ID   NEF_HV2EH               Reviewed;         238 AA.
AC   Q89868;
DT   27-JUN-2006, integrated into UniProtKB/Swiss-Prot.
DT   23-JAN-2007, sequence version 3.
DT   03-AUG-2022, entry version 87.
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 B (isolate EHO) (HIV-2).
OC   Viruses; Riboviria; Pararnavirae; Artverviricota; Revtraviricetes;
OC   Ortervirales; Retroviridae; Orthoretrovirinae; Lentivirus.
OX   NCBI_TaxID=388821;
OH   NCBI_TaxID=9606; Homo sapiens (Human).
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX   PubMed=7546916; DOI=10.1089/aid.1995.11.873;
RA   Galabru J., Rey-Cuille M.A., Hovanessian A.G.;
RT   "Nucleotide sequence of the HIV-2 EHO genome, a divergent HIV-2 isolate.";
RL   AIDS Res. Hum. Retroviruses 11:873-874(1995).
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:0000250}.
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   -!- 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   -!- MISCELLANEOUS: This isolate is from a Gambian case of 'neuro-AIDS'.
CC   -!- SIMILARITY: Belongs to the lentivirus primate group Nef protein family.
CC       {ECO:0000305}.
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DR   EMBL; U27200; AAC54474.1; -; Genomic_DNA.
DR   SMR; Q89868; -.
DR   PRIDE; Q89868; -.
DR   Proteomes; UP000007423; 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..238
FT                   /note="Protein Nef"
FT                   /id="PRO_0000244817"
FT   REGION          1..85
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          70..77
FT                   /note="Acidic"
FT   REGION          122..138
FT                   /note="Mediates dimerization"
FT                   /evidence="ECO:0000250"
FT   MOTIF           86..89
FT                   /note="PxxP"
FT   COMPBIAS        12..35
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   LIPID           2
FT                   /note="N-myristoyl glycine; by host"
FT                   /evidence="ECO:0000250"
SQ   SEQUENCE   238 AA;  27004 MW;  B4CA7838844B8301 CRC64;
     MGSAGSKKQS KQQPGLRERL LRARRGPRGE SSGERQERSL QYPGGSDKGL NSPSCDGQKT
     LGAEGGGKQD SDEDDEDNEV GVRVRPGVPL RPMTFKLAVD MSHFLKEKGE LEGIFYSERR
     HKILDTYLEN EEGIVSGWQN YTHGPGVRYP KFFGWLWKLV PINMIAEPED EETHCLVHPA
     QTSAWDDPHE ETLVWQFDSL LAYDYVAFSR FPEEFGYQSG MPEKEWKAKL RARGIPTE