AP2S1 adaptor related protein complex 2 subunit sigma 1 [Homo sapiens (human)] - Gene

Summary

Official Symbol: AP2S1provided by HGNC
Official Full Name: adaptor related protein complex 2 subunit sigma 1provided by HGNC
Primary source: HGNC:HGNC:565
See related: Ensembl:ENSG00000042753 MIM:602242; AllianceGenome:HGNC:565
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: AP17; FBH3; HHC3; FBHOk; CLAPS2
Summary: One of two major clathrin-associated adaptor complexes, AP-2, is a heterotetramer which is associated with the plasma membrane. This complex is composed of two large chains, a medium chain, and a small chain. This gene encodes the small chain of this complex. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2014]
Expression: Ubiquitous expression in placenta (RPKM 25.3), brain (RPKM 23.2) and 25 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 19q13.32

Exon count:: 6

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	19	NC_000019.10 (46838167..46850846, complement)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	19	NC_060943.1 (49664001..49676674, complement)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	19	NC_000019.9 (47341424..47354103, complement)

Chromosome 19 - NC_000019.10 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

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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?

AP2S1 regulates APP degradation through late endosome-lysosome fusion in cells and APP/PS1 mice.
Title: AP2S1 regulates APP degradation through late endosome-lysosome fusion in cells and APP/PS1 mice.
Mechanism of p38 MAPK-induced EGFR endocytosis and its crosstalk with ligand-induced pathways.
Title: Mechanism of p38 MAPK-induced EGFR endocytosis and its crosstalk with ligand-induced pathways.
Hypercalcemia-associated AP2sigma mutations reduced calcium-sensing receptor (CaSR) signaling via Galphaq/11 and Galphai/o pathways. The mutations also delayed CaSR internalization due to prolonged residency time of CaSR in clathrin structures that impaired or abolished endosomal signaling.
Title: AP2σ Mutations Impair Calcium-Sensing Receptor Trafficking and Signaling, and Show an Endosomal Pathway to Spatially Direct G-Protein Selectivity.
CaSR and AP2S1 sequencing is worthwhile in patients with familial hyperparathyroidism and phenotype suggesting familial hypocalciuric hypercalcemia as it can diagnose up to 50% of cases.
Title: Stepwise CaSR, AP2S1, and GNA11 sequencing in patients with suspected familial hypocalciuric hypercalcemia.
In 33 CASR-negative patients with suspected FHH, Data found two (~6%) with a mutation in AP2S1 (p.Arg15Leu and p.Arg15His). Family screening confirmed the genotype-phenotype correlations. Data did not identify any pathogenic mutations in GNA11.
Title: AP2S1 and GNA11 mutations - not a common cause of familial hypocalciuric hypercalcemia.
our studies demonstrate AP2sigma2 mutations to result in a more severe FHH phenotype with genotype-phenotype correlations, and a dominant-negative mechanism of action with mutational bias at the Arg15 residue.
Title: Adaptor protein-2 sigma subunit mutations causing familial hypocalciuric hypercalcaemia type 3 (FHH3) demonstrate genotype-phenotype correlations, codon bias and dominant-negative effects.
The results affirm that a significant number of patients suspected of having Familial hypocalciuric hypercalcemia but proven negative for CASR mutation have AP2S1 p.R15 mutations.
Title: Codon Arg15 mutations of the AP2S1 gene: common occurrence in familial hypocalciuric hypercalcemia cases negative for calcium-sensing receptor (CASR) mutations.
The absence of AP2S1 abnormalities in hypocalcemic patients, suggests that autosomal dominant hypocalcemia 3 (ADH3) may not occur or otherwise represents a rare hypocalcemic disorder.
Title: Mutational analysis of the adaptor protein 2 sigma subunit (AP2S1) gene: search for autosomal dominant hypocalcemia type 3 (ADH3).
None of the 60 patients presented with nucleotidic changes or copy number variation in the AP2S1 gene, thereby excluding AP2S1 defects as a frequent cause of isolated hypoparathyroidism.
Title: Analysis of AP2S1, a calcium-sensing receptor regulator, in familial and sporadic isolated hypoparathyroidism.
Mutations in AP2S1 cause familial hypocalciuric hypercalcemia type 3.
Title: Mutations in AP2S1 cause familial hypocalciuric hypercalcemia type 3.

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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

Associated conditions

Description	Tests
Familial hypocalciuric hypercalcemia 3 MedGen: C1833372 OMIM: 600740 GeneReviews: Not available	Compare labs

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
Envelope transmembrane glycoprotein gp41	env	Two independent motifs, a membrane proximal conserved GYxxO motif (residues 711-715) and a C-terminal dileucine motif (residues 855-856), of the HIV-1 gp41 protein mediate endocytosis through interaction with the clathrin adaptor AP-2	PubMed
	env	The cytoplasmic domain (residues 707-856) of HIV-1 gp41 interacts with whole clathrin-associated AP-1 and AP-2 adaptor complexes	PubMed
Nef	nef	Mutation of Arg to Glu at position 134 in HIV-1 Nef abolishes its binding to the AP-2 alpha1-sigma2 hemicomplex	PubMed
	nef	HIV-1 Nef (residues 54-203) binds with low micromolar affinity to the AP-2 alpha1 (residues 1-392)-sigma2 (residues 1-142) hemicomplex. The central loop (residues 149-179) and the core (residues 55-65) of Nef are involved in the binding	PubMed
	nef	Interaction of HIV-1 Nef with AP-2 alpha-sigma dimer is required for Nef-mediated CD4 downregulation. The dileucine L164L165 and M168L170 motifs bind to the sigma unit, while the acidic motif E174 and D175 binds to the alpha unit	PubMed
Pr55(Gag)	gag	HIV-1 Gag binds to AP-2, and this binding is dependent on tyrosine residue 132 and valine residue 135 at the matrix-capsid junction in the Gag polyprotein	PubMed
Tat	tat	HIV-1 Tat enters T cells by using clathrin/AP2-mediated endocytosis followed by low-pH-induced and Hsp90-assisted endosomal translocation, which leads to cell responses that are induced from the cytosol	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

RH47043 (e-PCR)
- UniSTS:16195

G62010 (e-PCR)
- UniSTS:139085

STS-X97074 (e-PCR)
- UniSTS:5853

RH80522 (e-PCR)
- UniSTS:89839

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
contributes_to clathrin adaptor activity	TAS Traceable Author Statement more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
involved_in clathrin coat assembly	TAS Traceable Author Statement more info	PubMed
involved_in clathrin-dependent endocytosis	NAS Non-traceable Author Statement more info	PubMed
involved_in clathrin-dependent endocytosis	TAS Traceable Author Statement more info	PubMed
involved_in intracellular protein transport	IEA Inferred from Electronic Annotation more info
involved_in postsynaptic neurotransmitter receptor internalization	NAS Non-traceable Author Statement more info	PubMed
involved_in regulation of endocytosis	TAS Traceable Author Statement more info	PubMed
involved_in synaptic vesicle endocytosis	IDA Inferred from Direct Assay more info	PubMed
involved_in synaptic vesicle endocytosis	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in synaptic vesicle endocytosis	NAS Non-traceable Author Statement more info	PubMed
involved_in vesicle-mediated transport	IBA Inferred from Biological aspect of Ancestor more info
involved_in vesicle-mediated transport	NAS Non-traceable Author Statement more info	PubMed

Component	Evidence Code	Pubs
part_of AP-2 adaptor complex	NAS Non-traceable Author Statement more info	PubMed
part_of AP-2 adaptor complex	TAS Traceable Author Statement more info	PubMed
located_in clathrin-coated endocytic vesicle	NAS Non-traceable Author Statement more info	PubMed
located_in clathrin-coated endocytic vesicle membrane	TAS Traceable Author Statement more info
located_in cytoplasmic side of plasma membrane	NAS Non-traceable Author Statement more info	PubMed
located_in cytosol	TAS Traceable Author Statement more info
located_in endocytic vesicle membrane	TAS Traceable Author Statement more info
located_in endolysosome membrane	TAS Traceable Author Statement more info
is_active_in intracellular membrane-bounded organelle	IBA Inferred from Biological aspect of Ancestor more info
located_in plasma membrane	TAS Traceable Author Statement more info
located_in postsynapse	IEA Inferred from Electronic Annotation more info
located_in presynapse	IEA Inferred from Electronic Annotation more info

General protein information

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Preferred Names: AP-2 complex subunit sigma

Names: HA2 17 kDa subunit; adaptor protein complex AP-2 subunit sigma; adaptor related protein complex 2 sigma 1 subunit; clathrin assembly protein 2 sigma small chain; clathrin coat assembly protein AP17; clathrin coat-associated protein AP17; clathrin-associated/assembly/adaptor protein, small 2 (17kD); plasma membrane adaptor AP-2 17 kDa protein; sigma-2; sigma2-adaptin

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_033136.1 RefSeqGene

Range

5101..17780

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001301076.3 → NP_001288005.1 AP-2 complex subunit sigma isoform 3

See identical proteins and their annotated locations for NP_001288005.1

Status: REVIEWED

Description

Transcript Variant: This variant (3) encodes the longest isoform (3).

Source sequence(s)

AC098794, AI139089, BC006337, BQ221562, CA454481

Consensus CDS

CCDS77321.1

UniProtKB/TrEMBL

M0QYZ2

Related

ENSP00000470176.1, ENST00000601498.5

Conserved Domains (1) summary

cd14833
Location:18 → 157

AP2_sigma; AP-2 complex subunit sigma
NM_001301078.3 → NP_001288007.1 AP-2 complex subunit sigma isoform 4

Status: REVIEWED

Description

Transcript Variant: This variant (4) contains an alternate 5' terminal exon, initiates translation at an alternate start codon and uses an alternate in-frame splice site in the 5' coding region, compared to variant 3. It encodes isoform 4, which is shorter and has a distinct N-terminus, compared to isoform 3.

Source sequence(s)

AI139089, BC006337, BG282225, CB108423, DB472500

Consensus CDS

CCDS77323.1

UniProtKB/TrEMBL

X6R390

Related

ENSP00000263271.6, ENST00000352203.8

Conserved Domains (1) summary

pfam01217
Location:1 → 156

Clat_adaptor_s; Clathrin adaptor complex small chain
NM_001301081.3 → NP_001288010.1 AP-2 complex subunit sigma isoform 5

See identical proteins and their annotated locations for NP_001288010.1

Status: REVIEWED

Description

Transcript Variant: This variant (5) contains an alternate 5' terminal exon and initiates translation at an alternate start codon, compared to variant 3. It encodes isoform 5, which has a shorter and distinct N-terminus, compared to isoform 3.

Source sequence(s)

AC098794, AI139089, BC006337, BI561502

Consensus CDS

CCDS77322.1

UniProtKB/TrEMBL

M0R0N4

Related

ENSP00000471340.1, ENST00000599990.5

Conserved Domains (1) summary

cd14833
Location:4 → 143

AP2_sigma; AP-2 complex subunit sigma
NM_004069.6 → NP_004060.2 AP-2 complex subunit sigma isoform AP17

See identical proteins and their annotated locations for NP_004060.2

Status: REVIEWED

Description

Transcript Variant: This variant (AP17) contains an alternate 5' terminal exon and initiates translation at an alternate start codon, compared to variant 3. It encodes isoform AP17, which has a shorter and distinct N-terminus, compared to isoform 3.

Source sequence(s)

AI139089, BC006337, DB472500

Consensus CDS

CCDS33062.1

UniProtKB/Swiss-Prot

B2R4Z4, O75977, P53680, Q6PK67

Related

ENSP00000263270.6, ENST00000263270.11

Conserved Domains (1) summary

cd14833
Location:1 → 141

AP2_sigma; AP-2 complex subunit sigma
NM_021575.5 → NP_067586.1 AP-2 complex subunit sigma isoform AP17delta

See identical proteins and their annotated locations for NP_067586.1

Status: REVIEWED

Description

Transcript Variant: This variant (AP17delta) contains an alternate 5' terminal exon, initiates translation at an alternate start codon and lacks an alternate in-frame exon in the coding region, compared to variant 3. It encodes isoform AP17delta, which is shorter and has a distinct N-terminus, compared to isoform 3. .

Source sequence(s)

AI139089, AJ713543, BC006337, DB472500

Consensus CDS

CCDS12693.1

UniProtKB/Swiss-Prot

P53680

Related

ENSP00000470898.1, ENST00000601649.1

Conserved Domains (1) summary

cl38905
Location:1 → 103

longin-like; Longin-like domains

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_000019.10 Reference GRCh38.p14 Primary Assembly

Range

46838167..46850846 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_011526424.4 → XP_011524726.1 AP-2 complex subunit sigma isoform X2

Conserved Domains (1) summary

pfam01217
Location:4 → 158

Clat_adaptor_s; Clathrin adaptor complex small chain
XM_011526423.3 → XP_011524725.1 AP-2 complex subunit sigma isoform X1

Conserved Domains (1) summary

pfam01217
Location:18 → 172

Clat_adaptor_s; Clathrin adaptor complex small chain