KLK5_HUMAN
ID KLK5_HUMAN Reviewed; 293 AA.
AC Q9Y337; A0A024R4G4; Q53ZR3; Q9HBG8;
DT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot.
DT 25-OCT-2017, sequence version 3.
DT 03-AUG-2022, entry version 187.
DE RecName: Full=Kallikrein-5 {ECO:0000312|HGNC:HGNC:6366};
DE EC=3.4.21.-;
DE AltName: Full=Kallikrein-like protein 2;
DE Short=KLK-L2;
DE AltName: Full=Stratum corneum tryptic enzyme;
DE Flags: Precursor;
GN Name=KLK5 {ECO:0000312|HGNC:HGNC:6366};
GN Synonyms=SCTE {ECO:0000312|HGNC:HGNC:6366}; ORFNames=UNQ570/PRO1132;
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=Stratum corneum;
RX PubMed=10514489; DOI=10.1074/jbc.274.42.30033;
RA Brattsand M., Egelrud T.;
RT "Purification, molecular cloning, and expression of a human stratum corneum
RT trypsin-like serine protease with possible function in desquamation.";
RL J. Biol. Chem. 274:30033-30040(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=10652563;
RA Yousef G.M., Luo L.-Y., Diamandis E.P.;
RT "Identification of novel human kallikrein-like genes on chromosome 19q13.3-
RT q13.4.";
RL Anticancer Res. 19:2843-2852(1999).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=11054574; DOI=10.1016/s0378-1119(00)00382-6;
RA Gan L., Lee I., Smith R., Argonza-Barrett R., Lei H., McCuaig J., Moss P.,
RA Paeper B., Wang K.;
RT "Sequencing and expression analysis of the serine protease gene cluster
RT located in chromosome 19q13 region.";
RL Gene 257:119-130(2000).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=15361712; DOI=10.1159/000079147;
RA Kurlender L., Yousef G.M., Memari N., Robb J.D., Michael I.P., Borgono C.,
RA Katsaros D., Stephan C., Jung K., Diamandis E.P.;
RT "Differential expression of a human kallikrein 5 (KLK5) splice variant in
RT ovarian and prostate cancer.";
RL Tumor Biol. 25:149-156(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=28224083; DOI=10.1016/j.ymgmr.2017.01.009;
RA Premzl M.;
RT "Comparative genomic analysis of eutherian kallikrein genes.";
RL Mol. Genet. Metab. Rep. 10:96-99(2017).
RN [6]
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 [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor vector.";
RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15057824; DOI=10.1038/nature02399;
RA Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E.,
RA Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A.,
RA Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S.,
RA Carrano A.V., Caoile C., Chan Y.M., Christensen M., Cleland C.A.,
RA Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J.,
RA Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M.,
RA Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W.,
RA Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V.,
RA Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D.,
RA McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I.,
RA Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L.,
RA Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A.,
RA She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M.,
RA Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J.,
RA Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E.,
RA Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M.,
RA Rubin E.M., Lucas S.M.;
RT "The DNA sequence and biology of human chromosome 19.";
RL Nature 428:529-535(2004).
RN [9]
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 (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [10]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Ovary;
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 [11]
RP INTERACTION WITH SPINK9.
RX PubMed=19194479; DOI=10.1038/jid.2008.448;
RA Brattsand M., Stefansson K., Hubiche T., Nilsson S.K., Egelrud T.;
RT "SPINK9: a selective, skin-specific Kazal-type serine protease inhibitor.";
RL J. Invest. Dermatol. 129:1656-1665(2009).
RN [12]
RP TISSUE SPECIFICITY.
RX PubMed=19190773; DOI=10.1371/journal.pone.0004372;
RA Meyer-Hoffert U., Wu Z., Schroeder J.M.;
RT "Identification of lympho-epithelial Kazal-type inhibitor 2 in human skin
RT as a kallikrein-related peptidase 5-specific protease inhibitor.";
RL PLoS ONE 4:E4372-E4372(2009).
RN [13]
RP X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 67-293 ALONE AND IN COMPLEX WITH
RP ZINC, ACTIVITY REGULATION, ACTIVE SITE, GLYCOSYLATION AT ASN-208, AND
RP DISULFIDE BONDS.
RX PubMed=17881000; DOI=10.1016/j.jmb.2007.08.042;
RA Debela M., Goettig P., Magdolen V., Huber R., Schechter N.M., Bode W.;
RT "Structural basis of the zinc inhibition of human tissue kallikrein 5.";
RL J. Mol. Biol. 373:1017-1031(2007).
CC -!- FUNCTION: May be involved in desquamation.
CC -!- ACTIVITY REGULATION: Inhibited by Zn2+. {ECO:0000269|PubMed:17881000}.
CC -!- SUBUNIT: Interacts with SPINK9. {ECO:0000269|PubMed:17881000,
CC ECO:0000269|PubMed:19194479}.
CC -!- INTERACTION:
CC Q9Y337; P20930: FLG; NbExp=4; IntAct=EBI-9057524, EBI-1058782;
CC Q9Y337; Q9NQG1: MANBAL; NbExp=3; IntAct=EBI-9057524, EBI-3867271;
CC -!- SUBCELLULAR LOCATION: Secreted.
CC -!- TISSUE SPECIFICITY: Expressed in skin, breast, brain and testis.
CC Expressed at the stratum granulosum of palmar skin.
CC {ECO:0000269|PubMed:19190773}.
CC -!- SIMILARITY: Belongs to the peptidase S1 family. Kallikrein subfamily.
CC {ECO:0000255|PROSITE-ProRule:PRU00274}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAG33358.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
CC Sequence=AAG33358.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/KLK5ID41085ch19q13.html";
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DR EMBL; AF168768; AAF03101.1; -; mRNA.
DR EMBL; AF135028; AAD26429.1; -; Genomic_DNA.
DR EMBL; AF243527; AAG33358.1; ALT_SEQ; Genomic_DNA.
DR EMBL; AY279380; AAP42275.1; -; mRNA.
DR EMBL; AY279381; AAP42276.1; -; mRNA.
DR EMBL; LT631554; SFW93201.1; -; Genomic_DNA.
DR EMBL; AY359010; AAQ89369.1; -; mRNA.
DR EMBL; BT006867; AAP35513.1; -; mRNA.
DR EMBL; AC011483; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471135; EAW71946.1; -; Genomic_DNA.
DR EMBL; CH471135; EAW71948.1; -; Genomic_DNA.
DR EMBL; CH471135; EAW71949.1; -; Genomic_DNA.
DR EMBL; CH471135; EAW71950.1; -; Genomic_DNA.
DR EMBL; CH471135; EAW71952.1; -; Genomic_DNA.
DR EMBL; BC008036; AAH08036.1; -; mRNA.
DR CCDS; CCDS12810.1; -.
DR RefSeq; NP_001070959.1; NM_001077491.1.
DR RefSeq; NP_001070960.1; NM_001077492.1.
DR RefSeq; NP_036559.1; NM_012427.4.
DR RefSeq; XP_011525004.1; XM_011526702.1.
DR RefSeq; XP_011525005.1; XM_011526703.2.
DR PDB; 2PSX; X-ray; 2.30 A; A=67-293.
DR PDB; 2PSY; X-ray; 2.30 A; A=67-293.
DR PDB; 6QFE; X-ray; 1.67 A; A/B=67-293.
DR PDBsum; 2PSX; -.
DR PDBsum; 2PSY; -.
DR PDBsum; 6QFE; -.
DR AlphaFoldDB; Q9Y337; -.
DR SMR; Q9Y337; -.
DR BioGRID; 117346; 128.
DR IntAct; Q9Y337; 41.
DR MINT; Q9Y337; -.
DR STRING; 9606.ENSP00000337733; -.
DR BindingDB; Q9Y337; -.
DR ChEMBL; CHEMBL4447; -.
DR GuidetoPHARMACOLOGY; 2375; -.
DR MEROPS; S01.017; -.
DR GlyConnect; 1428; 1 N-Linked glycan (1 site).
DR GlyGen; Q9Y337; 5 sites, 1 N-linked glycan (1 site), 1 O-linked glycan (1 site).
DR iPTMnet; Q9Y337; -.
DR PhosphoSitePlus; Q9Y337; -.
DR BioMuta; KLK5; -.
DR DMDM; 296434569; -.
DR EPD; Q9Y337; -.
DR MassIVE; Q9Y337; -.
DR PaxDb; Q9Y337; -.
DR PeptideAtlas; Q9Y337; -.
DR PRIDE; Q9Y337; -.
DR ProteomicsDB; 85971; -.
DR Antibodypedia; 2601; 362 antibodies from 41 providers.
DR DNASU; 25818; -.
DR Ensembl; ENST00000336334.8; ENSP00000337733.2; ENSG00000167754.13.
DR Ensembl; ENST00000391809.6; ENSP00000375685.1; ENSG00000167754.13.
DR Ensembl; ENST00000593428.5; ENSP00000471966.1; ENSG00000167754.13.
DR GeneID; 25818; -.
DR KEGG; hsa:25818; -.
DR MANE-Select; ENST00000336334.8; ENSP00000337733.2; NM_012427.5; NP_036559.1.
DR UCSC; uc002pue.4; human.
DR CTD; 25818; -.
DR DisGeNET; 25818; -.
DR GeneCards; KLK5; -.
DR HGNC; HGNC:6366; KLK5.
DR HPA; ENSG00000167754; Tissue enriched (skin).
DR MIM; 605643; gene.
DR neXtProt; NX_Q9Y337; -.
DR OpenTargets; ENSG00000167754; -.
DR PharmGKB; PA30155; -.
DR VEuPathDB; HostDB:ENSG00000167754; -.
DR eggNOG; KOG3627; Eukaryota.
DR GeneTree; ENSGT01020000230389; -.
DR HOGENOM; CLU_006842_1_1_1; -.
DR InParanoid; Q9Y337; -.
DR OMA; HCRKPVY; -.
DR OrthoDB; 1314811at2759; -.
DR PhylomeDB; Q9Y337; -.
DR TreeFam; TF331065; -.
DR BRENDA; 3.4.21.B39; 2681.
DR PathwayCommons; Q9Y337; -.
DR Reactome; R-HSA-6809371; Formation of the cornified envelope.
DR SignaLink; Q9Y337; -.
DR BioGRID-ORCS; 25818; 7 hits in 1068 CRISPR screens.
DR ChiTaRS; KLK5; human.
DR EvolutionaryTrace; Q9Y337; -.
DR GeneWiki; KLK5; -.
DR GenomeRNAi; 25818; -.
DR Pharos; Q9Y337; Tchem.
DR PRO; PR:Q9Y337; -.
DR Proteomes; UP000005640; Chromosome 19.
DR RNAct; Q9Y337; protein.
DR Bgee; ENSG00000167754; Expressed in upper arm skin and 95 other tissues.
DR ExpressionAtlas; Q9Y337; baseline and differential.
DR Genevisible; Q9Y337; HS.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0097209; C:epidermal lamellar body; IDA:UniProtKB.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:0005615; C:extracellular space; IMP:UniProtKB.
DR GO; GO:0030141; C:secretory granule; IBA:GO_Central.
DR GO; GO:0008233; F:peptidase activity; IMP:UniProtKB.
DR GO; GO:0004252; F:serine-type endopeptidase activity; IDA:UniProtKB.
DR GO; GO:0008236; F:serine-type peptidase activity; TAS:ProtInc.
DR GO; GO:0097186; P:amelogenesis; IBA:GO_Central.
DR GO; GO:0070268; P:cornification; TAS:Reactome.
DR GO; GO:0008544; P:epidermis development; TAS:ProtInc.
DR GO; GO:0022617; P:extracellular matrix disassembly; IBA:GO_Central.
DR GO; GO:0002803; P:positive regulation of antibacterial peptide production; IMP:UniProtKB.
DR GO; GO:0045745; P:positive regulation of G protein-coupled receptor signaling pathway; IDA:UniProtKB.
DR GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR CDD; cd00190; Tryp_SPc; 1.
DR Gene3D; 2.40.10.10; -; 2.
DR InterPro; IPR009003; Peptidase_S1_PA.
DR InterPro; IPR043504; Peptidase_S1_PA_chymotrypsin.
DR InterPro; IPR001314; Peptidase_S1A.
DR InterPro; IPR001254; Trypsin_dom.
DR InterPro; IPR018114; TRYPSIN_HIS.
DR InterPro; IPR033116; TRYPSIN_SER.
DR Pfam; PF00089; Trypsin; 1.
DR PRINTS; PR00722; CHYMOTRYPSIN.
DR SMART; SM00020; Tryp_SPc; 1.
DR SUPFAM; SSF50494; SSF50494; 1.
DR PROSITE; PS50240; TRYPSIN_DOM; 1.
DR PROSITE; PS00134; TRYPSIN_HIS; 1.
DR PROSITE; PS00135; TRYPSIN_SER; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Disulfide bond; Glycoprotein; Hydrolase; Protease;
KW Reference proteome; Secreted; Serine protease; Signal.
FT SIGNAL 1..22
FT /evidence="ECO:0000255"
FT CHAIN 23..293
FT /note="Kallikrein-5"
FT /id="PRO_0000027939"
FT DOMAIN 67..290
FT /note="Peptidase S1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT REGION 37..68
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 108
FT /note="Charge relay system"
FT /evidence="ECO:0000269|PubMed:17881000"
FT ACT_SITE 153
FT /note="Charge relay system"
FT /evidence="ECO:0000269|PubMed:17881000"
FT ACT_SITE 245
FT /note="Charge relay system"
FT /evidence="ECO:0000269|PubMed:17881000"
FT SITE 150
FT /note="Major binding site for inhibitory zinc"
FT CARBOHYD 69
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 173
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 208
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:17881000"
FT CARBOHYD 252
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 73..206
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274,
FT ECO:0000269|PubMed:17881000"
FT DISULFID 93..109
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274,
FT ECO:0000269|PubMed:17881000"
FT DISULFID 178..279
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274,
FT ECO:0000269|PubMed:17881000"
FT DISULFID 185..251
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274,
FT ECO:0000269|PubMed:17881000"
FT DISULFID 217..231
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274,
FT ECO:0000269|PubMed:17881000"
FT DISULFID 241..266
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274,
FT ECO:0000269|PubMed:17881000"
FT VARIANT 55
FT /note="G -> R (in dbSNP:rs2232532)"
FT /id="VAR_051853"
FT VARIANT 153
FT /note="D -> N (in dbSNP:rs183854)"
FT /id="VAR_051854"
FT STRAND 81..86
FT /evidence="ECO:0007829|PDB:6QFE"
FT TURN 87..89
FT /evidence="ECO:0007829|PDB:6QFE"
FT STRAND 90..99
FT /evidence="ECO:0007829|PDB:6QFE"
FT STRAND 102..105
FT /evidence="ECO:0007829|PDB:6QFE"
FT HELIX 107..109
FT /evidence="ECO:0007829|PDB:2PSX"
FT STRAND 114..119
FT /evidence="ECO:0007829|PDB:6QFE"
FT STRAND 122..124
FT /evidence="ECO:0007829|PDB:6QFE"
FT STRAND 132..134
FT /evidence="ECO:0007829|PDB:6QFE"
FT STRAND 136..141
FT /evidence="ECO:0007829|PDB:6QFE"
FT STRAND 147..149
FT /evidence="ECO:0007829|PDB:2PSX"
FT STRAND 155..161
FT /evidence="ECO:0007829|PDB:6QFE"
FT STRAND 167..169
FT /evidence="ECO:0007829|PDB:6QFE"
FT STRAND 184..191
FT /evidence="ECO:0007829|PDB:6QFE"
FT STRAND 193..197
FT /evidence="ECO:0007829|PDB:6QFE"
FT STRAND 205..211
FT /evidence="ECO:0007829|PDB:6QFE"
FT HELIX 214..220
FT /evidence="ECO:0007829|PDB:6QFE"
FT TURN 222..224
FT /evidence="ECO:0007829|PDB:6QFE"
FT STRAND 229..232
FT /evidence="ECO:0007829|PDB:6QFE"
FT STRAND 248..251
FT /evidence="ECO:0007829|PDB:6QFE"
FT STRAND 254..261
FT /evidence="ECO:0007829|PDB:6QFE"
FT STRAND 273..277
FT /evidence="ECO:0007829|PDB:6QFE"
FT HELIX 278..281
FT /evidence="ECO:0007829|PDB:6QFE"
FT HELIX 282..291
FT /evidence="ECO:0007829|PDB:6QFE"
SQ SEQUENCE 293 AA; 32020 MW; D92C92F5609E5946 CRC64;
MATARPPWMW VLCALITALL LGVTEHVLAN NDVSCDHPSN TVPSGSNQDL GAGAGEDARS
DDSSSRIING SDCDMHTQPW QAALLLRPNQ LYCGAVLVHP QWLLTAAHCR KKVFRVRLGH
YSLSPVYESG QQMFQGVKSI PHPGYSHPGH SNDLMLIKLN RRIRPTKDVR PINVSSHCPS
AGTKCLVSGW GTTKSPQVHF PKVLQCLNIS VLSQKRCEDA YPRQIDDTMF CAGDKAGRDS
CQGDSGGPVV CNGSLQGLVS WGDYPCARPN RPGVYTNLCK FTKWIQETIQ ANS
