P69720 (VIF_HV1B1) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Virion infectivity factor
Short name=Vif

Alternative name(s):
SOR protein

Cleaved into the following 2 chains:

1. p17
2. p7

Gene names

Name:

vif

Organism

Human immunodeficiency virus type 1 group M subtype B (isolate BH10) (HIV-1) [Complete proteome]

Taxonomic identifier

11678 [NCBI]

Taxonomic lineage

Viruses › Retro-transcribing viruses › Retroviridae › Orthoretrovirinae › Lentivirus › Primate lentivirus group › Human immunodeficiency virus 1 › HIV-1 unknown group

Virus host

Homo sapiens (Human) [TaxID: 9606]

Protein attributes

Sequence length	192 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at transcript level

General annotation (Comments)

Function	Counteracts the innate antiviral activity of human APOBEC3F and APOBEC3G. Forms a complex with host APOBEC3F and APOBEC3G thus preventing the entry of these lethally hypermutating enzymes into progeny virions. Recruits an active E3 ubiquitin ligase complex composed of elongin BC, CUL5, and RBX2 to induce polyubiquitination of APOBEC3G and APOBEC3F. In turn, they are directed to the 26S proteasome for degradation. Vif interaction with APOBEC3G also blocks its cytidine deaminase activity in a proteasome-independent manner, suggesting a dual inhibitory mechanism. May interact directly with APOBEC3G mRNA in order to inhibit its translation. Seems to play a role in viral morphology by affecting the stability of the viral nucleoprotein core. Finally, Vif also contributes to the G2 cell cycle arrest observed in HIV infected cells By similarity.
Subunit structure	Homomultimer; in vitro and presumably in vivo. Interacts with viral RNA and Pr55Gag precursor; these interactions mediate Vif incorporation into the virion. Interacts with the viral reverse transcriptase. Interacts with human APOBEC3F and APOBEC3G. Interacts with host UBCE7IP1 isoform 3/ZIN and possibly with SAT. Interacts with host tyrosine kinases HCK and FYN; these interactions may decrease level of phosphorylated APOBEC3G incorporation into virions. Interacts with host ABCE1; this interaction may play a role in protecting viral RNA from damage during viral assembly. Forms an E3 ligase complex by interacting with human CUL5 and elongin BC complex (TCEB1 and TCEB2). Interacts with host MDM2; this interaction targets Vif for degradation by the proteasome By similarity.
Subcellular location	Host cytoplasm By similarity. Host cell membrane; Peripheral membrane protein; Cytoplasmic side By similarity. Virion By similarity. Note: In the cytoplasm, seems to colocalize with intermediate filament vimentin. A fraction is associated with the cytoplasmic side of cellular membranes, presumably via the interaction with Pr55Gag precursor. Incorporated in virions at a ratio of approximately 7 to 20 molecules per virion By similarity.
Induction	Expressed late during infection in a Rev-dependent manner.
Domain	The BC-like-box motif mediates the interaction with elongin BC complex By similarity. The HCCH motif (H-x(5)-C-x(18)-C-x(5)-H) mediates the interaction with CUL5 By similarity.
Post-translational modification	Processed in virion by the viral protease By similarity. Highly phosphorylated on serines and threonines residues. Thr-96 and Ser-165 are phosphorylated by the mitogen activated kinase MAP4K1. As the HIV-1 replication can be activated by stress and mitogens, these phosphorylations could be involved in this process. Ser-144 phosphorylation may inhibit elongin BC complex binding By similarity. Polyubiquitinated and degraded by the proteasome in the presence of APOBEC3G By similarity.
Miscellaneous	Required for replication in 'nonpermissive' cells, including primary T-cells, macrophages and certain T-cell lines, but is dispensable for replication in 'permissive' cell lines, such as 293T cells. In nonpermissive cells, Vif-defective viruses can produce virions, but they fail to complete reverse transcription and cannot successfully infect new cells. Vif-defective viruses show catastrophic failure in reverse transcription due to APOBEC-induced mutations that initiate a DNA base repair pathway and compromise the structural integrity of the ssDNA. In the absence of Vif, the virion is morphologically abnormal. HIV-1 lineages are divided in three main groups, M (for Major), O (for Outlier), and N (for New, or Non-M, Non-O). The vast majority of strains found worldwide belong to the group M. Group O seems to be endemic to and largely confined to Cameroon and neighboring countries in West Central Africa, where these viruses represent a small minority of HIV-1 strains. The group N is represented by a limited number of isolates from Cameroonian persons. The group M is further subdivided in 9 clades or subtypes (A to D, F to H, J and K).
Sequence similarities	Belongs to the primate lentivirus group Vif protein family.

Ontologies

Keywords
Biological process	Host-virus interaction Ubl conjugation pathway
Cellular component	Host cell membrane Host cytoplasm Host membrane Membrane Virion
Disease	AIDS
Ligand	RNA-binding
PTM	Phosphoprotein Ubl conjugation
Technical term	Complete proteome
Gene Ontology (GO)
Biological_process	RNA-dependent DNA replication Traceable author statement. Source: Reactome entry into host cell Traceable author statement. Source: Reactome uncoating of virus Traceable author statement. Source: Reactome viral infectious cycle Inferred from electronic annotation. Source: InterPro virus-host interaction Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	cytosol Traceable author statement. Source: Reactome host cell cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell host cell plasma membrane Inferred from electronic annotation. Source: UniProtKB-SubCell membrane Inferred from electronic annotation. Source: UniProtKB-KW nucleoplasm Traceable author statement. Source: Reactome virion Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	RNA binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 192	192	Virion infectivity factor		PRO_0000085312
	Chain	1 – 150	150	p17		PRO_0000244708
	Chain	151 – 192	42	p7		PRO_0000244709
Regions
	Region	14 – 17	4	Interaction with host APOBEC3F; F1-box By similarity
	Region	40 – 44	5	Interaction with host APOBEC3G; G-box By similarity
	Region	54 – 72	19	Interaction with host APOBEC3F and APOBEC3G; FG-box By similarity
	Region	74 – 79	6	Interaction with host APOBEC3F; F2-box By similarity
	Region	75 – 114	40	RNA-binding Potential
	Region	151 – 164	14	Multimerization By similarity
	Region	171 – 172	2	Membrane association By similarity
	Motif	108 – 139	32	HCCH motif By similarity
	Motif	144 – 153	10	BC-box-like motif
Sites
	Site	150 – 151	2	Cleavage in virion (by viral protease) By similarity
Amino acid modifications
	Modified residue	96	1	Phosphothreonine; by host MAP4K1 By similarity
	Modified residue	144	1	Phosphoserine; by host By similarity
	Modified residue	155	1	Phosphothreonine; by host By similarity
	Modified residue	165	1	Phosphoserine; by host MAP4K1 By similarity
	Modified residue	188	1	Phosphothreonine; by host By similarity

Sequences

	Sequence		Length	Mass (Da)
	P69720 [UniParc]. Last modified August 13, 1987. Version 1. Checksum: D22589F3955CBE40	FASTA	192	22,513
	10 20 30 40 50 60 MENRWQVMIV WQVDRMRIRT WKSLVKHHMY VSGKARGWFY RHHYESPHPR ISSEVHIPLG 70 80 90 100 110 120 DARLVITTYW GLHTGERDWH LGQGVSIEWR KKRYSTQVDP ELADQLIHLY YFDCFSDSAI 130 140 150 160 170 180 RKALLGHIVS PRCEYQAGHN KVGSLQYLAL AALITPKKIK PPLPSVTKLT EDRWNKPQKT 190 KGHRGSHTMN GH

References

[1]	"Complete nucleotide sequence of the AIDS virus, HTLV-III." Ratner L., Haseltine W.A., Patarca R., Livak K.J., Starcich B.R., Josephs S.F., Doran E.R., Rafalski J.A., Whitehorn E.A., Baumeister K., Ivanoff L., Petteway S.R. Jr., Pearson M.L., Lautenberger J.A., Papas T.S., Ghrayeb J., Chang N.T., Gallo R.C., Wong-Staal F. Nature 313:277-284(1985) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
[2]	"Nucleic acid structure and expression of the human AIDS/lymphadenopathy retrovirus." Muesing M.A., Smith D.H., Cabradilla C.D., Benton C.V., Lasky L.A., Capon D.J. Nature 313:450-458(1985) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Strain: Isolate PV22.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	M15654 Genomic RNA. Translation: AAA44202.1. K02083 Genomic DNA. Translation: AAB59868.1. X01762 Genomic RNA. No translation available.
RefSeq	NP_057851.1. NC_001802.1.
3D structure databases
ProteinModelPortal	P69720.
ModBase	Search...
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
GeneID	155459.
Enzyme and pathway databases
Reactome	REACT_116125. Disease.
Family and domain databases
InterPro	IPR000475. Viral_infect. [Graphical view]
Pfam	PF00559. Vif. 1 hit. [Graphical view]
PRINTS	PR00349. VIRIONINFFCT.
ProtoNet	Search...

Entry information

Entry name

VIF_HV1B1

Accession

Primary (citable) accession number: P69720
Secondary accession number(s): P03401, P69724

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 21, 1986
Last sequence update:	August 13, 1987
Last modified:	April 3, 2013
This is version 55 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Viral Protein Annotation Program