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WFDC2 Gene

protein-coding   GIFtS: 54
GCID: GC20P044098

WAP Four-Disulfide Core Domain 2

  See WFDC2-related disease
at  

(According to 1HGNC, 2Entrez Gene,
3UniProtKB/Swiss-Prot, 4UniProtKB/TrEMBL, 5OMIM, 6GeneLoc, 7Ensembl, 8DME, 9miRBase, 10fRNAdb, 12H-InvDB, 13NCBI, 14NONCODE, and/or 15RNAdb)
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This gene clusters with an RNA gene
Subcategory (RNA class): lncRNA

Quality score for the ORGUL clustered with this gene is 3

Aliases
WAP Four-Disulfide Core Domain 21 2     WAP52 3
Epididymal Protein 41 2     EDDM42
Epididymal Secretory Protein E42 3     dJ461P17.62
Major Epididymis-Specific Protein E42 3     Epididymis-Specific, Whey-Acidic Protein Type, Four-Disulfide Core2
Putative Protease Inhibitor WAP52 3     WAP Domain Containing Protein HE4-V42
HE42 3     WAP Four-Disulfide Core Domain Protein 22

External Ids:    HGNC: 159391   Entrez Gene: 104062   Ensembl: ENSG000001014437   UniProtKB: Q145083   
ORGUL members:         

Export aliases for WFDC2 gene to outside databases

Previous GC identifers: GC20P043826 GC20P044736 GC20P044783 GC20P043532 GC20P040839


(According to Entrez Gene, GeneCards, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
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Entrez Gene summary for WFDC2 Gene:
This gene encodes a protein that is a member of the WFDC domain family. The WFDC domain, or WAP Signature motif,
contains eight cysteines forming four disulfide bonds at the core of the protein, and functions as a protease
inhibitor in many family members. This gene is expressed in pulmonary epithelial cells, and was also found to be
expressed in some ovarian cancers. The encoded protein is a small secretory protein, which may be involved in
sperm maturation. (provided by RefSeq, Jul 2008)

GeneCards Summary for WFDC2 Gene:
WFDC2 (WAP four-disulfide core domain 2) is a protein-coding gene. Diseases associated with WFDC2 include ovarian cancer. GO annotations related to this gene include serine-type endopeptidase inhibitor activity and cysteine-type endopeptidase inhibitor activity.

UniProtKB/Swiss-Prot: WFDC2_HUMAN, Q14508
Function: Broad range protease inhibitor

Gene Wiki entry for WFDC2 Gene


(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 75), Regulatory elements and Epigenetics data according to QIAGEN, and/or SwitchGear Genomics)
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RefSeq DNA sequence at NCBI GenBank:
NC_000020.10  NC_018931.2  NT_011362.11  
Regulatory elements:
   Regulatory transcription factor binding sites in the WFDC2 gene promoter:
         STAT1   Sp1   Pax-6   Pax-2   STAT1beta   Nkx2-5   IRF-1   Pax-2a   STAT1alpha   COMP1   
         Other transcription factors

SwitchGear Promoter luciferase reporter plasmidWFDC2 promoter sequence
   Search Chromatin IP Primers for WFDC2

Epigenetics:
DNA Methylation CpG Assay Predesigned for Pyrosequencing in human, mouse, rat WFDC2


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

Entrez Gene cytogenetic band: 20q13.12   Ensembl cytogenetic band:  20q13.12   HGNC cytogenetic band: 20q13.12

WFDC2 Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
WFDC2 gene location

GeneLoc information about chromosome 20         GeneLoc Exon Structure

GeneLoc location for GC20P044098:  view genomic region     (about GC identifiers)

Start:
44,098,346 bp from pter      End:
44,110,172 bp from pter
Size:
11,827 bases      Orientation:
plus strand

(According to 1UniProtKB, HORDE, 2neXtProt, Ensembl, and/or Reactome, Modification sites according to PhosphoSitePlus, Specific Peptides from DME, 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, Cloud-Clone Corp., and/or eBioscience,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, Cloud-Clone Corp., and/or eBioscience, Antibodies by EMD Millipore, R&D Systems, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, LSBio, Abcam, Cloud-Clone Corp, and/or others.)
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UniProtKB/Swiss-Prot: WFDC2_HUMAN, Q14508 (See protein sequence)
Recommended Name: WAP four-disulfide core domain protein 2 precursor  
Size: 124 amino acids; 12993 Da
Subunit: Homotrimer; disulfide-linked
Secondary accessions: A2A2A5 A2A2A6 A6PVD5 Q6IB27 Q8WXV9 Q8WXW0 Q8WXW1 Q8WXW2 Q96KJ1
Alternative splicing: 5 isoforms:  Q14508-1   Q14508-2   Q14508-3   Q14508-4   Q14508-5   

Explore the universe of human proteins at neXtProt for WFDC2: NX_Q14508

Explore proteomics data for WFDC2 at MOPED

Post-translational modifications: 

  • Glycosylation2 at Asn44

  • See WFDC2 Protein Expression from SPIRE MOPED, PaxDB, and MaxQB

    REFSEQ proteins: NP_006094.3  
    ENSEMBL proteins: 
     ENSP00000361761   ENSP00000217425   ENSP00000404760   ENSP00000340215   ENSP00000342890  

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    (According to HGNC, IUPHAR, InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
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    HGNC Gene Families:
    WFDC: WAP four-disulfide core domain containing

    1 InterPro protein domain:
     IPR008197 WAP-type_4-diS_core

    Graphical View of Domain Structure for InterPro Entry Q14508

    ProtoNet protein and cluster: Q14508

    UniProtKB/Swiss-Prot: WFDC2_HUMAN, Q14508
    Similarity: Contains 2 WAP domains


    Find genes that share domains with WFDC2           About GenesLikeMe


    (According to 1UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or 2DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013, inGenious Targeting Laboratory, genOway,
    transcription factor targeting from QIAGEN and/or HOMER, miRNA Gene Targets from miRTarBase, shRNA from OriGene, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, SwitchGear Genomics, Gene Editing from DNA2.0, Clones from OriGene, GenScript, Sino Biological, DNA2.0, Vector BioLabs and/or Addgene, Cell Lines from GenScript, ESI BIO, In Situ Hybridization Assays from Advanced Cell Diagnostics, Flow cytometry from eBioscience, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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    Molecular Function:

         UniProtKB/Swiss-Prot Summary: WFDC2_HUMAN, Q14508
    Function: Broad range protease inhibitor

         Gene Ontology (GO): 5 molecular function terms:    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0004866endopeptidase inhibitor activity TAS1686187
    GO:0004867serine-type endopeptidase inhibitor activity IEA--
    GO:0004869cysteine-type endopeptidase inhibitor activity IEA--
    GO:0019828aspartic-type endopeptidase inhibitor activity IEA--
    GO:0030414peptidase inhibitor activity ----
         
    Find genes that share ontologies with WFDC2           About GenesLikeMe


    Phenotypes:
         1 GenomeRNAi human phenotype for WFDC2:
     Proliferating cells 

    Animal Models:
       inGenious Targeting Laboratory: Let us create your new Knockout/Knockin mouse model for WFDC2
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    1 qRT-PCR Assays for microRNA that regulate WFDC2:
    hsa-miR-3652
    SwitchGear 3'UTR luciferase reporter plasmidWFDC2 3' UTR sequence
    Inhib. RNA
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    (According to UniProtKB, COMPARTMENTS Subcellular localization database, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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    Subcellular locations from UniProtKB/Swiss-Prot
    WFDC2_HUMAN, Q14508: Secreted
    Subcellular locations from COMPARTMENTS: 

    CompartmentConfidence
    extracellular5

    Gene Ontology (GO): 2 cellular component terms:    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0005576extracellular region ----
    GO:0005615extracellular space TAS1686187

    Find genes that share ontologies with WFDC2           About GenesLikeMe


    (SuperPaths according to PathCards, Pathways according to R&D Systems, Cell Signaling Technology, KEGG, PharmGKB, BioSystems, Sino Biological, Reactome, Tocris Bioscience, GeneGo (Thomson Reuters), QIAGEN, and/or UniProtKB, Sets of similar genes according to GeneDecks, Interaction Networks according to QIAGEN, 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 Apr 2014 via Entrez Gene).
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        Custom Pathway & Disease-focused RT2 Profiler PCR Arrays for WFDC2
    Interactions:

        Search GeneGlobe Interaction Network for WFDC2

    1 Interacting protein for WFDC2 (Q145082, 3) via UniProtKB, MINT, STRING, and/or I2D
    InteractantInteraction Details
    GeneCardExternal ID(s)
    PTNP212462, 3MINT-64174 I2D: score=5 
    About this table

    Gene Ontology (GO): 3 biological process terms:    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0006508proteolysis TAS1686187
    GO:0007283spermatogenesis TAS1686187
    GO:0010951negative regulation of endopeptidase activity TAS1686187

    Find genes that share ontologies with WFDC2           About GenesLikeMe



    (Chemical Compounds according to UniProtKB, Enzo Life Sciences, EMD Millipore, Tocris Bioscience, ApexBio, HMDB, BitterDB, and/or Novoseek, Ligands according to IUPHAR, and Drugs according to DrugBank, Enzo Life Sciences, and/or PharmGKB)
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    Browse Small Molecules at EMD Millipore
       Browse drugs & compounds from Enzo Life Sciences
      Browse compounds at ApexBio 

    Browse Tocris compounds for WFDC2

    2 Novoseek inferred chemical compound relationships for WFDC2 gene    About this table
    Compound   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    oligonucleotide 26.4 1 16607372 (1)
    testosterone 6.76 1 11574662 (1)



    Find genes that share compounds with WFDC2           About GenesLikeMe



    (Secondary structures according to fRNAdb,
    GenBank/EMBL/DDBJ Accessions according to
    Unigene (Build 236 Homo sapiens; Apr 25 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,
    siRNAs from OriGene, QIAGEN, shRNA from OriGene, microRNA from QIAGEN, SwitchGear Genomics,
    Tagged/untagged cDNA clones from OriGene, GenScript, DNA2.0, Vector BioLabs, and/or Addgene, Primers from OriGene, and/or QIAGEN, Flow cytometry from eBioscience )
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    REFSEQ mRNAs for WFDC2 gene (5 alternative transcripts): 
    NM_006103.3  NM_080733.1  NM_080734.1  NM_080735.1  NM_080736.1  

    Unigene Cluster for WFDC2:

    WAP four-disulfide core domain 2
    Hs.2719  [show with all ESTs]
    Unigene Representative Sequence: BM921431
    7 Ensembl transcripts including schematic representations, and UCSC links where relevant:
    ENST00000372676(uc002xoo.3 uc002xop.3) ENST00000217425 ENST00000447118(uc002xoq.3)
    ENST00000339946 ENST00000462062 ENST00000342873(uc002xor.3) ENST00000488143

    miRNA
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    1 qRT-PCR Assays for microRNA that regulate WFDC2:
    hsa-miR-3652
    SwitchGear 3'UTR luciferase reporter plasmidWFDC2 3' UTR sequence
    Inhib. RNA
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    Additional mRNA sequence: 

    AF330260.1 AF330261.1 AF330262.1 AK225528.1 AK290288.1 AK311966.1 AY212888.1 BC039816.1 
    BC046106.1 CR456977.1 X63187.1 

    7 DOTS entries:

    DT.455898  DT.100817289  DT.92425100  DT.95072592  DT.100817290  DT.100672779  DT.120798237 

    Selected AceView cDNA sequences (see all 174):

    AA402537 AA385556 AW170346 AI298658 BM990005 BX096167 AA476938 NM_080736 
    BM722604 H50634 BU742202 AA290981 AI087799 BM976636 AA385354 BC046106 
    AI521428 AW054677 AI491895 BM982702 BM679249 AA284324 AA411533 AI800229 

    GeneLoc Exon Structure


    (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™, Protein expression images according to data from SPIRE 1MOPED, 2PaxDb, and 3MaxQB, plus additional links to SOURCE, and/or BioGPS, and/or UniProtKB,
    PCR Arrays from QIAGEN, Primers from OriGene, and/or QIAGEN, In Situ Hybridization Assays from Advanced Cell Diagnostics)
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    WFDC2 expression in normal human tissues (normalized intensities)
    See probesets specificity/sensitivity at GeneAnnot
    About this imageBioGPS <intensity>2/3
    CGAP TAG: CCTGCTTGTC
    WFDC2 Expression
    About this image


    WFDC2 expression in embryonic tissues and stem cells    About this table
    Data from LifeMap, the Embryonic Development and Stem Cells Database
     selected tissues (see all 14) fully expand
     
     Kidney (Urinary System)    fully expand to see all 7 entries
             Ureteric Bud Cells Ureteric Bud
             Renal Collecting Duct System
     
     Epithelial Cells
             Presumptive Podocytes Podocyte Layer
     
     Ovary (Reproductive System)
             Oviduct
     
     Neural Tube (Nervous System)
             Telencephalon
     
     Eye (Sensory Organs)
             Type1 Off Cone Bipolar Cells Inner Nuclear Layer
    WFDC2 Protein expression data from MOPED1, PaxDb2 and MaxQB3    About this image

    WFDC2 Protein Expression

    SOURCE GeneReport for Unigene cluster: Hs.2719

    UniProtKB/Swiss-Prot: WFDC2_HUMAN, Q14508
    Tissue specificity: Expressed in a number of normal tissues, including male reproductive system, regions of the
    respiratory tract and nasopharynx. Highly expressed in a number of tumors cells lines, such ovarian, colon,
    breast, lung and renal cells lines. Initially described as being exclusively transcribed in the epididymis

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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)
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    This gene was present in the common ancestor of chordates.

    Orthologs for WFDC2 gene from Selected species (see all 8)    About this table
    Organism Taxonomic
    classification
    Gene Description Human
    Similarity
    Orthology
    Type
    Details
    mouse
    (Mus musculus)
    Mammalia Wfdc21 , 5 WAP four-disulfide core domain 21, 5 74.04(n)1
    63.93(a)1
      2 (85.20 cM)5
    677011  NM_026323.21  NP_080599.11 
     1645624135 
    chicken
    (Gallus gallus)
    Aves WFDC26
    WAP four-disulfide core domain 2
    6(a)
    1 ↔ 1
    20(10829801-10840153)


    ENSEMBL Gene Tree for WFDC2 (if available)
    TreeFam Gene Tree for WFDC2 (if available)

    (Paralogs according to 1HomoloGene,
    2Ensembl, and 3SIMAP, Pseudogenes according to 4Pseudogene.org Build 68)
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    Paralogs for WFDC2 gene
    1 SIMAP similar gene for WFDC2 using alignment to 2 protein entries:     WFDC2_HUMAN (see all proteins):
    WFDC12

    Find genes that share paralogs with WFDC2           About GenesLikeMe



    (SNPs/Variants according to the 1NCBI SNP Database, 2Ensembl, 3PupaSUITE, 4UniProtKB, 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), the Human Cytochrome P450 Allele Nomenclature Database, and the Locus Specific Mutation Databases (LSDB), Blood group antigen gene mutations by BGMUT, Resequencing Primers, Cancer Mutation PCR Arrays and Assays, and Copy Number PCR Arrays from QIAGEN)
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    Selected SNPs for WFDC2 (see all 322)    About this table                                 

    Genomic DataTranscription Related DataAllele Frequencies
    SNP IDValidClinical
    significance
    Chr 20 posSequence#AA
    Chg
    TypeMore#Allele
    freq
    PopTotal
    sample
    More
    ----------
    rs790268691,2
    C,F--44096480(+) ACCTAG/ACACGG 1 -- us2k11Minor allele frequency- A:0.06EA 120
    rs1382765891,2
    --44096483(+) TAGCAC/TGGAAC 1 -- us2k10--------
    rs1429582671,2
    --44096526(+) TTGACG/TGATGA 1 -- us2k10--------
    rs61041731,2
    C,F--44096559(+) CCTGGC/TCCTGC 1 -- us2k17Minor allele frequency- T:0.20NA WA CSA EA 365
    rs1911298521,2
    --44096560(+) CTGGCC/TCTGCC 1 -- us2k10--------
    rs1168744541,2
    F--44096581(+) AGTCTG/ATATTC 1 -- us2k11Minor allele frequency- A:0.01NA 120
    rs1461366651,2
    --44096700(+) CAGCAA/GTGCCT 1 -- us2k10--------
    rs1388867221,2
    --44096738(+) GTCCAC/TGGGCT 1 -- us2k10--------
    rs22395331,2
    C,F,A,H--44096817(+) TGTGTC/TCCCAC 1 -- us2k117Minor allele frequency- T:0.46EA NS NA WA CSA 2589
    rs1494393301,2
    C--44097021(+) CCCAGG/TGCCCC 1 -- us2k10--------

    HapMap Linkage Disequilibrium report for WFDC2 (44098346 - 44110172 bp)

    Structural Variations
         Database of Genomic Variants (DGV) 1 variation for WFDC2:    About this table    
    Variant IDTypeSubtypePubMed ID
    nsv912892CNV Loss21882294

    Site Specific Mutation Identification with 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.)
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    1 disease for WFDC2:    
    About MalaCards
    ovarian cancer

    1 disease from the University of Copenhagen DISEASES database for WFDC2:
    Ovarian cancer

    Find genes that share disorders with WFDC2           About GenesLikeMe

    6 Novoseek inferred disease relationships for WFDC2 gene    About this table

    Disease   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    ovarian carcinoma 57.4 9 12839961 (3), 15781627 (2), 19053170 (1), 20126474 (1)
    ovarian cancer 53.6 11 19337252 (3), 20478777 (3), 11965550 (2), 15781627 (1)
    carcinoma 16.6 4 15781627 (2), 16607372 (1)
    adenocarcinoma 4.71 4 16600032 (2), 16607372 (1)
    tumors 0 7 15161682 (2), 15781627 (1), 16607372 (1), 17982616 (1)
    cancer 0 2 16455481 (1), 19337252 (1)

    Genetic Association Database (GAD): WFDC2

    Export disorders for WFDC2 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)
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    PubMed articles for WFDC2 gene, integrated from 10 sources (see all 84):
    (articles sorted by number of sources associating them with WFDC2)
        Utopia: connect your pdf to the dynamic
    world of online information

    1. A major human epididymis-specific cDNA encodes a protein with sequence homology to extracellular proteinase inhibitors. (PubMed id 1686187)1, 2, 3, 9 Kirchhoff C.... Krull N. (Biol. Reprod. 1991)
    2. Human epididymis protein 4 (HE4) is a secreted glycoprotein that is overexpressed by serous and endometrioid ovarian carcinomas. (PubMed id 15781627)1, 2, 9 Drapkin R....Hecht J.L. (Cancer Res. 2005)
    3. The HE4 (WFDC2) protein is a biomarker for ovarian carcinoma. (PubMed id 12839961)1, 2, 9 Hellstrom I.... Hellstrom K.E. (Cancer Res. 2003)
    4. The putative ovarian tumour marker gene HE4 (WFDC2), is expressed in normal tissues and undergoes complex alternative splicing to yield multiple protein isoforms. (PubMed id 11965550)1, 2, 9 Bingle L.... Bingle C.D. (Oncogene 2002)
    5. Human epididymis protein-4 (HE-4): a novel cross-class protease inhibitor. (PubMed id 23139753)1, 2 Chhikara N.... Yadav S. (PLoS ONE 2012)
    6. Voxelwise genome-wide association study (vGWAS). (PubMed id 20171287)1, 4 Stein J.L....Thompson P. (Neuroimage 2010)
    7. Identification of N-linked glycoproteins in human saliva by glycoprotein capture and mass spectrometry. (PubMed id 16740002)1, 2 Ramachandran P....Loo J.A. (J. Proteome Res. 2006)
    8. The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). (PubMed id 15489334)1, 2 Gerhard D.S.... Malek J. (Genome Res. 2004)
    9. The DNA sequence and comparative analysis of human chromosome 20. (PubMed id 11780052)1, 2 Deloukas P....Rogers J. (Nature 2001)
    10. Comparative hybridization of an array of 21,500 ovarian cDNAs for the discovery of genes overexpressed in ovarian carcinomas. (PubMed id 10570965)1, 3 Schummer M....Hood L. (Gene 1999)

    (in PubMed, OMIM, and NCBI Bookshelf)
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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: 10406 HGNC: 15939 AceView: WFDC2 Ensembl:ENSG00000101443 euGenes: HUgn10406
    ECgene: WFDC2 H-InvDB: WFDC2

    (According to HUGE)
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    (According to PharmGKB, ATLAS, HORDE, IMGT, LEIDEN, UniProtKB/Swiss-Prot, UniProtKB/TrEMBL, and/or others, e.g. Wikipedia and GeneReviews, via UniProtKB/Swiss-Prot)
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    NameDescription
    PharmGKB entry for WFDC2 Pharmacogenomics, SNPs, Pathways
    ATLAS Chromosomes in Cancer entry for WFDC2 Genetics and Cytogenetics in Oncology and Haematology

    (Patent information from GeneIP,
    Licensable technologies from WIS Yeda, Salk, Tufts,
    IP news from LifeMap Sciences, Inc.)
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    Patent Information for WFDC2 gene:
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