Zinc finger CCCH-type antiviral protein 1 (ZC3HAV1)
The protein contains 902 amino acids for an estimated molecular weight of 101431 Da.
Antiviral protein which inhibits the replication of viruses by recruiting the cellular RNA degradation machineries to degrade the viral mRNAs. Binds to a ZAP-responsive element (ZRE) present in the target viral mRNA, recruits cellular poly(A)-specific ribonuclease PARN to remove the poly(A) tail, and the 3'-5' exoribonuclease complex exosome to degrade the RNA body from the 3'-end. It also recruits the decapping complex DCP1-DCP2 through RNA helicase p72 (DDX17) to remove the cap structure of the viral mRNA to initiate its degradation from the 5'-end. Its target viruses belong to families which include retroviridae: human immunodeficiency virus type 1 (HIV-1), moloney and murine leukemia virus (MoMLV) and xenotropic MuLV-related virus (XMRV), filoviridae: ebola virus (EBOV) and marburg virus (MARV), togaviridae: sindbis virus (SINV) and Ross river virus (RRV). Specifically targets the multiply spliced but not unspliced or singly spliced HIV-1 mRNAs for degradation. Isoform 1 is a more potent viral inhibitor than isoform 2. Isoform 2 acts as a positive regulator of DDX58/RIG-I signaling resulting in activation of the downstream effector IRF3 leading to the expression of type I IFNs and IFN stimulated genes (ISGs). (updated: March 4, 2015)
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.
- 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.
- 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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| Variant | Description |
|---|---|
| dbSNP:rs2236426 | |
| dbSNP:rs2297241 | |
| dbSNP:rs2297236 | |
| dbSNP:rs3735007 |
Biological Process
Defense response to virus
Innate immune response
Negative regulation of viral genome replication
Positive regulation of I-kappaB kinase/NF-kappaB signaling
Positive regulation of interferon-alpha production
Positive regulation of interferon-beta production
Positive regulation of mRNA catabolic process
Positive regulation of RIG-I signaling pathway
Protein ADP-ribosylation
Response to virus
The reference OMIM entry for this protein is 607312
Zinc finger ccch domain-containing antiviral protein 1; zc3hav1
Zinc finger antiviral protein; zap
DESCRIPTION
ZC3HAV1 is a CCCH-type zinc finger protein that prevents infection by retroviruses.CLONING
In their analysis of genes expressed in human fetal liver, Yu et al. (2001) identified ZC3HAV1, which they called ZAP, as a 1,524-bp cDNA (GenBank GENBANK AF138863) with an open reading frame of 264 amino acids. Gao et al. (2002) screened mammalian cDNA libraries for genes that prevent infection by a genetically marked retrovirus. Virus-resistant cells were selected from pools of transduced clones, and an active antiviral cDNA was recovered. The gene encodes a CCCH-type zinc finger protein designated ZAP for 'zinc finger antiviral protein.' Gao et al. (2002) cloned a full-length rat Zap cDNA, which contained 776 codons. Northern blot analysis of rat Zap showed that mRNA was highly expressed in kidney and liver, but undetectable in brain and testis. Two mRNAs (3.5 and 4.5 kb) were observed in most tissues, possibly corresponding to alternative splice variants. Expression of the gene caused profound and specific loss of viral mRNAs from the cytoplasm of rat and mouse cells without affecting the levels of nuclear mRNAs. This observation suggested the existence of a previously unknown machinery for the inhibition of virus replication, targeting a step in viral gene expression. By database searching with evolutionarily conserved sequences in the TIPARP gene (612480), Katoh and Katoh (2003) identified 2 human genes, FLJ22693 (PARP12; 612481) and ZC3HAV1, encoding deduced proteins with the same conserved domains: a WWE domain, a PARP-like domain, and a TPH domain. The N-terminal domain of the TPH domain in all 3 genes contains a CCCH-type zinc finger. Katoh and Katoh (2003) noted that PARP12 and ZCH3HAV1 share 27.5% and 26% overall amino acid sequence identity with TIPARP, respectively. They stated that the deduced ZC3HAV1 protein contains 902 amino acids.MAPPING
Yu et al. (2001) assigned the human ZAP gene to chromosome 7. By analysis of mouse genomic sequences, Gao et al. (2002) mapped the Zap gene to chromosome 6. ... More on the omim web site
Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated
Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 607312 was added.
Feb. 24, 2016: Protein entry updated
Automatic update: model status changed