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Aliases for ROS1 Gene

Aliases for ROS1 Gene

  • ROS Proto-Oncogene 1, Receptor Tyrosine Kinase 2 3 5
  • V-Ros Avian UR2 Sarcoma Virus Oncogene Homolog 1 2 3
  • C-Ros Oncogene 1 , Receptor Tyrosine Kinase 2 3
  • Proto-Oncogene C-Ros-1 3 4
  • MCF3 3 4
  • ROS 3 4
  • V-Ros UR2 Sarcoma Virus Oncogene Homolog 1 (Avian) 2
  • ROS Proto-Oncogene 1 , Receptor Tyrosine Kinase 3
  • Transmembrane Tyrosine-Specific Protein Kinase 3
  • Proto-Oncogene Tyrosine-Protein Kinase ROS 3
  • Receptor Tyrosine Kinase C-Ros Oncogene 1 4
  • C-Ros Receptor Tyrosine Kinase 4
  • Proto-Oncogene C-Ros 4
  • EC 2.7.10.1 4
  • C-Ros-1 3

External Ids for ROS1 Gene

Previous GeneCards Identifiers for ROS1 Gene

  • GC06M117444
  • GC06M117632
  • GC06M117655
  • GC06M117716
  • GC06M117609
  • GC06M115190

Summaries for ROS1 Gene

Entrez Gene Summary for ROS1 Gene

  • This proto-oncogene, highly-expressed in a variety of tumor cell lines, belongs to the sevenless subfamily of tyrosine kinase insulin receptor genes. The protein encoded by this gene is a type I integral membrane protein with tyrosine kinase activity. The protein may function as a growth or differentiation factor receptor. [provided by RefSeq, Jul 2008]

CIViC summary for ROS1 Gene

  • ROS1 is a receptor tyrosine kinase that is frequently involved in genetic rearrangement in a variety of human cancers (e.g. NSCLC, gastric cancer, ovarian cancer, cholangiocarcinoma, colorectal cancer, angiosarcoma...). The resulting fusion protein harbors the constitutively active ROS1 kinase domain and drives cellular proliferation (Davies et. al.). In NSCLC about 1% harbor a ROS1 rearrangement. These patients are predominantely female and have a lower T-stage (Warth et. al.). Treatment with crizotinib leads to a reported objective response rate of appr. 70% and a median duration of response of 18 months (Shaw et. al.). Resistance mechanisms to crizotinib have been described and involve mutations in the kinase domain. More selective inhibitors of ROS1 might overcome this resistance (Davare et. al.).

GeneCards Summary for ROS1 Gene

ROS1 (ROS Proto-Oncogene 1, Receptor Tyrosine Kinase) is a Protein Coding gene. Diseases associated with ROS1 include Lung Large Cell Carcinoma and Gastric Adenocarcinoma. Among its related pathways are GPCR Pathway and Spinal Cord Injury. GO annotations related to this gene include transferase activity, transferring phosphorus-containing groups and protein tyrosine kinase activity. An important paralog of this gene is INSRR.

UniProtKB/Swiss-Prot for ROS1 Gene

  • 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.

Gene Wiki entry for ROS1 Gene

No data available for Tocris Summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for ROS1 Gene

Genomics for ROS1 Gene

Regulatory Elements for ROS1 Gene

Enhancers for ROS1 Gene
GeneHancer Identifier Enhancer Score Enhancer Sources Gene-Enhancer Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor Binding Sites within enhancer Gene Targets for Enhancer
GH06G117547 1.1 Ensembl ENCODE 10.3 -123.4 -123413 3.8 ELF3 PKNOX1 FOXA2 INSM2 SIN3A FEZF1 SLC30A9 GATA2 SCRT2 FOS DCBLD1 GOPC ENSG00000226181 RNU6-253P ROS1 NUS1 PIR41328 ENSG00000282218
GH06G117388 0.9 ENCODE 11 +36.2 36246 2.4 ELF3 ZSCAN9 RARA YY1 CREM THAP11 CEBPB MIER2 KAT8 ATF4 ROS1 RNU6-253P PIR54307
GH06G117555 0.9 Ensembl ENCODE 10.3 -130.0 -129992 0.2 GATAD2A CTCF ZNF654 TRIM22 REST RAD21 ARID3A SMC3 ZNF143 DCBLD1 ENSG00000226181 GOPC RNU6-253P ROS1 NUS1 ENSG00000282218 PIR41328
GH06G117439 1.5 Ensembl ENCODE dbSUPER 5.3 -15.4 -15382 3.0 PKNOX1 FOXA2 ATF1 MLX DMAP1 BRCA1 YY1 SLC30A9 CBX5 FOS DCBLD1 NUS1 ROS1 RAP1BP3 ENSG00000226181
GH06G117556 0.6 ENCODE 10.3 -130.2 -130171 0.1 GATAD2A CTCF ZNF654 TRIM22 REST RAD21 ARID3A SMC3 ZNF143 ENSG00000226181 DCBLD1 GOPC RNU6-253P ROS1 NUS1 ENSG00000282218 PIR41328
- Elite enhancer and/or Elite enhancer-gene association Download GeneHancer data dump

Enhancers around ROS1 on UCSC Golden Path with GeneCards custom track

Genomic Location for ROS1 Gene

Chromosome:
6
Start:
117,287,918 bp from pter
End:
117,425,922 bp from pter
Size:
138,005 bases
Orientation:
Minus strand

Genomic View for ROS1 Gene

Genes around ROS1 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
ROS1 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for ROS1 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for ROS1 Gene

Proteins for ROS1 Gene

  • Protein details for ROS1 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    P08922-ROS1_HUMAN
    Recommended name:
    Proto-oncogene tyrosine-protein kinase ROS
    Protein Accession:
    P08922
    Secondary Accessions:
    • Q15368
    • Q5TDB5

    Protein attributes for ROS1 Gene

    Size:
    2347 amino acids
    Molecular mass:
    263915 Da
    Quaternary structure:
    • 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.

    Three dimensional structures from OCA and Proteopedia for ROS1 Gene

neXtProt entry for ROS1 Gene

Post-translational modifications for ROS1 Gene

  • Phosphorylated. Probably autophosphorylates. Phosphorylation at Tyr-2274 is required for the interaction with PTPN6 that mediates ROS1 dephosphorylation (By similarity). Phosphorylation at Tyr-2274 stimulates the kinase activity and the activation of the ERK1 signaling cascade (By similarity). Phosphorylation at Tyr-2274 and/or Tyr-2334 recruits PTPN11.
  • Glycosylation at isoforms=52, isoforms=114, Asn123, isoforms=324, Asn352, isoforms=396, isoforms=471, isoforms=607, isoforms=628, isoforms=706, Asn714, Asn732, Asn939, Asn961, isoforms=1015, isoforms=1087, Asn1090, Asn1095, isoforms=1211, Asn1272, Asn1330, Asn1458, Asn1461, isoforms=1474, isoforms=1499, isoforms=1565, Asn1669, Asn1715, isoforms=1738, and Asn1808
  • Modification sites at PhosphoSitePlus

Assay Products

  • Cloud-Clone Corp. Assay Kits for ROS1

No data available for DME Specific Peptides for ROS1 Gene

Domains & Families for ROS1 Gene

Suggested Antigen Peptide Sequences for ROS1 Gene

Graphical View of Domain Structure for InterPro Entry

P08922

UniProtKB/Swiss-Prot:

ROS1_HUMAN :
  • Belongs to the protein kinase superfamily. Tyr protein kinase family. Insulin receptor subfamily.
Family:
  • Belongs to the protein kinase superfamily. Tyr protein kinase family. Insulin receptor subfamily.
genes like me logo Genes that share domains with ROS1: view

Function for ROS1 Gene

Molecular function for ROS1 Gene

GENATLAS Biochemistry:
avian UR2 sarcoma virus oncogene (v-ros) homolog
UniProtKB/Swiss-Prot CatalyticActivity:
ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.
UniProtKB/Swiss-Prot EnzymeRegulation:
Inhibited by dephosphorylation by PTPN6.
UniProtKB/Swiss-Prot 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.

Enzyme Numbers (IUBMB) for ROS1 Gene

Gene Ontology (GO) - Molecular Function for ROS1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0004672 protein kinase activity IEA --
GO:0004713 protein tyrosine kinase activity IDA,IEA 16885344
GO:0004714 transmembrane receptor protein tyrosine kinase activity IEA --
GO:0005515 protein binding IPI 17416557
GO:0005524 ATP binding IEA --
genes like me logo Genes that share ontologies with ROS1: view
genes like me logo Genes that share phenotypes with ROS1: view

Animal Models for ROS1 Gene

MGI Knock Outs for ROS1:

Animal Model Products

CRISPR Products

miRNA for ROS1 Gene

miRTarBase miRNAs that target ROS1

Inhibitory RNA Products

No data available for Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for ROS1 Gene

Localization for ROS1 Gene

Subcellular locations from UniProtKB/Swiss-Prot for ROS1 Gene

Cell membrane; Single-pass type I membrane protein.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for ROS1 gene
Compartment Confidence
plasma membrane 5
extracellular 1
peroxisome 1
nucleus 1
lysosome 1

Gene Ontology (GO) - Cellular Components for ROS1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005886 plasma membrane IEA --
GO:0009986 cell surface IEA --
GO:0016020 membrane TAS,IEA 3785223
GO:0016021 integral component of membrane IEA --
GO:0048471 perinuclear region of cytoplasm IEA --
genes like me logo Genes that share ontologies with ROS1: view

Pathways & Interactions for ROS1 Gene

genes like me logo Genes that share pathways with ROS1: view

SIGNOR curated interactions for ROS1 Gene

Is inactivated by:

Gene Ontology (GO) - Biological Process for ROS1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0002066 columnar/cuboidal epithelial cell development IEA,ISS --
GO:0006468 protein phosphorylation IEA,IDA 16885344
GO:0007169 transmembrane receptor protein tyrosine kinase signaling pathway IEA --
GO:0007283 spermatogenesis ISS,IEA --
GO:0008283 cell proliferation ISS,IEA --
genes like me logo Genes that share ontologies with ROS1: view

Drugs & Compounds for ROS1 Gene

(11) Drugs for ROS1 Gene - From: PharmGKB, ClinicalTrials, ApexBio, DGIdb, HMDB, and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Crizotinib Approved Pharma Inhibition, Biomarker, inhibitor C-MET/ALK inhibitor,potent and ATP-competitve, cMET Inhibitors, Kinase Inhibitors, Anaplastic lymphoma kinase (ALK) inhibitor, Potent c-MET/ALK inhibitor 104
cabozantinib Approved Pharma Kinase Inhibitors, Vascular endothelial growth factor (VEGF) and VEGF receptor (VEGFR) inhibitors 0
Ceritinib Approved Pharma 37
Adenosine triphosphate Approved Nutra 0
tyrosine Nutra 699

(1) Additional Compounds for ROS1 Gene - From: HMDB

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
ADP
  • Adenosindiphosphorsaeure
  • Adenosine 5'-pyrophosphate
  • Adenosine diphosphate
  • Adenosine pyrophosphate
  • Adenosine-5'-diphosphate
Full agonist, Agonist 58-64-0

(1) ApexBio Compounds for ROS1 Gene

Compound Action Cas Number
Dovitinib (TKI-258, CHIR-258) Multitargeted RTK inhibitor 405169-16-6
genes like me logo Genes that share compounds with ROS1: view

Drug Products

Transcripts for ROS1 Gene

Unigene Clusters for ROS1 Gene

C-ros oncogene 1 , receptor tyrosine kinase:
Representative Sequences:

CRISPR Products

Inhibitory RNA Products

Alternative Splicing Database (ASD) splice patterns (SP) for ROS1 Gene

No ASD Table

Relevant External Links for ROS1 Gene

GeneLoc Exon Structure for
ROS1
ECgene alternative splicing isoforms for
ROS1

Expression for ROS1 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and CGAP SAGE for ROS1 Gene

mRNA differential expression in normal tissues according to GTEx for ROS1 Gene

This gene is overexpressed in Lung (x37.5).

Protein differential expression in normal tissues from HIPED for ROS1 Gene

This gene is overexpressed in Amniocyte (42.0) and Tlymphocyte (16.1).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, PaxDb, and MOPED for ROS1 Gene



NURSA nuclear receptor signaling pathways regulating expression of ROS1 Gene:

ROS1

SOURCE GeneReport for Unigene cluster for ROS1 Gene:

Hs.1041

mRNA Expression by UniProt/SwissProt for ROS1 Gene:

P08922-ROS1_HUMAN
Tissue specificity: Expressed in brain. Expression is increased in primary gliomas.

Evidence on tissue expression from TISSUES for ROS1 Gene

  • Lung(3.2)
genes like me logo Genes that share expression patterns with ROS1: view

Primer Products

No data available for mRNA expression in embryonic tissues and stem cells from LifeMap Discovery , Protein tissue co-expression partners and Phenotype-based relationships between genes and organs from Gene ORGANizer for ROS1 Gene

Orthologs for ROS1 Gene

This gene was present in the common ancestor of animals.

Orthologs for ROS1 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia ROS1 34 35
  • 99.43 (n)
cow
(Bos Taurus)
Mammalia ROS1 34 35
  • 87.48 (n)
dog
(Canis familiaris)
Mammalia ROS1 34 35
  • 87.43 (n)
mouse
(Mus musculus)
Mammalia Ros1 34 16 35
  • 83.68 (n)
rat
(Rattus norvegicus)
Mammalia Ros1 34
  • 82.71 (n)
oppossum
(Monodelphis domestica)
Mammalia ROS1 35
  • 72 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia ROS1 35
  • 49 (a)
OneToOne
chicken
(Gallus gallus)
Aves ROS1 34 35
  • 62.99 (n)
lizard
(Anolis carolinensis)
Reptilia -- 35
  • 23 (a)
ManyToMany
tropical clawed frog
(Silurana tropicalis)
Amphibia ros1 34
  • 56.83 (n)
zebrafish
(Danio rerio)
Actinopterygii ros1 34 35
  • 54.59 (n)
fruit fly
(Drosophila melanogaster)
Insecta sev 36 34 35
  • 41.53 (n)
African malaria mosquito
(Anopheles gambiae)
Insecta AgaP_AGAP000015 34
  • 40.66 (n)
worm
(Caenorhabditis elegans)
Secernentea R151.4 36
  • 37 (a)
T21G5.1 36
  • 37 (a)
ZK593.9 36
  • 33 (a)
ddr-1 35
  • 16 (a)
ManyToMany
Species where no ortholog for ROS1 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea squirt (Ciona intestinalis)
  • sea squirt (Ciona savignyi)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)

Evolution for ROS1 Gene

ENSEMBL:
Gene Tree for ROS1 (if available)
TreeFam:
Gene Tree for ROS1 (if available)

Paralogs for ROS1 Gene

Variants for ROS1 Gene

Sequence variations from dbSNP and Humsavar for ROS1 Gene

SNP ID Clin Chr 06 pos Sequence Context AA Info Type
VAR_041447 A gastric adenocarcinoma sample
VAR_041450 A lung large cell carcinoma sample
VAR_041456 A colorectal adenocarcinoma sample
VAR_041457 A gastric adenocarcinoma sample
rs1000059640 -- 117,398,896(+) TGAAC(C/T)CAGGA intron-variant

Structural Variations from Database of Genomic Variants (DGV) for ROS1 Gene

Variant ID Type Subtype PubMed ID
dgv6141n100 CNV gain 25217958
esv2635247 CNV deletion 19546169
esv2759465 CNV loss 17122850
esv2763593 CNV gain 21179565
esv3303146 CNV mobile element insertion 20981092
esv3383830 CNV insertion 20981092
esv3610491 CNV loss 21293372
nsv478464 CNV novel sequence insertion 20440878
nsv510048 OTHER sequence alteration 20534489
nsv526934 CNV loss 19592680
nsv830785 CNV gain 17160897

Variation tolerance for ROS1 Gene

Residual Variation Intolerance Score: 57.3% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 17.08; 98.04% of all genes are more intolerant (likely to be disease-causing)

Relevant External Links for ROS1 Gene

Human Gene Mutation Database (HGMD)
ROS1
SNPedia medical, phenotypic, and genealogical associations of SNPs for
ROS1

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for ROS1 Gene

Disorders for ROS1 Gene

MalaCards: The human disease database

(8) MalaCards diseases for ROS1 Gene - From: DISEASES, Novoseek, and GeneCards

Disorder Aliases PubMed IDs
lung large cell carcinoma
  • large cell carcinoma of lung
gastric adenocarcinoma
  • adenocarcinoma of stomach
adenocarcinoma
  • adenocarcinoma nos
large cell carcinoma
  • carcinoma large cell
adenosquamous cell lung carcinoma
  • adenosquamous lung carcinoma
- elite association - COSMIC cancer census association via MalaCards
Search ROS1 in MalaCards View complete list of genes associated with diseases

UniProtKB/Swiss-Prot

ROS1_HUMAN
  • 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. {ECO:0000269 PubMed:12661006}.

Relevant External Links for ROS1

Genetic Association Database (GAD)
ROS1
Human Genome Epidemiology (HuGE) Navigator
ROS1
Tumor Gene Database (TGDB):
ROS1
Atlas of Genetics and Cytogenetics in Oncology and Haematology:
ROS1
genes like me logo Genes that share disorders with ROS1: view

No data available for Genatlas for ROS1 Gene

Publications for ROS1 Gene

  1. Fusion of FIG to the receptor tyrosine kinase ROS in a glioblastoma with an interstitial del(6)(q21q21). (PMID: 12661006) Charest A. … Housman D. (Genes Chromosomes Cancer 2003) 3 4 22 64
  2. Characterization of ROS1 cDNA from a human glioblastoma cell line. (PMID: 2352949) Birchmeier C. … Wigler M. (Proc. Natl. Acad. Sci. U.S.A. 1990) 3 4 22 64
  3. Variations of specific non-candidate genes and risk of myocardial infarction: a replication study. (PMID: 19709766) Koch W. … Kastrati A. (Int. J. Cardiol. 2011) 3 46 64
  4. Genetic susceptibility to distinct bladder cancer subphenotypes. (PMID: 19692168) Guey L.T. … Malats N. (Eur. Urol. 2010) 3 46 64
  5. Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score. (PMID: 20379614) Rose J.E. … Uhl G.R. (Mol. Med. 2010) 3 46 64

Products for ROS1 Gene

  • Addgene plasmids for ROS1

Sources for ROS1 Gene

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