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P08922 (ROS1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 153. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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 names
Name:ROS1
Synonyms:MCF3, ROS
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length2347 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.6 Ref.9

Catalytic activity

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

Enzyme regulation

Inhibited by dephosphorylation by PTPN6 By similarity.

Subunit structure

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. Ref.6 Ref.9

Subcellular location

Cell membrane; Single-pass type I membrane protein Probable.

Tissue specificity

Expressed in brain. Expression is increased in primary gliomas. Ref.5

Post-translational modification

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. Ref.8

Involvement in disease

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. Ref.7

Sequence similarities

Belongs to the protein kinase superfamily. Tyr protein kinase family. Insulin receptor subfamily.

Contains 9 fibronectin type-III domains.

Contains 1 protein kinase domain.

Ontologies

Keywords
   Cellular componentCell membrane
Membrane
   Coding sequence diversityChromosomal rearrangement
Polymorphism
   DiseaseProto-oncogene
   DomainRepeat
Signal
Transmembrane
Transmembrane helix
   LigandATP-binding
Nucleotide-binding
   Molecular functionKinase
Receptor
Transferase
Tyrosine-protein kinase
   PTMGlycoprotein
Phosphoprotein
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processcell differentiation

Inferred from sequence or structural similarity. Source: UniProtKB

cell growth

Inferred from direct assay Ref.9. Source: UniProtKB

cell proliferation

Inferred from sequence or structural similarity. Source: UniProtKB

columnar/cuboidal epithelial cell development

Inferred from sequence or structural similarity. Source: UniProtKB

negative regulation of gene expression

Inferred from electronic annotation. Source: Ensembl

peptidyl-tyrosine phosphorylation

Inferred from direct assay Ref.9. Source: GOC

protein phosphorylation

Inferred from direct assay Ref.9. Source: UniProtKB

regulation of ERK1 and ERK2 cascade

Inferred from sequence or structural similarity. Source: UniProtKB

regulation of TOR signaling

Inferred from direct assay Ref.9. Source: UniProtKB

regulation of phosphate transport

Inferred from electronic annotation. Source: Ensembl

spermatogenesis

Inferred from sequence or structural similarity. Source: UniProtKB

transmembrane receptor protein tyrosine kinase signaling pathway

Inferred from electronic annotation. Source: InterPro

   Cellular_componentintegral component of membrane

Inferred from electronic annotation. Source: UniProtKB-KW

membrane

Traceable author statement Ref.4. Source: ProtInc

plasma membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

   Molecular_functionATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

protein binding

Inferred from physical interaction PubMed 17416557. Source: IntAct

protein phosphatase binding

Inferred from physical interaction Ref.9. Source: UniProtKB

protein tyrosine kinase activity

Inferred from direct assay Ref.9. Source: UniProtKB

transmembrane receptor protein tyrosine kinase activity

Inferred from electronic annotation. Source: UniProtKB-EC

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

PTPN1P180313EBI-7371065,EBI-968788
PTPN6P293502EBI-7371065,EBI-78260

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2727 Potential
Chain28 – 23472320Proto-oncogene tyrosine-protein kinase ROS
PRO_0000016722

Regions

Topological domain28 – 18591832Extracellular Potential
Transmembrane1860 – 188223Helical; Potential
Topological domain1883 – 2347465Cytoplasmic Potential
Domain101 – 19696Fibronectin type-III 1
Domain197 – 28589Fibronectin type-III 2
Domain557 – 671115Fibronectin type-III 3
Domain947 – 104296Fibronectin type-III 4
Domain1043 – 1150108Fibronectin type-III 5
Domain1450 – 1556107Fibronectin type-III 6
Domain1557 – 1656100Fibronectin type-III 7
Domain1658 – 175194Fibronectin type-III 8
Domain1752 – 1854103Fibronectin type-III 9
Domain1945 – 2222278Protein kinase
Nucleotide binding1951 – 19599ATP By similarity

Sites

Active site20791Proton acceptor By similarity
Binding site19801ATP Probable
Site1852 – 18532Breakpoint for translocation to form SLC34A2-ROS1 and CD74-ROS1 fusion proteins
Site1880 – 18812Breakpoint for translocation to form GOPC-ROS1 fusion protein

Amino acid modifications

Modified residue22741Phosphotyrosine; by autocatalysis Probable
Modified residue23341Phosphotyrosine; by autocatalysis Probable
Glycosylation521N-linked (GlcNAc...) Potential
Glycosylation1141N-linked (GlcNAc...) Potential
Glycosylation1231N-linked (GlcNAc...) Potential
Glycosylation3241N-linked (GlcNAc...) Potential
Glycosylation3521N-linked (GlcNAc...) Potential
Glycosylation3961N-linked (GlcNAc...) Potential
Glycosylation4711N-linked (GlcNAc...) Potential
Glycosylation6071N-linked (GlcNAc...) Potential
Glycosylation6281N-linked (GlcNAc...) Potential
Glycosylation7061N-linked (GlcNAc...) Potential
Glycosylation7141N-linked (GlcNAc...) Potential
Glycosylation7321N-linked (GlcNAc...) Potential
Glycosylation9391N-linked (GlcNAc...) Potential
Glycosylation9611N-linked (GlcNAc...) Potential
Glycosylation10151N-linked (GlcNAc...) Potential
Glycosylation10871N-linked (GlcNAc...) Potential
Glycosylation10901N-linked (GlcNAc...) Potential
Glycosylation10951N-linked (GlcNAc...) Potential
Glycosylation12111N-linked (GlcNAc...) Potential
Glycosylation12721N-linked (GlcNAc...) Potential
Glycosylation13301N-linked (GlcNAc...) Potential
Glycosylation14581N-linked (GlcNAc...) Potential
Glycosylation14611N-linked (GlcNAc...) Potential
Glycosylation14741N-linked (GlcNAc...) Potential
Glycosylation14991N-linked (GlcNAc...) Potential
Glycosylation15651N-linked (GlcNAc...) Potential
Glycosylation16691N-linked (GlcNAc...) Potential
Glycosylation17151N-linked (GlcNAc...) Potential
Glycosylation17381N-linked (GlcNAc...) Potential
Glycosylation18081N-linked (GlcNAc...) Potential

Natural variations

Natural variant131N → S. Ref.10
Corresponds to variant rs45606237 [ dbSNP | Ensembl ].
VAR_041442
Natural variant1261G → V. Ref.10
Corresponds to variant rs34245787 [ dbSNP | Ensembl ].
VAR_041443
Natural variant1451T → P. Ref.10
Corresponds to variant rs1998206 [ dbSNP | Ensembl ].
VAR_030648
Natural variant1671R → Q. Ref.10
Corresponds to variant rs2243380 [ dbSNP | Ensembl ].
VAR_030649
Natural variant2241P → S. Ref.10
Corresponds to variant rs55959124 [ dbSNP | Ensembl ].
VAR_041444
Natural variant3381Y → C. Ref.10
Corresponds to variant rs55707658 [ dbSNP | Ensembl ].
VAR_041445
Natural variant3701S → P. Ref.10
Corresponds to variant rs56274823 [ dbSNP | Ensembl ].
VAR_041446
Natural variant4191Y → H in a gastric adenocarcinoma sample; somatic mutation. Ref.10
VAR_041447
Natural variant5371I → M. Ref.10
Corresponds to variant rs28639589 [ dbSNP | Ensembl ].
VAR_041448
Natural variant6531S → F. Ref.10
Corresponds to variant rs34203286 [ dbSNP | Ensembl ].
VAR_041449
Natural variant7901N → S.
Corresponds to variant rs34582164 [ dbSNP | Ensembl ].
VAR_049712
Natural variant8651Q → H in a lung large cell carcinoma sample; somatic mutation. Ref.10
VAR_041450
Natural variant11091S → L. Ref.10
Corresponds to variant rs2229079 [ dbSNP | Ensembl ].
VAR_030650
Natural variant12391Y → F. Ref.10
Corresponds to variant rs56192249 [ dbSNP | Ensembl ].
VAR_041451
Natural variant13531Y → S. Ref.10
Corresponds to variant rs35269727 [ dbSNP | Ensembl ].
VAR_041452
Natural variant13701C → R. Ref.10
Corresponds to variant rs36106063 [ dbSNP | Ensembl ].
VAR_041453
Natural variant14391F → S.
Corresponds to variant rs17079086 [ dbSNP | Ensembl ].
VAR_030651
Natural variant15061R → G. Ref.10
Corresponds to variant rs35841892 [ dbSNP | Ensembl ].
VAR_041454
Natural variant17761D → H. Ref.10
Corresponds to variant rs12664076 [ dbSNP | Ensembl ].
VAR_030652
Natural variant19021E → K. Ref.10
Corresponds to variant rs9489124 [ dbSNP | Ensembl ].
VAR_030653
Natural variant19991H → N. Ref.10
Corresponds to variant rs45569132 [ dbSNP | Ensembl ].
VAR_041455
Natural variant20031K → R in a colorectal adenocarcinoma sample; somatic mutation. Ref.10
VAR_041456
Natural variant20391R → H.
Corresponds to variant rs3752566 [ dbSNP | Ensembl ].
VAR_030654
Natural variant21381F → S in a gastric adenocarcinoma sample; somatic mutation. Ref.10
VAR_041457
Natural variant22031D → N. Ref.10
VAR_041458
Natural variant22131D → E. Ref.10
Corresponds to variant rs75510639 [ dbSNP | Ensembl ].
VAR_041459
Natural variant22131D → N. Ref.1 Ref.10
Corresponds to variant rs529038 [ dbSNP | Ensembl ].
VAR_030655
Natural variant22281K → Q. Ref.1 Ref.10
Corresponds to variant rs529156 [ dbSNP | Ensembl ].
VAR_041460
Natural variant22291S → C. Ref.1 Ref.10
Corresponds to variant rs619203 [ dbSNP | Ensembl ].
VAR_030656
Natural variant22401N → K. Ref.10
Corresponds to variant rs210968 [ dbSNP | Ensembl ].
VAR_030657
Natural variant23281K → R.
Corresponds to variant rs35932630 [ dbSNP | Ensembl ].
VAR_049713

Experimental info

Mutagenesis19801K → M: Loss of kinase activity. Ref.7
Mutagenesis22741Y → F: Loss of phosphorylation at Y-2274 and loss of interaction with PTPN11. Ref.8
Mutagenesis23341Y → F: Loss of phosphorylation at Y-2334 and loss of interaction with PTPN11. Ref.8
Sequence conflict2246 – 226015EDGDV…DDIMP → KFDSSEFSSFRCTVN in AAA60277. Ref.3
Sequence conflict22621A → V in AAA60278. Ref.1

Secondary structure

......................................... 2347
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P08922 [UniParc].

Last modified February 20, 2007. Version 3.
Checksum: 98902B9A59ACB8F5

FASTA2,347263,915
        10         20         30         40         50         60 
MKNIYCLIPK LVNFATLGCL WISVVQCTVL NSCLKSCVTN LGQQLDLGTP HNLSEPCIQG 

        70         80         90        100        110        120 
CHFWNSVDQK NCALKCRESC EVGCSSAEGA YEEEVLENAD LPTAPFASSI GSHNMTLRWK 

       130        140        150        160        170        180 
SANFSGVKYI IQWKYAQLLG SWTYTKTVSR PSYVVKPLHP FTEYIFRVVW IFTAQLQLYS 

       190        200        210        220        230        240 
PPSPSYRTHP HGVPETAPLI RNIESSSPDT VEVSWDPPQF PGGPILGYNL RLISKNQKLD 

       250        260        270        280        290        300 
AGTQRTSFQF YSTLPNTIYR FSIAAVNEVG EGPEAESSIT TSSSAVQQEE QWLFLSRKTS 

       310        320        330        340        350        360 
LRKRSLKHLV DEAHCLRLDA IYHNITGISV DVHQQIVYFS EGTLIWAKKA ANMSDVSDLR 

       370        380        390        400        410        420 
IFYRGSGLIS SISIDWLYQR MYFIMDELVC VCDLENCSNI EEITPPSISA PQKIVADSYN 

       430        440        450        460        470        480 
GYVFYLLRDG IYRADLPVPS GRCAEAVRIV ESCTLKDFAI KPQAKRIIYF NDTAQVFMST 

       490        500        510        520        530        540 
FLDGSASHLI LPRIPFADVK SFACENNDFL VTDGKVIFQQ DALSFNEFIV GCDLSHIEEF 

       550        560        570        580        590        600 
GFGNLVIFGS SSQLHPLPGR PQELSVLFGS HQALVQWKPP ALAIGANVIL ISDIIELFEL 

       610        620        630        640        650        660 
GPSAWQNWTY EVKVSTQDPP EVTHIFLNIS GTMLNVPELQ SAMKYKVSVR ASSPKRPGPW 

       670        680        690        700        710        720 
SEPSVGTTLV PASEPPFIMA VKEDGLWSKP LNSFGPGEFL SSDIGNVSDM DWYNNSLYYS 

       730        740        750        760        770        780 
DTKGDVFVWL LNGTDISENY HLPSIAGAGA LAFEWLGHFL YWAGKTYVIQ RQSVLTGHTD 

       790        800        810        820        830        840 
IVTHVKLLVN DMVVDSVGGY LYWTTLYSVE STRLNGESSL VLQTQPWFSG KKVIALTLDL 

       850        860        870        880        890        900 
SDGLLYWLVQ DSQCIHLYTA VLRGQSTGDT TITEFAAWST SEISQNALMY YSGRLFWING 

       910        920        930        940        950        960 
FRIITTQEIG QKTSVSVLEP ARFNQFTIIQ TSLKPLPGNF SFTPKVIPDS VQESSFRIEG 

       970        980        990       1000       1010       1020 
NASSFQILWN GPPAVDWGVV FYSVEFSAHS KFLASEQHSL PVFTVEGLEP YALFNLSVTP 

      1030       1040       1050       1060       1070       1080 
YTYWGKGPKT SLSLRAPETV PSAPENPRIF ILPSGKCCNK NEVVVEFRWN KPKHENGVLT 

      1090       1100       1110       1120       1130       1140 
KFEIFYNISN QSITNKTCED WIAVNVTPSV MSFQLEGMSP RCFIAFQVRA FTSKGPGPYA 

      1150       1160       1170       1180       1190       1200 
DVVKSTTSEI NPFPHLITLL GNKIVFLDMD QNQVVWTFSA ERVISAVCYT ADNEMGYYAE 

      1210       1220       1230       1240       1250       1260 
GDSLFLLHLH NRSSSELFQD SLVFDITVIT IDWISRHLYF ALKESQNGMQ VFDVDLEHKV 

      1270       1280       1290       1300       1310       1320 
KYPREVKIHN RNSTIISFSV YPLLSRLYWT EVSNFGYQMF YYSIISHTLH RILQPTATNQ 

      1330       1340       1350       1360       1370       1380 
QNKRNQCSCN VTEFELSGAM AIDTSNLEKP LIYFAKAQEI WAMDLEGCQC WRVITVPAML 

      1390       1400       1410       1420       1430       1440 
AGKTLVSLTV DGDLIYWIIT AKDSTQIYQA KKGNGAIVSQ VKALRSRHIL AYSSVMQPFP 

      1450       1460       1470       1480       1490       1500 
DKAFLSLASD TVEPTILNAT NTSLTIRLPL AKTNLTWYGI TSPTPTYLVY YAEVNDRKNS 

      1510       1520       1530       1540       1550       1560 
SDLKYRILEF QDSIALIEDL QPFSTYMIQI AVKNYYSDPL EHLPPGKEIW GKTKNGVPEA 

      1570       1580       1590       1600       1610       1620 
VQLINTTVRS DTSLIISWRE SHKPNGPKES VRYQLAISHL ALIPETPLRQ SEFPNGRLTL 

      1630       1640       1650       1660       1670       1680 
LVTRLSGGNI YVLKVLACHS EEMWCTESHP VTVEMFNTPE KPYSLVPENT SLQFNWKAPL 

      1690       1700       1710       1720       1730       1740 
NVNLIRFWVE LQKWKYNEFY HVKTSCSQGP AYVCNITNLQ PYTSYNVRVV VVYKTGENST 

      1750       1760       1770       1780       1790       1800 
SLPESFKTKA GVPNKPGIPK LLEGSKNSIQ WEKAEDNGCR ITYYILEIRK STSNNLQNQN 

      1810       1820       1830       1840       1850       1860 
LRWKMTFNGS CSSVCTWKSK NLKGIFQFRV VAANNLGFGE YSGISENIIL VGDDFWIPET 

      1870       1880       1890       1900       1910       1920 
SFILTIIVGI FLVVTIPLTF VWHRRLKNQK SAKEGVTVLI NEDKELAELR GLAAGVGLAN 

      1930       1940       1950       1960       1970       1980 
ACYAIHTLPT QEEIENLPAF PREKLTLRLL LGSGAFGEVY EGTAVDILGV GSGEIKVAVK 

      1990       2000       2010       2020       2030       2040 
TLKKGSTDQE KIEFLKEAHL MSKFNHPNIL KQLGVCLLNE PQYIILELME GGDLLTYLRK 

      2050       2060       2070       2080       2090       2100 
ARMATFYGPL LTLVDLVDLC VDISKGCVYL ERMHFIHRDL AARNCLVSVK DYTSPRIVKI 

      2110       2120       2130       2140       2150       2160 
GDFGLARDIY KNDYYRKRGE GLLPVRWMAP ESLMDGIFTT QSDVWSFGIL IWEILTLGHQ 

      2170       2180       2190       2200       2210       2220 
PYPAHSNLDV LNYVQTGGRL EPPRNCPDDL WNLMTQCWAQ EPDQRPTFHR IQDQLQLFRN 

      2230       2240       2250       2260       2270       2280 
FFLNSIYKSR DEANNSGVIN ESFEGEDGDV ICLNSDDIMP VALMETKNRE GLNYMVLATE 

      2290       2300       2310       2320       2330       2340 
CGQGEEKSEG PLGSQESESC GLRKEEKEPH ADKDFCQEKQ VAYCPSGKPE GLNYACLTHS 


GYGDGSD 

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References

« Hide 'large scale' references
[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. expand/collapse author list , 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. expand/collapse author list , 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.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
M34353 mRNA. Translation: AAA60278.1.
Z98880, AL132671 Genomic DNA. Translation: CAI42374.1.
AL132671, Z98880 Genomic DNA. Translation: CAI23378.1.
M13599 expand/collapse EMBL AC list , M13368, M13591, M13592, M13593, M13594, M13595, M13596, M13597, M13598 Genomic DNA. Translation: AAA60277.1.
M13880 mRNA. Translation: AAA36580.1.
CCDSCCDS5116.1.
PIRTVHURS. A35512.
RefSeqNP_002935.2. NM_002944.2.
UniGeneHs.1041.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
3ZBFX-ray2.20A1934-2232[»]
ProteinModelPortalP08922.
SMRP08922. Positions 99-185, 191-279, 632-668, 943-1147, 1484-1537, 1657-1849, 1881-2229.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid112025. 5 interactions.
IntActP08922. 2 interactions.
MINTMINT-2800684.
STRING9606.ENSP00000357494.

Chemistry

BindingDBP08922.
ChEMBLCHEMBL5568.
GuidetoPHARMACOLOGY1840.

PTM databases

PhosphoSiteP08922.

Polymorphism databases

DMDM126302596.

Proteomic databases

PaxDbP08922.
PRIDEP08922.

Protocols and materials databases

DNASU6098.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000368508; ENSP00000357494; ENSG00000047936.
GeneID6098.
KEGGhsa:6098.
UCSCuc003pxp.1. human.

Organism-specific databases

CTD6098.
GeneCardsGC06M117609.
H-InvDBHIX0207391.
HGNCHGNC:10261. ROS1.
HPAHPA049098.
MIM165020. gene.
neXtProtNX_P08922.
PharmGKBPA34633.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0515.
HOGENOMHOG000137937.
HOVERGENHBG058631.
InParanoidP08922.
KOK05088.
OMAYWLVQDS.
OrthoDBEOG7GN2KT.
PhylomeDBP08922.
TreeFamTF351636.

Enzyme and pathway databases

BRENDA2.7.10.1. 2681.
SignaLinkP08922.

Gene expression databases

ArrayExpressP08922.
BgeeP08922.
CleanExHS_ROS1.
GenevestigatorP08922.

Family and domain databases

Gene3D2.120.10.30. 3 hits.
2.60.40.10. 7 hits.
InterProIPR011042. 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]
PfamPF00041. fn3. 4 hits.
PF07714. Pkinase_Tyr. 1 hit.
[Graphical view]
PRINTSPR00109. TYRKINASE.
SMARTSM00060. FN3. 9 hits.
SM00135. LY. 4 hits.
SM00219. TyrKc. 1 hit.
[Graphical view]
SUPFAMSSF49265. SSF49265. 5 hits.
SSF56112. SSF56112. 1 hit.
PROSITEPS50853. 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]
ProtoNetSearch...

Other

ChiTaRSROS1. human.
GeneWikiROS1_(gene).
GenomeRNAi6098.
NextBio23723.
PROP08922.
SOURCESearch...

Entry information

Entry nameROS1_HUMAN
AccessionPrimary (citable) accession number: P08922
Secondary accession number(s): Q15368, Q5TDB5
Entry history
Integrated into UniProtKB/Swiss-Prot: November 1, 1988
Last sequence update: February 20, 2007
Last modified: July 9, 2014
This is version 153 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

Human and mouse protein kinases

Human and mouse protein kinases: classification and index

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 6

Human chromosome 6: entries, gene names and cross-references to MIM