WFIKKN1 WAP, follistatin/kazal, immunoglobulin, kunitz and netrin domain containing 1 [Homo sapiens (human)] - Gene

Summary

Official Symbol: WFIKKN1provided by HGNC
Official Full Name: WAP, follistatin/kazal, immunoglobulin, kunitz and netrin domain containing 1provided by HGNC
Primary source: HGNC:HGNC:30912
See related: Ensembl:ENSG00000127578 MIM:608021; AllianceGenome:HGNC:30912
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: RJD2; WFIKKN; WFDC20A; C16orf12
Summary: This gene encodes a secreted multidomain protein consisting of a signal peptide, a WAP domain, a follistatin domain, an immunoglobulin domain, two tandem Kunitz domains, and an NTR domain. These domains have been implicated frequently in inhibition of various types of proteases, suggesting that the encoded protein may be a multivalent protease inhibitor and may control the action of multiple types of serine proteases as well as metalloproteinases. [provided by RefSeq, Jul 2008]
Expression: Low expression observed in reference dataset See more
Orthologs: mouse all
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Genomic context

Location:: 16p13.3

Exon count:: 2

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	16	NC_000016.10 (630985..634117)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	16	NC_060940.1 (635019..638150)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	16	NC_000016.9 (680985..684117)

Chromosome 16 - NC_000016.10 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

In this review, we summarize current knowledge about the WFIKKN proteins and propose that they are "companion" proteins for various growth factors by providing localized and sustained presentation of TGFB proteins to their respective receptors, thus regulating the balance between the activation of Smad and non-Smad pathways by TGFB.
Title: WFIKKN1 and WFIKKN2: "Companion" proteins regulating TGFB activity.
Data show that the KKN1 fragment generated by BMP1-cleavage of WFIKKN1 protein contributes most significantly to the observed enhancer activity.
Title: Influence of WFIKKN1 on BMP1-mediated activation of latent myostatin.
Data suggest that myostatin binding to its receptor (activin receptors type II) can be blocked by WFIKKN1 but not WFIKKN2; various forms of myostatin (promyostatin, myostatin pro-domain, and latent/processed myostatin) bind WFIKKN1 but not WFIKKN2.
Title: Latent myostatin has significant activity and this activity is controlled more efficiently by WFIKKN1 than by WFIKKN2.
data indicate that WFIKKN proteins are antagonists of GDF8 and GDF11, but in the case of TGFbeta1, BMP2 and BMP4 they function as growth factor binding proteins
Title: WFIKKN1 and WFIKKN2 bind growth factors TGFβ1, BMP2 and BMP4 but do not inhibit their signalling activity.
Both WFIKKN1 and WFIKKN2 have high affinity for growth and differentiation factors 8 and 11.
Title: Both WFIKKN1 and WFIKKN2 have high affinity for growth and differentiation factors 8 and 11.
Newly discovered WFIKKNPR gene structure and tissue distribution of gene expression is commpared with that of the WFIKKN gene in adult and fetal tissues and organs.
Title: Distinct expression pattern of two related human proteins containing multiple types of protease-inhibitory modules.
Data suggest that the physiological target of WFIKKN protein may be trypsin.
Title: Expression, purification and characterization of the second Kunitz-type protease inhibitor domain of the human WFIKKN protein.
three-dimensional structure of a Kunitz domain with a tryptophan residue at the P02 site of the protease-recognition loop
Title: Second Kunitz-type protease inhibitor domain of the human WFIKKN1 protein.

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Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

NoName (e-PCR)
- UniSTS:480584

A009L31 (e-PCR)
- UniSTS:29001

RH41911 (e-PCR)
- UniSTS:34757

SHGC-60694 (e-PCR)
- UniSTS:22236

G32656 (e-PCR)
- UniSTS:117238

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables receptor antagonist activity	IBA Inferred from Biological aspect of Ancestor more info
enables receptor antagonist activity	IDA Inferred from Direct Assay more info	PubMed
enables serine-type endopeptidase inhibitor activity	IEA Inferred from Electronic Annotation more info
enables transforming growth factor beta binding	IBA Inferred from Biological aspect of Ancestor more info
enables transforming growth factor beta binding	IDA Inferred from Direct Assay more info	PubMed

Process	Evidence Code	Pubs
involved_in muscle cell development	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of peptidase activity	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of transforming growth factor beta receptor signaling pathway	IDA Inferred from Direct Assay more info	PubMed
involved_in roof of mouth development	IEA Inferred from Electronic Annotation more info
involved_in skeletal system development	IEA Inferred from Electronic Annotation more info
involved_in transforming growth factor beta receptor signaling pathway	IBA Inferred from Biological aspect of Ancestor more info

Component	Evidence Code	Pubs
is_active_in extracellular space	IBA Inferred from Biological aspect of Ancestor more info

General protein information

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Preferred Names: WAP, Kazal, immunoglobulin, Kunitz and NTR domain-containing protein 1

Names: GASP-2; WAP four-disulfide core domain 20A; WAP, FS, Ig, KU, and NTR-containing protein; WAP, follistatin, immunoglobulin, kunitz and NTR domain-containing protein; growth and differentiation factor-associated serum protein 2; hGASP-2

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

NM_053284.3 → NP_444514.1 WAP, Kazal, immunoglobulin, Kunitz and NTR domain-containing protein 1 precursor

See identical proteins and their annotated locations for NP_444514.1

Status: REVIEWED

Source sequence(s)

AF422194, AK075356, CN425794, Z84479

Consensus CDS

CCDS10414.1

UniProtKB/Swiss-Prot

Q7LDW0, Q8NBQ1, Q96NZ8, Q96S20

Related

ENSP00000324763.2, ENST00000319070.3

Conserved Domains (6) summary

cd05765
Location:200 → 280

Ig_3; Subgroup of the immunoglobulin (Ig) superfamily

cd00104
Location:120 → 155

KAZAL_FS; Kazal type serine protease inhibitors and follistatin-like domains. Kazal inhibitors inhibit serine proteases, such as, trypsin, chyomotrypsin, avian ovomucoids, and elastases. The inhibitory domain has one reactive site peptide bond, which serves the ...

cd03575
Location:427 → 537

NTR_WFIKKN; NTR domain, WFIKKN subfamily; WFIKKN proteins contain a C-terminal NTR domain and are putative secreted proteins which may be multivalent protease inhibitors that act on serine proteases as well as metalloproteases. Human WFIKKN and a related protein ...

pfam00014
Location:358 → 409

Kunitz_BPTI; Kunitz/Bovine pancreatic trypsin inhibitor domain

cl00101
Location:307 → 351

KU; BPTI/Kunitz family of serine protease inhibitors; Structure is a disulfide rich alpha+beta fold. BPTI (bovine pancreatic trypsin inhibitor) is an extensively studied model structure.

pfam00095
Location:29 → 76

WAP; WAP-type (Whey Acidic Protein) 'four-disulfide core'