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
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Genomic context

Location:: 6q22.1

Exon count:: 46

Annotation release	Status	Assembly	Chr	Location
109.20201120	current	GRCh38.p13 (GCF_000001405.39)	6	NC_000006.12 (117287353..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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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 Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Lorlatinib in previously treated anaplastic lymphoma kinase-rearranged non-small cell lung cancer: Japanese subgroup analysis of a global study.
Title: Lorlatinib in previously treated anaplastic lymphoma kinase-rearranged non-small cell lung cancer: Japanese subgroup analysis of a global study.
Beyond EGFR, ALK and ROS1: Current evidence and future perspectives on newly targetable oncogenic drivers in lung adenocarcinoma.
Title: Beyond EGFR, ALK and ROS1: Current evidence and future perspectives on newly targetable oncogenic drivers in lung adenocarcinoma.
Functional coding/non-coding variants in EGFR, ROS1 and ALK genes and their role in liquid biopsy as a personalized therapy.
Title: Functional coding/non-coding variants in EGFR, ROS1 and ALK genes and their role in liquid biopsy as a personalized therapy.
Spitz Tumors With ROS1 Fusions: A Clinicopathological Study of 6 Cases, Including FISH for Chromosomal Copy Number Alterations and Mutation Analysis Using Next-Generation Sequencing.
Title: Spitz Tumors With ROS1 Fusions: A Clinicopathological Study of 6 Cases, Including FISH for Chromosomal Copy Number Alterations and Mutation Analysis Using Next-Generation Sequencing.
Assessment of a New ROS1 Immunohistochemistry Clone (SP384) for the Identification of ROS1 Rearrangements in Patients with Non-Small Cell Lung Carcinoma: the ROSING Study.
Title: Assessment of a New ROS1 Immunohistochemistry Clone (SP384) for the Identification of ROS1 Rearrangements in Patients with Non-Small Cell Lung Carcinoma: the ROSING Study.
Crizotinib activity in patients with ROS1-translocated tumours was confirmed. In the c-MET-mutation and c-MET >/=6 copies cohorts, despite insufficient ORR after two cycles of crizotinib, there are signs of late response not sufficient to justify the development of crizotinib in this indication
Title: Crizotinib in c-MET- or ROS1-positive NSCLC: results of the AcSé phase II trial.
We provide confirmation that patients with 5' ROS1 deletions might respond to anti-ALK/ROS1 therapy by analogy with ALK.
Title: Clinical significance of ROS1 5' deletions in non-small cell lung cancer.
ROS1 rearrangements seem to be very rare in biliary tract adenocarcinomas
Title: Testing for ROS1, ALK, MET, and HER2 rearrangements and amplifications in a large series of biliary tract adenocarcinomas.
GOPC-ROS1 Fusion Due to Microdeletion at 6q22 Is an Oncogenic Driver in a Subset of Pediatric Gliomas and Glioneuronal Tumors.
Title: GOPC-ROS1 Fusion Due to Microdeletion at 6q22 Is an Oncogenic Driver in a Subset of Pediatric Gliomas and Glioneuronal Tumors.
In multivariable analysis, the odds of a TEE were significantly higher for ROS1+ compared to EGFR+ and KRAS+ cohorts, the odds ratio (OR) was 2.44, with a 95% confidence interval of 1.31-4.57 (p = 0.005), and OR: 2.62, with a 95% confidence interval of 1.26-5.46 (p = 0.01), respectively.
Title: ROS1 Gene Rearrangements Are Associated With an Elevated Risk of Peridiagnosis Thromboembolic Events.

Submit: New GeneRIF Correction See all GeneRIFs (126)

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

Associated conditions

Description	Tests
Drug-gene interactions and the search for missing heritability: a cross-sectional pharmacogenomics study of the QT interval. GeneReviews: Not available
Genome-wide association analysis identifies new lung cancer susceptibility loci in never-smoking women in Asia. GeneReviews: Not available

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

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: 261 organisms have orthologs with human gene ROS1
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
columnar/cuboidal epithelial cell development	ISS Inferred from Sequence or Structural Similarity more info
gene expression	IEA Inferred from Electronic Annotation more info
multicellular organism development	IBA Inferred from Biological aspect of Ancestor more info	PubMed
negative regulation of gene expression	IEA Inferred from Electronic Annotation more info
peptidyl-tyrosine autophosphorylation	IEA Inferred from Electronic Annotation more info
positive regulation of kinase activity	IBA Inferred from Biological aspect of Ancestor more info	PubMed
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
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

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_001365820.1

EC 2.7.10.1

NP_001365831.1

EC 2.7.10.1

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_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_001378891.1 → NP_001365820.1 proto-oncogene tyrosine-protein kinase ROS isoform 2 precursor

Status: REVIEWED

Source sequence(s)

AL132671, Z98880
NM_001378902.1 → NP_001365831.1 proto-oncogene tyrosine-protein kinase ROS isoform 3 precursor

Status: REVIEWED

Source sequence(s)

AL132671, Z98880

Related

ENSP00000357493.3, ENST00000368507.7
NM_002944.3 → NP_002935.2 proto-oncogene tyrosine-protein kinase ROS isoform 1 precursor

See identical proteins and their annotated locations for NP_002935.2

Status: REVIEWED

Source sequence(s)

AL132671, Z98880

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 Updated Annotation Release 109.20201120

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

Reference GRCh38.p13 Primary Assembly

Genomic

NC_000006.12 Reference GRCh38.p13 Primary Assembly

Range

117287353..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

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_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 ...