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
109.20190905	current	GRCh38.p13 (GCF_000001405.39)	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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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?

Brain metastases are common in treatment-naive stage IV ROS1-positive NSCLC, though the incidence does not differ from that in other oncogene cohorts.
Title: The Incidence of Brain Metastases in Stage IV ROS1-Rearranged Non-Small Cell Lung Cancer and Rate of Central Nervous System Progression on Crizotinib.
C-ROS-1 promotes osteogenic differentiation of TWIST-1 haploinsufficient calvarial osteogenic progenitor cells.
Title: Tyrosine kinase receptor c-ros-oncogene 1 inhibition alleviates aberrant bone formation of TWIST-1 haploinsufficient calvarial cells from Saethre-Chotzen syndrome patients.
ROS1-positive NSCLC has distinct clinical characteristics, with an effective and durable response to both TKIs and pemetrexed-based chemotherapies.
Title: Characteristics and Outcome of ROS1-Positive Non-Small Cell Lung Cancer Patients in Routine Clinical Practice.
In conclusion, our study revealed that celastrol caused G2/M phase arrest and trigged apoptosis and autophagy by activating ROS/JNK signaling and blocking the Akt/mTOR signaling pathway
Title: Celastrol mediates autophagy and apoptosis via the ROS/JNK and Akt/mTOR signaling pathways in glioma cells.
Patients with CD74-ROS1 fusion partners are associated with brain metastases in Non-Small Cell Lung Cancer.
Title: Efficacy of Crizotinib among Different Types of ROS1 Fusion Partners in Patients with ROS1-Rearranged Non-Small Cell Lung Cancer.
In the largest consecutive routine Asian non-small cell lung cancer (NSCLC) cohort analyzed to date, we found that high PD-L1 expression frequently overlapped with ROS1 rearrangement, while it negatively correlated with EGFR mutations.
Title: PD-L1 expression in ROS1-rearranged non-small cell lung cancer: A study using simultaneous genotypic screening of EGFR, ALK, and ROS1.
Findings suggest that the measurement of C-terminal ALK or ROS1 protein could be a reliable diagnostic method for each fusion in lung cancer.
Title: Expression of C-terminal ALK, RET, or ROS1 in lung cancer cells with or without fusion.
Detection of the gene status of EGFR, ROS1, and MET will facilitate screening more NSCL adenocarcinoma patients who might benefit from targeted therapy.
Title: Analysis of the status of EGFR, ROS1 and MET genes in non-small cell lung adenocarcinoma.
The present study revealed the detailed inhibitory mechanism of loratinib as potent WT and G2032R mutated ROS1 inhibitor, which was expected to provide a basis for rational drug design
Title: Investigation on the binding mechanism of loratinib with the c-ros oncogene 1 (ROS1) receptor tyrosine kinase via molecular dynamics simulation and binding free energy calculations.
CD74-ROS1 G2032R mutation mediated EMT phenotype by increasing the expression of Twist1, resulting in drug resistance. Combination of Twist1 silence and ROS1 inhibitor may provide a potent strategy to treat the ROS1(+) NSCLC patients with crizotinib resistance.
Title: CD74-ROS1 G2032R mutation transcriptionally up-regulates Twist1 in non-small cell lung cancer cells leading to increased migration, invasion, and resistance to crizotinib.

Submit: New GeneRIF Correction See all GeneRIFs (109)

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: 219 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
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

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 109.20190905

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

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 ...