ISK6_HUMAN
ID ISK6_HUMAN Reviewed; 80 AA.
AC Q6UWN8; E0X656; Q8N5P0;
DT 01-FEB-2005, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2004, sequence version 1.
DT 03-AUG-2022, entry version 130.
DE RecName: Full=Serine protease inhibitor Kazal-type 6;
DE AltName: Full=Kallikrein inhibitor;
DE Flags: Precursor;
GN Name=SPINK6; ORFNames=UNQ844/PRO1782;
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], FUNCTION, AND VARIANT THR-36.
RC TISSUE=Foreskin;
RX PubMed=20667819; DOI=10.1074/jbc.m109.091850;
RA Meyer-Hoffert U., Wu Z., Kantyka T., Fischer J., Latendorf T., Hansmann B.,
RA Bartels J., He Y., Glaser R., Schroder J.M.;
RT "Isolation of SPINK6 in human skin: selective inhibitor of kallikrein-
RT related peptidases.";
RL J. Biol. Chem. 285:32174-32181(2010).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=12975309; DOI=10.1101/gr.1293003;
RA Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J.,
RA Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P.,
RA Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E., Heldens S., Huang A.,
RA Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D.,
RA Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L.,
RA Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C.,
RA Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J.,
RA Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M.;
RT "The secreted protein discovery initiative (SPDI), a large-scale effort to
RT identify novel human secreted and transmembrane proteins: a bioinformatics
RT assessment.";
RL Genome Res. 13:2265-2270(2003).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT THR-36.
RC TISSUE=Skin;
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 PROTEIN SEQUENCE OF 24-38.
RX PubMed=15340161; DOI=10.1110/ps.04682504;
RA Zhang Z., Henzel W.J.;
RT "Signal peptide prediction based on analysis of experimentally verified
RT cleavage sites.";
RL Protein Sci. 13:2819-2824(2004).
RN [6]
RP FUNCTION.
RX PubMed=21439340; DOI=10.1016/j.peptides.2011.03.009;
RA Kantyka T., Fischer J., Wu Z., Declercq W., Reiss K., Schroder J.M.,
RA Meyer-Hoffert U.;
RT "Inhibition of kallikrein-related peptidases by the serine protease
RT inhibitor of Kazal-type 6.";
RL Peptides 32:1187-1192(2011).
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:0000269|PubMed:20667819,
CC ECO:0000269|PubMed:21439340}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000250|UniProtKB:Q8BT20}.
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DR EMBL; GQ504704; ADM46526.1; -; mRNA.
DR EMBL; GQ504705; ADM46527.1; -; mRNA.
DR EMBL; AY358716; AAQ89078.1; -; mRNA.
DR EMBL; CH471062; EAW61813.1; -; Genomic_DNA.
DR EMBL; BC032003; AAH32003.1; -; mRNA.
DR CCDS; CCDS34268.1; -.
DR RefSeq; NP_001182219.1; NM_001195290.1.
DR RefSeq; NP_995313.2; NM_205841.3.
DR PDB; 2N52; NMR; -; A=21-80.
DR PDBsum; 2N52; -.
DR AlphaFoldDB; Q6UWN8; -.
DR SMR; Q6UWN8; -.
DR BioGRID; 135647; 1.
DR STRING; 9606.ENSP00000324870; -.
DR DrugBank; DB02107; Leucine - Reduced Carbonyl.
DR MEROPS; I01.015; -.
DR iPTMnet; Q6UWN8; -.
DR PhosphoSitePlus; Q6UWN8; -.
DR BioMuta; SPINK6; -.
DR MassIVE; Q6UWN8; -.
DR PaxDb; Q6UWN8; -.
DR PeptideAtlas; Q6UWN8; -.
DR PRIDE; Q6UWN8; -.
DR ProteomicsDB; 67506; -.
DR Antibodypedia; 53308; 103 antibodies from 21 providers.
DR DNASU; 404203; -.
DR Ensembl; ENST00000325630.3; ENSP00000324870.2; ENSG00000178172.7.
DR Ensembl; ENST00000621437.4; ENSP00000481309.1; ENSG00000178172.7.
DR GeneID; 404203; -.
DR KEGG; hsa:404203; -.
DR MANE-Select; ENST00000325630.3; ENSP00000324870.2; NM_205841.4; NP_995313.2.
DR UCSC; uc003lpa.4; human.
DR CTD; 404203; -.
DR DisGeNET; 404203; -.
DR GeneCards; SPINK6; -.
DR HGNC; HGNC:29486; SPINK6.
DR HPA; ENSG00000178172; Tissue enhanced (lymphoid tissue, salivary gland, vagina).
DR MIM; 615868; gene.
DR neXtProt; NX_Q6UWN8; -.
DR OpenTargets; ENSG00000178172; -.
DR PharmGKB; PA134915474; -.
DR VEuPathDB; HostDB:ENSG00000178172; -.
DR eggNOG; KOG3649; Eukaryota.
DR GeneTree; ENSGT00530000064225; -.
DR HOGENOM; CLU_169765_1_0_1; -.
DR InParanoid; Q6UWN8; -.
DR OMA; DCGEFRD; -.
DR OrthoDB; 1636538at2759; -.
DR PhylomeDB; Q6UWN8; -.
DR PathwayCommons; Q6UWN8; -.
DR Reactome; R-HSA-6809371; Formation of the cornified envelope.
DR BioGRID-ORCS; 404203; 9 hits in 1063 CRISPR screens.
DR ChiTaRS; SPINK6; human.
DR GenomeRNAi; 404203; -.
DR Pharos; Q6UWN8; Tbio.
DR PRO; PR:Q6UWN8; -.
DR Proteomes; UP000005640; Chromosome 5.
DR RNAct; Q6UWN8; protein.
DR Bgee; ENSG00000178172; Expressed in right hemisphere of cerebellum and 84 other tissues.
DR ExpressionAtlas; Q6UWN8; baseline and differential.
DR Genevisible; Q6UWN8; HS.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:0004867; F:serine-type endopeptidase inhibitor activity; IBA:GO_Central.
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; IEA:Ensembl.
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 Pfam; PF00050; Kazal_1; 1.
DR SMART; SM00280; KAZAL; 1.
DR SUPFAM; SSF100895; SSF100895; 1.
DR PROSITE; PS00282; KAZAL_1; 1.
DR PROSITE; PS51465; KAZAL_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Direct protein sequencing; Disulfide bond;
KW Protease inhibitor; Pyrrolidone carboxylic acid; Reference proteome;
KW Secreted; Serine protease inhibitor; Signal.
FT SIGNAL 1..23
FT /evidence="ECO:0000269|PubMed:15340161"
FT CHAIN 24..80
FT /note="Serine protease inhibitor Kazal-type 6"
FT /id="PRO_0000016575"
FT DOMAIN 24..80
FT /note="Kazal-like"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00798"
FT SITE 42..43
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 30..62
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00798"
FT DISULFID 40..59
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00798"
FT DISULFID 48..80
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00798"
FT VARIANT 36
FT /note="P -> T (in dbSNP:rs12186491)"
FT /evidence="ECO:0000269|PubMed:15489334,
FT ECO:0000269|PubMed:20667819"
FT /id="VAR_034020"
FT STRAND 26..29
FT /evidence="ECO:0007829|PDB:2N52"
FT STRAND 34..37
FT /evidence="ECO:0007829|PDB:2N52"
FT STRAND 47..49
FT /evidence="ECO:0007829|PDB:2N52"
FT STRAND 54..57
FT /evidence="ECO:0007829|PDB:2N52"
FT HELIX 58..66
FT /evidence="ECO:0007829|PDB:2N52"
FT TURN 67..70
FT /evidence="ECO:0007829|PDB:2N52"
FT STRAND 74..78
FT /evidence="ECO:0007829|PDB:2N52"
SQ SEQUENCE 80 AA; 8585 MW; C83CCA45AE69A900 CRC64;
MKLSGMFLLL SLALFCFLTG VFSQGGQVDC GEFQDPKVYC TRESNPHCGS DGQTYGNKCA
FCKAIVKSGG KISLKHPGKC
