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Q86WA6 (BPHL_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 116. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (4) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length291 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence 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 diversityAlternative splicing
   DomainSignal
   Molecular functionHydrolase
   PTMAcetylation
   Technical term3D-structure
Complete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processcellular amino acid metabolic process

Traceable author statement Ref.1. Source: ProtInc

response to toxic substance

Traceable author statement Ref.1. Source: ProtInc

   Cellular_componentmitochondrion

Inferred from sequence or structural similarity. Source: UniProtKB

   Molecular_functionhydrolase 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 keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 3737 Ref.7
Chain38 – 291254Valacyclovir hydrolase
PRO_0000017841

Sites

Active site1391Nucleophile Ref.13
Active site2441Charge relay system Ref.13
Active site2721Charge relay system Ref.13
Site1401Binding of alpha-amino group of substrate

Amino acid modifications

Modified residue861N6-acetyllysine By similarity
Modified residue1191N6-acetyllysine By similarity
Modified residue1261N6-acetyllysine; alternate Ref.11
Modified residue1261N6-succinyllysine; alternate By similarity
Modified residue1841N6-succinyllysine By similarity
Modified residue1911N6-acetyllysine; alternate By similarity
Modified residue1911N6-succinyllysine; alternate By similarity
Modified residue2171N6-acetyllysine By similarity
Modified residue2431N6-acetyllysine By similarity
Modified residue2601N6-acetyllysine; alternate By similarity
Modified residue2601N6-succinyllysine; alternate By similarity
Modified residue2711N6-acetyllysine; alternate By similarity
Modified residue2711N6-succinyllysine; alternate By similarity

Natural variations

Alternative sequence1 – 3636MVAVL…AAAFG → MPRNLLYSLLSSHLSPHFS in isoform 2.
VSP_009115

Experimental info

Mutagenesis1391S → A: <0.1% of wild type activity. Ref.13
Mutagenesis2441D → N: <0.1% of wild type activity. Ref.13
Mutagenesis2721H → A: Complete loss of activity. Ref.13
Sequence conflict1821V → R in CAA40859. Ref.6
Sequence conflict2611G → A in CAA40859. Ref.6

Secondary structure

................................................ 291
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 (Beta) [UniParc].

Last modified June 1, 2003. Version 1.
Checksum: 830B948492160244

FASTA29132,543
        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 

« Hide

Isoform 2 (Alpha) [UniParc].

Checksum: 12B7F8595B0EBB0C
Show »

FASTA27431,107

References

« Hide '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. expand/collapse author list , 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. expand/collapse author list , 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, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[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.
CCDSCCDS4483.2. [Q86WA6-1]
PIRA56716.
RefSeqNP_004323.2. NM_004332.2. [Q86WA6-1]
UniGeneHs.10136.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2OCGX-ray1.75A38-291[»]
2OCIX-ray1.90A38-291[»]
2OCKX-ray1.85A38-291[»]
2OCLX-ray1.90A38-291[»]
ProteinModelPortalQ86WA6.
SMRQ86WA6. Positions 38-291.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid107138. 1 interaction.

Protein family/group databases

MEROPSS33.982.

PTM databases

PhosphoSiteQ86WA6.

Polymorphism databases

DMDM39931107.

Proteomic databases

MaxQBQ86WA6.
PaxDbQ86WA6.
PRIDEQ86WA6.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000380375; ENSP00000369734; ENSG00000137274. [Q86WA6-2]
ENST00000380379; ENSP00000369739; ENSG00000137274. [Q86WA6-1]
ENST00000434640; ENSP00000390472; ENSG00000137274. [Q86WA6-2]
GeneID670.
KEGGhsa:670.
UCSCuc003muy.3. human. [Q86WA6-2]
uc003mva.3. human. [Q86WA6-1]

Organism-specific databases

CTD670.
GeneCardsGC06P003118.
H-InvDBHIX0020996.
HGNCHGNC:1094. BPHL.
HPAHPA036752.
MIM603156. gene.
neXtProtNX_Q86WA6.
PharmGKBPA25402.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0596.
HOGENOMHOG000044258.
HOVERGENHBG048762.
InParanoidQ86WA6.
KOK01175.
OMAGYDYFAR.
OrthoDBEOG741Z38.
PhylomeDBQ86WA6.
TreeFamTF318389.

Enzyme and pathway databases

SABIO-RKQ86WA6.

Gene expression databases

ArrayExpressQ86WA6.
BgeeQ86WA6.
CleanExHS_BPHL.
GenevestigatorQ86WA6.

Family and domain databases

Gene3D3.40.50.1820. 1 hit.
InterProIPR029058. AB_hydrolase.
[Graphical view]
SUPFAMSSF53474. SSF53474. 1 hit.
PROSITEPS00120. LIPASE_SER. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSBPHL. human.
EvolutionaryTraceQ86WA6.
GenomeRNAi670.
NextBio2744.
PROQ86WA6.
SOURCESearch...

Entry information

Entry nameBPHL_HUMAN
AccessionPrimary (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: July 9, 2014
This is version 116 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human chromosome 6

Human chromosome 6: entries, gene names and cross-references to MIM