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Protein

Proto-oncogene tyrosine-protein kinase ROS

Gene

Ros1

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at transcript 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 (By similarity).By similarity

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
Binding sitei1972 – 19721ATPPROSITE-ProRule annotation
Active sitei2071 – 20711Proton acceptorPROSITE-ProRule annotation

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi1943 – 19519ATPPROSITE-ProRule annotation

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Kinase, Receptor, Transferase, Tyrosine-protein kinase

Keywords - Ligandi

ATP-binding, Nucleotide-binding

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
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Chromosome 20

Organism-specific databases

RGDi3591. Ros1.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini28 – 18531826ExtracellularSequence analysisAdd
BLAST
Transmembranei1854 – 187421HelicalSequence analysisAdd
BLAST
Topological domaini1875 – 2338464CytoplasmicSequence analysisAdd
BLAST

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2727Sequence analysisAdd
BLAST
Chaini28 – 23382311Proto-oncogene tyrosine-protein kinase ROSPRO_0000278116Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi52 – 521N-linked (GlcNAc...)Sequence analysis
Glycosylationi77 – 771N-linked (GlcNAc...)Sequence analysis
Glycosylationi333 – 3331N-linked (GlcNAc...)Sequence analysis
Glycosylationi361 – 3611N-linked (GlcNAc...)Sequence analysis
Glycosylationi480 – 4801N-linked (GlcNAc...)Sequence analysis
Glycosylationi623 – 6231N-linked (GlcNAc...)Sequence analysis
Glycosylationi934 – 9341N-linked (GlcNAc...)Sequence analysis
Glycosylationi1010 – 10101N-linked (GlcNAc...)Sequence analysis
Glycosylationi1298 – 12981N-linked (GlcNAc...)Sequence analysis
Glycosylationi1675 – 16751N-linked (GlcNAc...)Sequence analysis
Modified residuei2266 – 22661Phosphotyrosine; by autocatalysisBy similarity
Modified residuei2325 – 23251Phosphotyrosine; by autocatalysisBy similarity

Post-translational modificationi

Phosphorylated. Probably autophosphorylates. Phosphorylation at Tyr-2266 is required for the interaction with PTPN6 that mediates ROS1 dephosphorylation. Phosphorylation at Tyr-2266 stimulates the kinase activity and the activation of the ERK1 signaling cascade. Phosphorylation at Tyr-2266 and/or Tyr-2325 recruits PTPN11 (By similarity).By similarity

Keywords - PTMi

Glycoprotein, Phosphoprotein

Proteomic databases

PaxDbiQ63132.
PRIDEiQ63132.

PTM databases

PhosphoSiteiQ63132.

Expressioni

Tissue specificityi

Expressed in heart, lung, kidney and testis.1 Publication

Gene expression databases

ExpressionAtlasiQ63132. baseline and differential.
GenevisibleiQ63132. RN.

Interactioni

Subunit structurei

Interacts with PTPN11; may activate the PI3 kinase-mTOR signaling pathway. Interacts with VAV3; constitutive interaction mediating VAV3 phosphorylation. Interacts with PTPN6 (via SH2 1 domain); the interaction is direct and promotes ROS1 dephosphorylation (By similarity).By similarity

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000000459.

Structurei

3D structure databases

ProteinModelPortaliQ63132.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini110 – 20596Fibronectin type-III 1PROSITE-ProRule annotationAdd
BLAST
Domaini206 – 29489Fibronectin type-III 2PROSITE-ProRule annotationAdd
BLAST
Domaini566 – 666101Fibronectin type-III 3PROSITE-ProRule annotationAdd
BLAST
Domaini942 – 103796Fibronectin type-III 4PROSITE-ProRule annotationAdd
BLAST
Domaini1038 – 1145108Fibronectin type-III 5PROSITE-ProRule annotationAdd
BLAST
Domaini1440 – 1548109Fibronectin type-III 6PROSITE-ProRule annotationAdd
BLAST
Domaini1549 – 1648100Fibronectin type-III 7PROSITE-ProRule annotationAdd
BLAST
Domaini1650 – 174394Fibronectin type-III 8PROSITE-ProRule annotationAdd
BLAST
Domaini1744 – 1845102Fibronectin type-III 9PROSITE-ProRule annotationAdd
BLAST
Domaini1937 – 2210274Protein 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

eggNOGiKOG1095. Eukaryota.
ENOG410XPVX. LUCA.
HOGENOMiHOG000137937.
HOVERGENiHBG058631.
InParanoidiQ63132.
KOiK05088.
PhylomeDBiQ63132.
TreeFamiTF351636.

Family and domain databases

Gene3Di2.120.10.30. 3 hits.
2.60.40.10. 8 hits.
InterProiIPR011042. 6-blade_b-propeller_TolB-like.
IPR003961. FN3_dom.
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.
[Graphical view]
PfamiPF00041. fn3. 3 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.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q63132-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MKRIRWLTPK PATFVVLGCV WISVAQGTIL SSCLTSCVTN LGRQLDSGTR
60 70 80 90 100
YNLSEACIQG CQFWNSIDQE KCALKCNDTY VTICERESCE VGCSNAEGSY
110 120 130 140 150
EEEVLDNTEL PTAPFASSIG SNGVTLRWNP ANISGVKYII QWKYAQLPGS
160 170 180 190 200
WAYTETVSKL SYMVEPLHPF TEYIFRVVWI FTAQLHLYSP PSPSYRTHPY
210 220 230 240 250
GVPETAPFIT NIESSSPDTV EVSWAPPYFP GGPILGYNLR LISKTQKLDS
260 270 280 290 300
GTQRTSFQFY STLPNTTYRF SIAAVNEVGE GPEAESMITT PSPAVQEEEQ
310 320 330 340 350
WLFLSRKTSL RKRSLKYLVD EAHCLWSDAI RHNITGISVN TQQEVVYFSE
360 370 380 390 400
GTIIWMKGAA NMSDVSDLRI FYRGSALVSS ISVDWLYQRM YFIMDNRVHV
410 420 430 440 450
CDLKHCSNLE EITPFSIVAP QKVVVDSYNG YVFYLLRDGI YRVHLPLPSV
460 470 480 490 500
RDTKAVRIVE SGTLKDFAVK PQSKRIIYFN GTMQVFMSTF LDGSAFHRVL
510 520 530 540 550
PWVPLADVKS FACENNDFLI TDGKAIFQQD SLSFNEFIVG CDLSHIEEFG
560 570 580 590 600
FGNLVIFGSS VQSYPLPGHP QEVSVLFGSR EALIQWKPPI LAIGASPSAW
610 620 630 640 650
QNWTYEVKVS SQDILETTQV FLNISRTVLN VPKLQSSTKY MVSVRASSPK
660 670 680 690 700
GPGPWSEPSV GTTLVPATEP PFIMAVKEDG LWSKPLSSFG PGEFLSSDVG
710 720 730 740 750
NVSDMDWYNN SLYYSDTKGN VYVRPLNGMD ISENYHISSI AGACALAFEW
760 770 780 790 800
LGHFLYWAGK TYVIQRQSVL TGHTDIVTHV KLLVNDMAVD PVGGYLYWTT
810 820 830 840 850
LYSVESTRLN GESSLVLQAQ PWLSGKKVIA LTLDLSDGLL YWLVQDNQCI
860 870 880 890 900
HLYTAVLRGW SGADATITEF AAWSTSEISQ NALMYYSGRL FWINGFRIIT
910 920 930 940 950
AQEIGQRTSV SVSEPGKFNQ FTIIQTSLKP LPGNFSSTPT VIPDSVQESS
960 970 980 990 1000
FRIEGHTSSF RILWNEPPAV DWGIVFYSVE FSAHSKFLAI EQQSLPVFTV
1010 1020 1030 1040 1050
EGLEPYALFN LSVTPYTYWG KGQKTSLSFR APESVPSAPE NPRIFILSLG
1060 1070 1080 1090 1100
RYTRKNEVVV EFRWNKPKHE NGVLTKSEIF YHISKQSGTN KSTEDWVSVS
1110 1120 1130 1140 1150
VTPPVMSFQL EAMSPGYIVS FQVRVFTSKG PGPFSDIVMS KTSEIKPCPY
1160 1170 1180 1190 1200
LISLLGNKIE FLDMDQNQVV WTFSLEGAVS TVGYTADDEM GYFAQGDALF
1210 1220 1230 1240 1250
LLNLHNHSSS KLFQDVLASD IAVIAVDWIA RHLYFALKAS QDGTQIFDVD
1260 1270 1280 1290 1300
LEHKVKSPRE VKICKSHTAI ISFSMYPLLS RLYWTEVSDL GYQMFYCNIS
1310 1320 1330 1340 1350
SHTLHHVLQP KASNQHGRRQ CSCNVTESEL SGAMTVDTSD PDRPWIYFTK
1360 1370 1380 1390 1400
QQEIWAMDLE GCQCWKVIMV PATPGKRIIS LTVDGEFIYW ITTMKDDTEI
1410 1420 1430 1440 1450
YQAKKGSGAI LSQVKAPRSK HILAYSSALQ PFPDKAYLSV ASNMVEASIL
1460 1470 1480 1490 1500
NATNTSLILK LPPVKTNLTW HGITTPTSTY LVYYMEANRA NSSDRKHNML
1510 1520 1530 1540 1550
ESQENVARIE GLQPFSTYVI QIAVKNYYSD PLEHLSLGKE IQGKTKSGVP
1560 1570 1580 1590 1600
GAVCHINATV LSDTSLLVFW TESHKPNGPK ELVRYQLVMS YLAPIPETPL
1610 1620 1630 1640 1650
RQDEFPSARL SLLVTKLSGG QQYVLKILAC HSEEMWCTES HPVSVNMFDT
1660 1670 1680 1690 1700
PEKPSALVPE NTSLLLDWKA PSNANLTRFW FELQKWKYSE FYHVKASCSQ
1710 1720 1730 1740 1750
GPVYVCNIAN LQPYTPYNIR VVVVYTTGEN SSSIPESFKT KAGVPSKPGI
1760 1770 1780 1790 1800
PKLLEGSKNS IQWEKAEDNG NRLMYYTLEV RKSISNDSRD QSLRWTAVFN
1810 1820 1830 1840 1850
GSCSSICTWR SKNLKGTFQF RAVASNAIGF GEYSEISEDI TLVEDGFWIT
1860 1870 1880 1890 1900
ETSFILTIIV GIFLVATVPL TFVWHRSLKN HKATKEGLSV LNDNDQELAE
1910 1920 1930 1940 1950
LRGLAAGVGL ANACYAVHTL PTQEEIESLP AFPREKLSLR LLLGSGAFGE
1960 1970 1980 1990 2000
VYEGTAVDIL GRGSGEIKVA VKTLKKGSTD QEKIEFLKEA HLMSKFNHPN
2010 2020 2030 2040 2050
ILKQLGVCLL SEPQYIILEL MEGGDLLSYL RKARGTTLSG PLLTLADLVE
2060 2070 2080 2090 2100
LCVDISKGCV YLEQMHFIHR DLAARNCLVS VKDYTSPRVV KIGDFGLARE
2110 2120 2130 2140 2150
IYKHDYYRKR GEGLLPVRWM APENLMDGIF TSQSDVWSFG ILVWEILTLG
2160 2170 2180 2190 2200
HQPYPAHSNL DVLNYVQAGG RLEPPRNCPD DLWNLMFRCW AQEPDQRPTF
2210 2220 2230 2240 2250
YNIQDQLQLF RNVSLNNVSH CGQAAPAGGV INKGFEGEDN EMATLNSDDT
2260 2270 2280 2290 2300
MPVALMETRN QEGLNYMVLA TKCSQSEDRY EGPLGSKESG LHDLKKDERQ
2310 2320 2330
PADKDFCQQP QVAYGSPGHS EGLNYACLAH SGHGDVSE
Length:2,338
Mass (Da):261,656
Last modified:November 1, 1996 - v1
Checksum:iFF45FE561A058453
GO
Isoform 2 (identifier: Q63132-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     431-451: Missing.

Show »
Length:2,317
Mass (Da):259,097
Checksum:i4117901E3B0A6449
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti1873 – 18742VW → AC in AAA40967 (PubMed:2139140).Curated

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei431 – 45121Missing in isoform 2. 1 PublicationVSP_023127Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M35104 mRNA. Translation: AAA40966.1.
M35105 mRNA. Translation: AAA40967.1.
M35106 mRNA. Translation: AAA40968.1.
PIRiI73957.
RefSeqiNP_037006.1. NM_012874.1. [Q63132-1]
XP_008771084.1. XM_008772862.1. [Q63132-2]
UniGeneiRn.87436.

Genome annotation databases

EnsembliENSRNOT00000000459; ENSRNOP00000000459; ENSRNOG00000000406. [Q63132-1]
ENSRNOT00000080444; ENSRNOP00000068996; ENSRNOG00000000406. [Q63132-1]
GeneIDi25346.
KEGGirno:25346.
UCSCiRGD:3591. rat. [Q63132-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M35104 mRNA. Translation: AAA40966.1.
M35105 mRNA. Translation: AAA40967.1.
M35106 mRNA. Translation: AAA40968.1.
PIRiI73957.
RefSeqiNP_037006.1. NM_012874.1. [Q63132-1]
XP_008771084.1. XM_008772862.1. [Q63132-2]
UniGeneiRn.87436.

3D structure databases

ProteinModelPortaliQ63132.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000000459.

PTM databases

PhosphoSiteiQ63132.

Proteomic databases

PaxDbiQ63132.
PRIDEiQ63132.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSRNOT00000000459; ENSRNOP00000000459; ENSRNOG00000000406. [Q63132-1]
ENSRNOT00000080444; ENSRNOP00000068996; ENSRNOG00000000406. [Q63132-1]
GeneIDi25346.
KEGGirno:25346.
UCSCiRGD:3591. rat. [Q63132-1]

Organism-specific databases

CTDi6098.
RGDi3591. Ros1.

Phylogenomic databases

eggNOGiKOG1095. Eukaryota.
ENOG410XPVX. LUCA.
HOGENOMiHOG000137937.
HOVERGENiHBG058631.
InParanoidiQ63132.
KOiK05088.
PhylomeDBiQ63132.
TreeFamiTF351636.

Miscellaneous databases

PROiQ63132.

Gene expression databases

ExpressionAtlasiQ63132. baseline and differential.
GenevisibleiQ63132. RN.

Family and domain databases

Gene3Di2.120.10.30. 3 hits.
2.60.40.10. 8 hits.
InterProiIPR011042. 6-blade_b-propeller_TolB-like.
IPR003961. FN3_dom.
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.
[Graphical view]
PfamiPF00041. fn3. 3 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.
[Graphical view]
ProtoNetiSearch...

Publicationsi

  1. "Tissue-specific expression of rat c-ros-1 gene and partial structural similarity of its predicted products with sev protein of Drosophila melanogaster."
    Matsushime H., Shibuya M.
    J. Virol. 64:2117-2125(1990) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), TISSUE SPECIFICITY.

Entry informationi

Entry nameiROS1_RAT
AccessioniPrimary (citable) accession number: Q63132
Secondary accession number(s): Q63130, Q63131
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 20, 2007
Last sequence update: November 1, 1996
Last modified: June 8, 2016
This is version 124 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.