NEF_HV2D1
ID NEF_HV2D1 Reviewed; 257 AA.
AC P17753;
DT 01-AUG-1990, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 03-AUG-2022, entry version 108.
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 D194) (HIV-2).
OC Viruses; Riboviria; Pararnavirae; Artverviricota; Revtraviricetes;
OC Ortervirales; Retroviridae; Orthoretrovirinae; Lentivirus.
OX NCBI_TaxID=11713;
OH NCBI_TaxID=9606; Homo sapiens (Human).
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=2467304; DOI=10.1073/pnas.86.7.2383;
RA Kuehnel H., von Briesen H., Dietrich U., Adamski M., Mix D., Biesert L.,
RA Kreutz R., Immelmann A., Henco K., Meichsner C., Andreesen R.,
RA Gelderblom H., Ruebsamen-Waigmann H.;
RT "Molecular cloning of two west African human immunodeficiency virus type 2
RT isolates that replicate well in macrophages: a Gambian isolate, from a
RT patient with neurologic acquired immunodeficiency syndrome, and a highly
RT divergent Ghanian isolate.";
RL Proc. Natl. Acad. Sci. U.S.A. 86:2383-2387(1989).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=2235509; DOI=10.1093/nar/18.20.6142;
RA Kuehnel H., Kreutz R., Ruebsamen-Waigmann H.;
RT "Nucleotide sequence of HIV-2D194, an isolate from a Gambian case of
RT 'neuro-AIDS', which showed excellent growth in macrophages.";
RL Nucleic Acids Res. 18:6142-6142(1990).
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; J04542; AAA76848.1; -; Genomic_DNA.
DR EMBL; X52223; CAA36472.1; -; Genomic_DNA.
DR PIR; S12160; S12160.
DR SMR; P17753; -.
DR Proteomes; UP000007422; 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; Viral immunoevasion; 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_0000085229"
FT REGION 1..70
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 COMPBIAS 10..25
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 33..70
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; 29449 MW; 2C5E1EB5C8ABBCF3 CRC64;
MGASGSKKRS EHSQGLRERL LRARGGGYVK QRNASGGESS QSQEGSGREQ KSPSCEGQQY
QQGEFMNTPW RTPAAIGQKN SYKQQNMDDV DSDDDDLVGV PVMPRVPLRE MTYKLAIDMS
HFIKEKGGLE GIFYSRERHR ILDLFLEKEE GIIPDWQNYT HGPGTRYPMY FGWLWKLVPV
DISQEAEEVE TNCLVHPAQT SRYDDEHGET LVWRFDPMLA YSYKAFILHP EEFGHKSGLP
EKEWKAKLKA RGIPYSE
