Protein 4.1 (EPB41)

The protein contains 864 amino acids for an estimated molecular weight of 97017 Da.

 

Protein 4.1 is a major structural element of the erythrocyte membrane skeleton. It plays a key role in regulating membrane physical properties of mechanical stability and deformability by stabilizing spectrin-actin interaction. Recruits DLG1 to membranes. Required for dynein-dynactin complex and NUMA1 recruitment at the mitotic cell cortex during anaphase (PubMed:23870127). (updated: Jan. 31, 2018)

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.
Protein sequence (FASTA)
Protein coevolution profile (FreeContact)
Multiple Sequence Alignment (Muscle)

This protein is annotated as membranous in Gene Ontology.


Interpro domains
Total structural coverage: 34%
Model score: 35
MODL_I-TASSER-3.0

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VariantDescription
dbSNP:rs111642750

The reference OMIM entry for this protein is 130500

Erythrocyte membrane protein band 4.1; epb41
Protein 4.1, red blood cell type; 4.1r
El1 gene

CLONING

Conboy et al. (1986) reported the molecular cloning and characterization of human erythrocyte protein 4.1 cDNA and the complete amino acid sequence of the protein. Probes prepared from the cloned erythrocyte protein 4.1 cDNA hybridized with distinct mRNA species from a wide variety of nonerythroid tissues, including brain, liver, placenta, pancreas, and intestine, implying substantial homology between erythroid and nonerythroid protein 4.1. Brain protein 4.1, also known as synapsin I (313440), is the best characterized of the nonerythroid forms. Tang et al. (1988) compared nucleotide sequences of mRNA encoding erythroid and lymphoid protein 4.1 isoforms. The lymphoid protein 4.1 isoforms exhibited several nucleotide sequence motifs that appeared either to be inserted into or deleted from the mRNA by alternative splicing of a common mRNA precursor. One of the motifs, located within the spectrin-actin binding domain, was found only in erythroid cells and was specifically produced during erythroid cell maturation. Conboy et al. (1988) demonstrated that alternative splicing accounts for multiple isoforms of protein 4.1 in red cells. In his Figure 2, Conboy (1993) provided a map of the alternative splicing of protein 4.1 mRNA, emphasizing the total chromosome relative to many combinatorial splicing possibilities among the exons of the EPB41 gene. There are, furthermore, 2 AUG initiation codons, 1 of which accounts for an N-terminal extension on the 80-kD gene product. By tissue screening, Baklouti et al. (1997) examined the complex pattern of alternative splicing variants of the protein 4.1 gene. They noted that many splicing variations occur in the spectrin/actin binding (SAB) domain. In particular, they found a 51-bp exon that was expressed almost exclusively in muscle.

GENE STRUCTURE

By genomic sequence analysis, Baklouti et al. (1997) determined that 22 exons spanning approximately 200 kb contain the entire erythroid and nonerythroid coding sequences of the human protein 4.1 gene.

MAPPING

The protein 4.1 gene was mapped to chromosome 1pter-p32 (Conboy et al., 1985, 1986) by hybridization to chromosomes sorted onto nitrocellulose filters using a fluorescence-activated cell sorter. Studies of translocations also localized the gene to chromosome 1pter-p32, the region of the Rh gene (Kan, 1986). Thus, it seemed certain that the protein 4.1 gene is mutant in Rh-linked elliptocytosis-1 (EL1; 611804). Tang and Tang (1991) concluded that the EL1 gene is located in band 1p34.2-p33 on the basis of the FLpter value (the fractional length of the total chromosome relative to the terminus of the short arm). Parra et al. (1998) stated that the EPB41 gene is located on chromosome 1p33-p32. Bahary et al. (1991) assigned the mouse Epb41 gene to chromosome 4.

GENE FUNCTION

The red cell membrane cytoskeletal network consists of spectrin (bands 1 and 2; see 182860 and 182870), actin (band 5; see 102630), and protein 4.1. Actin and protein 4.1 interact with spectrin at the junction of spectrin heterotetramers. The resulting complex plays a critical role in erythrocyte shape and deformability. (The protein band nomenclature given here is that of Fairbanks et al., 1971.) Correas et al. (1986) determined the complete primary structure of the functional site of protein 4.1 involved in spectrin-actin associations. Antibodies against 2 different synthetic peptides of this portion of the protein inhibited associati ... More on the omim web site

Subscribe to this protein entry history

Feb. 10, 2018: 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 130500 was added.

Jan. 25, 2016: Protein entry updated
Automatic update: model status changed