WFKN2_MOUSE
ID WFKN2_MOUSE Reviewed; 571 AA.
AC Q7TQN3; Q5SUS5;
DT 23-OCT-2007, integrated into UniProtKB/Swiss-Prot.
DT 23-OCT-2007, sequence version 2.
DT 03-AUG-2022, entry version 138.
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=mGASP-1;
DE Flags: Precursor;
GN Name=Wfikkn2; Synonyms=Gasp1;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 30-40, IDENTIFICATION BY
RP MASS SPECTROMETRY, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND
RP INTERACTION WITH MSTN.
RC STRAIN=BALB/cJ;
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).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
CC -!- FUNCTION: Protease-inhibitor that contains multiple distinct protease
CC inhibitor domains. Probably has serine protease- and metalloprotease-
CC inhibitor activity (By similarity). Inhibits the biological activity of
CC mature myostatin, but not activin. {ECO:0000250}.
CC -!- SUBUNIT: Interacts with both mature and propeptide myostatin/MSTN.
CC {ECO:0000269|PubMed:12595574}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:12595574}.
CC -!- TISSUE SPECIFICITY: Widely expressed, with high expression in skeletal
CC muscle and heart. Also expressed in brain, lung and testis. Weakly
CC expressed in liver and kidney. {ECO:0000269|PubMed:12595574}.
CC -!- SIMILARITY: Belongs to the WFIKKN family. {ECO:0000305}.
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DR EMBL; AY308804; AAP72503.1; -; mRNA.
DR EMBL; AL645846; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR CCDS; CCDS25251.1; -.
DR RefSeq; NP_861540.2; NM_181819.2.
DR RefSeq; XP_006533561.1; XM_006533498.3.
DR RefSeq; XP_006533562.1; XM_006533499.3.
DR RefSeq; XP_006533563.1; XM_006533500.3.
DR RefSeq; XP_006533564.1; XM_006533501.3.
DR RefSeq; XP_006533565.1; XM_006533502.2.
DR RefSeq; XP_011247365.1; XM_011249063.2.
DR PDB; 6MAA; X-ray; 1.39 A; A=97-172.
DR PDBsum; 6MAA; -.
DR AlphaFoldDB; Q7TQN3; -.
DR SMR; Q7TQN3; -.
DR BioGRID; 234985; 3.
DR STRING; 10090.ENSMUSP00000053238; -.
DR MEROPS; I02.954; -.
DR GlyGen; Q7TQN3; 2 sites.
DR PhosphoSitePlus; Q7TQN3; -.
DR PaxDb; Q7TQN3; -.
DR PRIDE; Q7TQN3; -.
DR ProteomicsDB; 299767; -.
DR Antibodypedia; 2618; 123 antibodies from 17 providers.
DR DNASU; 278507; -.
DR Ensembl; ENSMUST00000061469; ENSMUSP00000053238; ENSMUSG00000044177.
DR GeneID; 278507; -.
DR KEGG; mmu:278507; -.
DR UCSC; uc007kyg.2; mouse.
DR CTD; 124857; -.
DR MGI; MGI:2669209; Wfikkn2.
DR VEuPathDB; HostDB:ENSMUSG00000044177; -.
DR eggNOG; KOG4597; Eukaryota.
DR GeneTree; ENSGT00940000160624; -.
DR HOGENOM; CLU_037211_1_0_1; -.
DR InParanoid; Q7TQN3; -.
DR OMA; EATCEHF; -.
DR OrthoDB; 324177at2759; -.
DR PhylomeDB; Q7TQN3; -.
DR TreeFam; TF315349; -.
DR BioGRID-ORCS; 278507; 3 hits in 74 CRISPR screens.
DR PRO; PR:Q7TQN3; -.
DR Proteomes; UP000000589; Chromosome 11.
DR RNAct; Q7TQN3; protein.
DR Bgee; ENSMUSG00000044177; Expressed in otolith organ and 64 other tissues.
DR Genevisible; Q7TQN3; MM.
DR GO; GO:0005576; C:extracellular region; IDA:MGI.
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; ISO:MGI.
DR GO; GO:0004867; F:serine-type endopeptidase inhibitor activity; IEA:UniProtKB-KW.
DR GO; GO:0050431; F:transforming growth factor beta binding; ISO:MGI.
DR GO; GO:0055001; P:muscle cell development; IMP:MGI.
DR GO; GO:0043392; P:negative regulation of DNA binding; IDA:MGI.
DR GO; GO:0032091; P:negative regulation of protein binding; IDA:MGI.
DR GO; GO:0030512; P:negative regulation of transforming growth factor beta receptor signaling pathway; ISO:MGI.
DR GO; GO:0060021; P:roof of mouth development; IGI:MGI.
DR GO; GO:0001501; P:skeletal system development; IGI:MGI.
DR GO; GO:0007179; P:transforming growth factor beta receptor signaling pathway; IDA:MGI.
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 3D-structure; Direct protein sequencing; Disulfide bond; Glycoprotein;
KW Immunoglobulin domain; Metalloenzyme inhibitor; Metalloprotease inhibitor;
KW Protease inhibitor; Reference proteome; Repeat; Secreted;
KW Serine protease inhibitor; Signal.
FT SIGNAL 1..29
FT /evidence="ECO:0000269|PubMed:12595574"
FT CHAIN 30..571
FT /note="WAP, Kazal, immunoglobulin, Kunitz and NTR domain-
FT containing protein 2"
FT /id="PRO_0000307821"
FT DOMAIN 34..87
FT /note="WAP"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00722"
FT DOMAIN 121..172
FT /note="Kazal-like"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00798"
FT DOMAIN 205..298
FT /note="Ig-like C2-type"
FT DOMAIN 323..373
FT /note="BPTI/Kunitz inhibitor 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00031"
FT DOMAIN 381..431
FT /note="BPTI/Kunitz inhibitor 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00031"
FT DOMAIN 440..561
FT /note="NTR"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00295"
FT SITE 135..136
FT /note="Reactive bond"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00798"
FT CARBOHYD 314
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 514
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 41..74
FT /evidence="ECO:0000250"
FT DISULFID 57..78
FT /evidence="ECO:0000250"
FT DISULFID 61..73
FT /evidence="ECO:0000250"
FT DISULFID 67..83
FT /evidence="ECO:0000250"
FT DISULFID 129..159
FT /evidence="ECO:0000250"
FT DISULFID 133..152
FT /evidence="ECO:0000250"
FT DISULFID 141..170
FT /evidence="ECO:0000250"
FT DISULFID 226..282
FT /evidence="ECO:0000250"
FT DISULFID 323..373
FT /evidence="ECO:0000250"
FT DISULFID 332..356
FT /evidence="ECO:0000250"
FT DISULFID 348..369
FT /evidence="ECO:0000250"
FT DISULFID 381..431
FT /evidence="ECO:0000250"
FT DISULFID 390..414
FT /evidence="ECO:0000250"
FT DISULFID 406..427
FT /evidence="ECO:0000250"
FT DISULFID 440..510
FT /evidence="ECO:0000250"
FT DISULFID 443..512
FT /evidence="ECO:0000250"
FT DISULFID 454..561
FT /evidence="ECO:0000250"
FT CONFLICT 380
FT /note="I -> T (in Ref. 1; AAP72503)"
FT /evidence="ECO:0000305"
FT STRAND 116..121
FT /evidence="ECO:0007829|PDB:6MAA"
FT STRAND 124..129
FT /evidence="ECO:0007829|PDB:6MAA"
FT STRAND 140..142
FT /evidence="ECO:0007829|PDB:6MAA"
FT STRAND 147..150
FT /evidence="ECO:0007829|PDB:6MAA"
FT HELIX 151..161
FT /evidence="ECO:0007829|PDB:6MAA"
SQ SEQUENCE 571 AA; 63333 MW; 3A75A449F53703AA CRC64;
MCAPGYHRFW FHWGLLLLLL LEAPLRGLAL PPIRYSHAGI CPNDMNPNLW VDAQSTCKRE
CETDQECETY EKCCPNVCGT KSCVAARYMD VKGKKGPVGM PKEATCDHFM CLQQGSECDI
WDGQPVCKCK DRCEKEPSFT CASDGLTYYN RCFMDAEACS KGITLSVVTC RYHFTWPNTS
PPPPETTVHP TTASPETLGL DMAAPALLNH PVHQSVTVGE TVSFLCDVVG RPRPELTWEK
QLEDRENVVM RPNHVRGNVV VTNIAQLVIY NVQPQDAGIY TCTARNVAGV LRADFPLSVV
RGGQARATSE SSLNGTAFPA TECLKPPDSE DCGEEQTRWH FDAQANNCLT FTFGHCHHNL
NHFETYEACM LACMSGPLAI CSLPALQGPC KAYVPRWAYN SQTGLCQSFV YGGCEGNGNN
FESREACEES CPFPRGNQHC RACKPRQKLV TSFCRSDFVI LGRVSELTEE QDSGRALVTV
DEVLKDEKMG LKFLGREPLE VTLLHVDWTC PCPNVTVGET PLIIMGEVDG GMAMLRPDSF
VGASSTRRVR KLREVMYKKT CDVLKDFLGL Q
