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; AllianceGenome:HGNC:10261
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
110	current	GRCh38.p14 (GCF_000001405.40)	6	NC_000006.12 (117287353..117425942, complement)
110	current	T2T-CHM13v2.0 (GCF_009914755.1)	6	NC_060930.1 (118471267..118609847, complement)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	6	NC_000006.11 (117608516..117747105, 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?

SNP rs9387478 at ROS1-DCBLD1 Locus is Significantly Associated with Lung Cancer Risk and Poor Survival in Indian Population.
Title: SNP rs9387478 at ROS1-DCBLD1 Locus is Significantly Associated with Lung Cancer Risk and Poor Survival in Indian Population.
ROS1 genomic rearrangements are rare actionable drivers in microsatellite stable colorectal cancer.
Title: ROS1 genomic rearrangements are rare actionable drivers in microsatellite stable colorectal cancer.
FISH patterns of ROS1, MET, and ALK with a correlation of ALK immunohistochemistry in lung cancer: a case for introducing ALK immunohistochemistry 'Equivocal' interpretation category in the Ventana anti-ALK (D5F3) CDx assay - A tertiary cancer center experience.
Title: FISH patterns of ROS1, MET, and ALK with a correlation of ALK immunohistochemistry in lung cancer: a case for introducing ALK immunohistochemistry 'Equivocal' interpretation category in the Ventana anti-ALK (D5F3) CDx assay - A tertiary cancer center experience.
ROS1 altered breast cancers - a distinctive molecular subtype of PR- metastatic breast cancers: Expanding the scope of targeted therapeutics.
Title: ROS1 altered breast cancers - a distinctive molecular subtype of PR- metastatic breast cancers: Expanding the scope of targeted therapeutics.
Clinical and economic impact of 'ROS1-testing' strategy compared to a 'no-ROS1-testing' strategy in advanced NSCLC in Spain.
Title: Clinical and economic impact of 'ROS1-testing' strategy compared to a 'no-ROS1-testing' strategy in advanced NSCLC in Spain.
Spectrum of Mechanisms of Resistance to Crizotinib and Lorlatinib in ROS1 Fusion-Positive Lung Cancer.
Title: Spectrum of Mechanisms of Resistance to Crizotinib and Lorlatinib in <i>ROS1</i> Fusion-Positive Lung Cancer.
Uterine inflammatory myofibroblastic tumor: First report of a ROS1 fusion.
Title: Uterine inflammatory myofibroblastic tumor: First report of a ROS1 fusion.
Clinical characteristics of non-small cell lung cancer patients with EGFR mutations and ALK&ROS1 fusions.
Title: Clinical characteristics of non-small cell lung cancer patients with EGFR mutations and ALK&ROS1 fusions.
GOPC:ROS1 and other ROS1 fusions represent a rare but recurrent drug target in a variety of glioma types.
Title: GOPC:ROS1 and other ROS1 fusions represent a rare but recurrent drug target in a variety of glioma types.
Crizotinib efficacy in advanced non-squamous NSCLC patients with ALK or ROS1 rearrangement.
Title: Crizotinib efficacy in advanced non-squamous NSCLC patients with ALK or ROS1 rearrangement.

Submit: New GeneRIF Correction See all GeneRIFs (164)

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

EBI GWAS Catalog

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

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: 336 organisms have orthologs with human gene ROS1
Orthologs

Gene Ontology Provided by GOA

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

Process	Evidence Code	Pubs
involved_in cell differentiation	ISS Inferred from Sequence or Structural Similarity more info
involved_in columnar/cuboidal epithelial cell development	ISS Inferred from Sequence or Structural Similarity more info
involved_in multicellular organism development	IBA Inferred from Biological aspect of Ancestor more info	PubMed
involved_in peptidyl-tyrosine phosphorylation	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of kinase activity	IBA Inferred from Biological aspect of Ancestor more info	PubMed
involved_in protein phosphorylation	IDA Inferred from Direct Assay more info	PubMed
involved_in regulation of ERK1 and ERK2 cascade	ISS Inferred from Sequence or Structural Similarity more info
involved_in regulation of TOR signaling	IBA Inferred from Biological aspect of Ancestor more info	PubMed
involved_in regulation of TOR signaling	IDA Inferred from Direct Assay more info	PubMed
involved_in regulation of cell growth	IDA Inferred from Direct Assay more info	PubMed
involved_in spermatogenesis	ISS Inferred from Sequence or Structural Similarity more info
involved_in transmembrane receptor protein tyrosine kinase signaling pathway	IBA Inferred from Biological aspect of Ancestor more info	PubMed

Component	Evidence Code	Pubs
located_in membrane	TAS Traceable Author Statement more info	PubMed
is_active_in plasma membrane	IBA Inferred from Biological aspect of Ancestor more info	PubMed
part_of 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

XP_047275187.1

EC 2.7.10.1

XP_047275188.1

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

Conserved Domains (2) 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
NM_001378902.1 → NP_001365831.1 proto-oncogene tyrosine-protein kinase ROS isoform 3 precursor

Status: REVIEWED

Source sequence(s)

AL132671, Z98880

Consensus CDS

CCDS93994.1

UniProtKB/TrEMBL

Q5H8Y1

Related

ENSP00000357493.3, ENST00000368507.8
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, Q5TDB5

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 110 details...

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

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000006.12 Reference GRCh38.p14 Primary Assembly

Range

117287353..117425942 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_017011173.2 → XP_016866662.1 proto-oncogene tyrosine-protein kinase ROS isoform X6
XM_017011172.2 → XP_016866661.1 proto-oncogene tyrosine-protein kinase ROS isoform X5
XM_011536051.3 → 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_011536053.3 → XP_011534355.1 proto-oncogene tyrosine-protein kinase ROS isoform X7

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_006715548.5 → XP_006715611.1 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:1945 → 2211

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

pfam07714
Location:1940 → 2210

Pkinase_Tyr; Protein tyrosine kinase
XM_011536050.3 → 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_011536054.3 → XP_011534356.1 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 ...

pfam07714
Location:1955 → 2200

Pkinase_Tyr; Protein tyrosine kinase

cl21453
Location:1960 → 2200

PKc_like; Protein Kinases, catalytic domain
XM_011536049.3 → XP_011534351.1 proto-oncogene tyrosine-protein kinase ROS isoform X1

Conserved Domains (2) 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
XM_011536055.3 → XP_011534357.1 proto-oncogene tyrosine-protein kinase ROS isoform X9

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_011536056.3 → XP_011534358.1 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_011536057.4 → XP_011534359.1 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_047419232.1 → XP_047275188.1 proto-oncogene tyrosine-protein kinase ROS isoform X14
XM_047419231.1 → XP_047275187.1 proto-oncogene tyrosine-protein kinase ROS isoform X13
XM_011536058.3 → XP_011534360.1 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 ...