UniProtKB - Q78DX7 (ROS1_MOUSE)
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Protein
Proto-oncogene tyrosine-protein kinase ROS
Gene
Ros1
Organism
Mus musculus (Mouse)
Status
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 PLCG2.5 Publications
Catalytic activityi
ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.PROSITE-ProRule annotation
Enzyme regulationi
Inhibited by dephosphorylation by PTPN6.1 Publication
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Binding sitei | 1973 | ATPPROSITE-ProRule annotation | 1 | |
Active sitei | 2072 | Proton acceptorPROSITE-ProRule annotation | 1 |
Regions
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Nucleotide bindingi | 1944 – 1952 | ATPPROSITE-ProRule annotation | 9 |
GO - Molecular functioni
- ATP binding Source: UniProtKB-KW
- protein phosphatase binding Source: UniProtKB
- protein tyrosine kinase activity Source: UniProtKB
- transmembrane receptor protein tyrosine kinase activity Source: UniProtKB-EC
GO - Biological processi
- cell differentiation Source: UniProtKB
- cell proliferation Source: UniProtKB
- columnar/cuboidal epithelial cell development Source: UniProtKB
- negative regulation of gene expression Source: MGI
- peptidyl-tyrosine autophosphorylation Source: MGI
- protein phosphorylation Source: UniProtKB
- regulation of cell growth Source: UniProtKB
- regulation of ERK1 and ERK2 cascade Source: UniProtKB
- regulation of phosphate transport Source: MGI
- regulation of TOR signaling Source: UniProtKB
- signal transduction by protein phosphorylation Source: MGI
- spermatogenesis Source: UniProtKB
Keywordsi
Molecular function | Kinase, Receptor, Transferase, Tyrosine-protein kinase |
Ligand | 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 Synonyms:Ros, Ros-1 |
Organismi | Mus musculus (Mouse) |
Taxonomic identifieri | 10090 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Myomorpha › Muroidea › Muridae › Murinae › Mus › Mus |
Proteomesi |
|
Organism-specific databases
MGIi | MGI:97999 Ros1 |
Subcellular locationi
Topology
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Topological domaini | 29 – 1854 | ExtracellularSequence analysisAdd BLAST | 1826 | |
Transmembranei | 1855 – 1875 | HelicalSequence analysisAdd BLAST | 21 | |
Topological domaini | 1876 – 2340 | CytoplasmicSequence analysisAdd BLAST | 465 |
Keywords - Cellular componenti
Cell membrane, MembranePathology & Biotechi
Disruption phenotypei
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.1 Publication
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 2267 | Y → F: Abrogates interaction with PTPN6. 1 Publication | 1 |
Keywords - Diseasei
Proto-oncogeneChemistry databases
ChEMBLi | CHEMBL2034802 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Signal peptidei | 1 – 28 | Sequence analysisAdd BLAST | 28 | |
ChainiPRO_0000278115 | 29 – 2340 | Proto-oncogene tyrosine-protein kinase ROSAdd BLAST | 2312 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Glycosylationi | 53 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Glycosylationi | 334 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Glycosylationi | 362 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Glycosylationi | 935 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Glycosylationi | 1011 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Glycosylationi | 1243 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Glycosylationi | 1676 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Modified residuei | 2267 | Phosphotyrosine; by autocatalysis1 Publication | 1 | |
Modified residuei | 2327 | Phosphotyrosine; by autocatalysisBy similarity | 1 |
Post-translational modificationi
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.By similarity1 Publication
Keywords - PTMi
Glycoprotein, PhosphoproteinProteomic databases
PaxDbi | Q78DX7 |
PRIDEi | Q78DX7 |
PTM databases
iPTMneti | Q78DX7 |
PhosphoSitePlusi | Q78DX7 |
Expressioni
Tissue specificityi
Expressed by epithelial cells of the caput epididymis (at protein level).1 Publication
Gene expression databases
Bgeei | ENSMUSG00000019893 |
CleanExi | MM_ROS1 |
ExpressionAtlasi | Q78DX7 baseline and differential |
Genevisiblei | Q78DX7 MM |
Interactioni
Subunit structurei
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.By similarity1 Publication
Binary interactionsi
With | Entry | #Exp. | IntAct | Notes |
---|---|---|---|---|
Ptpn6 | P29351 | 3 | EBI-7800362,EBI-2620699 |
GO - Molecular functioni
- protein phosphatase binding Source: UniProtKB
Protein-protein interaction databases
IntActi | Q78DX7 3 interactors. |
MINTi | Q78DX7 |
STRINGi | 10090.ENSMUSP00000020045 |
Chemistry databases
BindingDBi | Q78DX7 |
Structurei
3D structure databases
ProteinModelPortali | Q78DX7 |
SMRi | Q78DX7 |
ModBasei | Search... |
MobiDBi | Search... |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 111 – 206 | Fibronectin type-III 1PROSITE-ProRule annotationAdd BLAST | 96 | |
Domaini | 207 – 295 | Fibronectin type-III 2PROSITE-ProRule annotationAdd BLAST | 89 | |
Domaini | 567 – 667 | Fibronectin type-III 3PROSITE-ProRule annotationAdd BLAST | 101 | |
Domaini | 943 – 1038 | Fibronectin type-III 4PROSITE-ProRule annotationAdd BLAST | 96 | |
Domaini | 1039 – 1146 | Fibronectin type-III 5PROSITE-ProRule annotationAdd BLAST | 108 | |
Domaini | 1442 – 1549 | Fibronectin type-III 6PROSITE-ProRule annotationAdd BLAST | 108 | |
Domaini | 1550 – 1649 | Fibronectin type-III 7PROSITE-ProRule annotationAdd BLAST | 100 | |
Domaini | 1651 – 1744 | Fibronectin type-III 8PROSITE-ProRule annotationAdd BLAST | 94 | |
Domaini | 1745 – 1846 | Fibronectin type-III 9PROSITE-ProRule annotationAdd BLAST | 102 | |
Domaini | 1938 – 2216 | Protein kinasePROSITE-ProRule annotationAdd BLAST | 279 |
Sequence similaritiesi
Belongs to the protein kinase superfamily. Tyr protein kinase family. Insulin receptor subfamily.PROSITE-ProRule annotation
Keywords - Domaini
Repeat, Signal, Transmembrane, Transmembrane helixPhylogenomic databases
eggNOGi | ENOG410IQAA Eukaryota ENOG410XSTC LUCA |
GeneTreei | ENSGT00760000118818 |
HOGENOMi | HOG000137937 |
HOVERGENi | HBG058631 |
InParanoidi | Q78DX7 |
KOi | K05088 |
OMAi | YWLVQDS |
OrthoDBi | EOG091G003T |
PhylomeDBi | Q78DX7 |
TreeFami | TF351636 |
Family and domain databases
CDDi | cd00063 FN3, 8 hits |
Gene3Di | 2.120.10.303 hits 2.60.40.108 hits |
InterProi | View protein in InterPro IPR011042 6-blade_b-propeller_TolB-like IPR003961 FN3_dom IPR036116 FN3_sf IPR013783 Ig-like_fold IPR011009 Kinase-like_dom_sf 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 |
Pfami | View protein in Pfam PF00041 fn3, 3 hits PF07714 Pkinase_Tyr, 1 hit |
PRINTSi | PR00109 TYRKINASE |
SMARTi | View protein in SMART SM00060 FN3, 9 hits SM00135 LY, 3 hits SM00219 TyrKc, 1 hit |
SUPFAMi | SSF49265 SSF49265, 5 hits SSF56112 SSF56112, 1 hit |
PROSITEi | View protein in PROSITE PS50853 FN3, 9 hits PS00107 PROTEIN_KINASE_ATP, 1 hit PS50011 PROTEIN_KINASE_DOM, 1 hit PS00109 PROTEIN_KINASE_TYR, 1 hit |
i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
Q78DX7-1 [UniParc]FASTAAdd to basket
10 20 30 40 50
MKNICWLTLK LVKFVVLGCI IWISVAQSTV LSSCLTSCVT NLGRQLDSGT
60 70 80 90 100
RYNLSEACIH GCQFWNSVDQ ETCALKCNDT YATICERESC EVGCSNAEGS
110 120 130 140 150
YEEEVLESTE LPTAPFASSI GSHGVTLRWN PANISGVKYI IQWKYAQLPG
160 170 180 190 200
SWTFTETVSK LSYTVEPLHP FTEYIFRVVW IFTAQLHLYS PPSPSYRTHP
210 220 230 240 250
YGVPETAPLI LNMESWSPDT VEVSWAPPHF PGGPILGYNL RLISKNQKLD
260 270 280 290 300
SGTQRTSFQF YSTLPNTTYR FSIAAVNEVG EGPEAESTVT TPSPSVQEEE
310 320 330 340 350
QWLFLSRKTS LRKRSLKYLV DEAHCLWSDA IHHNITGISV YAQQQVVYFS
360 370 380 390 400
EGTVIWMKGA ANMSDVSDLR IFYQGSGLVS SISIDWLYQR MYFIMDKLVY
410 420 430 440 450
VCELKNCSNL EEITPFSLIA PQKVVVDSYN GYLFYLLRDG IYRVNLPLPS
460 470 480 490 500
GRDTKAVRIV ESGTLKDFAV KPQSKRIIYF NDTMQLFMST FLDGSAFHRV
510 520 530 540 550
LPWVPLVTVK SFACENNDFL ITDGKAIFQQ DSLSFNEFIV GCDLSHIEEF
560 570 580 590 600
GFGNLVIFGS SVQSYPLPGH PQEVSVLFGS REALIQWTPP ALAIGASPSA
610 620 630 640 650
WQNWTYEVKV YSQDILEITQ VFSNISGTML NVPELQSSTK YTVSVRASSP
660 670 680 690 700
KGPGPWSAPS VGTTLVPATE PPFIMAVKED GLWSKPLCSF GPGEFLSSDV
710 720 730 740 750
GNVSDMDWYN NSLYYSDTKG NVYVRPLNGM DISENYHIPS IVGAGALAFE
760 770 780 790 800
WLGHFLYWAG KTYVIQRQSV LTGHTDIVTH VKLLVNDMAV DSVGGYLYWT
810 820 830 840 850
TLYSVESTRL NGESSLVLQA QPWLSGKKVI ALTLDLSDGL LYWLVQDNQC
860 870 880 890 900
IHLYTAVLRG WSGGDATITE FAAWSTSEIS QNALMYYSGR LFWINGFRII
910 920 930 940 950
TAQEIGQRTS VSVSEPAKFN QFTIIQTSLK PLPGNFSSTP KVIPDPVQES
960 970 980 990 1000
SFRIEGHTSS FQILWNEPPA VDWGIVFYSV EFSTHSKFLI IEQQSLPIFT
1010 1020 1030 1040 1050
VEGLEPYTLF NLSVTPYTYW GKGQKTSLSF RAPESVPSAP ENPRIFILSS
1060 1070 1080 1090 1100
GRYTKKNEVV VEFRWNKPKH ENGVLTKFEI FYHISKQSGT NRSTEDWMSA
1110 1120 1130 1140 1150
SVIPPVMSFQ LEAVSPEYTV AFQVRVFTSK GPGPFSDIVM SKTSEIKPCP
1160 1170 1180 1190 1200
YLISLLGNKI VFLDMDQNQV LWTFSLEGDV STVGYTTDDE MGYFAQGDTL
1210 1220 1230 1240 1250
FLLNLRNHSS SKLFQDALVS DIRVIAVDWI ARHLYFALKA SQNGTQIFNV
1260 1270 1280 1290 1300
DLEHKVKSPR EVKTCKAHTT IISFSIYPLL SRLYWTEVSD LGHQMFYCNI
1310 1320 1330 1340 1350
SNHTSQHVLQ PKASNQHGRS QCSCNVTESE LSGAMTVDTS DPDRPWIYFT
1360 1370 1380 1390 1400
KRQEIWAMDL EGCQCWKVIM VPTIPGKRII SLTVDGEFIY WIMKTKDDAQ
1410 1420 1430 1440 1450
IYQAKKGSGA ILSQVKASRS KHILAYSSAL QPFPDKAYLS LASDMVEATI
1460 1470 1480 1490 1500
LYATNTSLTL KLPPVKTNLT WHGITHPTST YLIYYMEANR ANSSDRRHKM
1510 1520 1530 1540 1550
LESQENVARI EGLQPFSMYM IQIAVKNYYS EPLEHLPLGK EIQGQTKSGV
1560 1570 1580 1590 1600
PGAVCHINAT VLSDTSLHVF WTESHKPNGP KESVRYQLVM SYLAPIPETP
1610 1620 1630 1640 1650
LRQGEFPSAK LSLLITKLSG GQLYVMKVLA CHPEEMWCTE SHPVSVNMFD
1660 1670 1680 1690 1700
TPEKPSALVP ENTSLQLDWK ARSNVNLTGF WFELQKWKYN EFYHVKASCS
1710 1720 1730 1740 1750
QGPVYVCNIT DLQPYTSYNI RVVVVYTTGE NSSSIPESFK TKAGVPSKPG
1760 1770 1780 1790 1800
IPKLLEGSKN SIQWEKAEDN GSRLMYYTLE VRKGISNDSQ NQSSRWKVVF
1810 1820 1830 1840 1850
NGSCSSICTW RSKNLKGTFQ FRAVAANEIG LGEYSEISED ITLVEDGVWI
1860 1870 1880 1890 1900
TETSFILTII VGIFLVATVP LTFVWHRSLK SHKASKEGLS VLNDNDKELA
1910 1920 1930 1940 1950
ELRGLAAGVG LANACYAVHT VPTQEEIENL PAFPREKLSL RLLLGSGAFG
1960 1970 1980 1990 2000
EVYEGTAIDI LGVGSGEIKV AVKTLKKGST DQEKIEFLKE AHLMSKFNHP
2010 2020 2030 2040 2050
NILKQLGVCL LGEPQYIILE LMEGGDLLSY LRKARGTTFH GPSLTLLDLV
2060 2070 2080 2090 2100
ELCVDISKGC VYLEQMHFIH RDLAARNCLV SVKDYTSPRV VKIGDFGLAR
2110 2120 2130 2140 2150
EIYKNDYYRK RGEGLLPVRW MAPENLMDGI FTSQSDVWSF GILVWEILTL
2160 2170 2180 2190 2200
GHQPYPAHSN LDVLNYVQAG GRLEPPRNCP DDLWNLMSQC WAQEPDQRPT
2210 2220 2230 2240 2250
FHNIQNQLQL FRNVFLNNVS HCGEAAPTGG VINKGFEGED DEMVTLNSDD
2260 2270 2280 2290 2300
TMPVALMETK NQEGLNYMVL ATKCSQGEGS YEGPLGPKEL GSCDLKKDKK
2310 2320 2330 2340
QPQADKDFCQ EPQVAYGSPG LSEGLNYACL AHSEHGDVSE
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 27 | Q → L in AAA50600 (PubMed:8544427).Curated | 1 | |
Sequence conflicti | 109 – 111 | TEL → QAI in AAA50600 (PubMed:8544427).Curated | 3 | |
Sequence conflicti | 329 | D → Y in AAA50600 (PubMed:8544427).Curated | 1 | |
Sequence conflicti | 419 | I → V in AAA50600 (PubMed:8544427).Curated | 1 | |
Sequence conflicti | 591 | A → P in AAA50600 (PubMed:8544427).Curated | 1 | |
Sequence conflicti | 595 | G → P in AAA50600 (PubMed:8544427).Curated | 1 | |
Sequence conflicti | 631 – 632 | NV → KL in AAA50600 (PubMed:8544427).Curated | 2 | |
Sequence conflicti | 642 – 645 | TVSV → PFSC in AAA50600 (PubMed:8544427).Curated | 4 | |
Sequence conflicti | 656 | W → G in AAA50600 (PubMed:8544427).Curated | 1 | |
Sequence conflicti | 671 – 672 | PP → LL in AAA50600 (PubMed:8544427).Curated | 2 | |
Sequence conflicti | 830 | I → V in AAA50600 (PubMed:8544427).Curated | 1 | |
Sequence conflicti | 1050 | S → R in AAA50600 (PubMed:8544427).Curated | 1 | |
Sequence conflicti | 1066 | N → D in AAA50600 (PubMed:8544427).Curated | 1 | |
Sequence conflicti | 1085 | S → F in AAA50600 (PubMed:8544427).Curated | 1 | |
Sequence conflicti | 1235 | Y → C in AAA50600 (PubMed:8544427).Curated | 1 | |
Sequence conflicti | 1276 | I → T in AAA50600 (PubMed:8544427).Curated | 1 | |
Sequence conflicti | 1371 | V → L in AAA50600 (PubMed:8544427).Curated | 1 | |
Sequence conflicti | 1428 – 1429 | SA → FR in AAA50600 (PubMed:8544427).Curated | 2 | |
Sequence conflicti | 1486 – 1487 | ME → IK in AAA50600 (PubMed:8544427).Curated | 2 | |
Sequence conflicti | 1541 – 1545 | EIQGQ → RFKDK in AAA50600 (PubMed:8544427).Curated | 5 | |
Sequence conflicti | 1585 – 1592 | RYQLVMSY → AISWLMSD in AAA50600 (PubMed:8544427).Curated | 8 | |
Sequence conflicti | 1669 | W → R in AAA50600 (PubMed:8544427).Curated | 1 | |
Sequence conflicti | 1778 | T → S in AAA50600 (PubMed:8544427).Curated | 1 | |
Sequence conflicti | 1893 | N → S in AAA50600 (PubMed:8544427).Curated | 1 | |
Sequence conflicti | 1917 – 1918 | AV → GI in AAA50600 (PubMed:8544427).Curated | 2 | |
Sequence conflicti | 2087 | S → N in AAA50600 (PubMed:8544427).Curated | 1 | |
Sequence conflicti | 2118 | V → A in AAA50600 (PubMed:8544427).Curated | 1 | |
Sequence conflicti | 2270 – 2272 | LAT → VPQ in AAA50600 (PubMed:8544427).Curated | 3 | |
Sequence conflicti | 2333 | S → R in AAA50600 (PubMed:8544427).Curated | 1 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | X81650 mRNA Translation: CAA57310.1 U15443 mRNA Translation: AAA50600.1 |
CCDSi | CCDS23838.1 |
RefSeqi | NP_035412.2, NM_011282.2 |
UniGenei | Mm.236163 |
Genome annotation databases
Ensembli | ENSMUST00000020045; ENSMUSP00000020045; ENSMUSG00000019893 |
GeneIDi | 19886 |
KEGGi | mmu:19886 |
UCSCi | uc007fbb.1 mouse |
Similar proteinsi
Entry informationi
Entry namei | ROS1_MOUSE | |
Accessioni | Q78DX7Primary (citable) accession number: Q78DX7 Secondary accession number(s): Q60705 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | February 20, 2007 |
Last sequence update: | July 5, 2004 | |
Last modified: | March 28, 2018 | |
This is version 128 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program |