WFKN1_HUMAN
ID WFKN1_HUMAN Reviewed; 548 AA.
AC Q96NZ8; Q7LDW0; Q8NBQ1; Q96S20;
DT 23-OCT-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-2001, sequence version 1.
DT 03-AUG-2022, entry version 160.
DE RecName: Full=WAP, Kazal, immunoglobulin, Kunitz and NTR domain-containing protein 1;
DE AltName: Full=Growth and differentiation factor-associated serum protein 2;
DE Short=GASP-2;
DE Short=hGASP-2;
DE AltName: Full=WAP, follistatin, immunoglobulin, Kunitz and NTR domain-containing protein;
DE Flags: Precursor;
GN Name=WFIKKN1; Synonyms=C16orf12, GASP2, WFIKKN; ORFNames=PSEC0040;
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].
RC TISSUE=Lung;
RX PubMed=11274388; DOI=10.1073/pnas.061028398;
RA Trexler M., Banyai L., Patthy L.;
RT "A human protein containing multiple types of protease-inhibitory
RT modules.";
RL Proc. Natl. Acad. Sci. U.S.A. 98:3705-3709(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Teratocarcinoma;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=11157797; DOI=10.1093/hmg/10.4.339;
RA Daniels R.J., Peden J.F., Lloyd C., Horsley S.W., Clark K., Tufarelli C.,
RA Kearney L., Buckle V.J., Doggett N.A., Flint J., Higgs D.R.;
RT "Sequence, structure and pathology of the fully annotated terminal 2 Mb of
RT the short arm of human chromosome 16.";
RL Hum. Mol. Genet. 10:339-352(2001).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP IDENTIFICATION.
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 [6]
RP DOMAIN.
RX PubMed=12709070; DOI=10.1046/j.1432-1033.2003.03593.x;
RA Nagy A., Trexler M., Patthy L.;
RT "Expression, purification and characterization of the second Kunitz-type
RT protease inhibitor domain of the human WFIKKN protein.";
RL Eur. J. Biochem. 270:2101-2107(2003).
RN [7]
RP STRUCTURE BY NMR OF 357-411.
RX PubMed=16791741; DOI=10.1007/s10858-006-9013-1;
RA Liepinsh E., Nagy A., Trexler M., Patthy L., Otting G.;
RT "Second Kunitz-type protease inhibitor domain of the human WFIKKN1
RT protein.";
RL J. Biomol. NMR 35:73-78(2006).
CC -!- FUNCTION: Protease-inhibitor that contains multiple distinct protease
CC inhibitor domains. Probably has serine protease- and metalloprotease-
CC inhibitor activity (By similarity). {ECO:0000250}.
CC -!- INTERACTION:
CC Q96NZ8; Q92624: APPBP2; NbExp=3; IntAct=EBI-2363713, EBI-743771;
CC Q96NZ8; O14793: MSTN; NbExp=4; IntAct=EBI-2363713, EBI-8542977;
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Expressed in pancreas, kidney, liver, placenta, and
CC lung.
CC -!- DOMAIN: The second BPTI/Kunitz inhibitor domain is able to inhibit
CC trypsin. It has however no activity toward chymotrypsin, elastase,
CC plasmin, pancreatic kallikrein, lung tryptase, plasma kallikrein,
CC thrombin, urokinase or tissue plasminogen activator.
CC {ECO:0000269|PubMed:12709070}.
CC -!- SIMILARITY: Belongs to the WFIKKN family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAK61237.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
CC Sequence=BAC11566.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; AF422194; AAL18839.1; -; mRNA.
DR EMBL; AK075356; BAC11566.1; ALT_FRAME; mRNA.
DR EMBL; AE006464; AAK61237.1; ALT_SEQ; Genomic_DNA.
DR EMBL; BC101602; AAI01603.1; -; mRNA.
DR EMBL; BC101606; AAI01607.1; -; mRNA.
DR CCDS; CCDS10414.1; -.
DR RefSeq; NP_444514.1; NM_053284.2.
DR PDB; 2DDI; NMR; -; A=357-411.
DR PDB; 2DDJ; NMR; -; A=357-411.
DR PDBsum; 2DDI; -.
DR PDBsum; 2DDJ; -.
DR AlphaFoldDB; Q96NZ8; -.
DR SMR; Q96NZ8; -.
DR BioGRID; 125565; 48.
DR IntAct; Q96NZ8; 11.
DR MINT; Q96NZ8; -.
DR STRING; 9606.ENSP00000324763; -.
DR MEROPS; I02.033; -.
DR MEROPS; I02.953; -.
DR MEROPS; I17.951; -.
DR GlyGen; Q96NZ8; 1 site.
DR iPTMnet; Q96NZ8; -.
DR PhosphoSitePlus; Q96NZ8; -.
DR BioMuta; WFIKKN1; -.
DR DMDM; 74717044; -.
DR EPD; Q96NZ8; -.
DR MassIVE; Q96NZ8; -.
DR PaxDb; Q96NZ8; -.
DR PeptideAtlas; Q96NZ8; -.
DR PRIDE; Q96NZ8; -.
DR ProteomicsDB; 77582; -.
DR TopDownProteomics; Q96NZ8; -.
DR Antibodypedia; 42371; 41 antibodies from 11 providers.
DR DNASU; 117166; -.
DR Ensembl; ENST00000319070.3; ENSP00000324763.2; ENSG00000127578.7.
DR GeneID; 117166; -.
DR KEGG; hsa:117166; -.
DR MANE-Select; ENST00000319070.3; ENSP00000324763.2; NM_053284.3; NP_444514.1.
DR UCSC; uc002cht.2; human.
DR CTD; 117166; -.
DR GeneCards; WFIKKN1; -.
DR HGNC; HGNC:30912; WFIKKN1.
DR HPA; ENSG00000127578; Low tissue specificity.
DR MIM; 608021; gene.
DR neXtProt; NX_Q96NZ8; -.
DR OpenTargets; ENSG00000127578; -.
DR PharmGKB; PA134897686; -.
DR VEuPathDB; HostDB:ENSG00000127578; -.
DR eggNOG; KOG4597; Eukaryota.
DR GeneTree; ENSGT00940000158031; -.
DR HOGENOM; CLU_037211_1_0_1; -.
DR InParanoid; Q96NZ8; -.
DR OMA; KIDWSCP; -.
DR OrthoDB; 324177at2759; -.
DR PhylomeDB; Q96NZ8; -.
DR TreeFam; TF315349; -.
DR PathwayCommons; Q96NZ8; -.
DR SignaLink; Q96NZ8; -.
DR BioGRID-ORCS; 117166; 16 hits in 1061 CRISPR screens.
DR ChiTaRS; WFIKKN1; human.
DR EvolutionaryTrace; Q96NZ8; -.
DR GeneWiki; WFIKKN1; -.
DR GenomeRNAi; 117166; -.
DR Pharos; Q96NZ8; Tbio.
DR PRO; PR:Q96NZ8; -.
DR Proteomes; UP000005640; Chromosome 16.
DR RNAct; Q96NZ8; protein.
DR Bgee; ENSG00000127578; Expressed in right hemisphere of cerebellum and 99 other tissues.
DR Genevisible; Q96NZ8; HS.
DR GO; GO:0005615; C:extracellular space; IBA:GO_Central.
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 CDD; cd00109; KU; 1.
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; 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; 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; PF00014; Kunitz_BPTI; 2.
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; 2.
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; Disulfide bond; Glycoprotein; Immunoglobulin domain;
KW Metalloenzyme inhibitor; Metalloprotease inhibitor; Protease inhibitor;
KW Reference proteome; Repeat; Secreted; Serine protease inhibitor; Signal.
FT SIGNAL 1..19
FT /evidence="ECO:0000255"
FT CHAIN 20..548
FT /note="WAP, Kazal, immunoglobulin, Kunitz and NTR domain-
FT containing protein 1"
FT /id="PRO_0000307816"
FT DOMAIN 26..79
FT /note="WAP"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00722"
FT DOMAIN 108..159
FT /note="Kazal-like"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00798"
FT DOMAIN 186..279
FT /note="Ig-like C2-type"
FT DOMAIN 299..351
FT /note="BPTI/Kunitz inhibitor 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00031"
FT DOMAIN 359..409
FT /note="BPTI/Kunitz inhibitor 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00031"
FT DOMAIN 409..540
FT /note="NTR"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00295"
FT REGION 164..184
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT SITE 122..123
FT /note="Reactive bond"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00798"
FT CARBOHYD 493
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 33..66
FT /evidence="ECO:0000250"
FT DISULFID 49..70
FT /evidence="ECO:0000250"
FT DISULFID 53..65
FT /evidence="ECO:0000250"
FT DISULFID 59..75
FT /evidence="ECO:0000250"
FT DISULFID 116..146
FT /evidence="ECO:0000250"
FT DISULFID 120..139
FT /evidence="ECO:0000250"
FT DISULFID 128..157
FT /evidence="ECO:0000250"
FT DISULFID 207..263
FT /evidence="ECO:0000250"
FT DISULFID 299..351
FT /evidence="ECO:0000250"
FT DISULFID 306..334
FT /evidence="ECO:0000250"
FT DISULFID 326..347
FT /evidence="ECO:0000250"
FT DISULFID 359..409
FT /evidence="ECO:0000250"
FT DISULFID 368..392
FT /evidence="ECO:0000250"
FT DISULFID 384..405
FT /evidence="ECO:0000250"
FT DISULFID 417..489
FT /evidence="ECO:0000250"
FT DISULFID 420..491
FT /evidence="ECO:0000250"
FT DISULFID 431..540
FT /evidence="ECO:0000250"
FT HELIX 358..360
FT /evidence="ECO:0007829|PDB:2DDI"
FT STRAND 372..378
FT /evidence="ECO:0007829|PDB:2DDI"
FT HELIX 379..381
FT /evidence="ECO:0007829|PDB:2DDI"
FT STRAND 383..389
FT /evidence="ECO:0007829|PDB:2DDI"
FT STRAND 391..393
FT /evidence="ECO:0007829|PDB:2DDI"
FT STRAND 399..401
FT /evidence="ECO:0007829|PDB:2DDI"
FT HELIX 402..408
FT /evidence="ECO:0007829|PDB:2DDI"
FT STRAND 409..411
FT /evidence="ECO:0007829|PDB:2DDJ"
SQ SEQUENCE 548 AA; 58798 MW; 72BB28708D3EFB1F CRC64;
MPALRPLLPL LLLLRLTSGA GLLPGLGSHP GVCPNQLSPN LWVDAQSTCE RECSRDQDCA
AAEKCCINVC GLHSCVAARF PGSPAAPTTA ASCEGFVCPQ QGSDCDIWDG QPVCRCRDRC
EKEPSFTCAS DGLTYYNRCY MDAEACLRGL HLHIVPCKHV LSWPPSSPGP PETTARPTPG
AAPVPPALYS SPSPQAVQVG GTASLHCDVS GRPPPAVTWE KQSHQRENLI MRPDQMYGNV
VVTSIGQLVL YNARPEDAGL YTCTARNAAG LLRADFPLSV VQREPARDAA PSIPAPAECL
PDVQACTGPT SPHLVLWHYD PQRGGCMTFP ARGCDGAARG FETYEACQQA CARGPGDACV
LPAVQGPCRG WEPRWAYSPL LQQCHPFVYG GCEGNGNNFH SRESCEDACP VPRTPPCRAC
RLRSKLALSL CRSDFAIVGR LTEVLEEPEA AGGIARVALE DVLKDDKMGL KFLGTKYLEV
TLSGMDWACP CPNMTAGDGP LVIMGEVRDG VAVLDAGSYV RAASEKRVKK ILELLEKQAC
ELLNRFQD