STX4 syntaxin 4 [Homo sapiens (human)] - Gene

Summary

Official Symbol: STX4provided by HGNC
Official Full Name: syntaxin 4provided by HGNC
Primary source: HGNC:HGNC:11439
See related: Ensembl:ENSG00000103496 MIM:186591; AllianceGenome:HGNC:11439
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: STX4A; p35-2; DFNB123
Summary: Enables sphingomyelin phosphodiesterase activator activity. Involved in several processes, including cornified envelope assembly; positive regulation of immune effector process; and positive regulation of protein localization. Located in several cellular components, including basolateral plasma membrane; cytoplasmic vesicle; and lamellipodium. Part of SNARE complex. Is active in glutamatergic synapse and postsynapse. Implicated in autosomal recessive nonsyndromic deafness. [provided by Alliance of Genome Resources, Nov 2024]
Expression: Ubiquitous expression in spleen (RPKM 17.8), adrenal (RPKM 16.5) and 25 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 16p11.2

Exon count:: 13

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	16	NC_000016.10 (31033095..31040168)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	16	NC_060940.1 (31420532..31430402)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	16	NC_000016.9 (31044416..31051489)

Chromosome 16 - NC_000016.10 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: 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?

Phosphorylation of Syntaxin 4 by the Insulin Receptor Drives Exocytic SNARE Complex Formation to Deliver GLUT4 to the Cell Surface.
Title: Phosphorylation of Syntaxin 4 by the Insulin Receptor Drives Exocytic SNARE Complex Formation to Deliver GLUT4 to the Cell Surface.
Syntaxin-4 and SNAP23 are involved in neutrophil degranulation, but not in the release of mitochondrial DNA during NET formation.
Title: Syntaxin-4 and SNAP23 are involved in neutrophil degranulation, but not in the release of mitochondrial DNA during NET formation.
Syntaxin 4 is essential for hearing in human and zebrafish.
Title: Syntaxin 4 is essential for hearing in human and zebrafish.
Up-regulation expression and prognostic significance of Syntaxin4 in kidney renal clear cell carcinoma.
Title: Up-regulation expression and prognostic significance of Syntaxin4 in kidney renal clear cell carcinoma.
Nitric Oxide Generated by Tumor-Associated Macrophages Is Responsible for Cancer Resistance to Cisplatin and Correlated With Syntaxin 4 and Acid Sphingomyelinase Inhibition.
Title: Nitric Oxide Generated by Tumor-Associated Macrophages Is Responsible for Cancer Resistance to Cisplatin and Correlated With Syntaxin 4 and Acid Sphingomyelinase Inhibition.
these results indicate that the activation of beta-ARs induces secretory granules and cell membrane fusion via the interaction of VAMP-2 and syntaxin-4 in a PKA- and F-actin-dependent manner in human submandibular gland. Up-regulated beta-ARs might participate in altering protein secretion in transplanted submandibular gland by promoting the interaction of VAMP-2 with syntaxin-4.
Title: β-adrenoceptor activation increased VAMP-2 and syntaxin-4 in secretory granules are involved in protein secretion of submandibular gland through the PKA/F-actin pathway.
Confocal immunofluorescence microscopy revealed a colocalization of syntaxin 4 with a MVB-specific marker, exosomes and hepatitis C virus (HCV) core, which suggests a fraction of syntaxin 4 is associated with exosomes loaded with HCV. Altogether, it is assumed that syntaxin 4 is a novel essential cellular factor for the release of HCV.
Title: Identification of syntaxin 4 as an essential factor for the hepatitis C virus life cycle.
The authors found that activation of dendritic cells by bacterial lipopolysaccharide leads to increased Forster resonance energy transfer-fluorescence of fluorescently labeled syntaxin 4 with VAMP3 specifically at the plasma membrane, indicating increased SNARE complex formation, whereas FRET with other tested SNAREs was unaltered.
Title: Fluorescence Lifetime Imaging Microscopy reveals rerouting of SNARE trafficking driving dendritic cell activation.
Data suggest MUNC18C is required for STX4-mediated invadopodium formation and tumor invasion of extracellular matrix; N-terminal STX4 fragment binds to MUNC18C and inhibits interactions of STX4 with synaptosome-associated protein 23 (SNAP23) and vesicle-associated membrane protein 2 (VAMP2). Fibrosarcoma/adenocarcinoma cell lines were used in these studies. (MUNC18C = syntaxin binding protein MUNC18C; STX4 = syntaxin 4)
Title: Interaction of Munc18c and syntaxin4 facilitates invadopodium formation and extracellular matrix invasion of tumor cells.
The analysis revealed three candidate genes GSK3B, PTPN1, STX4 that are differentially expressed in study subjects. GSK3B was highly significant in Ps-T2D (P=0.00018, FR=-26.6), followed by Ps (P=0.0028, FR=-14.5) and T2D groups (P=0.032, FR=-5.9). PTPN1 showed significant association only with PS-T2D (P=0.00027, FR=-8.5). STX4 showed significant association with both Ps (P=0.0002, FR=-20) and Ps-T2D (P=0.0016, FR=-11.2).
Title: De-regulation of diabetic regulatory genes in psoriasis: Deciphering the unsolved riddle.

Submit: New GeneRIF Correction See all GeneRIFs (25)

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

Associated conditions

Description	Tests
Hearing loss, autosomal recessive 123 MedGen: CN376948 OMIM: 620745 GeneReviews: Not available	not available

EBI GWAS Catalog

Description
A genome-wide scan for common genetic variants with a large influence on warfarin maintenance dose. 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

RH48799 (e-PCR)
- UniSTS:88576

RH11484 (e-PCR)
- UniSTS:88850

SHGC-146535 (e-PCR)
- UniSTS:175276

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables SNAP receptor activity	IBA Inferred from Biological aspect of Ancestor more info
enables SNARE binding	IBA Inferred from Biological aspect of Ancestor more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables sphingomyelin phosphodiesterase activator activity	IMP Inferred from Mutant Phenotype more info	PubMed

Process	Evidence Code	Pubs
involved_in SNARE complex assembly	IEA Inferred from Electronic Annotation more info
involved_in cellular response to oxidative stress	IDA Inferred from Direct Assay more info	PubMed
involved_in cellular response to type II interferon	IEA Inferred from Electronic Annotation more info
involved_in cornified envelope assembly	IDA Inferred from Direct Assay more info	PubMed
involved_in exocytosis	IBA Inferred from Biological aspect of Ancestor more info
involved_in intracellular protein transport	IBA Inferred from Biological aspect of Ancestor more info
involved_in long-term synaptic potentiation	IDA Inferred from Direct Assay more info	PubMed
involved_in neurotransmitter transport	IEA Inferred from Electronic Annotation more info
involved_in organelle fusion	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of catalytic activity	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of cell adhesion	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of cell migration	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of cell population proliferation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of chemotaxis	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of eosinophil degranulation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of immunoglobulin production	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of insulin secretion involved in cellular response to glucose stimulus	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of insulin secretion involved in cellular response to glucose stimulus	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of protein localization to cell surface	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of protein localization to plasma membrane	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in protein localization to cell surface	ISS Inferred from Sequence or Structural Similarity more info
involved_in regulation of exocytosis	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of extrinsic apoptotic signaling pathway via death domain receptors	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of postsynaptic membrane neurotransmitter receptor levels	IEA Inferred from Electronic Annotation more info
involved_in sensory perception of sound	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in vesicle docking	IBA Inferred from Biological aspect of Ancestor more info
involved_in vesicle fusion	IBA Inferred from Biological aspect of Ancestor more info

Component	Evidence Code	Pubs
part_of SNARE complex	IBA Inferred from Biological aspect of Ancestor more info
part_of SNARE complex	IDA Inferred from Direct Assay more info	PubMed
located_in Schaffer collateral - CA1 synapse	IEA Inferred from Electronic Annotation more info
located_in basolateral plasma membrane	IDA Inferred from Direct Assay more info	PubMed
located_in cell surface	IDA Inferred from Direct Assay more info	PubMed
located_in cytosol	TAS Traceable Author Statement more info
located_in dendritic spine	IDA Inferred from Direct Assay more info	PubMed
is_active_in endomembrane system	IBA Inferred from Biological aspect of Ancestor more info
located_in endosome	IDA Inferred from Direct Assay more info	PubMed
located_in extracellular exosome	HDA more info	PubMed
located_in extracellular space	IDA Inferred from Direct Assay more info	PubMed
is_active_in glutamatergic synapse	IDA Inferred from Direct Assay more info	PubMed
is_active_in glutamatergic synapse	IMP Inferred from Mutant Phenotype more info	PubMed
located_in lamellipodium	IDA Inferred from Direct Assay more info	PubMed
located_in lateral loop	IEA Inferred from Electronic Annotation more info
located_in membrane	IDA Inferred from Direct Assay more info	PubMed
located_in myelin sheath adaxonal region	IEA Inferred from Electronic Annotation more info
located_in neuron projection membrane	ISS Inferred from Sequence or Structural Similarity more info
located_in perinuclear region of cytoplasm	IEA Inferred from Electronic Annotation more info
located_in phagocytic vesicle membrane	TAS Traceable Author Statement more info
is_active_in plasma membrane	IBA Inferred from Biological aspect of Ancestor more info
located_in plasma membrane	IDA Inferred from Direct Assay more info	PubMed
located_in plasma membrane	TAS Traceable Author Statement more info
is_active_in postsynapse	IDA Inferred from Direct Assay more info	PubMed
is_active_in postsynapse	IMP Inferred from Mutant Phenotype more info	PubMed
located_in somatodendritic compartment	IDA Inferred from Direct Assay more info	PubMed
located_in specific granule	IDA Inferred from Direct Assay more info	PubMed
located_in stereocilium	ISS Inferred from Sequence or Structural Similarity more info
located_in storage vacuole	IEA Inferred from Electronic Annotation more info
located_in synapse	IDA Inferred from Direct Assay more info	PubMed
located_in trans-Golgi network	IEA Inferred from Electronic Annotation more info
located_in vacuole	TAS Traceable Author Statement more info	PubMed

General protein information

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Preferred Names: syntaxin-4

Names: renal carcinoma antigen NY-REN-31; syntaxin 4A (placental)

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_001272095.1 → NP_001259024.1 syntaxin-4 isoform 1

See identical proteins and their annotated locations for NP_001259024.1

Status: VALIDATED

Description

Transcript Variant: This variant (1) represents the longest transcript and encodes the shortest protein (isoform 1).

Source sequence(s)

AK296652, BI755734, BQ775670

UniProtKB/TrEMBL

B7Z425

Conserved Domains (2) summary

pfam00804
Location:1 → 157

Syntaxin

pfam05739
Location:158 → 209

SNARE; SNARE domain
NM_001272096.1 → NP_001259025.1 syntaxin-4 isoform 2

See identical proteins and their annotated locations for NP_001259025.1

Status: VALIDATED

Description

Transcript Variant: This variant (2) contains a distinct 5' UTR, initiates translation at an alternate upstream start codon and uses alternate splice sites at internal exons, compared to variant 1. The encoded isoform (2) has a distinct N-terminus and is longer than isoform 1.

Source sequence(s)

AK091833, BC002436, BQ775670

Consensus CDS

CCDS61916.1

UniProtKB/Swiss-Prot

Q12846

Related

ENSP00000378447.1, ENST00000394998.5

Conserved Domains (2) summary

cd00179
Location:42 → 187

SynN; Syntaxin N-terminus domain; syntaxins are nervous system-specific proteins implicated in the docking of synaptic vesicles with the presynaptic plasma membrane; they are a family of receptors for intracellular transport vesicles; each target membrane may ...

cd15883
Location:197 → 259

SNARE_syntaxin4; SNARE motif of syntaxin 4
NM_004604.5 → NP_004595.2 syntaxin-4 isoform 3

See identical proteins and their annotated locations for NP_004595.2

Status: VALIDATED

Description

Transcript Variant: This variant (3) initiates translation at an alternate downstream start codon and uses alternate splice sites at internal exons, compared to variant 1. The encoded isoform (3) has a distinct N-terminus and is longer than isoform 1.

Source sequence(s)

BC002436, BI755734

Consensus CDS

CCDS10700.1

UniProtKB/Swiss-Prot

A8MXY0, Q12846, Q15525, Q6FHE8

Related

ENSP00000317714.3, ENST00000313843.8

Conserved Domains (2) summary

cd00179
Location:39 → 189

SynN; Syntaxin N-terminus domain; syntaxins are nervous system-specific proteins implicated in the docking of synaptic vesicles with the presynaptic plasma membrane; they are a family of receptors for intracellular transport vesicles; each target membrane may ...

cd15883
Location:199 → 261

SNARE_syntaxin4; SNARE motif of syntaxin 4

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_000016.10 Reference GRCh38.p14 Primary Assembly

Range

31033095..31040168

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_005255521.2 → XP_005255578.1 syntaxin-4 isoform X1

See identical proteins and their annotated locations for XP_005255578.1

Conserved Domains (3) summary

cd00179
Location:40 → 185

SynN; Syntaxin N-terminus domain; syntaxins are nervous system-specific proteins implicated in the docking of synaptic vesicles with the presynaptic plasma membrane; they are a family of receptors for intracellular transport vesicles; each target membrane may ...

cd15883
Location:195 → 257

SNARE_syntaxin4; SNARE motif of syntaxin 4

pfam00804
Location:40 → 231

Syntaxin; Syntaxin
XM_047434542.1 → XP_047290498.1 syntaxin-4 isoform X2
XM_047434543.1 → XP_047290499.1 syntaxin-4 isoform X3