ID Q90VU7_9HIV1 Unreviewed; 206 AA. AC Q90VU7; DT 01-DEC-2001, integrated into UniProtKB/TrEMBL. DT 01-DEC-2001, sequence version 1. DT 02-DEC-2020, entry version 135. DE RecName: Full=Protein Nef {ECO:0000256|HAMAP-Rule:MF_04078}; DE AltName: Full=3'ORF {ECO:0000256|HAMAP-Rule:MF_04078}; DE AltName: Full=Negative factor {ECO:0000256|HAMAP-Rule:MF_04078}; DE Short=F-protein {ECO:0000256|HAMAP-Rule:MF_04078}; DE Contains: DE RecName: Full=C-terminal core protein {ECO:0000256|HAMAP-Rule:MF_04078}; GN Name=nef {ECO:0000256|HAMAP-Rule:MF_04078, GN ECO:0000313|EMBL:AAB60579.1}; OS Human immunodeficiency virus 1. OC Viruses; Riboviria; Pararnavirae; Artverviricota; Revtraviricetes; OC Ortervirales; Retroviridae; Orthoretrovirinae; Lentivirus. OX NCBI_TaxID=11676 {ECO:0000313|EMBL:AAB60579.1, ECO:0000313|Proteomes:UP000160754}; OH NCBI_TaxID=9606; Homo sapiens (Human). RN [1] {ECO:0000313|EMBL:AAB60579.1, ECO:0000313|Proteomes:UP000160754} RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=NL4-3 {ECO:0000313|EMBL:AAB60579.1}; RX PubMed=3016298; RA Adachi A., Gendelman H.E., Koenig S., Folks T., Willey R., Rabson A., RA Martin M.A.; RT "Production of acquired immunodeficiency syndrome-associated retrovirus in RT human and nonhuman cells transfected with an infectious molecular clone."; RL J. Virol. 59:284-291(1986). RN [2] {ECO:0000313|EMBL:AAB60579.1, ECO:0000313|Proteomes:UP000160754} RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=NL4-3 {ECO:0000313|EMBL:AAB60579.1}; RX PubMed=7483282; DOI=10.1006/viro.1995.1548; RA Salminen M.O., Koch C., Sanders-Buell E., Ehrenberg P.K., Michael N.L., RA Carr J.K., Burke D.S., McCutchan F.E.; RT "Recovery of virtually full-length HIV-1 provirus of diverse subtypes from RT primary virus cultures using the polymerase chain reaction."; RL Virology 213:80-86(1995). RN [3] {ECO:0000313|EMBL:AAB60579.1} RP NUCLEOTIDE SEQUENCE. RC STRAIN=NL4-3 {ECO:0000313|EMBL:AAB60579.1}; RA Salminen M.S.; RL Submitted (MAY-1995) to the EMBL/GenBank/DDBJ databases. RN [4] {ECO:0000313|EMBL:CAH64567.1} RP NUCLEOTIDE SEQUENCE. RX PubMed=16032733; DOI=10.1002/jmv.20408; RA Parreira R., Padua E., Piedade J., Venenno T., Paixao M.T., Esteves A.; RT "Genetic analysis of human immunodeficiency virus type 1 nef in Portugal: RT subtyping, identification of mosaic genes, and amino acid sequence RT variability."; RL J. Med. Virol. 77:8-16(2005). RN [5] {ECO:0000313|EMBL:ABY49078.1} RP NUCLEOTIDE SEQUENCE. RC STRAIN=184003/B8 {ECO:0000313|EMBL:ABY49078.1}; RX PubMed=18184702; DOI=10.1128/JVI.02260-07; RA Turk G., Gherardi M.M., Laufer N., Saracco M., Luzzi R., Cox J.H., Cahn P., RA Salomon H.; RT "Magnitude, breadth, and functional profile of T-cell responses during RT human immunodeficiency virus primary infection with B and BF viral RT variants."; RL J. Virol. 82:2853-2866(2008). RN [6] {ECO:0000313|EMBL:ACM50127.1} RP NUCLEOTIDE SEQUENCE. RC STRAIN=F781 {ECO:0000313|EMBL:ACM50127.1}; RX PubMed=19036810; DOI=10.1128/JVI.01061-08; RA Wang Y.E., Li B., Carlson J.M., Streeck H., Gladden A.D., Goodman R., RA Schneidewind A., Power K.A., Toth I., Frahm N., Alter G., Brander C., RA Carrington M., Walker B.D., Altfeld M., Heckerman D., Allen T.M.; RT "Protective HLA class I alleles that restrict acute-phase CD8+ T-cell RT responses are associated with viral escape mutations located in highly RT conserved regions of human immunodeficiency virus type 1."; RL J. Virol. 83:1845-1855(2009). RN [7] {ECO:0000313|EMBL:ADB03681.1} RP NUCLEOTIDE SEQUENCE. RC STRAIN=BEC73 {ECO:0000313|EMBL:ADB03681.1}; RA Miura T., Brumme C.J., Brockman M.A., Brumme Z.L., Pereyra F., Block B.L., RA Trocha A., John M., Mallal S., Harrigan P.R., Walker B.D.; RT "HLA-associated viral mutations are common in Human immunodeficiency virus RT type 1 elite controllers."; RL J. Virol. 84:1212-1212(2010). RN [8] {ECO:0000313|EMBL:ADJ17496.1} RP NUCLEOTIDE SEQUENCE. RC STRAIN=5569.6 {ECO:0000313|EMBL:ADJ17498.1}, 5569.7 RC {ECO:0000313|EMBL:ADJ17499.1}, 5569.81 {ECO:0000313|EMBL:ADJ17500.1}, RC 5569.82 {ECO:0000313|EMBL:ADJ17501.1}, 5569.83 RC {ECO:0000313|EMBL:ADJ17502.1}, and 5569.at RC {ECO:0000313|EMBL:ADJ17496.1}; RX PubMed=20463068; DOI=10.1128/JVI.00619-10; RA Specht A., Telenti A., Martinez R., Fellay J., Bailes E., Evans D.T., RA Carrington M., Hahn B.H., Goldstein D.B., Kirchhoff F.; RT "Counteraction of HLA-C-mediated immune control of HIV-1 by Nef."; RL J. Virol. 84:7300-7311(2010). RN [9] {ECO:0000213|PDB:4EMZ, ECO:0000213|PDB:4EN2} RP X-RAY CRYSTALLOGRAPHY (2.58 ANGSTROMS). RX PubMed=22705789; DOI=10.1038/nsmb.2328; RA Jia X., Singh R., Homann S., Yang H., Guatelli J., Xiong Y.; RT "Structural basis of evasion of cellular adaptive immunity by HIV-1 Nef."; RL Nat. Struct. Mol. Biol. 19:701-706(2012). RN [10] {ECO:0000313|EMBL:AFM44079.1, ECO:0000313|Proteomes:UP000114822} RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=HIV/US/BID-V4141 {ECO:0000313|EMBL:AFM44079.1}; RX PubMed=22412369; DOI=10.1371/journal.ppat.1002529; RA Henn M.R., Boutwell C.L., Charlebois P., Lennon N.J., Power K.A., RA Macalalad A.R., Berlin A.M., Malboeuf C.M., Ryan E.M., Gnerre S., RA Zody M.C., Erlich R.L., Green L.M., Berical A., Wang Y., Casali M., RA Streeck H., Bloom A.K., Dudek T., Tully D., Newman R., Axten K.L., RA Gladden A.D., Battis L., Kemper M., Zeng Q., Shea T.P., Gujja S., RA Zedlack C., Gasser O., Brander C., Hess C., Gunthard H.F., Brumme Z.L., RA Brumme C.J., Bazner S., Rychert J., Tinsley J.P., Mayer K.H., Rosenberg E., RA Pereyra F., Levin J.Z., Young S.K., Jessen H., Altfeld M., Birren B.W., RA Walker B.D., Allen T.M.; RT "Whole genome deep sequencing of HIV-1 reveals the impact of early minor RT variants upon immune recognition during acute infection."; RL PLoS Pathog. 8:E1002529-E1002529(2012). RN [11] {ECO:0000313|EMBL:AGV32938.1} RP NUCLEOTIDE SEQUENCE. RC STRAIN=16CB1_20F5 {ECO:0000313|EMBL:AGV32938.1}, 16CB1_20F7 RC {ECO:0000313|EMBL:AGV32939.1}, and 22CB6_23G3 RC {ECO:0000313|EMBL:AGV33378.1}; RA Ho Y.-C., Shan L., Hosmane N.N., Wang J., Laskey S.B., Rosenbloom D.I., RA Lai J., Blankson J.N., Siliciano R.F.; RT "Replication-competent non-induced proviruses in the latent reservoir RT increase barrier to HIV-1 cure."; RL Submitted (AUG-2013) to the EMBL/GenBank/DDBJ databases. RN [12] {ECO:0000313|EMBL:AIW80604.1} RP NUCLEOTIDE SEQUENCE. RA Whitcomb J.; RT "Reference sequence used by Monogram Biosciences for genotyping assays of RT HIV."; RL Submitted (AUG-2014) to the EMBL/GenBank/DDBJ databases. RN [13] {ECO:0000313|EMBL:AKR15819.1} RP NUCLEOTIDE SEQUENCE. RC STRAIN=FP_24 {ECO:0000313|EMBL:AKR15834.1}, FP_25 RC {ECO:0000313|EMBL:AKR15835.1}, FP_26 {ECO:0000313|EMBL:AKR15836.1}, RC FP_27 {ECO:0000313|EMBL:AKR15837.1}, FP_28 RC {ECO:0000313|EMBL:AKR15838.1}, FP_29 {ECO:0000313|EMBL:AKR15839.1}, RC FP_30 {ECO:0000313|EMBL:AKR15840.1}, FP_31 RC {ECO:0000313|EMBL:AKR15841.1}, FP_32 {ECO:0000313|EMBL:AKR15842.1}, RC LTNP_4 {ECO:0000313|EMBL:AKR15819.1}, LTNP_7 RC {ECO:0000313|EMBL:AKR15822.1}, LTNP_8 {ECO:0000313|EMBL:AKR15823.1}, RC LTNP_9 {ECO:0000313|EMBL:AKR15824.1}, SP_11 RC {ECO:0000313|EMBL:AKR15825.1}, SP_12 {ECO:0000313|EMBL:AKR15826.1}, RC SP_13 {ECO:0000313|EMBL:AKR15827.1}, SP_14 RC {ECO:0000313|EMBL:AKR15828.1}, SP_15 {ECO:0000313|EMBL:AKR15829.1}, RC SP_19 {ECO:0000313|EMBL:AKR15830.1}, SP_20 RC {ECO:0000313|EMBL:AKR15831.1}, SP_22 {ECO:0000313|EMBL:AKR15832.1}, RC SP_23 {ECO:0000313|EMBL:AKR15833.1}, SP_5 RC {ECO:0000313|EMBL:AKR15820.1}, and SP_6 {ECO:0000313|EMBL:AKR15821.1}; RA Kondapi A.K., Rao S.K., Bommakanti A.; RT "Analysis of human immunodeficiency virus type-1 nef sequences in RT paediatric seropositive population."; RL Submitted (FEB-2015) to the EMBL/GenBank/DDBJ databases. RN [14] {ECO:0000313|EMBL:AKZ17633.1} RP NUCLEOTIDE SEQUENCE. RA Singh J., Ronsard L., Ramachandran V.G., Banerjea A.C.; RT "Genetic and functional characterization of HIV-1 nef gene."; RL Submitted (MAY-2015) to the EMBL/GenBank/DDBJ databases. RN [15] {ECO:0000213|PDB:6CM9, ECO:0000213|PDB:6D83, ECO:0000213|PDB:6D84} RP STRUCTURE BY ELECTRON MICROSCOPY (3.73 ANGSTROMS). RX PubMed=30053425; DOI=10.1016/j.cell.2018.07.004; RA Morris K.L., Buffalo C.Z., Sturzel C.M., Heusinger E., Kirchhoff F., RA Ren X., Hurley J.H.; RT "HIV-1 Nefs Are Cargo-Sensitive AP-1 Trimerization Switches in Tetherin RT Downregulation."; RL Cell 174:659-671.e14(2018). RN [16] {ECO:0000313|EMBL:QCS35511.1} RP NUCLEOTIDE SEQUENCE. RC STRAIN=Strain0526 {ECO:0000313|EMBL:QCS35511.1}; RX PubMed=30939815; RA Banin A.N., Tuen M., Bimela J.S., Tongo M., Zappile P., RA Khodadadi-Jamayran A., Nanfack A.J., Meli J., Wang X., Mbanya D., RA Ngogang J., Heguy A., Nyambi P.N., Fokunang C., Duerr R.; RT "Development of a Versatile, Near Full Genome Amplification and Sequencing RT Approach for a Broad Variety of HIV-1 Group M Variants."; RL Viruses 11:0-E317(2019). RN [17] {ECO:0000213|PDB:6URI} RP X-RAY CRYSTALLOGRAPHY (3.00 ANGSTROMS) OF 26-206. RX PubMed=32719457; DOI=10.1038/s41594-020-0463-z; RA Kwon Y., Kaake R.M., Echeverria I., Suarez M., Karimian Shamsabadi M., RA Stoneham C., Ramirez P.W., Kress J., Singh R., Sali A., Krogan N., RA Guatelli J., Jia X.; RT "Structural basis of CD4 downregulation by HIV-1 Nef."; RL Nat. Struct. Mol. Biol. 0:0-0(2020). 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:0000256|HAMAP-Rule:MF_04078}. CC -!- FUNCTION: Extracellular Nef protein targets CD4(+) T-lymphocytes for CC apoptosis by interacting with CXCR4 surface receptors. CC {ECO:0000256|HAMAP-Rule:MF_04078}. 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:0000256|HAMAP-Rule:MF_04078}. 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:0000256|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 host BAD. CC {ECO:0000256|HAMAP-Rule:MF_04078}. 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:0000256|HAMAP-Rule:MF_04078}. CC -!- INTERACTION: CC Q90VU7; P08631: HCK; Xeno; NbExp=2; IntAct=EBI-7460704, EBI-346340; CC Q90VU7; Q8WUM4: PDCD6IP; Xeno; NbExp=4; IntAct=EBI-7460704, EBI-310624; CC -!- SUBCELLULAR LOCATION: Host cell membrane {ECO:0000256|HAMAP- CC Rule:MF_04078}; Lipid-anchor {ECO:0000256|HAMAP-Rule:MF_04078}; CC Cytoplasmic side {ECO:0000256|HAMAP-Rule:MF_04078}. Virion CC {ECO:0000256|HAMAP-Rule:MF_04078}. Secreted {ECO:0000256|HAMAP- CC Rule:MF_04078}. Host Golgi apparatus membrane {ECO:0000256|HAMAP- CC Rule:MF_04078}. Note=TGN localization requires PACS1. Associates with CC the inner plasma membrane through its N-terminal domain. Nef stimulates CC its own export via the release of exosomes. Incorporated in virions at CC a rate of about 10 molecules per virion, where it is cleaved. CC {ECO:0000256|HAMAP-Rule:MF_04078}. CC -!- INDUCTION: Expressed early in the viral replication cycle. CC {ECO:0000256|HAMAP-Rule:MF_04078}. 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:0000256|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:0000256|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:0000256|HAMAP-Rule:MF_04078}. CC -!- DOMAIN: The dileucine internalization motif and a diacidic motif seem CC to be required for binding to AP-2. {ECO:0000256|HAMAP-Rule:MF_04078}. CC -!- PTM: Myristoylated. {ECO:0000256|HAMAP-Rule:MF_04078}. CC -!- PTM: Phosphorylated on serine residues, probably by host PKCdelta and CC theta. {ECO:0000256|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:0000256|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:0000256|HAMAP-Rule:MF_04078}. CC -!- SIMILARITY: Belongs to the lentivirus primate group Nef protein family. CC {ECO:0000256|ARBA:ARBA00006933, ECO:0000256|HAMAP-Rule:MF_04078, CC ECO:0000256|RuleBase:RU000344}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; U26942; AAB60579.1; -; Genomic_DNA. DR EMBL; EU312175; ABY49078.1; -; Genomic_DNA. DR EMBL; FJ469736; ACM50127.1; -; Genomic_DNA. DR EMBL; GU046594; ADB03681.1; -; Genomic_DNA. DR EMBL; HM244488; ADJ17496.1; -; Genomic_RNA. DR EMBL; HM244490; ADJ17498.1; -; Genomic_RNA. DR EMBL; HM244491; ADJ17499.1; -; Genomic_RNA. DR EMBL; HM244492; ADJ17500.1; -; Genomic_RNA. DR EMBL; HM244493; ADJ17501.1; -; Genomic_RNA. DR EMBL; HM244494; ADJ17502.1; -; Genomic_RNA. DR EMBL; JQ403040; AFM44079.1; -; Genomic_RNA. DR EMBL; KF526172; AGV32938.1; -; Genomic_DNA. DR EMBL; KF526173; AGV32939.1; -; Genomic_DNA. DR EMBL; KF526308; AGV33378.1; -; Genomic_DNA. DR EMBL; KM390026; AIW80604.1; -; Viral_cRNA. DR EMBL; KP851719; AKR15819.1; -; Genomic_DNA. DR EMBL; KP851720; AKR15820.1; -; Genomic_DNA. DR EMBL; KP851721; AKR15821.1; -; Genomic_DNA. DR EMBL; KP851722; AKR15822.1; -; Genomic_DNA. DR EMBL; KP851723; AKR15823.1; -; Genomic_DNA. DR EMBL; KP851724; AKR15824.1; -; Genomic_DNA. DR EMBL; KP851725; AKR15825.1; -; Genomic_DNA. DR EMBL; KP851726; AKR15826.1; -; Genomic_DNA. DR EMBL; KP851727; AKR15827.1; -; Genomic_DNA. DR EMBL; KP851728; AKR15828.1; -; Genomic_DNA. DR EMBL; KP851729; AKR15829.1; -; Genomic_DNA. DR EMBL; KP851730; AKR15830.1; -; Genomic_DNA. DR EMBL; KP851731; AKR15831.1; -; Genomic_DNA. DR EMBL; KP851732; AKR15832.1; -; Genomic_DNA. DR EMBL; KP851733; AKR15833.1; -; Genomic_DNA. DR EMBL; KP851734; AKR15834.1; -; Genomic_DNA. DR EMBL; KP851735; AKR15835.1; -; Genomic_DNA. DR EMBL; KP851736; AKR15836.1; -; Genomic_DNA. DR EMBL; KP851737; AKR15837.1; -; Genomic_DNA. DR EMBL; KP851738; AKR15838.1; -; Genomic_DNA. DR EMBL; KP851739; AKR15839.1; -; Genomic_DNA. DR EMBL; KP851740; AKR15840.1; -; Genomic_DNA. DR EMBL; KP851741; AKR15841.1; -; Genomic_DNA. DR EMBL; KP851742; AKR15842.1; -; Genomic_DNA. DR EMBL; KR818790; AKZ17633.1; -; Genomic_DNA. DR EMBL; KR818792; AKZ17634.1; -; Genomic_DNA. DR EMBL; AJ850868; CAH64567.1; -; Genomic_DNA. DR EMBL; MK086129; QCS35511.1; -; Genomic_RNA. DR PIR; JC5400; JC5400. DR PIR; JQ1620; JQ1620. DR PIR; S03244; S03244. DR PIR; S43467; S43467. DR PDB; 4EMZ; X-ray; 2.90 A; B/C=1-206. DR PDB; 4EN2; X-ray; 2.58 A; B/C=1-206. DR PDB; 6CM9; EM; 3.73 A; L/N/T=1-206. DR PDB; 6D83; EM; 4.27 A; L/T=1-206. DR PDB; 6D84; EM; 6.72 A; L/O/R/T=1-206. DR PDB; 6DFF; EM; 3.90 A; L/T=1-206. DR PDB; 6URI; X-ray; 3.00 A; N=26-206. DR PDBsum; 4EMZ; -. DR PDBsum; 4EN2; -. DR PDBsum; 6CM9; -. DR PDBsum; 6D83; -. DR PDBsum; 6D84; -. DR PDBsum; 6DFF; -. DR DIP; DIP-43762N; -. DR IntAct; Q90VU7; 13. DR Proteomes; UP000114822; Genome. DR Proteomes; UP000160754; 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:0051117; F:ATPase binding; ISS:UniProtKB. DR GO; GO:0042609; F:CD4 receptor binding; ISS:UniProtKB. DR GO; GO:0005525; F:GTP binding; IEA:UniProtKB-UniRule. DR GO; GO:0042288; F:MHC class I protein binding; ISS:UniProtKB. DR GO; GO:0019901; F:protein kinase binding; ISS:UniProtKB. DR GO; GO:0017124; F:SH3 domain binding; IEA:UniProtKB-UniRule. DR GO; GO:0005102; F:signaling receptor binding; ISS:UniProtKB. DR GO; GO:0031996; F:thioesterase binding; ISS:UniProtKB. DR GO; GO:0045225; P:negative regulation of CD4 production; ISS:UniProtKB. DR GO; GO:0009405; P:pathogenesis; ISS:UniProtKB. DR GO; GO:0050848; P:regulation of calcium-mediated signaling; ISS:UniProtKB. DR GO; GO:0052085; P:suppression by symbiont of host T-cell mediated immune response; ISS:UniProtKB. 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; ISS:UniProtKB. 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:0019058; P:viral life cycle; ISS:UniProtKB. DR Gene3D; 3.30.62.10; -; 1. DR Gene3D; 4.10.890.10; -; 1. DR HAMAP; MF_04078; NEF_HIV; 1. 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 {ECO:0000213|PDB:4EMZ, ECO:0000213|PDB:4EN2, KW ECO:0000213|PDB:6CM9, ECO:0000213|PDB:6D83}; KW Apoptosis {ECO:0000256|ARBA:ARBA00022703, ECO:0000256|HAMAP-Rule:MF_04078}; KW Early protein {ECO:0000256|HAMAP-Rule:MF_04078}; KW Host cell membrane {ECO:0000256|HAMAP-Rule:MF_04078}; KW Host Golgi apparatus {ECO:0000256|HAMAP-Rule:MF_04078}; KW Host membrane {ECO:0000256|ARBA:ARBA00022870, ECO:0000256|HAMAP- KW Rule:MF_04078}; Host-virus interaction {ECO:0000256|HAMAP-Rule:MF_04078}; KW Inhibition of host adaptive immune response by virus {ECO:0000256|HAMAP- KW Rule:MF_04078}; KW Inhibition of host autophagy by virus {ECO:0000256|HAMAP-Rule:MF_04078}; KW Inhibition of host MHC class I molecule presentation by virus KW {ECO:0000256|HAMAP-Rule:MF_04078}; KW Inhibition of host MHC class II molecule presentation by virus KW {ECO:0000256|HAMAP-Rule:MF_04078}; KW Lipoprotein {ECO:0000256|HAMAP-Rule:MF_04078, KW ECO:0000256|RuleBase:RU000344}; Membrane {ECO:0000256|HAMAP-Rule:MF_04078}; KW Myristate {ECO:0000256|ARBA:ARBA00022707, ECO:0000256|HAMAP-Rule:MF_04078, KW ECO:0000256|RuleBase:RU000344}; KW Phosphoprotein {ECO:0000256|ARBA:ARBA00022553, ECO:0000256|HAMAP- KW Rule:MF_04078}; Reference proteome {ECO:0000313|Proteomes:UP000160754}; KW Secreted {ECO:0000256|HAMAP-Rule:MF_04078}; KW SH3-binding {ECO:0000256|ARBA:ARBA00023036, ECO:0000256|HAMAP- KW Rule:MF_04078}; KW Viral immunoevasion {ECO:0000256|ARBA:ARBA00023280, ECO:0000256|HAMAP- KW Rule:MF_04078, ECO:0000256|RuleBase:RU000344}; KW Virion {ECO:0000256|HAMAP-Rule:MF_04078}; KW Virulence {ECO:0000256|ARBA:ARBA00023026, ECO:0000256|HAMAP-Rule:MF_04078, KW ECO:0000256|RuleBase:RU000344}. FT INIT_MET 1 FT /note="Removed; by host" FT /evidence="ECO:0000256|HAMAP-Rule:MF_04078" FT CHAIN 2..206 FT /note="Protein Nef" FT /evidence="ECO:0000256|HAMAP-Rule:MF_04078" FT /id="PRO_5027174303" FT CHAIN 58..206 FT /note="C-terminal core protein" FT /evidence="ECO:0000256|HAMAP-Rule:MF_04078" FT /id="PRO_5027174302" 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:0000256|HAMAP-Rule:MF_04078" FT REGION 69..78 FT /note="SH3-binding; interaction with Src family tyrosine FT kinases" FT /evidence="ECO:0000256|HAMAP-Rule:MF_04078" FT REGION 108..124 FT /note="Mediates dimerization, Nef-PTE1 interaction" FT /evidence="ECO:0000256|HAMAP-Rule:MF_04078" FT REGION 148..180 FT /note="Binding to ATP6V1H" FT /evidence="ECO:0000256|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:0000256|HAMAP-Rule:MF_04078" FT MOTIF 164..165 FT /note="Dileucine internalization motif; necessary for CD4 FT internalization" FT /evidence="ECO:0000256|HAMAP-Rule:MF_04078" FT MOTIF 174..175 FT /note="Diacidic; necessary for CD4 internalization" FT /evidence="ECO:0000256|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:0000256|HAMAP-Rule:MF_04078" FT SITE 57..58 FT /note="Cleavage; by viral protease" FT /evidence="ECO:0000256|HAMAP-Rule:MF_04078" FT MOD_RES 6 FT /note="Phosphoserine; by host" FT /evidence="ECO:0000256|HAMAP-Rule:MF_04078" FT LIPID 2 FT /note="N-myristoyl glycine; by host" FT /evidence="ECO:0000256|HAMAP-Rule:MF_04078" SQ SEQUENCE 206 AA; 23367 MW; 65AF3B6184DC2FE7 CRC64; MGGKWSKSSV IGWPAVRERM RRAEPAADGV GAVSRDLEKH GAITSSNTAA NNAACAWLEA QEEEEVGFPV TPQVPLRPMT YKAAVDLSHF LKEKGGLEGL IHSQRRQDIL DLWIYHTQGY FPDWQNYTPG PGVRYPLTFG WCYKLVPVEP DKVEEANKGE NTSLLHPVSL HGMDDPEREV LEWRFDSRLA FHHVARELHP EYFKNC //