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Database: UniProt
Entry: NEF_HV1H2
LinkDB: NEF_HV1H2
Original site: NEF_HV1H2 
ID   NEF_HV1H2               Reviewed;         206 AA.
AC   P04601; O09780; Q85587;
DT   13-AUG-1987, integrated into UniProtKB/Swiss-Prot.
DT   09-FEB-2010, sequence version 5.
DT   17-JUN-2020, entry version 155.
DE   RecName: Full=Protein Nef {ECO:0000255|HAMAP-Rule:MF_04078};
DE   AltName: Full=3'ORF {ECO:0000255|HAMAP-Rule:MF_04078};
DE   AltName: Full=Negative factor {ECO:0000255|HAMAP-Rule:MF_04078};
DE            Short=F-protein {ECO:0000255|HAMAP-Rule:MF_04078};
DE   Contains:
DE     RecName: Full=C-terminal core protein {ECO:0000255|HAMAP-Rule:MF_04078};
GN   Name=nef {ECO:0000255|HAMAP-Rule:MF_04078};
OS   Human immunodeficiency virus type 1 group M subtype B (isolate HXB2)
OS   (HIV-1).
OC   Viruses; Ortervirales; Retroviridae; Orthoretrovirinae; Lentivirus.
OX   NCBI_TaxID=11706;
OH   NCBI_TaxID=9606; Homo sapiens (Human).
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RX   PubMed=2999715; DOI=10.1093/nar/13.22.8219;
RA   Ratner L., Starcich B.R., Josephs S.F., Hahn B.H., Reddy E.P., Livak K.J.,
RA   Petteway S.R. Jr., Pearson M.L., Haseltine W.A., Arya S.K., Wong-staal F.;
RT   "Polymorphism of the 3' open reading frame of the virus associated with the
RT   acquired immune deficiency syndrome, human T-lymphotropic virus type III.";
RL   Nucleic Acids Res. 13:8219-8229(1985).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RX   PubMed=3040055; DOI=10.1089/aid.1987.3.57;
RA   Ratner L., Fisher A., Jagodzinski L.L., Mitsuya H., Liou R.-S., Gallo R.C.,
RA   Wong-Staal F.;
RT   "Complete nucleotide sequences of functional clones of the AIDS virus.";
RL   AIDS Res. Hum. Retroviruses 3:57-69(1987).
RN   [3]
RP   SEQUENCE REVISION.
RA   Ratner L., Fisher A., Jagodzinski L.L., Mitsuya H., Liou R.-S., Gallo R.C.,
RA   Wong-Staal F.;
RL   Submitted (APR-1997) to the EMBL/GenBank/DDBJ databases.
RN   [4]
RP   INDUCTION.
RX   PubMed=1707154;
RA   Hewlett I.K., Geyer S.J., Hawthorne C.A., Ruta M., Epstein J.S.;
RT   "Kinetics of early HIV-1 gene expression in infected H9 cells assessed by
RT   PCR.";
RL   Oncogene 6:491-493(1991).
RN   [5]
RP   FUNCTION, AND DILEUCINE MOTIF.
RC   STRAIN=Isolate HXB2-R7;
RX   PubMed=8124721; DOI=10.1016/0092-8674(94)90360-3;
RA   Aiken C., Konner J., Landau N.R., Lenburg M.E., Trono D.;
RT   "Nef induces CD4 endocytosis: requirement for a critical dileucine motif in
RT   the membrane-proximal CD4 cytoplasmic domain.";
RL   Cell 76:853-864(1994).
RN   [6]
RP   FUNCTION.
RX   PubMed=9450757; DOI=10.1038/34929;
RA   Collins K.L., Chen B.K., Kalams S.A., Walker B.D., Baltimore D.;
RT   "HIV-1 Nef protein protects infected primary cells against killing by
RT   cytotoxic T lymphocytes.";
RL   Nature 391:397-401(1998).
RN   [7]
RP   FUNCTION.
RC   STRAIN=Isolate HXB2-R7;
RX   PubMed=9971776;
RA   Mangasarian A., Piguet V., Wang J.-K., Chen Y.-L., Trono D.;
RT   "Nef-induced CD4 and major histocompatibility complex class I (MHC-I) down-
RT   regulation are governed by distinct determinants: N-terminal alpha helix
RT   and proline repeat of Nef selectively regulate MHC-I trafficking.";
RL   J. Virol. 73:1964-1973(1999).
RN   [8]
RP   FUNCTION, INTERACTION WITH HOST PACS1, AND SUBCELLULAR LOCATION.
RC   STRAIN=Isolate HXB2-R7;
RX   PubMed=10707087; DOI=10.1038/35004038;
RA   Piguet V., Wan L., Borel C., Mangasarian A., Demaurex N., Thomas G.,
RA   Trono D.;
RT   "HIV-1 Nef protein binds to the cellular protein PACS-1 to downregulate
RT   class I major histocompatibility complexes.";
RL   Nat. Cell Biol. 2:163-167(2000).
RN   [9]
RP   FUNCTION.
RX   PubMed=11593029; DOI=10.1073/pnas.221256498;
RA   Stumptner-Cuvelette P., Morchoisne S., Dugast M., Le Gall S., Raposo G.,
RA   Schwartz O., Benaroch P.;
RT   "HIV-1 Nef impairs MHC class II antigen presentation and surface
RT   expression.";
RL   Proc. Natl. Acad. Sci. U.S.A. 98:12144-12149(2001).
RN   [10]
RP   FUNCTION, MUTAGENESIS OF MET-20; 63-GLU--GLU-65; PRO-72 AND PRO-75, AND
RP   REGION ACIDIC.
RC   STRAIN=Isolate HXB2D;
RX   PubMed=12526811; DOI=10.1016/s0092-8674(02)01162-5;
RA   Blagoveshchenskaya A.D., Thomas L., Feliciangeli S.F., Hung C.-H.,
RA   Thomas G.;
RT   "HIV-1 Nef downregulates MHC-I by a PACS-1- and PI3K-regulated ARF6
RT   endocytic pathway.";
RL   Cell 111:853-866(2002).
RN   [11]
RP   IDENTIFICATION IN A AP1-NEF-MHC-I COMPLEX.
RX   PubMed=15569716; DOI=10.1083/jcb.200407031;
RA   Roeth J.F., Williams M., Kasper M.R., Filzen T.M., Collins K.L.;
RT   "HIV-1 Nef disrupts MHC-I trafficking by recruiting AP-1 to the MHC-I
RT   cytoplasmic tail.";
RL   J. Cell Biol. 167:903-913(2004).
RN   [12]
RP   ACIDIC REGION, INTERACTION WITH HOST PACS1, AND MUTAGENESIS OF
RP   62-GLU--GLU-65.
RX   PubMed=18653452; DOI=10.1128/jvi.00107-08;
RA   Baugh L.L., Garcia J.V., Foster J.L.;
RT   "Functional characterization of the human immunodeficiency virus type 1 Nef
RT   acidic domain.";
RL   J. Virol. 82:9657-9667(2008).
RN   [13]
RP   INTERACTION WITH HOST PACS2, INTERACTION WITH HOST PACS1, AND MUTAGENESIS
RP   OF 62-GLU--GLU-65.
RX   PubMed=18296443; DOI=10.1074/jbc.m707572200;
RA   Atkins K.M., Thomas L., Youker R.T., Harriff M.J., Pissani F., You H.,
RA   Thomas G.;
RT   "HIV-1 Nef binds PACS-2 to assemble a multikinase cascade that triggers
RT   major histocompatibility complex class I (MHC-I) down-regulation: analysis
RT   using short interfering RNA and knock-out mice.";
RL   J. Biol. Chem. 283:11772-11784(2008).
RN   [14]
RP   FUNCTION, AND IDENTIFICATION IN A AP1(MU)-NEF-MHC-I COMPLEX.
RX   PubMed=18073204; DOI=10.1074/jbc.m707760200;
RA   Wonderlich E.R., Williams M., Collins K.L.;
RT   "The tyrosine binding pocket in the adaptor protein 1 (AP-1) mu1 subunit is
RT   necessary for Nef to recruit AP-1 to the major histocompatibility complex
RT   class I cytoplasmic tail.";
RL   J. Biol. Chem. 283:3011-3022(2008).
RN   [15]
RP   CLEAVAGE BY VIRAL PROTEASE.
RX   PubMed=18987145; DOI=10.1128/jvi.01633-08;
RA   Laguette N., Benichou S., Basmaciogullari S.;
RT   "Human immunodeficiency virus type 1 Nef incorporation into virions does
RT   not increase infectivity.";
RL   J. Virol. 83:1093-1104(2009).
RN   [16]
RP   FUNCTION, AND SUBCELLULAR LOCATION.
RX   PubMed=19912576; DOI=10.1111/j.1600-0854.2009.01006.x;
RA   Lenassi M., Cagney G., Liao M., Vaupotic T., Bartholomeeusen K., Cheng Y.,
RA   Krogan N.J., Plemenitas A., Peterlin B.M.;
RT   "HIV Nef is secreted in exosomes and triggers apoptosis in bystander CD4(+)
RT   T cells.";
RL   Traffic 11:110-122(2010).
RN   [17]
RP   FUNCTION, AND IDENTIFICATION IN A AP1(MU)-NEF-MHC-I COMPLEX.
RX   PubMed=20020046; DOI=10.1371/journal.pone.0008364;
RA   Singh R.K., Lau D., Noviello C.M., Ghosh P., Guatelli J.C.;
RT   "An MHC-I cytoplasmic domain/HIV-1 Nef fusion protein binds directly to the
RT   mu subunit of the AP-1 endosomal coat complex.";
RL   PLoS ONE 4:E8364-E8364(2009).
RN   [18] {ECO:0000244|PDB:4NEE}
RP   X-RAY CRYSTALLOGRAPHY (2.88 ANGSTROMS) OF 63-203, INTERACTION WITH HOST AP2
RP   SUBUNIT ALPHA, AND INTERACTION WITH HOST AP2 SUBUNIT SIGMA2.
RX   PubMed=24473078; DOI=10.7554/elife.01754;
RA   Ren X., Park S.Y., Bonifacino J.S., Hurley J.H.;
RT   "How HIV-1 Nef hijacks the AP-2 clathrin adaptor to downregulate CD4.";
RL   Elife 3:E01754-E01754(2014).
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. {ECO:0000255|HAMAP-Rule:MF_04078,
CC       ECO:0000269|PubMed:9450757}.
CC   -!- FUNCTION: In infected CD4(+) T-lymphocytes, down-regulates the surface
CC       MHC-I, mature MHC-II, CD4, CD28, CCR5 and CXCR4 molecules. Mediates
CC       internalization and degradation of host CD4 through the interaction of
CC       with the cytoplasmic tail of CD4, the recruitment of AP-2 (clathrin
CC       adapter protein complex 2), internalization through clathrin coated
CC       pits, and subsequent transport to endosomes and lysosomes for
CC       degradation. Diverts host MHC-I molecules to the trans-Golgi network-
CC       associated endosomal compartments by an endocytic pathway to finally
CC       target them for degradation. MHC-I down-regulation may involve AP-1
CC       (clathrin adapter protein complex 1) or possibly Src family kinase-
CC       ZAP70/Syk-PI3K cascade recruited by PACS2. In consequence infected
CC       cells are masked for immune recognition by cytotoxic T-lymphocytes.
CC       Decreasing the number of immune receptors also prevents reinfection by
CC       more HIV particles (superinfection). Down-regulates host SERINC3 and
CC       SERINC5 thereby excluding these proteins from the viral particles.
CC       Virion infectivity is drastically higher when SERINC3 or SERINC5 are
CC       excluded from the viral envelope, because these host antiviral proteins
CC       impare the membrane fusion event necessary for subsequent virion
CC       penetration. {ECO:0000255|HAMAP-Rule:MF_04078,
CC       ECO:0000269|PubMed:12526811, ECO:0000269|PubMed:24473078,
CC       ECO:0000269|PubMed:8124721}.
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. {ECO:0000255|HAMAP-Rule:MF_04078}.
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. Inhibits the Fas and TNFR-
CC       mediated death signals by blocking MAP3K5/ASK1. Decreases the half-life
CC       of TP53, protecting the infected cell against p53-mediated apoptosis.
CC       Inhibits the apoptotic signals regulated by the Bcl-2 family proteins
CC       through the formation of a Nef/PI3-kinase/PAK2 complex that leads to
CC       activation of PAK2 and induces phosphorylation of Bad.
CC       {ECO:0000255|HAMAP-Rule:MF_04078}.
CC   -!- FUNCTION: Extracellular Nef protein targets CD4(+) T-lymphocytes for
CC       apoptosis by interacting with CXCR4 surface receptors.
CC       {ECO:0000255|HAMAP-Rule:MF_04078, ECO:0000269|PubMed:19912576}.
CC   -!- SUBUNIT: Monomer; cytosolic form. Homodimer; membrane bound form.
CC       Interacts with Nef associated p21-activated kinase (PAK2); this
CC       interaction activates PAK2. Associates with the Nef-MHC-I-AP1 complex;
CC       this complex is required for MHC-I internalization. Interacts (via C-
CC       terminus) with host PI3-kinase. Interacts with host PACS1; this
CC       interaction seems to be weak. Interacts with host PACS2. Interacts with
CC       host LCK and MAPK3; these interactions inhibit the kinase activity of
CC       the latters. Interacts with host ATP6V1H; this interaction may play a
CC       role in CD4 endocytosis. Associates with the CD4-Nef-AP2 complex; this
CC       complex is required for CD4 internalization. Interacts with host AP2
CC       subunit alpha and AP2 subunit sigma2. Interacts with TCR-zeta chain;
CC       this interaction up-regulates the Fas ligand (FasL) surface expression.
CC       Interacts with host HCK, LYN, and SRC; these interactions activate the
CC       Src family kinases. Interacts with MAP3K5; this interaction inhibits
CC       the Fas and TNFR-mediated death signals. Interacts with beta-COP and
CC       PTE1. Interacts with human RACK1; this increases Nef phosphorylation by
CC       PKC. Interacts with TP53; this interaction decreases the half-life of
CC       TP53, protecting the infected cell against p53-mediated apoptosis.
CC       {ECO:0000255|HAMAP-Rule:MF_04078, ECO:0000269|PubMed:10707087,
CC       ECO:0000269|PubMed:15569716, ECO:0000269|PubMed:18073204,
CC       ECO:0000269|PubMed:18296443, ECO:0000269|PubMed:18653452,
CC       ECO:0000269|PubMed:20020046, ECO:0000269|PubMed:24473078}.
CC   -!- INTERACTION:
CC       P04601; O14734: ACOT8; Xeno; NbExp=7; IntAct=EBI-6164028, EBI-1237371;
CC   -!- SUBCELLULAR LOCATION: Host cell membrane {ECO:0000255|HAMAP-
CC       Rule:MF_04078}; Lipid-anchor {ECO:0000255|HAMAP-Rule:MF_04078};
CC       Cytoplasmic side {ECO:0000255|HAMAP-Rule:MF_04078}. Virion
CC       {ECO:0000255|HAMAP-Rule:MF_04078}. Secreted {ECO:0000255|HAMAP-
CC       Rule:MF_04078, ECO:0000269|PubMed:19912576}. Host Golgi apparatus
CC       membrane {ECO:0000255|HAMAP-Rule:MF_04078}. Note=TGN localization
CC       requires PACS1. Associates with the inner plasma membrane through its
CC       N-terminal domain. Nef stimulates its own export via the release of
CC       exosomes. Incorporated in virions at a rate of about 10 molecules per
CC       virion, where it is cleaved. {ECO:0000255|HAMAP-Rule:MF_04078,
CC       ECO:0000269|PubMed:19912576}.
CC   -!- INDUCTION: Expressed early in the viral replication cycle.
CC       {ECO:0000255|HAMAP-Rule:MF_04078, ECO:0000269|PubMed:1707154}.
CC   -!- DOMAIN: The dileucine internalization motif and a diacidic motif seem
CC       to be required for binding to AP-2. {ECO:0000255|HAMAP-Rule:MF_04078}.
CC   -!- DOMAIN: The acidic region binds to the sorting protein PACS-2, which
CC       targets Nef to the paranuclear region, enabling the PxxP motif to
CC       direct assembly of an SFK/ZAP-70/PI3K complex that accelerates
CC       endocytosis of cell-surface MHC-I. {ECO:0000255|HAMAP-Rule:MF_04078,
CC       ECO:0000269|PubMed:12526811}.
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
CC       TP53. {ECO:0000255|HAMAP-Rule:MF_04078}.
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. The same motifs also mediates the association
CC       with MAPK3, PI3-kinase and TCR-zeta. {ECO:0000255|HAMAP-Rule:MF_04078}.
CC   -!- PTM: Phosphorylated on serine residues, probably by host PKCdelta and
CC       theta. {ECO:0000255|HAMAP-Rule:MF_04078}.
CC   -!- PTM: Myristoylated. {ECO:0000255|HAMAP-Rule:MF_04078}.
CC   -!- PTM: The virion-associated Nef proteins are cleaved by the viral
CC       protease to release the soluble C-terminal core protein. Nef is
CC       probably cleaved concomitantly with viral structural proteins on
CC       maturation of virus particles. {ECO:0000255|HAMAP-Rule:MF_04078}.
CC   -!- MISCELLANEOUS: HIV-1 lineages are divided in three main groups, M (for
CC       Major), O (for Outlier), and N (for New, or Non-M, Non-O). The vast
CC       majority of strains found worldwide belong to the group M. Group O
CC       seems to be endemic to and largely confined to Cameroon and neighboring
CC       countries in West Central Africa, where these viruses represent a small
CC       minority of HIV-1 strains. The group N is represented by a limited
CC       number of isolates from Cameroonian persons. The group M is further
CC       subdivided in 9 clades or subtypes (A to D, F to H, J and K).
CC       {ECO:0000255|HAMAP-Rule:MF_04078}.
CC   -!- SIMILARITY: Belongs to the lentivirus primate group Nef protein family.
CC       {ECO:0000255|HAMAP-Rule:MF_04078}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=AAB50263.1; Type=Miscellaneous discrepancy; Note=Readthrough of a premature stop codon in position 123 that truncates the Nef protein. The sequence displayed is that of wild-type full-length HXB2-R7 clone.; Evidence={ECO:0000305};
CC       Sequence=AAC82597.1; Type=Miscellaneous discrepancy; Note=Readthrough of a premature stop codon in position 123 that truncates the Nef protein. The sequence displayed is that of wild-type full-length HXB2-R7 clone.; Evidence={ECO:0000305};
CC       Sequence=CAA26946.1; Type=Miscellaneous discrepancy; Note=Readthrough of a premature stop codon in position 123 that truncates the Nef protein. The sequence displayed is that of wild-type full-length HXB2-R7 clone.; Evidence={ECO:0000305};
CC   -!- WEB RESOURCE: Name=BioAfrica HIV proteomics resource; Note=Nef entry;
CC       URL="http://www.bioafrica.net/proteomics/NEFprot.html";
DR   EMBL; X03187; CAA26946.1; ALT_SEQ; Genomic_RNA.
DR   EMBL; K03455; AAB50263.1; ALT_SEQ; Genomic_RNA.
DR   EMBL; AF033819; AAC82597.1; ALT_SEQ; Genomic_RNA.
DR   RefSeq; NP_057857.2; NC_001802.1.
DR   PDB; 3RL2; X-ray; 2.39 A; C=73-82.
DR   PDB; 4NEE; X-ray; 2.88 A; C/E/H/K=63-203.
DR   PDB; 4WU5; X-ray; 2.40 A; C/F=134-141.
DR   PDB; 4WU7; X-ray; 2.30 A; C/F=136-141.
DR   PDB; 5HGA; X-ray; 2.20 A; C/F=136-141.
DR   PDB; 5HGB; X-ray; 2.40 A; C/F/I/L=134-141.
DR   PDB; 5HGD; X-ray; 2.07 A; C/F=136-142.
DR   PDB; 5HGH; X-ray; 2.39 A; C=134-142.
DR   PDBsum; 3RL2; -.
DR   PDBsum; 4NEE; -.
DR   PDBsum; 4WU5; -.
DR   PDBsum; 4WU7; -.
DR   PDBsum; 5HGA; -.
DR   PDBsum; 5HGB; -.
DR   PDBsum; 5HGD; -.
DR   PDBsum; 5HGH; -.
DR   SMR; P04601; -.
DR   BioGRID; 1205545; 75.
DR   DIP; DIP-61724N; -.
DR   ELM; P04601; -.
DR   IntAct; P04601; 10.
DR   PRIDE; P04601; -.
DR   GeneID; 156110; -.
DR   KEGG; vg:156110; -.
DR   KO; K22891; -.
DR   Reactome; R-HSA-162585; Uncoating of the HIV Virion.
DR   Reactome; R-HSA-162588; Budding and maturation of HIV virion.
DR   Reactome; R-HSA-162599; Late Phase of HIV Life Cycle.
DR   Reactome; R-HSA-164939; Nef mediated downregulation of CD28 cell surface expression.
DR   Reactome; R-HSA-164940; Nef mediated downregulation of MHC class I complex cell surface expression.
DR   Reactome; R-HSA-164944; Nef and signal transduction.
DR   Reactome; R-HSA-167590; Nef Mediated CD4 Down-regulation.
DR   Reactome; R-HSA-173107; Binding and entry of HIV virion.
DR   Reactome; R-HSA-175474; Assembly Of The HIV Virion.
DR   Reactome; R-HSA-182218; Nef Mediated CD8 Down-regulation.
DR   Proteomes; UP000002241; Genome.
DR   Proteomes; UP000105453; Genome.
DR   GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR   GO; GO:0044178; C:host cell Golgi membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0020002; C:host cell plasma membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0016020; C:membrane; IEA:UniProtKB-UniRule.
DR   GO; GO:0019012; C:virion; IEA:UniProtKB-SubCell.
DR   GO; GO:0005525; F:GTP binding; IEA:UniProtKB-UniRule.
DR   GO; GO:0017124; F:SH3 domain binding; IEA:UniProtKB-UniRule.
DR   GO; GO:0019064; P:fusion of virus membrane with host plasma membrane; TAS:Reactome.
DR   GO; GO:0009405; P:pathogenesis; IEA:UniProtKB-KW.
DR   GO; GO:0050690; P:regulation of defense response to virus by virus; TAS:Reactome.
DR   GO; GO:0039504; P:suppression by virus of host adaptive immune response; IEA:UniProtKB-UniRule.
DR   GO; GO:0046776; P:suppression by virus of host antigen processing and presentation of peptide antigen via MHC class I; IEA:UniProtKB-UniRule.
DR   GO; GO:0039505; P:suppression by virus of host antigen processing and presentation of peptide antigen via MHC class II; IEA:UniProtKB-UniRule.
DR   GO; GO:0039521; P:suppression by virus of host autophagy; IEA:UniProtKB-UniRule.
DR   GO; GO:0019061; P:uncoating of virus; TAS:Reactome.
DR   GO; GO:0019058; P:viral life cycle; TAS:Reactome.
DR   GO; GO:0019068; P:virion assembly; TAS:Reactome.
DR   Gene3D; 3.30.62.10; -; 1.
DR   Gene3D; 4.10.890.10; -; 1.
DR   HAMAP; MF_04078; NEF_HIV; 1.
DR   IDEAL; IID90019; -.
DR   InterPro; IPR027480; HIV-1_Nef_anchor_sf.
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   1: Evidence at protein level;
KW   3D-structure; AIDS; Apoptosis; Early protein; Host cell membrane;
KW   Host Golgi apparatus; Host membrane; Host-virus interaction;
KW   Inhibition of host adaptive immune response by virus;
KW   Inhibition of host autophagy by virus;
KW   Inhibition of host MHC class I molecule presentation by virus;
KW   Inhibition of host MHC class II molecule presentation by virus;
KW   Lipoprotein; Membrane; Myristate; Phosphoprotein; Reference proteome;
KW   Secreted; SH3-binding; Viral immunoevasion; Virion; Virulence.
FT   INIT_MET        1
FT                   /note="Removed; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04078"
FT   CHAIN           2..206
FT                   /note="Protein Nef"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04078"
FT                   /id="PRO_0000038365"
FT   CHAIN           58..206
FT                   /note="C-terminal core protein"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04078"
FT                   /id="PRO_0000038366"
FT   REGION          62..65
FT                   /note="Acidic; interacts with host PACS1 and PACS2;
FT                   stabilizes the interaction of NEF/MHC-I with host AP1M1;
FT                   necessary for MHC-I internalization"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04078,
FT                   ECO:0000269|PubMed:10707087, ECO:0000269|PubMed:12526811"
FT   REGION          69..78
FT                   /note="SH3-binding; interaction with Src family tyrosine
FT                   kinases"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04078"
FT   REGION          108..124
FT                   /note="Mediates dimerization, Nef-PTE1 interaction"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04078"
FT   REGION          148..180
FT                   /note="Binding to ATP6V1H"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04078"
FT   MOTIF           72..75
FT                   /note="PxxP; stabilizes the interaction of NEF/MHC-I with
FT                   host AP1M1; necessary for MHC-I internalization"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04078,
FT                   ECO:0000269|PubMed:12526811"
FT   MOTIF           164..165
FT                   /note="Dileucine internalization motif; necessary for CD4
FT                   internalization"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04078,
FT                   ECO:0000269|PubMed:8124721"
FT   MOTIF           174..175
FT                   /note="Diacidic; necessary for CD4 internalization"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04078"
FT   SITE            20
FT                   /note="Might play a role in AP-1 recruitment to the Nef-
FT                   MHC-I complex"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04078,
FT                   ECO:0000269|PubMed:18073204"
FT   SITE            57..58
FT                   /note="Cleavage; by viral protease"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04078"
FT   MOD_RES         6
FT                   /note="Phosphoserine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04078"
FT   LIPID           2
FT                   /note="N-myristoyl glycine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04078"
FT   MUTAGEN         20
FT                   /note="M->A: Complete loss of Nef-induced MHC-I down-
FT                   regulation, MHC-I is internalized but not sequestred in
FT                   TGN."
FT                   /evidence="ECO:0000269|PubMed:12526811"
FT   MUTAGEN         62..65
FT                   /note="EEEE->AAAA: Complete loss of Nef-induced MHC-I down-
FT                   regulation, MHC-I is not internalized. Reduced interaction
FT                   with host PACS1 and PACS2."
FT                   /evidence="ECO:0000269|PubMed:18296443,
FT                   ECO:0000269|PubMed:18653452"
FT   MUTAGEN         62..65
FT                   /note="EEEE->AAEA: About 50% loss of Nef-induced MHC-I
FT                   down-regulation."
FT                   /evidence="ECO:0000269|PubMed:18296443,
FT                   ECO:0000269|PubMed:18653452"
FT   MUTAGEN         62..65
FT                   /note="EEEE->AEAA: About 50% loss of Nef-induced MHC-I
FT                   down-regulation."
FT                   /evidence="ECO:0000269|PubMed:18296443,
FT                   ECO:0000269|PubMed:18653452"
FT   MUTAGEN         62..65
FT                   /note="EEEE->DDDD: No effect on Nef-induced MHC-I down-
FT                   regulation."
FT                   /evidence="ECO:0000269|PubMed:18296443,
FT                   ECO:0000269|PubMed:18653452"
FT   MUTAGEN         62..64
FT                   /note="EEE->AAA: About 50% loss of Nef-induced MHC-I down-
FT                   regulation."
FT   MUTAGEN         62..63
FT                   /note="EE->AA: Almost no effect on Nef-induced MHC-I down-
FT                   regulation."
FT   MUTAGEN         63..65
FT                   /note="EEE->AAA: About 50% loss of Nef-induced MHC-I down-
FT                   regulation."
FT                   /evidence="ECO:0000269|PubMed:12526811"
FT   MUTAGEN         63..64
FT                   /note="EE->AA: Almost no effect on Nef-induced MHC-I down-
FT                   regulation."
FT   MUTAGEN         64..65
FT                   /note="EE->AA: Almost no effect on Nef-induced MHC-I down-
FT                   regulation."
FT   MUTAGEN         72
FT                   /note="P->A: Complete loss of Nef-induced MHC-I down-
FT                   regulation, MHC-I is not internalized; when associated with
FT                   A-75."
FT                   /evidence="ECO:0000269|PubMed:12526811"
FT   MUTAGEN         75
FT                   /note="P->A: Complete loss of Nef-induced MHC-I down-
FT                   regulation, MHC-I is not internalized; when associated with
FT                   A-72."
FT                   /evidence="ECO:0000269|PubMed:12526811"
FT   MUTAGEN         123
FT                   /note="D->E: Complete loss of Nef-induced MHC-I down-
FT                   regulation, CD4 down-regulation, and enhancement of
FT                   infectivity. Activates PAK2 twofold over wild-type levels."
FT   CONFLICT        29
FT                   /note="R -> G (in Ref. 1; CAA26946)"
FT                   /evidence="ECO:0000305"
FT   HELIX           81..94
FT                   /evidence="ECO:0000244|PDB:4NEE"
FT   HELIX           104..118
FT                   /evidence="ECO:0000244|PDB:4NEE"
FT   STRAND          130..132
FT                   /evidence="ECO:0000244|PDB:4NEE"
FT   STRAND          136..138
FT                   /evidence="ECO:0000244|PDB:4NEE"
FT   STRAND          143..147
FT                   /evidence="ECO:0000244|PDB:4NEE"
FT   HELIX           150..157
FT                   /evidence="ECO:0000244|PDB:4NEE"
FT   HELIX           167..170
FT                   /evidence="ECO:0000244|PDB:4NEE"
FT   STRAND          172..175
FT                   /evidence="ECO:0000244|PDB:4NEE"
FT   STRAND          181..185
FT                   /evidence="ECO:0000244|PDB:4NEE"
FT   HELIX           188..191
FT                   /evidence="ECO:0000244|PDB:4NEE"
FT   HELIX           194..198
FT                   /evidence="ECO:0000244|PDB:4NEE"
FT   HELIX           200..202
FT                   /evidence="ECO:0000244|PDB:4NEE"
SQ   SEQUENCE   206 AA;  23469 MW;  5A26976E95483E9C CRC64;
     MGGKWSKSSV IGWPTVRERM RRAEPAADRV GAASRDLEKH GAITSSNTAA TNAACAWLEA
     QEEEEVGFPV TPQVPLRPMT YKAAVDLSHF LKEKGGLEGL IHSQRRQDIL DLWIYHTQGY
     FPDWQNYTPG PGVRYPLTFG WCYKLVPVEP DKIEEANKGE NTSLLHPVSL HGMDDPEREV
     LEWRFDSRLA FHHVARELHP EYFKNC
//
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