AP1M1 adaptor related protein complex 1 subunit mu 1 [Homo sapiens (human)] - Gene

Summary

Official Symbol: AP1M1provided by HGNC
Official Full Name: adaptor related protein complex 1 subunit mu 1provided by HGNC
Primary source: HGNC:HGNC:13667
See related: Ensembl:ENSG00000072958 MIM:603535; AllianceGenome:HGNC:13667
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: AP47; mu1A; CLTNM; MU-1A; CLAPM2
Summary: The protein encoded by this gene is the medium chain of the trans-Golgi network clathrin-associated protein complex AP-1. The other components of this complex are beta-prime-adaptin, gamma-adaptin, and the small chain AP1S1. This complex is located at the Golgi vesicle and links clathrin to receptors in coated vesicles. These vesicles are involved in endocytosis and Golgi processing. Alternatively spliced transcript variants encoding distinct protein isoforms have been found for this gene. [provided by RefSeq, Jul 2008]
Expression: Ubiquitous expression in testis (RPKM 31.3), brain (RPKM 17.8) and 25 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 19p13.11

Exon count:: 13

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	19	NC_000019.10 (16197911..16245906)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	19	NC_060943.1 (16331982..16379983)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	19	NC_000019.9 (16308722..16356717)

Chromosome 19 - NC_000019.10 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?

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.
Here, the authors demonstrate that dileucine motifs in the hepatitis C virus NS2 protein mediate AP-1A, AP-1B, and AP-4 binding and cell-free virus release. Moreover, they reveal that AP-4, an adaptor not previously implicated in viral infections, mediates cell-to-cell spread and hepatitis C virus trafficking.
Title: Interactions between the Hepatitis C Virus Nonstructural 2 Protein and Host Adaptor Proteins 1 and 4 Orchestrate Virus Release.
found 31 ORF9p interaction partners, among which was AP1M1, the mu subunit of the adaptor protein complex 1 (AP-1). AP-1 is a heterotetramer involved in intracellular vesicle-mediated transport and regulates the shuttling of cargo proteins between endosomes and the trans-Golgi network via clathrin-coated vesicles.
Title: Varicella-Zoster Virus ORF9p Binding to Cellular Adaptor Protein Complex 1 Is Important for Viral Infectivity.
Acidic clusters act as sorting signals for packaging cargo into clathrin-coated vesicles (CCVs), and also facilitate down-regulation of MHC-I by HIV-1 Nef. The basic patch on micro1 that interacts with the Nef acidic cluster also contributes to the binding of endogenous acidic cluster proteins.
Title: Contribution of the clathrin adaptor AP-1 subunit µ1 to acidic cluster protein sorting.
CNNM4 is sorted to the basolateral membrane by the complementary function of AP-1A and AP-1B
Title: Basolateral sorting of the Mg²⁺ transporter CNNM4 requires interaction with AP-1A and AP-1B.
Adaptor protein 1 promotes cross-presentation through the same tyrosine signal in major histocompatibility complex class I as that targeted by HIV-1.
Title: Adaptor protein 1 promotes cross-presentation through the same tyrosine signal in major histocompatibility complex class I as that targeted by HIV-1.
IRS-1 associates with mu1A of the ubiquitously expressed AP-1 complex through three protein interaction motifs.
Title: The AP-1 complex regulates intracellular localization of insulin receptor substrate 1, which is required for insulin-like growth factor I-dependent cell proliferation.
Mu1A binding to the N terminus of HIV-1 Nef determines its ability to downregulate major histocompatibility complex class I in T lymphocytes.
Title: A noncanonical mu-1A-binding motif in the N terminus of HIV-1 Nef determines its ability to downregulate major histocompatibility complex class I in T lymphocytes.
AP-1 mu1A is involved in the kAE1 trafficking of kidney alpha-intercalated cells
Title: Human kidney anion exchanger 1 interacts with adaptor-related protein complex 1 μ1A (AP-1 mu1A).
These data identify the micro subunit of AP-1 (micro1) as the key target of the MHC-I CD/Nef complex, and they indicate that both Y320 in the MHC-I CD and E62-65 in Nef interact directly with micro1.
Title: Cooperative binding of the class I major histocompatibility complex cytoplasmic domain and human immunodeficiency virus type 1 Nef to the endosomal AP-1 complex via its mu subunit.

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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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Protein interactions

Protein	Gene	Interaction	Pubs
Envelope surface glycoprotein gp160, precursor	env	HIV-1 gp160 is identified to have a physical interaction with adaptor-related protein complex 1, mu 1 subunit (AP1M1) in human HEK293 and/or Jurkat cell lines by using affinity tagging and purification mass spectrometry analyses	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
Envelope transmembrane glycoprotein gp41	env	The cytoplasmic domain (residues 707-856) of HIV-1 gp41 interacts with whole clathrin-associated AP-1 and AP-2 adaptor complexes	PubMed
	env	The highly conserved C-terminal dileucine motif (residues 851-856) in the cytosolic domain of HIV-1 gp41 interacts with clathrin-associated AP-1 adaptor complexes	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
Nef	nef	HIV-1 Nef downregulates CD4 and MHC I by connecting these receptors with the endocytic machinery through direct interactions between Nef and the mu medium chains of AP complexes, essential components of clathrin-coated pits	PubMed
	nef	Two distinct regions in Nef, from amino acids 140-150 and from 180-190, can both interact with the mu subunit of the adaptor protein complex 1 (AP-1)	PubMed
	nef	A leucine-based motif near the C-terminus of HIV-1 Nef interacts with AP-1 complexes; residues 164 and 165 in Nef are required for the interaction with AP-1	PubMed
	nef	Adaptor-related protein complex 1 (AP-1) is necessary for cross-presentation by MHC-I HLA-A and HLA-B molecules containing a cytoplasmic tail tyrosine signal and that HIV-1 Nef inhibits the cross-presentation in antigen-presenting cells	PubMed
	nef	Dominant active ARF1 (Q71L) potently stabilizes interactions among AP-1 mu1, HIV-1 Nef, and HLA-A2 and that the formation of a static complex sequesters necessary trafficking components	PubMed
	nef	A quadruple mutation of mu 1 (K274E/K298E/K302E/R303D) abolishes binding to HIV-1 Nef, but a complementary mutation in the acidic cluster in Nef (62EEEE65 to 62KKKK65) restores their interaction	PubMed
	nef	Asp327 and Tyr320 of MHC-I, Asp123 of Nef, and Arg225, Arg393, Lys396, Arg211, and Arg246 of mu 1 are involved in a crucial three-way electrostatic network, which results in the Nef-MHC-I CD-mu 1 complex formation	PubMed
	nef	Exogenous Nef and TNF-alpha synergistically activate NF-kappaB and AP-1 resulting in enhancing viral replication in both chronically infected promonocytic cells and acutely infected primary macrophages	PubMed
	nef	HIV-1 Nef acidic (Glu62-65) and polyproline domains (Pro75/78) stabilize the interaction between the HLA-A2/Nef fusion protein and AP-1 mu1	PubMed
	nef	The mu1 subunit of AP-1 uses its canonical tyrosine binding pocket for Nef-induced downregulation of HLA-A2. M20 is the only amino acid in the N-terminal domain of Nef needed for HLA-A2 downregulation	PubMed
	nef	Mutating three amino acids (Y320, A324, and D327) in the cytoplasmic tail of HLA-A2 abrogates Nef-induced downregulation of HLA-A2 through a failuer to recruit the mu1 or gamma subunits of AP-1	PubMed
	nef	Knocking down either AP-1 gamma, AP-1 mu1, or clathrin strongly inhibits Nef-induced downregulation of HLA-A2	PubMed
	nef	A fusion protein, composed of the cytoplasmic domain (CD) of MHC-I and HIV-1 Nef, shows its binding to the mu subunit of AP-1, which requires the tyrosine residue of the YSQA sequence in the MHC-I CD and Nef residues E62-65 and P78	PubMed
	nef	HIV-1 Nef acts in cis to induce the rapid endocytosis of CD8-Nef fusion proteins via binding to the mu 1 chain of the adaptor protein type 1 (AP1) complex	PubMed
	nef	HIV-1 Nef stabilizes AP-1 complexes on endosomal membranes after ADP-ribosylation factor-1 (ARF1) -dependent attachment	PubMed
Pr55(Gag)	gag	HIV-1 Gag mutant lacking the matrix domain is insensitive to AP-1 mu depletion, suggesting that AP-1 mu participates in HIV-1 release through a direct interaction with the MA domain of Gag	PubMed
	gag	HIV-1 Gag interacts with adaptor complex AP-1 mu in vitro. The release of HIV-1 Gag is inhibited by silencing AP-1 mu in cells	PubMed
Vpu	vpu	HIV-1 Vpu physically interacts with the mu subunit of adaptor-related protein complex 1 (AP1) in cells, and Vpu R44 and L/I45 potentially interact with the mu 1 subunit	PubMed
	vpu	Fusion of the Vpu cytoplasmic domain (residues 28-80) to the BST2 cytoplasmic domain (residues 1-21) enhances binding to the beta, mu, and sigma subunits of adaptor-related protein complex 1 (AP1) in cells	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

A009I07 (e-PCR)
- UniSTS:43033

G32561 (e-PCR)
- UniSTS:117145

RH15920 (e-PCR)
- UniSTS:43177

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables clathrin adaptor activity	IBA Inferred from Biological aspect of Ancestor more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
involved_in endosome to melanosome transport	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in intracellular protein transport	IEA Inferred from Electronic Annotation more info
involved_in melanosome assembly	NAS Non-traceable Author Statement more info	PubMed
involved_in melanosome organization	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in platelet dense granule organization	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-1 adaptor complex	NAS Non-traceable Author Statement more info	PubMed
located_in Golgi membrane	TAS Traceable Author Statement more info
is_active_in clathrin-coated vesicle	IBA Inferred from Biological aspect of Ancestor more info
located_in cytoplasmic vesicle membrane	TAS Traceable Author Statement more info
located_in cytosol	IDA Inferred from Direct Assay more info
located_in cytosol	TAS Traceable Author Statement more info
located_in early endosome	NAS Non-traceable Author Statement more info	PubMed
located_in extracellular exosome	HDA more info	PubMed
located_in intracellular membrane-bounded organelle	IDA Inferred from Direct Assay more info
located_in lysosomal membrane	NAS Non-traceable Author Statement more info	PubMed
located_in lysosomal membrane	TAS Traceable Author Statement more info
located_in membrane	HDA more info	PubMed
located_in plasma membrane	TAS Traceable Author Statement more info
located_in specific granule membrane	TAS Traceable Author Statement more info
located_in synapse	IEA Inferred from Electronic Annotation more info
located_in trans-Golgi network membrane	NAS Non-traceable Author Statement more info	PubMed
located_in trans-Golgi network membrane	TAS Traceable Author Statement more info

General protein information

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Preferred Names: AP-1 complex subunit mu-1

Names: AP-mu chain family member mu1A; HA1 47 kDa subunit; adapter-related protein complex 1 subunit mu-1; adaptor protein complex AP-1 mu-1 subunit; adaptor protein complex AP-1 subunit mu-1; adaptor related protein complex 1 mu 1 subunit; clathrin adaptor protein AP47; clathrin assembly protein complex 1 medium chain 1; clathrin assembly protein complex 1 mu-1 medium chain 1; clathrin assembly protein complex 1, medium chain; clathrin assembly protein complex AP1, mu subunit; clathrin coat assembly protein AP47; clathrin coat-associated protein AP47; golgi adaptor AP-1 47 kDa protein; golgi adaptor HA1/AP1 adaptin mu-1 subunit; mu-adaptin 1; mu1A-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.

mRNA and Protein(s)

NM_001130524.2 → NP_001123996.1 AP-1 complex subunit mu-1 isoform 1

See identical proteins and their annotated locations for NP_001123996.1

Status: REVIEWED

Description

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

Source sequence(s)

AB209808, AC020911, BQ014582, BU729646, DC386056, DQ059565

Consensus CDS

CCDS46008.1

UniProtKB/TrEMBL

B3KNH5

Related

ENSP00000388996.1, ENST00000444449.6

Conserved Domains (2) summary

cd09258
Location:153 → 434

AP-1_Mu1A_Cterm; C-terminal domain of medium Mu1A subunit in ubiquitously expressed clathrin-associated adaptor protein (AP) complex AP-1

cd14835
Location:4 → 142

AP1_Mu_N; AP-1 complex subunit mu N-terminal domain
NM_032493.4 → NP_115882.1 AP-1 complex subunit mu-1 isoform 2

See identical proteins and their annotated locations for NP_115882.1

Status: REVIEWED

Description

Transcript Variant: This variant (2) lacks a coding exon in the middle region, as compared to variant 1. The reading frame is not affected and the resulting isoform (2) lacks an internal segment, as compared to isoform 1.

Source sequence(s)

AC020911, AK027528, BC017469, BQ014582, BU729646, DC386056

Consensus CDS

CCDS12342.1

UniProtKB/Swiss-Prot

Q4TTY5, Q9BXS5

UniProtKB/TrEMBL

B3KNH5

Related

ENSP00000291439.2, ENST00000291439.8

Conserved Domains (2) summary

cd09258
Location:153 → 422

AP-1_Mu1A_Cterm; C-terminal domain of medium Mu1A subunit in ubiquitously expressed clathrin-associated adaptor protein (AP) complex AP-1

cd14835
Location:4 → 142

AP1_Mu_N; AP-1 complex subunit mu N-terminal domain