ROS1_HUMAN » Proto-oncogene tyrosine-protein kinase ROS

ROS1_HUMAN » Proto-oncogene tyrosine-protein kinase ROS
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Topology in Plasma membrane
Topologyextracellular side
cytoplasmic side
ROS1_HUMAN » Proto-oncogene tyrosine-protein kinase ROS » Proto-oncogene c-Ros;Proto-oncogene c-Ros-1;Receptor tyrosine kinase c-ros oncogene 1;c-Ros receptor tyrosine kinase;
Hydrophobic Thickness 34.4 ± 1.6 Å
Tilt Angle 1 ± 13°
ΔGtransfer -28.5 kcal/mol
ΔGfold -21.4 kcal/mol
Links UniProtKB, Pfam, Interpro, iHOP, STRING, HGNC
Topology Out
TM Segments 1860-1883 (1858-1886)
Pathways

MAPK signaling pathway - fly (KEGG)

PDB 3zbf (1934-2232), 4uxl (A=1934-2232)
OPM none
Complexes none
Interactions

EGFR, Complex: ROS1:EGFR, PubMed

Domains

AA: 100-176, PDBID: 2CUH, Subunit A, Seq Identity:28%, Fibronectin type III domain

AA: 196-275, PDBID: 2DJS, Subunit A, Seq Identity:28%, Fibronectin type III domain

AA: 1659-1741, PDBID: 2H41, Subunit A, Seq Identity:27%, Fibronectin type III domain

AA: 1945-2215, PDBID: 3ZBF, Subunit A, Seq Identity:100%, Protein tyrosine kinase

UniProt annotation for ROS1_HUMAN » Proto-oncogene tyrosine-protein kinase ROS
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.

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

ENZYME REGULATION: Inhibited by dephosphorylation by PTPN6.

SUBUNIT: 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.

TISSUE SPECIFICITY: Expressed in brain. Expression is increased in primary gliomas.

DISEASE: Note=A chromosomal aberration involving ROS1 is found in a glioblastoma multiforme sample. An intra-chromosomal deletion del(6)(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.

UniProt features for ROS1_HUMAN » Proto-oncogene tyrosine-protein kinase ROS
SIGNAL 1 27 Potential.
CHAIN 28 2347 Proto-oncogene tyrosine-protein kinase ROS.
DOMAIN 98 188 Fibronectin type-III 1.
DOMAIN 194 281 Fibronectin type-III 2.
DOMAIN 558 668 Fibronectin type-III 3.
DOMAIN 944 1036 Fibronectin type-III 4.
DOMAIN 1041 1147 Fibronectin type-III 5.
DOMAIN 1450 1548 Fibronectin type-III 6.
DOMAIN 1558 1653 Fibronectin type-III 7.
DOMAIN 1655 1748 Fibronectin type-III 8.
DOMAIN 1749 1851 Fibronectin type-III 9.
DOMAIN 1945 2222 Protein kinase.
ACT_SITE 2079 2079 Proton acceptor (By similarity).
SITE 1852 1853 Breakpoint for translocation to form SLC34A2-ROS1 and CD74-ROS1 fusion proteins.
SITE 1880 1881 Breakpoint for translocation to form GOPC-ROS1 fusion protein.
Amino Acid Sequence for ROS1_HUMAN » Proto-oncogene tyrosine-protein kinase ROS
MKNIYCLIPK LVNFATLGCL WISVVQCTVL NSCLKSCVTN LGQQLDLGTP HNLSEPCIQG CHFWNSVDQK NCALKCRESC EVGCSSAEGA YEEEVLENAD LPTAPFASSI GSHNMTLRWK SANFSGVKYI IQWKYAQLLG SWTYTKTVSR PSYVVKPLHP FTEYIFRVVW IFTAQLQLYS PPSPSYRTHP HGVPETAPLI RNIESSSPDT VEVSWDPPQF PGGPILGYNL RLISKNQKLD AGTQRTSFQF YSTLPNTIYR FSIAAVNEVG EGPEAESSIT TSSSAVQQEE QWLFLSRKTS LRKRSLKHLV DEAHCLRLDA IYHNITGISV DVHQQIVYFS EGTLIWAKKA ANMSDVSDLR IFYRGSGLIS SISIDWLYQR MYFIMDELVC VCDLENCSNI EEITPPSISA PQKIVADSYN GYVFYLLRDG IYRADLPVPS GRCAEAVRIV ESCTLKDFAI KPQAKRIIYF NDTAQVFMST FLDGSASHLI LPRIPFADVK SFACENNDFL VTDGKVIFQQ DALSFNEFIV GCDLSHIEEF GFGNLVIFGS SSQLHPLPGR PQELSVLFGS HQALVQWKPP ALAIGANVIL ISDIIELFEL GPSAWQNWTY EVKVSTQDPP EVTHIFLNIS GTMLNVPELQ SAMKYKVSVR ASSPKRPGPW SEPSVGTTLV PASEPPFIMA VKEDGLWSKP LNSFGPGEFL SSDIGNVSDM DWYNNSLYYS DTKGDVFVWL LNGTDISENY HLPSIAGAGA LAFEWLGHFL YWAGKTYVIQ RQSVLTGHTD IVTHVKLLVN DMVVDSVGGY LYWTTLYSVE STRLNGESSL VLQTQPWFSG KKVIALTLDL SDGLLYWLVQ DSQCIHLYTA VLRGQSTGDT TITEFAAWST SEISQNALMY YSGRLFWING FRIITTQEIG QKTSVSVLEP ARFNQFTIIQ TSLKPLPGNF SFTPKVIPDS VQESSFRIEG NASSFQILWN GPPAVDWGVV FYSVEFSAHS KFLASEQHSL PVFTVEGLEP YALFNLSVTP YTYWGKGPKT SLSLRAPETV PSAPENPRIF ILPSGKCCNK NEVVVEFRWN KPKHENGVLT KFEIFYNISN QSITNKTCED WIAVNVTPSV MSFQLEGMSP RCFIAFQVRA FTSKGPGPYA DVVKSTTSEI NPFPHLITLL GNKIVFLDMD QNQVVWTFSA ERVISAVCYT ADNEMGYYAE GDSLFLLHLH NRSSSELFQD SLVFDITVIT IDWISRHLYF ALKESQNGMQ VFDVDLEHKV KYPREVKIHN RNSTIISFSV YPLLSRLYWT EVSNFGYQMF YYSIISHTLH RILQPTATNQ QNKRNQCSCN VTEFELSGAM AIDTSNLEKP LIYFAKAQEI WAMDLEGCQC WRVITVPAML AGKTLVSLTV DGDLIYWIIT AKDSTQIYQA KKGNGAIVSQ VKALRSRHIL AYSSVMQPFP DKAFLSLASD TVEPTILNAT NTSLTIRLPL AKTNLTWYGI TSPTPTYLVY YAEVNDRKNS SDLKYRILEF QDSIALIEDL QPFSTYMIQI AVKNYYSDPL EHLPPGKEIW GKTKNGVPEA VQLINTTVRS DTSLIISWRE SHKPNGPKES VRYQLAISHL ALIPETPLRQ SEFPNGRLTL LVTRLSGGNI YVLKVLACHS EEMWCTESHP VTVEMFNTPE KPYSLVPENT SLQFNWKAPL NVNLIRFWVE LQKWKYNEFY HVKTSCSQGP AYVCNITNLQ PYTSYNVRVV VVYKTGENST SLPESFKTKA GVPNKPGIPK LLEGSKNSIQ WEKAEDNGCR ITYYILEIRK STSNNLQNQN LRWKMTFNGS CSSVCTWKSK NLKGIFQFRV VAANNLGFGE YSGISENIIL VGDDFWIPET SFILTIIVGI FLVVTIPLTF VWHRRLKNQK SAKEGVTVLI NEDKELAELR GLAAGVGLAN ACYAIHTLPT QEEIENLPAF PREKLTLRLL LGSGAFGEVY EGTAVDILGV GSGEIKVAVK TLKKGSTDQE KIEFLKEAHL MSKFNHPNIL KQLGVCLLNE PQYIILELME GGDLLTYLRK ARMATFYGPL LTLVDLVDLC VDISKGCVYL ERMHFIHRDL AARNCLVSVK DYTSPRIVKI GDFGLARDIY KNDYYRKRGE GLLPVRWMAP ESLMDGIFTT QSDVWSFGIL IWEILTLGHQ PYPAHSNLDV LNYVQTGGRL EPPRNCPDDL WNLMTQCWAQ EPDQRPTFHR IQDQLQLFRN FFLNSIYKSR DEANNSGVIN ESFEGEDGDV ICLNSDDIMP VALMETKNRE GLNYMVLATE CGQGEEKSEG PLGSQESESC GLRKEEKEPH ADKDFCQEKQ VAYCPSGKPE GLNYACLTHS GYGDGSD