40-kDa huntingtin-associated protein (F8A3)
The protein contains 371 amino acids for an estimated molecular weight of 39103 Da.
RAB5A effector molecule that is involved in vesicular trafficking of early endosomes (PubMed:16476778). Mediates the recruitment of HTT by RAB5A onto early endosomes. The HTT-F8A1/F8A2/F8A3-RAB5A complex stimulates early endosomal interaction with actin filaments and inhibits interaction with microtubules, leading to the reduction of endosome motility (PubMed:16476778). (updated: Oct. 16, 2019)
Protein identification was indicated in the following studies:
- Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
- 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.
- 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.
- Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
- D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
- 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.
| Publication | Identification 1 | Uniprot mapping 2 | Not mapped / Obsolete | TrEMBL | Swiss-Prot |
|---|---|---|---|---|---|
| Goodman (2013) | 2289 (gene list) | 2278 | 53 | 20599 | 2269 |
| Lange (2014) | 1234 | 1234 | 7 | 28 | 1224 |
| Hegedus (2015) | 2638 | 2622 | 0 | 235 | 2387 |
| Wilson (2016) | 1658 | 1528 | 170 | 291 | 1068 |
| d'Alessandro (2017) | 1826 | 1817 | 2 | 0 | 1815 |
| Bryk (2017) | 2090 | 2060 | 10 | 108 | 1942 |
| Chu (2018) | 1853 | 1804 | 55 | 362 | 1387 |
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.
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No binding partner found
Biological Process
Negative regulation of proteasomal protein catabolic process
Vesicle cytoskeletal trafficking
Molecular Function
The reference OMIM entry for this protein is 305423
Factor viii-associated gene 1; f8a
Dxs522e
Hap40
CLONING
Levinson et al. (1990) found a curious example of a gene within a gene. While looking for transcripts from the Xq28 region, they found one that hybridized to a region in exon 22 of the factor VIII gene (F8; 300841). The transcribed region was in reverse orientation to the F8 exons and was contained entirely within intron 22. The gene is small (less than 2 kb), contains no introns, and is G-C rich. Computer analysis of the sequence suggested that it codes for a protein, with the complication that codon usage analysis suggested a frameshift halfway through the gene. The transcript cDNA also bound to mouse, monkey, and rat genomic DNA in a 'zoo blot.' Probably significantly, human intron 22 is hypomethylated on the active X and methylated on the inactive X. Inaba et al. (1990) described an MspI RFLP in intron 22 of the F8 gene. Japanese showed 45% heterozygosity and Asian Indians showed 13%; polymorphism was not found in American blacks or Caucasians. In the mouse, Levinson et al. (1992) found that the F8a gene has no introns and codes for 380 amino acids with 85% identity to the predicted human sequence. The murine gene is linked to the factor VIII locus, although physical mapping suggests that it lies outside the factor VIII gene. Like the human gene, the mouse F8a gene is highly expressed in a wide variety of tissues.GENE FUNCTION
Peters and Ross (2001) showed that huntingtin (613004), the protein that is mutant in Huntington disease (HD; 143100), copurifies with a single novel 40-kD protein termed HAP40. They showed that HAP40 is encoded by the open reading frame F8A gene located within intron 22 of the factor VIII gene. Recombinant HAP40 is cytoplasmic in the presence of huntingtin but is actively targeted to the nucleus in the absence of huntingtin. These data indicated that HAP40 is likely to contribute to the function of normal huntingtin and is a candidate for involvement in the aberrant nuclear localization of mutant huntingtin found in degenerating neurons in Huntington disease. ... More on the omim web site
Oct. 27, 2019: Protein entry updated
Automatic update: Entry updated from uniprot information.
May 12, 2019: Protein entry updated
Automatic update: model status changed
Nov. 17, 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. 27, 2017: Protein entry updated
Automatic update: model status changed
March 25, 2017: Additional information
No protein expression data in P. Mayeux work for F8A3
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 305423 was added.
Feb. 25, 2016: Protein entry updated
Automatic update: model status changed
Feb. 24, 2016: Protein entry updated
Automatic update: model status changed
Jan. 24, 2016: Protein entry updated
Automatic update: model status changed