Acidic leucine-rich nuclear phosphoprotein 32 family member A (ANP32A)
The protein contains 249 amino acids for an estimated molecular weight of 28585 Da.
Multifunctional protein that is involved in the regulation of many processes including tumor suppression, apoptosis, cell cycle progression or transcription (PubMed:16341127, PubMed:11360199, PubMed:18439902, PubMed:10400610). Promotes apoptosis by favouring the activation of caspase-9/CASP9 and allowing apoptosome formation (PubMed:18439902). In addition, plays a role in the modulation of histone acetylation and transcription as part of the INHAT (inhibitor of histone acetyltransferases) complex. Inhibits the histone-acetyltranferase activity of EP300/CREBBP (CREB-binding protein) and EP300/CREBBP-associated factor by histone masking (PubMed:11830591). Preferentially binds to unmodified histone H3 and sterically inhibiting its acetylation and phosphorylation leading to cell growth inhibition (PubMed:16341127). Participates in other biochemical processes such as regulation of mRNA nuclear-to-cytoplasmic translocation and stability by its association with ELAVL1 (Hu-antigen R) (PubMed:18180367). Plays a role in E4F1-mediated transcriptional repression as well as inhibition of protein phosphatase 2A (PubMed:15642345, PubMed:17557114).', '(Microbial infection) Plays an essential role in influenza A, B and C viral genome replication (PubMed:32694517, PubMed:33045004, PubMed:33208942, PubMed:30666459). Mechanistically, mediates the assembly of the viral replicase asymmetric dimers composed of PB1, PB2 and PA via its N-terminal region (PubMed:33208942). Plays also an essential rol (updated: April 7, 2021)
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.
- 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.
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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Biological Process
Gene expression
Intracellular signal transduction
Nucleocytoplasmic transport
Regulation of apoptotic process
Regulation of mRNA stability
Regulation of transcription, DNA-templated
Transcription, DNA-templated
Viral process
Cellular Component
Cytoplasm
Endoplasmic reticulum
Nucleoplasm
Nucleus
Perinuclear region of cytoplasm
The reference OMIM entry for this protein is 600832
Acidic leucine-rich nuclear phosphoprotein 32 family, member a; anp32a
Putative human hla class ii-associated protein; phap1
Phap i
Leucine-rich acidic nuclear protein; lanp
CLONING
The putative HLA class II-associated proteins PHAP I and PHAP II were purified and cloned on the basis of their ability to bind to the cytoplasmic domain of the HLA DR-alpha chain (142860) (Vaesen et al., 1994). They may be components of the transmembrane signaling pathway that is activated after extracellular binding of ligands during the immune response. Both proteins share extensive stretches of highly acidic amino acids in their terminal regions, which suggested a nuclear localization. Indeed, PHAP I is likely to be the human homolog of the rat 'leucine-rich acidic nuclear protein' (LANP) (83.6% identity), which is localized in the nuclei of Purkinje cells. Sequence identity demonstrated that PHAP II is identical to the protein encoded by the gene SET (600960). Mutation in ataxin-1 (ATX1; 601556) causes spinocerebellar ataxia (SCA1; 164400). Using a yeast 2-hybrid screen of a mouse brain cDNA library with mutant human ATX1 as bait, Matilla et al. (1997) isolated a mouse cDNA encoding Lanp, which is 89% identical to the human protein and is expressed in cerebellum and brainstem. Binding analysis indicated that the strongest interaction between the proteins is with the N-terminal 147 residues on Lanp, which contain 5 leucine-rich repeats, and a full-length ataxin-1 containing 82 glutamines. Immunohistochemical analysis demonstrated highest levels of Lanp, like Atx1, in the nuclei of cerebellar Purkinje cells.MAPPING
Fink et al. (1995) mapped the PHAP1 gene to 15q22.3-q23 by fluorescence in situ hybridization.CYTOGENETICS
The SET gene is located on 9q34 and was found to be fused to the putative oncogene CAN (114350) in a patient with acute undifferentiated leukemia (von Lindern et al., 1992). The similarities between PHAP I and SET suggested to Fink et al. (1995) that the PHAP1 gene might also form a fusion protein with CAN. In the SET-CAN fusion gene, the breakpoint is located 3-prime of the SET gene, but the last exon of SET is removed in the fusion transcript. This exon encodes the last 7 amino acids (EDEGEDD) of SET that are identical with the end of PHAP I except that PHAP I carries an additional D (EDEGEDDD). The vast majority of cases in which CAN is involved in acute myeloid leukemia show a specificity for the t(6;9) translocation (Sandberg et al., 1983) that fuses the 3-prime part of the CAN gene on 9q34 (von Lindern et al., 1990) to almost the complete coding region of the DEK gene (125264) on 6p23 (von Lindern et al., 1992). The translocation breakpoints always occur in intron icb-9 of CAN. The PHAP1/CAN translocation would be expected to cause acute leukemia. Like DEK and SET, PHAP I contains an extended acidic region that could result in a transforming capacity.GENE FUNCTION
By micropeptide sequence analysis of a PP2A (PPP2CA; 176915) inhibitor and database screening, Li et al. (1996) determined that the inhibitor, termed I1PP2A, was identical to PHAP1. SDS-PAGE analysis indicated that both proteins, which contain 249 amino acids and a highly acidic C-terminal tail, have an apparent molecular mass of 30 kD. Functional analysis showed that recombinant PHAP1 is a potent and specific inhibitor of PP2A and acts by binding to the C subunit of the phosphatase. Jiang et al. (2003) identified a pathway that regulates mitochondria-initiated caspase activity. In this pathway, PHAP protein promoted caspase-9 (602234) activation after apoptosome formation, whereas PTMA (188390) ne ... More on the omim web site
April 10, 2021: 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 15, 2016: Protein entry updated
Automatic update: OMIM entry 600832 was added.
Jan. 24, 2016: Protein entry updated
Automatic update: model status changed