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Protein

Valacyclovir hydrolase

Gene

BPHL

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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.1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei139Nucleophile1 Publication1
Sitei140Binding of alpha-amino group of substrate1
Active sitei244Charge relay systemPROSITE-ProRule annotation1 Publication1
Active sitei272Charge relay systemPROSITE-ProRule annotation1 Publication1

GO - Molecular functioni

GO - Biological processi

  • cellular amino acid metabolic process Source: ProtInc
  • response to toxic substance Source: ProtInc
  • xenobiotic metabolic process Source: Reactome
Complete GO annotation...

Keywords - Molecular functioni

Hydrolase

Enzyme and pathway databases

ReactomeiR-HSA-211945. Phase 1 - Functionalization of compounds.
SABIO-RKQ86WA6.

Protein family/group databases

ESTHERihuman-BPHL. Valacyclovir-hydrolase.
MEROPSiS33.982.

Names & Taxonomyi

Protein namesi
Recommended name:
Valacyclovir hydrolase (EC:3.1.-.-)
Short name:
VACVase
Short name:
Valacyclovirase
Alternative name(s):
Biphenyl hydrolase-like protein
Biphenyl hydrolase-related protein
Short name:
Bph-rp
Breast epithelial mucin-associated antigen
Short name:
MCNAA
Gene namesi
Name:BPHL
Synonyms:MCNAA
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 6

Organism-specific databases

HGNCiHGNC:1094. BPHL.

Subcellular locationi

GO - Cellular componenti

  • extracellular exosome Source: UniProtKB
  • mitochondrial outer membrane Source: Reactome
  • mitochondrion Source: UniProtKB
Complete GO annotation...

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi139S → A: <0.1% of wild type activity. 1 Publication1
Mutagenesisi244D → N: <0.1% of wild type activity. 1 Publication1
Mutagenesisi272H → A: Complete loss of activity. 1 Publication1

Organism-specific databases

OpenTargetsiENSG00000137274.
PharmGKBiPA25402.

Polymorphism and mutation databases

BioMutaiBPHL.
DMDMi39931107.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 371 PublicationAdd BLAST37
ChainiPRO_000001784138 – 291Valacyclovir hydrolaseAdd BLAST254

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei86N6-acetyllysineBy similarity1
Modified residuei119N6-acetyllysineBy similarity1
Modified residuei126N6-acetyllysine; alternateCombined sources1
Modified residuei126N6-succinyllysine; alternateBy similarity1
Modified residuei184N6-succinyllysineBy similarity1
Modified residuei191N6-acetyllysine; alternateBy similarity1
Modified residuei191N6-succinyllysine; alternateBy similarity1
Modified residuei217N6-acetyllysineBy similarity1
Modified residuei243N6-acetyllysineBy similarity1
Modified residuei260N6-acetyllysine; alternateBy similarity1
Modified residuei260N6-succinyllysine; alternateBy similarity1
Modified residuei271N6-acetyllysine; alternateBy similarity1
Modified residuei271N6-succinyllysine; alternateBy similarity1

Keywords - PTMi

Acetylation

Proteomic databases

EPDiQ86WA6.
MaxQBiQ86WA6.
PaxDbiQ86WA6.
PeptideAtlasiQ86WA6.
PRIDEiQ86WA6.

PTM databases

iPTMnetiQ86WA6.
PhosphoSitePlusiQ86WA6.

Expressioni

Tissue specificityi

Expressed at high levels in liver and kidney and lower levels in heart, intestine and skeletal muscle.1 Publication

Gene expression databases

BgeeiENSG00000137274.
CleanExiHS_BPHL.
ExpressionAtlasiQ86WA6. baseline and differential.
GenevisibleiQ86WA6. HS.

Organism-specific databases

HPAiHPA036752.
HPA036753.

Interactioni

Subunit structurei

Monomer. May also form homodimers.2 Publications

Protein-protein interaction databases

BioGridi107138. 7 interactors.
STRINGi9606.ENSP00000369739.

Structurei

Secondary structure

1291
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi40 – 46Combined sources7
Beta strandi49 – 57Combined sources9
Beta strandi60 – 66Combined sources7
Helixi73 – 76Combined sources4
Helixi78 – 83Combined sources6
Turni86 – 88Combined sources3
Beta strandi89 – 94Combined sources6
Helixi113 – 127Combined sources15
Beta strandi131 – 138Combined sources8
Helixi140 – 151Combined sources12
Turni153 – 155Combined sources3
Beta strandi156 – 163Combined sources8
Helixi170 – 177Combined sources8
Helixi182 – 184Combined sources3
Helixi187 – 197Combined sources11
Helixi199 – 214Combined sources16
Helixi215 – 218Combined sources4
Helixi220 – 222Combined sources3
Beta strandi223 – 225Combined sources3
Helixi226 – 231Combined sources6
Beta strandi236 – 241Combined sources6
Beta strandi245 – 247Combined sources3
Helixi249 – 258Combined sources10
Beta strandi263 – 267Combined sources5
Helixi274 – 277Combined sources4
Helixi279 – 290Combined sources12

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2OCGX-ray1.75A38-291[»]
2OCIX-ray1.90A38-291[»]
2OCKX-ray1.85A38-291[»]
2OCLX-ray1.90A38-291[»]
ProteinModelPortaliQ86WA6.
SMRiQ86WA6.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ86WA6.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini62 – 181AB hydrolase-1Sequence analysisAdd BLAST120

Sequence similaritiesi

Belongs to the AB hydrolase superfamily. Lipase family.Curated

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiKOG2984. Eukaryota.
ENOG410YNJD. LUCA.
GeneTreeiENSGT00390000004746.
HOGENOMiHOG000044258.
HOVERGENiHBG048762.
InParanoidiQ86WA6.
KOiK18399.
OMAiKWVDGIR.
OrthoDBiEOG091G0EEA.
PhylomeDBiQ86WA6.
TreeFamiTF318389.

Family and domain databases

Gene3Di3.40.50.1820. 1 hit.
InterProiIPR029058. AB_hydrolase.
IPR000073. AB_hydrolase_1.
[Graphical view]
PfamiPF00561. Abhydrolase_1. 1 hit.
[Graphical view]
SUPFAMiSSF53474. SSF53474. 1 hit.
PROSITEiPS00120. LIPASE_SER. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q86WA6-1) [UniParc]FASTAAdd to basket
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.

« Hide

        10         20         30         40         50
MVAVLGGRGV LRLRLLLSAL KPGIHVPRAG PAAAFGTSVT SAKVAVNGVQ
60 70 80 90 100
LHYQQTGEGD HAVLLLPGML GSGETDFGPQ LKNLNKKLFT VVAWDPRGYG
110 120 130 140 150
HSRPPDRDFP ADFFERDAKD AVDLMKALKF KKVSLLGWSD GGITALIAAA
160 170 180 190 200
KYPSYIHKMV IWGANAYVTD EDSMIYEGIR DVSKWSERTR KPLEALYGYD
210 220 230 240 250
YFARTCEKWV DGIRQFKHLP DGNICRHLLP RVQCPALIVH GEKDPLVPRF
260 270 280 290
HADFIHKHVK GSRLHLMPEG KHNLHLRFAD EFNKLAEDFL Q
Length:291
Mass (Da):32,543
Last modified:June 1, 2003 - v1
Checksum:i830B948492160244
GO
Isoform 2 (identifier: Q86WA6-2) [UniParc]FASTAAdd to basket
Also known as: Alpha

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

Show »
Length:274
Mass (Da):31,107
Checksum:i12B7F8595B0EBB0C
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti182V → R in CAA40859 (PubMed:2393862).Curated1
Sequence conflicti261G → A in CAA40859 (PubMed:2393862).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0091151 – 36MVAVL…AAAFG → MPRNLLYSLLSSHLSPHFS in isoform 2. 2 PublicationsAdd BLAST36

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS4483.2. [Q86WA6-1]
CCDS78105.1. [Q86WA6-2]
PIRiA56716.
RefSeqiNP_001289706.1. NM_001302777.1. [Q86WA6-2]
NP_004323.2. NM_004332.3. [Q86WA6-1]
UniGeneiHs.10136.

Genome annotation databases

EnsembliENST00000380375; ENSP00000369734; ENSG00000137274. [Q86WA6-2]
ENST00000380379; ENSP00000369739; ENSG00000137274. [Q86WA6-1]
ENST00000434640; ENSP00000390472; ENSG00000137274. [Q86WA6-2]
GeneIDi670.
KEGGihsa:670.
UCSCiuc003mva.4. human. [Q86WA6-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS4483.2. [Q86WA6-1]
CCDS78105.1. [Q86WA6-2]
PIRiA56716.
RefSeqiNP_001289706.1. NM_001302777.1. [Q86WA6-2]
NP_004323.2. NM_004332.3. [Q86WA6-1]
UniGeneiHs.10136.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2OCGX-ray1.75A38-291[»]
2OCIX-ray1.90A38-291[»]
2OCKX-ray1.85A38-291[»]
2OCLX-ray1.90A38-291[»]
ProteinModelPortaliQ86WA6.
SMRiQ86WA6.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi107138. 7 interactors.
STRINGi9606.ENSP00000369739.

Protein family/group databases

ESTHERihuman-BPHL. Valacyclovir-hydrolase.
MEROPSiS33.982.

PTM databases

iPTMnetiQ86WA6.
PhosphoSitePlusiQ86WA6.

Polymorphism and mutation databases

BioMutaiBPHL.
DMDMi39931107.

Proteomic databases

EPDiQ86WA6.
MaxQBiQ86WA6.
PaxDbiQ86WA6.
PeptideAtlasiQ86WA6.
PRIDEiQ86WA6.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000380375; ENSP00000369734; ENSG00000137274. [Q86WA6-2]
ENST00000380379; ENSP00000369739; ENSG00000137274. [Q86WA6-1]
ENST00000434640; ENSP00000390472; ENSG00000137274. [Q86WA6-2]
GeneIDi670.
KEGGihsa:670.
UCSCiuc003mva.4. human. [Q86WA6-1]

Organism-specific databases

CTDi670.
GeneCardsiBPHL.
H-InvDBHIX0020996.
HGNCiHGNC:1094. BPHL.
HPAiHPA036752.
HPA036753.
MIMi603156. gene.
neXtProtiNX_Q86WA6.
OpenTargetsiENSG00000137274.
PharmGKBiPA25402.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG2984. Eukaryota.
ENOG410YNJD. LUCA.
GeneTreeiENSGT00390000004746.
HOGENOMiHOG000044258.
HOVERGENiHBG048762.
InParanoidiQ86WA6.
KOiK18399.
OMAiKWVDGIR.
OrthoDBiEOG091G0EEA.
PhylomeDBiQ86WA6.
TreeFamiTF318389.

Enzyme and pathway databases

ReactomeiR-HSA-211945. Phase 1 - Functionalization of compounds.
SABIO-RKQ86WA6.

Miscellaneous databases

ChiTaRSiBPHL. human.
EvolutionaryTraceiQ86WA6.
GenomeRNAii670.
PROiQ86WA6.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000137274.
CleanExiHS_BPHL.
ExpressionAtlasiQ86WA6. baseline and differential.
GenevisibleiQ86WA6. HS.

Family and domain databases

Gene3Di3.40.50.1820. 1 hit.
InterProiIPR029058. AB_hydrolase.
IPR000073. AB_hydrolase_1.
[Graphical view]
PfamiPF00561. Abhydrolase_1. 1 hit.
[Graphical view]
SUPFAMiSSF53474. SSF53474. 1 hit.
PROSITEiPS00120. LIPASE_SER. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiBPHL_HUMAN
AccessioniPrimary (citable) accession number: Q86WA6
Secondary accession number(s): Q00306, Q13855, Q3KP51
Entry historyi
Integrated into UniProtKB/Swiss-Prot: December 15, 2003
Last sequence update: June 1, 2003
Last modified: November 2, 2016
This is version 139 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 6
    Human chromosome 6: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  4. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.