RIC8A RIC8 guanine nucleotide exchange factor A [Homo sapiens (human)] - Gene

Summary

Official Symbol: RIC8Aprovided by HGNC
Official Full Name: RIC8 guanine nucleotide exchange factor Aprovided by HGNC
Primary source: HGNC:HGNC:29550
See related: Ensembl:ENSG00000177963 MIM:609146; AllianceGenome:HGNC:29550
Gene type: protein coding
RefSeq status: VALIDATED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: RIC8
Summary: Predicted to enable G-protein alpha-subunit binding activity; GTPase regulator activity; and protein folding chaperone. Predicted to be involved in G protein-coupled receptor signaling pathway. Predicted to act upstream of or within several processes, including basement membrane organization; gastrulation; and visual learning. Predicted to be located in membrane. Predicted to be active in cytoplasm and plasma membrane. [provided by Alliance of Genome Resources, Dec 2024]
Expression: Ubiquitous expression in testis (RPKM 20.2), brain (RPKM 15.3) and 25 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 11p15.5

Exon count:: 10

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	11	NC_000011.10 (207708..215113)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	11	NC_060935.1 (248906..256311)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	11	NC_000011.9 (207708..215113)

Chromosome 11 - NC_000011.10 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: Tissue-specific circular RNA induction during human fetal development
Description: 35 human fetal samples from 6 tissues (3 - 7 replicates per tissue) collected between 10 and 20 weeks gestational time were sequenced using Illumina TruSeq Stranded Total RNA
BioProject: PRJNA270632
Publication: PMID 26076956
Analysis date: Mon Apr 2 22:54:59 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Neomorphic Galphao mutations gain interaction with Ric8 proteins in GNAO1 encephalopathies.
Title: Neomorphic Gαo mutations gain interaction with Ric8 proteins in GNAO1 encephalopathies.
circPDE4B prevents articular cartilage degeneration and promotes repair by acting as a scaffold for RIC8A and MID1.
Title: circPDE4B prevents articular cartilage degeneration and promotes repair by acting as a scaffold for RIC8A and MID1.
Structures of Galpha Proteins in Complex with Their Chaperone Reveal Quality Control Mechanisms.
Title: Structures of Gα Proteins in Complex with Their Chaperone Reveal Quality Control Mechanisms.
These results indicate that dual phosphorylation represents a critical form of conserved Ric-8 regulation and demonstrate that Ric-8 proteins are needed for effective Galpha signaling.
Title: Dual phosphorylation of Ric-8A enhances its ability to mediate G protein α subunit folding and to stimulate guanine nucleotide exchange.
Human NCS-1 and Ric8a reproduce the binding and maintain the structural requirements at these key positions. Drosophila Ric8a and Galphas regulate synapse number and neurotransmitter release, and both are functionally linked to Frq2.
Title: The guanine-exchange factor Ric8a binds to the Ca²⁺ sensor NCS-1 to regulate synapse number and neurotransmitter release.
Results confirmed that Ric-8A can directly bind to AGS3S but failed to facilitate Galpha(i)-induced suppression of adenylyl cyclase, suggesting that it may not serve as a guanine exchange factor for AGS3/Galpha(i/o)-GDP complex in a cellular environment.
Title: Activator of G protein signaling 3 forms a complex with resistance to inhibitors of cholinesterase-8A without promoting nucleotide exchange on Gα(i3).
Ric-8A co-localized with Vps34 at the midbody.
Title: Resistance to inhibitors of cholinesterase (Ric)-8A and Gαi contribute to cytokinesis abscission by controlling vacuolar protein-sorting (Vps)34 activity.
The ubiquitination of Galphai2 and Galphaq is suppressed by expression of Ric-8A. The suppression likely requires Ric-8A interaction with these Galpha proteins; the C-terminal truncation of Galphaq and Galphai2 completely abrogates their interaction with Ric-8A.
Title: Ubiquitination of the heterotrimeric G protein α subunits Gαi2 and Gαq is prevented by the guanine nucleotide exchange factor Ric-8A.
NCAM180 regulates Ric8A membrane localization and potentiates beta-adrenergic response
Title: NCAM180 regulates Ric8A membrane localization and potentiates β-adrenergic response.
RGS14 can form complexes with GPCRs in cells that are dependent on Galpha(i/o) and these RGS14.Galpha(i1).GPCR complexes may be substrates for other signaling partners such as Ric-8A
Title: G protein-coupled receptors and resistance to inhibitors of cholinesterase-8A (Ric-8A) both regulate the regulator of g protein signaling 14 RGS14·Gαi1 complex in live cells.

Submit: New GeneRIF Correction See all GeneRIFs (12)

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- and phenome-wide association study to identify genetic variants influencing platelet count and volume and their pleiotropic effects. EBI GWAS Catalog EBI GWAS CatalogPubMed
A genome-wide association study identifies three loci associated with susceptibility to uterine fibroids. 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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Replication interactions

Interaction	Pubs
HIV-1 infection (VSV-G pseudotyped) of CEMT4 T cells downregulates plasma membrane expression of RIC8A	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

G19667 (e-PCR)
- UniSTS:59448

A001U35 (e-PCR)
- UniSTS:59449

A004P12 (e-PCR)
- UniSTS:55647

WI-19967 (e-PCR)
- UniSTS:54372

G43176 (e-PCR)
- UniSTS:94892

Clone Names

MGC104517, MGC131931, MGC148073, MGC148074

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables G-protein alpha-subunit binding	IBA Inferred from Biological aspect of Ancestor more info
enables G-protein alpha-subunit binding	ISS Inferred from Sequence or Structural Similarity more info
enables guanyl-nucleotide exchange factor activity	IBA Inferred from Biological aspect of Ancestor more info
enables guanyl-nucleotide exchange factor activity	ISS Inferred from Sequence or Structural Similarity more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein folding chaperone	ISS Inferred from Sequence or Structural Similarity more info

Process	Evidence Code	Pubs
involved_in G protein-coupled receptor signaling pathway	IBA Inferred from Biological aspect of Ancestor more info
involved_in G protein-coupled receptor signaling pathway	ISS Inferred from Sequence or Structural Similarity more info
involved_in adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in basement membrane organization	IEA Inferred from Electronic Annotation more info
involved_in cell migration involved in gastrulation	IEA Inferred from Electronic Annotation more info
involved_in cell-cell adhesion involved in gastrulation	IEA Inferred from Electronic Annotation more info
involved_in in utero embryonic development	IEA Inferred from Electronic Annotation more info
involved_in protein folding	IEA Inferred from Electronic Annotation more info
involved_in vasculature development	IEA Inferred from Electronic Annotation more info
involved_in visual learning	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
located_in cell cortex	IEA Inferred from Electronic Annotation more info
is_active_in cytoplasm	IBA Inferred from Biological aspect of Ancestor more info
located_in cytoplasm	ISS Inferred from Sequence or Structural Similarity more info
is_active_in plasma membrane	IBA Inferred from Biological aspect of Ancestor more info
located_in plasma membrane	ISS Inferred from Sequence or Structural Similarity more info

General protein information

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Preferred Names: synembryn-A

Names: resistance to inhibitors of cholinesterase 8 homolog A

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_001286134.2 → NP_001273063.1 synembryn-A isoform 2

See identical proteins and their annotated locations for NP_001273063.1

Status: VALIDATED

Description

Transcript Variant: This variant (2) uses an alternate in-frame splice site, compared to variant 1. The encoded isoform (2) is shorter than isoform 1.

Source sequence(s)

AC069287

Consensus CDS

CCDS65982.1

UniProtKB/Swiss-Prot

Q0P508, Q2T9J1, Q7Z352, Q96EZ1, Q96SZ2, Q9H064, Q9H5H3, Q9H9E7, Q9NPQ8

Related

ENSP00000432008.1, ENST00000526104.6

Conserved Domains (1) summary

pfam10165
Location:67 → 498

Ric8; Guanine nucleotide exchange factor synembryn
NM_001386941.1 → NP_001373870.1 synembryn-A isoform 3

Status: VALIDATED

Source sequence(s)

AC069287

Conserved Domains (1) summary

pfam10165
Location:71 → 497

Ric8; Guanine nucleotide exchange factor synembryn
NM_001386942.1 → NP_001373871.1 synembryn-A isoform 4

Status: VALIDATED

Source sequence(s)

AC069287

Related

ENSP00000434833.1, ENST00000527696.5

Conserved Domains (1) summary

pfam10165
Location:2 → 383

Ric8; Guanine nucleotide exchange factor synembryn
NM_021932.6 → NP_068751.4 synembryn-A isoform 1

See identical proteins and their annotated locations for NP_068751.4

Status: VALIDATED

Description

Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (1).

Source sequence(s)

AC069287, AL136935

Consensus CDS

CCDS7690.1

UniProtKB/Swiss-Prot

Q9NPQ8

Related

ENSP00000325941.5, ENST00000325207.9

Conserved Domains (1) summary

pfam10165
Location:67 → 504

Ric8; Guanine nucleotide exchange factor synembryn