ISK6_MOUSE
ID ISK6_MOUSE Reviewed; 105 AA.
AC Q8BT20;
DT 01-FEB-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2003, sequence version 1.
DT 03-AUG-2022, entry version 120.
DE RecName: Full=Serine protease inhibitor Kazal-type 6;
DE Flags: Precursor;
GN Name=Spink6;
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 [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [2]
RP TISSUE SPECIFICITY, INDUCTION, SUBCELLULAR LOCATION, AND FUNCTION.
RX PubMed=24352040; DOI=10.1038/jid.2013.502;
RA Fischer J., Wu Z., Kantyka T., Sperrhacke M., Dimitrieva O., Koblyakova Y.,
RA Ahrens K., Graumann N., Baurecht H., Reiss K., Schroder J.M., Proksch E.,
RA Meyer-Hoffert U.;
RT "Characterization of Spink6 in mouse skin: the conserved inhibitor of
RT kallikrein-related peptidases is reduced by barrier injury.";
RL J. Invest. Dermatol. 134:1305-1312(2014).
CC -!- FUNCTION: Serine protease inhibitor selective for kallikreins.
CC Efficiently inhibits KLK5 and human KLK2, KLK4, KLK5, KLK6, KLK7,
CC KLK12, KLK13 and KLK14. Doesn't inhibit human KLK1 and KLK8.
CC {ECO:0000269|PubMed:24352040}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:24352040}.
CC -!- TISSUE SPECIFICITY: Expressed in the upper epidermis and in skin
CC appendages. {ECO:0000269|PubMed:24352040}.
CC -!- INDUCTION: Release of soluble SPINK6 is down-regulated by TNF-alpha.
CC IFN-gamma and retinoic acid. Expression is reduced after mechanical and
CC metabolic injury to the skin barrier. {ECO:0000269|PubMed:24352040}.
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DR EMBL; AK028032; BAC25711.1; -; mRNA.
DR CCDS; CCDS29224.1; -.
DR RefSeq; NP_001013819.1; NM_001013797.1.
DR AlphaFoldDB; Q8BT20; -.
DR SMR; Q8BT20; -.
DR STRING; 10090.ENSMUSP00000069247; -.
DR MEROPS; I01.015; -.
DR PaxDb; Q8BT20; -.
DR PRIDE; Q8BT20; -.
DR Antibodypedia; 53308; 103 antibodies from 21 providers.
DR DNASU; 433180; -.
DR Ensembl; ENSMUST00000068473; ENSMUSP00000069247; ENSMUSG00000055095.
DR GeneID; 433180; -.
DR KEGG; mmu:433180; -.
DR UCSC; uc008eur.1; mouse.
DR CTD; 404203; -.
DR MGI; MGI:3648654; Spink6.
DR VEuPathDB; HostDB:ENSMUSG00000055095; -.
DR eggNOG; KOG3649; Eukaryota.
DR GeneTree; ENSGT00530000064225; -.
DR HOGENOM; CLU_169765_1_0_1; -.
DR InParanoid; Q8BT20; -.
DR OrthoDB; 1636538at2759; -.
DR PhylomeDB; Q8BT20; -.
DR BioGRID-ORCS; 433180; 2 hits in 71 CRISPR screens.
DR PRO; PR:Q8BT20; -.
DR Proteomes; UP000000589; Chromosome 18.
DR RNAct; Q8BT20; protein.
DR Bgee; ENSMUSG00000055095; Expressed in lip and 5 other tissues.
DR ExpressionAtlas; Q8BT20; baseline and differential.
DR GO; GO:0005576; C:extracellular region; IDA:MGI.
DR GO; GO:0004867; F:serine-type endopeptidase inhibitor activity; IDA:MGI.
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; IDA:MGI.
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 2: Evidence at transcript level;
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_0000016576"
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; 11609 MW; CB59A06715C2C589 CRC64;
MKVAGVFLLL SLALLCFFSG AFSQGGQDKR GWITRSEGRF PGKGVLRHRL FQINCGEFRD
PKVFCTRESD PLCGSDGQTY GNKCAFCKAL EKSSGKINLK HRGKC
