K15_HHV8P
ID K15_HHV8P Reviewed; 489 AA.
AC Q9QR69;
DT 16-OCT-2013, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 03-AUG-2022, entry version 56.
DE RecName: Full=Protein K15;
DE Flags: Precursor;
GN Name=K15;
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=12915550; DOI=10.1128/jvi.77.17.9346-9358.2003;
RA Brinkmann M.M., Glenn M., Rainbow L., Kieser A., Henke-Gendo C.,
RA Schulz T.F.;
RT "Activation of mitogen-activated protein kinase and NF-kappaB pathways by a
RT Kaposi's sarcoma-associated herpesvirus K15 membrane protein.";
RL J. Virol. 77:9346-9358(2003).
RN [4]
RP INTERACTION WITH HOST ITSN2.
RX PubMed=17696407; DOI=10.1021/bi700357s;
RA Lim C.S., Seet B.T., Ingham R.J., Gish G., Matskova L., Winberg G.,
RA Ernberg I., Pawson T.;
RT "The K15 protein of Kaposi's sarcoma-associated herpesvirus recruits the
RT endocytic regulator intersectin 2 through a selective SH3 domain
RT interaction.";
RL Biochemistry 46:9874-9885(2007).
RN [5]
RP FUNCTION, AND INTERACTION WITH HOST LYN.
RX PubMed=18985015; DOI=10.3858/emm.2008.40.5.565;
RA Cho N.H., Choi Y.K., Choi J.K.;
RT "Multi-transmembrane protein K15 of Kaposi's sarcoma-associated herpesvirus
RT targets Lyn kinase in the membrane raft and induces NFAT/AP1 activities.";
RL Exp. Mol. Med. 40:565-573(2008).
RN [6]
RP FUNCTION.
RX PubMed=20534855; DOI=10.1128/jvi.01696-09;
RA Pietrek M., Brinkmann M.M., Glowacka I., Enlund A., Havemeier A.,
RA Dittrich-Breiholz O., Kracht M., Lewitzky M., Saksela K., Feller S.M.,
RA Schulz T.F.;
RT "Role of the Kaposi's sarcoma-associated herpesvirus K15 SH3 binding site
RT in inflammatory signaling and B-cell activation.";
RL J. Virol. 84:8231-8240(2010).
RN [7]
RP FUNCTION.
RX PubMed=23028325; DOI=10.1371/journal.ppat.1002927;
RA Bala K., Bosco R., Gramolelli S., Haas D.A., Kati S., Pietrek M.,
RA Havemeier A., Yakushko Y., Singh V.V., Dittrich-Breiholz O., Kracht M.,
RA Schulz T.F.;
RT "Kaposi's sarcoma herpesvirus K15 protein contributes to virus-induced
RT angiogenesis by recruiting PLCgamma1 and activating NFAT1-dependent RCAN1
RT expression.";
RL PLoS Pathog. 8:E1002927-E1002927(2012).
RN [8]
RP SUBCELLULAR LOCATION.
RX PubMed=28835496; DOI=10.1128/jvi.01370-17;
RA Smith C.G., Kharkwal H., Wilson D.W.;
RT "Expression and Subcellular Localization of the Kaposi's Sarcoma-Associated
RT Herpesvirus K15P Protein during Latency and Lytic Reactivation in Primary
RT Effusion Lymphoma Cells.";
RL J. Virol. 91:0-0(2017).
RN [9]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=28938025; DOI=10.1371/journal.ppat.1006639;
RA Abere B., Mamo T.M., Hartmann S., Samarina N., Hage E., Rueckert J.,
RA Hotop S.K., Buesche G., Schulz T.F.;
RT "The Kaposi's sarcoma-associated herpesvirus (KSHV) non-structural membrane
RT protein K15 is required for viral lytic replication and may represent a
RT therapeutic target.";
RL PLoS Pathog. 13:E1006639-E1006639(2017).
CC -!- FUNCTION: Plays a crucial role for reactivation of the virus from
CC latency, early viral gene expression and virus production. Modulates
CC host signaling pathways including activation of MAP kinases c-JUN-N-
CC terminal kinase (JNK), ERK2, and NF-kappa-B resulting in the activation
CC of AP-1 and NFAT-dependent gene expression in B-lymphocytes. When
CC expressed in epithelial cells, induces the expression of several
CC inflammatory and angiogenic genes. Interferes also with B-lymphocytes
CC signaling through interaction with host LYN kinase.
CC {ECO:0000269|PubMed:12915550, ECO:0000269|PubMed:18985015,
CC ECO:0000269|PubMed:20534855, ECO:0000269|PubMed:23028325,
CC ECO:0000269|PubMed:28938025}.
CC -!- SUBUNIT: Interacts with host LYN; this interaction modulates B-cells
CC signaling. Interacts with host ITSN2. {ECO:0000269|PubMed:17696407,
CC ECO:0000269|PubMed:18985015}.
CC -!- SUBCELLULAR LOCATION: Host cell membrane {ECO:0000269|PubMed:28835496,
CC ECO:0000269|PubMed:28938025}; Multi-pass membrane protein
CC {ECO:0000305}. Host Golgi apparatus, host trans-Golgi network
CC {ECO:0000269|PubMed:28835496, ECO:0000269|PubMed:28938025}.
CC Note=Localizes to the trans-Golgi network (TGN) compartment during
CC latency and relocalizes to the cell periphery when the lytic program is
CC induced. {ECO:0000269|PubMed:28835496}.
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DR EMBL; AF148805; AAD46505.1; -; Genomic_DNA.
DR RefSeq; YP_001129435.1; NC_009333.1.
DR PDB; 7NXE; X-ray; 2.10 A; C/D=478-489.
DR PDBsum; 7NXE; -.
DR SMR; Q9QR69; -.
DR GeneID; 4961473; -.
DR KEGG; vg:4961473; -.
DR Proteomes; UP000000942; Genome.
DR GO; GO:0044177; C:host cell Golgi apparatus; IEA:UniProtKB-SubCell.
DR GO; GO:0020002; C:host cell plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR InterPro; IPR009304; Herpes_LAMP2.
DR Pfam; PF06126; Herpes_LAMP2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Host cell membrane; Host Golgi apparatus; Host membrane;
KW Host-virus interaction; Membrane; Reference proteome; Signal;
KW Transmembrane; Transmembrane helix.
FT SIGNAL 1..26
FT /evidence="ECO:0000255"
FT CHAIN 27..489
FT /note="Protein K15"
FT /id="PRO_0000423885"
FT TRANSMEM 29..49
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 63..83
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 89..109
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 121..141
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 148..168
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 175..195
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 200..220
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 237..257
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 264..284
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 296..316
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 324..344
FT /note="Helical"
FT /evidence="ECO:0000255"
SQ SEQUENCE 489 AA; 54316 MW; 0FDB473474121743 CRC64;
MKTLIFFWNL WLWALLVCFW CITLVCVTTN SIDTMASLLV MCILFVSAIN KYTQAISSNN
PKWPSSWHLG IIACIVLKLW NLSTTNSVTY ACLITTAILS LVTAFLTLIK HCTACKLQLE
HGILFTSTFA VLMTNMLVHM SNTWQSSWIF FPISFTLSLP FLYAFATVKT GNIKLVSSVS
FICAGLVMGY PVSCCKTHTC TATAAGLSLS SIYLGFTGII STLHKSWAPP KRGILTFLLL
QGGVLTTQTL TTELLAITST TGNIKGHEIL LLVCLIFLWC LYVWQSFNKA SLVTGMLHLI
AAWSHTGGCV QLVMLLPSGL TRGILTMIIC ISTLFSTLQG LLVFYLYKEK KVVAVNSYRQ
RRRRIYTRDQ NLHHNDNHLG NNVISPPPLP PFFRQPVRLP SHVTDRGRGS QLLNEVELQE
VNRDPPNVFG YASILVSGAE ESREPSPQPD QSGMSILRVD GGSAFRIDTA QAATQPTDDL
YEEVLFPRN
