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Database: UniProt
Entry: NEF_SIVTN
LinkDB: NEF_SIVTN
Original site: 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   17-JUN-2020, entry version 83.
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; 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-lymphocytes 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}.
DR   EMBL; AF447763; AAO13967.1; -; Genomic_RNA.
DR   SMR; 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:0019012; C:virion; IEA:UniProtKB-SubCell.
DR   GO; GO:0005525; F:GTP binding; IEA:InterPro.
DR   GO; GO:0017124; F:SH3 domain binding; IEA:UniProtKB-KW.
DR   GO; GO:0030683; P:mitigation of host immune response by virus; IEA:UniProtKB-KW.
DR   GO; GO:0009405; P:pathogenesis; 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
//
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