ID   NEF_HV2NZ               Reviewed;         180 AA.
AC   P05860;
DT   01-NOV-1988, integrated into UniProtKB/Swiss-Prot.
DT   23-JAN-2007, sequence version 3.
DT   03-AUG-2022, entry version 107.
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 NIH-Z) (HIV-2).
OC   Viruses; Riboviria; Pararnavirae; Artverviricota; Revtraviricetes;
OC   Ortervirales; Retroviridae; Orthoretrovirinae; Lentivirus.
OX   NCBI_TaxID=11719;
OH   NCBI_TaxID=9606; Homo sapiens (Human).
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX   PubMed=3261862; DOI=10.1073/pnas.85.16.5941;
RA   Zagury J.F., Franchini G., Reitz M.S. Jr., Collalti E., Starcich B.R.,
RA   Hall L., Fargnoli K.A., Jagodzinski L.L., Guo H.-G., Laure F., Arya S.K.,
RA   Josephs S.F., Zagury D., Wong-Staal F., Gallo R.C.;
RT   "Genetic variability between isolates of human immunodeficiency virus (HIV)
RT   type 2 is comparable to the variability among HIV type 1.";
RL   Proc. Natl. Acad. Sci. U.S.A. 85:5941-5945(1988).
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 (By similarity).
CC       {ECO:0000250}.
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}.
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DR   EMBL; J03654; AAB00762.1; -; Genomic_DNA.
DR   SMR; P05860; -.
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; Viral immunoevasion; Virulence.
FT   INIT_MET        1
FT                   /note="Removed; by host"
FT                   /evidence="ECO:0000250"
FT   CHAIN           2..180
FT                   /note="Protein Nef"
FT                   /id="PRO_0000085236"
FT   REGION          1..103
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          88..96
FT                   /note="Acidic"
FT   MOTIF           104..107
FT                   /note="PxxP"
FT   COMPBIAS        44..68
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        73..88
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   180 AA;  20409 MW;  C2DBE78AEC267887 CRC64;
     MGASGSKKRS KPLQGLQERL LQARGETCGG RCNESGGGYL QSHEGSGREQ NSPSCEGQRY
     QQGDFVNTPW RTPAAEREKE LYKQQNMDDV DLDDDDQVGF PVTPRVPLRP MTFKLAVDMS
     HFIKEKGGLE GLFYSQRRHR ILDLYLDKAF TLYPEEFGHN SGLPEKEWKA RLKARGIPFS