ID   ISK6_RAT                Reviewed;         105 AA.
AC   Q6IE47;
DT   01-FEB-2005, integrated into UniProtKB/Swiss-Prot.
DT   05-JUL-2004, sequence version 1.
DT   25-MAY-2022, entry version 96.
DE   RecName: Full=Serine protease inhibitor Kazal-type 6;
DE   Flags: Precursor;
GN   Name=Spink6; Synonyms=Spink5l1;
OS   Rattus norvegicus (Rat).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Rattus.
OX   NCBI_TaxID=10116;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=Brown Norway;
RX   PubMed=15057822; DOI=10.1038/nature02426;
RA   Gibbs R.A., Weinstock G.M., Metzker M.L., Muzny D.M., Sodergren E.J.,
RA   Scherer S., Scott G., Steffen D., Worley K.C., Burch P.E., Okwuonu G.,
RA   Hines S., Lewis L., Deramo C., Delgado O., Dugan-Rocha S., Miner G.,
RA   Morgan M., Hawes A., Gill R., Holt R.A., Adams M.D., Amanatides P.G.,
RA   Baden-Tillson H., Barnstead M., Chin S., Evans C.A., Ferriera S.,
RA   Fosler C., Glodek A., Gu Z., Jennings D., Kraft C.L., Nguyen T.,
RA   Pfannkoch C.M., Sitter C., Sutton G.G., Venter J.C., Woodage T., Smith D.,
RA   Lee H.-M., Gustafson E., Cahill P., Kana A., Doucette-Stamm L.,
RA   Weinstock K., Fechtel K., Weiss R.B., Dunn D.M., Green E.D.,
RA   Blakesley R.W., Bouffard G.G., De Jong P.J., Osoegawa K., Zhu B., Marra M.,
RA   Schein J., Bosdet I., Fjell C., Jones S., Krzywinski M., Mathewson C.,
RA   Siddiqui A., Wye N., McPherson J., Zhao S., Fraser C.M., Shetty J.,
RA   Shatsman S., Geer K., Chen Y., Abramzon S., Nierman W.C., Havlak P.H.,
RA   Chen R., Durbin K.J., Egan A., Ren Y., Song X.-Z., Li B., Liu Y., Qin X.,
RA   Cawley S., Cooney A.J., D'Souza L.M., Martin K., Wu J.Q.,
RA   Gonzalez-Garay M.L., Jackson A.R., Kalafus K.J., McLeod M.P.,
RA   Milosavljevic A., Virk D., Volkov A., Wheeler D.A., Zhang Z., Bailey J.A.,
RA   Eichler E.E., Tuzun E., Birney E., Mongin E., Ureta-Vidal A., Woodwark C.,
RA   Zdobnov E., Bork P., Suyama M., Torrents D., Alexandersson M., Trask B.J.,
RA   Young J.M., Huang H., Wang H., Xing H., Daniels S., Gietzen D., Schmidt J.,
RA   Stevens K., Vitt U., Wingrove J., Camara F., Mar Alba M., Abril J.F.,
RA   Guigo R., Smit A., Dubchak I., Rubin E.M., Couronne O., Poliakov A.,
RA   Huebner N., Ganten D., Goesele C., Hummel O., Kreitler T., Lee Y.-A.,
RA   Monti J., Schulz H., Zimdahl H., Himmelbauer H., Lehrach H., Jacob H.J.,
RA   Bromberg S., Gullings-Handley J., Jensen-Seaman M.I., Kwitek A.E.,
RA   Lazar J., Pasko D., Tonellato P.J., Twigger S., Ponting C.P., Duarte J.M.,
RA   Rice S., Goodstadt L., Beatson S.A., Emes R.D., Winter E.E., Webber C.,
RA   Brandt P., Nyakatura G., Adetobi M., Chiaromonte F., Elnitski L.,
RA   Eswara P., Hardison R.C., Hou M., Kolbe D., Makova K., Miller W.,
RA   Nekrutenko A., Riemer C., Schwartz S., Taylor J., Yang S., Zhang Y.,
RA   Lindpaintner K., Andrews T.D., Caccamo M., Clamp M., Clarke L., Curwen V.,
RA   Durbin R.M., Eyras E., Searle S.M., Cooper G.M., Batzoglou S., Brudno M.,
RA   Sidow A., Stone E.A., Payseur B.A., Bourque G., Lopez-Otin C., Puente X.S.,
RA   Chakrabarti K., Chatterji S., Dewey C., Pachter L., Bray N., Yap V.B.,
RA   Caspi A., Tesler G., Pevzner P.A., Haussler D., Roskin K.M., Baertsch R.,
RA   Clawson H., Furey T.S., Hinrichs A.S., Karolchik D., Kent W.J.,
RA   Rosenbloom K.R., Trumbower H., Weirauch M., Cooper D.N., Stenson P.D.,
RA   Ma B., Brent M., Arumugam M., Shteynberg D., Copley R.R., Taylor M.S.,
RA   Riethman H., Mudunuri U., Peterson J., Guyer M., Felsenfeld A., Old S.,
RA   Mockrin S., Collins F.S.;
RT   "Genome sequence of the Brown Norway rat yields insights into mammalian
RT   evolution.";
RL   Nature 428:493-521(2004).
RN   [2]
RP   IDENTIFICATION.
RX   PubMed=15060002; DOI=10.1101/gr.1946304;
RA   Puente X.S., Lopez-Otin C.;
RT   "A genomic analysis of rat proteases and protease inhibitors.";
RL   Genome Res. 14:609-622(2004).
CC   -!- FUNCTION: Serine protease inhibitor selective for kallikreins.
CC       Efficiently inhibits KLK4, KLK5, KLK6, KLK7, KLK12, KLK13 and KLK14.
CC       Doesn't inhibit KLK8. {ECO:0000250|UniProtKB:Q6UWN8}.
CC   -!- SUBCELLULAR LOCATION: Secreted {ECO:0000250|UniProtKB:Q8BT20}.
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DR   EMBL; AC095532; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; BN000346; CAE51398.1; -; mRNA.
DR   RefSeq; NP_001008874.1; NM_001008874.1.
DR   AlphaFoldDB; Q6IE47; -.
DR   SMR; Q6IE47; -.
DR   STRING; 10116.ENSRNOP00000017489; -.
DR   MEROPS; I01.015; -.
DR   PaxDb; Q6IE47; -.
DR   PRIDE; Q6IE47; -.
DR   GeneID; 408235; -.
DR   KEGG; rno:408235; -.
DR   UCSC; RGD:1303338; rat.
DR   CTD; 404203; -.
DR   RGD; 1303338; Spink6.
DR   eggNOG; KOG3649; Eukaryota.
DR   InParanoid; Q6IE47; -.
DR   PhylomeDB; Q6IE47; -.
DR   PRO; PR:Q6IE47; -.
DR   Proteomes; UP000002494; Unplaced.
DR   GO; GO:0005576; C:extracellular region; ISO:RGD.
DR   GO; GO:0004867; F:serine-type endopeptidase inhibitor activity; ISO:RGD.
DR   GO; GO:0030154; P:cell differentiation; IBA:GO_Central.
DR   GO; GO:0007417; P:central nervous system development; IBA:GO_Central.
DR   GO; GO:1900004; P:negative regulation of serine-type endopeptidase activity; ISO:RGD.
DR   GO; GO:1902572; P:negative regulation of serine-type peptidase activity; IBA:GO_Central.
DR   InterPro; IPR002350; Kazal_dom.
DR   InterPro; IPR036058; Kazal_dom_sf.
DR   InterPro; IPR001239; Prot_inh_Kazal-m.
DR   Pfam; PF00050; Kazal_1; 1.
DR   PRINTS; PR00290; KAZALINHBTR.
DR   SMART; SM00280; KAZAL; 1.
DR   SUPFAM; SSF100895; SSF100895; 1.
DR   PROSITE; PS00282; KAZAL_1; 1.
DR   PROSITE; PS51465; KAZAL_2; 1.
PE   3: Inferred from homology;
KW   Disulfide bond; Protease inhibitor; Pyrrolidone carboxylic acid;
KW   Reference proteome; Secreted; Serine protease inhibitor; Signal.
FT   SIGNAL          1..23
FT                   /evidence="ECO:0000255"
FT   CHAIN           24..105
FT                   /note="Serine protease inhibitor Kazal-type 6"
FT                   /id="PRO_0000016577"
FT   DOMAIN          49..105
FT                   /note="Kazal-like"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00798"
FT   SITE            67..68
FT                   /note="Reactive bond"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00798"
FT   MOD_RES         24
FT                   /note="Pyrrolidone carboxylic acid"
FT                   /evidence="ECO:0000250|UniProtKB:P01001"
FT   DISULFID        55..87
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00798"
FT   DISULFID        65..84
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00798"
FT   DISULFID        73..105
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00798"
SQ   SEQUENCE   105 AA;  11667 MW;  9F5DE46712A8684E CRC64;
     MKVAGVFLLL SLALLCFFSG EFSQGGQDKR GWITRSEGRF PGKGVLRHRL FQINCGEFRD
     PKVFCTRESD PLCGSDGQTY GNKCAFCKAL EKSSGKINLK HRGKC