RAP1A RAP1A, member of RAS oncogene family [Homo sapiens (human)] - Gene

Summary

Official Symbol: RAP1Aprovided by HGNC
Official Full Name: RAP1A, member of RAS oncogene familyprovided by HGNC
Primary source: HGNC:HGNC:9855
See related: Ensembl:ENSG00000116473 MIM:179520
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: RAP1; C21KG; G-22K; KREV1; KREV-1; SMGP21
Summary: This gene encodes a member of the Ras family of small GTPases. The encoded protein undergoes a change in conformational state and activity, depending on whether it is bound to GTP or GDP. This protein is activated by several types of guanine nucleotide exchange factors (GEFs), and inactivated by two groups of GTPase-activating proteins (GAPs). The activation status of the encoded protein is therefore affected by the balance of intracellular levels of GEFs and GAPs. The encoded protein regulates signaling pathways that affect cell proliferation and adhesion, and may play a role in tumor malignancy. Pseudogenes of this gene have been defined on chromosomes 14 and 17. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2014]
Expression: Ubiquitous expression in appendix (RPKM 12.2), esophagus (RPKM 11.3) and 25 other tissues See more
Orthologs: mouse all

Genomic context

Location:: 1p13.2

Exon count:: 12

Annotation release	Status	Assembly	Chr	Location
109.20191205	current	GRCh38.p13 (GCF_000001405.39)	1	NC_000001.11 (111542009..111716695)
105	previous assembly	GRCh37.p13 (GCF_000001405.25)	1	NC_000001.10 (112162405..112256807)

Chromosome 1 - NC_000001.11 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 Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

we firstly found that miR-142-5p was downregulated in pancreatic cancer tumor tissues while Ras-related protein Rap-1 A (RAP1A) was upregulated compared with para-carcinoma non-tumor tissues. Then, we found that RAP1A could be a putative target gene of miR-142-5p
Title: miR-142-5p regulates pancreatic cancer cell proliferation and apoptosis by regulation of RAP1A.
genome-wide association study Identification as a novel susceptibility gene for Crohn's disease in Japanese individuals
Title: A Genome-wide Association Study Identifying RAP1A as a Novel Susceptibility Gene for Crohn's Disease in Japanese Individuals.
MiR-337-3p was discovered to be decreased in cervical cancer, and miR-337-3p up-regulation may inhibit the proliferation, migration and invasion and promote the apoptosis of cervical cancer cells via down-regulating Rap1A.
Title: Role of miR-337-3p and its target Rap1A in modulating proliferation, invasion, migration and apoptosis of cervical cancer cells.
RRSP is a critical virulence factor that robustly inactivates Ras and Rap1 and augments the pathogenicity of invading bacteria via the combined effects of its N and C lobes.
Title: Structural basis of inactivation of Ras and Rap1 small GTPases by Ras/Rap1-specific endopeptidase from the sepsis-causing pathogen <i>Vibrio vulnificus</i>.
results indicate that CD38 promotes RasGRP2/Rap1-mediated CLL cell adhesion and migration by increasing intracellular Ca2+ levels.
Title: Calcium-RasGRP2-Rap1 signaling mediates CD38-induced migration of chronic lymphocytic leukemia cells.
Microarray analysis revealed RAP1A promoted CRC growth partly through phosphatase and tensin homolog (PTEN)/forkhead box O3(FOXO3)/cyclin D1(CCND1) signaling pathway. FOXO3 overexpression could partly mimic the inhibitory effect of RAP1A knockdown in CRC growth.
Title: High expression of Ras-related protein 1A promotes an aggressive phenotype in colorectal cancer via PTEN/FOXO3/CCND1 pathway.
Simultaneous phosphorylation of synGAP by Plk2 and CDK5 at distinct sites produces an additive increase in GAP activity toward HRas ( approximately 230%) and a smaller, non-additive increase in activity toward Rap1.
Title: Phosphorylation of synaptic GTPase-activating protein (synGAP) by polo-like kinase (Plk2) alters the ratio of its GAP activity toward HRas, Rap1 and Rap2 GTPases.
modulation of Rap1 by Pde6delta accommodates key mechanisms underlying neuronal activity
Title: Modifying Rap1-signalling by targeting Pde6δ is neuroprotective in models of Alzheimer's disease.
HL-60 neutrophil-like cells expressing Rap1a(G12V) or Radil have an elongated phenotype because of enhanced uropod adhesion as they attempt to migrate on fibronectin. This elongated phenotype driven by Rap1a(G12V) or Radil is reversed by Galphai1(Q204L), but not by WT Galphai1 expression, suggesting that Galphai-GTP also regulates adhesion in immune cells at the level of, or downstream of, Radil.
Title: Activated heterotrimeric G protein α<sub>i</sub> subunits inhibit Rap-dependent cell adhesion and promote cell migration.
these data highlight a signaling pathway in which SHP-1 acts through CrkII to reshape the pattern of Rap1 activation in the immunological synapse.
Title: The tyrosine phosphatase SHP-1 promotes T cell adhesion by activating the adaptor protein CrkII in the immunological synapse.

Submit: New GeneRIF Correction See all GeneRIFs (129)

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
An integration of genome-wide association study and gene expression profiling to prioritize the discovery of novel susceptibility Loci for osteoporosis-related traits. 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
capsid	gag	Prostaglandin E2-mediated HIV-1 inhibition requires the EPAC/RAP/RhoA signaling pathway by downregulation of HIV-1 CA production	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

AL010000 (e-PCR)
- UniSTS:73811

D1S3458 (e-PCR)
- UniSTS:154712

SHGC-141 (e-PCR)
- UniSTS:19325

Rap1a (e-PCR), detects polymorphism
- UniSTS:532892

Homology

Homologs of the RAP1A gene: The RAP1A gene is conserved in chimpanzee, Rhesus monkey, dog, cow, mouse, rat, chicken, zebrafish, fruit fly, mosquito, E.gossypii, M.oryzae, N.crassa, and frog.
Orthologs from Annotation Pipeline: 244 organisms have orthologs with human gene RAP1A
Orthologs

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
GDP binding	IBA Inferred from Biological aspect of Ancestor more info	PubMed
GTP binding	IBA Inferred from Biological aspect of Ancestor more info	PubMed
GTPase activity	IBA Inferred from Biological aspect of Ancestor more info	PubMed
Rap guanyl-nucleotide exchange factor activity	ISS Inferred from Sequence or Structural Similarity more info
protein binding	IPI Inferred from Physical Interaction more info	PubMed
protein-containing complex binding	IDA Inferred from Direct Assay more info	PubMed

Process	Evidence Code	Pubs
Rap protein signal transduction	IBA Inferred from Biological aspect of Ancestor more info	PubMed
Rap protein signal transduction	IMP Inferred from Mutant Phenotype more info	PubMed
cellular response to cAMP	IBA Inferred from Biological aspect of Ancestor more info	PubMed
cellular response to cAMP	IDA Inferred from Direct Assay more info	PubMed
cellular response to drug	IEA Inferred from Electronic Annotation more info
cellular response to glucose stimulus	IEA Inferred from Electronic Annotation more info
cellular response to nerve growth factor stimulus	ISS Inferred from Sequence or Structural Similarity more info
establishment of endothelial barrier	IMP Inferred from Mutant Phenotype more info	PubMed
liver regeneration	IEA Inferred from Electronic Annotation more info
NOT microvillus assembly	IMP Inferred from Mutant Phenotype more info	PubMed
negative regulation of collagen biosynthetic process	IEA Inferred from Electronic Annotation more info
negative regulation of synaptic vesicle exocytosis	IBA Inferred from Biological aspect of Ancestor more info	PubMed
nerve growth factor signaling pathway	ISS Inferred from Sequence or Structural Similarity more info
neutrophil degranulation	TAS Traceable Author Statement more info
positive regulation of ERK1 and ERK2 cascade	ISS Inferred from Sequence or Structural Similarity more info
positive regulation of Fc-gamma receptor signaling pathway involved in phagocytosis	IEA Inferred from Electronic Annotation more info
positive regulation of GTPase activity	ISS Inferred from Sequence or Structural Similarity more info
positive regulation of glucose import	IEA Inferred from Electronic Annotation more info
positive regulation of neuron projection development	ISS Inferred from Sequence or Structural Similarity more info
positive regulation of protein kinase activity	ISS Inferred from Sequence or Structural Similarity more info
positive regulation of vasculogenesis	ISS Inferred from Sequence or Structural Similarity more info
protein localization to plasma membrane	IDA Inferred from Direct Assay more info	PubMed
regulation of cell junction assembly	IMP Inferred from Mutant Phenotype more info	PubMed
regulation of insulin secretion	TAS Traceable Author Statement more info
regulation of neurotransmitter receptor localization to postsynaptic specialization membrane	IDA Inferred from Direct Assay more info	PubMed
regulation of neurotransmitter receptor localization to postsynaptic specialization membrane	IMP Inferred from Mutant Phenotype more info	PubMed
response to antineoplastic agent	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
cell	IEA Inferred from Electronic Annotation more info
cell junction	ISS Inferred from Sequence or Structural Similarity more info
cytoplasm	IDA Inferred from Direct Assay more info	PubMed
cytosol	TAS Traceable Author Statement more info
early endosome	ISS Inferred from Sequence or Structural Similarity more info
extracellular exosome	HDA more info	PubMed
glutamatergic synapse	IDA Inferred from Direct Assay more info	PubMed
glutamatergic synapse	IMP Inferred from Mutant Phenotype more info	PubMed
guanyl-nucleotide exchange factor complex	IEA Inferred from Electronic Annotation more info
late endosome	ISS Inferred from Sequence or Structural Similarity more info
neuron projection	IEA Inferred from Electronic Annotation more info
perinuclear region of cytoplasm	IDA Inferred from Direct Assay more info	PubMed
phagocytic vesicle	IEA Inferred from Electronic Annotation more info
plasma membrane	IBA Inferred from Biological aspect of Ancestor more info	PubMed
plasma membrane	TAS Traceable Author Statement more info
specific granule membrane	TAS Traceable Author Statement more info

General protein information

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Preferred Names: ras-related protein Rap-1A

Names: GTP-binding protein smg p21A; Ras-related protein Krev-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.

mRNA and Protein(s)

NM_001010935.2 → NP_001010935.1 ras-related protein Rap-1A precursor

See identical proteins and their annotated locations for NP_001010935.1

Status: REVIEWED

Description

Transcript Variant: This variant (1) differs in the 5' UTR, compared to variant 4. Variants 1-5 encode the same protein.

Source sequence(s)

AK094737, BC014086, BG743233, BI460853, BQ220294, BU167449, BU189979, BX473371, CA446565, DA102623, DB312010

Consensus CDS

CCDS840.1

UniProtKB/Swiss-Prot

P62834

UniProtKB/TrEMBL

A8KAH9

Conserved Domains (1) summary

cd04175
Location:3 → 167

Rap1; Rap1 family GTPase consists of Rap1a and Rap1b isoforms
NM_001291896.1 → NP_001278825.1 ras-related protein Rap-1A precursor

See identical proteins and their annotated locations for NP_001278825.1

Status: REVIEWED

Description

Transcript Variant: This variant (3) differs in the 5' UTR, compared to variant 4. Variants 1-5 encode the same protein.

Source sequence(s)

AK094737, AK293044, AL139012, BC014086, BG743233, BU167449, BU189979, BX473371, CA446565, DA102623, DB312010

Consensus CDS

CCDS840.1

UniProtKB/Swiss-Prot

P62834

UniProtKB/TrEMBL

A8KAH9

Conserved Domains (1) summary

cd04175
Location:3 → 167

Rap1; Rap1 family GTPase consists of Rap1a and Rap1b isoforms
NM_001370216.1 → NP_001357145.1 ras-related protein Rap-1A precursor

Status: REVIEWED

Description

Transcript Variant: This variant (4) represents the longest transcript. Variants 1-5 encode the same protein.

Source sequence(s)

AL049557, AL390195

Related

ENSP00000348786.1, ENST00000356415.5

Conserved Domains (1) summary

cd04175
Location:3 → 167

Rap1; Rap1 family GTPase consists of Rap1a and Rap1b isoforms
NM_001370217.1 → NP_001357146.1 ras-related protein Rap-1A precursor

Status: REVIEWED

Description

Transcript Variant: This variant (5) differs in the 5' UTR, compared to variant 4. Variants 1-5 encode the same protein.

Source sequence(s)

AL049557

Conserved Domains (1) summary

cd04175
Location:3 → 167

Rap1; Rap1 family GTPase consists of Rap1a and Rap1b isoforms
NM_002884.3 → NP_002875.1 ras-related protein Rap-1A precursor

See identical proteins and their annotated locations for NP_002875.1

Status: REVIEWED

Description

Transcript Variant: This variant (2) differs in the 5' UTR, compared to variant 4. Variants 1-5 encode the same protein.

Source sequence(s)

AK094737, BC014086, BG743233, BI460853, BU167449, BU189979, BX473371, CA446565, CD108761, DA102623, DB312010

Consensus CDS

CCDS840.1

UniProtKB/Swiss-Prot

P62834

UniProtKB/TrEMBL

A8KAH9

Related

ENSP00000358723.3, ENST00000369709.3

Conserved Domains (1) summary

cd04175
Location:3 → 167

Rap1; Rap1 family GTPase consists of Rap1a and Rap1b isoforms