HBZ_HTL1C
ID HBZ_HTL1C Reviewed; 209 AA.
AC P0C745;
DT 28-JUL-2009, integrated into UniProtKB/Swiss-Prot.
DT 28-JUL-2009, sequence version 1.
DT 03-AUG-2022, entry version 32.
DE RecName: Full=HTLV-1 basic zipper factor;
DE Short=HBZ;
GN Name=HBZ;
OS Human T-cell leukemia virus 1 (isolate Caribbea HS-35 subtype A) (HTLV-1).
OC Viruses; Riboviria; Pararnavirae; Artverviricota; Revtraviricetes;
OC Ortervirales; Retroviridae; Orthoretrovirinae; Deltaretrovirus.
OX NCBI_TaxID=11927;
OH NCBI_TaxID=9606; Homo sapiens (Human).
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=2899128; DOI=10.1099/0022-1317-69-7-1695;
RA Malik K.T.A., Even J., Karpas A.;
RT "Molecular cloning and complete nucleotide sequence of an adult T cell
RT leukaemia virus/human T cell leukaemia virus type I (ATLV/HTLV-I) isolate
RT of Caribbean origin: relationship to other members of the ATLV/HTLV-I
RT subgroup.";
RL J. Gen. Virol. 69:1695-1710(1988).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RA Chappey C.;
RL Submitted (NOV-1997) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP FUNCTION.
RX PubMed=16424388; DOI=10.1182/blood-2005-11-4551;
RA Arnold J., Yamamoto B., Li M., Phipps A.J., Younis I., Lairmore M.D.,
RA Green P.L.;
RT "Enhancement of infectivity and persistence in vivo by HBZ, a natural
RT antisense coded protein of HTLV-1.";
RL Blood 107:3976-3982(2006).
RN [4]
RP FUNCTION, AND INTERACTION WITH HOST EP300 AND CREBBP.
RX PubMed=18599479; DOI=10.1074/jbc.m803116200;
RA Clerc I., Polakowski N., Andre-Arpin C., Cook P., Barbeau B., Mesnard J.M.,
RA Lemasson I.;
RT "An interaction between the human T cell leukemia virus type 1 basic
RT leucine zipper factor (HBZ) and the KIX domain of p300/CBP contributes to
RT the down-regulation of tax-dependent viral transcription by HBZ.";
RL J. Biol. Chem. 283:23903-23913(2008).
RN [5]
RP FUNCTION.
RX PubMed=21552325; DOI=10.1371/journal.ppat.1002025;
RA Zhi H., Yang L., Kuo Y.L., Ho Y.K., Shih H.M., Giam C.Z.;
RT "NF-kappaB hyper-activation by HTLV-1 tax induces cellular senescence, but
RT can be alleviated by the viral anti-sense protein HBZ.";
RL PLoS Pathog. 7:E1002025-E1002025(2011).
RN [6]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH HOST EP300.
RX PubMed=22434882; DOI=10.1093/nar/gks244;
RA Wurm T., Wright D.G., Polakowski N., Mesnard J.M., Lemasson I.;
RT "The HTLV-1-encoded protein HBZ directly inhibits the acetyl transferase
RT activity of p300/CBP.";
RL Nucleic Acids Res. 40:5910-5925(2012).
RN [7]
RP FUNCTION, INTERACTION WITH HOST IRF7 AND IKBKE, AND SUBCELLULAR LOCATION.
RX PubMed=28768861; DOI=10.1128/jvi.00853-17;
RA Narulla M.S., Alasiri A., Charmier L., Noonan S., Conroy D., Hall W.W.,
RA Sheehy N.;
RT "Positive and Negative Regulation of Type I Interferons by the Human T Cell
RT Leukemia Virus Antisense Protein HBZ.";
RL J. Virol. 91:0-0(2017).
RN [8]
RP REVIEW ON FUNCTION.
RX PubMed=29515558; DOI=10.3389/fmicb.2018.00285;
RA Fochi S., Mutascio S., Bertazzoni U., Zipeto D., Romanelli M.G.;
RT "HTLV Deregulation of the NF-kappaB Pathway: An Update on Tax and Antisense
RT Proteins Role.";
RL Front. Microbiol. 9:285-285(2018).
RN [9]
RP INTERACTION WITH HOST UBR5, AND UBIQUITINATION.
RX PubMed=29441057; DOI=10.3389/fmicb.2018.00080;
RA Panfil A.R., Al-Saleem J., Howard C.M., Shkriabai N., Kvaratskhelia M.,
RA Green P.L.;
RT "Stability of the HTLV-1 Antisense-Derived Protein, HBZ, Is Regulated by
RT the E3 Ubiquitin-Protein Ligase, UBR5.";
RL Front. Microbiol. 9:80-80(2018).
RN [10]
RP FUNCTION, AND INTERACTION WITH HOST XRCC5 AND XRCC6.
RX PubMed=29769340; DOI=10.1128/jvi.00672-18;
RA Rushing A.W., Hoang K., Polakowski N., Lemasson I.;
RT "non-homologous end joining (NHEJ).";
RL J. Virol. 0:0-0(2018).
CC -!- FUNCTION: Enhances viral infectivity and persistence, and facilitates
CC proliferation of HTLV-1-infected lymphocytes (PubMed:16424388).
CC Mechanistically, inhibits Tax-mediated viral replication and NF-kappa-B
CC activation (PubMed:18599479, PubMed:21552325). Plays a role in allowing
CC infected T-cells to escape the cytotoxic T-lymphocyte response by
CC maintaining low levels of viral protein production. Inhibits also host
CC EP300 histone acetyltransferase (HAT) activity, reducing levels of
CC acetylated histone H3 at 'Lys-18' (H3K18ac) in infected cells
CC (PubMed:22434882). Contributes to the accumulation of chromosomal
CC abnormalities by inhibiting double-stranded DNA breaks (DSB) repair
CC through the NHEJ pathway (PubMed:29769340). Participates in the
CC modulation of host immune response at multiple levels contributing to
CC abnormal interferon signaling and viral pathogenesis (PubMed:28768861).
CC {ECO:0000269|PubMed:16424388, ECO:0000269|PubMed:18599479,
CC ECO:0000269|PubMed:21552325, ECO:0000269|PubMed:22434882,
CC ECO:0000269|PubMed:28768861, ECO:0000269|PubMed:29769340}.
CC -!- SUBUNIT: Interacts with host ATF4; this interaction inhibits viral RNA
CC transcriptional activation by preventing ATF4 binding to Tax-responsive
CC elements. Interacts with host CREB1; this interaction inhibits host
CC CREB1 transcriptional activity. Interacts with host JUN, JUNB and JUND
CC (By similarity). Interacts with host EP300 and CREBBP; these
CC interactions inhibit the association of the coactivators with the viral
CC promoter (PubMed:18599479, PubMed:22434882). Interacts with host UBR5;
CC this interaction regulates HBZ protein stability (PubMed:29441057).
CC Interacts with XRCC5 and XRCC6 (PubMed:29769340). Interacts with IRF7
CC and IKBKE; this interaction modulates host interferon signaling
CC (PubMed:28768861). {ECO:0000250|UniProtKB:P0C746,
CC ECO:0000269|PubMed:18599479, ECO:0000269|PubMed:22434882,
CC ECO:0000269|PubMed:28768861, ECO:0000269|PubMed:29441057,
CC ECO:0000269|PubMed:29769340}.
CC -!- INTERACTION:
CC P0C745; Q8N1K5: THEMIS; Xeno; NbExp=3; IntAct=EBI-16218595, EBI-2873538;
CC -!- SUBCELLULAR LOCATION: Host nucleus {ECO:0000269|PubMed:22434882,
CC ECO:0000269|PubMed:28768861}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=HBZ;
CC IsoId=P0C745-1; Sequence=Displayed;
CC Name=HBZ-SI;
CC IsoId=P0C745-2; Sequence=VSP_037728;
CC -!- DOMAIN: Contains three nuclear localization signals NLS-1 and NLS-2,
CC corresponding to two regions rich in basic amino acids, and NLS-3
CC corresponding to its DNA-binding domain.
CC -!- PTM: Ubiquitinated by host E3 ligase UBR5 leading to HBZ degradation.
CC {ECO:0000269|PubMed:29441057}.
CC -!- MISCELLANEOUS: Expressed from antisense transcripts. While mRNA
CC expression levels of HBZ-SI were similar to those of HBZ, HBZ-SI seems
CC slightly more expressed at the protein level ex vivo.
CC -!- SIMILARITY: Belongs to the HTLV-1 HBZ protein family. {ECO:0000305}.
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DR EMBL; D13784; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AF033817; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR SMR; P0C745; -.
DR IntAct; P0C745; 1.
DR Proteomes; UP000001061; Genome.
DR Proteomes; UP000110593; Genome.
DR GO; GO:0042025; C:host cell nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0003677; F:DNA binding; IEA:UniProtKB-KW.
DR GO; GO:0039503; P:suppression by virus of host innate immune response; IEA:UniProtKB-KW.
DR GO; GO:0039644; P:suppression by virus of host NF-kappaB cascade; IDA:UniProtKB.
DR InterPro; IPR026220; HTLV1ZIPPER.
DR PRINTS; PR02097; HTLV1ZIPPER.
PE 1: Evidence at protein level;
KW Alternative splicing; DNA-binding; Host nucleus; Host-virus interaction;
KW Inhibition of host innate immune response by virus; Reference proteome;
KW Ubl conjugation; Viral immunoevasion.
FT CHAIN 1..209
FT /note="HTLV-1 basic zipper factor"
FT /id="PRO_0000379888"
FT REGION 41..165
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 87..92
FT /note="Nuclear localization signal 1"
FT /evidence="ECO:0000250"
FT MOTIF 116..120
FT /note="Nuclear localization signal 2"
FT /evidence="ECO:0000250"
FT MOTIF 137..141
FT /note="Nuclear localization signal 3"
FT /evidence="ECO:0000250"
FT COMPBIAS 43..63
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 72..163
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VAR_SEQ 1..7
FT /note="MVNFVSV -> MAAS (in isoform HBZ-SI)"
FT /evidence="ECO:0000305"
FT /id="VSP_037728"
SQ SEQUENCE 209 AA; 24936 MW; 55323CF9189A7D54 CRC64;
MVNFVSVGLF RCLPVPCPED LLVEELVDGL LSLEEELKDK EEEETVLDGL LSLEEESRGR
LRRGPPGGKA PPRGETHRDR QRRAEEKRKR KKEREKEEEK QIAEYLKRKE EEKARRRKRA
EEKAADFARR KQEEQERRER KWRQGAEKAK QHSARKEKMQ ELGVDGYTRQ LEGEVESLEA
ERRRLLQEKE DLMGEVNYWQ GRLEAMWLQ
