ROS1 ROS proto-oncogene 1, receptor tyrosine kinase [Homo sapiens (human)] - Gene

Summary

Official Symbol: ROS1provided by HGNC
Official Full Name: ROS proto-oncogene 1, receptor tyrosine kinaseprovided by HGNC
Primary source: HGNC:HGNC:10261
See related: Ensembl:ENSG00000047936 MIM:165020
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: ROS; MCF3; c-ros-1
Summary: 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]
Expression: Restricted expression toward lung (RPKM 10.3) See more
Orthologs: mouse all

Genomic context

Location:: 6q22.1

Exon count:: 46

Annotation release	Status	Assembly	Chr	Location
109	current	GRCh38.p12 (GCF_000001405.38)	6	NC_000006.12 (117287918..117426065, complement)
105	previous assembly	GRCh37.p13 (GCF_000001405.25)	6	NC_000006.11 (117609530..117747018, complement)

Chromosome 6 - NC_000006.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Jun 15 11:32:44 2016

Bibliography

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GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

Study based on 47 tissue samples from spitzoid tumors revealed 2 BAP1-inactived cases. The absence of anomalous expression of translocation-related proteins ALK and ROS1 in this series, composed predominantly of low-grade/low-risk tumors, indicates that translocated spitzoid lesions may not be as prevalent as initially suggested, at least in some populations.
Title: Immunoexpression of BAP1, ROS1, and ALK in Spitzoid Melanocytic Tumors.
None of the genitourinary pseudosarcomatous myofibroblastic proliferations was found to harbour USP6 (0/12), ROS1 (0/8) or ETV6 (0/7) rearrangements
Title: Pseudosarcomatous myofibroblastic proliferations of the genitourinary tract are genetically different from nodular fasciitis and lack USP6, ROS1 and ETV6 gene rearrangements.
the results from three transcriptome-based platforms (Nanostring Elements, Agena LungFusion panel and ThermoFisher NGS fusion panel) were compared to those obtained from ALK, ROS1 and RET Fluorescence In Situ Hybridization on 51 clinical specimens.
Title: Multiplexed transcriptome analysis to detect ALK, ROS1 and RET rearrangements in lung cancer.
lung adenocarcinoma in Asian patients aged </=50 years had a higher gene mutation rate than in those aged >50 years, especially EML4-ALK and ROS1 fusion. Mutation analysis may be helpful in determining targeted therapy for the majority of these patients
Title: Driver mutations of young lung adenocarcinoma patients with malignant pleural effusion.
The frequencies of ALK, ROS1 and RET rearrangements are low in non-adenocarcinoma NSCLC patients. And their clinical characteristics are similar to those in lung adenocarcinoma. Fusions of the above 3 genes are not prognostic factor for non-adnocarcinoma NSCLC patients.
Title: Clinicopathological characteristics and survival of ALK, ROS1 and RET rearrangements in non-adenocarcinoma non-small cell lung cancer patients.
Compared with ROS1-negative advanced NSCLCs,ROS1-rearranged advanced NSCLCs were associated with a younger age at presentation. ROS1 rearrangements were not significantly associated with sex, smoking history, drinking history and metastatic sites.
Title: Advanced lung adenocarcinomas with ROS1-rearrangement frequently show hepatoid cell.
ROS1 rearrangement was detected in 1.1% of CCA patients. Although rare, conduct of clinical trials using ROS1 inhibitors in these genetically unique patients is warranted.
Title: Rare Incidence of <i>ROS1</i> Rearrangement in Cholangiocarcinoma.
For intra-hepatic cholangiocarcinomas (IHCC)patients, ROS1, ALK and c-MET expression levels have prognostic significance on clinical outcomes. Although this finding may require further validation, it has led to proposal of a new stratification or enriched biomarker for future phase III trial of anti-EGFR therapy in IHCC
Title: Expression levels of ROS1/ALK/c-MET and therapeutic efficacy of cetuximab plus chemotherapy in advanced biliary tract cancer.
Polymorphisms rs1333049 and rs10757278 are associated with SCD in men and rs499818 in the women aged over 50 years.
Title: Association of the genetic markers for myocardial infarction with sudden cardiac death.
Overcome crizotinib resistance in a ROS1-rearranged cancer.
Title: A Novel Crizotinib-Resistant Solvent-Front Mutation Responsive to Cabozantinib Therapy in a Patient with ROS1-Rearranged Lung Cancer.

Submit: New GeneRIF Correction See all GeneRIFs (91)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

NHGRI GWAS Catalog

Description
Drug-gene interactions and the search for missing heritability: a cross-sectional pharmacogenomics study of the QT interval. NHGRI GWA Catalog NHGRI GWA CatalogPubMed
Genome-wide association analysis identifies new lung cancer susceptibility loci in never-smoking women in Asia. NHGRI GWA Catalog NHGRI GWA CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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Protein interactions

Protein	Gene	Interaction	Pubs
Envelope surface glycoprotein gp120	env	HIV-1 gp120 upregulates the expression of ROS in umbilical cord blood mononuclear cells and T-cell lines	PubMed
Tat	tat	HIV-1 Tat induces endoplasmic reticulum (ER) stress response proteins CASP12 (Caspase 12), DDIT3 (CHOP), ROS1, ERN-1 (p-IRE1), EIF2AK3 (p-PERK), and ATF6 in human brain microvascular endothelial cells (HBMECs)	PubMed
	tat	Treatment of astrocytes with cell-permeable superoxide dismutase (SOD) leads to a decrease in Tat-induced ROS generation and NF-kappaB activation	PubMed
Vpr	vpr	Administration of recombinant Vpr to human neurons results in a slow but sustained elevation of intracellular calcium, which leads to ROS production and impairs glutamate signaling	PubMed

Go to the HIV-1, Human Interaction Database

Pathways from BioSystems

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NAD metabolism, sirtuins and aging, organism-specific biosystem (from WikiPathways)
NAD metabolism, sirtuins and aging, organism-specific biosystemA model for DNA damage, inflammation, NAD+, and aging. Two key events, the activation of PARP by DNA damage and the decreased NAMPT expression associated with inflammation, lead to decreased SIRT1 an...
Spinal Cord Injury, organism-specific biosystem (from WikiPathways)
Spinal Cord Injury, organism-specific biosystemThis pathway provides an overview of cell types, therapeutic targets, drugs, new proposed targets and pathways implicated in spinal cord injury. Spinal cord injury is a complex multistep process that...

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

RH69070 (e-PCR)
- UniSTS:68418

RH104060 (e-PCR)
- UniSTS:98385

D6S1072 (e-PCR)
- UniSTS:65143

RH119300 (e-PCR)
- UniSTS:133862

D6S1873 (e-PCR)
- UniSTS:80879

Homology

Homologs of the ROS1 gene: The ROS1 gene is conserved in chimpanzee, Rhesus monkey, dog, cow, mouse, rat, chicken, zebrafish, fruit fly, mosquito, and frog.
Orthologs from Annotation Pipeline: 198 organisms have orthologs with human gene ROS1
The Hierarchical Catalog of Orthologs

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
ATP binding	IEA Inferred from Electronic Annotation more info
protein binding	IPI Inferred from Physical Interaction more info	PubMed
protein phosphatase binding	IPI Inferred from Physical Interaction more info	PubMed
protein tyrosine kinase activity	IDA Inferred from Direct Assay more info	PubMed
transmembrane receptor protein tyrosine kinase activity	IBA Inferred from Biological aspect of Ancestor more info	PubMed

Process	Evidence Code	Pubs
cell differentiation	ISS Inferred from Sequence or Structural Similarity more info
cell proliferation	ISS Inferred from Sequence or Structural Similarity more info
columnar/cuboidal epithelial cell development	ISS Inferred from Sequence or Structural Similarity more info
negative regulation of gene expression	IEA Inferred from Electronic Annotation more info
peptidyl-tyrosine autophosphorylation	IEA Inferred from Electronic Annotation more info
protein phosphorylation	IDA Inferred from Direct Assay more info	PubMed
regulation of ERK1 and ERK2 cascade	ISS Inferred from Sequence or Structural Similarity more info
regulation of TOR signaling	IBA Inferred from Biological aspect of Ancestor more info	PubMed
regulation of TOR signaling	IDA Inferred from Direct Assay more info	PubMed
regulation of cell growth	IDA Inferred from Direct Assay more info	PubMed
regulation of phosphate transport	IEA Inferred from Electronic Annotation more info
signal transduction by protein phosphorylation	IEA Inferred from Electronic Annotation more info
spermatogenesis	ISS Inferred from Sequence or Structural Similarity more info
transmembrane receptor protein tyrosine kinase signaling pathway	IBA Inferred from Biological aspect of Ancestor more info	PubMed
transmembrane receptor protein tyrosine kinase signaling pathway	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
cell surface	IEA Inferred from Electronic Annotation more info
integral component of plasma membrane	IBA Inferred from Biological aspect of Ancestor more info	PubMed
membrane	TAS Traceable Author Statement more info	PubMed
perinuclear region of cytoplasm	IEA Inferred from Electronic Annotation more info
receptor complex	IBA Inferred from Biological aspect of Ancestor more info	PubMed

General protein information

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Preferred Names: proto-oncogene tyrosine-protein kinase ROS

Names: ROS proto-oncogene 1 , receptor tyrosine kinase; c-ros oncogene 1 , receptor tyrosine kinase; proto-oncogene c-Ros-1; transmembrane tyrosine-specific protein kinase; v-ros avian UR2 sarcoma virus oncogene homolog 1

NP_002935.2

EC 2.7.10.1

XP_006715611.1

EC 2.7.10.1

XP_011534351.1

EC 2.7.10.1

XP_011534352.1

EC 2.7.10.1

XP_011534353.1

EC 2.7.10.1

XP_011534354.1

EC 2.7.10.1

XP_011534355.1

EC 2.7.10.1

XP_011534356.1

EC 2.7.10.1

XP_011534357.1

EC 2.7.10.1

XP_011534358.1

EC 2.7.10.1

XP_011534359.1

EC 2.7.10.1

XP_011534360.1

EC 2.7.10.1

XP_016866661.1

EC 2.7.10.1

XP_016866662.1

EC 2.7.10.1

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_033929.1 RefSeqGene

Range

5001..142489

Download

GenBank, FASTA, Sequence Viewer (Graphics), LRG_997

mRNA and Protein(s)

NM_002944.2 → NP_002935.2 proto-oncogene tyrosine-protein kinase ROS precursor

See identical proteins and their annotated locations for NP_002935.2

Status: REVIEWED

Source sequence(s)

M34353

Consensus CDS

CCDS5116.1

UniProtKB/Swiss-Prot

P08922

Related

ENSP00000357494.3, ENST00000368508.7

Conserved Domains (3) summary

cd00063
Location:202 → 281

FN3; Fibronectin type 3 domain; One of three types of internal repeats found in the plasma protein fibronectin. Its tenth fibronectin type III repeat contains an RGD cell recognition sequence in a flexible loop between 2 strands. Approximately 2% of all ...

cd05044
Location:1950 → 2216

PTKc_c-ros; Catalytic domain of the Protein Tyrosine Kinase, C-ros

pfam07714
Location:1945 → 2215

Pkinase_Tyr; Protein tyrosine kinase

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 109 details...

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p12 Primary Assembly

Genomic

NC_000006.12 Reference GRCh38.p12 Primary Assembly

Range

117287918..117426065 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_017011173.1 → XP_016866662.1 proto-oncogene tyrosine-protein kinase ROS isoform X7
XM_017011172.1 → XP_016866661.1 proto-oncogene tyrosine-protein kinase ROS isoform X6
XM_011536051.2 → XP_011534353.1 proto-oncogene tyrosine-protein kinase ROS isoform X3

Conserved Domains (3) summary

cd00063
Location:202 → 281

FN3; Fibronectin type 3 domain; One of three types of internal repeats found in the plasma protein fibronectin. Its tenth fibronectin type III repeat contains an RGD cell recognition sequence in a flexible loop between 2 strands. Approximately 2% of all ...

cd05044
Location:1951 → 2217

PTKc_c-ros; Catalytic domain of the Protein Tyrosine Kinase, C-ros

pfam07714
Location:1946 → 2216

Pkinase_Tyr; Protein tyrosine kinase
XM_011536053.2 → XP_011534355.1 proto-oncogene tyrosine-protein kinase ROS isoform X8

Conserved Domains (3) summary

cd00063
Location:211 → 290

FN3; Fibronectin type 3 domain; One of three types of internal repeats found in the plasma protein fibronectin. Its tenth fibronectin type III repeat contains an RGD cell recognition sequence in a flexible loop between 2 strands. Approximately 2% of all ...

cd05044
Location:1902 → 2168

PTKc_c-ros; Catalytic domain of the Protein Tyrosine Kinase, C-ros

pfam07714
Location:1897 → 2167

Pkinase_Tyr; Protein tyrosine kinase
XM_006715548.4 → XP_006715611.1 proto-oncogene tyrosine-protein kinase ROS isoform X5

Related

ENSP00000357493.3, ENST00000368507.7

Conserved Domains (3) summary

cd00063
Location:211 → 290

FN3; Fibronectin type 3 domain; One of three types of internal repeats found in the plasma protein fibronectin. Its tenth fibronectin type III repeat contains an RGD cell recognition sequence in a flexible loop between 2 strands. Approximately 2% of all ...

cd05044
Location:1945 → 2211

PTKc_c-ros; Catalytic domain of the Protein Tyrosine Kinase, C-ros

pfam07714
Location:1940 → 2210

Pkinase_Tyr; Protein tyrosine kinase
XM_011536052.2 → XP_011534354.1 proto-oncogene tyrosine-protein kinase ROS isoform X4

Conserved Domains (3) summary

cd00063
Location:211 → 290

FN3; Fibronectin type 3 domain; One of three types of internal repeats found in the plasma protein fibronectin. Its tenth fibronectin type III repeat contains an RGD cell recognition sequence in a flexible loop between 2 strands. Approximately 2% of all ...

cd05044
Location:1946 → 2212

PTKc_c-ros; Catalytic domain of the Protein Tyrosine Kinase, C-ros

pfam07714
Location:1941 → 2211

Pkinase_Tyr; Protein tyrosine kinase
XM_011536050.2 → XP_011534352.1 proto-oncogene tyrosine-protein kinase ROS isoform X2

Conserved Domains (3) summary

cd00063
Location:211 → 290

FN3; Fibronectin type 3 domain; One of three types of internal repeats found in the plasma protein fibronectin. Its tenth fibronectin type III repeat contains an RGD cell recognition sequence in a flexible loop between 2 strands. Approximately 2% of all ...

cd05044
Location:1959 → 2225

PTKc_c-ros; Catalytic domain of the Protein Tyrosine Kinase, C-ros

pfam07714
Location:1954 → 2224

Pkinase_Tyr; Protein tyrosine kinase
XM_011536049.2 → XP_011534351.1 proto-oncogene tyrosine-protein kinase ROS isoform X1

Conserved Domains (3) summary

cd00063
Location:211 → 290

FN3; Fibronectin type 3 domain; One of three types of internal repeats found in the plasma protein fibronectin. Its tenth fibronectin type III repeat contains an RGD cell recognition sequence in a flexible loop between 2 strands. Approximately 2% of all ...

cd05044
Location:1960 → 2226

PTKc_c-ros; Catalytic domain of the Protein Tyrosine Kinase, C-ros

pfam07714
Location:1955 → 2225

Pkinase_Tyr; Protein tyrosine kinase
XM_011536054.2 → XP_011534356.1 proto-oncogene tyrosine-protein kinase ROS isoform X9

Conserved Domains (3) summary

cd00063
Location:211 → 290

FN3; Fibronectin type 3 domain; One of three types of internal repeats found in the plasma protein fibronectin. Its tenth fibronectin type III repeat contains an RGD cell recognition sequence in a flexible loop between 2 strands. Approximately 2% of all ...

pfam07714
Location:1955 → 2200

Pkinase_Tyr; Protein tyrosine kinase

cl21453
Location:1960 → 2200

PKc_like; Protein Kinases, catalytic domain
XM_011536055.2 → XP_011534357.1 proto-oncogene tyrosine-protein kinase ROS isoform X10

Conserved Domains (1) summary

cd00063
Location:211 → 290

FN3; Fibronectin type 3 domain; One of three types of internal repeats found in the plasma protein fibronectin. Its tenth fibronectin type III repeat contains an RGD cell recognition sequence in a flexible loop between 2 strands. Approximately 2% of all ...
XM_011536056.2 → XP_011534358.1 proto-oncogene tyrosine-protein kinase ROS isoform X11

Conserved Domains (1) summary

cd00063
Location:211 → 290

FN3; Fibronectin type 3 domain; One of three types of internal repeats found in the plasma protein fibronectin. Its tenth fibronectin type III repeat contains an RGD cell recognition sequence in a flexible loop between 2 strands. Approximately 2% of all ...
XM_011536057.3 → XP_011534359.1 proto-oncogene tyrosine-protein kinase ROS isoform X12

Conserved Domains (1) summary

cd00063
Location:211 → 290

FN3; Fibronectin type 3 domain; One of three types of internal repeats found in the plasma protein fibronectin. Its tenth fibronectin type III repeat contains an RGD cell recognition sequence in a flexible loop between 2 strands. Approximately 2% of all ...
XM_011536058.2 → XP_011534360.1 proto-oncogene tyrosine-protein kinase ROS isoform X13

Conserved Domains (1) summary

cd00063
Location:211 → 290

FN3; Fibronectin type 3 domain; One of three types of internal repeats found in the plasma protein fibronectin. Its tenth fibronectin type III repeat contains an RGD cell recognition sequence in a flexible loop between 2 strands. Approximately 2% of all ...