Q86WA6 (BPHL_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Valacyclovir hydrolase
Short name=VACVase
Short name=Valacyclovirase
EC=3.1.-.-

Alternative name(s):
Biphenyl hydrolase-like protein
Biphenyl hydrolase-related protein
Short name=Bph-rp
Breast epithelial mucin-associated antigen
Short name=MCNAA

Gene names

Name:	BPHL
Synonyms:	MCNAA

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	291 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Serine hydrolase that catalyzes the hydrolytic activation of amino acid ester prodrugs of nucleoside analogs such as valacyclovir and valganciclovir. Activates valacyclovir to acyclovir. May play a role in detoxification processes. It is a specific alpha-amino acid ester hydrolase that prefers small, hydrophobic, and aromatic side chains and does not have a stringent requirement for the leaving group other than preferring a primary alcohol. Ref.13
Subunit structure	Monomer. May also form homodimers. Ref.9 Ref.13
Tissue specificity	Expressed at high levels in liver and kidney and lower levels in heart, intestine and skeletal muscle. Ref.1
Sequence similarities	Belongs to the AB hydrolase superfamily. Lipase family.

Ontologies

Keywords
Coding sequence diversity	Alternative splicing
Domain	Signal
Molecular function	Hydrolase
PTM	Acetylation
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	cellular amino acid metabolic process Traceable author statement Ref.1. Source: ProtInc response to toxic substance Traceable author statement Ref.1. Source: ProtInc
Cellular_component	mitochondrion Inferred from sequence or structural similarity. Source: UniProtKB
Molecular_function	hydrolase activity Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q86WA6-1)

Also known as: Beta;

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: Q86WA6-2)

Also known as: Alpha;

The sequence of this isoform differs from the canonical sequence as follows:
     1-36: MVAVLGGRGVLRLRLLLSALKPGIHVPRAGPAAAFG → MPRNLLYSLLSSHLSPHFS

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 37

37

Ref.7

Chain

38 – 291

254

Valacyclovir hydrolase

PRO_0000017841

Sites

Active site

139

1

Nucleophile Ref.13

Active site

244

1

Charge relay system Ref.13

Active site

272

1

Charge relay system Ref.13

Site

140

1

Binding of alpha-amino group of substrate

Amino acid modifications

Modified residue

126

1

N6-acetyllysine Ref.11

Natural variations

Alternative sequence

1 – 36

36

MVAVL…AAAFG → MPRNLLYSLLSSHLSPHFS in isoform 2.

VSP_009115

Experimental info

Mutagenesis

139

1

S → A: <0.1% of wild type activity. Ref.13

Mutagenesis

244

1

D → N: <0.1% of wild type activity. Ref.13

Mutagenesis

272

1

H → A: Complete loss of activity. Ref.13

Sequence conflict

182

1

V → R in CAA40859. Ref.6

Sequence conflict

261

1

G → A in CAA40859. Ref.6

Secondary structure

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291

Helix Strand Turn

Details...

Beta strand

40 – 46

7

Beta strand

49 – 57

9

Beta strand

60 – 66

7

Helix

73 – 76

4

Helix

78 – 83

6

Turn

86 – 88

3

Beta strand

89 – 94

6

Helix

113 – 127

15

Beta strand

131 – 138

8

Helix

140 – 151

12

Turn

153 – 155

3

Beta strand

156 – 163

8

Helix

170 – 177

8

Helix

182 – 184

3

Helix

187 – 197

11

Helix

199 – 214

16

Helix

215 – 218

4

Helix

220 – 222

3

Beta strand

223 – 225

3

Helix

226 – 231

6

Beta strand

236 – 241

6

Beta strand

245 – 247

3

Helix

249 – 258

10

Beta strand

263 – 267

5

Helix

274 – 277

4

Helix

279 – 290

12

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (Beta) [UniParc]. Last modified June 1, 2003. Version 1. Checksum: 830B948492160244	FASTA	291	32,543
	10 20 30 40 50 60 MVAVLGGRGV LRLRLLLSAL KPGIHVPRAG PAAAFGTSVT SAKVAVNGVQ LHYQQTGEGD 70 80 90 100 110 120 HAVLLLPGML GSGETDFGPQ LKNLNKKLFT VVAWDPRGYG HSRPPDRDFP ADFFERDAKD 130 140 150 160 170 180 AVDLMKALKF KKVSLLGWSD GGITALIAAA KYPSYIHKMV IWGANAYVTD EDSMIYEGIR 190 200 210 220 230 240 DVSKWSERTR KPLEALYGYD YFARTCEKWV DGIRQFKHLP DGNICRHLLP RVQCPALIVH 250 260 270 280 290 GEKDPLVPRF HADFIHKHVK GSRLHLMPEG KHNLHLRFAD EFNKLAEDFL Q
	Isoform 2 (Alpha) [UniParc]. Checksum: 12B7F8595B0EBB0C	FASTA	274	31,107
	10 20 30 40 50 60 MPRNLLYSLL SSHLSPHFST SVTSAKVAVN GVQLHYQQTG EGDHAVLLLP GMLGSGETDF 70 80 90 100 110 120 GPQLKNLNKK LFTVVAWDPR GYGHSRPPDR DFPADFFERD AKDAVDLMKA LKFKKVSLLG 130 140 150 160 170 180 WSDGGITALI AAAKYPSYIH KMVIWGANAY VTDEDSMIYE GIRDVSKWSE RTRKPLEALY 190 200 210 220 230 240 GYDYFARTCE KWVDGIRQFK HLPDGNICRH LLPRVQCPAL IVHGEKDPLV PRFHADFIHK 250 260 270 HVKGSRLHLM PEGKHNLHLR FADEFNKLAE DFLQ

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning and expression analysis of a novel human serine hydrolase with sequence similarity to prokaryotic enzymes involved in the degradation of aromatic compounds." Puente X.S., Lopez-Otin C. J. Biol. Chem. 270:12926-12932(1995) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), PROTEIN SEQUENCE OF 152-158; 181-184 AND 209-214, TISSUE SPECIFICITY. Tissue: Mammary carcinoma.
[2]	Puente X.S. Submitted (DEC-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[3]	"The DNA sequence and analysis of human chromosome 6." Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L., Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R., Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D., Andrews T.D. , Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H., Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V., Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J., Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E., Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J., French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J., Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C., Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A., Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R., Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M., Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K., Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R., Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M., Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A., Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L., Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I., Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y., Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E., Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A., Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W., Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J., Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M., Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I., Rogers J., Beck S. Nature 425:805-811(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA] (ISOFORMS 1 AND 2). Tissue: Mammary carcinoma.
[4]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
[6]	"Cloning and sequencing of a complementary DNA encoding a M(r) 70,000 human breast epithelial mucin-associated antigen." Larocca D., Peterson J.A., Walkup G., Urrea R., Ceriani R.L. Cancer Res. 50:5925-5930(1990) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 182-280.
[7]	"Identification of a human valacyclovirase: biphenyl hydrolase-like protein as valacyclovir hydrolase." Kim I., Chu X.-Y., Kim S., Provoda C.J., Lee K.-D., Amidon G.L. J. Biol. Chem. 278:25348-25356(2003) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 38-56, CHARACTERIZATION.
[8]	"Structural characterization and chromosomal localization of the gene encoding human biphenyl hydrolase-related protein (BPHL)." Puente X.S., Pendas A.M., Lopez-Otin C. Genomics 51:459-462(1998) [PubMed] [Europe PMC] [Abstract] Cited for: CHROMOSOMAL LOCATION.
[9]	Kim I. Submitted (DEC-2003) to UniProtKB Cited for: SUBUNIT.
[10]	"A novel nucleoside prodrug-activating enzyme: substrate specificity of biphenyl hydrolase-like protein." Kim I., Song X., Vig B.S., Mittal S., Shin H.-C., Lorenzi P.J., Amidon G.L. Mol. Pharm. 1:117-127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: SUBSTRATE SPECIFICITY.
[11]	"Lysine acetylation targets protein complexes and co-regulates major cellular functions." Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C., Olsen J.V., Mann M. Science 325:834-840(2009) [PubMed] [Europe PMC] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-126, MASS SPECTROMETRY.
[12]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[13]	"Molecular basis of prodrug activation by human valacyclovirase, an alpha-amino acid ester hydrolase." Lai L., Xu Z., Zhou J., Lee K.D., Amidon G.L. J. Biol. Chem. 283:9318-9327(2008) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.75 ANGSTROMS) OF 38-291, FUNCTION, SUBUNIT, ACTIVE SITES, MUTAGENESIS OF SER-139; ASP-244 AND HIS-272.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

X81372 mRNA. Translation: CAA57137.1.
AJ617684 mRNA. Translation: CAE85120.1.
AL031963 Genomic DNA. Translation: CAD70626.1.
AL031963 Genomic DNA. Translation: CAD70627.1.
CH471087 Genomic DNA. Translation: EAW55122.1.
BC106901 mRNA. Translation: AAI06902.1.
X57653 mRNA. Translation: CAA40859.1.

IPI

IPI00003990.
IPI00384428.

PIR

A56716.

RefSeq

NP_004323.2. NM_004332.2.

UniGene

Hs.10136.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2OCG	X-ray	1.75	A	38-291	[»]
2OCI	X-ray	1.90	A	38-291	[»]
2OCK	X-ray	1.85	A	38-291	[»]
2OCL	X-ray	1.90	A	38-291	[»]

ProteinModelPortal

Q86WA6.

ModBase

Search...

Protein family/group databases

MEROPS

S33.982.

PTM databases

PhosphoSite

Q86WA6.

Polymorphism databases

DMDM

39931107.

Proteomic databases

PaxDb

Q86WA6.

PRIDE

Q86WA6.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000380375; ENSP00000369734; ENSG00000137274.
ENST00000380379; ENSP00000369739; ENSG00000137274.
ENST00000434640; ENSP00000390472; ENSG00000137274.

GeneID

670.

KEGG

hsa:670.

UCSC

uc003muy.3. human.
uc003mva.3. human.

Organism-specific databases

CTD

670.

GeneCards

GC06P003118.

H-InvDB

HIX0020996.

HGNC

HGNC:1094. BPHL.

HPA

HPA036752.

MIM

603156. gene.

neXtProt

NX_Q86WA6.

PharmGKB

PA25402.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG0596.

HOGENOM

HOG000044258.

HOVERGEN

HBG048762.

InParanoid

Q86WA6.

KO

K01175.

OMA

NAYVTEE.

PhylomeDB

Q86WA6.

Enzyme and pathway databases

SABIO-RK

Q86WA6.

Gene expression databases

ArrayExpress

Q86WA6.

Bgee

Q86WA6.

CleanEx

HS_BPHL.

Genevestigator

Q86WA6.

GermOnline

ENSG00000137274. Homo sapiens.

Family and domain databases

PROSITE

PS00120. LIPASE_SER. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

ChiTaRS

BPHL. human.

EvolutionaryTrace

Q86WA6.

GenomeRNAi

670.

NextBio

2744.

SOURCE

Search...

Entry information

Entry name

BPHL_HUMAN

Accession

Primary (citable) accession number: Q86WA6
Secondary accession number(s): Q00306, Q13855, Q3KP51

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 15, 2003
Last sequence update:	June 1, 2003
Last modified:	May 29, 2013
This is version 106 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.