(data stored in ACNUC3659 zone)

HOVERGEN: KLK14_HUMAN

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   13-OCT-2009, entry version 75.
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=ABU63131.1; Type=Erroneous gene model prediction;
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CC   -!- GENE_FAMILY: HBG013304 [ FAMILY / ALN / TREE ]
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; -.
DR   UniGene; Hs.283925; -.
DR   HSSP; P00760; 1EZX.
DR   STRING; Q9P0G3; -.
DR   MEROPS; S01.029; -.
DR   Ensembl; ENST00000156499; ENSP00000156499; ENSG00000129437; Homo sapiens.
DR   Ensembl; ENST00000391802; ENSP00000375678; ENSG00000129437; Homo sapiens.
DR   GeneID; 43847; -.
DR   KEGG; hsa:43847; -.
DR   UCSC; uc002pvs.1; human.
DR   GeneCards; GC19M056272; -.
DR   H-InvDB; HIX0039986; -.
DR   HGNC; HGNC:6362; KLK14.
DR   HPA; CAB026228; -.
DR   MIM; 606135; gene.
DR   PharmGKB; PA30151; -.
DR   HOVERGEN; 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 re...; IDA:UniProtKB.
DR   GO; GO:0045745; P:positive regulation of G-protein coupled re...; IDA:UniProtKB.
DR   GO; GO:0006508; P:proteolysis; IDA:UniProtKB.
DR   GO; GO:0070684; P:seminal clot liquefaction; IDA:UniProtKB.
DR   InterPro; IPR018114; Peptidase_S1/S6_AS.
DR   InterPro; IPR001254; Peptidase_S1_S6.
DR   InterPro; IPR001314; Peptidase_S1A.
DR   Pfam; PF00089; Trypsin; 1.
DR   PRINTS; PR00722; CHYMOTRYPSIN.
DR   SMART; SM00020; Tryp_SPc; 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;
DR   PRODOM; Q9P0G3.
DR   SWISS-2DPAGE; Q9P0G3.
KW   Complete proteome; Direct protein sequencing; Disulfide bond;
KW   Hydrolase; Polymorphism; Protease; Secreted; Serine protease; Signal;
KW   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
//

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