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Category   Symbol Source: HGNC EntrezGene Ensembl GeneCards RNA genes CroW21
GIFtS

WFIKKN2 Gene

protein-coding   GIFtS: 48
GCID: GC17P048912

WAP, follistatin/kazal, immunoglobulin, kunitz and netrin...

 Explore 3 diseases affiliated with
WFIKKN2 via our new
 Human Malady Compendium 
Biological research products
for WFIKKN2
    

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

Aliases
WAP, Follistatin/Kazal, Immunoglobulin, Kunitz And Netrin Domain Containing
21 2
     WFIKKN-Related Protein2 3
WFIKKNRP1 2 3 5     Multivalent Protease Inhibitor Protein2
WFDC20B1 2     WAP Four-Disulfide Core Domain 20B2
Growth And Differentiation Factor-Associated Serum Protein 12 3     WAP, FS, Ig, Two KU And NTR Module Related Protein2
WAP, Follistatin, Immunoglobulin, Kunitz And NTR Domain-Containing-Related
Protein2 3
     WAP, Kazal, Immunoglobulin, Kunitz And NTR Domain-Containing Protein 22
GASP-12 3     GASP13
HGASP-11     

External Ids:    HGNC: 309161   Entrez Gene: 1248572   Ensembl: ENSG000001737147   OMIM: 6108955   UniProtKB: Q8TEU83   

Export aliases for WFIKKN2 gene to outside databases

Previous GC identifers: GC17P046267 GC17P044279


(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 WFIKKN2:
The WFIKKN1 protein contains a WAP domain, follistatin domain, immunoglobulin domain, two tandem Kunitz domains, and an
NTR domain. This gene encodes a WFIKKN1-related protein which has the same domain organization as the WFIKKN1 protein.
The WAP-type, follistatin type, Kunitz-type, and NTR-type protease inhibitory domains may control the action of
multiple types of proteases. (provided by RefSeq, Jul 2008)

UniProtKB/Swiss-Prot: WFKN2_HUMAN, Q8TEU8
Function: Protease-inhibitor that contains multiple distinct protease inhibitor domains. Probably has serine protease-
and metalloprotease-inhibitor activity. Inhibits the biological activity of mature myostatin, but not activin (By
similarity)




(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_000017.10  NC_018928.1  NT_010783.15  
Regulatory elements:
   SABiosciences Regulatory transcription factor binding sites in the WFIKKN2 gene promoter:
         ISGF-3   RFX1   MAZR   CUTL1   LUN-1   C/EBPalpha   AREB6   N-Myc   c-Myb   ATF6   
         Other transcription factors

SwitchGear Promoter luciferase reporter plasmidWFIKKN2 promoter sequence
   Search SABiosciences Chromatin IP Primers for WFIKKN2

Epigenetics:
QIAGEN PyroMark CpG Assay predesigned Pyrosequencing DNA Methylation assays in human, mouse, rat WFIKKN2


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

Entrez Gene cytogenetic band: 17q21.33   Ensembl cytogenetic band:  17q21.33   HGNC cytogenetic band: 17q21.33

WFIKKN2 Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
WFIKKN2 gene location

GeneLoc information about chromosome 17         GeneLoc Exon Structure

GeneLoc location for GC17P048912:  view genomic region     (about GC identifiers)

Start:
48,912,011 bp from pter      End:
48,919,709 bp from pter
Size:
7,699 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: WFKN2_HUMAN, Q8TEU8 (See protein sequence)
Recommended Name: WAP, Kazal, immunoglobulin, Kunitz and NTR domain-containing protein 2 precursor  
Size: 576 amino acids; 63941 Da
Subunit: Interacts with both mature and propeptide myostatin/MSTN
Subcellular location: Secreted (By similarity)
Secondary accessions: Q6UXZ9

Explore the universe of human proteins at neXtProt for WFIKKN2: NX_Q8TEU8

Post-translational modifications:

  • View modification sites using PhosphoSitePlus2
  • View neXtProt modification sites for NX_Q8TEU8

  • WFIKKN2 Protein expression data from MOPED and PaxDb:    About this image 
    Estimated protein expression log10 (pmol).

    REFSEQ proteins: NP_783165.1  
    ENSEMBL proteins: 
     ENSP00000405889   ENSP00000311184  

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    Uscn Proteins for WFIKKN2

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

    GO IDQualified GO termEvidencePubMed IDs
    GO:0005576extracellular region IEA--


    WFIKKN2 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

    WFIKKN2 for domains           About GeneDecksing

    5/12 InterPro domains/families (see all 12):
     IPR003598 Ig_sub2
     IPR007110 Ig-like_dom
     IPR008993 TIMP-like_OB-fold
     IPR002350 Prot_inh_Kazal
     IPR013098 Ig_I-set

    Graphical View of Domain Structure for InterPro Entry Q8TEU8

    ProtoNet protein and cluster: Q8TEU8

    4 Blocks protein families:
    IPB003598 Immunoglobulin C-2 type
    IPB008197 4-disulphide core signature
    IPB011497 Protease inhibitor
    IPB013098 Immunoglobulin I-set


    UniProtKB/Swiss-Prot: WFKN2_HUMAN, Q8TEU8
    Similarity: Belongs to the WFIKKN family
    Similarity: Contains 2 BPTI/Kunitz inhibitor domains
    Similarity: Contains 1 Ig-like C2-type (immunoglobulin-like) domain
    Similarity: Contains 1 Kazal-like domain
    Similarity: Contains 1 NTR domain
    Similarity: Contains 1 WAP domain


    (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: WFKN2_HUMAN, Q8TEU8
    Function: Protease-inhibitor that contains multiple distinct protease inhibitor domains. Probably has serine protease-
    and metalloprotease-inhibitor activity. Inhibits the biological activity of mature myostatin, but not activin (By
    similarity)

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    Gene Ontology (GO): 3 molecular function terms (GO ID links to tree view):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0004867serine-type endopeptidase inhibitor activity IEA--
    GO:0005515protein binding ----
    GO:0008191metalloendopeptidase inhibitor activity IEA--


    WFIKKN2 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 CentralTM Interacting Genes and Proteins Networks for WFIKKN2

    STRING Interaction Network Preview (showing 5 interactants - click image to see 7)

    5/7 Interacting proteins for WFIKKN2 (Q8TEU82, 3 ENSP000003111844) via UniProtKB, MINT, STRING, and/or I2D (see all 7)
    InteractantInteraction Details
    GeneCardExternal ID(s)
    BMP4P126442, 3, ENSP000002454514MINT-8044135 I2D: score=1 STRING: ENSP00000245451
    BMP8BP348202, 3, ENSP000003619154MINT-8044393 I2D: score=1 STRING: ENSP00000361915
    TGFB1P011372, 3, ENSP000002219304MINT-8044312 I2D: score=1 STRING: ENSP00000221930
    BMP2P126432, 3, ENSP000003681044MINT-8044372 I2D: score=1 STRING: ENSP00000368104
    BMP3P126452, 3, ENSP000002827014MINT-8044382 I2D: score=1 STRING: ENSP00000282701
    About this table

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

    GO IDQualified GO termEvidencePubMed IDs
    GO:0007179transforming growth factor beta receptor signaling pathway IEA--


    WFIKKN2 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
    Browse Small Molecules at EMD Millipore
    Browse drugs & compounds from Enzo Life Sciences

    Browse Tocris compounds for WFIKKN2
    Search CenterWatch for drugs/clinical trials and news about WFIKKN2 / WFKN2 

    (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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    About This Section

    REFSEQ mRNAs for WFIKKN2 gene: 
    NM_175575.5  

    Unigene Cluster for WFIKKN2:

    WAP, follistatin/kazal, immunoglobulin, kunitz and netrin domain containing 2
    Hs.211475  [show with all ESTs]
    Unigene Representative Sequence: NM_175575
    2 Ensembl transcripts including schematic representations, and UCSC links where relevant:
    ENST00000426127 ENST00000311378(uc010dbu.3 uc002isv.4)

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    Additional cDNA sequence: 

    AF468657.1 AK127743.1 AK131196.1 AK298172.1 AK312821.1 AY358142.1 BC140842.1 BC140844.1 

    1 DOTS entry:

    DT.101979443 

    24/26 AceView cDNA sequences (see all 26):

    AF468657 F27556 BQ954191 BX108923 NM_175575 AY358142 BX461258 AW468704 
    AI932781 AA364422 AL540240 AK127743 AL537450 BX452077 AI919298 BX464797 
    CA394579 AI833106 BX433163 CD671934 BX424452 AL540239 BG221308 AL537449 

    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™, 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

    WFIKKN2 expression in normal human tissues (normalized intensities)
    See probesets specificity/sensitivity at GeneAnnot
    About this imageBioGPS
    CGAP TAG: GGCAATAGCA

    Microarray
    RNAseq (Illumina Body Map)
    (100×FPKM)½
    SAGE (Serial Analysis of Gene Expression)

    About this image

    WFIKKN2 expression in embryonic tissues and stem cells
    Expression by the Database of Embryonic development, Stem cell research, and Regenerative medicine    About this table
    3 LifeMap In Vivo Development Anatomical Compartments/Cells 
    Tissue Anatomical Compartment CellCategory (developmental path)
    EyeInner Nuclear LayerGABAergic Amacrine CellsAmacrine, Retina
    BrainChoroid PlexusBrain
    Neural TubeMetencephalonNeural Tube
    Expression: Positive    Negative     Selective marker
    Experimental details: Curated     Microarrays     In-situ hybridization

    See WFIKKN2 Protein Expression from SPIRE MOPED and PaxDB
    Genevestigator expression for WFIKKN2

    SOURCE GeneReport for Unigene cluster: Hs.211475

    UniProtKB/Swiss-Prot: WFKN2_HUMAN, Q8TEU8
    Tissue specificity: Primarily expressed in ovary, testis and brain, but not in liver. In fetal tissues, it is primarily
    expressed in brain, skeletal muscle, thymus and kidney

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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 chordates.

    Orthologs for WFIKKN2 gene from 4/13 species (see all 13)    About this table
    Organism Taxonomic
    classification
    Gene Description Human
    Similarity
    Orthology
    Type
    Details
    chicken
    (Gallus gallus)
    Aves WFIKKN21 WAP, follistatin/kazal, immunoglobulin, kunitz and more 73.67(n)
    78.99(a)
      422097  XM_420100.2  XP_420100.2 
    lizard
    (Anolis carolinensis)
    Reptilia WFIKKN26
    --
    --
    75(a)
    4(a)
    1 ↔ 1
    possible ortholog
    2(117410002-117416186)
    GL343690.1(197936-206598)
    African clawed frog
    (Xenopus laevis)
    Amphibia Xl.175612 Xenopus laevis transcribed sequence with weak similarity more 77.97(n)    BG812819.1 
    zebrafish
    (Danio rerio)
    Actinopterygii LOC5649921 WAP, kazal, immunoglobulin, kunitz and NTR domain-containing more 68.47(n)
    67.6(a)
      564992  XM_688302.4  XP_693394.4 


    ENSEMBL Gene Tree for WFIKKN2 (if available)
    TreeFam Gene Tree for WFIKKN2 (if available) 

    (Paralogs according to 1HomoloGene,
    2Ensembl, and 3SIMAP, Pseudogenes according to 4Pseudogene.org Build 68)
    About This Section
    Paralogs for WFIKKN2 gene
    AMBP2  SPINT32  WFDC82  TFPI2  WFIKKN12  SPINT22  TFPI22  EPPIN2  
    EPPIN-WFDC62  
    5 SIMAP similar genes for WFIKKN2 using alignment to 2 protein entries:     WFKN2_HUMAN (see all proteins):
    WFIKKN1    SPINT3    ITIL    TFPI2    EPPIN

    WFIKKN2 for paralogs           About GeneDecksing



    (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

    10/214 NCBI SNPs in WFIKKN2 are shown (see all 214    About this table
    Genomic DataTranscription Related DataAllele Frequencies
    SNP IDValidClinical
    significance
    Chr 17 posSequence#AA
    Chg
    TypeMore#Allele
    freq
    PopTotal
    sample
    More
    ----------
    rs783315861,2
    C,Fother48917215(+) ACCACC/TTGAGA 2 P L mis11Minor allele frequency- T:0.33NA 6
    rs588389061,2
    C--44283842(+) CTTTT-/CCTCTT
            
    AGAGT
    1 -- int11Minor allele frequency- CCTCTT:0.00NA 2
    rs1408216131,2
    --48910644(+) TGGGAA/GACTTG 1 -- us2k10--------
    rs1833811361,2
    --48910649(+) GACTTC/GGAAGG 1 -- us2k10--------
    rs1873436271,2
    --48910655(+) GAAGGG/TCTGGA 1 -- us2k10--------
    rs1917994331,2
    --48910696(+) TTTCCC/TGATGC 1 -- us2k10--------
    rs46115021,2
    C,F,A,H,--48910781(+) CCAGGT/CTGGGT 1 -- us2k115Minor allele frequency- C:0.42NS EA NA WA CSA 791
    rs1825384761,2
    --48910785(+) GTTGGG/TTGTGG 1 -- us2k10--------
    rs1447780371,2
    --48911158(+) ATTACA/GGGGAA 1 -- us2k10--------
    rs1868626601,2
    --48911229(+) AGTTTA/TTTCCA 1 -- us2k10--------

    HapMap Linkage Disequilibrium report for WFIKKN2 (48912011 - 48919709 bp)
    Structural Variations (Copy Number Variations, Insertions/Deletions, Inversions)
          Database of Genomic Variants (DGV) variations for WFIKKN2: --

    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, Genatlas, GeneTests, GAD, HuGE Navigator, and/or TGDB.)
    About This Section

    WFIKKN2 for disorders           About GeneDecksing

    OMIM gene information: 610895    OMIM disorders: --

    3 diseases for WFIKKN2:    About MalaCards
    hereditary angioedema    angioedema    carcinoma


    Export disorders for WFIKKN2 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 WFIKKN2 gene, integrated from 9 sources (see all 14):
    (articles sorted by number of sources associating them with WFIKKN2)
        Utopia: connect your pdf to the dynamic
    world of online information

    1. Distinct expression pattern of two related human proteins containing multiple types of protease-inhibitory modules. (PubMed id 11928817)1, 2, 3, 9 Trexler M.... Patthy L. (2002)
    2. Regulation of myostatin in vivo by growth and differentiation factor- associated serum protein-1: a novel protein with protease inhibitor and follistatin domains. (PubMed id 12595574)1, 2 Hill J.J.... Wolfman N.M. (2003)
    3. Expression, purification and characterization of the second Kunitz-type protease inhibitor domain of the human WFIKKN protein. (PubMed id 12709070)1, 3 Nagy A....Patthy L. (2003)
    4. The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment. (PubMed id 12975309)1, 2 Clark H.F.... Gray A.M. (2003)
    5. Both WFIKKN1 and WFIKKN2 have high affinity for growth and differentiation factors 8 and 11. (PubMed id 18596030)1, 9 Kondas K....Patthy L. (2008)
    6. Hormone therapy and maximal eccentric exercise alters myostatin-related gene expression in postmenopausal women. (PubMed id 22395277)1 Dieli-Conwright C.M....Schroeder E.T. (2012)
    7. Effects of oral creatine and resistance training on s erum myostatin and GASP-1. (PubMed id 20026378)1 Saremi A....Omidfar K. (2010)
    8. WFIKKN1 and WFIKKN2 bind growth factors TGFI^1, BMP2 a nd BMP4 but do not inhibit their signalling activity. (PubMed id 21054789)1 SzlA!ma G....Patthy L. (2010)
    9. Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes. (PubMed id 16344560)1 Kimura K.... Sugano S. (2006)
    10. Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. (PubMed id 12477932)1 Strausberg R.L....Marra M.A. (2002)

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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: 124857 HGNC: 30916 AceView: WFIKKN2 Ensembl:ENSG00000173714 euGenes: HUgn124857
    ECgene: WFIKKN2 H-InvDB: WFIKKN2

    (According to HUGE)
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    (According to PharmGKB, ATLAS, HORDE, IMGT, LEIDEN, UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL,
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    NameDescription
    PharmGKB entry for WFIKKN2 Pharmacogenomics, SNPs, Pathways

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