ID UBE2T_HUMAN Reviewed; 197 AA.
AC Q9NPD8; Q2TU36;
DT 16-AUG-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2000, sequence version 1.
DT 01-MAY-2013, entry version 108.
DE RecName: Full=Ubiquitin-conjugating enzyme E2 T;
DE EC=6.3.2.19;
DE AltName: Full=Cell proliferation-inducing gene 50 protein;
DE AltName: Full=Ubiquitin carrier protein T;
DE AltName: Full=Ubiquitin-protein ligase T;
GN Name=UBE2T; ORFNames=HSPC150, PIG50;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Okaze H., Hayashi A., Kozuma S., Saito T.;
RT "Ubiquitin-conjugating enzyme isolog.";
RL Submitted (OCT-1999) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Adrenal gland;
RX PubMed=10931946; DOI=10.1073/pnas.160270997;
RA Hu R.-M., Han Z.-G., Song H.-D., Peng Y.-D., Huang Q.-H., Ren S.-X.,
RA Gu Y.-J., Huang C.-H., Li Y.-B., Jiang C.-L., Fu G., Zhang Q.-H.,
RA Gu B.-W., Dai M., Mao Y.-F., Gao G.-F., Rong R., Ye M., Zhou J.,
RA Xu S.-H., Gu J., Shi J.-X., Jin W.-R., Zhang C.-K., Wu T.-M.,
RA Huang G.-Y., Chen Z., Chen M.-D., Chen J.-L.;
RT "Gene expression profiling in the human hypothalamus-pituitary-adrenal
RT axis and full-length cDNA cloning.";
RL Proc. Natl. Acad. Sci. U.S.A. 97:9543-9548(2000).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Blood;
RX PubMed=11042152; DOI=10.1101/gr.140200;
RA Zhang Q.-H., Ye M., Wu X.-Y., Ren S.-X., Zhao M., Zhao C.-J., Fu G.,
RA Shen Y., Fan H.-Y., Lu G., Zhong M., Xu X.-R., Han Z.-G., Zhang J.-W.,
RA Tao J., Huang Q.-H., Zhou J., Hu G.-X., Gu J., Chen S.-J., Chen Z.;
RT "Cloning and functional analysis of cDNAs with open reading frames for
RT 300 previously undefined genes expressed in CD34+ hematopoietic
RT stem/progenitor cells.";
RL Genome Res. 10:1546-1560(2000).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Carcinoma;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Kim J.W.;
RT "Identification of a human cell proliferation inducing gene.";
RL Submitted (FEB-2004) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D.,
RA Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A.,
RA Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F.,
RA McDonald L., Evans R., Phillips K., Atkinson A., Cooper R., Jones C.,
RA Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P.,
RA Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K.,
RA Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G.,
RA Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D.,
RA Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G.,
RA Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J.,
RA Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R.,
RA Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D.,
RA Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G.,
RA Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M.,
RA Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J.,
RA Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M.,
RA Loveland J., Lovell J., Lush M.J., Lyne R., Martin S.,
RA Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S.,
RA Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C.,
RA Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z.,
RA Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E.,
RA Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A.,
RA Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R.,
RA Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V.,
RA Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Lung;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [9]
RP FUNCTION, INTERACTION WITH FANCL, UBIQUITINATION AT LYS-91, AND
RP MUTAGENESIS OF CYS-86.
RX PubMed=16916645; DOI=10.1016/j.molcel.2006.06.024;
RA Machida Y.J., Machida Y., Chen Y., Gurtan A.M., Kupfer G.M.,
RA D'Andrea A.D., Dutta A.;
RT "UBE2T is the E2 in the Fanconi anemia pathway and undergoes negative
RT autoregulation.";
RL Mol. Cell 23:589-596(2006).
RN [10]
RP FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH FANCL, AND
RP MUTAGENESIS OF CYS-86.
RX PubMed=17938197; DOI=10.1128/MCB.00504-07;
RA Alpi A., Langevin F., Mosedale G., Machida Y.J., Dutta A., Patel K.J.;
RT "UBE2T, the Fanconi anemia core complex, and FANCD2 are recruited
RT independently to chromatin: a basis for the regulation of FANCD2
RT monoubiquitination.";
RL Mol. Cell. Biol. 27:8421-8430(2007).
RN [11]
RP FUNCTION, INTERACTION WITH FANCL, UBIQUITINATION AT LYS-91 AND
RP LYS-182, AND MUTAGENESIS OF CYS-86; LYS-91 AND 182-LYS--LYS-191.
RX PubMed=19111657; DOI=10.1016/j.molcel.2008.12.003;
RA Alpi A.F., Pace P.E., Babu M.M., Patel K.J.;
RT "Mechanistic insight into site-restricted monoubiquitination of FANCD2
RT by Ube2t, FANCL, and FANCI.";
RL Mol. Cell 32:767-777(2008).
RN [12]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [13]
RP FUNCTION, SUBCELLULAR LOCATION, MUTAGENESIS OF CYS-86, AND INTERACTION
RP WITH BRCA1.
RX PubMed=19887602; DOI=10.1158/0008-5472.CAN-09-1809;
RA Ueki T., Park J.H., Nishidate T., Kijima K., Hirata K., Nakamura Y.,
RA Katagiri T.;
RT "Ubiquitination and downregulation of BRCA1 by ubiquitin-conjugating
RT enzyme E2T overexpression in human breast cancer cells.";
RL Cancer Res. 69:8752-8760(2009).
RN [14]
RP FUNCTION, AND MUTAGENESIS OF CYS-86.
RX PubMed=19589784; DOI=10.1074/jbc.C109.038075;
RA Longerich S., San Filippo J., Liu D., Sung P.;
RT "FANCI binds branched DNA and is monoubiquitinated by UBE2T-FANCL.";
RL J. Biol. Chem. 284:23182-23186(2009).
RN [15]
RP FUNCTION.
RX PubMed=20061386; DOI=10.1074/jbc.M109.089003;
RA David Y., Ziv T., Admon A., Navon A.;
RT "The E2 ubiquitin-conjugating enzymes direct polyubiquitination to
RT preferred lysines.";
RL J. Biol. Chem. 285:8595-8604(2010).
RN [16]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [17]
RP INTERACTION WITH FANCL, AND MUTAGENESIS OF PHE-63.
RX PubMed=21775430; DOI=10.1074/jbc.M111.244632;
RA Hodson C., Cole A.R., Lewis L.P., Miles J.A., Purkiss A., Walden H.;
RT "Structural analysis of human FANCL, the E3 ligase in the Fanconi
RT anemia pathway.";
RL J. Biol. Chem. 286:32628-32637(2011).
RN [18]
RP INDUCTION.
RX PubMed=21722982; DOI=10.1016/j.radonc.2011.05.059;
RA Ramaekers C.H., van den Beucken T., Meng A., Kassam S., Thoms J.,
RA Bristow R.G., Wouters B.G.;
RT "Hypoxia disrupts the Fanconi anemia pathway and sensitizes cells to
RT chemotherapy through regulation of UBE2T.";
RL Radiother. Oncol. 101:190-197(2011).
RN [19]
RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 1-167.
RA Walker J.R., Avvakumov G.V., Newman E.M., Mackenzie F.,
RA Kozieradzki I., Sundstrom M., Arrowsmith C., Edwards A., Bochkarev A.,
RA Dhe-Paganon S.;
RT "Ubiquitin-conjugating enzyme HSPC150.";
RL Submitted (FEB-2005) to the PDB data bank.
CC -!- FUNCTION: Accepts ubiquitin from the E1 complex and catalyzes its
CC covalent attachment to other proteins. Catalyzes
CC monoubiquitination. Involved in mitomycin-C (MMC)-induced DNA
CC repair: acts as a specific E2 ubiquitin-conjugating enzyme for the
CC Fanconi anemia complex by associating with E3 ubiquitin-protein
CC ligase FANCL and catalyzing monoubiquitination of FANCD2, a key
CC step in the DNA damage pathway. Also mediates monoubiquitination
CC of FANCL and FANCI. May contribute to ubiquitination and
CC degradation of BRCA1. In vitro able to promote polyubiquitination
CC using all 7 ubiquitin Lys residues, but may prefer 'Lys-11'-,
CC 'Lys-27'-, 'Lys-48'- and 'Lys-63'-linked polyubiquitination.
CC -!- CATALYTIC ACTIVITY: ATP + ubiquitin + protein lysine = AMP +
CC diphosphate + protein N-ubiquityllysine.
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC -!- SUBUNIT: Interacts with FANCL and BRCA1.
CC -!- SUBCELLULAR LOCATION: Nucleus. Note=Accumulates to chromatin.
CC -!- INDUCTION: Down-regulated following hypoxia. Up-regulated in
CC breast cancers.
CC -!- PTM: Auto-ubiquitinated. Effects of auto-monoubiquitination at
CC Lys-91 and Lys-182 are unclear: according to a report,
CC monoubiquitination inactivates E2 enzyme activity
CC (PubMed:16916645). In contrast, according to another report,
CC autoubiquitination does not affect E2 enzyme activity
CC (PubMed:19111657).
CC -!- SIMILARITY: Belongs to the ubiquitin-conjugating enzyme family.
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DR EMBL; AB032931; BAA93711.1; -; mRNA.
DR EMBL; AF160215; AAF67016.1; -; mRNA.
DR EMBL; AF161499; AAF29114.1; -; mRNA.
DR EMBL; AK000504; BAA91211.1; -; mRNA.
DR EMBL; AY542309; AAT08178.1; -; mRNA.
DR EMBL; AL356953; CAI15933.1; -; Genomic_DNA.
DR EMBL; CH471067; EAW91411.1; -; Genomic_DNA.
DR EMBL; BC004152; AAH04152.1; -; mRNA.
DR EMBL; BC019284; AAH19284.1; -; mRNA.
DR IPI; IPI00023087; -.
DR RefSeq; NP_054895.1; NM_014176.3.
DR UniGene; Hs.5199; -.
DR PDB; 1YH2; X-ray; 2.00 A; A=1-167.
DR PDBsum; 1YH2; -.
DR ProteinModelPortal; Q9NPD8; -.
DR IntAct; Q9NPD8; 10.
DR STRING; 9606.ENSP00000356243; -.
DR PhosphoSite; Q9NPD8; -.
DR DMDM; 73622065; -.
DR PaxDb; Q9NPD8; -.
DR PRIDE; Q9NPD8; -.
DR DNASU; 29089; -.
DR Ensembl; ENST00000367274; ENSP00000356243; ENSG00000077152.
DR GeneID; 29089; -.
DR KEGG; hsa:29089; -.
DR UCSC; uc001gxx.4; human.
DR CTD; 29089; -.
DR GeneCards; GC01M202300; -.
DR HGNC; HGNC:25009; UBE2T.
DR HPA; HPA002831; -.
DR MIM; 610538; gene.
DR neXtProt; NX_Q9NPD8; -.
DR PharmGKB; PA142670655; -.
DR eggNOG; COG5078; -.
DR HOGENOM; HOG000233455; -.
DR HOVERGEN; HBG063308; -.
DR InParanoid; Q9NPD8; -.
DR KO; K13960; -.
DR OMA; GITCWQE; -.
DR OrthoDB; EOG40GCRT; -.
DR PhylomeDB; Q9NPD8; -.
DR Reactome; REACT_216; DNA Repair.
DR UniPathway; UPA00143; -.
DR ChiTaRS; UBE2T; human.
DR EvolutionaryTrace; Q9NPD8; -.
DR GenomeRNAi; 29089; -.
DR NextBio; 52094; -.
DR Bgee; Q9NPD8; -.
DR CleanEx; HS_UBE2T; -.
DR Genevestigator; Q9NPD8; -.
DR GermOnline; ENSG00000077152; Homo sapiens.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0003682; F:chromatin binding; IDA:UniProtKB.
DR GO; GO:0004842; F:ubiquitin-protein ligase activity; IDA:UniProtKB.
DR GO; GO:0006281; P:DNA repair; IMP:UniProtKB.
DR GO; GO:0051865; P:protein autoubiquitination; IDA:UniProtKB.
DR GO; GO:0070979; P:protein K11-linked ubiquitination; IDA:UniProtKB.
DR GO; GO:0044314; P:protein K27-linked ubiquitination; IDA:UniProtKB.
DR GO; GO:0035519; P:protein K29-linked ubiquitination; IDA:UniProtKB.
DR GO; GO:0070936; P:protein K48-linked ubiquitination; IDA:UniProtKB.
DR GO; GO:0085020; P:protein K6-linked ubiquitination; IDA:UniProtKB.
DR GO; GO:0070534; P:protein K63-linked ubiquitination; IDA:UniProtKB.
DR GO; GO:0006513; P:protein monoubiquitination; IDA:UniProtKB.
DR Gene3D; 3.10.110.10; -; 1.
DR InterPro; IPR000608; UBQ-conjugat_E2.
DR InterPro; IPR023313; UBQ-conjugating_AS.
DR InterPro; IPR016135; UBQ-conjugating_enzyme/RWD.
DR Pfam; PF00179; UQ_con; 1.
DR SUPFAM; SSF54495; UBQ-conjugat/RWD-like; 1.
DR PROSITE; PS00183; UBIQUITIN_CONJUGAT_1; 1.
DR PROSITE; PS50127; UBIQUITIN_CONJUGAT_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; ATP-binding; Complete proteome; DNA damage; DNA repair;
KW Isopeptide bond; Ligase; Nucleotide-binding; Nucleus;
KW Reference proteome; Ubl conjugation; Ubl conjugation pathway.
FT CHAIN 1 197 Ubiquitin-conjugating enzyme E2 T.
FT /FTId=PRO_0000082509.
FT ACT_SITE 86 86 Glycyl thioester intermediate.
FT CROSSLNK 91 91 Glycyl lysine isopeptide (Lys-Gly)
FT (interchain with G-Cter in ubiquitin).
FT CROSSLNK 182 182 Glycyl lysine isopeptide (Lys-Gly)
FT (interchain with G-Cter in ubiquitin).
FT MUTAGEN 63 63 F->A: Decreased binding to FANCL.
FT MUTAGEN 86 86 C->A: Loss of E2 enzyme activity.
FT MUTAGEN 91 91 K->R: Decreased monoubiquitination.
FT MUTAGEN 182 191 Missing: Decreased monoubiquitination.
FT HELIX 1 16
FT STRAND 22 29
FT STRAND 33 39
FT TURN 45 48
FT STRAND 50 56
FT TURN 59 62
FT STRAND 67 72
FT HELIX 88 90
FT TURN 93 95
FT HELIX 104 116
FT HELIX 126 134
FT HELIX 136 150
SQ SEQUENCE 197 AA; 22521 MW; 6C02D774A7FA928A CRC64;
MQRASRLKRE LHMLATEPPP GITCWQDKDQ MDDLRAQILG GANTPYEKGV FKLEVIIPER
YPFEPPQIRF LTPIYHPNID SAGRICLDVL KLPPKGAWRP SLNIATVLTS IQLLMSEPNP
DDPLMADISS EFKYNKPAFL KNARQWTEKH ARQKQKADEE EMLDNLPEAG DSRVHNSTQK
RKASQLVGIE KKFHPDV
//
