GRINA glutamate ionotropic receptor NMDA type subunit associated protein 1 [Homo sapiens (human)] - Gene

Summary

Official Symbol: GRINAprovided by HGNC
Official Full Name: glutamate ionotropic receptor NMDA type subunit associated protein 1provided by HGNC
Primary source: HGNC:HGNC:4589
See related: Ensembl:ENSG00000178719 MIM:138251; AllianceGenome:HGNC:4589
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: LFG1; HNRGW; TMBIM3; NMDARA1
Summary: Predicted to enable transmembrane transporter binding activity. Predicted to be involved in negative regulation of apoptotic signaling pathway. Predicted to act upstream of or within endoplasmic reticulum calcium ion homeostasis and negative regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway. Predicted to be active in Golgi apparatus; endoplasmic reticulum; and membrane. [provided by Alliance of Genome Resources, Dec 2024]
Expression: Ubiquitous expression in fat (RPKM 80.7), brain (RPKM 68.3) and 25 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 8q24.3

Exon count:: 7

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	8	NC_000008.11 (143990056..143993415)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	8	NC_060932.1 (145150254..145153613)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	8	NC_000008.10 (145064224..145067583)

Chromosome 8 - NC_000008.11 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: 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?

Glutamate receptor, ionotropic, Nmethyl Daspartateassociated protein 1 promotes colorectal cancer cell proliferation and metastasis, and is negatively regulated by miR2963p.
Title: Glutamate receptor, ionotropic, N‑methyl D‑aspartate‑associated protein 1 promotes colorectal cancer cell proliferation and metastasis, and is negatively regulated by miR‑296‑3p.
Glutamate receptor, ionotropic, N-methyl D-aspartate-associated protein 1, a potential target of miR-296, facilitates proliferation and migration of rectal cancer cells.
Title: Glutamate receptor, ionotropic, N-methyl D-aspartate-associated protein 1, a potential target of miR-296, facilitates proliferation and migration of rectal cancer cells.
PLEC encodes plectin, a cytoskeletal protein that maintains tissue integrity. GRINA encodes TMBIM3, which regulates cell survival. We hypothesized that in a joint predisposed to Osteoarthritis (OA), expression of these genes alters to combat aberrant biomechanics and is epigenetically regulated. However, carriage of the OA risk-conferring allele at this locus hinders this response and contributes to disease development.
Title: Prioritization of PLEC and GRINA as Osteoarthritis Risk Genes Through the Identification and Characterization of Novel Methylation Quantitative Trait Loci.
The cytoplasmic N-terminal half of GRINA (which spans a Proline-rich domain) contains a potential DNA-binding sequence, in addition to cleavage target sites and probable PY-nuclear localization sequences, that may enable it to be released from the rest of the protein and enter the nucleus under suitable conditions, where it could participate in the transcription, alternative splicing, and mRNA export. [review]
Title: Deciphering GRINA/Lifeguard1: Nuclear Location, Ca(2+) Homeostasis and Vesicle Transport.
Human gastric cancers have increased levels of GRINA, which promotes growth of gastric cancer and inhibits tumor cells apoptosis.
Title: Transmembrane protein GRINA modulates aerobic glycolysis and promotes tumor progression in gastric cancer.
Extraintestinal manifestations of celiac disease are explained on the basis of 33-mer gliadin binding to glutamate receptor GRINA.
Title: Extraintestinal manifestations of celiac disease: 33-mer gliadin binding to glutamate receptor GRINA as a new explanation.
These results suggest that the TMBIM family has comparable functions in the maintenance of intracellular Ca(2) homeostasis in a wide variety of tissues
Title: The transmembrane Bax inhibitor motif (TMBIM) containing protein family: Tissue expression, intracellular localization and effects on the ER CA²⁺-filling state.
The role of TMBIM3/GRINA in the control of cell death in cellular and animal models of ER stress possibly owing to the regulation of ER calcium homeostasis.
Title: TMBIM3/GRINA is a novel unfolded protein response (UPR) target gene that controls apoptosis through the modulation of ER calcium homeostasis.
Data showed that GRINA-C was associated with Gb3 synthase, and may demonstrate a new type of posttranscriptional regulation of glycosyltransferases.
Title: Transmembrane BAX inhibitor motif containing (TMBIM) family proteins perturbs a trans-Golgi network enzyme, Gb3 synthase, and reduces Gb3 biosynthesis.
The tmbim3 may participate in cell death regulation by interacting with proteins of Bcl-2 family, promoting tumor metastasis, which is deduced from the evolutionary conservation of the membrane protein family containing multiple membrane spanning segments
Title: Comparative genomics and function analysis on BI1 family.

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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

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
Knockdown of glutamate receptor, ionotropic, N-methyl D-aspartate-associated protein 1 (GRINA) by siRNA has both activating and inhibiting activities on HIV-1 replication in HeLa P4/R5 cells, suggesting a regulatory role in HIV replication	PubMed

Protein interactions

Protein	Gene	Interaction	Pubs
Envelope surface glycoprotein gp120	env	HIV-1 gp120-induced dephosphorylation of KV2.1 is dependent on NMDA receptor-mediated activation of protein phosphatase 2B or calcineurin	PubMed
	env	HIV-1 gp120 activates forward trafficking and surface clustering of NMDA receptors in membrane microdomains by a PKA-dependent phosphorylation of the NR1 C-terminal Ser897, followed by a PKC-dependent phosphorylation of Ser896	PubMed
	env	HIV-1 gp120 activates NMDA receptor directly and phosphorylates JNK through a gp120-mediated apoptotic pathway in human neuroblastoma cells	PubMed
	env	HIV-1 gp120 binds to cells expressing epsilon1/zeta1 or epsilon2/zeta1 combined NMDA receptor subunits, but not to cells expressing a single epsilon1, epsilon2, or zeta1 NMDA receptor subunit	PubMed
	env	HIV-1 gp120 causes an activation of phospholipase A2, resulting in the increased release of arachidonic acid, which may sensitize the NMDA receptor	PubMed
	env	HIV-1 gp120-mediated human cell death involves the NMDA receptor complex; antagonists of the NMDA receptor reverse the gp120-mediated effects	PubMed
Tat	tat	HIV-1 Tat binding to NMDA receptors results in subsequent loss of postsynaptic densities and an NMDA receptor antagonist inhibits this loss	PubMed
	tat	HIV-1 Tat and methamphetamine inhibit the normal conjunction of signaling between D1 and NMDA receptors, resulting in neural dysfunction and death	PubMed
	tat	HIV-1 Tat induces apoptosis of neurons and neurotoxicity through the activation of both NMDA and non-NMDA receptors	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

RH80294 (e-PCR)
- UniSTS:86066

SHGC-153430 (e-PCR)
- UniSTS:177743

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables calcium channel activity	IBA Inferred from Biological aspect of Ancestor more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables transmembrane transporter binding	IEA Inferred from Electronic Annotation more info

Process	Evidence Code	Pubs
involved_in apoptotic signaling pathway	IBA Inferred from Biological aspect of Ancestor more info
involved_in calcium ion transmembrane transport	IEA Inferred from Electronic Annotation more info
involved_in endoplasmic reticulum calcium ion homeostasis	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of extrinsic apoptotic signaling pathway via death domain receptors	IBA Inferred from Biological aspect of Ancestor more info
involved_in negative regulation of neuron apoptotic process	IBA Inferred from Biological aspect of Ancestor more info

Component	Evidence Code	Pubs
is_active_in Golgi apparatus	IBA Inferred from Biological aspect of Ancestor more info
located_in Golgi membrane	IDA Inferred from Direct Assay more info	PubMed
is_active_in endoplasmic reticulum	IBA Inferred from Biological aspect of Ancestor more info
is_active_in membrane	IBA Inferred from Biological aspect of Ancestor more info

General protein information

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Preferred Names: protein lifeguard 1

Names: NMDA receptor glutamate-binding subunit; glutamate [NMDA] receptor-associated protein 1; glutamate receptor, NMDA subtype, glutamate-binding subunit; glutamate receptor, ionotropic, N-methyl D-aspartate-associated protein 1 (glutamate binding); lifeguard 1; putative MAPK-activating protein PM02; transmembrane BAX inhibitor motif containing 3; transmembrane BAX inhibitor motif-containing protein 3

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_000837.2 → NP_000828.1 protein lifeguard 1

See identical proteins and their annotated locations for NP_000828.1

Status: VALIDATED

Description

Transcript Variant: This variant (1) represents the longer transcript. Variants 1 and 2 both encode the same protein.

Source sequence(s)

AC109322

Consensus CDS

CCDS34961.1

UniProtKB/Swiss-Prot

B3KXM7, O43836, Q7Z429, Q8IVW7

UniProtKB/TrEMBL

B4DFJ6

Related

ENSP00000314380.5, ENST00000313269.5

Conserved Domains (2) summary

cd10428
Location:151 → 367

LFG_like; Proteins similar to and including lifeguard (LFG), a putative regulator of apoptosis

pfam15240
Location:43 → 139

Pro-rich; Proline-rich
NM_001009184.2 → NP_001009184.1 protein lifeguard 1

See identical proteins and their annotated locations for NP_001009184.1

Status: VALIDATED

Description

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

Source sequence(s)

AC109322

Consensus CDS

CCDS34961.1

UniProtKB/Swiss-Prot

B3KXM7, O43836, Q7Z429, Q8IVW7

UniProtKB/TrEMBL

B4DFJ6

Related

ENSP00000378507.4, ENST00000395068.9

Conserved Domains (2) summary

cd10428
Location:151 → 367

LFG_like; Proteins similar to and including lifeguard (LFG), a putative regulator of apoptosis

pfam15240
Location:43 → 139

Pro-rich; Proline-rich