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Category Symbol Source: HGNC EntrezGene Ensembl GeneCards RNA genes CroW21

GIFtS
-

BPHL Gene

protein-coding GIFtS: 50
GCID: GC06P003118

biphenyl hydrolase-like (serine hydrolase)

(Previous symbol: MCNAA)

Explore 4 diseases affiliated with
BPHL via

MalaCards

our new
Human Malady Compendium

(According to ¹HGNC, ²Entrez Gene,
³UniProtKB/Swiss-Prot, ⁴UniProtKB/TrEMBL, ⁵OMIM, ⁶GeneLoc, ⁷Ensembl, ⁸DME, ⁹miRBase, and/or ¹⁰fRNAdb)
About This Section

Aliases
Biphenyl Hydrolase-Like (Serine Hydrolase)¹ ²		VACVASE²
MCNAA¹ ² ³		Valacyclovir Hydrolase²
Bph-Rp¹		Valacyclovirase³
Biphenyl Hydrolase-Like Protein² ³		EC 3.1.-.-³
Biphenyl Hydrolase-Related Protein² ³		VACVase³
Breast Epithelial Mucin-Associated Antigen² ³		Valacyclovirase³
BPH-RP²

External Ids:	HGNC: 1094¹	Entrez Gene: 670²	Ensembl: ENSG00000137274⁷	OMIM: 603156⁵	UniProtKB: Q86WA6³

Export aliases for BPHL gene to outside databases

Previous GC identifers: GC06P003104 GC06P003063 GC06P002998

(According to Entrez Gene, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
About This Section

Entrez Gene summary for BPHL:

This gene encodes a member of the serine protease family of hydrolytic enzymes which contain a serine in their active

site. The encoded protein may play a role in activation of the antiviral prodrug valacyclovir. Alternatively spliced

transcript variants have been described.(provided by RefSeq, Jan 2009)

UniProtKB/Swiss-Prot: BPHL_HUMAN, Q86WA6

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

(According to GeneLoc and/or HGNC, and/or
Entrez Gene (NCBI build 37),
and/or miRBase,
Genomic Views according to UCSC (hg19) and Ensembl (release 69), Regulatory elements and Epigenetics data according to QIAGEN, SABiosciences, and/or SwitchGear Genomics)
About This Section

RefSeq DNA sequence:

NC_000006.11 NC_018917.1 NT_007592.15

Regulatory elements:

SABiosciences Regulatory transcription factor binding sites in the BPHL gene promoter:
TBP RFX1 AML1a FOXD1 Olf-1 Evi-1 C/EBPalpha RORalpha1 AREB6 POU2F1a
Other transcription factors

SwitchGear Promoter luciferase reporter plasmid: BPHL promoter sequence

Search SABiosciences Chromatin IP Primers for BPHL

Epigenetics:

QIAGEN PyroMark CpG Assay predesigned Pyrosequencing DNA Methylation assays in human, mouse, rat BPHL

Genomic Location:
Genomic View: UCSC Golden Path with GeneCards custom track

Entrez Gene cytogenetic band: 6p25 Ensembl cytogenetic band: 6p25.2 HGNC cytogenetic band: 6p25

BPHL Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
BPHL gene location

GeneLoc information about chromosome 6 GeneLoc Exon Structure

GeneLoc location for GC06P003118: view genomic region (about GC identifiers)

Start:	3,118,608 bp from pter	End:	3,153,812 bp from pter
Size:	35,205 bases	Orientation:	plus strand

(According to ¹UniProtKB, HORDE, neXtProt, Ensembl, and/or Reactome, Modification sites according to ²PhosphoSitePlus, Specific Peptides from DME, Protein expression images according to data from SPIRE MOPED and PaxDb, RefSeq according to NCBI, PDB rendering according to OCA and/or Proteopedia, Recombinant Proteins from EMD Millipore, R&D Systems, GenScript, Enzo Life Sciences, OriGene, Novus Biologicals, Sino Biological, ProSpec, and/or Uscn,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, and/or Uscn, Ontologies according to Gene Ontology Consortium 01 Mar 2013 and Entrez Gene, Antibodies by EMD Millipore, R&D Systems, GenScript, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, Abcam, and/or Uscn)
About This Section

UniProtKB/Swiss-Prot: BPHL_HUMAN, Q86WA6 (See protein sequence)

Recommended Name: Valacyclovir hydrolase precursor

Size: 291 amino acids; 32543 Da

Subunit: Monomer. May also form homodimers

4 PDB 3D structures from and Proteopedia for BPHL:

2OCG (3D)

2OCI (3D)

2OCK (3D)

2OCL (3D)

Secondary accessions: Q00306 Q13855 Q3KP51

Alternative splicing: 2 isoforms: Q86WA6-1 Q86WA6-2

Explore the universe of human proteins at neXtProt for BPHL: NX_Q86WA6

Post-translational modifications:

View modification sites using PhosphoSitePlus²

View neXtProt modification sites for NX_Q86WA6

BPHL Protein expression data from MOPED and PaxDb: About this image

REFSEQ proteins: NP_004323.2

ENSEMBL proteins:

ENSP00000390472 ENSP00000394072 ENSP00000396637 ENSP00000413762 ENSP00000369739

ENSP00000395744 ENSP00000369734 ENSP00000369726

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Gene Ontology (GO): 1 cellular component term (GO ID links to tree view): About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0005739	mitochondrion	ISS	--

BPHL for ontologies About GeneDecksing

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(According to InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
About This Section

ProtoNet protein and cluster: Q86WA6

3 Blocks protein families:

IPB000073 Alpha/beta hydrolase fold

IPB003089 Alpha/beta hydrolase fold signature

IPB008262 Lipase

UniProtKB/Swiss-Prot: BPHL_HUMAN, Q86WA6

Similarity: Belongs to the AB hydrolase superfamily. Lipase family

(According to ¹UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or ²DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013,
bound targets from SABiosciences, miRNA Gene Targets from miRTarBase shRNA from OriGene, RNAi from EMD Millipore, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, Gene Editing from DNA2.0, Clones from EMD Millipore, OriGene, SwitchGear Genomics, GenScript, Sino Biological, DNA2.0, and Vector BioLabs, Cell Lines from GenScript, LifeMap BioReagents, In Situ Hybridization Assays from Advanced Cell Diagnostics, Ontologies according to Gene Ontology Consortium 01 Mar 2013 via Entrez Gene.)
About This Section

Function Summary:

UniProtKB/Swiss-Prot: BPHL_HUMAN, Q86WA6

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

Genatlas biochemistry entry for BPHL:

biphenyl hydrolase related protein,highly expressed in liver and kidney,involved in the degradation of polychlorinated

biphenyls

Enzyme Number (IUBMB): EC 3.1.-.-¹

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Gene Ontology (GO): 1 molecular function term (GO ID links to tree view): About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0016787	hydrolase activity	IEA	--

BPHL for ontologies About GeneDecksing

(Pathways according to EMD Millipore, R&D Systems, Cell Signaling Technology, KEGG, PharmGKB, BioSystems, Reactome, Tocris Bioscience, GeneGo (Thomson Reuters), QIAGEN, and/or UniProtKB, Sets of similar genes according to GeneDecks, Interaction Networks according to SABiosciences, and/or STRING, Interactions according to ¹UniProtKB, ²MINT, ³I2D, and/or ⁴STRING, with links to IntAct and Ensembl, Ontologies according to Gene Ontology Consortium 01 Mar 2013 via Entrez Gene).
About This Section

Interactions:

Search SABiosciences Gene Network Central^TM Interacting Genes and Proteins Networks for BPHL

Gene Ontology (GO): 2 biological process terms (GO ID links to tree view): About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0006520	cellular amino acid metabolic process	TAS	7759552
GO:0009636	response to toxin	TAS	7759552

BPHL for ontologies About GeneDecksing

(Chemical Compounds according to UniProtKB, Enzo Life Sciences, EMD Millipore, Tocris Bioscience HMDB, BitterDB, and/or Novoseek, and Drugs according to DrugBank, Enzo Life Sciences, and/or PharmGKB, with drugs/clinical trials/news search links to CenterWatch)
About This Section

BPHL for compounds About GeneDecksing

Browse Small Molecules at EMD Millipore

Browse drugs & compounds from Enzo Life Sciences

Browse Tocris compounds for BPHL

1 DrugBank Compound for BPHL About this table

Compound	Synonyms	CAS #	Type	Actions	PubMed Ids
L-Tyrosinamide	L-Tyrosine amide (see all 2)	4985-46-0	target	--	10592235

5 Novoseek chemical compound relationships for BPHL gene About this table

Compound	-log (P-Val)	Hits	PubMed IDs for Articles with Shared Sentences (# sentences)
valacyclovir	83.5	9	12732646 (3), 15832508 (2), 16028355 (1)
acyclovir	58.4	5	15832508 (1), 16028355 (1)
serine	47.2	15	9721218 (3), 16028355 (2), 7759552 (1), 12732646 (1) (see all 5)
zidovudine	42.9	1	15832508 (1)
nucleoside	36.4	14	15832508 (6), 16028355 (3)

Search CenterWatch for drugs/clinical trials and news about BPHL

(Secondary structures according to fRNAdb,
GenBank/EMBL/DDBJ Accessions according to
Unigene (Build 235 Homo sapiens; Mar 10 2013) or GenBank,
RefSeq according to Entrez Gene,
DOTS (version 10), and/or AceView, transcript ids from Ensembl with links to UCSC,
exon structure from GeneLoc, alternative splicing isoforms according to ASD and/or ECgene,
RNAi Products from EMD Millipore,
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Tagged/untagged cDNA clones from OriGene, SwitchGear Genomics, GenScript, DNA2.0, Vector BioLabs, Primers from OriGene, SABiosciences, and/or QIAGEN )
About This Section

REFSEQ mRNAs for BPHL gene:

NM_004332.2

Unigene Cluster for BPHL:

Biphenyl hydrolase-like (serine hydrolase)

Hs.10136 [show with all ESTs]

Unigene Representative Sequence: AK124783

12 Ensembl transcripts including schematic representations, and UCSC links where relevant:

ENST00000434640 ENST00000424847 ENST00000430655(uc003muz.3 uc011dht.2)

ENST00000433912 ENST00000380379(uc003mva.3) ENST00000490918 ENST00000479273

ENST00000488487 ENST00000423798 ENST00000464040 ENST00000380375(uc003muy.3)

ENST00000380368

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Additional cDNA sequence:

AJ617684.1 AK124783.1 AK297518.1 AK314909.1 AY927635.1 AY927636.1 BC037778.1 BC106901.1

NR_026648.1 NR_026649.1 NR_026650.1 X57653.1 X81372.1

14 DOTS entries:

DT.91682147 DT.453725 DT.100893166 DT.99932223 DT.101982346 DT.75193493 DT.95158504 DT.92427973

DT.100059854 DT.92050082 DT.95158498 DT.97824571 DT.95183922 DT.99986278

24/121 AceView cDNA sequences (see all 121):

X81372 AI565320 AI360932 CA420674 BQ669554 CA306822 AJ617684 AI268326

AI017491 AA887327 BP376230 AI418120 AI383521 AW276222 NM_004332 AW872800

AI161218 Z41013 CK904003 AI818871 BM052802 AI167945 BM476445 BU736294

GeneLoc Exon Structure

5/6 Alternative Splicing Database (ASD) splice patterns (SP) for BPHL (see all 6) About this scheme

ExUns:	1a	·	1b	·	1c	^	2	^	3a	·	3b	^	4a	·	4b	^	5	^	6a	·	6b	^	7	^	8	^	9
SP1:											-		-								-
SP2:											-		-										-
SP3:							-				-		-										-
SP4:											-		-
SP5:

ECgene alternative splicing isoforms for BPHL

(RNA expression data according to H-InvDB, NONCODE, miRBase, and RNAdb, Expression images according to data from BioGPS, Illumina Human BodyMap, and CGAP SAGE, Sets of similar genes according to GeneDecks, in vivo and in vitro expression data from LifeMap Discovery™, plus additional links to Genevestigator, and/or SOURCE, and/or BioGPS, and/or UniProtKB,
PCR Arrays from SABiosciences, Primers from OriGene, SABiosciences, and/or QIAGEN, In Situ Hybridization Assays from Advanced Cell Diagnostics)
About This Section

BPHL expression in normal human tissues (normalized intensities)
See probesets specificity/sensitivity at GeneAnnot
About this imageBioGPS
CGAP TAG: ATGCCTTTGA

About this image

BPHL expression in embryonic tissues and stem cells

Expression by the Database of Embryonic development, Stem cell research, and Regenerative medicine About this table

4 LifeMap In Vivo Development Anatomical Compartments/Cells

Tissue

Anatomical Compartment

Cell

Category (developmental path)

Brain

Brain

Brain

Neural Tube

Expression:

Positive

Negative

Selective marker

Experimental details:

Curated

Microarrays

In-situ hybridization

See BPHL Protein Expression from SPIRE MOPED and PaxDB
Genevestigator expression for BPHL

SOURCE GeneReport for Unigene cluster: Hs.10136

UniProtKB/Swiss-Prot: BPHL_HUMAN, Q86WA6

Tissue specificity: Expressed at high levels in liver and kidney and lower levels in heart, intestine and skeletal

muscle

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In Situ
Assay Products:

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(Orthologs according to ^1,2HomoloGene (²older version, for species not in ¹newer version), ³euGenes, ⁴SGD , ⁵MGI Mar 06 2013, with possible further links to Flybase and/or WormBase, and/or ⁶Ensembl pan taxonomic compara , Gene Trees according to Ensembl and TreeFam)
About This Section

This gene was present in the common ancestor of animals.

Orthologs for BPHL gene from 6/20 species (see all 20) About this table

Organism	Taxonomic classification	Gene	Description	Human Similarity	Orthology Type	Details
mouse (Mus musculus)	Mammalia	Bphl^{1 , 5}	biphenyl hydrolase-like (serine hydrolase, breast epithelial more^{1, 5}	82.74(n)¹ 84.64(a)¹		13 (14.02 cM)⁵ 68021¹ NM_026512.1¹ NP_080788.1¹ 34037641⁵
chicken (Gallus gallus)	Aves	BPHL¹	biphenyl hydrolase-like (serine hydrolase)	73.79(n) 78.24(a)		420885 XM_418972.3 XP_418972.1
lizard (Anolis carolinensis)	Reptilia	BPHL⁶	--	72(a)	1 ↔ 1	GL343247.1(1017320-1044452)
zebrafish (Danio rerio)	Actinopterygii	Dr.12500²	Danio rerio, Similar to RIKEN cDNA 2010012D11 gene, more	71.96(n)		BC045899.1
fruit fly (Drosophila melanogaster)	Insecta	CG5377^{1 , 3}	serine hydrolase³ CG5377¹	45(a)³ 51.6(n)¹ 46(a)¹		94A16³ 42645¹ NM_142795.3¹ NP_651052.1¹
worm (Caenorhabditis elegans)	Secernentea	K01A2.5¹	Protein K01A2.5	42.14(n) 25.61(a)		173418 NM_061300.3 NP_493701.1

ENSEMBL Gene Tree for BPHL (if available)
TreeFam Gene Tree for BPHL (if available)

(Paralogs according to ¹HomoloGene,
²Ensembl, and ³SIMAP, Pseudogenes according to ⁴Pseudogene.org Build 68)
About This Section

(SNPs/Variants according to the ¹NCBI SNP Database, ²Ensembl, ³PupaSUITE, UniProtKB, and DNA2.0, Linkage Disequilibrium by HapMap, Structural Variations(CNVs/InDels/Inversions) from the Database of Genomic Variants, Mutations from the Human Gene Mutation Database (HGMD) and the Locus Specific Mutation Databases (LSDB), Blood group antigen gene mutations by BGMUT, Resequencing Primers from QIAGEN, Cancer Mutation PCR Arrays and Assays and Copy Number PCR Arrays from SABiosciences)
About This Section

SNP ID	Valid	Clinical significance	Chr 6 pos	Sequence	#	AA Chg	Type	More	#	Allele freq	Pop	Total sample	More
Genomic Data					Transcription Related Data				Allele Frequencies
				--	--	--		--	--
rs6596951^1,2	C,F,A,	--	3116944(+)	`TTAGCT/CGGGCA`	4	--	us2k¹		6		NA WA CSA	11
rs112204652^1,2		--	3116952(+)	`GCATGG/ATGGCG`	4	--	us2k¹		1		CSA	2
rs148151711^1,2		--	3117061(+)	`CCAGCC/GTGGGC`	4	--	us2k¹		0	--	--	--	--
rs6913730^1,2	C,F,H,	--	3117196(+)	`TCATTT/GCTGAG`	4	--	us2k¹		6		NS EA WA	536
rs115753736^1,2	C,F,	--	3117201(+)	`TCTGAG/TATGAA`	4	--	us2k¹		1		WA	118
rs6930190^1,2	C,F,A,	--	3117271(+)	`TCAAAC/TGATAT`	4	--	us2k¹		9		NA WA CSA EA	250
rs9501924^1,2	C,F,A,H,	--	3117521(+)	`GAGGAG/AAAGAA`	4	--	us2k¹ trp³		8		NS EA NA WA CSA	542
rs74977824^1,2	F,	--	3117537(+)	`ATATGC/TAAAGA`	4	--	us2k¹		1		WA	118
rs76162526^1,2	F,	--	3117538(+)	`TATGCA/GAAGAA`	4	--	us2k¹		1		WA	118
rs187330106^1,2		--	3117635(+)	`TAAAAA/GGCAAT`	4	--	us2k¹		0	--	--	--	--

HapMap Linkage Disequilibrium report for BPHL (3118608 - 3153812 bp)
Structural Variations (Copy Number Variations, Insertions/Deletions, Inversions)
Database of Genomic Variants (DGV): 4 variations for BPHL
3 CNVs: 69300 69302 69301
1 Indel: 28266

SABiosciences Cancer Mutation PCR Assays

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(in which this Gene is Involved, According to MalaCards, OMIM, UniProtKB, the University of Copenhagen DISEASES database, Novoseek, Genatlas, GeneTests, GAD, HuGE Navigator, and/or TGDB.)
About This Section

BPHL for disorders           About GeneDecksing

OMIM gene information: 603156    OMIM disorders: --

4 diseases for BPHL:    About MalaCards

hepatitis b breast cancer hepatitis alcoholism

3 Novoseek disease relationships for BPHL gene About this table

Disease	-log (P-Val)	Hits	PubMed IDs for Articles with Shared Sentences (# sentences)
breast cancer	43.2	2	2100557 (1), 1377884 (1)
breast carcinoma	42	2	12732646 (1)
tumors	0	2	2095928 (1), 7493358 (1)

Human Genome Epidemiology (HuGE) Navigator: BPHL (2 documents)

Export disorders for BPHL gene to outside databases

(in PubMed. Associations of this gene to articles via ¹Entrez Gene, ²UniProtKB/Swiss-Prot, ³HGNC, ⁴GAD, ⁵PharmGKB, ⁶HMDB, ⁷DrugBank, ⁸UniProtKB/TrEMBL, ⁹ Novoseek, and/or ¹⁰fRNAdb)
About This Section

PubMed articles for BPHL gene, integrated from 9 sources (see all 26):
(articles sorted by number of sources associating them with BPHL)

Utopia: connect your pdf to the dynamic
world of online information

A novel nucleoside prodrug-activating enzyme: substrate specificity of biphenyl hydrolase-like protein. (PubMed id 15832508)^{1, 2, 3, 9} Kim I....Amidon G.L. (2004)
Structural characterization and chromosomal localization of the gene encoding human biphenyl hydrolase-related protein (BPHL). (PubMed id 9721218)^{1, 2, 3, 9} Puente X.S.... Lopez-Otin C. (1998)
Cloning and expression analysis of a novel human serine hydrolase with sequence similarity to prokaryotic enzymes involved in the degradation of aromatic compounds. (PubMed id 7759552)^{1, 2, 3, 9} Puente X.S. and Lopez-Otin C. (1995)
Identification of a human valacyclovirase: biphenyl hydrolase-like protein as valacyclovir hydrolase. (PubMed id 12732646)^{1, 2, 9} Kim I.... Amidon G.L. (2003)
Molecular basis of prodrug activation by human valacyclovirase, an alpha-amino acid ester hydrolase. (PubMed id 18256025)^{1, 2, 9} Lai L....Amidon G.L. (2008)
Cloning and sequencing of a complementary DNA encoding a M(r) 70,000 human breast epithelial mucin-associated antigen. (PubMed id 2393862)^{1, 2, 9} Larocca D.... Ceriani R.L. (1990)
The DNA sequence and analysis of human chromosome 6. (PubMed id 14574404)^{1, 2} Mungall A.J.... Beck S. (2003)
Structure and specificity of a human valacyclovir activating enzyme: a homology model of BPHL. (PubMed id 16028355)^{1, 9} Kim I....Amidon G.L. (2004)
Initial characterization of the human central proteome. (PubMed id 21269460)² Burkard T.R.... Colinge J. (2011)
A proteome-wide, quantitative survey of in vivo ubiqui tylation sites reveals widespread regulatory roles. (PubMed id 21890473)¹ Wagner S.A....Choudhary C. (2011)

(in PubMed, OMIM, and NCBI Bookshelf)
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		AND	OR
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(According to Entrez Gene, HGNC, AceView, euGenes, Ensembl, miRBase, ECgene, Kegg, and/or H-InvDB)
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Entrez Gene: 670	HGNC: 1094	AceView: BPHL	Ensembl:ENSG00000137274	euGenes: HUgn670
ECgene: BPHL	H-InvDB: BPHL

(According to HUGE)
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(According to PharmGKB, ATLAS, HORDE, IMGT, LEIDEN, UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL,
Wikipedia and/or GeneReviews via UniProtKB/Swiss-Prot)
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Name	Description
PharmGKB entry for BPHL	Pharmacogenomics, SNPs, Pathways

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biphenyl hydrolase-like (serine hydrolase)

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biphenyl hydrolase-like (serine hydrolase)

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