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Database: UniProt
Entry: NEF_HV2BE
LinkDB: NEF_HV2BE
Original site: 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   22-APR-2020, entry version 104.
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; 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-lymphocytes 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}.
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   KO; K22891; -.
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   GO; GO:0030683; P:mitigation of host immune response by virus; IEA:UniProtKB-KW.
DR   GO; GO:0009405; P:pathogenesis; IEA:UniProtKB-KW.
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          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   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
//
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