P08922 (ROS1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

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 names

Name:	ROS1
Synonyms:	MCF3, ROS

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	2347 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence 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 Ref.9
Involvement in disease	Note=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 component	Cell membrane Membrane
Coding sequence diversity	Chromosomal rearrangement Polymorphism
Disease	Proto-oncogene
Domain	Repeat Signal Transmembrane Transmembrane helix
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Receptor Transferase Tyrosine-protein kinase
PTM	Glycoprotein Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	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 regulation of ERK1 and ERK2 cascade Inferred from sequence or structural similarity. Source: UniProtKB regulation of TOR signaling cascade Inferred from direct assay Ref.9. Source: UniProtKB spermatogenesis Inferred from sequence or structural similarity. Source: UniProtKB transmembrane receptor protein tyrosine kinase signaling pathway Inferred from electronic annotation. Source: InterPro
Cellular component	integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW membrane fraction Traceable author statement. Source: ProtInc plasma membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW protein phosphatase binding Inferred from physical interaction Ref.9. Source: UniProtKB transmembrane receptor protein tyrosine kinase activity Inferred from electronic annotation. Source: EC
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 27	27	Potential
	Chain	28 – 2347	2320	Proto-oncogene tyrosine-protein kinase ROS		PRO_0000016722
Regions
	Topological domain	28 – 1859	1832	Extracellular Potential
	Transmembrane	1860 – 1882	23	Helical; Potential
	Topological domain	1883 – 2347	465	Cytoplasmic Potential
	Domain	98 – 188	91	Fibronectin type-III 1
	Domain	194 – 281	88	Fibronectin type-III 2
	Domain	558 – 668	111	Fibronectin type-III 3
	Domain	944 – 1036	93	Fibronectin type-III 4
	Domain	1041 – 1147	107	Fibronectin type-III 5
	Domain	1450 – 1548	99	Fibronectin type-III 6
	Domain	1558 – 1653	96	Fibronectin type-III 7
	Domain	1655 – 1748	94	Fibronectin type-III 8
	Domain	1749 – 1851	103	Fibronectin type-III 9
	Domain	1945 – 2222	278	Protein kinase
	Nucleotide binding	1951 – 1959	9	ATP By similarity
Sites
	Active site	2079	1	Proton acceptor By similarity
	Binding site	1980	1	ATP Probable
	Site	1852 – 1853	2	Breakpoint for translocation to form SLC34A2-ROS1 and CD74-ROS1 fusion proteins
	Site	1880 – 1881	2	Breakpoint for translocation to form GOPC-ROS1 fusion protein
Amino acid modifications
	Modified residue	2274	1	Phosphotyrosine; by autocatalysis Probable
	Modified residue	2334	1	Phosphotyrosine; by autocatalysis Probable
	Glycosylation	52	1	N-linked (GlcNAc...) Potential
	Glycosylation	114	1	N-linked (GlcNAc...) Potential
	Glycosylation	123	1	N-linked (GlcNAc...) Potential
	Glycosylation	324	1	N-linked (GlcNAc...) Potential
	Glycosylation	352	1	N-linked (GlcNAc...) Potential
	Glycosylation	396	1	N-linked (GlcNAc...) Potential
	Glycosylation	471	1	N-linked (GlcNAc...) Potential
	Glycosylation	607	1	N-linked (GlcNAc...) Potential
	Glycosylation	628	1	N-linked (GlcNAc...) Potential
	Glycosylation	706	1	N-linked (GlcNAc...) Potential
	Glycosylation	714	1	N-linked (GlcNAc...) Potential
	Glycosylation	732	1	N-linked (GlcNAc...) Potential
	Glycosylation	939	1	N-linked (GlcNAc...) Potential
	Glycosylation	961	1	N-linked (GlcNAc...) Potential
	Glycosylation	1015	1	N-linked (GlcNAc...) Potential
	Glycosylation	1087	1	N-linked (GlcNAc...) Potential
	Glycosylation	1090	1	N-linked (GlcNAc...) Potential
	Glycosylation	1095	1	N-linked (GlcNAc...) Potential
	Glycosylation	1211	1	N-linked (GlcNAc...) Potential
	Glycosylation	1272	1	N-linked (GlcNAc...) Potential
	Glycosylation	1330	1	N-linked (GlcNAc...) Potential
	Glycosylation	1458	1	N-linked (GlcNAc...) Potential
	Glycosylation	1461	1	N-linked (GlcNAc...) Potential
	Glycosylation	1474	1	N-linked (GlcNAc...) Potential
	Glycosylation	1499	1	N-linked (GlcNAc...) Potential
	Glycosylation	1565	1	N-linked (GlcNAc...) Potential
	Glycosylation	1669	1	N-linked (GlcNAc...) Potential
	Glycosylation	1715	1	N-linked (GlcNAc...) Potential
	Glycosylation	1738	1	N-linked (GlcNAc...) Potential
	Glycosylation	1808	1	N-linked (GlcNAc...) Potential
Natural variations
	Natural variant	13	1	N → S. Ref.11 Corresponds to variant rs45606237 [ dbSNP | Ensembl ].		VAR_041442
	Natural variant	126	1	G → V. Ref.11 Corresponds to variant rs34245787 [ dbSNP | Ensembl ].		VAR_041443
	Natural variant	145	1	T → P. Ref.11 Corresponds to variant rs1998206 [ dbSNP | Ensembl ].		VAR_030648
	Natural variant	167	1	R → Q. Ref.11 Corresponds to variant rs2243380 [ dbSNP | Ensembl ].		VAR_030649
	Natural variant	224	1	P → S. Ref.11 Corresponds to variant rs55959124 [ dbSNP | Ensembl ].		VAR_041444
	Natural variant	338	1	Y → C. Ref.11 Corresponds to variant rs55707658 [ dbSNP | Ensembl ].		VAR_041445
	Natural variant	370	1	S → P. Ref.11 Corresponds to variant rs56274823 [ dbSNP | Ensembl ].		VAR_041446
	Natural variant	419	1	Y → H in a gastric adenocarcinoma sample; somatic mutation. Ref.11		VAR_041447
	Natural variant	537	1	I → M. Ref.11 Corresponds to variant rs28639589 [ dbSNP | Ensembl ].		VAR_041448
	Natural variant	653	1	S → F. Ref.11 Corresponds to variant rs34203286 [ dbSNP | Ensembl ].		VAR_041449
	Natural variant	790	1	N → S. Corresponds to variant rs34582164 [ dbSNP | Ensembl ].		VAR_049712
	Natural variant	865	1	Q → H in a lung large cell carcinoma sample; somatic mutation. Ref.11		VAR_041450
	Natural variant	1109	1	S → L. Ref.11 Corresponds to variant rs2229079 [ dbSNP | Ensembl ].		VAR_030650
	Natural variant	1239	1	Y → F. Ref.11 Corresponds to variant rs56192249 [ dbSNP | Ensembl ].		VAR_041451
	Natural variant	1353	1	Y → S. Ref.11 Corresponds to variant rs35269727 [ dbSNP | Ensembl ].		VAR_041452
	Natural variant	1370	1	C → R. Ref.11 Corresponds to variant rs36106063 [ dbSNP | Ensembl ].		VAR_041453
	Natural variant	1439	1	F → S. Corresponds to variant rs17079086 [ dbSNP | Ensembl ].		VAR_030651
	Natural variant	1506	1	R → G. Ref.11 Corresponds to variant rs35841892 [ dbSNP | Ensembl ].		VAR_041454
	Natural variant	1776	1	D → H. Ref.11 Corresponds to variant rs12664076 [ dbSNP | Ensembl ].		VAR_030652
	Natural variant	1902	1	E → K. Ref.11 Corresponds to variant rs9489124 [ dbSNP | Ensembl ].		VAR_030653
	Natural variant	1999	1	H → N. Ref.11 Corresponds to variant rs45569132 [ dbSNP | Ensembl ].		VAR_041455
	Natural variant	2003	1	K → R in a colorectal adenocarcinoma sample; somatic mutation. Ref.11		VAR_041456
	Natural variant	2039	1	R → H. Corresponds to variant rs3752566 [ dbSNP | Ensembl ].		VAR_030654
	Natural variant	2138	1	F → S in a gastric adenocarcinoma sample; somatic mutation. Ref.11		VAR_041457
	Natural variant	2203	1	D → N. Ref.11		VAR_041458
	Natural variant	2213	1	D → E. Ref.11		VAR_041459
	Natural variant	2213	1	D → N. Ref.1 Ref.11 Corresponds to variant rs529038 [ dbSNP | Ensembl ].		VAR_030655
	Natural variant	2228	1	K → Q. Ref.1 Ref.11 Corresponds to variant rs529156 [ dbSNP | Ensembl ].		VAR_041460
	Natural variant	2229	1	S → C. Ref.1 Ref.11 Corresponds to variant rs619203 [ dbSNP | Ensembl ].		VAR_030656
	Natural variant	2240	1	N → K. Ref.11 Corresponds to variant rs210968 [ dbSNP | Ensembl ].		VAR_030657
	Natural variant	2328	1	K → R. Corresponds to variant rs35932630 [ dbSNP | Ensembl ].		VAR_049713
Experimental info
	Mutagenesis	1980	1	K → M: Loss of kinase activity. Ref.7
	Mutagenesis	2274	1	Y → F: Loss of phosphorylation at Y-2274 and loss of interaction with PTPN11. Ref.8
	Mutagenesis	2334	1	Y → F: Loss of phosphorylation at Y-2334 and loss of interaction with PTPN11. Ref.8
	Sequence conflict	2246 – 2260	15	EDGDV…DDIMP → KFDSSEFSSFRCTVN in AAA60277. Ref.3
	Sequence conflict	2262	1	A → V in AAA60278. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	P08922 [UniParc]. Last modified February 20, 2007. Version 3. Checksum: 98902B9A59ACB8F5	FASTA	2,347	263,915
	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

References

	« Hide 'large scale' referencesShow '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: 2352949] [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: 14574404] [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: 3023956] [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: 3785223] [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: 8143271] [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: 11094073] [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: 12661006] [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: 12538861] [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: 16885344] [Abstract] Cited for: FUNCTION IN CELL PROLIFERATION AND DIFFERENTATION, FUNCTION IN PHOSPHORYLATION OF PTPN11, INTERACTION WITH PTPN11.
[10]	"Global survey of phosphotyrosine signaling identifies oncogenic kinases in lung cancer." Rikova K., Guo A., Zeng Q., Possemato A., Yu J., Haack H., Nardone J., Lee K., Reeves C., Li Y., Hu Y., Tan Z., Stokes M., Sullivan L., Mitchell J., Wetzel R., Macneill J., Ren J.M. , Yuan J., Bakalarski C.E., Villen J., Kornhauser J.M., Smith B., Li D., Zhou X., Gygi S.P., Gu T.-L., Polakiewicz R.D., Rush J., Comb M.J. Cell 131:1190-1203(2007) [PubMed: 18083107] [Abstract] Cited for: CHROMOSOMAL TRANSLOCATION WITH CD74 AND SLC34A2.
[11]	"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: 17344846] [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 , M13368, M13591, M13592, M13593, M13594, M13595, M13596, M13597, M13598 Genomic DNA. Translation: AAA60277.1. M13880 mRNA. Translation: AAA36580.1.
IPI	IPI00288965.
PIR	TVHURS. A35512.
RefSeq	NP_002935.2. NM_002944.2.
UniGene	Hs.1041.
3D structure databases
ProteinModelPortal	P08922.
SMR	P08922. Positions 110-280, 555-668, 997-1152, 1556-1598, 1710-1851, 1935-2221.
ModBase	Search...
Protein-protein interaction databases
MINT	MINT-2800684.
STRING	P08922.
PTM databases
PhosphoSite	P08922.
Polymorphism databases
DMDM	126302596.
Proteomic databases
PRIDE	P08922.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000368508; ENSP00000357494; ENSG00000047936.
GeneID	6098.
KEGG	hsa:6098.
UCSC	uc003pxp.1. human.
Organism-specific databases
CTD	6098.
GeneCards	GC06M117609.
HGNC	HGNC:10261. ROS1.
MIM	165020. gene.
neXtProt	NX_P08922.
PharmGKB	PA34633.
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG09325.
GeneTree	ENSGT00600000084105.
HOGENOM	HBG279743.
HOVERGEN	HBG058631.
InParanoid	P08922.
OMA	FQFYSTL.
OrthoDB	EOG4PK26W.
PhylomeDB	P08922.
Enzyme and pathway databases
BRENDA	2.7.10.1. 2681.
Gene expression databases
ArrayExpress	P08922.
Bgee	P08922.
CleanEx	HS_ROS1.
Genevestigator	P08922.
GermOnline	ENSG00000047936. Homo sapiens.
Family and domain databases
InterPro	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_cat_dom. IPR017441. Protein_kinase_ATP_BS. IPR001245. Ser-Thr/Tyr_kinase. IPR008266. Tyr_kinase_AS. IPR020635. Tyr_kinase_cat_dom. IPR002011. Tyr_kinase_rcpt_2_CS. [Graphical view]
Gene3D	G3DSA:2.120.10.30. 6-blade_b-propeller_TolB-like. 3 hits. G3DSA:2.60.40.10. Ig-like_fold. 8 hits.
KO	K05088.
Pfam	PF00041. fn3. 4 hits. PF07714. Pkinase_Tyr. 1 hit. [Graphical view]
PRINTS	PR00109. TYRKINASE.
SMART	SM00060. FN3. 9 hits. SM00135. LY. 4 hits. SM00219. TyrKc. 1 hit. [Graphical view]
SUPFAM	SSF49265. FN_III-like. 8 hits. SSF56112. Kinase_like. 1 hit.
PROSITE	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]
ProtoNet	Search...
Other
NextBio	23723.
SOURCE	Search...

Entry information

Entry name

ROS1_HUMAN

Accession

Primary (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:	January 25, 2012
This is version 128 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.