Cell cycle control protein 50A (TMEM30A)

The protein contains 361 amino acids for an estimated molecular weight of 40684 Da.

 

Accessory component of a P4-ATPase flippase complex which catalyzes the hydrolysis of ATP coupled to the transport of aminophospholipids from the outer to the inner leaflet of various membranes and ensures the maintenance of asymmetric distribution of phospholipids. Phospholipid translocation seems also to be implicated in vesicle formation and in uptake of lipid signaling molecules. The beta subunit may assist in binding of the phospholipid substrate. Required for the proper folding, assembly and ER to Golgi exit of the ATP8A2:TMEM30A flippase complex. ATP8A2:TMEM30A may be involved in regulation of neurite outgrowth, and, reconstituted to liposomes, predomiminantly transports phosphatidylserine (PS) and to a lesser extent phosphatidylethanolamine (PE). The ATP8A1:TMEM30A flippase complex seems to play a role in regulation of cell migration probably involving flippase-mediated translocation of phosphatidylethanolamine (PE) at the plasma membrane. Required for the formation of the ATP8A2, ATP8B1 and ATP8B2 P-type ATPAse intermediate phosphoenzymes. Involved in uptake of platelet-activating factor (PAF), synthetic drug alkylphospholipid edelfosine, and, probably in association with ATP8B1, of perifosine. Also mediates the export of alpha subunits ATP8A1, ATP8B1, ATP8B2, ATP8B4, ATP10A, ATP10B, ATP10D, ATP11A, ATP11B and ATP11C from the ER to other membrane localizations. (updated: Sept. 18, 2019)

Protein identification was indicated in the following studies:

  1. Lange and co-workers. (2014) Annotating N termini for the human proteome project: N termini and Nα-acetylation status differentiate stable cleaved protein species from degradation remnants in the human erythrocyte proteome. J Proteome Res. 13(4), 2028-2044.
  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.
  6. 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.

This protein is annotated as membranous in Gene Ontology, is annotated as membranous in UniProt, is predicted to be membranous by TOPCONS.


Interpro domains
Total structural coverage: 0%
Model score: 0
No model available.

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The reference OMIM entry for this protein is 611028

Transmembrane protein 30a; tmem30a
Cdc50, s. cerevisiae, homolog of, a; cdc50a

CLONING

By searching databases for homologs of yeast Cdc50 family proteins, which are involved in polarized cell division, Katoh and Katoh (2004) identified 3 human CDC50 genes, including TMEM30A, which they called CDC50A. The predicted CDC50A protein contains 361 amino acids. The human and yeast CDC50 proteins all have 2 transmembrane domains and an extracellular loop with 3 cysteines and an N-glycosylation site. In silico expression analysis revealed that CDC50A was expressed in embryonic stem cells, placenta, brain, and chondrosarcoma.

MAPPING

By genomic sequence analysis, Katoh and Katoh (2004) mapped the TMEM30A gene to chromosome 6q14.1.

GENE FUNCTION

Using a haploid genetic screen in human cells, Segawa et al. (2014) found that ATP11C (300516) and CDC50A are required for aminophospholipid translocation from the outer to the inner plasma membrane leaflet; that is, they display flippase activity. ATP11C contained caspase recognition sites, and mutations at these sites generated caspase-resistant ATP11C without affecting its flippase activity. Cells expressing caspase-resistant ATP11C did not expose phosphatidylserine during apoptosis and were not engulfed by macrophages, which suggests that inactivation of the flippase activity is required for apoptotic phosphatidylserine exposure. CDC50A-deficient cells displayed phosphatidylserine on their surface and were engulfed by macrophages, indicating that phosphatidylserine is sufficient as an 'eat me' signal. ... More on the omim web site

Subscribe to this protein entry history

June 30, 2020: Protein entry updated
Automatic update: OMIM entry 611028 was added.

Sept. 22, 2019: Protein entry updated
Automatic update: Entry updated from uniprot information.

Oct. 19, 2018: Additional information
Initial protein addition to the database. This entry was referenced in Bryk and co-workers. (2017).