ROS1_RAT
ID ROS1_RAT Reviewed; 2338 AA.
AC Q63132; Q63130; Q63131;
DT 20-FEB-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 03-AUG-2022, entry version 158.
DE RecName: Full=Proto-oncogene tyrosine-protein kinase ROS;
DE EC=2.7.10.1;
DE AltName: Full=Proto-oncogene c-Ros;
DE AltName: Full=Proto-oncogene c-Ros-1;
DE AltName: Full=Receptor tyrosine kinase c-ros oncogene 1;
DE AltName: Full=c-Ros receptor tyrosine kinase;
DE Flags: Precursor;
GN Name=Ros1;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), AND TISSUE SPECIFICITY.
RX PubMed=2139140; DOI=10.1128/jvi.64.5.2117-2125.1990;
RA Matsushime H., Shibuya M.;
RT "Tissue-specific expression of rat c-ros-1 gene and partial structural
RT similarity of its predicted products with sev protein of Drosophila
RT melanogaster.";
RL J. Virol. 64:2117-2125(1990).
CC -!- FUNCTION: Orphan receptor tyrosine kinase (RTK) that plays a role in
CC epithelial cell differentiation and regionalization of the proximal
CC epididymal epithelium. May activate several downstream signaling
CC pathways related to cell differentiation, proliferation, growth and
CC survival including the PI3 kinase-mTOR signaling pathway. Mediates the
CC phosphorylation of PTPN11, an activator of this pathway. May also
CC phosphorylate and activate the transcription factor STAT3 to control
CC anchorage-independent cell growth. Mediates the phosphorylation and the
CC activation of VAV3, a guanine nucleotide exchange factor regulating
CC cell morphology. May activate other downstream signaling proteins
CC including AKT1, MAPK1, MAPK3, IRS1 and PLCG2 (By similarity).
CC {ECO:0000250}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-tyrosyl-[protein] = ADP + H(+) + O-phospho-L-tyrosyl-
CC [protein]; Xref=Rhea:RHEA:10596, Rhea:RHEA-COMP:10136, Rhea:RHEA-
CC COMP:10137, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:46858,
CC ChEBI:CHEBI:82620, ChEBI:CHEBI:456216; EC=2.7.10.1;
CC Evidence={ECO:0000255|PROSITE-ProRule:PRU10028};
CC -!- ACTIVITY REGULATION: Inhibited by dephosphorylation by PTPN6.
CC {ECO:0000250}.
CC -!- SUBUNIT: Interacts with PTPN11; may activate the PI3 kinase-mTOR
CC signaling pathway. Interacts with VAV3; constitutive interaction
CC mediating VAV3 phosphorylation. Interacts with PTPN6 (via SH2 1
CC domain); the interaction is direct and promotes ROS1 dephosphorylation
CC (By similarity). {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000305}; Single-pass type I
CC membrane protein {ECO:0000305}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q63132-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q63132-2; Sequence=VSP_023127;
CC -!- TISSUE SPECIFICITY: Expressed in heart, lung, kidney and testis.
CC {ECO:0000269|PubMed:2139140}.
CC -!- PTM: Phosphorylated. Probably autophosphorylates. Phosphorylation at
CC Tyr-2266 is required for the interaction with PTPN6 that mediates ROS1
CC dephosphorylation. Phosphorylation at Tyr-2266 stimulates the kinase
CC activity and the activation of the ERK1 signaling cascade.
CC Phosphorylation at Tyr-2266 and/or Tyr-2325 recruits PTPN11 (By
CC similarity). {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. Tyr protein
CC kinase family. Insulin receptor subfamily. {ECO:0000255|PROSITE-
CC ProRule:PRU00159}.
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DR EMBL; M35104; AAA40966.1; -; mRNA.
DR EMBL; M35105; AAA40967.1; -; mRNA.
DR EMBL; M35106; AAA40968.1; -; mRNA.
DR PIR; I73957; I73957.
DR RefSeq; NP_037006.1; NM_012874.1. [Q63132-1]
DR RefSeq; XP_008771084.1; XM_008772862.2. [Q63132-2]
DR AlphaFoldDB; Q63132; -.
DR SMR; Q63132; -.
DR STRING; 10116.ENSRNOP00000000459; -.
DR GlyGen; Q63132; 10 sites.
DR PhosphoSitePlus; Q63132; -.
DR PaxDb; Q63132; -.
DR PRIDE; Q63132; -.
DR GeneID; 25346; -.
DR KEGG; rno:25346; -.
DR UCSC; RGD:3591; rat. [Q63132-1]
DR CTD; 6098; -.
DR RGD; 3591; Ros1.
DR VEuPathDB; HostDB:ENSRNOG00000000406; -.
DR eggNOG; KOG1095; Eukaryota.
DR HOGENOM; CLU_000798_0_0_1; -.
DR InParanoid; Q63132; -.
DR OMA; SCKFGCS; -.
DR OrthoDB; 203310at2759; -.
DR PhylomeDB; Q63132; -.
DR TreeFam; TF351636; -.
DR PRO; PR:Q63132; -.
DR Proteomes; UP000002494; Chromosome 20.
DR Bgee; ENSRNOG00000000406; Expressed in pancreas and 10 other tissues.
DR Genevisible; Q63132; RN.
DR GO; GO:0009986; C:cell surface; ISO:RGD.
DR GO; GO:0005887; C:integral component of plasma membrane; IBA:GO_Central.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; ISO:RGD.
DR GO; GO:0043235; C:receptor complex; IBA:GO_Central.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0019903; F:protein phosphatase binding; ISO:RGD.
DR GO; GO:0004713; F:protein tyrosine kinase activity; ISS:UniProtKB.
DR GO; GO:0004714; F:transmembrane receptor protein tyrosine kinase activity; IBA:GO_Central.
DR GO; GO:0030154; P:cell differentiation; ISS:UniProtKB.
DR GO; GO:0002066; P:columnar/cuboidal epithelial cell development; ISS:UniProtKB.
DR GO; GO:0010467; P:gene expression; ISO:RGD.
DR GO; GO:0010629; P:negative regulation of gene expression; ISO:RGD.
DR GO; GO:0038083; P:peptidyl-tyrosine autophosphorylation; ISO:RGD.
DR GO; GO:0033674; P:positive regulation of kinase activity; IBA:GO_Central.
DR GO; GO:0006468; P:protein phosphorylation; ISS:UniProtKB.
DR GO; GO:0001558; P:regulation of cell growth; ISS:UniProtKB.
DR GO; GO:0070372; P:regulation of ERK1 and ERK2 cascade; ISS:UniProtKB.
DR GO; GO:0010966; P:regulation of phosphate transport; ISO:RGD.
DR GO; GO:0032006; P:regulation of TOR signaling; ISS:UniProtKB.
DR GO; GO:0007165; P:signal transduction; ISO:RGD.
DR GO; GO:0007283; P:spermatogenesis; ISS:UniProtKB.
DR GO; GO:0007169; P:transmembrane receptor protein tyrosine kinase signaling pathway; IBA:GO_Central.
DR CDD; cd00063; FN3; 7.
DR Gene3D; 2.120.10.30; -; 3.
DR Gene3D; 2.60.40.10; -; 8.
DR InterPro; IPR011042; 6-blade_b-propeller_TolB-like.
DR InterPro; IPR003961; FN3_dom.
DR InterPro; IPR036116; FN3_sf.
DR InterPro; IPR013783; Ig-like_fold.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR000033; LDLR_classB_rpt.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR001245; Ser-Thr/Tyr_kinase_cat_dom.
DR InterPro; IPR008266; Tyr_kinase_AS.
DR InterPro; IPR020635; Tyr_kinase_cat_dom.
DR Pfam; PF00041; fn3; 2.
DR Pfam; PF07714; PK_Tyr_Ser-Thr; 1.
DR PRINTS; PR00109; TYRKINASE.
DR SMART; SM00060; FN3; 9.
DR SMART; SM00135; LY; 4.
DR SMART; SM00219; TyrKc; 1.
DR SUPFAM; SSF49265; SSF49265; 5.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS50853; FN3; 9.
DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00109; PROTEIN_KINASE_TYR; 1.
PE 2: Evidence at transcript level;
KW Alternative splicing; ATP-binding; Cell membrane; Glycoprotein; Kinase;
KW Membrane; Nucleotide-binding; Phosphoprotein; Receptor; Reference proteome;
KW Repeat; Signal; Transferase; Transmembrane; Transmembrane helix;
KW Tyrosine-protein kinase.
FT SIGNAL 1..27
FT /evidence="ECO:0000255"
FT CHAIN 28..2338
FT /note="Proto-oncogene tyrosine-protein kinase ROS"
FT /id="PRO_0000278116"
FT TOPO_DOM 28..1853
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 1854..1874
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1875..2338
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 110..205
FT /note="Fibronectin type-III 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00316"
FT DOMAIN 206..294
FT /note="Fibronectin type-III 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00316"
FT DOMAIN 566..666
FT /note="Fibronectin type-III 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00316"
FT DOMAIN 942..1037
FT /note="Fibronectin type-III 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00316"
FT DOMAIN 1038..1145
FT /note="Fibronectin type-III 5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00316"
FT DOMAIN 1440..1548
FT /note="Fibronectin type-III 6"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00316"
FT DOMAIN 1549..1648
FT /note="Fibronectin type-III 7"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00316"
FT DOMAIN 1650..1743
FT /note="Fibronectin type-III 8"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00316"
FT DOMAIN 1744..1845
FT /note="Fibronectin type-III 9"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00316"
FT DOMAIN 1937..2210
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 2277..2314
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2281..2304
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 2071
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10028"
FT BINDING 1943..1951
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 1972
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 2266
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:P08922"
FT MOD_RES 2325
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:P08922"
FT CARBOHYD 52
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 77
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 333
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 361
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 480
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 623
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 934
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1010
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1298
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1675
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VAR_SEQ 431..451
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:2139140"
FT /id="VSP_023127"
FT CONFLICT 1873..1874
FT /note="VW -> AC (in Ref. 1; AAA40967)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 2338 AA; 261656 MW; FF45FE561A058453 CRC64;
MKRIRWLTPK PATFVVLGCV WISVAQGTIL SSCLTSCVTN LGRQLDSGTR YNLSEACIQG
CQFWNSIDQE KCALKCNDTY VTICERESCE VGCSNAEGSY EEEVLDNTEL PTAPFASSIG
SNGVTLRWNP ANISGVKYII QWKYAQLPGS WAYTETVSKL SYMVEPLHPF TEYIFRVVWI
FTAQLHLYSP PSPSYRTHPY GVPETAPFIT NIESSSPDTV EVSWAPPYFP GGPILGYNLR
LISKTQKLDS GTQRTSFQFY STLPNTTYRF SIAAVNEVGE GPEAESMITT PSPAVQEEEQ
WLFLSRKTSL RKRSLKYLVD EAHCLWSDAI RHNITGISVN TQQEVVYFSE GTIIWMKGAA
NMSDVSDLRI FYRGSALVSS ISVDWLYQRM YFIMDNRVHV CDLKHCSNLE EITPFSIVAP
QKVVVDSYNG YVFYLLRDGI YRVHLPLPSV RDTKAVRIVE SGTLKDFAVK PQSKRIIYFN
GTMQVFMSTF LDGSAFHRVL PWVPLADVKS FACENNDFLI TDGKAIFQQD SLSFNEFIVG
CDLSHIEEFG FGNLVIFGSS VQSYPLPGHP QEVSVLFGSR EALIQWKPPI LAIGASPSAW
QNWTYEVKVS SQDILETTQV FLNISRTVLN VPKLQSSTKY MVSVRASSPK GPGPWSEPSV
GTTLVPATEP PFIMAVKEDG LWSKPLSSFG PGEFLSSDVG NVSDMDWYNN SLYYSDTKGN
VYVRPLNGMD ISENYHISSI AGACALAFEW LGHFLYWAGK TYVIQRQSVL TGHTDIVTHV
KLLVNDMAVD PVGGYLYWTT LYSVESTRLN GESSLVLQAQ PWLSGKKVIA LTLDLSDGLL
YWLVQDNQCI HLYTAVLRGW SGADATITEF AAWSTSEISQ NALMYYSGRL FWINGFRIIT
AQEIGQRTSV SVSEPGKFNQ FTIIQTSLKP LPGNFSSTPT VIPDSVQESS FRIEGHTSSF
RILWNEPPAV DWGIVFYSVE FSAHSKFLAI EQQSLPVFTV EGLEPYALFN LSVTPYTYWG
KGQKTSLSFR APESVPSAPE NPRIFILSLG RYTRKNEVVV EFRWNKPKHE NGVLTKSEIF
YHISKQSGTN KSTEDWVSVS VTPPVMSFQL EAMSPGYIVS FQVRVFTSKG PGPFSDIVMS
KTSEIKPCPY LISLLGNKIE FLDMDQNQVV WTFSLEGAVS TVGYTADDEM GYFAQGDALF
LLNLHNHSSS KLFQDVLASD IAVIAVDWIA RHLYFALKAS QDGTQIFDVD LEHKVKSPRE
VKICKSHTAI ISFSMYPLLS RLYWTEVSDL GYQMFYCNIS SHTLHHVLQP KASNQHGRRQ
CSCNVTESEL SGAMTVDTSD PDRPWIYFTK QQEIWAMDLE GCQCWKVIMV PATPGKRIIS
LTVDGEFIYW ITTMKDDTEI YQAKKGSGAI LSQVKAPRSK HILAYSSALQ PFPDKAYLSV
ASNMVEASIL NATNTSLILK LPPVKTNLTW HGITTPTSTY LVYYMEANRA NSSDRKHNML
ESQENVARIE GLQPFSTYVI QIAVKNYYSD PLEHLSLGKE IQGKTKSGVP GAVCHINATV
LSDTSLLVFW TESHKPNGPK ELVRYQLVMS YLAPIPETPL RQDEFPSARL SLLVTKLSGG
QQYVLKILAC HSEEMWCTES HPVSVNMFDT PEKPSALVPE NTSLLLDWKA PSNANLTRFW
FELQKWKYSE FYHVKASCSQ GPVYVCNIAN LQPYTPYNIR VVVVYTTGEN SSSIPESFKT
KAGVPSKPGI PKLLEGSKNS IQWEKAEDNG NRLMYYTLEV RKSISNDSRD QSLRWTAVFN
GSCSSICTWR SKNLKGTFQF RAVASNAIGF GEYSEISEDI TLVEDGFWIT ETSFILTIIV
GIFLVATVPL TFVWHRSLKN HKATKEGLSV LNDNDQELAE LRGLAAGVGL ANACYAVHTL
PTQEEIESLP AFPREKLSLR LLLGSGAFGE VYEGTAVDIL GRGSGEIKVA VKTLKKGSTD
QEKIEFLKEA HLMSKFNHPN ILKQLGVCLL SEPQYIILEL MEGGDLLSYL RKARGTTLSG
PLLTLADLVE LCVDISKGCV YLEQMHFIHR DLAARNCLVS VKDYTSPRVV KIGDFGLARE
IYKHDYYRKR GEGLLPVRWM APENLMDGIF TSQSDVWSFG ILVWEILTLG HQPYPAHSNL
DVLNYVQAGG RLEPPRNCPD DLWNLMFRCW AQEPDQRPTF YNIQDQLQLF RNVSLNNVSH
CGQAAPAGGV INKGFEGEDN EMATLNSDDT MPVALMETRN QEGLNYMVLA TKCSQSEDRY
EGPLGSKESG LHDLKKDERQ PADKDFCQQP QVAYGSPGHS EGLNYACLAH SGHGDVSE
