LANA1_HHV8P
ID LANA1_HHV8P Reviewed; 1129 AA.
AC Q9QR71;
DT 16-OCT-2013, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 03-AUG-2022, entry version 84.
DE RecName: Full=Protein LANA1;
GN Name=LANA1; ORFNames=ORF73;
OS Human herpesvirus 8 type P (isolate GK18) (HHV-8) (Kaposi's
OS sarcoma-associated herpesvirus).
OC Viruses; Duplodnaviria; Heunggongvirae; Peploviricota; Herviviricetes;
OC Herpesvirales; Herpesviridae; Gammaherpesvirinae; Rhadinovirus.
OX NCBI_TaxID=868565;
OH NCBI_TaxID=9606; Homo sapiens (Human).
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=10400794; DOI=10.1128/jvi.73.8.6953-6963.1999;
RA Glenn M., Rainbow L., Aurade F., Davison A., Schulz T.F.;
RT "Identification of a spliced gene from Kaposi's sarcoma-associated
RT herpesvirus encoding a protein with similarities to latent membrane
RT proteins 1 and 2A of Epstein-Barr virus.";
RL J. Virol. 73:6953-6963(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16760382; DOI=10.1099/vir.0.81919-0;
RA Rezaee S.A.R., Cunningham C., Davison A.J., Blackbourn D.J.;
RT "Kaposi's sarcoma-associated herpesvirus immune modulation: an overview.";
RL J. Gen. Virol. 87:1781-1804(2006).
RN [3]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=10213686; DOI=10.1126/science.284.5414.641;
RA Ballestas M.E., Chatis P.A., Kaye K.M.;
RT "Efficient persistence of extrachromosomal KSHV DNA mediated by latency-
RT associated nuclear antigen.";
RL Science 284:641-644(1999).
RN [4]
RP SUBCELLULAR LOCATION.
RX PubMed=10580050; DOI=10.1099/0022-1317-80-11-2889;
RA Szekely L., Kiss C., Mattsson K., Kashuba E., Pokrovskaja K., Juhasz A.,
RA Holmvall P., Klein G.;
RT "Human herpesvirus-8-encoded LNA-1 accumulates in
RT heterochromatin- associated nuclear bodies.";
RL J. Gen. Virol. 80:2889-2900(1999).
RN [5]
RP INTERACTION WITH HOST BRD2, AND FUNCTION.
RX PubMed=16227282; DOI=10.1128/jvi.79.21.13618-13629.2005;
RA Viejo-Borbolla A., Ottinger M., Bruening E., Buerger A., Koenig R.,
RA Kati E., Sheldon J.A., Schulz T.F.;
RT "Brd2/RING3 interacts with a chromatin-binding domain in the Kaposi's
RT Sarcoma-associated herpesvirus latency-associated nuclear antigen 1 (LANA-
RT 1) that is required for multiple functions of LANA-1.";
RL J. Virol. 79:13618-13629(2005).
RN [6]
RP FUNCTION, AND INTERACTION WITH HOST HISTONES H2A AND H2B.
RX PubMed=16469929; DOI=10.1126/science.1120541;
RA Barbera A.J., Chodaparambil J.V., Kelley-Clarke B., Joukov V., Walter J.C.,
RA Luger K., Kaye K.M.;
RT "The nucleosomal surface as a docking station for Kaposi's sarcoma
RT herpesvirus LANA.";
RL Science 311:856-861(2006).
RN [7]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH HOST RELA; CUL5; ELOB
RP AND ELOC.
RX PubMed=21697472; DOI=10.1128/jvi.00733-11;
RA Li X., Liang D., Lin X., Robertson E.S., Lan K.;
RT "Kaposi's sarcoma-associated herpesvirus-encoded latency-associated nuclear
RT antigen reduces interleukin-8 expression in endothelial cells and impairs
RT neutrophil chemotaxis by degrading nuclear p65.";
RL J. Virol. 85:8606-8615(2011).
RN [8]
RP FUNCTION, INTERACTION WITH HOST TRIM28, AND SUBCELLULAR LOCATION.
RX PubMed=24741090; DOI=10.1128/jvi.00596-14;
RA Sun R., Liang D., Gao Y., Lan K.;
RT "Kaposi's sarcoma-associated herpesvirus-encoded LANA interacts with host
RT KAP1 to facilitate establishment of viral latency.";
RL J. Virol. 88:7331-7344(2014).
RN [9]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH HOST NFE2L2/NRF2.
RX PubMed=25995248; DOI=10.1128/jvi.00895-15;
RA Gjyshi O., Roy A., Dutta S., Veettil M.V., Dutta D., Chandran B.;
RT "Activated Nrf2 Interacts with Kaposi's Sarcoma-Associated Herpesvirus
RT Latency Protein LANA-1 and Host Protein KAP1 To Mediate Global Lytic Gene
RT Repression.";
RL J. Virol. 89:7874-7892(2015).
RN [10]
RP FUNCTION, AND INTERACTION WITH HOST BUB1 AND PCNA.
RX PubMed=26223641; DOI=10.1128/jvi.01524-15;
RA Sun Z., Jha H.C., Robertson E.S.;
RT "Bub1 in Complex with LANA Recruits PCNA To Regulate Kaposi's Sarcoma-
RT Associated Herpesvirus Latent Replication and DNA Translesion Synthesis.";
RL J. Virol. 89:10206-10218(2015).
RN [11]
RP FUNCTION, INTERACTION WITH HOST NAP1L1, AND SUBCELLULAR LOCATION.
RX PubMed=27599637; DOI=10.1038/srep32633;
RA Gupta N., Thakker S., Verma S.C.;
RT "KSHV encoded LANA recruits Nucleosome Assembly Protein NAP1L1 for
RT regulating viral DNA replication and transcription.";
RL Sci. Rep. 6:32633-32633(2016).
RN [12]
RP FUNCTION.
RX PubMed=28696226; DOI=10.1083/jcb.201702013;
RA Chiu Y.F., Sugden A.U., Fox K., Hayes M., Sugden B.;
RT "Kaposi's sarcoma-associated herpesvirus stably clusters its genomes across
RT generations to maintain itself extrachromosomally.";
RL J. Cell Biol. 216:2745-2758(2017).
RN [13]
RP X-RAY CRYSTALLOGRAPHY (2.87 ANGSTROMS) OF 975-1113, REGION, AND SUBUNIT.
RX PubMed=25947153; DOI=10.1073/pnas.1421804112;
RA Hellert J., Weidner-Glunde M., Krausze J., Lunsdorf H., Ritter C.,
RA Schulz T.F., Luhrs T.;
RT "The 3D structure of Kaposi sarcoma herpesvirus LANA C-terminal domain
RT bound to DNA.";
RL Proc. Natl. Acad. Sci. U.S.A. 112:6694-6699(2015).
RN [14]
RP X-RAY CRYSTALLOGRAPHY (2.70 ANGSTROMS) OF 5-15.
RX PubMed=28534629; DOI=10.1021/jacs.7b02138;
RA Amamoto Y., Aoi Y., Nagashima N., Suto H., Yoshidome D., Arimura Y.,
RA Osakabe A., Kato D., Kurumizaka H., Kawashima S.A., Yamatsugu K., Kanai M.;
RT "Synthetic Posttranslational Modifications: Chemical Catalyst-Driven
RT Regioselective Histone Acylation of Native Chromatin.";
RL J. Am. Chem. Soc. 139:7568-7576(2017).
CC -!- FUNCTION: Multifunctional protein that plays a role in the replication
CC and long-term persistence of the viral episomal genome in dividing
CC cells. Binds to mitotic chromosomes via its N-terminal region and to a
CC 16-bp imperfect palindrome within the origin of replication (oriP)
CC located in the viral terminal repeat (TR) through its C-terminal.
CC Tethers viral episomes to chromosomes during mitosis. Plays a critical
CC role in the shutdown of lytic gene expression during the early stage of
CC infection by interacting with host TRIM28. Also plays a role in the
CC repression of host NF-kappa-B activity upon TNF-alpha stimulation by
CC promoting the proteasomal degradation of host RELA (PubMed:21697472).
CC {ECO:0000269|PubMed:10213686, ECO:0000269|PubMed:16227282,
CC ECO:0000269|PubMed:16469929, ECO:0000269|PubMed:21697472,
CC ECO:0000269|PubMed:24741090, ECO:0000269|PubMed:25995248,
CC ECO:0000269|PubMed:26223641, ECO:0000269|PubMed:27599637,
CC ECO:0000269|PubMed:28696226}.
CC -!- SUBUNIT: Homooligomer (PubMed:25947153). Interacts with host BRD2
CC (PubMed:16227282). Interacts with host RELA, ELOB, ELOC and CUL5; these
CC interactions induce the proteasomal degradation of host RELA
CC (PubMed:21697472). Interacts with host TRIM28 and NFE2L2/NRF2; these
CC interactions are essential for the shutdown of lytic gene expression
CC during the early stage of infection (PubMed:24741090, PubMed:25995248).
CC Interacts (via N-terminus) with host histones H2A and H2B; these
CC interactions are essential to dock LANA1 onto chromosomes
CC (PubMed:16469929). Interacts with host BUB1 and PCNA (PubMed:26223641).
CC Interacts with host NAP1L1; this interaction is required for LANA1-
CC dependent DNA replication (PubMed:27599637).
CC {ECO:0000269|PubMed:16227282, ECO:0000269|PubMed:16469929,
CC ECO:0000269|PubMed:21697472, ECO:0000269|PubMed:24741090,
CC ECO:0000269|PubMed:25947153, ECO:0000269|PubMed:25995248,
CC ECO:0000269|PubMed:26223641, ECO:0000269|PubMed:27599637}.
CC -!- INTERACTION:
CC Q9QR71; P26358: DNMT1; Xeno; NbExp=2; IntAct=EBI-15602554, EBI-719459;
CC Q9QR71; Q9Y6K1: DNMT3A; Xeno; NbExp=3; IntAct=EBI-15602554, EBI-923653;
CC Q9QR71; Q9UBC3: DNMT3B; Xeno; NbExp=2; IntAct=EBI-15602554, EBI-80125;
CC Q9QR71; Q6FI13: H2AC19; Xeno; NbExp=3; IntAct=EBI-15602554, EBI-353620;
CC Q9QR71; O60814: H2BC12; Xeno; NbExp=3; IntAct=EBI-15602554, EBI-4409738;
CC Q9QR71; P62805: H4C9; Xeno; NbExp=2; IntAct=EBI-15602554, EBI-302023;
CC -!- SUBCELLULAR LOCATION: Host nucleus {ECO:0000269|PubMed:10213686,
CC ECO:0000269|PubMed:10580050, ECO:0000269|PubMed:21697472,
CC ECO:0000269|PubMed:25995248, ECO:0000269|PubMed:27599637}.
CC Note=Colocalizes with viral episomes on host chromosomes.
CC {ECO:0000269|PubMed:10213686, ECO:0000269|PubMed:10580050}.
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DR EMBL; AF148805; AAD46501.1; -; Genomic_DNA.
DR RefSeq; YP_001129431.1; NC_009333.1.
DR PDB; 2ND0; NMR; -; B=1098-1116.
DR PDB; 4UZB; X-ray; 2.87 A; A/B=975-1113.
DR PDB; 4UZC; X-ray; 3.70 A; A/B/C/D=980-1116.
DR PDB; 5GTC; X-ray; 2.70 A; K=5-15.
DR PDBsum; 2ND0; -.
DR PDBsum; 4UZB; -.
DR PDBsum; 4UZC; -.
DR PDBsum; 5GTC; -.
DR BMRB; Q9QR71; -.
DR SASBDB; Q9QR71; -.
DR SMR; Q9QR71; -.
DR BioGRID; 1777030; 119.
DR DIP; DIP-61278N; -.
DR IntAct; Q9QR71; 8.
DR BindingDB; Q9QR71; -.
DR iPTMnet; Q9QR71; -.
DR GeneID; 4961527; -.
DR KEGG; vg:4961527; -.
DR PRO; PR:Q9QR71; -.
DR Proteomes; UP000000942; Genome.
DR GO; GO:0042025; C:host cell nucleus; IDA:UniProtKB.
DR GO; GO:0003677; F:DNA binding; IEA:UniProtKB-KW.
DR GO; GO:0039644; P:suppression by virus of host NF-kappaB cascade; IDA:UniProtKB.
DR Gene3D; 3.30.70.390; -; 1.
DR InterPro; IPR037007; EBNA1_DNA-bd_sf.
PE 1: Evidence at protein level;
KW 3D-structure; DNA-binding; Host nucleus; Host-virus interaction;
KW Inhibition of host NF-kappa-B by virus; Reference proteome.
FT CHAIN 1..1129
FT /note="Protein LANA1"
FT /id="PRO_0000423799"
FT REGION 1..988
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1008..1129
FT /note="DNA-binding domain"
FT /evidence="ECO:0000269|PubMed:25947153"
FT REGION 1110..1129
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 24..54
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 83..120
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 157..187
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 188..216
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 291..324
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 325..415
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 422..476
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 477..526
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 527..598
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 599..892
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT HELIX 991..993
FT /evidence="ECO:0007829|PDB:4UZB"
FT HELIX 996..998
FT /evidence="ECO:0007829|PDB:4UZB"
FT HELIX 999..1009
FT /evidence="ECO:0007829|PDB:4UZB"
FT HELIX 1010..1013
FT /evidence="ECO:0007829|PDB:4UZB"
FT STRAND 1023..1030
FT /evidence="ECO:0007829|PDB:4UZB"
FT HELIX 1032..1041
FT /evidence="ECO:0007829|PDB:4UZB"
FT STRAND 1043..1049
FT /evidence="ECO:0007829|PDB:4UZB"
FT STRAND 1058..1061
FT /evidence="ECO:0007829|PDB:4UZB"
FT STRAND 1067..1075
FT /evidence="ECO:0007829|PDB:4UZB"
FT HELIX 1076..1092
FT /evidence="ECO:0007829|PDB:4UZB"
FT STRAND 1100..1108
FT /evidence="ECO:0007829|PDB:4UZB"
SQ SEQUENCE 1129 AA; 131346 MW; 8F63855B45F79109 CRC64;
MAPPGMRLRS GRSTGAPLTR GSCRKRNRSP ERCDLGDDLH LQPRRKHVAD SVDGRECGPH
TLPIPGSPTV FTSGLPAFVS SPTLPVAPIP SPAPATPLPP PALLPPVTTS SSPIPPSHPV
SPGTTDTHSP SPALPPTQSP ESSQRPPLSS PTGRPDSSTP MRPPPSQQTT PPHSPTTPPP
EPPSKSSPDS LAPSTLRSLR KRRLSSPQGP STLNPICQSP PVSPPRCDFA NRSVYPPWAT
ESPIYVGSSS DGDTPPRQPP TSPISIGSSS PSEGSWGDDT AMLVLLAEIA EEASKNEKEC
SENNQAGEDN GDNEISKESQ VDKDDNDNKD DEEEQETDEE DEEDDEEDDE EDDEEDDEED
DEEDDEEDDE EEDEEEDEEE DEEEDEEEEE DEEDDDDEDN EDEEDDEEED KKEDEEDGGD
GNKTLSIQSS QQQQEPQQQE PQQQEPQQQE PQQQEPQQQE PQQQEPQQQE PQQREPQQRE
PQQREPQQRE PQQREPQQRE PQQREPQQRE PQQREPQQRE PQQREPQQRE PQQQEPQQQE
PQQQEPQQQE PQQQEPQQQE PQQQEPQQQE PQQQEPQQQE PQQQEPQQQE PQQQDEQQQD
EQQQDEQQQD EQQQDEQQQD EQQQDEQQQD EQEQQDEQQQ DEQQQQDEQE QQEEQEQQEE
QQQDEQQQDE QQQDEQQQDE QEQQDEQQQD EQQQQDEQEQ QEEQEQQEEQ EQQEEQEQQE
EQEQELEEQE QELEEQEQEL EEQEQELEEQ EQELEEQEQE LEEQEQELEE QEQELEEQEQ
ELEEQEQELE EQEQELEEQE QELEEQEQEL EEQEQELEEQ EQEQELEEVE EQEQEQEEQE
LEEVEEQEQE QEEQEEQELE EVEEQEEQEL EEVEEQEEQE LEEVEEQEQQ GVEQQEQETV
EEPIILHGSS SEDEMEVDYP VVSTHEQIAS SPPGDNTPDD DPQPGPSREY RYVLRTSPPH
RPGVRMRRVP VTHPKKPHPR YQQPPVPYRQ IDDCPAKARP QHIFYRRFLG KDGRRDPKCQ
WKFAVIFWGN DPYGLKKLSQ AFQFGGVKAG PVSCLPHPGP DQSPITYCVY VYCQNKDTSK
KVQMARLAWE ASHPLAGNLQ SSIVKFKKPL PLTQPGENQG PGDSPQEMT
