BPHL_MOUSE
ID BPHL_MOUSE Reviewed; 291 AA.
AC Q8R164; Q8BVH2; Q8R589; Q9DCC6;
DT 15-DEC-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2002, sequence version 1.
DT 03-AUG-2022, entry version 134.
DE RecName: Full=Valacyclovir hydrolase;
DE Short=VACVase;
DE Short=Valacyclovirase;
DE EC=3.1.-.-;
DE AltName: Full=Biphenyl hydrolase-like protein;
DE Flags: Precursor;
GN Name=Bphl;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Olfactory bulb;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Salivary gland;
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 project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [3]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas,
RC Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [4]
RP SUCCINYLATION [LARGE SCALE ANALYSIS] AT LYS-74; LYS-126; LYS-184; LYS-191;
RP LYS-260 AND LYS-271, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP ANALYSIS].
RC TISSUE=Embryonic fibroblast, and Liver;
RX PubMed=23806337; DOI=10.1016/j.molcel.2013.06.001;
RA Park J., Chen Y., Tishkoff D.X., Peng C., Tan M., Dai L., Xie Z., Zhang Y.,
RA Zwaans B.M., Skinner M.E., Lombard D.B., Zhao Y.;
RT "SIRT5-mediated lysine desuccinylation impacts diverse metabolic
RT pathways.";
RL Mol. Cell 50:919-930(2013).
RN [5]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-74; LYS-86; LYS-119; LYS-126;
RP LYS-191; LYS-217; LYS-243; LYS-260 AND LYS-271, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=23576753; DOI=10.1073/pnas.1302961110;
RA Rardin M.J., Newman J.C., Held J.M., Cusack M.P., Sorensen D.J., Li B.,
RA Schilling B., Mooney S.D., Kahn C.R., Verdin E., Gibson B.W.;
RT "Label-free quantitative proteomics of the lysine acetylome in mitochondria
RT identifies substrates of SIRT3 in metabolic pathways.";
RL Proc. Natl. Acad. Sci. U.S.A. 110:6601-6606(2013).
CC -!- FUNCTION: Serine hydrolase that catalyzes the hydrolytic activation of
CC amino acid ester prodrugs of nucleoside analogs such as valacyclovir
CC and valganciclovir. Activates valacyclovir to acyclovir. May play a
CC role in detoxification processes. It is a specific alpha-amino acid
CC ester hydrolase that prefers small, hydrophobic, and aromatic side
CC chains and does not have a stringent requirement for the leaving group
CC other than preferring a primary alcohol (By similarity). {ECO:0000250}.
CC -!- SUBUNIT: Monomer. May also form homodimers (By similarity).
CC {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the AB hydrolase superfamily. Lipase family.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAC37185.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; AK002907; BAB22447.1; -; mRNA.
DR EMBL; AK078232; BAC37185.1; ALT_INIT; mRNA.
DR EMBL; BC025162; AAH25162.1; -; mRNA.
DR EMBL; BC023146; AAH23146.1; -; mRNA.
DR CCDS; CCDS49229.1; -.
DR RefSeq; NP_080788.1; NM_026512.1.
DR AlphaFoldDB; Q8R164; -.
DR SMR; Q8R164; -.
DR STRING; 10090.ENSMUSP00000046168; -.
DR ESTHER; mouse-bphl; Valacyclovir-hydrolase.
DR MEROPS; S33.982; -.
DR iPTMnet; Q8R164; -.
DR PhosphoSitePlus; Q8R164; -.
DR SwissPalm; Q8R164; -.
DR EPD; Q8R164; -.
DR jPOST; Q8R164; -.
DR MaxQB; Q8R164; -.
DR PaxDb; Q8R164; -.
DR PRIDE; Q8R164; -.
DR ProteomicsDB; 265226; -.
DR Antibodypedia; 24354; 131 antibodies from 24 providers.
DR DNASU; 68021; -.
DR Ensembl; ENSMUST00000040656; ENSMUSP00000046168; ENSMUSG00000038286.
DR GeneID; 68021; -.
DR KEGG; mmu:68021; -.
DR UCSC; uc007qaz.1; mouse.
DR CTD; 670; -.
DR MGI; MGI:1915271; Bphl.
DR VEuPathDB; HostDB:ENSMUSG00000038286; -.
DR eggNOG; KOG2984; Eukaryota.
DR GeneTree; ENSGT00390000004746; -.
DR HOGENOM; CLU_020336_50_5_1; -.
DR InParanoid; Q8R164; -.
DR OMA; RFPQLWA; -.
DR OrthoDB; 1061420at2759; -.
DR PhylomeDB; Q8R164; -.
DR TreeFam; TF318389; -.
DR Reactome; R-MMU-211945; Phase I - Functionalization of compounds.
DR BioGRID-ORCS; 68021; 2 hits in 72 CRISPR screens.
DR ChiTaRS; Bphl; mouse.
DR PRO; PR:Q8R164; -.
DR Proteomes; UP000000589; Chromosome 13.
DR RNAct; Q8R164; protein.
DR Bgee; ENSMUSG00000038286; Expressed in floor plate of midbrain and 267 other tissues.
DR ExpressionAtlas; Q8R164; baseline and differential.
DR Genevisible; Q8R164; MM.
DR GO; GO:0005739; C:mitochondrion; IDA:UniProtKB.
DR GO; GO:0047658; F:alpha-amino-acid esterase activity; ISO:MGI.
DR Gene3D; 3.40.50.1820; -; 1.
DR InterPro; IPR029058; AB_hydrolase.
DR InterPro; IPR000073; AB_hydrolase_1.
DR Pfam; PF00561; Abhydrolase_1; 1.
DR SUPFAM; SSF53474; SSF53474; 1.
DR PROSITE; PS00120; LIPASE_SER; 1.
PE 1: Evidence at protein level;
KW Acetylation; Cytoplasm; Hydrolase; Reference proteome; Signal.
FT SIGNAL 1..37
FT /evidence="ECO:0000250"
FT CHAIN 38..291
FT /note="Valacyclovir hydrolase"
FT /id="PRO_0000017842"
FT DOMAIN 62..173
FT /note="AB hydrolase-1"
FT /evidence="ECO:0000255"
FT ACT_SITE 139
FT /note="Nucleophile"
FT /evidence="ECO:0000250"
FT ACT_SITE 244
FT /note="Charge relay system"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10037"
FT ACT_SITE 272
FT /note="Charge relay system"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10037"
FT SITE 140
FT /note="Binding of alpha-amino group of substrate"
FT /evidence="ECO:0000250"
FT MOD_RES 74
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:23576753"
FT MOD_RES 74
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 86
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:23576753"
FT MOD_RES 119
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:23576753"
FT MOD_RES 126
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:23576753"
FT MOD_RES 126
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 184
FT /note="N6-succinyllysine"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 191
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:23576753"
FT MOD_RES 191
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 217
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:23576753"
FT MOD_RES 243
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:23576753"
FT MOD_RES 260
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:23576753"
FT MOD_RES 260
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 271
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:23576753"
FT MOD_RES 271
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:23806337"
FT CONFLICT 62
FT /note="A -> V (in Ref. 2; AAH23146)"
FT /evidence="ECO:0000305"
FT CONFLICT 218..219
FT /note="QL -> HC (in Ref. 1; BAB22447)"
FT /evidence="ECO:0000305"
FT CONFLICT 290
FT /note="L -> F (in Ref. 1; BAB22447)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 291 AA; 32851 MW; D3831D8B0674CF7A CRC64;
MATATVRPAA QRLRLLLSPL KSRICVPQAE PVATFGTAVT SAKVAVNGVH LHYQRVGEGE
HAILLLPGML GSGKTDFAPQ LQSLNKKRFT LVAWDPRGYG YSRPPDRDFP RDFFERDAKD
AVDLMKALQF KQVSLLGWSD GGITALIAAA KYPSYIRKMV IWGANAYVTE EDSRIYQGIR
DVSKWSEKAR KPLEALYGYD YLAKTCEDWV DGISQFKQLP EGNICRHLLP LVQCPTLIVH
GEKDPLVPRF HADFLLQHVK GSRLHLMPEG KHNLHLRFAD EFNRLVEDFL Q
