NEF_HV2BE
ID NEF_HV2BE Reviewed; 257 AA.
AC P18092;
DT 01-NOV-1990, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 03-AUG-2022, entry version 111.
DE RecName: Full=Protein Nef;
DE AltName: Full=3'ORF;
DE AltName: Full=Negative factor;
DE Short=F-protein;
GN Name=nef;
OS Human immunodeficiency virus type 2 subtype A (isolate BEN) (HIV-2).
OC Viruses; Riboviria; Pararnavirae; Artverviricota; Revtraviricetes;
OC Ortervirales; Retroviridae; Orthoretrovirinae; Lentivirus.
OX NCBI_TaxID=11714;
OH NCBI_TaxID=9606; Homo sapiens (Human).
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=2353457; DOI=10.1016/0042-6822(90)90484-9;
RA Kirchhoff F., Jentsch K., Bachmann B., Stuke A., Laloux C., Lueke W.,
RA Stahl-Henning C., Schneider J., Nieselt K., Eigen M., Hunsmann G.;
RT "A novel proviral clone of HIV-2: biological and phylogenetic relationship
RT to other primate immunodeficiency viruses.";
RL Virology 177:305-311(1990).
RN [2]
RP FUNCTION.
RX PubMed=16051847; DOI=10.1128/jvi.79.16.10547-10560.2005;
RA Munch J., Schindler M., Wildum S., Rucker E., Bailer N., Knoop V.,
RA Novembre F.J., Kirchhoff F.;
RT "Primary sooty mangabey simian immunodeficiency virus and human
RT immunodeficiency virus type 2 nef alleles modulate cell surface expression
RT of various human receptors and enhance viral infectivity and replication.";
RL J. Virol. 79:10547-10560(2005).
CC -!- FUNCTION: Factor of infectivity and pathogenicity, required for optimal
CC virus replication. Alters numerous pathways of T-lymphocyte function
CC and down-regulates immunity surface molecules in order to evade host
CC defense and increase viral infectivity. Alters the functionality of
CC other immunity cells, like dendritic cells, monocytes/macrophages and
CC NK cells. One of the earliest and most abundantly expressed viral
CC proteins (By similarity). {ECO:0000250}.
CC -!- FUNCTION: In infected CD4(+) T-lymphocytes, down-regulates cell surface
CC expression of CD4, CD28, CD3, and MHC-I or MHC-II molecules.
CC {ECO:0000305|PubMed:16051847}.
CC -!- FUNCTION: Interferes with TCR signaling from the cell membrane.
CC Interacts with CD247/TCRZ (TCR zeta chain) and exert potent down-
CC regulation of cell surface TCR/CD3 complexes.
CC {ECO:0000269|PubMed:16051847}.
CC -!- FUNCTION: Plays a role in optimizing the host cell environment for
CC viral replication without causing cell death by apoptosis. Protects the
CC infected cells from apoptosis in order to keep them alive until the
CC next virus generation is ready to strike (By similarity).
CC {ECO:0000250}.
CC -!- FUNCTION: Extracellular Nef protein targets CD4(+) T-lymphocytes for
CC apoptosis by interacting with CXCR4 surface receptors. {ECO:0000250}.
CC -!- SUBUNIT: Homodimer (By similarity). Interacts with host CD247/TCRZ;
CC this interaction induces down-regulation of cell surface TCR/CD3
CC complexes. {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Host cell membrane {ECO:0000250}; Lipid-anchor
CC {ECO:0000250}; Cytoplasmic side {ECO:0000250}. Note=Associates with the
CC inner plasma membrane through its N-terminal domain. {ECO:0000250}.
CC -!- DOMAIN: The N-terminal domain is composed of the N-myristoyl glycine
CC and of a cluster of positively charged amino acids. It is required for
CC inner plasma membrane targeting of Nef and virion incorporation, and
CC thereby for infectivity (By similarity). {ECO:0000250}.
CC -!- MISCELLANEOUS: This isolate is from a German AIDS patient (with
CC predominantly neurological complications) who was probably infected in
CC Mali.
CC -!- SIMILARITY: Belongs to the lentivirus primate group Nef protein family.
CC {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; M30502; AAB00744.1; -; Genomic_DNA.
DR RefSeq; NP_056845.1; NC_001722.1.
DR SMR; P18092; -.
DR PRIDE; P18092; -.
DR GeneID; 1724715; -.
DR KEGG; vg:1724715; -.
DR Proteomes; UP000002242; Genome.
DR GO; GO:0020002; C:host cell plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016020; C:membrane; IEA:UniProtKB-KW.
DR GO; GO:0005525; F:GTP binding; IEA:InterPro.
DR Gene3D; 3.30.62.10; -; 1.
DR InterPro; IPR027481; HIV-1_Nef_core_sf.
DR InterPro; IPR001558; HIV_Nef.
DR Pfam; PF00469; F-protein; 1.
DR SUPFAM; SSF55671; SSF55671; 1.
PE 3: Inferred from homology;
KW AIDS; Host cell membrane; Host membrane; Host-virus interaction;
KW Lipoprotein; Membrane; Myristate; Reference proteome; Viral immunoevasion;
KW Virulence.
FT INIT_MET 1
FT /note="Removed; by host"
FT /evidence="ECO:0000250"
FT CHAIN 2..257
FT /note="Protein Nef"
FT /id="PRO_0000085230"
FT REGION 1..72
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 88..96
FT /note="Acidic"
FT REGION 140..156
FT /note="Mediates dimerization"
FT /evidence="ECO:0000250"
FT MOTIF 104..107
FT /note="PxxP"
FT /evidence="ECO:0000250"
FT COMPBIAS 36..72
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT LIPID 2
FT /note="N-myristoyl glycine; by host"
FT /evidence="ECO:0000250"
SQ SEQUENCE 257 AA; 29911 MW; B8F8B58B21A813A1 CRC64;
MGASGSKKLS KHSRGLRERL LRARGDGYGK QRDASGGEYS QFQEESGREQ NSPSCEGQQY
QQGEYMNSPW RNPATERQKD LYRQQNMDDV DSDDDDLIGV PVTPRVPRRE MTYKLAIDMS
HFIKEKGGLQ GMFYSRRRHR ILDIYLEKEE GIIPDWQNYT HGPGVRYPMY FGWLWKLVSV
ELSQEAEEDE ANCLVHPAQT SRHDDEHGET LVWQFDSMLA YNYKAFTLYP EEFGHKSGLP
EKEWKAKLKA RGIPYSE
