UniProt Accession

 ZCCHV_HUMAN; Q7Z2W4; A4D1R2; A4D1S4; Q8IW57; Q8TAJ3; Q96N79; Q9H8R9; Q9P0Y7 

Genbank Protein ID

 AF138863; AK055851; AK023350; BX571742; CH236950; CH236950; BC025308; BC027462; BC033105; BC040956 

Genbank Nucleotide ID

 AAF61195.1; BAB71028.1; BAB14537.1; CAE11868.1; EAL24040.1; EAL24041.1; AAH25308.1; AAH27462.1; AAH33105.1; AAH40956.1 

Protein Name

 Zinc finger CCCH-type antiviral protein 1 

Protein Synonyms/Alias

 ADP-ribosyltransferase diphtheria toxin-like 13; ARTD13; Zinc finger CCCH domain-containing protein 2; Zinc finger antiviral protein; ZAP 

Gene Name

 ZC3HAV1 

Gene Synonyms/Alias

 ZC3HDC2; PRO1677 

Created Date

 July 27, 2013 

Organism

 Homo sapiens (Human) 

NCBI Taxa ID

 9606 

Lysine Modification

Position	Peptide	Type	References
783	SQMKEEGKLLFYATS	ubiquitination	[1, 2]

Reference

 [1] A proteome-wide, quantitative survey of in vivo ubiquitylation sites reveals widespread regulatory roles.
 Wagner SA, Beli P, Weinert BT, Nielsen ML, Cox J, Mann M, Choudhary C.
 Mol Cell Proteomics. 2011 Oct;10(10):M111.013284. [PMID: 21890473]
 [2] Proteome-wide identification of ubiquitylation sites by conjugation of engineered lysine-less ubiquitin.
 Oshikawa K, Matsumoto M, Oyamada K, Nakayama KI.
 J Proteome Res. 2012 Feb 3;11(2):796-807. [PMID: 22053931] 

Functional Description

 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). 

Sequence Annotation

 DOMAIN 594 681 WWE.
 DOMAIN 716 902 PARP catalytic.
 ZN_FING 73 86 C3H1-type 1.
 ZN_FING 88 110 C3H1-type 2.
 ZN_FING 150 172 C3H1-type 3.
 ZN_FING 169 193 C3H1-type 4.
 REGION 2 254 N-terminal domain.
 REGION 224 254 Binding to EXOSC5 (By similarity).
 MOTIF 69 76 Nuclear localization signal (By
 MOTIF 285 292 Nuclear export signal (By similarity).
 MOD_RES 2 2 N-acetylalanine.
 MOD_RES 257 257 Phosphoserine; by GSK3-beta.
 MOD_RES 263 263 Phosphoserine; by GSK3-beta (By
 MOD_RES 267 267 Phosphoserine; by GSK3-beta (By
 MOD_RES 271 271 Phosphoserine; by GSK3-beta.
 MOD_RES 273 273 Phosphothreonine.
 MOD_RES 275 275 Phosphoserine.
 MOD_RES 284 284 Phosphoserine.
 MOD_RES 302 302 Phosphoserine.
 MOD_RES 327 327 Phosphoserine (By similarity).
 MOD_RES 335 335 Phosphoserine.
 MOD_RES 355 355 Phosphoserine (By similarity).
 MOD_RES 378 378 Phosphoserine.
 MOD_RES 387 387 Phosphoserine.
 MOD_RES 393 393 Phosphothreonine.
 MOD_RES 492 492 Phosphoserine.  

Keyword

 3D-structure; Acetylation; Alternative splicing; Antiviral defense; Complete proteome; Cytoplasm; Immunity; Innate immunity; Metal-binding; Nucleus; Phosphoprotein; Polymorphism; Reference proteome; Repeat; RNA-binding; Zinc; Zinc-finger. 

Sequence Source

 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 

Protein Length

 902 AA 

Protein Sequence

Gene Ontology

 GO:0005737; C:cytoplasm; IDA:UniProtKB.
 GO:0005794; C:Golgi apparatus; IDA:HPA.
 GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
 GO:0005886; C:plasma membrane; IDA:HPA.
 GO:0003950; F:NAD+ ADP-ribosyltransferase activity; IEA:InterPro.
 GO:0003723; F:RNA binding; IEA:UniProtKB-KW.
 GO:0008270; F:zinc ion binding; IEA:InterPro.
 GO:0071360; P:cellular response to exogenous dsRNA; IEA:Compara.
 GO:0051607; P:defense response to virus; IEA:UniProtKB-KW.
 GO:0045087; P:innate immune response; IEA:UniProtKB-KW.
 GO:0045071; P:negative regulation of viral genome replication; IDA:UniProtKB.
 GO:0043123; P:positive regulation of I-kappaB kinase/NF-kappaB cascade; IMP:UniProtKB.
 GO:0032727; P:positive regulation of interferon-alpha production; IDA:UniProtKB.
 GO:0032728; P:positive regulation of interferon-beta production; IDA:UniProtKB.
 GO:0061014; P:positive regulation of mRNA catabolic process; IDA:UniProtKB.
 GO:1900246; P:positive regulation of RIG-I signaling pathway; IMP:UniProtKB.
 GO:0032481; P:positive regulation of type I interferon production; IEA:Compara.
 GO:0009615; P:response to virus; IDA:UniProtKB. 

Interpro

 IPR012317; Poly(ADP-ribose)pol_cat_dom.
 IPR004170; WWE-dom.
 IPR000571; Znf_CCCH. 

Pfam

 PF00644; PARP 

SMART

  

PROSITE

 PS51059; PARP_CATALYTIC
 PS50918; WWE
 PS50103; ZF_C3H1 

PRINTS