNP | Ensembl ].
    VAR_041445
    Natural varianti370 – 3701S → P.1 Publication
    Corresponds to variant rs56274823 [ dbSNP | Ensembl ].
    VAR_041446
    Natural varianti419 – 4191Y → H in a gastric adenocarcinoma sample; somatic mutation. 1 Publication
    VAR_041447
    Natural varianti537 – 5371I → M.1 Publication
    Corresponds to variant rs28639589 [ dbSNP | Ensembl ].
    VAR_041448
    Natural varianti653 – 6531S → F.1 Publication
    Corresponds to variant rs34203286 [ dbSNP | Ensembl ].
    VAR_041449
    Natural varianti790 – 7901N → S.
    Corresponds to variant rs34582164 [ dbSNP | Ensembl ].
    VAR_049712
    Natural varianti865 – 8651Q → H in a lung large cell carcinoma sample; somatic mutation. 1 Publication
    VAR_041450
    Natural varianti1109 – 11091S → L.1 Publication
    Corresponds to variant rs2229079 [ dbSNP | Ensembl ].
    VAR_030650
    Natural varianti1239 – 12391Y → F.1 Publication
    Corresponds to variant rs56192249 [ dbSNP | Ensembl ].
    VAR_041451
    Natural varianti1353 – 13531Y → S.1 Publication
    Corresponds to variant rs35269727 [ dbSNP | Ensembl ].
    VAR_041452
    Natural varianti1370 – 13701C → R.1 Publication
    Corresponds to variant rs36106063 [ dbSNP | Ensembl ].
    VAR_041453
    Natural varianti1439 – 14391F → S.
    Corresponds to variant rs17079086 [ dbSNP | Ensembl ].
    VAR_030651
    Natural varianti1506 – 15061R → G.1 Publication
    Corresponds to variant rs35841892 [ dbSNP | Ensembl ].
    VAR_041454
    Natural varianti1776 – 17761D → H.1 Publication
    Corresponds to variant rs12664076 [ dbSNP | Ensembl ].
    VAR_030652
    Natural varianti1902 – 19021E → K.1 Publication
    Corresponds to variant rs9489124 [ dbSNP | Ensembl ].
    VAR_030653
    Natural varianti1999 – 19991H → N.1 Publication
    Corresponds to variant rs45569132 [ dbSNP | Ensembl ].
    VAR_041455
    Natural varianti2003 – 20031K → R in a colorectal adenocarcinoma sample; somatic mutation. 1 Publication
    VAR_041456
    Natural varianti2039 – 20391R → H.
    Corresponds to variant rs3752566 [ dbSNP | Ensembl ].
    VAR_030654
    Natural varianti2138 – 21381F → S in a gastric adenocarcinoma sample; somatic mutation. 1 Publication
    VAR_041457
    Natural varianti2203 – 22031D → N.1 Publication
    VAR_041458
    Natural varianti2213 – 22131D → E.1 Publication
    Corresponds to variant rs75510639 [ dbSNP | Ensembl ].
    VAR_041459
    Natural varianti2213 – 22131D → N.2 Publications
    Corresponds to variant rs529038 [ dbSNP | Ensembl ].
    VAR_030655
    Natural varianti2228 – 22281K → Q.2 Publications
    Corresponds to variant rs529156 [ dbSNP | Ensembl ].
    VAR_041460
    Natural varianti2229 – 22291S → C.2 Publications
    Corresponds to variant rs619203 [ dbSNP | Ensembl ].
    VAR_030656
    Natural varianti2240 – 22401N → K.1 Publication
    Corresponds to variant rs210968 [ dbSNP | Ensembl ].
    VAR_030657
    Natural varianti2328 – 23281K → R.
    Corresponds to variant rs35932630 [ dbSNP | Ensembl ].
    VAR_049713

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    M34353 mRNA. Translation: AAA60278.1.
    Z98880, AL132671 Genomic DNA. Translation: CAI42374.1.
    AL132671, Z98880 Genomic DNA. Translation: CAI23378.1.
    M13599
    , M13368, M13591, M13592, M13593, M13594, M13595, M13596, M13597, M13598 Genomic DNA. Translation: AAA60277.1.
    M13880 mRNA. Translation: AAA36580.1.
    CCDSiCCDS5116.1.
    PIRiA35512. TVHURS.
    RefSeqiNP_002935.2. NM_002944.2.
    UniGeneiHs.1041.

    Genome annotation databases

    EnsembliENST00000368508; ENSP00000357494; ENSG00000047936.
    GeneIDi6098.
    KEGGihsa:6098.
    UCSCiuc003pxp.1. human.

    Polymorphism databases

    DMDMi126302596.

    Keywords - Coding sequence diversityi

    Chromosomal rearrangement, Polymorphism

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    M34353 mRNA. Translation: AAA60278.1 .
    Z98880 , AL132671 Genomic DNA. Translation: CAI42374.1 .
    AL132671 , Z98880 Genomic DNA. Translation: CAI23378.1 .
    M13599
    , M13368 , M13591 , M13592 , M13593 , M13594 , M13595 , M13596 , M13597 , M13598 Genomic DNA. Translation: AAA60277.1 .
    M13880 mRNA. Translation: AAA36580.1 .
    CCDSi CCDS5116.1.
    PIRi A35512. TVHURS.
    RefSeqi NP_002935.2. NM_002944.2.
    UniGenei Hs.1041.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    3ZBF X-ray 2.20 A 1934-2232 [» ]
    ProteinModelPortali P08922.
    SMRi P08922. Positions 99-185, 191-279, 632-668, 943-1147, 1484-1537, 1657-1849, 1881-2229.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 112025. 5 interactions.
    IntActi P08922. 3 interactions.
    MINTi MINT-2800684.
    STRINGi 9606.ENSP00000357494.

    Chemistry

    BindingDBi P08922.
    ChEMBLi CHEMBL5568.
    GuidetoPHARMACOLOGYi 1840.

    PTM databases

    PhosphoSitei P08922.

    Polymorphism databases

    DMDMi 126302596.

    Proteomic databases

    PaxDbi P08922.
    PRIDEi P08922.

    Protocols and materials databases

    DNASUi 6098.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000368508 ; ENSP00000357494 ; ENSG00000047936 .
    GeneIDi 6098.
    KEGGi hsa:6098.
    UCSCi uc003pxp.1. human.

    Organism-specific databases

    CTDi 6098.
    GeneCardsi GC06M117609.
    H-InvDB HIX0207391.
    HGNCi HGNC:10261. ROS1.
    HPAi HPA049098.
    MIMi 165020. gene.
    neXtProti NX_P08922.
    PharmGKBi PA34633.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi COG0515.
    HOGENOMi HOG000137937.
    HOVERGENi HBG058631.
    InParanoidi P08922.
    KOi K05088.
    OMAi YWLVQDS.
    OrthoDBi EOG7GN2KT.
    PhylomeDBi P08922.
    TreeFami TF351636.

    Enzyme and pathway databases

    BRENDAi 2.7.10.1. 2681.
    SignaLinki P08922.

    Miscellaneous databases

    ChiTaRSi ROS1. human.
    GeneWikii ROS1_(gene).
    GenomeRNAii 6098.
    NextBioi 23723.
    PROi P08922.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi P08922.
    Bgeei P08922.
    CleanExi HS_ROS1.
    Genevestigatori P08922.

    Family and domain databases

    Gene3Di 2.120.10.30. 3 hits.
    2.60.40.10. 7 hits.
    InterProi IPR011042. 6-blade_b-propeller_TolB-like.
    IPR003961. Fibronectin_type3.
    IPR013783. Ig-like_fold.
    IPR011009. Kinase-like_dom.
    IPR000033. LDLR_classB_rpt.
    IPR000719. Prot_kinase_dom.
    IPR017441. Protein_kinase_ATP_BS.
    IPR001245. Ser-Thr/Tyr_kinase_cat_dom.
    IPR008266. Tyr_kinase_AS.
    IPR020635. Tyr_kinase_cat_dom.
    IPR002011. Tyr_kinase_rcpt_2_CS.
    [Graphical view ]
    Pfami PF00041. fn3. 4 hits.
    PF07714. Pkinase_Tyr. 1 hit.
    [Graphical view ]
    PRINTSi PR00109. TYRKINASE.
    SMARTi SM00060. FN3. 9 hits.
    SM00135. LY. 4 hits.
    SM00219. TyrKc. 1 hit.
    [Graphical view ]
    SUPFAMi SSF49265. SSF49265. 5 hits.
    SSF56112. SSF56112. 1 hit.
    PROSITEi PS50853. FN3. 9 hits.
    PS00107. PROTEIN_KINASE_ATP. 1 hit.
    PS50011. PROTEIN_KINASE_DOM. 1 hit.
    PS00109. PROTEIN_KINASE_TYR. 1 hit.
    PS00239. RECEPTOR_TYR_KIN_II. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "Characterization of ROS1 cDNA from a human glioblastoma cell line."
      Birchmeier C., O'Neill K., Riggs M., Wigler M.
      Proc. Natl. Acad. Sci. U.S.A. 87:4799-4803(1990) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANTS ASN-2213; GLN-2228 AND CYS-2229.
    2. "The DNA sequence and analysis of human chromosome 6."
      Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L., Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R., Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D., Andrews T.D.
      , Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H., Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V., Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J., Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E., Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J., French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J., Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C., Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A., Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R., Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M., Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K., Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R., Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M., Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A., Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L., Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I., Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y., Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E., Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A., Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W., Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J., Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M., Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I., Rogers J., Beck S.
      Nature 425:805-811(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    3. "Human c-ros-1 gene homologous to the v-ros sequence of UR2 sarcoma virus encodes for a transmembrane receptorlike molecule."
      Matsushime H., Wang L.-H., Shibuya M.
      Mol. Cell. Biol. 6:3000-3004(1986) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1790-2260.
    4. "Characterization of an activated human ros gene."
      Birchmeier C., Birnbaum D., Waitches G., Fasano O., Wigler M.
      Mol. Cell. Biol. 6:3109-3116(1986) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1854-2347.
    5. "Analysis of oncogene expression in primary human gliomas: evidence for increased expression of the ros oncogene."
      Watkins D., Dion F., Poisson M., Delattre J.Y., Rouleau G.A.
      Cancer Genet. Cytogenet. 72:130-136(1994) [PubMed] [Europe PMC] [Abstract]
      Cited for: TISSUE SPECIFICITY.
    6. "Vav3 mediates receptor protein tyrosine kinase signaling, regulates GTPase activity, modulates cell morphology, and induces cell transformation."
      Zeng L., Sachdev P., Yan L., Chan J.L., Trenkle T., McClelland M., Welsh J., Wang L.H.
      Mol. Cell. Biol. 20:9212-9224(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION IN VAV3 ACTIVATION, INTERACTION WITH VAV3.
    7. "Fusion of FIG to the receptor tyrosine kinase ROS in a glioblastoma with an interstitial del(6)(q21q21)."
      Charest A., Lane K., McMahon K., Park J., Preisinger E., Conroy H., Housman D.
      Genes Chromosomes Cancer 37:58-71(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: DISEASE, CHROMOSOMAL TRANSLOCATION WITH GOPC, MUTAGENESIS OF LYS-1980.
    8. "Oncogenic targeting of an activated tyrosine kinase to the Golgi apparatus in a glioblastoma."
      Charest A., Kheifets V., Park J., Lane K., McMahon K., Nutt C.L., Housman D.
      Proc. Natl. Acad. Sci. U.S.A. 100:916-921(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION AT TYR-2274 AND TYR-2334, MUTAGENESIS OF TYR-2274 AND TYR-2334.
    9. "ROS fusion tyrosine kinase activates a SH2 domain-containing phosphatase-2/phosphatidylinositol 3-kinase/mammalian target of rapamycin signaling axis to form glioblastoma in mice."
      Charest A., Wilker E.W., McLaughlin M.E., Lane K., Gowda R., Coven S., McMahon K., Kovach S., Feng Y., Yaffe M.B., Jacks T., Housman D.
      Cancer Res. 66:7473-7481(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION IN CELL PROLIFERATION AND DIFFERENTATION, FUNCTION IN PHOSPHORYLATION OF PTPN11, INTERACTION WITH PTPN11.
    10. "Patterns of somatic mutation in human cancer genomes."
      Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G.
      , Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R.
      Nature 446:153-158(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANTS [LARGE SCALE ANALYSIS] SER-13; VAL-126; PRO-145; GLN-167; SER-224; CYS-338; PRO-370; HIS-419; MET-537; PHE-653; HIS-865; LEU-1109; PHE-1239; SER-1353; ARG-1370; GLY-1506; HIS-1776; LYS-1902; ASN-1999; ARG-2003; SER-2138; ASN-2203; GLU-2213; ASN-2213; GLN-2228; CYS-2229 AND LYS-2240.

    Entry informationi

    Entry nameiROS1_HUMAN
    AccessioniPrimary (citable) accession number: P08922
    Secondary accession number(s): Q15368, Q5TDB5
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: November 1, 1988
    Last sequence update: February 20, 2007
    Last modified: October 1, 2014
    This is version 154 of the entry and version 3 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program
    DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

    Miscellaneousi

    Keywords - Technical termi

    3D-structure, Complete proteome, Reference proteome

    Documents

    1. Human chromosome 6
      Human chromosome 6: entries, gene names and cross-references to MIM
    2. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    3. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    4. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    5. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    6. Human and mouse protein kinases
      Human and mouse protein kinases: classification and index
    7. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3