Protein 4.2 (EPB42)

The protein contains 691 amino acids for an estimated molecular weight of 77009 Da.

 

Probably plays an important role in the regulation of erythrocyte shape and mechanical properties. (updated: Oct. 7, 2020)

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. 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.
  3. 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.
  4. 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.
  5. Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
  6. D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
  7. 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.


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

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VariantDescription
SPH5
SPH5
SPH5
SPH5

The reference OMIM entry for this protein is 177070

Protein 4.2, erythrocytic; epb42

CLONING

Korsgren et al. (1990) cloned and sequenced protein band 4.2 from a human reticulocyte cDNA library. The deduced 691-amino acid band 4.2 protein has homology with 2 closely related calcium-dependent crosslinking proteins, guinea pig liver transglutaminase and the alpha subunit of human coagulation factor XIII (F13A1; 134570). Within the 5 contiguous consensus residues of the transglutaminase active site, band 4.2 has an amino acid substitution which leads to loss of transglutaminase activity. Sung et al. (1990) also cloned protein 4.2 and likewise found homology to the 2 transglutaminases, as well as the lack of the critical residue required for enzymatic crosslinking of substrates. Korsgren and Cohen (1991) showed that reticulocytes contain 2 different sized EPB42 messages; the major, smaller, message is produced by alternative splicing. They found that the human and murine proteins share 72% sequence identity.

GENE STRUCTURE

Korsgren and Cohen (1991) showed that the band 4.2 gene is about 20 kb long and contains 13 exons. Alignment of the band 4.2 amino acid sequence with that of F13A2 and division of the sequences into exons showed a remarkable correspondence, and in most cases identity, in the sizes of the paired exons. Korsgren and Cohen (1994) found that the organization and size of the human and mouse EPB42 genes are identical.

MAPPING

Sung et al. (1991) mapped the EPB42 gene to 15q15-q21 by fluorescence in situ hybridization. Najfeld et al. (1992) assigned the gene to 15q15 by fluorescence in situ hybridization. White et al. (1992) mapped the Epb42 gene to mouse chromosome 2, which shares an extensive segment of syntenic homology with human chromosome 15. By long-range genomic PCR, Grenard et al. (2001) mapped the EPB42 gene to a 100-kb region of 15q15.2, arranged in tandem with 2 other transglutaminase genes, TGM5 (603805) and TGM7 (606776). By radiation hybrid analysis, Grenard et al. (2001) mapped the mouse Epb42, Tgm5, and Tgm7 genes in close proximity on chromosome 2.

GENE FUNCTION

In the red cell membrane skeleton, protein 4.2 may regulate the association of protein 3 (109270) with ankyrin (612641) (Davies and Lux, 1989). Azim et al. (1996) demonstrated that both protein 4.2 and dematin (125305) are ATP-binding proteins. Bruce et al. (2002) observed that protein 4.2 and CD47 interact in the human red cell membrane, which provided further evidence for an association between the band 3 complex (which includes protein 4.2) and the Rh complex, and defined a point of attachment between the Rh complex and the red cell cytoskeleton.

MOLECULAR GENETICS

In 4 unrelated Japanese patients with autosomal recessive hereditary spherocytosis (612690), Bouhassira et al. (1991, 1992) identified homozygosity for a mutation in the EPB42 gene (177070.0001). In a Portuguese woman with recessively transmitted hemolytic anemia, Hayette et al. (1995) identified a mutation in the EPB42 gene (177070.0002). In Tunisian sibs with autosomal recessive hemolytic anemia reported by Ghanem et al. (1990), Hayette et al. (1995) identified homozygosity for a mutation in the EPB42 gene (177070.0003).

ANIMAL MODEL

The mouse 'pallid' mutation (see 604310) produces defects in at least 3 subcellular organelles: platelet-dense granules, melanosomes, and kidney lysosomes. White et al. (1992) noted that the mouse Epb42 gene mapped to the same region as the pallid mutation in the mouse. Prompted ... More on the omim web site

Subscribe to this protein entry history

Oct. 20, 2020: Protein entry updated
Automatic update: Entry updated from uniprot information.

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 177070 was added.