TRIP4 thyroid hormone receptor interactor 4 [Homo sapiens (human)] - Gene

Summary

Official Symbol: TRIP4provided by HGNC
Official Full Name: thyroid hormone receptor interactor 4provided by HGNC
Primary source: HGNC:HGNC:12310
See related: Ensembl:ENSG00000103671 MIM:604501; AllianceGenome:HGNC:12310
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: ASC1; ASC-1; MDCDC; SMABF1; ZC2HC5; HsT17391
Summary: This gene encodes a subunit of the tetrameric nuclear activating signal cointegrator 1 (ASC-1) complex, which associates with transcriptional coactivators, nuclear receptors and basal transcription factors to facilitate nuclear receptors-mediated transcription. This protein is localized in the nucleus and contains an E1A-type zinc finger domain, which mediates interaction with transcriptional coactivators and ligand-bound nuclear receptors, such as thyroid hormone receptor and retinoid X receptor alpha, but not glucocorticoid receptor. Mutations in this gene are associated with spinal muscular atrophy with congenital bone fractures-1 (SMABF1). [provided by RefSeq, Apr 2016]
Expression: Ubiquitous expression in thyroid (RPKM 15.4), kidney (RPKM 11.6) and 25 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 15q22.31

Exon count:: 13

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	15	NC_000015.10 (64387836..64455303)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	15	NC_060939.1 (62197257..62264725)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	15	NC_000015.9 (64680035..64747502)

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 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?

Structure and mechanisms of transport of human Asc1/CD98hc amino acid transporter.
Title: Structure and mechanisms of transport of human Asc1/CD98hc amino acid transporter.
LINC00668 promoted non-small lung cancer progression by miR-518c-3p/TRIP4 axis.
Title: LINC00668 promoted non-small lung cancer progression by miR-518c-3p/TRIP4 axis.
ASC1 complex related conditions: Two novel paediatric patients with TRIP4 pathogenic variants and review of literature.
Title: ASC1 complex related conditions: Two novel paediatric patients with TRIP4 pathogenic variants and review of literature.
Inherited Defects of the ASC-1 Complex in Congenital Neuromuscular Diseases.
Title: Inherited Defects of the ASC-1 Complex in Congenital Neuromuscular Diseases.
MicroRNA-518-3p suppresses cell proliferation, invasiveness, and migration in colorectal cancer via targeting TRIP4.
Title: MicroRNA-518-3p suppresses cell proliferation, invasiveness, and migration in colorectal cancer via targeting TRIP4.
results expand the spectrum of TRIP4-associated disease to include mild adult forms, associate ASC-1 depletion with isolated primary muscle involvement, and establish TRIP4 as a causative gene for several congenital muscle diseases, including nemaline, core, centronuclear, and cytoplasmic-body myopathies. They also identify ASC-1 as a novel cell cycle regulator with a key role in cell proliferation.
Title: ASC-1 Is a Cell Cycle Regulator Associated with Severe and Mild Forms of Myopathy.
TRIP4 promotes tumor growth and metastasis and regulates radiosensitivity of cervical cancer by activating MAPK, PI3K/AKT, and hTERT signaling.
Title: TRIP4 promotes tumor growth and metastasis and regulates radiosensitivity of cervical cancer by activating MAPK, PI3K/AKT, and hTERT signaling.
Study showed that TRIP4 promoted melanoma growth through modulation of COX-2 and iNOS expression partially by activating NF-kappaB signaling indirectly and partially by the direct anchoring of itself at COX-2 and iNOS promoter via synergy with p300. Clinical data showed that high expression of TRIP4 was positively correlated with increased expression of COX-2 and iNOS and predicted poor prognosis in melanoma patients.
Title: The Tumor-Promoting Role of TRIP4 in Melanoma Progression and its Involvement in Response to BRAF-Targeted Therapy.
Reports reveal the first TRIP4 mutation defining a novel form of congenital muscle disease and establish the importance of ASC-1 in human skeletal muscle, identify transcriptional co-regulation as novel pathophysiological pathway, define ASC-1 as a regulator of late myogenic differentiation and suggest defects in myotube growth as a novel myopathic mechanism.
Title: The transcription coactivator ASC-1 is a regulator of skeletal myogenesis, and its deficiency causes a novel form of congenital muscle disease.
GWAS in a large Spanish sample identifies TRIP4 (rs74615166) as a significant locus for Alzheimer's disease risk.
Title: Follow-up of loci from the International Genomics of Alzheimer's Disease Project identifies TRIP4 as a novel susceptibility gene.

Submit: New GeneRIF Correction See all GeneRIFs (11)

Phenotypes

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Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Congenital muscular dystrophy-respiratory failure-skin abnormalities-joint hyperlaxity syndrome MedGen: C4310736 OMIM: 617066 GeneReviews: Not available	not available
Spinal muscular atrophy with congenital bone fractures 1 MedGen: C4225177 OMIM: 616866 GeneReviews: Not available	not available

EBI GWAS Catalog

Description
Meta-analysis of 74,046 individuals identifies 11 new susceptibility loci for Alzheimer's disease. 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)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

RH78914 (e-PCR)
- UniSTS:78459

SGC30293 (e-PCR)
- UniSTS:59544

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables histone acetyltransferase binding	IPI Inferred from Physical Interaction more info	PubMed
enables nuclear estrogen receptor binding	IPI Inferred from Physical Interaction more info	PubMed
enables nuclear receptor binding	IDA Inferred from Direct Assay more info	PubMed
enables protease binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein kinase binding	IPI Inferred from Physical Interaction more info	PubMed
enables transcription coactivator activity	IMP Inferred from Mutant Phenotype more info	PubMed
enables ubiquitin-like protein ligase binding	IPI Inferred from Physical Interaction more info	PubMed
enables zinc ion binding	IEA Inferred from Electronic Annotation more info

Process	Evidence Code	Pubs
involved_in estrogen receptor signaling pathway	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of DNA-templated transcription	IBA Inferred from Biological aspect of Ancestor more info
involved_in positive regulation of DNA-templated transcription	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of DNA-templated transcription	IDA Inferred from Direct Assay more info	PubMed
involved_in regulation of DNA-templated transcription	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of myoblast differentiation	ISS Inferred from Sequence or Structural Similarity more info
involved_in rescue of stalled ribosome	IDA Inferred from Direct Assay more info	PubMed
involved_in rescue of stalled ribosome	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in ribosome disassembly	IDA Inferred from Direct Assay more info	PubMed
involved_in ribosome disassembly	NAS Non-traceable Author Statement more info	PubMed
involved_in ribosome-associated ubiquitin-dependent protein catabolic process	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in ribosome-associated ubiquitin-dependent protein catabolic process	NAS Non-traceable Author Statement more info	PubMed

Component	Evidence Code	Pubs
part_of RQC-trigger complex	IEA Inferred from Electronic Annotation more info
part_of activating signal cointegrator 1 complex	IDA Inferred from Direct Assay more info	PubMed
colocalizes_with centrosome	IDA Inferred from Direct Assay more info	PubMed
located_in cytoplasm	IDA Inferred from Direct Assay more info	PubMed
located_in cytosol	IEA Inferred from Electronic Annotation more info
located_in neuromuscular junction	IMP Inferred from Mutant Phenotype more info	PubMed
located_in nuclear body	IDA Inferred from Direct Assay more info
located_in nucleoplasm	IDA Inferred from Direct Assay more info
is_active_in nucleus	IBA Inferred from Biological aspect of Ancestor more info
located_in nucleus	IDA Inferred from Direct Assay more info	PubMed
part_of protein-containing complex	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: activating signal cointegrator 1

Names: TR-interacting protein 4; TRIP-4; thyroid receptor-interacting protein 4; zinc finger, C2HC5-type

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_046848.1 RefSeqGene

Range

5033..72500

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001321924.2 → NP_001308853.1 activating signal cointegrator 1 isoform 2

Status: REVIEWED

Description

Transcript Variant: This variant (2) uses an alternate donor splice site at the 5' terminal exon, which results in translation initiation at an in-frame downstream start codon compared to variant 1. The resulting isoform (2) has a shorter N-terminus compared to isoform 1.

Source sequence(s)

AK314319, BC012448, DA712387

UniProtKB/Swiss-Prot

Q15650

Conserved Domains (1) summary

cd06554
Location:204 → 317

ASCH_ASC-1_like; ASC-1 homology domain, ASC-1-like subfamily. The ASCH domain, a small beta-barrel domain found in all three kingdoms of life, resembles the RNA-binding PUA domain and may also interact with RNA. ASCH has been proposed to function as an RNA-binding domain ...
NM_016213.5 → NP_057297.2 activating signal cointegrator 1 isoform 1

See identical proteins and their annotated locations for NP_057297.2

Status: REVIEWED

Description

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

Source sequence(s)

AK314319, BC012448, BG166305

Consensus CDS

CCDS10194.1

UniProtKB/Swiss-Prot

B2RAS0, Q15650, Q96ED7, Q9UKH0

Related

ENSP00000261884.3, ENST00000261884.8

Conserved Domains (2) summary

cd06554
Location:434 → 547

ASCH_ASC-1_like; ASC-1 homology domain, ASC-1-like subfamily. The ASCH domain, a small beta-barrel domain found in all three kingdoms of life, resembles the RNA-binding PUA domain and may also interact with RNA. ASCH has been proposed to function as an RNA-binding domain ...

pfam06221
Location:168 → 216

zf-C2HC5; Putative zinc finger motif, C2HC5-type

RNA

NR_135855.2 RNA Sequence

Status: REVIEWED

Description

Transcript Variant: This variant (3) lacks an internal exon compared to variant 1. It is represented as non-coding because the use of the 5'-most translational start codon, as used in variant 1, renders this transcript a candidate for nonsense-mediated mRNA decay (NMD).

Source sequence(s)

AK314319, BC012448, BG166305