RASGRF1 Ras protein specific guanine nucleotide releasing factor 1 [Homo sapiens (human)] - Gene

Summary

Official Symbol: RASGRF1provided by HGNC
Official Full Name: Ras protein specific guanine nucleotide releasing factor 1provided by HGNC
Primary source: HGNC:HGNC:9875
See related: Ensembl:ENSG00000058335 MIM:606600; AllianceGenome:HGNC:9875
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: GNRP; GRF1; CDC25; GRF55; CDC25L; H-GRF55; PP13187; ras-GRF1
Summary: The protein encoded by this gene is a guanine nucleotide exchange factor (GEF) similar to the Saccharomyces cerevisiae CDC25 gene product. Functional analysis has demonstrated that this protein stimulates the dissociation of GDP from RAS protein. The studies of the similar gene in mouse suggested that the Ras-GEF activity of this protein in brain can be activated by Ca2+ influx, muscarinic receptors, and G protein beta-gamma subunit. Mouse studies also indicated that the Ras-GEF signaling pathway mediated by this protein may be important for long-term memory. Alternatively spliced transcript variants encoding distinct isoforms have been reported. [provided by RefSeq, Mar 2009]
Expression: Biased expression in brain (RPKM 10.4) and lung (RPKM 4.4) See more
Orthologs: mouse all
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Genomic context

Location:: 15q25.1

Exon count:: 31

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	15	NC_000015.10 (78959906..79090780, complement)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	15	NC_060939.1 (76823565..76954487, complement)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	15	NC_000015.9 (79252248..79383122, complement)

Chromosome 15 - NC_000015.10 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?

RASGRF1-rearranged Cutaneous Melanocytic Neoplasms With Spitzoid Cytomorphology: A Clinicopathologic and Genetic Study of 3 Cases.
Title: RASGRF1-rearranged Cutaneous Melanocytic Neoplasms With Spitzoid Cytomorphology: A Clinicopathologic and Genetic Study of 3 Cases.
Benzothiazole amphiphiles promote RasGRF1-associated dendritic spine formation in human stem cell-derived neurons.
Title: Benzothiazole amphiphiles promote RasGRF1-associated dendritic spine formation in human stem cell-derived neurons.
Low RASGRF1 expression due to hypermethylation is associated with Colorectal Cancer.
Title: RASGRF1 Hypermethylation, a Putative Biomarker of Colorectal Cancer.
Our studies have shown that the heritability of myopia makes 66.4% in Lithuania. We detected significant associations between the combinations of GJD2 CC and RASGRF1 GT and odds ratio of developing myopia.
Title: Heritability of myopia and its relation with GDJ2 and RASGRF1 genes in Lithuania.
genetic variants in BICC1 and RASGRF1 are closely associated with high myopia, which appears to be a potential candidate for high myopia in Chinese Han population.
Title: Assessment of BicC family RNA binding protein 1 and Ras protein specific guanine nucleotide releasing factor 1 as candidate genes for high myopia: A case-control study.
Endoplasmic reticulum stress triggers a localized signaling module on the ER surface involving Nox4-dependent calcium mobilization, which directs local Ras activation through ER-associated, calcium-responsive RasGRF.
Title: RasGRF Couples Nox4-Dependent Endoplasmic Reticulum Signaling to Ras.
Data show that microRNA miR-137 directly recognized the 3'-UTR (3'-untranslated region) of the RASGRF1 (Ras protein-specific guanine nucleotide-releasing factor 1) transcript and regulated RASGRF1 expression.
Title: miR-137 acts as a tumor suppressor in astrocytoma by targeting RASGRF1.
Impaired RASGRF1/ERK-mediated GM-CSF response characterizes CARD9 deficiency in French-Canadians.
Title: Impaired RASGRF1/ERK-mediated GM-CSF response characterizes CARD9 deficiency in French-Canadians.
Carriers of the rs8027411 G allele in the RASGRF1 gene may be at a lower risk of high myopia in Chinese and Japanese populations. (Meta-analysis)
Title: Polymorphism in the RASGRF1 gene with high myopia: A meta-analysis.
Rasgrf-1 is a novel GEF protein that has a role in BCR signaling and its overexpression further activates the Ras/Erk/MAPK pathway in CLL specimens.
Title: Amplification of B cell receptor-Erk signaling by Rasgrf-1 overexpression in chronic lymphocytic leukemia.

Submit: New GeneRIF Correction See all GeneRIFs (26)

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
A genome-wide association scan of RR and QT interval duration in 3 European genetically isolated populations: the EUROSPAN project. EBI GWAS Catalog EBI GWAS CatalogPubMed
A genome-wide association study (GWAS) for bronchopulmonary dysplasia. EBI GWAS Catalog EBI GWAS CatalogPubMed
A genome-wide association study for myopia and refractive error identifies a susceptibility locus at 15q25. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide meta-analyses of multiancestry cohorts identify multiple new susceptibility loci for refractive error and myopia. 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	Downregulation of guanine nucleotide-releasing protein, CD151/PETA-3, neuronatin, neuroendocrine differentiation factor, mitochondria 16s rRNA, and signal recognition particle is observed in HIV-1 infected and HIV-1 gp120-treated astrocytes	PubMed

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Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

D15S1337 (e-PCR)
- UniSTS:8259

D15S788 (e-PCR)
- UniSTS:52055

RH46141 (e-PCR)
- UniSTS:2180

G63209 (e-PCR)
- UniSTS:140183

SHGC-84765 (e-PCR)
- UniSTS:104151

STS-L26584 (e-PCR)
- UniSTS:14301

A004I12 (e-PCR)
- UniSTS:35806

SHGC-3223 (e-PCR)
- UniSTS:45295

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables glutamate receptor binding	IEA Inferred from Electronic Annotation more info
enables guanyl-nucleotide exchange factor activity	IBA Inferred from Biological aspect of Ancestor more info
enables guanyl-nucleotide exchange factor activity	IMP Inferred from Mutant Phenotype more info	PubMed

Process	Evidence Code	Pubs
involved_in Ras protein signal transduction	IBA Inferred from Biological aspect of Ancestor more info
involved_in activation of GTPase activity	ISS Inferred from Sequence or Structural Similarity more info
involved_in long-term memory	NAS Non-traceable Author Statement more info	PubMed
involved_in neuron projection development	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of GTPase activity	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of Ras protein signal transduction	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of Ras protein signal transduction	TAS Traceable Author Statement more info	PubMed
involved_in regulation of Rac protein signal transduction	ISS Inferred from Sequence or Structural Similarity more info
involved_in regulation of Ras protein signal transduction	ISS Inferred from Sequence or Structural Similarity more info
involved_in regulation of neuronal synaptic plasticity	IEA Inferred from Electronic Annotation more info
involved_in regulation of synaptic plasticity	ISS Inferred from Sequence or Structural Similarity more info
involved_in response to endoplasmic reticulum stress	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in signal transduction	TAS Traceable Author Statement more info	PubMed
involved_in type B pancreatic cell proliferation	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
located_in cytosol	ISS Inferred from Sequence or Structural Similarity more info
located_in growth cone	ISS Inferred from Sequence or Structural Similarity more info
located_in neuron projection	NAS Non-traceable Author Statement more info	PubMed
is_active_in plasma membrane	IBA Inferred from Biological aspect of Ancestor more info
located_in plasma membrane	NAS Non-traceable Author Statement more info	PubMed
located_in plasma membrane	TAS Traceable Author Statement more info

General protein information

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Preferred Names: ras-specific guanine nucleotide-releasing factor 1

Names: CDC25 like; Ras-specific guanine nucleotide-releasing factor, CDC25 homolog; Ras-specific nucleotide exchange factor CDC25; guanine nucleotide exchange factor; guanine nucleotide-releasing factor 1; guanine nucleotide-releasing factor, 55 kD; guanine nucleotide-releasing protein

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.

mRNA and Protein(s)

NM_001145648.3 → NP_001139120.1 ras-specific guanine nucleotide-releasing factor 1 isoform 3

See identical proteins and their annotated locations for NP_001139120.1

Status: REVIEWED

Description

Transcript Variant: This variant (3) lacks an in-frame coding exon, as compared to variant 1. The resulting isoform (3) lacks an internal segment, as compared to isoform 1.

Source sequence(s)

AC011944, AK226101, AL355696, BC040275, DA126882

Consensus CDS

CCDS45320.1

UniProtKB/TrEMBL

Q8IUU5

Related

ENSP00000452781.2, ENST00000558480.7

Conserved Domains (6) summary

smart00147
Location:1018 → 1254

RasGEF; Guanine nucleotide exchange factor for Ras-like small GTPases

smart00325
Location:244 → 425

RhoGEF; Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases

cd13261
Location:19 → 154

PH_RasGRF1_2; Ras-specific guanine nucleotide-releasing factors 1 and 2 Pleckstrin homology (PH) domain

pfam00618
Location:634 → 682

RasGEF_N; RasGEF N-terminal motif

cl02520
Location:922 → 991

REM; Guanine nucleotide exchange factor for Ras-like GTPases; N-terminal domain (RasGef_N), also called REM domain (Ras exchanger motif). This domain is common in nucleotide exchange factors for Ras-like small GTPases and is typically found immediately ...

cl17171
Location:431 → 582

PH-like; Pleckstrin homology-like domain
NM_002891.6 → NP_002882.3 ras-specific guanine nucleotide-releasing factor 1 isoform 1

See identical proteins and their annotated locations for NP_002882.3

Status: REVIEWED

Description

Transcript Variant: This variant (1) encodes the longest isoform (1).

Source sequence(s)

AC011944, AK226101, AK290135, AL355696, DA126882

Consensus CDS

CCDS10309.1

UniProtKB/Swiss-Prot

F8VPA5, H0YKF2, J3KQP9, Q13972, Q16027

UniProtKB/TrEMBL

Q8IUU5

Related

ENSP00000405963.3, ENST00000419573.7

Conserved Domains (7) summary

smart00147
Location:1034 → 1270

RasGEF; Guanine nucleotide exchange factor for Ras-like small GTPases

smart00325
Location:244 → 425

RhoGEF; Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases

cd13261
Location:19 → 154

PH_RasGRF1_2; Ras-specific guanine nucleotide-releasing factors 1 and 2 Pleckstrin homology (PH) domain

pfam00169
Location:24 → 129

PH; PH domain

pfam00618
Location:647 → 695

RasGEF_N; RasGEF N-terminal motif

cl02520
Location:938 → 1007

REM; Guanine nucleotide exchange factor for Ras-like GTPases; N-terminal domain (RasGef_N), also called REM domain (Ras exchanger motif). This domain is common in nucleotide exchange factors for Ras-like small GTPases and is typically found immediately ...

cl17171
Location:431 → 582

PH-like; Pleckstrin homology-like domain
NM_153815.3 → NP_722522.1 ras-specific guanine nucleotide-releasing factor 1 isoform 2

See identical proteins and their annotated locations for NP_722522.1

Status: REVIEWED

Description

Transcript Variant: This variant (2) lacks multiple 5' exon, but has an alternate 5' exon, as compared to variant 1. The resulting isoform (2) has a much shorter N-terminus, as compared to isoform 1.

Source sequence(s)

AC011944, AK226101, AL355696

Consensus CDS

CCDS42065.1

UniProtKB/Swiss-Prot

Q13972

Related

ENSP00000378228.3, ENST00000394745.3

Conserved Domains (2) summary

smart00147
Location:250 → 486

RasGEF; Guanine nucleotide exchange factor for Ras-like small GTPases

cl02520
Location:154 → 223

REM; Guanine nucleotide exchange factor for Ras-like GTPases; N-terminal domain (RasGef_N), also called REM domain (Ras exchanger motif). This domain is common in nucleotide exchange factors for Ras-like small GTPases and is typically found immediately ...

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

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

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000015.10 Reference GRCh38.p14 Primary Assembly

Range

78959906..79090780 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_017022456.3 → XP_016877945.1 ras-specific guanine nucleotide-releasing factor 1 isoform X3

UniProtKB/TrEMBL

Q8IUU5
XM_017022455.3 → XP_016877944.1 ras-specific guanine nucleotide-releasing factor 1 isoform X1

UniProtKB/TrEMBL

Q8IUU5
XM_047432926.1 → XP_047288882.1 ras-specific guanine nucleotide-releasing factor 1 isoform X6
XM_017022458.3 → XP_016877947.1 ras-specific guanine nucleotide-releasing factor 1 isoform X5

UniProtKB/TrEMBL

Q8IUU5
XM_017022457.3 → XP_016877946.1 ras-specific guanine nucleotide-releasing factor 1 isoform X4

UniProtKB/TrEMBL

Q8IUU5
XM_011521866.4 → XP_011520168.1 ras-specific guanine nucleotide-releasing factor 1 isoform X2

UniProtKB/TrEMBL

Q8IUU5

Conserved Domains (7) summary

smart00325
Location:244 → 425

RhoGEF; Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases

cd13261
Location:19 → 154

PH_RasGRF1_2; Ras-specific guanine nucleotide-releasing factors 1 and 2 Pleckstrin homology (PH) domain

pfam00169
Location:24 → 129

PH; PH domain

pfam00617
Location:1041 → 1181

RasGEF; RasGEF domain

pfam00618
Location:647 → 695

RasGEF_N; RasGEF N-terminal motif

cl02520
Location:938 → 1007

REM; Guanine nucleotide exchange factor for Ras-like GTPases; N-terminal domain (RasGef_N), also called REM domain (Ras exchanger motif). This domain is common in nucleotide exchange factors for Ras-like small GTPases and is typically found immediately ...

cl17171
Location:431 → 582

PH-like; Pleckstrin homology-like domain

Alternate T2T-CHM13v2.0

Genomic

NC_060939.1 Alternate T2T-CHM13v2.0

Range

76823565..76954487 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_054378577.1 → XP_054234552.1 ras-specific guanine nucleotide-releasing factor 1 isoform X3
XM_054378576.1 → XP_054234551.1 ras-specific guanine nucleotide-releasing factor 1 isoform X1
XM_054378575.1 → XP_054234550.1 ras-specific guanine nucleotide-releasing factor 1 isoform X10
XM_054378574.1 → XP_054234549.1 ras-specific guanine nucleotide-releasing factor 1 isoform X9
XM_054378573.1 → XP_054234548.1 ras-specific guanine nucleotide-releasing factor 1 isoform X8
XM_054378572.1 → XP_054234547.1 ras-specific guanine nucleotide-releasing factor 1 isoform X7