AP-2 complex subunit sigma (AP2S1)

The protein contains 142 amino acids for an estimated molecular weight of 17018 Da.

 

Component of the adaptor protein complex 2 (AP-2). Adaptor protein complexes function in protein Transport via Transport vesicles in different membrane traffic pathways. Adaptor protein complexes are vesicle coat components and appear to be involved in cargo selection and vesicle formation. 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. The clathrin lattice serves as a mechanical scaffold but is itself unable to bind directly to membrane components. 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. AP-2 also serves as a cargo receptor to selectively sort the membrane proteins involved in receptor-mediated endocytosis. AP-2 seems to play a role in the recycling of synaptic vesicle membranes from the presynaptic surface. AP-2 recognizes Y-X-X-[FILMV] (Y-X-X-Phi) and [ED]-X-X-X-L-[LI] endocytosis signal motifs within the cytosolic tails of transmembrane cargo molecules. AP-2 may also play a role in maintaining normal post-endocytic trafficking through the ARF6-regulated, non-clathrin pathway. The AP-2 alpha and AP-2 sigma subunits are thought to contribute to the recognition of the [ED]-X-X-X-L-[LI] motif (By similarity). May (updated: April 1, 2015)

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. Wilson and co-workers. (2016) Comparison of the Proteome of Adult and Cord Erythroid Cells, and Changes in the Proteome Following Reticulocyte Maturation. Mol Cell Proteomics. 15(6), 1938-1946.
  4. Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
  5. D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.

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
No model available.

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VariantDescription
HHC3
HHC3
HHC3

The reference OMIM entry for this protein is 600740

Hypocalciuric hypercalcemia, familial, type iii; hhc3
Familial benign hypercalcemia, type iii; fbh3
Hypercalcemia, familial benign, type iii
Hypercalcemia, familial benign, oklahoma type

A number sign (#) is used with this entry because of evidence that familial hypocalciuric hypercalcemia type III (HHC3) is caused by heterozygous mutation in the AP2S1 gene (602242) on chromosome 19q13. For a general phenotypic description and discussion of genetic heterogeneity of hypocalciuric hypercalcemia, see HCC1 (145980).

CLINICAL FEATURES

McMurtry et al. (1992) provided clinical and metabolic characterization of familial hypocalciuric hypercalcemia in a kindred from Oklahoma. Nineteen affected members were found. Immunoreactive parathyroid hormone (iPTH) levels, determined in 3 separate immunoassays, became supranormal by about age 30 years in the group of 15 hypercalcemic subjects examined biochemically and appeared to increase further thereafter. Serum alkaline phosphatase activity and creatinine levels were normal in these individuals, but inorganic phosphate levels were lower than in unaffected members of the kindred. Three of 5 affected adults older than age 40 years who were studied radiographically had changes suggestive of osteomalacia. Biopsy of the iliac crest in one of these subjects, a 51-year-old woman, confirmed the presence of defective skeletal mineralization. Differentiation from primary hyperparathyroidism was especially difficult in this kindred because serum iPTH levels may be elevated. Furthermore, the disorder may not be totally benign. Osteomalacia, perhaps due to mild hypophosphatemia, can develop during adulthood in these patients. Nesbit et al. (2010) studied a kindred from Northern Ireland in which 16 individuals over 3 generations had hypocalciuric hypercalcemia in association with normal or elevated PTH concentrations. In addition, the 16 individuals had significantly higher serum magnesium and PTH levels than their normocalcemic relatives, and hypercalcemic individuals above the age of 30 years had a significantly lower serum phosphate concentration than those below the age of 30 years. Nesbit et al. (2010) noted that these features were all consistent with HHC3, although unlike the Oklahoma family originally described by McMurtry et al. (1992), the Northern Ireland kindred did not exhibit developmental elevations in serum PTH concentration or hypophosphatemic osteomalacia in older affected members.

MAPPING

Trump et al. (1995) studied a 5-generation kindred from Oklahoma, originally reported by McMurtry et al. (1992), in which there were 19 individuals with hypocalciuric hypercalcemia and 2 obligate carriers. Trump et al. (1995) demonstrated lack of linkage to the sites of familial benign hypocalciuric hypercalcemia (HCC1) on 3q21-q24 (145980; see also 601199) and 19p13.3 (HHC2; 145981), as well as lack of linkage to 11q13 and 11p15, where the genes for multiple endocrine neoplasia type I (MEN1; 131100) and PTH (168450) have been mapped, respectively. Thus, this form of FHH, designated the Oklahoma variant, represents a distinct genetic entity. Lloyd et al. (1999) established linkage between the Oklahoma form of familial benign hypercalcemia and 8 loci in the 19q13 region, with the highest lod score, 6.67 (recombination fraction = 0.00), obtained with D19S606. Recombination events narrowed the critical region to an approximately 12-cM interval flanked by D19S908 and D19S866. In the Oklahoma kindred with hypocalciuric hypercalcemia that was originally described by McMurtry et al. (1992), Hannan et al. (2010) used 24 polymorphic loci to refine further the HHC3 locus to a 4.1-Mb r ... More on the omim web site

Subscribe to this protein entry history

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

March 16, 2016: Protein entry updated
Automatic update: OMIM entry 600740 was added.