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P08922

- ROS1_HUMAN

UniProt

P08922 - ROS1_HUMAN

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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

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 phosphatase binding Source: UniProtKB
  3. protein tyrosine kinase activity Source: UniProtKB
  4. 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
Complete GO annotation...

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

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini28 – 18591832ExtracellularSequence AnalysisAdd
BLAST
Transmembranei1860 – 188223HelicalSequence AnalysisAdd
BLAST
Topological domaini1883 – 2347465CytoplasmicSequence AnalysisAdd
BLAST

GO - Cellular componenti

  1. integral component of membrane Source: UniProtKB-KW
  2. membrane Source: ProtInc
  3. plasma membrane Source: UniProtKB-KW
Complete GO annotation...

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

BgeeiP08922.
CleanExiHS_ROS1.
ExpressionAtlasiP08922. baseline and differential.
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 – 19443Combined sources
Beta strandi1945 – 19528Combined sources
Beta strandi1959 – 19657Combined sources
Beta strandi1974 – 19818Combined sources
Helixi1988 – 200215Combined sources
Beta strandi2012 – 20165Combined sources
Beta strandi2018 – 20214Combined sources
Beta strandi2023 – 20275Combined sources
Helixi2034 – 204310Combined sources
Helixi2053 – 207220Combined sources
Helixi2082 – 20843Combined sources
Beta strandi2085 – 20884Combined sources
Beta strandi2090 – 20945Combined sources
Beta strandi2098 – 21003Combined sources
Helixi2125 – 21273Combined sources
Helixi2130 – 21356Combined sources
Helixi2140 – 215516Combined sources
Helixi2167 – 21759Combined sources
Helixi2188 – 219710Combined sources
Helixi2202 – 22043Combined sources
Helixi2208 – 222720Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
3ZBFX-ray2.20A1934-2232[»]
ProteinModelPortaliP08922.
SMRiP08922. Positions 99-185, 193-276, 632-668, 943-1147, 1484-1537, 1657-1849, 1881-2229.
ModBaseiSearch...
MobiDBiSearch...

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.
GeneTreeiENSGT00760000118818.
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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        10         20         30         40         50
MKNIYCLIPK LVNFATLGCL WISVVQCTVL NSCLKSCVTN LGQQLDLGTP
60 70 80 90 100
HNLSEPCIQG CHFWNSVDQK NCALKCRESC EVGCSSAEGA YEEEVLENAD
110 120 130 140 150
LPTAPFASSI GSHNMTLRWK SANFSGVKYI IQWKYAQLLG SWTYTKTVSR
160 170 180 190 200
PSYVVKPLHP FTEYIFRVVW IFTAQLQLYS PPSPSYRTHP HGVPETAPLI
210 220 230 240 250
RNIESSSPDT VEVSWDPPQF PGGPILGYNL RLISKNQKLD AGTQRTSFQF
260 270 280 290 300
YSTLPNTIYR FSIAAVNEVG EGPEAESSIT TSSSAVQQEE QWLFLSRKTS
310 320 330 340 350
LRKRSLKHLV DEAHCLRLDA IYHNITGISV DVHQQIVYFS EGTLIWAKKA
360 370 380 390 400
ANMSDVSDLR IFYRGSGLIS SISIDWLYQR MYFIMDELVC VCDLENCSNI
410 420 430 440 450
EEITPPSISA PQKIVADSYN GYVFYLLRDG IYRADLPVPS GRCAEAVRIV
460 470 480 490 500
ESCTLKDFAI KPQAKRIIYF NDTAQVFMST FLDGSASHLI LPRIPFADVK
510 520 530 540 550
SFACENNDFL VTDGKVIFQQ DALSFNEFIV GCDLSHIEEF GFGNLVIFGS
560 570 580 590 600
SSQLHPLPGR PQELSVLFGS HQALVQWKPP ALAIGANVIL ISDIIELFEL
610 620 630 640 650
GPSAWQNWTY EVKVSTQDPP EVTHIFLNIS GTMLNVPELQ SAMKYKVSVR
660 670 680 690 700
ASSPKRPGPW SEPSVGTTLV PASEPPFIMA VKEDGLWSKP LNSFGPGEFL
710 720 730 740 750
SSDIGNVSDM DWYNNSLYYS DTKGDVFVWL LNGTDISENY HLPSIAGAGA
760 770 780 790 800
LAFEWLGHFL YWAGKTYVIQ RQSVLTGHTD IVTHVKLLVN DMVVDSVGGY
810 820 830 840 850
LYWTTLYSVE STRLNGESSL VLQTQPWFSG KKVIALTLDL SDGLLYWLVQ
860 870 880 890 900
DSQCIHLYTA VLRGQSTGDT TITEFAAWST SEISQNALMY YSGRLFWING
910 920 930 940 950
FRIITTQEIG QKTSVSVLEP ARFNQFTIIQ TSLKPLPGNF SFTPKVIPDS
960 970 980 990 1000
VQESSFRIEG NASSFQILWN GPPAVDWGVV FYSVEFSAHS KFLASEQHSL
1010 1020 1030 1040 1050
PVFTVEGLEP YALFNLSVTP YTYWGKGPKT SLSLRAPETV PSAPENPRIF
1060 1070 1080 1090 1100
ILPSGKCCNK NEVVVEFRWN KPKHENGVLT KFEIFYNISN QSITNKTCED
1110 1120 1130 1140 1150
WIAVNVTPSV MSFQLEGMSP RCFIAFQVRA FTSKGPGPYA DVVKSTTSEI
1160 1170 1180 1190 1200
NPFPHLITLL GNKIVFLDMD QNQVVWTFSA ERVISAVCYT ADNEMGYYAE
1210 1220 1230 1240 1250
GDSLFLLHLH NRSSSELFQD SLVFDITVIT IDWISRHLYF ALKESQNGMQ
1260 1270 1280 1290 1300
VFDVDLEHKV KYPREVKIHN RNSTIISFSV YPLLSRLYWT EVSNFGYQMF
1310 1320 1330 1340 1350
YYSIISHTLH RILQPTATNQ QNKRNQCSCN VTEFELSGAM AIDTSNLEKP
1360 1370 1380 1390 1400
LIYFAKAQEI WAMDLEGCQC WRVITVPAML AGKTLVSLTV DGDLIYWIIT
1410 1420 1430 1440 1450
AKDSTQIYQA KKGNGAIVSQ VKALRSRHIL AYSSVMQPFP DKAFLSLASD
1460 1470 1480 1490 1500
TVEPTILNAT NTSLTIRLPL AKTNLTWYGI TSPTPTYLVY YAEVNDRKNS
1510 1520 1530 1540 1550
SDLKYRILEF QDSIALIEDL QPFSTYMIQI AVKNYYSDPL EHLPPGKEIW
1560 1570 1580 1590 1600
GKTKNGVPEA VQLINTTVRS DTSLIISWRE SHKPNGPKES VRYQLAISHL
1610 1620 1630 1640 1650
ALIPETPLRQ SEFPNGRLTL LVTRLSGGNI YVLKVLACHS EEMWCTESHP
1660 1670 1680 1690 1700
VTVEMFNTPE KPYSLVPENT SLQFNWKAPL NVNLIRFWVE LQKWKYNEFY
1710 1720 1730 1740 1750
HVKTSCSQGP AYVCNITNLQ PYTSYNVRVV VVYKTGENST SLPESFKTKA
1760 1770 1780 1790 1800
GVPNKPGIPK LLEGSKNSIQ WEKAEDNGCR ITYYILEIRK STSNNLQNQN
1810 1820 1830 1840 1850
LRWKMTFNGS CSSVCTWKSK NLKGIFQFRV VAANNLGFGE YSGISENIIL
1860 1870 1880 1890 1900
VGDDFWIPET SFILTIIVGI FLVVTIPLTF VWHRRLKNQK SAKEGVTVLI
1910 1920 1930 1940 1950
NEDKELAELR GLAAGVGLAN ACYAIHTLPT QEEIENLPAF PREKLTLRLL
1960 1970 1980 1990 2000
LGSGAFGEVY EGTAVDILGV GSGEIKVAVK TLKKGSTDQE KIEFLKEAHL
2010 2020 2030 2040 2050
MSKFNHPNIL KQLGVCLLNE PQYIILELME GGDLLTYLRK ARMATFYGPL
2060 2070 2080 2090 2100
LTLVDLVDLC VDISKGCVYL ERMHFIHRDL AARNCLVSVK DYTSPRIVKI
2110 2120 2130 2140 2150
GDFGLARDIY KNDYYRKRGE GLLPVRWMAP ESLMDGIFTT QSDVWSFGIL
2160 2170 2180 2190 2200
IWEILTLGHQ PYPAHSNLDV LNYVQTGGRL EPPRNCPDDL WNLMTQCWAQ
2210 2220 2230 2240 2250
EPDQRPTFHR IQDQLQLFRN FFLNSIYKSR DEANNSGVIN ESFEGEDGDV
2260 2270 2280 2290 2300
ICLNSDDIMP VALMETKNRE GLNYMVLATE CGQGEEKSEG PLGSQESESC
2310 2320 2330 2340
GLRKEEKEPH ADKDFCQEKQ VAYCPSGKPE GLNYACLTHS GYGDGSD
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:
EMBLi
GenBanki
DDBJi
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:
EMBLi
GenBanki
DDBJi
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:
PDBei
RCSB PDBi
PDBji
Links Updated
Entry Method Resolution (Å) Chain Positions PDBsum
3ZBF X-ray 2.20 A 1934-2232 [» ]
ProteinModelPortali P08922.
SMRi P08922. Positions 99-185, 193-276, 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.
GeneTreei ENSGT00760000118818.
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

Bgeei P08922.
CleanExi HS_ROS1.
ExpressionAtlasi P08922. baseline and differential.
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

« Hide 'large scale' publications
  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: November 26, 2014
This is version 156 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