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Q78DX7 (ROS1_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 90. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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:Ros, Ros-1
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length2340 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence 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.3 Ref.4 Ref.5 Ref.6 Ref.7

Catalytic activity

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

Enzyme regulation

Inhibited by dephosphorylation by PTPN6. Ref.6

Subunit structure

Interacts with PTPN11; may activate the PI3 kinase-mTOR signaling pathway. Interacts with VAV3; constitutive interaction mediating VAV3 phosphorylation By similarity. Interacts with PTPN6 (via SH2 1 domain); the interaction is direct and promotes ROS1 dephosphorylation. Ref.6

Subcellular location

Cell membrane; Single-pass type I membrane protein Probable.

Tissue specificity

Expressed by epithelial cells of the caput epididymis (at protein level). Ref.3

Post-translational modification

Phosphorylated. Probably autophosphorylates. Phosphorylation at Tyr-2267 and/or Tyr-2327 recruits PTPN11 By similarity. Phosphorylation at Tyr-2267 is required for the interaction with PTPN6 that mediates ROS1 dephosphorylation. Phosphorylation at Tyr-2267 stimulates the kinase activity and the activation of the ERK1 signaling cascade. Ref.6

Disruption phenotype

Mice are viable and healthy. Females display normal fertility while males are sterile due a non-cell autonomous defect in sperm maturation. It is associated with the absence of tall columnar epithelial cells with long microvilli in the proximal part of the caput epididymidis. Ref.3

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 componentCell membrane
Membrane
   DiseaseProto-oncogene
   DomainRepeat
Signal
Transmembrane
Transmembrane helix
   LigandATP-binding
Nucleotide-binding
   Molecular functionKinase
Receptor
Transferase
Tyrosine-protein kinase
   PTMGlycoprotein
Phosphoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processcell differentiation

Inferred from direct assay Ref.6. Source: UniProtKB

cell growth

Inferred from sequence or structural similarity. Source: UniProtKB

cell proliferation

Inferred from direct assay Ref.6. Source: UniProtKB

columnar/cuboidal epithelial cell development

Inferred from mutant phenotype Ref.3. Source: UniProtKB

negative regulation of gene expression

Inferred from mutant phenotype PubMed 12773415. Source: MGI

peptidyl-tyrosine phosphorylation

Inferred from sequence or structural similarity. Source: GOC

protein phosphorylation

Inferred from direct assay Ref.6. Source: UniProtKB

regulation of ERK1 and ERK2 cascade

Inferred from direct assay Ref.6. Source: UniProtKB

regulation of TOR signaling

Inferred from sequence or structural similarity. Source: UniProtKB

regulation of phosphate transport

Inferred from mutant phenotype PubMed 12773415. Source: MGI

spermatogenesis

Inferred from mutant phenotype Ref.3. Source: UniProtKB

   Cellular_componentintegral component of membrane

Inferred from electronic annotation. Source: UniProtKB-KW

plasma membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

   Molecular_functionATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

protein phosphatase binding

Inferred from physical interaction Ref.6. Source: UniProtKB

protein tyrosine kinase activity

Inferred from sequence or structural similarity. Source: UniProtKB

transmembrane receptor protein tyrosine kinase activity

Inferred from electronic annotation. Source: UniProtKB-EC

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2828 Potential
Chain29 – 23402312Proto-oncogene tyrosine-protein kinase ROS
PRO_0000278115

Regions

Topological domain29 – 18541826Extracellular Potential
Transmembrane1855 – 187521Helical; Potential
Topological domain1876 – 2340465Cytoplasmic Potential
Domain111 – 20696Fibronectin type-III 1
Domain207 – 29589Fibronectin type-III 2
Domain567 – 667101Fibronectin type-III 3
Domain943 – 103896Fibronectin type-III 4
Domain1039 – 1146108Fibronectin type-III 5
Domain1442 – 1549108Fibronectin type-III 6
Domain1550 – 1649100Fibronectin type-III 7
Domain1651 – 174494Fibronectin type-III 8
Domain1745 – 1846102Fibronectin type-III 9
Domain1938 – 2216279Protein kinase
Nucleotide binding1944 – 19529ATP By similarity

Sites

Active site20721Proton acceptor By similarity
Binding site19731ATP By similarity

Amino acid modifications

Modified residue22671Phosphotyrosine; by autocatalysis
Modified residue23271Phosphotyrosine; by autocatalysis By similarity
Glycosylation531N-linked (GlcNAc...) Potential
Glycosylation3341N-linked (GlcNAc...) Potential
Glycosylation3621N-linked (GlcNAc...) Potential
Glycosylation9351N-linked (GlcNAc...) Potential
Glycosylation10111N-linked (GlcNAc...) Potential
Glycosylation12431N-linked (GlcNAc...) Potential
Glycosylation16761N-linked (GlcNAc...) Potential

Experimental info

Mutagenesis22671Y → F: Abrogates interaction with PTPN6. Ref.6
Sequence conflict271Q → L in AAA50600. Ref.2
Sequence conflict109 – 1113TEL → QAI in AAA50600. Ref.2
Sequence conflict3291D → Y in AAA50600. Ref.2
Sequence conflict4191I → V in AAA50600. Ref.2
Sequence conflict5911A → P in AAA50600. Ref.2
Sequence conflict5951G → P in AAA50600. Ref.2
Sequence conflict631 – 6322NV → KL in AAA50600. Ref.2
Sequence conflict642 – 6454TVSV → PFSC in AAA50600. Ref.2
Sequence conflict6561W → G in AAA50600. Ref.2
Sequence conflict671 – 6722PP → LL in AAA50600. Ref.2
Sequence conflict8301I → V in AAA50600. Ref.2
Sequence conflict10501S → R in AAA50600. Ref.2
Sequence conflict10661N → D in AAA50600. Ref.2
Sequence conflict10851S → F in AAA50600. Ref.2
Sequence conflict12351Y → C in AAA50600. Ref.2
Sequence conflict12761I → T in AAA50600. Ref.2
Sequence conflict13711V → L in AAA50600. Ref.2
Sequence conflict1428 – 14292SA → FR in AAA50600. Ref.2
Sequence conflict1486 – 14872ME → IK in AAA50600. Ref.2
Sequence conflict1541 – 15455EIQGQ → RFKDK in AAA50600. Ref.2
Sequence conflict1585 – 15928RYQLVMSY → AISWLMSD in AAA50600. Ref.2
Sequence conflict16691W → R in AAA50600. Ref.2
Sequence conflict17781T → S in AAA50600. Ref.2
Sequence conflict18931N → S in AAA50600. Ref.2
Sequence conflict1917 – 19182AV → GI in AAA50600. Ref.2
Sequence conflict20871S → N in AAA50600. Ref.2
Sequence conflict21181V → A in AAA50600. Ref.2
Sequence conflict2270 – 22723LAT → VPQ in AAA50600. Ref.2
Sequence conflict23331S → R in AAA50600. Ref.2

Sequences

Sequence LengthMass (Da)Tools
Q78DX7 [UniParc].

Last modified July 5, 2004. Version 1.
Checksum: A3A670B0C4151D7C

FASTA2,340261,967
        10         20         30         40         50         60 
MKNICWLTLK LVKFVVLGCI IWISVAQSTV LSSCLTSCVT NLGRQLDSGT RYNLSEACIH 

        70         80         90        100        110        120 
GCQFWNSVDQ ETCALKCNDT YATICERESC EVGCSNAEGS YEEEVLESTE LPTAPFASSI 

       130        140        150        160        170        180 
GSHGVTLRWN PANISGVKYI IQWKYAQLPG SWTFTETVSK LSYTVEPLHP FTEYIFRVVW 

       190        200        210        220        230        240 
IFTAQLHLYS PPSPSYRTHP YGVPETAPLI LNMESWSPDT VEVSWAPPHF PGGPILGYNL 

       250        260        270        280        290        300 
RLISKNQKLD SGTQRTSFQF YSTLPNTTYR FSIAAVNEVG EGPEAESTVT TPSPSVQEEE 

       310        320        330        340        350        360 
QWLFLSRKTS LRKRSLKYLV DEAHCLWSDA IHHNITGISV YAQQQVVYFS EGTVIWMKGA 

       370        380        390        400        410        420 
ANMSDVSDLR IFYQGSGLVS SISIDWLYQR MYFIMDKLVY VCELKNCSNL EEITPFSLIA 

       430        440        450        460        470        480 
PQKVVVDSYN GYLFYLLRDG IYRVNLPLPS GRDTKAVRIV ESGTLKDFAV KPQSKRIIYF 

       490        500        510        520        530        540 
NDTMQLFMST FLDGSAFHRV LPWVPLVTVK SFACENNDFL ITDGKAIFQQ DSLSFNEFIV 

       550        560        570        580        590        600 
GCDLSHIEEF GFGNLVIFGS SVQSYPLPGH PQEVSVLFGS REALIQWTPP ALAIGASPSA 

       610        620        630        640        650        660 
WQNWTYEVKV YSQDILEITQ VFSNISGTML NVPELQSSTK YTVSVRASSP KGPGPWSAPS 

       670        680        690        700        710        720 
VGTTLVPATE PPFIMAVKED GLWSKPLCSF GPGEFLSSDV GNVSDMDWYN NSLYYSDTKG 

       730        740        750        760        770        780 
NVYVRPLNGM DISENYHIPS IVGAGALAFE WLGHFLYWAG KTYVIQRQSV LTGHTDIVTH 

       790        800        810        820        830        840 
VKLLVNDMAV DSVGGYLYWT TLYSVESTRL NGESSLVLQA QPWLSGKKVI ALTLDLSDGL 

       850        860        870        880        890        900 
LYWLVQDNQC IHLYTAVLRG WSGGDATITE FAAWSTSEIS QNALMYYSGR LFWINGFRII 

       910        920        930        940        950        960 
TAQEIGQRTS VSVSEPAKFN QFTIIQTSLK PLPGNFSSTP KVIPDPVQES SFRIEGHTSS 

       970        980        990       1000       1010       1020 
FQILWNEPPA VDWGIVFYSV EFSTHSKFLI IEQQSLPIFT VEGLEPYTLF NLSVTPYTYW 

      1030       1040       1050       1060       1070       1080 
GKGQKTSLSF RAPESVPSAP ENPRIFILSS GRYTKKNEVV VEFRWNKPKH ENGVLTKFEI 

      1090       1100       1110       1120       1130       1140 
FYHISKQSGT NRSTEDWMSA SVIPPVMSFQ LEAVSPEYTV AFQVRVFTSK GPGPFSDIVM 

      1150       1160       1170       1180       1190       1200 
SKTSEIKPCP YLISLLGNKI VFLDMDQNQV LWTFSLEGDV STVGYTTDDE MGYFAQGDTL 

      1210       1220       1230       1240       1250       1260 
FLLNLRNHSS SKLFQDALVS DIRVIAVDWI ARHLYFALKA SQNGTQIFNV DLEHKVKSPR 

      1270       1280       1290       1300       1310       1320 
EVKTCKAHTT IISFSIYPLL SRLYWTEVSD LGHQMFYCNI SNHTSQHVLQ PKASNQHGRS 

      1330       1340       1350       1360       1370       1380 
QCSCNVTESE LSGAMTVDTS DPDRPWIYFT KRQEIWAMDL EGCQCWKVIM VPTIPGKRII 

      1390       1400       1410       1420       1430       1440 
SLTVDGEFIY WIMKTKDDAQ IYQAKKGSGA ILSQVKASRS KHILAYSSAL QPFPDKAYLS 

      1450       1460       1470       1480       1490       1500 
LASDMVEATI LYATNTSLTL KLPPVKTNLT WHGITHPTST YLIYYMEANR ANSSDRRHKM 

      1510       1520       1530       1540       1550       1560 
LESQENVARI EGLQPFSMYM IQIAVKNYYS EPLEHLPLGK EIQGQTKSGV PGAVCHINAT 

      1570       1580       1590       1600       1610       1620 
VLSDTSLHVF WTESHKPNGP KESVRYQLVM SYLAPIPETP LRQGEFPSAK LSLLITKLSG 

      1630       1640       1650       1660       1670       1680 
GQLYVMKVLA CHPEEMWCTE SHPVSVNMFD TPEKPSALVP ENTSLQLDWK ARSNVNLTGF 

      1690       1700       1710       1720       1730       1740 
WFELQKWKYN EFYHVKASCS QGPVYVCNIT DLQPYTSYNI RVVVVYTTGE NSSSIPESFK 

      1750       1760       1770       1780       1790       1800 
TKAGVPSKPG IPKLLEGSKN SIQWEKAEDN GSRLMYYTLE VRKGISNDSQ NQSSRWKVVF 

      1810       1820       1830       1840       1850       1860 
NGSCSSICTW RSKNLKGTFQ FRAVAANEIG LGEYSEISED ITLVEDGVWI TETSFILTII 

      1870       1880       1890       1900       1910       1920 
VGIFLVATVP LTFVWHRSLK SHKASKEGLS VLNDNDKELA ELRGLAAGVG LANACYAVHT 

      1930       1940       1950       1960       1970       1980 
VPTQEEIENL PAFPREKLSL RLLLGSGAFG EVYEGTAIDI LGVGSGEIKV AVKTLKKGST 

      1990       2000       2010       2020       2030       2040 
DQEKIEFLKE AHLMSKFNHP NILKQLGVCL LGEPQYIILE LMEGGDLLSY LRKARGTTFH 

      2050       2060       2070       2080       2090       2100 
GPSLTLLDLV ELCVDISKGC VYLEQMHFIH RDLAARNCLV SVKDYTSPRV VKIGDFGLAR 

      2110       2120       2130       2140       2150       2160 
EIYKNDYYRK RGEGLLPVRW MAPENLMDGI FTSQSDVWSF GILVWEILTL GHQPYPAHSN 

      2170       2180       2190       2200       2210       2220 
LDVLNYVQAG GRLEPPRNCP DDLWNLMSQC WAQEPDQRPT FHNIQNQLQL FRNVFLNNVS 

      2230       2240       2250       2260       2270       2280 
HCGEAAPTGG VINKGFEGED DEMVTLNSDD TMPVALMETK NQEGLNYMVL ATKCSQGEGS 

      2290       2300       2310       2320       2330       2340 
YEGPLGPKEL GSCDLKKDKK QPQADKDFCQ EPQVAYGSPG LSEGLNYACL AHSEHGDVSE

« Hide

References

[1]"Biochemical and functional characterization of the murine ros protooncogene."
Riethmacher D., Langholz O., Godecke S., Sachs M., Birchmeier C.
Oncogene 9:3617-3626(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Strain: NMRI.
Tissue: Intestine.
[2]"Cloning of mouse c-ros renal cDNA, its role in development and relationship to extracellular matrix glycoproteins."
Kanwar Y.S., Liu Z.Z., Kumar A., Wada J., Carone F.A.
Kidney Int. 48:1646-1659(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Strain: CD-1.
Tissue: Kidney.
[3]"The c-ros tyrosine kinase receptor controls regionalization and differentiation of epithelial cells in the epididymis."
Sonnenberg-Riethmacher E., Walter B., Riethmacher D., Goedecke S., Birchmeier C.
Genes Dev. 10:1184-1193(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: DISRUPTION PHENOTYPE, FUNCTION IN EPITHELIUM DIFFERENTIATION, TISSUE SPECIFICITY.
[4]"Two chimeric receptors of epidermal growth factor receptor and c-Ros that differ in their transmembrane domains have opposite effects on cell growth."
Xiong Q., Chan J.L., Zong C.S., Wang L.H.
Mol. Cell. Biol. 16:1509-1518(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN CELL PROLIFERATION.
[5]"Stat3 plays an important role in oncogenic Ros- and insulin-like growth factor I receptor-induced anchorage-independent growth."
Zong C.S., Zeng L., Jiang Y., Sadowski H.B., Wang L.H.
J. Biol. Chem. 273:28065-28072(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN STAT3 ACTIVATION.
[6]"Negative regulation of Ros receptor tyrosine kinase signaling. An epithelial function of the SH2 domain protein tyrosine phosphatase SHP-1."
Keilhack H., Mueller M., Boehmer S.A., Frank C., Weidner K.M., Birchmeier W., Ligensa T., Berndt A., Kosmehl H., Guenther B., Mueller T., Birchmeier C., Boehmer F.D.
J. Cell Biol. 152:325-334(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN CELL PROLIFERATION, INTERACTION WITH PTPN6, ENZYME REGULATION, AUTOPHOSPHORYLATION, MUTAGENESIS OF TYR-2267.
[7]"The role of phosphatidylinositol 3-kinase, rho family GTPases, and STAT3 in Ros-induced cell transformation."
Nguyen K.T., Zong C.S., Uttamsingh S., Sachdev P., Bhanot M., Le M.T., Chan J.L., Wang L.H.
J. Biol. Chem. 277:11107-11115(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN PI3 KINASE AND STAT3 ACTIVATION.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ		X81650 mRNA. Translation: CAA57310.1.
U15443 mRNA. Translation: AAA50600.1.
RefSeqNP_035412.2. NM_011282.2.
UniGeneMm.236163.

3D structure databases

ProteinModelPortalQ78DX7.
SMRQ78DX7. Positions 999-1143, 1927-2247.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

MINTMINT-192643.

Chemistry

ChEMBLCHEMBL2034802.

PTM databases

PhosphoSiteQ78DX7.

Proteomic databases

PaxDbQ78DX7.
PRIDEQ78DX7.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000020045; ENSMUSP00000020045; ENSMUSG00000019893.
GeneID19886.
KEGGmmu:19886.
UCSCuc007fbb.1. mouse.

Organism-specific databases

CTD6098.
MGIMGI:97999. Ros1.

Phylogenomic databases

eggNOGCOG0515.
GeneTreeENSGT00750000117362.
HOGENOMHOG000137937.
HOVERGENHBG058631.
InParanoidQ78DX7.
KOK05088.
OMAYWLVQDS.
PhylomeDBQ78DX7.
TreeFamTF351636.

Gene expression databases

ArrayExpressQ78DX7.
BgeeQ78DX7.
CleanExMM_ROS1.
GenevestigatorQ78DX7.

Family and domain databases

Gene3D2.120.10.30. 3 hits.
2.60.40.10. 9 hits.
InterProIPR011042. 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.
[Graphical view]
PfamPF00041. fn3. 4 hits.
PF07714. Pkinase_Tyr. 1 hit.
[Graphical view]
PRINTSPR00109. TYRKINASE.
SMARTSM00060. FN3. 9 hits.
SM00135. LY. 3 hits.
SM00219. TyrKc. 1 hit.
[Graphical view]
SUPFAMSSF49265. SSF49265. 5 hits.
SSF56112. SSF56112. 1 hit.
PROSITEPS50853. FN3. 9 hits.
PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00109. PROTEIN_KINASE_TYR. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

NextBio297396.
PROQ78DX7.
SOURCESearch...

Entry information

Entry nameROS1_MOUSE
AccessionPrimary (citable) accession number: Q78DX7
Secondary accession number(s): Q60705
Entry history
Integrated into UniProtKB/Swiss-Prot: February 20, 2007
Last sequence update: July 5, 2004
Last modified: April 16, 2014
This is version 90 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

Human and mouse protein kinases

Human and mouse protein kinases: classification and index

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot

to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents