AP2M1 adaptor related protein complex 2 subunit mu 1 [Homo sapiens (human)] - Gene

Summary

Official Symbol: AP2M1provided by HGNC
Official Full Name: adaptor related protein complex 2 subunit mu 1provided by HGNC
Primary source: HGNC:HGNC:564
See related: Ensembl:ENSG00000161203 MIM:601024; AllianceGenome:HGNC:564
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: mu2; AP50; MRD60; CLAPM1
Summary: This gene encodes a subunit of the heterotetrameric coat assembly protein complex 2 (AP2), which belongs to the adaptor complexes medium subunits family. The encoded protein is required for the activity of a vacuolar ATPase, which is responsible for proton pumping occurring in the acidification of endosomes and lysosomes. The encoded protein may also play an important role in regulating the intracellular trafficking and function of CTLA-4 protein. Three transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2015]
Expression: Ubiquitous expression in brain (RPKM 196.0), adrenal (RPKM 156.4) and 25 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 3q27.1

Exon count:: 14

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	3	NC_000003.12 (184174855..184184091)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	3	NC_060927.1 (186983791..186993030)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	3	NC_000003.11 (183892643..183901879)

Chromosome 3 - NC_000003.12 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
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?

SLC26A4-AP-2 mu2 interaction regulates SLC26A4 plasma membrane abundance in the endolymphatic sac.
Title: SLC26A4-AP-2 mu2 interaction regulates SLC26A4 plasma membrane abundance in the endolymphatic sac.
High expression of AP2M1 correlates with worse prognosis by regulating immune microenvironment and drug resistance to R-CHOP in diffuse large B cell lymphoma.
Title: High expression of AP2M1 correlates with worse prognosis by regulating immune microenvironment and drug resistance to R-CHOP in diffuse large B cell lymphoma.
AP2M1 mediates autophagy-induced CLDN2 (claudin 2) degradation through endocytosis and interaction with LC3 and reduces intestinal epithelial tight junction permeability.
Title: AP2M1 mediates autophagy-induced CLDN2 (claudin 2) degradation through endocytosis and interaction with LC3 and reduces intestinal epithelial tight junction permeability.
Regulation of BMP2K in AP2M1-mediated EGFR internalization during the development of gallbladder cancer.
Title: Regulation of BMP2K in AP2M1-mediated EGFR internalization during the development of gallbladder cancer.
Expression levels of SIX1, ME2, and AP2M1 in adenoid cystic carcinoma and mucoepidermoid carcinoma.
Title: Expression levels of SIX1, ME2, and AP2M1 in adenoid cystic carcinoma and mucoepidermoid carcinoma.
The knockdown of AP2M1 in the Dengue virus infected Huh7 cells displayed a reduction in the viral titer at 24 h post-infection.
Title: Suppression of µ1 subunit of the adaptor protein complex 2 reduces dengue virus release.
AP2M1 expression values fulfills a sufficient role as a novel prognostic marker for hepatocellular carcinoma, especially in, alcohol or hepatitis C subgroups.
Title: The AP2M1 gene expression is a promising biomarker for predicting survival of patients with hepatocellular carcinoma.
A Recurrent Missense Variant in AP2M1 Impairs Clathrin-Mediated Endocytosis and Causes Developmental and Epileptic Encephalopathy.
Title: A Recurrent Missense Variant in AP2M1 Impairs Clathrin-Mediated Endocytosis and Causes Developmental and Epileptic Encephalopathy.
It has been shown that the cytoplasmic domains of furin bind the mu subunits of AP-1 and AP-2 in a phosphorylation-dependent manner.
Title: Phosphoserine acidic cluster motifs bind distinct basic regions on the μ subunits of clathrin adaptor protein complexes.
AP2 has evolved as a key regulatory node to coordinate clarhtin-coated pit formation and cargo sorting and ensure high spatial and temporal regulation of cathrin-mediated endocytosis.
Title: Regulation of clathrin-mediated endocytosis by hierarchical allosteric activation of AP2.

Submit: New GeneRIF Correction See all GeneRIFs (32)

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
Intellectual developmental disorder 60 with seizures MedGen: C5231497 OMIM: 618587 GeneReviews: Not available	not available

EBI GWAS Catalog

Description
A mega-analysis of genome-wide association studies for major depressive disorder. 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
Knockdown of adaptor-related protein complex 2, mu 1 subunit (AP2M1) by siRNA inhibits HIV-1 replication in HeLa-derived TZM-bl cells	PubMed
Knockdown of AP2M1 by siRNA enhances the early stages of HIV-1 replication in HeLa-CD4 cells infected with viral pseudotypes HIV89.6R and HIV8.2N	PubMed

Protein interactions

Protein	Gene	Interaction	Pubs
Envelope surface glycoprotein gp120	env	Tandem affinity purification and mass spectrometry analysis identify adaptor-related protein complex 2 mu 1 subunit (AP2M1), HIV-1 Gag, Gag/Pol, gp120, and Nef incorporated into staufen1 RNP complexes isolated from HIV-1-expressing cells	PubMed
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	Two tyrosine-based endocytic signals (residues 704-710 and 760-766) in the cytosolic tail (gp41) of the HIV-1 envelope glycoprotein (Env) complex interact with members of the adaptor medium chain family, AP-1 mu1, AP-2 mu2 and AP-3 mu3A	PubMed
Gag-Pol	gag-pol	Tandem affinity purification and mass spectrometry analysis identify adaptor-related protein complex 2 mu 1 subunit (AP2M1), HIV-1 Gag, Gag/Pol, gp120, and Nef incorporated into staufen1 RNP complexes isolated from HIV-1-expressing cells	PubMed
Nef	nef	HIV-1 Nef interacts weakly and directly with AP2M1 (AP-2mu) in 293T cells and this interaction is dependent on Nef membrane localization as shown by FACS-Forster resonance energy transfer (FRET)-based and site-directed mutagenesis experiments	PubMed
	nef	Using RNA interference analyses, the downregulation of CD8beta by Nef requires an intact mu subunit of the AP-2 complex	PubMed
	nef	Tandem affinity purification and mass spectrometry analysis identify adaptor-related protein complex 2 mu 1 subunit (AP2M1), HIV-1 Gag, Gag/Pol, gp120, and Nef incorporated into staufen1 RNP complexes isolated from HIV-1-expressing cells	PubMed
	nef	HIV-1 Nef upregulates the expression of the invariant chain (Ii)/major histocompatibility complex class II (MHC-II) complex through the AP-2 mu2 pathway	PubMed
	nef	Nef-mediated CD4 downregulation is inhibited by RNA interference of AP-2 expression, indicating that Nef-mediated CD4 downregulation requires AP-2	PubMed
Pr55(Gag)	gag	Tandem affinity purification and mass spectrometry analysis identify adaptor-related protein complex 2 mu 1 subunit (AP2M1), HIV-1 Gag, Gag/Pol, gp120, and Nef incorporated into staufen1 RNP complexes isolated from HIV-1-expressing cells	PubMed
	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
Vpu	vpu	HIV-1 Vpu directly interacts with the mu subunit of clathrin-associated protein complex AP-2 in cells	PubMed
	vpu	The plasma membrane clathrin adaptor protein complex AP-2 (mu2) is required for optimal downregulation of cell surface BST-2 by Vpu	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

IB397 (e-PCR)
- UniSTS:24845

SHGC-77604 (e-PCR)
- UniSTS:23076

SHGC-77602 (e-PCR)
- UniSTS:13115

D3S2818E (e-PCR)
- UniSTS:150854

STS-R80399 (e-PCR)
- UniSTS:23916

Ap2m1 (e-PCR), detects polymorphism
- UniSTS:506732

RH92621 (e-PCR)
- UniSTS:84080

IB1255 (e-PCR)
- UniSTS:80498

UTR-04950 (e-PCR)
- UniSTS:82364

SHGC-7485 (e-PCR)
- UniSTS:13789

MARC_13450-13451:1002298269:1 (e-PCR)
- UniSTS:267498

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables clathrin adaptor activity	IBA Inferred from Biological aspect of Ancestor more info
contributes_to clathrin adaptor activity	TAS Traceable Author Statement more info	PubMed
enables disordered domain specific binding	IEA Inferred from Electronic Annotation more info
enables lipid binding	IEA Inferred from Electronic Annotation more info
enables low-density lipoprotein particle receptor binding	ISS Inferred from Sequence or Structural Similarity more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables signal sequence binding	IDA Inferred from Direct Assay more info	PubMed
enables transmembrane transporter binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
involved_in clathrin-dependent endocytosis	IBA Inferred from Biological aspect of Ancestor more info
involved_in clathrin-dependent endocytosis	IDA Inferred from Direct Assay 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 negative regulation of protein localization to plasma membrane	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of receptor internalization	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of synaptic vesicle endocytosis	IEA Inferred from Electronic Annotation more info
involved_in postsynaptic neurotransmitter receptor internalization	NAS Non-traceable Author Statement more info	PubMed
involved_in protein-containing complex assembly	TAS Traceable Author Statement more info	PubMed
involved_in receptor internalization	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of vesicle size	IMP Inferred from Mutant Phenotype 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 budding from membrane	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in vesicle-mediated transport	NAS Non-traceable Author Statement more info	PubMed

Component	Evidence Code	Pubs
part_of AP-2 adaptor complex	IBA Inferred from Biological aspect of Ancestor more info
part_of AP-2 adaptor complex	IDA Inferred from Direct Assay more info	PubMed
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 clathrin-coated pit	IDA Inferred from Direct Assay more info	PubMed
located_in cytoplasmic side of plasma membrane	NAS Non-traceable Author Statement more info	PubMed
is_active_in cytoplasmic vesicle	IBA Inferred from Biological aspect of Ancestor more info
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
located_in extracellular exosome	HDA more info	PubMed
located_in extrinsic component of presynaptic endocytic zone membrane	IEA Inferred from Electronic Annotation more info
located_in glutamatergic synapse	IEA Inferred from Electronic Annotation more info
located_in lysosomal membrane	TAS Traceable Author Statement more info
located_in plasma membrane	IDA Inferred from Direct Assay more info
located_in plasma membrane	TAS Traceable Author Statement more info
located_in postsynapse	IEA Inferred from Electronic Annotation more info
located_in synaptic vesicle	IEA Inferred from Electronic Annotation more info

General protein information

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Preferred Names: AP-2 complex subunit mu

Names: AP-2 mu 2 chain; HA2 50 kDA subunit; adaptin-mu2; adaptor protein complex AP-2 subunit mu; adaptor related protein complex 2 mu 1 subunit; adaptor-related protein complex 2 subunit mu; clathrin adaptor complex AP2, mu subunit; clathrin assembly protein complex 2 medium chain; clathrin assembly protein complex 2 mu medium chain; clathrin coat adaptor protein AP50; clathrin coat assembly protein AP50; clathrin coat-associated protein AP50; clathrin-associated/assembly/adaptor protein, medium 1; plasma membrane adaptor AP-2 50 kDa protein; plasma membrane adaptor AP-2 50kDA protein

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_001025205.2 → NP_001020376.1 AP-2 complex subunit mu isoform b

See identical proteins and their annotated locations for NP_001020376.1

Status: REVIEWED

Description

Transcript Variant: This variant (2) lacks three alternate in-frame exons compared to variant 3. The resulting isoform (b) has the same N- and C-termini but is shorter compared to isoform c.

Source sequence(s)

BC004996, BC013796, BI461415

Consensus CDS

CCDS43178.1

UniProtKB/TrEMBL

A0A087WY71

Related

ENSP00000371894.3, ENST00000382456.7

Conserved Domains (2) summary

cd09251
Location:166 → 432

AP-2_Mu2_Cterm; C-terminal domain of medium Mu2 subunit in ubiquitously expressed clathrin-associated adaptor protein (AP) complex AP-2

cd14836
Location:1 → 140

AP2_Mu_N; AP-2 complex subunit mu N-terminal domain
NM_001311198.2 → NP_001298127.1 AP-2 complex subunit mu isoform c

Status: REVIEWED

Description

Transcript Variant: This variant (3) represents the longest transcript and encodes the longest isoform (c).

Source sequence(s)

AK297849, BC004996

Consensus CDS

CCDS82880.1

UniProtKB/TrEMBL

B4DNB9, E9PFW3

Related

ENSP00000403362.2, ENST00000411763.6

Conserved Domains (1) summary

cd09251
Location:193 → 459

AP-2_Mu2_Cterm; C-terminal domain of medium Mu2 subunit in ubiquitously expressed clathrin-associated adaptor protein (AP) complex AP-2
NM_004068.4 → NP_004059.2 AP-2 complex subunit mu isoform a

See identical proteins and their annotated locations for NP_004059.2

Status: REVIEWED

Description

Transcript Variant: This variant (1) lacks two alternate in-frame exons compared to variant 3. The resulting isoform (a) has the same N- and C-termini but is shorter compared to isoform c.

Source sequence(s)

BC004996, BI461415

Consensus CDS

CCDS43177.1

UniProtKB/Swiss-Prot

A6NE12, D3DNT1, P20172, P53679, Q96CW1

UniProtKB/TrEMBL

A0A087WY71

Related

ENSP00000292807.5, ENST00000292807.9

Conserved Domains (2) summary

cd09251
Location:168 → 434

AP-2_Mu2_Cterm; C-terminal domain of medium Mu2 subunit in ubiquitously expressed clathrin-associated adaptor protein (AP) complex AP-2

cd14836
Location:1 → 140

AP2_Mu_N; AP-2 complex subunit mu N-terminal domain