ID KLK14_HUMAN Reviewed; 267 AA. AC Q9P0G3; A7UNK5; Q1RMZ2; Q6B089; DT 11-JAN-2001, integrated into UniProtKB/Swiss-Prot. DT 07-JUL-2009, sequence version 2. DT 25-JAN-2012, entry version 93. DE RecName: Full=Kallikrein-14; DE Short=hK14; DE EC=3.4.21.-; DE AltName: Full=Kallikrein-like protein 6; DE Short=KLK-L6; DE Flags: Precursor; GN Name=KLK14; Synonyms=KLKL6; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND TISSUE SPECIFICITY. RX PubMed=11309303; RA Yousef G.M., Magklara A., Chang A., Jung K., Katsaros D., RA Diamandis E.P.; RT "Cloning of a new member of the human kallikrein gene family, KLK14, RT which is down-regulated in different malignancies."; RL Cancer Res. 61:3425-3431(2001). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA], AND TISSUE SPECIFICITY. RX MEDLINE=21250997; PubMed=11352573; DOI=10.1006/geno.2000.6490; RA Hooper J.D., Bui L.T., Rae F.K., Harvey T.J., Myers S.A., RA Ashworth L.K., Clements J.A.; RT "Identification and characterization of KLK14, a novel kallikrein RT serine protease gene located on human chromosome 19q13.4 and expressed RT in prostate and skeletal muscle."; RL Genomics 73:117-122(2001). RN [3] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX PubMed=17922479; DOI=10.1002/gepi.20185; RA Andres A.M., Clark A.G., Shimmin L., Boerwinkle E., Sing C.F., RA Hixson J.E.; RT "Understanding the accuracy of statistical haplotype inference with RT sequence data of known phase."; RL Genet. Epidemiol. 31:659-671(2007). RN [4] 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., RA Lamerdin J.E., Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., RA Aerts A., Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., RA Caenepeel S., Carrano A.V., Caoile C., Chan Y.M., Christensen M., RA Cleland C.A., Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., RA Escobar J., Flowers D., Fotopulos D., Garcia C., Georgescu A.M., RA Glavina T., Gomez M., Gonzales E., Groza M., Hammon N., Hawkins T., RA Haydu L., Ho I., Huang W., Israni S., Jett J., Kadner K., Kimball H., RA Kobayashi A., Larionov V., Leem S.-H., Lopez F., Lou Y., Lowry S., RA Malfatti S., Martinez D., McCready P.M., Medina C., Morgan J., RA Nelson K., Nolan M., Ovcharenko I., Pitluck S., Pollard M., RA Popkie A.P., Predki P., Quan G., Ramirez L., Rash S., Retterer J., RA Rodriguez A., Rogers S., Salamov A., Salazar A., She X., Smith D., RA Slezak T., Solovyev V., Thayer N., Tice H., Tsai M., Ustaszewska A., RA Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J., Dubchak I., RA 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 [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R., RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., RA Venter J.C.; RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANTS ARG-33 AND RP TYR-45. RC TISSUE=Lung; 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 RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [7] RP TISSUE SPECIFICITY. RX MEDLINE=20545474; PubMed=10969073; DOI=10.1074/jbc.M004525200; RA Harvey T.J., Hooper J.D., Myers S.A., Stephenson S.A., Ashworth L.K., RA Clements J.A.; RT "Tissue-specific expression patterns and fine mapping of the human RT kallikrein (KLK) locus on proximal 19q13.4."; RL J. Biol. Chem. 275:37397-37406(2000). RN [8] RP INDUCTION BY STEROID HORMONE. RX PubMed=12645335; DOI=10.1309/0UA57MNAYV0MCE9U; RA Yousef G.M., Fracchioli S., Scorilas A., Borgono C.A., Iskander L., RA Puopolo M., Massobrio M., Diamandis E.P., Katsaros D.; RT "Steroid hormone regulation and prognostic value of the human RT kallikrein gene 14 in ovarian cancer."; RL Am. J. Clin. Pathol. 119:346-355(2003). RN [9] RP CHARACTERIZATION. RX PubMed=15843175; DOI=10.1515/BC.2005.035; RA Felber L.M., Borgono C.A., Cloutier S.M., Kuendig C., Kishi T., RA Ribeiro Chagas J., Jichlinski P., Gygi C.M., Leisinger H.-J., RA Diamandis E.P., Deperthes D.; RT "Enzymatic profiling of human kallikrein 14 using phage-display RT substrate technology."; RL Biol. Chem. 386:291-298(2005). RN [10] RP FUNCTION, SUBCELLULAR LOCATION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL RP PROPERTIES, AND ENZYME REGULATION. RX PubMed=15654974; DOI=10.1111/j.0022-202X.2004.23547.x; RA Brattsand M., Stefansson K., Lundh C., Haasum Y., Egelrud T.; RT "A proteolytic cascade of kallikreins in the stratum corneum."; RL J. Invest. Dermatol. 124:198-203(2005). RN [11] RP PROTEIN SEQUENCE OF 41-55, AND TISSUE SPECIFICITY. RX PubMed=16800737; DOI=10.1515/BC.2006.095; RA Stefansson K., Brattsand M., Ny A., Glas B., Egelrud T.; RT "Kallikrein-related peptidase 14 may be a major contributor to RT trypsin-like proteolytic activity in human stratum corneum."; RL Biol. Chem. 387:761-768(2006). RN [12] RP FUNCTION IN G PROTEIN-COUPLED RECEPTOR SIGNALING. RX PubMed=16885167; DOI=10.1074/jbc.M513138200; RA Oikonomopoulou K., Hansen K.K., Saifeddine M., Tea I., Blaber M., RA Blaber S.I., Scarisbrick I., Andrade-Gordon P., Cottrell G.S., RA Bunnett N.W., Diamandis E.P., Hollenberg M.D.; RT "Proteinase-activated receptors, targets for kallikrein signaling."; RL J. Biol. Chem. 281:32095-32112(2006). RN [13] RP TISSUE SPECIFICITY, AND SUBCELLULAR LOCATION. RX PubMed=16456535; DOI=10.1038/sj.jid.5700146; RA Komatsu N., Tsai B., Sidiropoulos M., Saijoh K., Levesque M.A., RA Takehara K., Diamandis E.P.; RT "Quantification of eight tissue kallikreins in the stratum corneum and RT sweat."; RL J. Invest. Dermatol. 126:925-929(2006). RN [14] RP SUBCELLULAR LOCATION, TISSUE SPECIFICITY, PROTEOLYTIC PROCESSING, RP BIOPHYSICOCHEMICAL PROPERTIES, AND ENZYME REGULATION. RX PubMed=17110383; DOI=10.1074/jbc.M608348200; RA Borgono C.A., Michael I.P., Shaw J.L.V., Luo L.-Y., Ghosh M.C., RA Soosaipillai A., Grass L., Katsaros D., Diamandis E.P.; RT "Expression and functional characterization of the cancer-related RT serine protease, human tissue kallikrein 14."; RL J. Biol. Chem. 282:2405-2422(2007). RN [15] RP FUNCTION, AND ENZYME REGULATION. RX PubMed=17158887; DOI=10.1074/jbc.M607567200; RA Borgono C.A., Michael I.P., Komatsu N., Jayakumar A., Kapadia R., RA Clayman G.L., Sotiropoulou G., Diamandis E.P.; RT "A potential role for multiple tissue kallikrein serine proteases in RT epidermal desquamation."; RL J. Biol. Chem. 282:3640-3652(2007). RN [16] RP FUNCTION. RX PubMed=18056261; DOI=10.1074/jbc.M707253200; RA Emami N., Diamandis E.P.; RT "Human kallikrein-related peptidase 14 (KLK14) is a new activator RT component of the KLK proteolytic cascade. Possible function in seminal RT plasma and skin."; RL J. Biol. Chem. 283:3031-3041(2008). RN [17] RP FUNCTION. RX PubMed=18482984; DOI=10.1074/jbc.M801194200; RA Emami N., Deperthes D., Malm J., Diamandis E.P.; RT "Major role of human KLK14 in seminal clot liquefaction."; RL J. Biol. Chem. 283:19561-19569(2008). RN [18] RP FUNCTION. RX PubMed=17625593; DOI=10.1038/sj.jid.5700965; RA Stefansson K., Brattsand M., Roosterman D., Kempkes C., Bocheva G., RA Steinhoff M., Egelrud T.; RT "Activation of proteinase-activated receptor-2 by human kallikrein- RT related peptidases."; RL J. Invest. Dermatol. 128:18-25(2008). CC -!- FUNCTION: Serine-type endopeptidase with a dual trypsin-like and CC chymotrypsin-like substrate specificity. May activate/inactivate CC the proteinase-activated receptors F2R, F2RL1 and F2RL3 and other CC kallikreins including KLK1, KLK3, KLK5 and KLK11. May function in CC seminal clot liquefaction through direct cleavage of the CC semenogelin SEMG1 and SEMG2 and activation of KLK3. May function CC through desmoglein DSG1 cleavage in epidermal desquamation a CC process by which the most superficial corneocytes are shed from CC the skin surface. May be involved in several aspects of tumor CC progression including growth, invasion and angiogenesis. CC -!- ENZYME REGULATION: Inhibited by SERPINA1, SERPINC1, SERPINE1, CC SERPINF2, aprotinin, soybean, trypsin inhibitor and leupeptin. CC Inhibited by serine protease inhibitor SPINK5. Has an CC autoproteolytic activity which may have a regulatory effect. CC Activated by citrate and inhibited by zinc and to a lower extent CC by manganese. CC -!- BIOPHYSICOCHEMICAL PROPERTIES: CC Kinetic parameters: CC KM=0.3 mM for S-2288; CC KM=0.2 mM for S-2222; CC KM=0.2 mM for S-2302; CC KM=0.7 mM for S-2586; CC KM=0.045 mM for Gln-Ala-Arg synthetic peptide; CC KM=0.043 mM for Val-Pro-Arg synthetic peptide; CC KM=0.09 mM for Pro-Phe-Arg synthetic peptide; CC KM=0.278 mM for Phe-Ser-Arg synthetic peptide; CC KM=0.0577 mM for Leu-Gly-Arg synthetic peptide; CC KM=0.139 mM for Gln-Gly-Arg synthetic peptide; CC KM=0.173 mM for Gly-Pro-Arg synthetic peptide; CC KM=0.0268 mM for Gln-Arg-Arg synthetic peptide; CC KM=0.130 mM for Gly-Gly-Arg synthetic peptide; CC KM=0.578 mM for Val-Leu-Lys synthetic peptide; CC Note=Has a higher catalytic efficiency for the trypsin-like CC enzyme substrates S-2288, S-2222 and S-2302 compared to S-2586 a CC chymotrypsin-like enzyme substrate. Has a lower catalytic CC activity compared to trypsin towards S-2288, S-2222 and S-2302. CC Cleaves preferentially after Arg residues; CC pH dependence: CC Optimum pH is 8.0; CC -!- SUBCELLULAR LOCATION: Secreted, extracellular space. CC -!- TISSUE SPECIFICITY: Highly expressed in CNS, bone marrow and fetal CC liver. Also expressed in breast, thyroid, kidney, colon, pancreas, CC spleen, prostate, uterus, small intestine, placenta and skeletal CC muscle. Among 40 tissues tested, the highest expression is CC detected in skin followed by breast and prostate (at protein CC level). Expressed in stratum corneum by sweat ducts and sweat CC glands and detected in sweat (at protein level). CC -!- INDUCTION: Up-regulated by steroid hormone. CC -!- PTM: Proteolytic cleavage of the activation peptide produces the CC active enzyme. CC -!- SIMILARITY: Belongs to the peptidase S1 family. Kallikrein CC subfamily. CC -!- SIMILARITY: Contains 1 peptidase S1 domain. CC -!- CAUTION: It is uncertain whether Met-1 or Met-17 is the initiator. CC -!- SEQUENCE CAUTION: CC Sequence=AAD50773.2; Type=Erroneous gene model prediction; CC Sequence=AAG23260.1; Type=Erroneous gene model prediction; CC Sequence=AAK48523.1; Type=Erroneous gene model prediction; CC Sequence=AAK48524.1; Type=Erroneous initiation; CC Sequence=ABU63131.1; Type=Erroneous gene model prediction; CC ----------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution-NoDerivs License CC ----------------------------------------------------------------------- DR EMBL; AF161221; AAD50773.2; ALT_SEQ; Genomic_DNA. DR EMBL; AF283669; AAK48523.1; ALT_SEQ; Genomic_DNA. DR EMBL; AF283670; AAK48524.1; ALT_INIT; mRNA. DR EMBL; EU091477; ABU63131.1; ALT_SEQ; Genomic_DNA. DR EMBL; AC011473; AAG23260.1; ALT_SEQ; Genomic_DNA. DR EMBL; CH471135; EAW71982.1; -; Genomic_DNA. DR EMBL; BC074904; AAH74904.2; -; mRNA. DR EMBL; BC074905; AAH74905.2; -; mRNA. DR EMBL; BC114614; AAI14615.2; -; mRNA. DR IPI; IPI00000700; -. DR RefSeq; NP_071329.2; NM_022046.4. DR UniGene; Hs.283925; -. DR ProteinModelPortal; Q9P0G3; -. DR SMR; Q9P0G3; 2-266. DR STRING; Q9P0G3; -. DR MEROPS; S01.029; -. DR DMDM; 251757292; -. DR PRIDE; Q9P0G3; -. DR Ensembl; ENST00000156499; ENSP00000156499; ENSG00000129437. DR Ensembl; ENST00000391802; ENSP00000375678; ENSG00000129437. DR GeneID; 43847; -. DR KEGG; hsa:43847; -. DR CTD; 43847; -. DR GeneCards; GC19M051580; -. DR HGNC; HGNC:6362; KLK14. DR HPA; CAB026228; -. DR MIM; 606135; gene. DR neXtProt; NX_Q9P0G3; -. DR PharmGKB; PA30151; -. DR GeneTree; ENSGT00580000081320; -. DR HOGENOM; HBG755338; -. DR HOVERGEN; HBG013304; -. DR InParanoid; Q9P0G3; -. DR OMA; SAPKMFL; -. DR OrthoDB; EOG43BMPJ; -. DR PhylomeDB; Q9P0G3; -. DR PMAP-CutDB; Q9P0G3; -. DR ArrayExpress; Q9P0G3; -. DR Bgee; Q9P0G3; -. DR CleanEx; HS_KLK14; -. DR Genevestigator; Q9P0G3; -. DR GermOnline; ENSG00000129437; Homo sapiens. DR GO; GO:0005615; C:extracellular space; IDA:UniProtKB. DR GO; GO:0004252; F:serine-type endopeptidase activity; IDA:UniProtKB. DR GO; GO:0048730; P:epidermis morphogenesis; IDA:UniProtKB. DR GO; GO:0009566; P:fertilization; IDA:UniProtKB. DR GO; GO:0045744; P:negative regulation of G-protein coupled receptor protein signaling pathway; IDA:UniProtKB. DR GO; GO:0045745; P:positive regulation of G-protein coupled receptor protein signaling pathway; IDA:UniProtKB. DR GO; GO:0006508; P:proteolysis; IDA:UniProtKB. DR GO; GO:0070684; P:seminal clot liquefaction; IDA:UniProtKB. DR InterPro; IPR009003; Pept_cys/ser_Trypsin-like. DR InterPro; IPR018114; Peptidase_S1/S6_AS. DR InterPro; IPR001254; Peptidase_S1_S6. DR InterPro; IPR001314; Peptidase_S1A. DR KO; K09622; -. DR Pfam; PF00089; Trypsin; 1. DR PRINTS; PR00722; CHYMOTRYPSIN. DR SMART; SM00020; Tryp_SPc; 1. DR SUPFAM; SSF50494; Pept_Ser_Cys; 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 Complete proteome; Direct protein sequencing; Disulfide bond; KW Hydrolase; Polymorphism; Protease; Reference proteome; Secreted; KW Serine protease; Signal; Zymogen. FT SIGNAL 1 34 FT PROPEP 35 40 Activation peptide. FT /FTId=PRO_0000027958. FT CHAIN 41 267 Kallikrein-14. FT /FTId=PRO_0000027959. FT DOMAIN 41 265 Peptidase S1. FT ACT_SITE 83 83 Charge relay system (By similarity). FT ACT_SITE 127 127 Charge relay system (By similarity). FT ACT_SITE 220 220 Charge relay system (By similarity). FT DISULFID 47 180 By similarity. FT DISULFID 68 84 By similarity. FT DISULFID 159 226 By similarity. FT DISULFID 191 205 By similarity. FT DISULFID 216 241 By similarity. FT VARIANT 33 33 Q -> R (in dbSNP:rs35287116). FT /FTId=VAR_058018. FT VARIANT 45 45 H -> Y (in dbSNP:rs2569491). FT /FTId=VAR_058019. FT VARIANT 64 64 R -> H (in dbSNP:rs2569490). FT /FTId=VAR_058020. SQ SEQUENCE 267 AA; 29122 MW; 0CE085DA7BD1D92B CRC64; MSLRVLGSGT WPSAPKMFLL LTALQVLAIA MTQSQEDENK IIGGHTCTRS SQPWQAALLA GPRRRFLCGG ALLSGQWVIT AAHCGRPILQ VALGKHNLRR WEATQQVLRV VRQVTHPNYN SRTHDNDLML LQLQQPARIG RAVRPIEVTQ ACASPGTSCR VSGWGTISSP IARYPASLQC VNINISPDEV CQKAYPRTIT PGMVCAGVPQ GGKDSCQGDS GGPLVCRGQL QGLVSWGMER CALPGYPGVY TNLCKYRSWI EETMRDK //