ID   NEF_HV2RO               Reviewed;         256 AA.
AC   P04600;
DT   13-AUG-1987, integrated into UniProtKB/Swiss-Prot.
DT   23-JAN-2007, sequence version 3.
DT   03-AUG-2022, entry version 112.
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 ROD) (HIV-2).
OC   Viruses; Riboviria; Pararnavirae; Artverviricota; Revtraviricetes;
OC   Ortervirales; Retroviridae; Orthoretrovirinae; Lentivirus.
OX   NCBI_TaxID=11720;
OH   NCBI_TaxID=9606; Homo sapiens (Human).
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX   PubMed=3031510; DOI=10.1038/326662a0;
RA   Guyader M., Emerman M., Sonigo P., Clavel F., Montagnier L., Alizon M.;
RT   "Genome organization and transactivation of the human immunodeficiency
RT   virus type 2.";
RL   Nature 326:662-669(1987).
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. Interacts with host CD247/TCRZ; this interaction
CC       induces down-regulation of cell surface TCR/CD3 complexes.
CC       {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   -!- 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; M15390; AAB00771.1; -; Genomic_DNA.
DR   EMBL; X05291; CAA28915.1; -; Genomic_RNA.
DR   PIR; D26262; ASLJH2.
DR   SMR; P04600; -.
DR   PRIDE; P04600; -.
DR   Proteomes; UP000007426; Genome.
DR   Proteomes; UP000246871; 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..256
FT                   /note="Protein Nef"
FT                   /id="PRO_0000085237"
FT   REGION          36..71
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   LIPID           2
FT                   /note="N-myristoyl glycine; by host"
FT                   /evidence="ECO:0000250"
SQ   SEQUENCE   256 AA;  29566 MW;  55BA1B78E71CCA85 CRC64;
     MGASGSKKHS RPPRGLQERL LRARAGACGG YWNESGGEYS RFQEGSDREQ KSPSCEGRQY
     QQGDFMNTPW KDPAAEREKN LYRQQNMDDV DSDDDDQVRV SVTPKVPLRP MTHRLAIDMS
     HLIKTRGGLE GMFYSERRHK ILNIYLEKEE GIIADWQNYT HGPGVRYPMF FGWLWKLVPV
     DVPQEGEDTE THCLVHPAQT SKFDDPHGET LVWEFDPLLA YSYEAFIRYP EEFGHKSGLP
     EEEWKARLKA RGIPFS