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   24-JAN-2024, entry version 156.
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   GlyCosmos; Q8TEU8; 2 sites, No reported glycans.
DR   GlyGen; Q8TEU8; 2 sites.
DR   iPTMnet; Q8TEU8; -.
DR   PhosphoSitePlus; Q8TEU8; -.
DR   BioMuta; WFIKKN2; -.
DR   DMDM; 74716081; -.
DR   MassIVE; Q8TEU8; -.
DR   PaxDb; 9606-ENSP00000311184; -.
DR   PeptideAtlas; Q8TEU8; -.
DR   ProteomicsDB; 74502; -.
DR   Antibodypedia; 2618; 126 antibodies from 18 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   AGR; HGNC:30916; -.
DR   CTD; 124857; -.
DR   DisGeNET; 124857; -.
DR   GeneCards; WFIKKN2; -.
DR   HGNC; HGNC:30916; WFIKKN2.
DR   HPA; ENSG00000173714; Tissue enriched (choroid).
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; LFTRWMW; -.
DR   OrthoDB; 5298642at2759; -.
DR   PhylomeDB; Q8TEU8; -.
DR   TreeFam; TF315349; -.
DR   PathwayCommons; Q8TEU8; -.
DR   SignaLink; Q8TEU8; -.
DR   BioGRID-ORCS; 124857; 12 hits in 1143 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 cell types or tissues.
DR   ExpressionAtlas; Q8TEU8; baseline and differential.
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: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; cd05765; IgI_3_WFIKKN-like; 1.
DR   CDD; cd00104; KAZAL_FS; 1.
DR   CDD; cd22605; Kunitz_WFIKKN_1-like; 1.
DR   CDD; cd22606; Kunitz_WFIKKN_2-like; 1.
DR   CDD; cd03575; NTR_WFIKKN; 1.
DR   Gene3D; 2.40.50.120; -; 1.
DR   Gene3D; 3.30.60.30; -; 1.
DR   Gene3D; 4.10.75.10; Elafin-like; 1.
DR   Gene3D; 2.60.40.10; Immunoglobulins; 1.
DR   Gene3D; 4.10.410.10; Pancreatic trypsin inhibitor Kunitz domain; 2.
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_Ig-like_3.
DR   PANTHER; PTHR45938; ACP24A4-RELATED; 1.
DR   PANTHER; PTHR45938:SF7; WAP, KAZAL, IMMUNOGLOBULIN, KUNITZ AND NTR DOMAIN-CONTAINING PROTEIN 2; 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; SSF57362; BPTI-like; 2.
DR   SUPFAM; SSF57256; Elafin-like; 1.
DR   SUPFAM; SSF48726; Immunoglobulin; 1.
DR   SUPFAM; SSF100895; Kazal-type serine protease inhibitors; 1.
DR   SUPFAM; SSF50242; TIMP-like; 1.
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.
DR   Genevisible; Q8TEU8; HS.
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
//