AP-2 complex subunit mu (AP2M1)

The protein contains 435 amino acids for an estimated molecular weight of 49655 Da.

 

Component of the adaptor protein complex 2 (AP-2) (PubMed:12694563, PubMed:12952941, PubMed:14745134, PubMed:14985334, PubMed:15473838, PubMed:31104773). Adaptor protein complexes function in protein transport via transport vesicles in different membrane traffic pathways (PubMed:12694563, PubMed:12952941, PubMed:14745134, PubMed:14985334, PubMed:15473838, PubMed:31104773). Adaptor protein complexes are vesicle coat components and appear to be involved in cargo selection and vesicle formation (PubMed:12694563, PubMed:12952941, PubMed:14745134, PubMed:14985334, PubMed:15473838, PubMed:31104773). AP-2 is involved in clathrin-dependent endocytosis in which cargo proteins are incorporated into vesicles surrounded by clathrin (clathrin-coated vesicles, CCVs) which are destined for fusion with the early endosome (PubMed:12694563, PubMed:12952941, PubMed:14745134, PubMed:14985334, PubMed:15473838, PubMed:31104773). The clathrin lattice serves as a mechanical scaffold but is itself unable to bind directly to membrane components (PubMed:12694563, PubMed:12952941, PubMed:14745134, PubMed:14985334, PubMed:15473838, PubMed:31104773). Clathrin-associated adaptor protein (AP) complexes which can bind directly to both the clathrin lattice and to the lipid and protein components of membranes are considered to be the major clathrin adaptors contributing the CCV formation (PubMed:12694563, PubMed:12952941, PubMed:14745134, PubMed:14985334, PubMed:15473838, PubMed:31104773). AP-2 also serves as (updated: Feb. 10, 2021)

Protein identification was indicated in the following studies:

  1. Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
  2. Hegedűs and co-workers. (2015) Inconsistencies in the red blood cell membrane proteome analysis: generation of a database for research and diagnostic applications. Database (Oxford) 1-8.
  3. Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
  4. D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
  5. Chu and co-workers. (2018) Quantitative mass spectrometry of human reticulocytes reveal proteome-wide modifications during maturation. Br J Haematol. 180(1), 118-133.

Methods

The following articles were analysed to gather the proteome content of erythrocytes.

The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.

PublicationIdentification 1Uniprot mapping 2Not mapped /
Obsolete		TrEMBLSwiss-Prot
Goodman (2013)2289 (gene list)227853205992269
Lange (2014)123412347281224
Hegedus (2015)2638262202352387
Wilson (2016)165815281702911068
d'Alessandro (2017)18261817201815
Bryk (2017)20902060101081942
Chu (2018)18531804553621387

1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry

The compilation of older studies can be retrieved from the Red Blood Cell Collection database.

The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.

No sequence conservation computed yet.
Protein sequence (FASTA)
Protein coevolution profile (FreeContact)
Multiple Sequence Alignment (Muscle)

This protein is annotated as membranous in Gene Ontology, is annotated as membranous in UniProt.


Interpro domains
Total structural coverage: 100%
Model score: 100
MODL_I-TASSER-3.0

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VariantDescription
MRD60

The reference OMIM entry for this protein is 601024

Adaptor-related protein complex 2, mu-1 subunit; ap2m1
Clathrin-associated/assembly/adaptor protein, medium 1; clapm1
Clathrin adaptor protein 50; ap50
Clathrin adaptor complex ap2, mu subunit
Mu-2

DESCRIPTION

AP50 is a 50-kD component of the AP2 coat assembly protein complex of clathrin-coated vesicles. The complex consists of 2 large 100-kD components, which are called the alpha (601026) and beta (601025) subunits, a 50-kD component (AP50), and a small 17-kD protein (602242) (summary by Thurieau et al., 1988).

CLONING

Thurieau et al. (1988) isolated AP50 cDNAs from rat brain mRNA and showed that the predicted 435-amino acid protein is highly conserved. Druck et al. (1995) cloned the human homolog, which they designated CLAPM1, using a rat cDNA as a probe.

GENE FUNCTION

Liu et al. (1994) showed that AP50 is required for both in vitro assembly and activity of a vacuolar ATPase which may be responsible for proton pumping that occurs in the acidification of endosomes and lysosomes. Krauss et al. (2006) found that the AP2 complex was a regulator of type I PIPK (see PIP5K1A; 603275)-mediated PtdIns(4,5)P2 synthesis in COS-7 and HeLa cells. AP2 via its mu-2 subunit directly interacted with the kinase core domain of the PIPK gamma-subunit (PIP5K1C; 606102) in vitro and in native protein extracts. Endocytic cargo protein binding to mu-2 stimulated PIPK activity. Krauss et al. (2006) concluded that there is a positive feedback loop consisting of endocytic cargo proteins, AP2M1, and PIPK type I, which may provide a specific pool of PtdIns(4,5)P2.

GENE STRUCTURE

Druck et al. (1995) showed that the CLAPM1 gene contains 6 exons spanning about 8 kb of genomic DNA.

BIOCHEMICAL FEATURES

- Crystal Structure Kelly et al. (2014) determined a structure of AP2 that includes the clathrin-binding beta-2 hinge and developed an AP2-dependent budding assay. The authors found that an autoinhibitory mechanism prevents clathrin recruitment by cytosolic AP2. A large-scale conformational change driven by the plasma membrane phosphoinositide phosphatidylinositol 4,5-bisphosphate and cargo relieves this autoinhibition, triggering clathrin recruitment and hence clathrin-coated bud formation. Kelly et al. (2014) concluded that this molecular switching mechanism can couple AP2's membrane recruitment to its key functions of cargo and clathrin binding.

MAPPING

Druck et al. (1995) assigned CLAPM1 to chromosome 3 by hybridization with a panel of somatic cell hybrid DNAs and regionalized it by in situ hybridization to 3q28. ... More on the omim web site

Subscribe to this protein entry history

Feb. 16, 2021: Protein entry updated
Automatic update: Entry updated from uniprot information.

Aug. 19, 2019: Protein entry updated
Automatic update: Entry updated from uniprot information.

May 12, 2019: Protein entry updated
Automatic update: model status changed

Nov. 16, 2018: Protein entry updated
Automatic update: model status changed

Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated

Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated

Nov. 23, 2017: Protein entry updated
Automatic update: Uniprot description updated

Oct. 26, 2017: Protein entry updated
Automatic update: model status changed

March 16, 2016: Protein entry updated
Automatic update: OMIM entry 601024 was added.

Feb. 24, 2016: Protein entry updated
Automatic update: model status changed