NEF_SIVTN
ID NEF_SIVTN Reviewed; 195 AA.
AC Q8AIH4;
DT 05-SEP-2006, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 03-AUG-2022, entry version 88.
DE RecName: Full=Protein Nef;
DE AltName: Full=3'ORF;
DE AltName: Full=Negative factor;
DE Short=F-protein;
OS Simian immunodeficiency virus (isolate TAN1) (SIV-cpz) (Chimpanzee
OS immunodeficiency virus).
OC Viruses; Riboviria; Pararnavirae; Artverviricota; Revtraviricetes;
OC Ortervirales; Retroviridae; Orthoretrovirinae; Lentivirus.
OX NCBI_TaxID=388910;
OH NCBI_TaxID=9598; Pan troglodytes (Chimpanzee).
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RX PubMed=12525658; DOI=10.1128/jvi.77.3.2233-2242.2003;
RA Santiago M.L., Bibollet-Ruche F., Bailes E., Kamenya S., Muller M.N.,
RA Lukasik M., Pusey A.E., Collins D.A., Wrangham R.W., Goodall J., Shaw G.M.,
RA Sharp P.M., Hahn B.H.;
RT "Amplification of a complete simian immunodeficiency virus genome from
RT fecal RNA of a wild chimpanzee.";
RL J. Virol. 77:2233-2242(2003).
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 the surface
CC MHC-I, mature MHC-II, CD4, CD28 and probably other immunity surface
CC molecules. In consequence infected cells are masked for immune
CC recognition by cytotoxic T-lymphocytes. Decreasing the number of immune
CC receptors also prevents reinfection by more HIV particles
CC (superinfection).
CC -!- FUNCTION: Bypasses host T-cell signaling by inducing a transcriptional
CC program nearly identical to that of anti-CD3 cell activation.
CC Interaction with TCR-zeta chain up-regulates the Fas ligand (FasL).
CC Increasing surface FasL molecules and decreasing surface MHC-I
CC molecules on infected CD4(+) cells send attacking cytotoxic CD8+ T-
CC lymphocytes into apoptosis (By similarity). {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 -!- SUBUNIT: Homodimer. {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Host cell membrane {ECO:0000250}; Lipid-anchor
CC {ECO:0000250}; Cytoplasmic side {ECO:0000250}. Host cytoplasm, host
CC perinuclear region {ECO:0000250}. Virion {ECO:0000250}. Secreted.
CC Note=Predominantly found in the paranuclear area, probably in the TGN.
CC Correct localization requires PACS1. Also associates with the inner
CC plasma membrane through its N-terminal domain. Nef stimulates its own
CC export via the release of exosomes. Also incorporated in virions at a
CC rate of about 10 molecules per virion, where it is cleaved (By
CC similarity). {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. This domain is also involved in binding to p53
CC (By similarity). {ECO:0000250}.
CC -!- DOMAIN: The SH3-binding domain constituted of PxxP motifs mediates
CC binding to several Src family proteins thereby regulating their
CC tyrosine kinase activity. {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the lentivirus primate group Nef protein family.
CC {ECO:0000305}.
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DR EMBL; AF447763; AAO13967.1; -; Genomic_RNA.
DR SMR; Q8AIH4; -.
DR PRIDE; Q8AIH4; -.
DR Proteomes; UP000007222; Genome.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0044220; C:host cell perinuclear region of cytoplasm; IEA:UniProtKB-SubCell.
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:0017124; F:SH3 domain binding; 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 Apoptosis; Early protein; Host cell membrane; Host cytoplasm;
KW Host membrane; Host-virus interaction; Lipoprotein; Membrane; Myristate;
KW Phosphoprotein; Secreted; SH3-binding; Viral immunoevasion; Virion;
KW Virulence.
FT INIT_MET 1
FT /note="Removed; by host"
FT /evidence="ECO:0000250"
FT CHAIN 2..195
FT /note="Protein Nef"
FT /id="PRO_0000248192"
FT REGION 2..53
FT /note="N-terminal; associates with the host plasma
FT membrane"
FT /evidence="ECO:0000250"
FT REGION 7..22
FT /note="Necessary for MHC-I internalization"
FT /evidence="ECO:0000250"
FT REGION 59..61
FT /note="Acidic"
FT REGION 65..74
FT /note="SH3-binding"
FT /evidence="ECO:0000250"
FT REGION 65..74
FT /note="SH3-binding; interaction with Src family tyrosine
FT kinases"
FT /evidence="ECO:0000250"
FT REGION 104..120
FT /note="Mediates dimerization"
FT /evidence="ECO:0000250"
FT REGION 144..171
FT /note="Binding to ATP6V1H"
FT /evidence="ECO:0000250"
FT MOTIF 68..71
FT /note="PxxP"
FT MOTIF 155..156
FT /note="Di-leucine internalization motif; necessary for CD4
FT internalization"
FT /evidence="ECO:0000250"
FT LIPID 2
FT /note="N-myristoyl glycine; by host"
FT /evidence="ECO:0000250"
SQ SEQUENCE 195 AA; 22007 MW; 490D82A8874330FB CRC64;
MGNIFGRWPG ARKAIEDLHN TSSEPVGQAS QDLQNKGGLT TNTLGTSADV LEYSADHTEE
EVGFPVRPAV PMRPMTEKLA IDLSWFLKEK GGLDGLFFSP KRAAILDTWM YNTQGVFPDW
QNYTPGPGIR YPLCRGWLFK LVPVDPPEDD EKNILLHPAC SHGTTDPDGE TLIWRFDSSL
ARRHIARERY PEYFK
