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WAP, Kazal, immunoglobulin, Kunitz and NTR domain-containing protein 2 (Growth and differentiation factor-associated serum protein 1) (GASP-1) (hGASP-1) (WAP, follistatin, immunoglobulin, Kunitz and NTR domain-containing-related protein) (WFIKKN-related protein)

 WFKN2_HUMAN             Reviewed;         576 AA.
Q8TEU8; Q6UXZ9;
23-OCT-2007, integrated into UniProtKB/Swiss-Prot.
01-JUN-2002, sequence version 1.
25-OCT-2017, entry version 124.
RecName: Full=WAP, Kazal, immunoglobulin, Kunitz and NTR domain-containing protein 2;
AltName: Full=Growth and differentiation factor-associated serum protein 1;
Short=GASP-1;
Short=hGASP-1;
AltName: Full=WAP, follistatin, immunoglobulin, Kunitz and NTR domain-containing-related protein;
AltName: Full=WFIKKN-related protein;
Flags: Precursor;
Name=WFIKKN2; Synonyms=GASP1, WFIKKNRP; ORFNames=UNQ9235/PRO31996;
Homo sapiens (Human).
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
Catarrhini; Hominidae; Homo.
NCBI_TaxID=9606;
[1]
NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
PubMed=11928817; DOI=10.1515/BC.2002.023;
Trexler M., Banyai L., Patthy L.;
"Distinct expression pattern of two related human proteins containing
multiple types of protease-inhibitory modules.";
Biol. Chem. 383:223-228(2002).
[2]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT GLN-31.
PubMed=12975309; DOI=10.1101/gr.1293003;
Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J.,
Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P.,
Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E., Heldens S.,
Huang A., Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J.,
Lewis L., Liao D., Mark M.R., Robbie E., Sanchez C., Schoenfeld J.,
Seshagiri S., Simmons L., Singh J., Smith V., Stinson J., Vagts A.,
Vandlen R.L., Watanabe C., Wieand D., Woods K., Xie M.-H.,
Yansura D.G., Yi S., Yu G., Yuan J., Zhang M., Zhang Z., Goddard A.D.,
Wood W.I., Godowski P.J., Gray A.M.;
"The secreted protein discovery initiative (SPDI), a large-scale
effort to identify novel human secreted and transmembrane proteins: a
bioinformatics assessment.";
Genome Res. 13:2265-2270(2003).
[3]
IDENTIFICATION BY MASS SPECTROMETRY, AND INTERACTION WITH MSTN.
PubMed=12595574; DOI=10.1210/me.2002-0366;
Hill J.J., Qiu Y., Hewick R.M., Wolfman N.M.;
"Regulation of myostatin in vivo by growth and differentiation factor-
associated serum protein-1: a novel protein with protease inhibitor
and follistatin domains.";
Mol. Endocrinol. 17:1144-1154(2003).
-!- 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).
{ECO:0000250}.
-!- SUBUNIT: Interacts with both mature and propeptide myostatin/MSTN.
{ECO:0000269|PubMed:12595574}.
-!- SUBCELLULAR LOCATION: Secreted {ECO:0000250}.
-!- 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.
{ECO:0000269|PubMed:11928817}.
-!- SIMILARITY: Belongs to the WFIKKN family. {ECO:0000305}.
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EMBL; AF468657; AAL77058.1; -; mRNA.
EMBL; AY358142; AAQ88509.1; -; mRNA.
CCDS; CCDS11575.1; -.
RefSeq; NP_001317270.1; NM_001330341.1.
RefSeq; NP_783165.1; NM_175575.5.
UniGene; Hs.211475; -.
ProteinModelPortal; Q8TEU8; -.
IntAct; Q8TEU8; 7.
MINT; MINT-8044275; -.
STRING; 9606.ENSP00000311184; -.
MEROPS; I02.954; -.
iPTMnet; Q8TEU8; -.
PhosphoSitePlus; Q8TEU8; -.
BioMuta; WFIKKN2; -.
DMDM; 74716081; -.
PaxDb; Q8TEU8; -.
PeptideAtlas; Q8TEU8; -.
PRIDE; Q8TEU8; -.
Ensembl; ENST00000311378; ENSP00000311184; ENSG00000173714.
GeneID; 124857; -.
KEGG; hsa:124857; -.
UCSC; uc002isv.5; human.
CTD; 124857; -.
EuPathDB; HostDB:ENSG00000173714.7; -.
GeneCards; WFIKKN2; -.
HGNC; HGNC:30916; WFIKKN2.
MIM; 610895; gene.
neXtProt; NX_Q8TEU8; -.
OpenTargets; ENSG00000173714; -.
PharmGKB; PA134864812; -.
eggNOG; ENOG410ITYX; Eukaryota.
eggNOG; ENOG410XRTD; LUCA.
GeneTree; ENSGT00740000114929; -.
HOGENOM; HOG000154855; -.
HOVERGEN; HBG108676; -.
InParanoid; Q8TEU8; -.
OMA; CPNVCGT; -.
OrthoDB; EOG091G09P2; -.
PhylomeDB; Q8TEU8; -.
TreeFam; TF315349; -.
GenomeRNAi; 124857; -.
PRO; PR:Q8TEU8; -.
Proteomes; UP000005640; Chromosome 17.
Bgee; ENSG00000173714; -.
CleanEx; HS_WFIKKN2; -.
ExpressionAtlas; Q8TEU8; baseline and differential.
Genevisible; Q8TEU8; HS.
GO; GO:0005615; C:extracellular space; IDA:UniProtKB.
GO; GO:0008191; F:metalloendopeptidase inhibitor activity; IEA:UniProtKB-KW.
GO; GO:0048019; F:receptor antagonist activity; IDA:UniProtKB.
GO; GO:0004867; F:serine-type endopeptidase inhibitor activity; IEA:UniProtKB-KW.
GO; GO:0050431; F:transforming growth factor beta binding; IDA:UniProtKB.
GO; GO:0048747; P:muscle fiber development; IEA:Ensembl.
GO; GO:0043392; P:negative regulation of DNA binding; IEA:Ensembl.
GO; GO:0032091; P:negative regulation of protein binding; IEA:Ensembl.
GO; GO:0030512; P:negative regulation of transforming growth factor beta receptor signaling pathway; IDA:UniProtKB.
GO; GO:0060021; P:palate development; IEA:Ensembl.
GO; GO:0001501; P:skeletal system development; IEA:Ensembl.
GO; GO:0007179; P:transforming growth factor beta receptor signaling pathway; ISS:UniProtKB.
CDD; cd00109; KU; 2.
Gene3D; 2.60.40.10; -; 1.
Gene3D; 4.10.410.10; -; 2.
Gene3D; 4.10.75.10; -; 1.
InterPro; IPR036645; Elafin-like_sf.
InterPro; IPR007110; Ig-like_dom.
InterPro; IPR036179; Ig-like_dom_sf.
InterPro; IPR013783; Ig-like_fold.
InterPro; IPR013098; Ig_I-set.
InterPro; IPR003599; Ig_sub.
InterPro; IPR003598; Ig_sub2.
InterPro; IPR002350; Kazal_dom.
InterPro; IPR036058; Kazal_dom_sf.
InterPro; IPR002223; Kunitz_BPTI.
InterPro; IPR036880; Kunitz_BPTI_sf.
InterPro; IPR001134; Netrin_domain.
InterPro; IPR018933; Netrin_module_non-TIMP.
InterPro; IPR020901; Prtase_inh_Kunz-CS.
InterPro; IPR008993; TIMP-like_OB-fold.
InterPro; IPR008197; WAP_dom.
InterPro; IPR033639; WFIKKN2.
PANTHER; PTHR10083:SF87; PTHR10083:SF87; 1.
Pfam; PF07679; I-set; 1.
Pfam; PF00014; Kunitz_BPTI; 2.
Pfam; PF01759; NTR; 1.
Pfam; PF00095; WAP; 1.
PRINTS; PR00759; BASICPTASE.
SMART; SM00409; IG; 1.
SMART; SM00408; IGc2; 1.
SMART; SM00131; KU; 2.
SMART; SM00217; WAP; 1.
SUPFAM; SSF100895; SSF100895; 1.
SUPFAM; SSF48726; SSF48726; 1.
SUPFAM; SSF50242; SSF50242; 1.
SUPFAM; SSF57256; SSF57256; 1.
SUPFAM; SSF57362; SSF57362; 2.
PROSITE; PS00280; BPTI_KUNITZ_1; 1.
PROSITE; PS50279; BPTI_KUNITZ_2; 2.
PROSITE; PS50835; IG_LIKE; 1.
PROSITE; PS51465; KAZAL_2; 1.
PROSITE; PS50189; NTR; 1.
PROSITE; PS51390; WAP; 1.
1: Evidence at protein level;
Complete proteome; Disulfide bond; Glycoprotein;
Immunoglobulin domain; Metalloenzyme inhibitor;
Metalloprotease inhibitor; Polymorphism; Protease inhibitor;
Reference proteome; Repeat; Secreted; Serine protease inhibitor;
Signal.
SIGNAL 1 34 {ECO:0000250}.
CHAIN 35 576 WAP, Kazal, immunoglobulin, Kunitz and
NTR domain-containing protein 2.
/FTId=PRO_0000307820.
DOMAIN 39 92 WAP. {ECO:0000255|PROSITE-
ProRule:PRU00722}.
DOMAIN 126 177 Kazal-like. {ECO:0000255|PROSITE-
ProRule:PRU00798}.
DOMAIN 210 303 Ig-like C2-type.
DOMAIN 328 378 BPTI/Kunitz inhibitor 1.
{ECO:0000255|PROSITE-ProRule:PRU00031}.
DOMAIN 386 436 BPTI/Kunitz inhibitor 2.
{ECO:0000255|PROSITE-ProRule:PRU00031}.
DOMAIN 445 566 NTR. {ECO:0000255|PROSITE-
ProRule:PRU00295}.
SITE 140 141 Reactive bond. {ECO:0000255|PROSITE-
ProRule:PRU00798}.
CARBOHYD 319 319 N-linked (GlcNAc...) asparagine.
{ECO:0000255}.
CARBOHYD 519 519 N-linked (GlcNAc...) asparagine.
{ECO:0000255}.
DISULFID 46 79 {ECO:0000250}.
DISULFID 62 83 {ECO:0000250}.
DISULFID 66 78 {ECO:0000250}.
DISULFID 72 88 {ECO:0000250}.
DISULFID 134 164 {ECO:0000250}.
DISULFID 138 157 {ECO:0000250}.
DISULFID 146 175 {ECO:0000250}.
DISULFID 231 287 {ECO:0000250}.
DISULFID 328 378 {ECO:0000250}.
DISULFID 337 361 {ECO:0000250}.
DISULFID 353 374 {ECO:0000250}.
DISULFID 386 436 {ECO:0000250}.
DISULFID 395 419 {ECO:0000250}.
DISULFID 411 432 {ECO:0000250}.
DISULFID 445 515 {ECO:0000250}.
DISULFID 448 517 {ECO:0000250}.
DISULFID 459 566 {ECO:0000250}.
VARIANT 31 31 R -> Q (in dbSNP:rs55700534).
{ECO:0000269|PubMed:12975309}.
/FTId=VAR_061984.
VARIANT 96 96 V -> M (in dbSNP:rs35300894).
/FTId=VAR_036692.
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


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