Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Basket 0
(max 400 entries)x

Your basket is currently empty.

Select item(s) and click on "Add to basket" to create your own collection here
(400 entries max)

Q86WA6

- BPHL_HUMAN

UniProt

Q86WA6 - BPHL_HUMAN

Protein

Valacyclovir hydrolase

Gene

BPHL

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
    • BLAST
    • Align
    • Format
    • Add to basket
    • History
      Entry version 118 (01 Oct 2014)
      Sequence version 1 (01 Jun 2003)
      Previous versions | rss
    • Help video
    • Feedback
    • Comment

    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)LengthDescriptionGraphical viewFeature identifierActions
    Active sitei139 – 1391Nucleophile1 Publication
    Sitei140 – 1401Binding of alpha-amino group of substrate
    Active sitei244 – 2441Charge relay system1 PublicationPROSITE-ProRule annotation
    Active sitei272 – 2721Charge relay system1 PublicationPROSITE-ProRule annotation

    GO - Molecular functioni

    1. hydrolase activity Source: UniProtKB-KW

    GO - Biological processi

    1. cellular amino acid metabolic process Source: ProtInc
    2. response to toxic substance Source: ProtInc

    Keywords - Molecular functioni

    Hydrolase

    Enzyme and pathway databases

    SABIO-RKQ86WA6.

    Protein family/group databases

    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
    ProteomesiUP000005640: Chromosome 6

    Organism-specific databases

    HGNCiHGNC:1094. BPHL.

    Subcellular locationi

    GO - Cellular componenti

    1. extracellular vesicular exosome Source: UniProt
    2. mitochondrion Source: UniProtKB

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi139 – 1391S → A: <0.1% of wild type activity. 1 Publication
    Mutagenesisi244 – 2441D → N: <0.1% of wild type activity. 1 Publication
    Mutagenesisi272 – 2721H → A: Complete loss of activity. 1 Publication

    Organism-specific databases

    PharmGKBiPA25402.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Signal peptidei1 – 37371 PublicationAdd
    BLAST
    Chaini38 – 291254Valacyclovir hydrolasePRO_0000017841Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei86 – 861N6-acetyllysineBy similarity
    Modified residuei119 – 1191N6-acetyllysineBy similarity
    Modified residuei126 – 1261N6-acetyllysine; alternate1 Publication
    Modified residuei126 – 1261N6-succinyllysine; alternateBy similarity
    Modified residuei184 – 1841N6-succinyllysineBy similarity
    Modified residuei191 – 1911N6-acetyllysine; alternateBy similarity
    Modified residuei191 – 1911N6-succinyllysine; alternateBy similarity
    Modified residuei217 – 2171N6-acetyllysineBy similarity
    Modified residuei243 – 2431N6-acetyllysineBy similarity
    Modified residuei260 – 2601N6-acetyllysine; alternateBy similarity
    Modified residuei260 – 2601N6-succinyllysine; alternateBy similarity
    Modified residuei271 – 2711N6-acetyllysine; alternateBy similarity
    Modified residuei271 – 2711N6-succinyllysine; alternateBy similarity

    Keywords - PTMi

    Acetylation

    Proteomic databases

    MaxQBiQ86WA6.
    PaxDbiQ86WA6.
    PRIDEiQ86WA6.

    PTM databases

    PhosphoSiteiQ86WA6.

    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

    ArrayExpressiQ86WA6.
    BgeeiQ86WA6.
    CleanExiHS_BPHL.
    GenevestigatoriQ86WA6.

    Organism-specific databases

    HPAiHPA036752.

    Interactioni

    Subunit structurei

    Monomer. May also form homodimers.2 Publications

    Protein-protein interaction databases

    BioGridi107138. 3 interactions.

    Structurei

    Secondary structure

    1
    291
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Beta strandi40 – 467
    Beta strandi49 – 579
    Beta strandi60 – 667
    Helixi73 – 764
    Helixi78 – 836
    Turni86 – 883
    Beta strandi89 – 946
    Helixi113 – 12715
    Beta strandi131 – 1388
    Helixi140 – 15112
    Turni153 – 1553
    Beta strandi156 – 1638
    Helixi170 – 1778
    Helixi182 – 1843
    Helixi187 – 19711
    Helixi199 – 21416
    Helixi215 – 2184
    Helixi220 – 2223
    Beta strandi223 – 2253
    Helixi226 – 2316
    Beta strandi236 – 2416
    Beta strandi245 – 2473
    Helixi249 – 25810
    Beta strandi263 – 2675
    Helixi274 – 2774
    Helixi279 – 29012

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    2OCGX-ray1.75A38-291[»]
    2OCIX-ray1.90A38-291[»]
    2OCKX-ray1.85A38-291[»]
    2OCLX-ray1.90A38-291[»]
    ProteinModelPortaliQ86WA6.
    SMRiQ86WA6. Positions 38-291.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiQ86WA6.

    Family & Domainsi

    Sequence similaritiesi

    Belongs to the AB hydrolase superfamily. Lipase family.Curated

    Keywords - Domaini

    Signal

    Phylogenomic databases

    eggNOGiCOG0596.
    HOGENOMiHOG000044258.
    HOVERGENiHBG048762.
    InParanoidiQ86WA6.
    KOiK01175.
    OMAiGYDYFAR.
    OrthoDBiEOG741Z38.
    PhylomeDBiQ86WA6.
    TreeFamiTF318389.

    Family and domain databases

    Gene3Di3.40.50.1820. 1 hit.
    InterProiIPR029058. AB_hydrolase.
    [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. Align

    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

    MVAVLGGRGV LRLRLLLSAL KPGIHVPRAG PAAAFGTSVT SAKVAVNGVQ    50
    LHYQQTGEGD HAVLLLPGML GSGETDFGPQ LKNLNKKLFT VVAWDPRGYG 100
    HSRPPDRDFP ADFFERDAKD AVDLMKALKF KKVSLLGWSD GGITALIAAA 150
    KYPSYIHKMV IWGANAYVTD EDSMIYEGIR DVSKWSERTR KPLEALYGYD 200
    YFARTCEKWV DGIRQFKHLP DGNICRHLLP RVQCPALIVH GEKDPLVPRF 250
    HADFIHKHVK GSRLHLMPEG KHNLHLRFAD EFNKLAEDFL Q 291
    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)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti182 – 1821V → R in CAA40859. (PubMed:2393862)Curated
    Sequence conflicti261 – 2611G → A in CAA40859. (PubMed:2393862)Curated

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei1 – 3636MVAVL…AAAFG → MPRNLLYSLLSSHLSPHFS in isoform 2. 2 PublicationsVSP_009115Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    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]
    PIRiA56716.
    RefSeqiNP_004323.2. NM_004332.2. [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.
    UCSCiuc003muy.3. human. [Q86WA6-2]
    uc003mva.3. human. [Q86WA6-1]

    Polymorphism databases

    DMDMi39931107.

    Keywords - Coding sequence diversityi

    Alternative splicing

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    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 .
    CCDSi CCDS4483.2. [Q86WA6-1 ]
    PIRi A56716.
    RefSeqi NP_004323.2. NM_004332.2. [Q86WA6-1 ]
    UniGenei Hs.10136.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    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 [» ]
    ProteinModelPortali Q86WA6.
    SMRi Q86WA6. Positions 38-291.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 107138. 3 interactions.

    Protein family/group databases

    MEROPSi S33.982.

    PTM databases

    PhosphoSitei Q86WA6.

    Polymorphism databases

    DMDMi 39931107.

    Proteomic databases

    MaxQBi Q86WA6.
    PaxDbi Q86WA6.
    PRIDEi Q86WA6.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000380375 ; ENSP00000369734 ; ENSG00000137274 . [Q86WA6-2 ]
    ENST00000380379 ; ENSP00000369739 ; ENSG00000137274 . [Q86WA6-1 ]
    ENST00000434640 ; ENSP00000390472 ; ENSG00000137274 . [Q86WA6-2 ]
    GeneIDi 670.
    KEGGi hsa:670.
    UCSCi uc003muy.3. human. [Q86WA6-2 ]
    uc003mva.3. human. [Q86WA6-1 ]

    Organism-specific databases

    CTDi 670.
    GeneCardsi GC06P003118.
    H-InvDB HIX0020996.
    HGNCi HGNC:1094. BPHL.
    HPAi HPA036752.
    MIMi 603156. gene.
    neXtProti NX_Q86WA6.
    PharmGKBi PA25402.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi COG0596.
    HOGENOMi HOG000044258.
    HOVERGENi HBG048762.
    InParanoidi Q86WA6.
    KOi K01175.
    OMAi GYDYFAR.
    OrthoDBi EOG741Z38.
    PhylomeDBi Q86WA6.
    TreeFami TF318389.

    Enzyme and pathway databases

    SABIO-RK Q86WA6.

    Miscellaneous databases

    ChiTaRSi BPHL. human.
    EvolutionaryTracei Q86WA6.
    GenomeRNAii 670.
    NextBioi 2744.
    PROi Q86WA6.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi Q86WA6.
    Bgeei Q86WA6.
    CleanExi HS_BPHL.
    Genevestigatori Q86WA6.

    Family and domain databases

    Gene3Di 3.40.50.1820. 1 hit.
    InterProi IPR029058. AB_hydrolase.
    [Graphical view ]
    SUPFAMi SSF53474. SSF53474. 1 hit.
    PROSITEi PS00120. LIPASE_SER. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    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. 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. 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.

    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: October 1, 2014
    This is version 118 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

    External Data

    Dasty 3