WFKN2_HUMAN
ID WFKN2_HUMAN Reviewed; 576 AA.
AC Q8TEU8; Q6UXZ9;
DT 23-OCT-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2002, sequence version 1.
DT 03-AUG-2022, entry version 149.
DE RecName: Full=WAP, Kazal, immunoglobulin, Kunitz and NTR domain-containing protein 2;
DE AltName: Full=Growth and differentiation factor-associated serum protein 1;
DE Short=GASP-1;
DE Short=hGASP-1;
DE AltName: Full=WAP, follistatin, immunoglobulin, Kunitz and NTR domain-containing-related protein;
DE AltName: Full=WFIKKN-related protein;
DE Flags: Precursor;
GN Name=WFIKKN2; Synonyms=GASP1, WFIKKNRP; ORFNames=UNQ9235/PRO31996;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
RX PubMed=11928817; DOI=10.1515/bc.2002.023;
RA Trexler M., Banyai L., Patthy L.;
RT "Distinct expression pattern of two related human proteins containing
RT multiple types of protease-inhibitory modules.";
RL Biol. Chem. 383:223-228(2002).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT GLN-31.
RX PubMed=12975309; DOI=10.1101/gr.1293003;
RA Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J.,
RA Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P.,
RA Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E., Heldens S., Huang A.,
RA Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D.,
RA Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L.,
RA Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C.,
RA Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J.,
RA Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M.;
RT "The secreted protein discovery initiative (SPDI), a large-scale effort to
RT identify novel human secreted and transmembrane proteins: a bioinformatics
RT assessment.";
RL Genome Res. 13:2265-2270(2003).
RN [3]
RP IDENTIFICATION BY MASS SPECTROMETRY, AND INTERACTION WITH MSTN.
RX PubMed=12595574; DOI=10.1210/me.2002-0366;
RA Hill J.J., Qiu Y., Hewick R.M., Wolfman N.M.;
RT "Regulation of myostatin in vivo by growth and differentiation factor-
RT associated serum protein-1: a novel protein with protease inhibitor and
RT follistatin domains.";
RL Mol. Endocrinol. 17:1144-1154(2003).
CC -!- FUNCTION: Protease-inhibitor that contains multiple distinct protease
CC inhibitor domains. Probably has serine protease- and metalloprotease-
CC inhibitor activity. Inhibits the biological activity of mature
CC myostatin, but not activin (By similarity). {ECO:0000250}.
CC -!- SUBUNIT: Interacts with both mature and propeptide myostatin/MSTN.
CC {ECO:0000269|PubMed:12595574}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Primarily expressed in ovary, testis and brain, but
CC not in liver. In fetal tissues, it is primarily expressed in brain,
CC skeletal muscle, thymus and kidney. {ECO:0000269|PubMed:11928817}.
CC -!- SIMILARITY: Belongs to the WFIKKN family. {ECO:0000305}.
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DR EMBL; AF468657; AAL77058.1; -; mRNA.
DR EMBL; AY358142; AAQ88509.1; -; mRNA.
DR CCDS; CCDS11575.1; -.
DR RefSeq; NP_001317270.1; NM_001330341.1.
DR RefSeq; NP_783165.1; NM_175575.5.
DR AlphaFoldDB; Q8TEU8; -.
DR SMR; Q8TEU8; -.
DR IntAct; Q8TEU8; 8.
DR MINT; Q8TEU8; -.
DR STRING; 9606.ENSP00000311184; -.
DR MEROPS; I02.954; -.
DR MEROPS; I02.955; -.
DR MEROPS; I17.952; -.
DR GlyGen; Q8TEU8; 2 sites.
DR iPTMnet; Q8TEU8; -.
DR PhosphoSitePlus; Q8TEU8; -.
DR BioMuta; WFIKKN2; -.
DR DMDM; 74716081; -.
DR MassIVE; Q8TEU8; -.
DR PaxDb; Q8TEU8; -.
DR PeptideAtlas; Q8TEU8; -.
DR PRIDE; Q8TEU8; -.
DR ProteomicsDB; 74502; -.
DR Antibodypedia; 2618; 123 antibodies from 17 providers.
DR DNASU; 124857; -.
DR Ensembl; ENST00000311378.5; ENSP00000311184.4; ENSG00000173714.8.
DR GeneID; 124857; -.
DR KEGG; hsa:124857; -.
DR MANE-Select; ENST00000311378.5; ENSP00000311184.4; NM_175575.6; NP_783165.1.
DR UCSC; uc002isv.5; human.
DR CTD; 124857; -.
DR DisGeNET; 124857; -.
DR GeneCards; WFIKKN2; -.
DR HGNC; HGNC:30916; WFIKKN2.
DR HPA; ENSG00000173714; Group enriched (choroid plexus, ovary).
DR MIM; 610895; gene.
DR neXtProt; NX_Q8TEU8; -.
DR OpenTargets; ENSG00000173714; -.
DR PharmGKB; PA134864812; -.
DR VEuPathDB; HostDB:ENSG00000173714; -.
DR eggNOG; KOG4597; Eukaryota.
DR GeneTree; ENSGT00940000160624; -.
DR InParanoid; Q8TEU8; -.
DR OMA; RWAYNGQ; -.
DR OrthoDB; 324177at2759; -.
DR PhylomeDB; Q8TEU8; -.
DR TreeFam; TF315349; -.
DR PathwayCommons; Q8TEU8; -.
DR SignaLink; Q8TEU8; -.
DR BioGRID-ORCS; 124857; 12 hits in 1065 CRISPR screens.
DR GenomeRNAi; 124857; -.
DR Pharos; Q8TEU8; Tbio.
DR PRO; PR:Q8TEU8; -.
DR Proteomes; UP000005640; Chromosome 17.
DR RNAct; Q8TEU8; protein.
DR Bgee; ENSG00000173714; Expressed in left ovary and 95 other tissues.
DR ExpressionAtlas; Q8TEU8; baseline and differential.
DR Genevisible; Q8TEU8; HS.
DR GO; GO:0005615; C:extracellular space; IDA:UniProtKB.
DR GO; GO:0008191; F:metalloendopeptidase inhibitor activity; IEA:UniProtKB-KW.
DR GO; GO:0048019; F:receptor antagonist activity; IDA:UniProtKB.
DR GO; GO:0004867; F:serine-type endopeptidase inhibitor activity; IEA:UniProtKB-KW.
DR GO; GO:0050431; F:transforming growth factor beta binding; IDA:UniProtKB.
DR GO; GO:0055001; P:muscle cell development; IEA:Ensembl.
DR GO; GO:0043392; P:negative regulation of DNA binding; IEA:Ensembl.
DR GO; GO:0032091; P:negative regulation of protein binding; IEA:Ensembl.
DR GO; GO:0030512; P:negative regulation of transforming growth factor beta receptor signaling pathway; IDA:UniProtKB.
DR GO; GO:0060021; P:roof of mouth development; IEA:Ensembl.
DR GO; GO:0001501; P:skeletal system development; IEA:Ensembl.
DR GO; GO:0007179; P:transforming growth factor beta receptor signaling pathway; ISS:UniProtKB.
DR CDD; cd00109; KU; 2.
DR Gene3D; 2.40.50.120; -; 1.
DR Gene3D; 2.60.40.10; -; 1.
DR Gene3D; 4.10.410.10; -; 2.
DR Gene3D; 4.10.75.10; -; 1.
DR InterPro; IPR036645; Elafin-like_sf.
DR InterPro; IPR007110; Ig-like_dom.
DR InterPro; IPR036179; Ig-like_dom_sf.
DR InterPro; IPR013783; Ig-like_fold.
DR InterPro; IPR013098; Ig_I-set.
DR InterPro; IPR003599; Ig_sub.
DR InterPro; IPR003598; Ig_sub2.
DR InterPro; IPR002350; Kazal_dom.
DR InterPro; IPR036058; Kazal_dom_sf.
DR InterPro; IPR002223; Kunitz_BPTI.
DR InterPro; IPR036880; Kunitz_BPTI_sf.
DR InterPro; IPR001134; Netrin_domain.
DR InterPro; IPR018933; Netrin_module_non-TIMP.
DR InterPro; IPR020901; Prtase_inh_Kunz-CS.
DR InterPro; IPR008993; TIMP-like_OB-fold.
DR InterPro; IPR008197; WAP_dom.
DR InterPro; IPR033638; WFIKKN1/2.
DR PANTHER; PTHR45938:SF6; PTHR45938:SF6; 1.
DR Pfam; PF07679; I-set; 1.
DR Pfam; PF00014; Kunitz_BPTI; 2.
DR Pfam; PF01759; NTR; 1.
DR Pfam; PF00095; WAP; 1.
DR PRINTS; PR00759; BASICPTASE.
DR SMART; SM00409; IG; 1.
DR SMART; SM00408; IGc2; 1.
DR SMART; SM00131; KU; 2.
DR SMART; SM00217; WAP; 1.
DR SUPFAM; SSF100895; SSF100895; 1.
DR SUPFAM; SSF48726; SSF48726; 1.
DR SUPFAM; SSF50242; SSF50242; 1.
DR SUPFAM; SSF57256; SSF57256; 1.
DR SUPFAM; SSF57362; SSF57362; 2.
DR PROSITE; PS00280; BPTI_KUNITZ_1; 1.
DR PROSITE; PS50279; BPTI_KUNITZ_2; 2.
DR PROSITE; PS50835; IG_LIKE; 1.
DR PROSITE; PS51465; KAZAL_2; 1.
DR PROSITE; PS50189; NTR; 1.
DR PROSITE; PS51390; WAP; 1.
PE 1: Evidence at protein level;
KW Disulfide bond; Glycoprotein; Immunoglobulin domain;
KW Metalloenzyme inhibitor; Metalloprotease inhibitor; Protease inhibitor;
KW Reference proteome; Repeat; Secreted; Serine protease inhibitor; Signal.
FT SIGNAL 1..34
FT /evidence="ECO:0000250"
FT CHAIN 35..576
FT /note="WAP, Kazal, immunoglobulin, Kunitz and NTR domain-
FT containing protein 2"
FT /id="PRO_0000307820"
FT DOMAIN 39..92
FT /note="WAP"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00722"
FT DOMAIN 126..177
FT /note="Kazal-like"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00798"
FT DOMAIN 210..303
FT /note="Ig-like C2-type"
FT DOMAIN 328..378
FT /note="BPTI/Kunitz inhibitor 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00031"
FT DOMAIN 386..436
FT /note="BPTI/Kunitz inhibitor 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00031"
FT DOMAIN 445..566
FT /note="NTR"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00295"
FT SITE 140..141
FT /note="Reactive bond"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00798"
FT CARBOHYD 319
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 519
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 46..79
FT /evidence="ECO:0000250"
FT DISULFID 62..83
FT /evidence="ECO:0000250"
FT DISULFID 66..78
FT /evidence="ECO:0000250"
FT DISULFID 72..88
FT /evidence="ECO:0000250"
FT DISULFID 134..164
FT /evidence="ECO:0000250"
FT DISULFID 138..157
FT /evidence="ECO:0000250"
FT DISULFID 146..175
FT /evidence="ECO:0000250"
FT DISULFID 231..287
FT /evidence="ECO:0000250"
FT DISULFID 328..378
FT /evidence="ECO:0000250"
FT DISULFID 337..361
FT /evidence="ECO:0000250"
FT DISULFID 353..374
FT /evidence="ECO:0000250"
FT DISULFID 386..436
FT /evidence="ECO:0000250"
FT DISULFID 395..419
FT /evidence="ECO:0000250"
FT DISULFID 411..432
FT /evidence="ECO:0000250"
FT DISULFID 445..515
FT /evidence="ECO:0000250"
FT DISULFID 448..517
FT /evidence="ECO:0000250"
FT DISULFID 459..566
FT /evidence="ECO:0000250"
FT VARIANT 31
FT /note="R -> Q (in dbSNP:rs55700534)"
FT /evidence="ECO:0000269|PubMed:12975309"
FT /id="VAR_061984"
FT VARIANT 96
FT /note="V -> M (in dbSNP:rs35300894)"
FT /id="VAR_036692"
SQ SEQUENCE 576 AA; 63941 MW; 08B4F2EDBE121F81 CRC64;
MWAPRCRRFW SRWEQVAALL LLLLLLGVPP RSLALPPIRY SHAGICPNDM NPNLWVDAQS
TCRRECETDQ ECETYEKCCP NVCGTKSCVA ARYMDVKGKK GPVGMPKEAT CDHFMCLQQG
SECDIWDGQP VCKCKDRCEK EPSFTCASDG LTYYNRCYMD AEACSKGITL AVVTCRYHFT
WPNTSPPPPE TTMHPTTASP ETPELDMAAP ALLNNPVHQS VTMGETVSFL CDVVGRPRPE
ITWEKQLEDR ENVVMRPNHV RGNVVVTNIA QLVIYNAQLQ DAGIYTCTAR NVAGVLRADF
PLSVVRGHQA AATSESSPNG TAFPAAECLK PPDSEDCGEE QTRWHFDAQA NNCLTFTFGH
CHRNLNHFET YEACMLACMS GPLAACSLPA LQGPCKAYAP RWAYNSQTGQ CQSFVYGGCE
GNGNNFESRE ACEESCPFPR GNQRCRACKP RQKLVTSFCR SDFVILGRVS ELTEEPDSGR
ALVTVDEVLK DEKMGLKFLG QEPLEVTLLH VDWACPCPNV TVSEMPLIIM GEVDGGMAML
RPDSFVGASS ARRVRKLREV MHKKTCDVLK EFLGLH
