KLK6_HUMAN
ID KLK6_HUMAN Reviewed; 244 AA.
AC Q92876; A6NJA1; A8MW09; Q6H301;
DT 15-DEC-1998, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1997, sequence version 1.
DT 03-AUG-2022, entry version 188.
DE RecName: Full=Kallikrein-6;
DE EC=3.4.21.-;
DE AltName: Full=Neurosin;
DE AltName: Full=Protease M;
DE AltName: Full=SP59;
DE AltName: Full=Serine protease 18;
DE AltName: Full=Serine protease 9;
DE AltName: Full=Zyme;
DE Flags: Precursor;
GN Name=KLK6; Synonyms=PRSS18, PRSS9;
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] (ISOFORM 1).
RX PubMed=8898378; DOI=10.1007/bf03401646;
RA Anisowicz A., Sotiropoulou G., Stenman G., Mok S.C., Sager R.;
RT "A novel protease homolog differentially expressed in breast and ovarian
RT cancer.";
RL Mol. Med. 2:624-636(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Colon;
RX PubMed=9003450; DOI=10.1016/s0167-4781(96)00187-x;
RA Yamashiro K., Tsuruoka N., Kodama S., Tsujimoto M., Yamamura Y., Tanaka T.,
RA Nakazato H., Yamaguchi N.;
RT "Molecular cloning of a novel trypsin-like serine protease (neurosin)
RT preferentially expressed in brain.";
RL Biochim. Biophys. Acta 1350:11-14(1997).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Brain;
RX PubMed=9312124; DOI=10.1074/jbc.272.40.25135;
RA Little S.P., Dixon E.P., Norris F., Buckley W., Becker G.W., Johnson M.,
RA Dobbins J.R., Wyrick T., Miller J.R., Mackellar W., Hepburn D.,
RA Corvalan J., McClure D., Liu X., Stephenson D., Clemens J., Johnstone E.M.;
RT "Zyme, a novel and potentially amyloidogenic enzyme cDNA isolated from
RT Alzheimer's disease brain.";
RL J. Biol. Chem. 272:25135-25142(1997).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=10610719; DOI=10.1006/geno.1999.6012;
RA Yousef G.M., Luo L.Y., Scherer S.W., Sotiropoulou G., Diamandis E.P.;
RT "Molecular characterization of Zyme/protease M/neurosin(PRSS9), a
RT hormonally regulated kallikrein-like serine protease.";
RL Genomics 62:251-259(1999).
RN [5]
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 [6]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2 AND 3).
RC TISSUE=Testis;
RX PubMed=15207701; DOI=10.1016/j.bbrc.2004.04.205;
RA Pampalakis G., Kurlender L., Diamandis E.P., Sotiropoulou G.;
RT "Cloning and characterization of novel isoforms of the human kallikrein 6
RT gene.";
RL Biochem. Biophys. Res. Commun. 320:54-61(2004).
RN [7]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND TISSUE SPECIFICITY.
RX PubMed=16800739; DOI=10.1515/bc.2006.097;
RA Pampalakis G., Sotiropoulou G.;
RT "Multiple mechanisms underlie the aberrant expression of the human
RT kallikrein 6 gene in breast cancer.";
RL Biol. Chem. 387:773-782(2006).
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
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 (OCT-2004) to the EMBL/GenBank/DDBJ databases.
RN [10]
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 [11]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.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 [12]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Colon;
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 [13]
RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=11018688; DOI=10.1016/s0009-9120(00)00145-4;
RA Diamandis E.P., Yousef G.M., Soosaipillai A.R., Grass L., Porter A.,
RA Little S., Sotiropoulou G.;
RT "Immunofluorometric assay of human kallikrein 6 (zyme/protease M/neurosin)
RT and preliminary clinical applications.";
RL Clin. Biochem. 33:369-375(2000).
RN [14]
RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=10997858; DOI=10.1046/j.1440-1819.2000.00731.x;
RA Ogawa K., Yamada T., Tsujioka Y., Taguchi J., Takahashi M., Tsuboi Y.,
RA Fujino Y., Nakajima M., Yamamoto T., Akatsu H., Mitsui S., Yamaguchi N.;
RT "Localization of a novel type trypsin-like serine protease, neurosin, in
RT brain tissues of Alzheimer's disease and Parkinson's disease.";
RL Psychiatry Clin. Neurosci. 54:419-426(2000).
RN [15]
RP TISSUE SPECIFICITY.
RX PubMed=11668196; DOI=10.1177/002215540104901111;
RA Petraki C.D., Karavana V.N., Skoufogiannis P.T., Little S.P.,
RA Howarth D.J.C., Yousef G.M., Diamandis E.P.;
RT "The spectrum of human kallikrein 6 (zyme/protease M/neurosin) expression
RT in human tissues as assessed by immunohistochemistry.";
RL J. Histochem. Cytochem. 49:1431-1441(2001).
RN [16]
RP FUNCTION, ACTIVITY REGULATION, BIOPHYSICOCHEMICAL PROPERTIES, AND
RP AUTOCATALYTIC CLEAVAGE.
RX PubMed=12878203; DOI=10.1016/s0006-291x(03)01271-3;
RA Magklara A., Mellati A.A., Wasney G.A., Little S.P., Sotiropoulou G.,
RA Becker G.W., Diamandis E.P.;
RT "Characterization of the enzymatic activity of human kallikrein 6:
RT autoactivation, substrate specificity, and regulation by inhibitors.";
RL Biochem. Biophys. Res. Commun. 307:948-955(2003).
RN [17]
RP FUNCTION, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=12928483; DOI=10.1093/hmg/ddg283;
RA Iwata A., Maruyama M., Akagi T., Hashikawa T., Kanazawa I., Tsuji S.,
RA Nukina N.;
RT "Alpha-synuclein degradation by serine protease neurosin: implication for
RT pathogenesis of synucleinopathies.";
RL Hum. Mol. Genet. 12:2625-2635(2003).
RN [18]
RP FUNCTION.
RX PubMed=15557757; DOI=10.1159/000081102;
RA Ghosh M.C., Grass L., Soosaipillai A., Sotiropoulou G., Diamandis E.P.;
RT "Human kallikrein 6 degrades extracellular matrix proteins and may enhance
RT the metastatic potential of tumour cells.";
RL Tumor Biol. 25:193-199(2004).
RN [19]
RP FUNCTION, AND INDUCTION.
RX PubMed=16987227; DOI=10.1111/j.1460-9568.2006.05021.x;
RA Scarisbrick I.A., Sabharwal P., Cruz H., Larsen N., Vandell A.G.,
RA Blaber S.I., Ameenuddin S., Papke L.M., Fehlings M.G., Reeves R.K.,
RA Blaber M., Windebank A.J., Rodriguez M.;
RT "Dynamic role of kallikrein 6 in traumatic spinal cord injury.";
RL Eur. J. Neurosci. 24:1457-1469(2006).
RN [20]
RP FUNCTION, AND ACTIVITY REGULATION.
RX PubMed=16321973; DOI=10.1074/jbc.m510096200;
RA Angelo P.F., Lima A.R., Alves F.M., Blaber S.I., Scarisbrick I.A.,
RA Blaber M., Juliano L., Juliano M.A.;
RT "Substrate specificity of human kallikrein 6: salt and glycosaminoglycan
RT activation effects.";
RL J. Biol. Chem. 281:3116-3126(2006).
RN [21]
RP AUTOCATALYTIC CLEAVAGE.
RX PubMed=17417874; DOI=10.1021/bi6025006;
RA Blaber S.I., Yoon H., Scarisbrick I.A., Juliano M.A., Blaber M.;
RT "The autolytic regulation of human kallikrein-related peptidase 6.";
RL Biochemistry 46:5209-5217(2007).
RN [22]
RP X-RAY CRYSTALLOGRAPHY (1.80 ANGSTROMS) OF 21-243, AUTOCATALYTIC CLEAVAGE,
RP ACTIVE SITES, AND DISULFIDE BONDS.
RX PubMed=12016211; DOI=10.1074/jbc.m201534200;
RA Gomis-Rueth F.X., Bayes A., Sotiropoulou G., Pampalakis G., Tsetsenis T.,
RA Villegas V., Aviles F.X., Coll M.;
RT "The structure of human prokallikrein 6 reveals a novel activation
RT mechanism for the kallikrein family.";
RL J. Biol. Chem. 277:27273-27281(2002).
RN [23]
RP X-RAY CRYSTALLOGRAPHY (1.75 ANGSTROMS) OF 22-244, PROTEIN SEQUENCE OF
RP 22-25, FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES, AUTOCATALYTIC CLEAVAGE,
RP DISULFIDE BONDS, AND MASS SPECTROMETRY.
RX PubMed=11983703; DOI=10.1074/jbc.m202392200;
RA Bernett M.J., Blaber S.I., Scarisbrick I.A., Dhanarajan P., Thompson S.M.,
RA Blaber M.;
RT "Crystal structure and biochemical characterization of human kallikrein 6
RT reveals that a trypsin-like kallikrein is expressed in the central nervous
RT system.";
RL J. Biol. Chem. 277:24562-24570(2002).
CC -!- FUNCTION: Serine protease which exhibits a preference for Arg over Lys
CC in the substrate P1 position and for Ser or Pro in the P2 position.
CC Shows activity against amyloid precursor protein, myelin basic protein,
CC gelatin, casein and extracellular matrix proteins such as fibronectin,
CC laminin, vitronectin and collagen. Degrades alpha-synuclein and
CC prevents its polymerization, indicating that it may be involved in the
CC pathogenesis of Parkinson disease and other synucleinopathies. May be
CC involved in regulation of axon outgrowth following spinal cord injury.
CC Tumor cells treated with a neutralizing KLK6 antibody migrate less than
CC control cells, suggesting a role in invasion and metastasis.
CC {ECO:0000269|PubMed:11983703, ECO:0000269|PubMed:12878203,
CC ECO:0000269|PubMed:12928483, ECO:0000269|PubMed:15557757,
CC ECO:0000269|PubMed:16321973, ECO:0000269|PubMed:16987227}.
CC -!- ACTIVITY REGULATION: Inhibited by a range of serine protease inhibitors
CC including soybean trypsin inhibitor, benzamidine and serpins. Activated
CC by a range of glycosaminoglycans including chondroitin sulfate,
CC dermatan sulfate, heparan sulfate and heparin.
CC {ECO:0000269|PubMed:12878203, ECO:0000269|PubMed:16321973}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=1562 uM for Tosyl-Gly-Pro-Arg-AMC {ECO:0000269|PubMed:11983703,
CC ECO:0000269|PubMed:12878203};
CC KM=777 uM for Tosyl-Gly-Pro-Lys-AMC {ECO:0000269|PubMed:11983703,
CC ECO:0000269|PubMed:12878203};
CC KM=0.410 mM for Phe-Ser-Arg-AMC {ECO:0000269|PubMed:11983703,
CC ECO:0000269|PubMed:12878203};
CC KM=0.455 mM for Gly-Gly-Arg-AMC {ECO:0000269|PubMed:11983703,
CC ECO:0000269|PubMed:12878203};
CC KM=0.335 mM for Asp-Pro-Arg-AMC {ECO:0000269|PubMed:11983703,
CC ECO:0000269|PubMed:12878203};
CC KM=0.758 mM for Gln-Gly-Arg-AMC {ECO:0000269|PubMed:11983703,
CC ECO:0000269|PubMed:12878203};
CC KM=0.625 mM for Pro-Phe-Arg-AMC {ECO:0000269|PubMed:11983703,
CC ECO:0000269|PubMed:12878203};
CC KM=0.271 mM for Val-Pro-Arg-AMC {ECO:0000269|PubMed:11983703,
CC ECO:0000269|PubMed:12878203};
CC KM=1.72 mM for Val-Leu-Lys-AMC {ECO:0000269|PubMed:11983703,
CC ECO:0000269|PubMed:12878203};
CC -!- INTERACTION:
CC Q92876; Q8NC06-3: ACBD4; NbExp=3; IntAct=EBI-2432309, EBI-12811089;
CC Q92876; P11117: ACP2; NbExp=3; IntAct=EBI-2432309, EBI-2907070;
CC Q92876; Q53FZ2-2: ACSM3; NbExp=3; IntAct=EBI-2432309, EBI-25887341;
CC Q92876; Q96BT7-2: ALKBH8; NbExp=3; IntAct=EBI-2432309, EBI-13329511;
CC Q92876; P05067: APP; NbExp=4; IntAct=EBI-2432309, EBI-77613;
CC Q92876; Q9NP61: ARFGAP3; NbExp=3; IntAct=EBI-2432309, EBI-2875816;
CC Q92876; Q5H9R4-2: ARMCX4; NbExp=3; IntAct=EBI-2432309, EBI-21899904;
CC Q92876; Q8WXK3-2: ASB13; NbExp=3; IntAct=EBI-2432309, EBI-12015080;
CC Q92876; Q12797-6: ASPH; NbExp=3; IntAct=EBI-2432309, EBI-12092171;
CC Q92876; Q9Y6H3: ATP23; NbExp=3; IntAct=EBI-2432309, EBI-12811889;
CC Q92876; P27449: ATP6V0C; NbExp=3; IntAct=EBI-2432309, EBI-721179;
CC Q92876; O95817: BAG3; NbExp=3; IntAct=EBI-2432309, EBI-747185;
CC Q92876; Q8TBE0: BAHD1; NbExp=3; IntAct=EBI-2432309, EBI-742750;
CC Q92876; Q9UQB8-3: BAIAP2; NbExp=3; IntAct=EBI-2432309, EBI-9091996;
CC Q92876; Q9UQB8-6: BAIAP2; NbExp=3; IntAct=EBI-2432309, EBI-9092016;
CC Q92876; P51572: BCAP31; NbExp=3; IntAct=EBI-2432309, EBI-77683;
CC Q92876; O15155-2: BET1; NbExp=3; IntAct=EBI-2432309, EBI-25846497;
CC Q92876; Q9BXY8: BEX2; NbExp=3; IntAct=EBI-2432309, EBI-745073;
CC Q92876; Q7L1Q6-2: BZW1; NbExp=3; IntAct=EBI-2432309, EBI-21557060;
CC Q92876; Q9H0W9-3: C11orf54; NbExp=3; IntAct=EBI-2432309, EBI-12108466;
CC Q92876; Q9H257-2: CARD9; NbExp=3; IntAct=EBI-2432309, EBI-11530605;
CC Q92876; Q86XM0: CATSPERD; NbExp=3; IntAct=EBI-2432309, EBI-10260328;
CC Q92876; O75309: CDH16; NbExp=3; IntAct=EBI-2432309, EBI-2837263;
CC Q92876; P49336-2: CDK8; NbExp=3; IntAct=EBI-2432309, EBI-11039720;
CC Q92876; Q9Y281: CFL2; NbExp=3; IntAct=EBI-2432309, EBI-351218;
CC Q92876; Q8NE62: CHDH; NbExp=3; IntAct=EBI-2432309, EBI-7127986;
CC Q92876; O75508: CLDN11; NbExp=3; IntAct=EBI-2432309, EBI-12820543;
CC Q92876; Q9BT09: CNPY3; NbExp=3; IntAct=EBI-2432309, EBI-2835965;
CC Q92876; P20849: COL9A1; NbExp=3; IntAct=EBI-2432309, EBI-2528238;
CC Q92876; Q86WV2: COX4I1; NbExp=3; IntAct=EBI-2432309, EBI-10260134;
CC Q92876; P68400: CSNK2A1; NbExp=3; IntAct=EBI-2432309, EBI-347804;
CC Q92876; P09668: CTSH; NbExp=3; IntAct=EBI-2432309, EBI-6189940;
CC Q92876; P09172: DBH; NbExp=3; IntAct=EBI-2432309, EBI-8589586;
CC Q92876; P61962: DCAF7; NbExp=3; IntAct=EBI-2432309, EBI-359808;
CC Q92876; Q9BTE7: DCUN1D5; NbExp=3; IntAct=EBI-2432309, EBI-3924013;
CC Q92876; Q6ZPD9-2: DPY19L3; NbExp=3; IntAct=EBI-2432309, EBI-25888224;
CC Q92876; P63167: DYNLL1; NbExp=3; IntAct=EBI-2432309, EBI-349105;
CC Q92876; Q13144: EIF2B5; NbExp=3; IntAct=EBI-2432309, EBI-4401110;
CC Q92876; P23588: EIF4B; NbExp=3; IntAct=EBI-2432309, EBI-970310;
CC Q92876; P16452: EPB42; NbExp=3; IntAct=EBI-2432309, EBI-1182496;
CC Q92876; Q5RHP9-3: ERICH3; NbExp=3; IntAct=EBI-2432309, EBI-20839496;
CC Q92876; Q6NXG1: ESRP1; NbExp=3; IntAct=EBI-2432309, EBI-10213520;
CC Q92876; Q6NXG1-3: ESRP1; NbExp=3; IntAct=EBI-2432309, EBI-21567429;
CC Q92876; Q7L5A8: FA2H; NbExp=3; IntAct=EBI-2432309, EBI-11337888;
CC Q92876; Q6NZ36-4: FAAP20; NbExp=3; IntAct=EBI-2432309, EBI-12013806;
CC Q92876; Q14296: FASTK; NbExp=3; IntAct=EBI-2432309, EBI-1754067;
CC Q92876; P31994: FCGR2B; NbExp=3; IntAct=EBI-2432309, EBI-724784;
CC Q92876; Q7L622: G2E3; NbExp=3; IntAct=EBI-2432309, EBI-751757;
CC Q92876; P24522: GADD45A; NbExp=3; IntAct=EBI-2432309, EBI-448167;
CC Q92876; P15976-2: GATA1; NbExp=3; IntAct=EBI-2432309, EBI-9090198;
CC Q92876; Q9NXC2: GFOD1; NbExp=3; IntAct=EBI-2432309, EBI-8799578;
CC Q92876; B2RAF7: hCG_1818547; NbExp=3; IntAct=EBI-2432309, EBI-25844370;
CC Q92876; P52790: HK3; NbExp=3; IntAct=EBI-2432309, EBI-2965780;
CC Q92876; Q9P0W2: HMG20B; NbExp=3; IntAct=EBI-2432309, EBI-713401;
CC Q92876; Q4VB01: HOXB1; NbExp=3; IntAct=EBI-2432309, EBI-17494170;
CC Q92876; Q7LGA3-3: HS2ST1; NbExp=3; IntAct=EBI-2432309, EBI-25887463;
CC Q92876; Q96D96-2: HVCN1; NbExp=3; IntAct=EBI-2432309, EBI-25888137;
CC Q92876; Q8IYA8: IHO1; NbExp=3; IntAct=EBI-2432309, EBI-8638439;
CC Q92876; Q14005-2: IL16; NbExp=3; IntAct=EBI-2432309, EBI-17178971;
CC Q92876; Q0VD86: INCA1; NbExp=3; IntAct=EBI-2432309, EBI-6509505;
CC Q92876; Q9BT40: INPP5K; NbExp=3; IntAct=EBI-2432309, EBI-749162;
CC Q92876; Q9Y283-3: INVS; NbExp=3; IntAct=EBI-2432309, EBI-11944909;
CC Q92876; P57682: KLF3; NbExp=3; IntAct=EBI-2432309, EBI-8472267;
CC Q92876; Q9Y2M5: KLHL20; NbExp=3; IntAct=EBI-2432309, EBI-714379;
CC Q92876; O60259: KLK8; NbExp=3; IntAct=EBI-2432309, EBI-3915857;
CC Q92876; P08727: KRT19; NbExp=3; IntAct=EBI-2432309, EBI-742756;
CC Q92876; Q14533: KRT81; NbExp=3; IntAct=EBI-2432309, EBI-739648;
CC Q92876; Q3LI72: KRTAP19-5; NbExp=3; IntAct=EBI-2432309, EBI-1048945;
CC Q92876; Q3SYF9: KRTAP19-7; NbExp=3; IntAct=EBI-2432309, EBI-10241353;
CC Q92876; Q8IUC2: KRTAP8-1; NbExp=3; IntAct=EBI-2432309, EBI-10261141;
CC Q92876; Q92615: LARP4B; NbExp=3; IntAct=EBI-2432309, EBI-1052558;
CC Q92876; Q14847-2: LASP1; NbExp=3; IntAct=EBI-2432309, EBI-9088686;
CC Q92876; Q6DKI2: LGALS9C; NbExp=3; IntAct=EBI-2432309, EBI-9088829;
CC Q92876; Q8TE12-2: LMX1A; NbExp=3; IntAct=EBI-2432309, EBI-25846312;
CC Q92876; O95332: LOC57228; NbExp=3; IntAct=EBI-2432309, EBI-25846778;
CC Q92876; Q96JB6: LOXL4; NbExp=3; IntAct=EBI-2432309, EBI-749562;
CC Q92876; Q99683: MAP3K5; NbExp=3; IntAct=EBI-2432309, EBI-476263;
CC Q92876; Q15759: MAPK11; NbExp=3; IntAct=EBI-2432309, EBI-298304;
CC Q92876; P42679: MATK; NbExp=3; IntAct=EBI-2432309, EBI-751664;
CC Q92876; Q8N6R0: METTL13; NbExp=3; IntAct=EBI-2432309, EBI-1053295;
CC Q92876; Q14728: MFSD10; NbExp=3; IntAct=EBI-2432309, EBI-11337904;
CC Q92876; A0A0A0MR05: MLST8; NbExp=3; IntAct=EBI-2432309, EBI-25835557;
CC Q92876; Q9BRA0: NAA38; NbExp=3; IntAct=EBI-2432309, EBI-9106509;
CC Q92876; Q92886: NEUROG1; NbExp=3; IntAct=EBI-2432309, EBI-10279647;
CC Q92876; P48645: NMU; NbExp=3; IntAct=EBI-2432309, EBI-10210351;
CC Q92876; Q9Y239: NOD1; NbExp=3; IntAct=EBI-2432309, EBI-1051262;
CC Q92876; P06748: NPM1; NbExp=3; IntAct=EBI-2432309, EBI-78579;
CC Q92876; Q6P4D5-2: PABIR3; NbExp=3; IntAct=EBI-2432309, EBI-9091052;
CC Q92876; Q8WW12: PCNP; NbExp=3; IntAct=EBI-2432309, EBI-10972020;
CC Q92876; Q16549: PCSK7; NbExp=3; IntAct=EBI-2432309, EBI-8059854;
CC Q92876; Q13371: PDCL; NbExp=3; IntAct=EBI-2432309, EBI-5772890;
CC Q92876; Q9NZ53-2: PODXL2; NbExp=3; IntAct=EBI-2432309, EBI-25887738;
CC Q92876; Q9GZS1: POLR1E; NbExp=3; IntAct=EBI-2432309, EBI-359458;
CC Q92876; P19388: POLR2E; NbExp=3; IntAct=EBI-2432309, EBI-395189;
CC Q92876; Q6ZMI0-5: PPP1R21; NbExp=3; IntAct=EBI-2432309, EBI-25835994;
CC Q92876; Q96QH2: PRAM1; NbExp=3; IntAct=EBI-2432309, EBI-2860740;
CC Q92876; Q86UA1: PRPF39; NbExp=3; IntAct=EBI-2432309, EBI-2803203;
CC Q92876; P61289: PSME3; NbExp=3; IntAct=EBI-2432309, EBI-355546;
CC Q92876; P21246: PTN; NbExp=3; IntAct=EBI-2432309, EBI-473725;
CC Q92876; P53801: PTTG1IP; NbExp=3; IntAct=EBI-2432309, EBI-3906138;
CC Q92876; Q9NWB1-5: RBFOX1; NbExp=3; IntAct=EBI-2432309, EBI-12123390;
CC Q92876; Q9BWF3: RBM4; NbExp=3; IntAct=EBI-2432309, EBI-2856454;
CC Q92876; P52756: RBM5; NbExp=3; IntAct=EBI-2432309, EBI-714003;
CC Q92876; P47804-3: RGR; NbExp=3; IntAct=EBI-2432309, EBI-25834767;
CC Q92876; Q9H0X6: RNF208; NbExp=3; IntAct=EBI-2432309, EBI-751555;
CC Q92876; Q969K3: RNF34; NbExp=3; IntAct=EBI-2432309, EBI-2340642;
CC Q92876; Q9BY12-3: SCAPER; NbExp=3; IntAct=EBI-2432309, EBI-25837959;
CC Q92876; Q86SQ7-2: SDCCAG8; NbExp=3; IntAct=EBI-2432309, EBI-10696955;
CC Q92876; Q9NTN9-3: SEMA4G; NbExp=3; IntAct=EBI-2432309, EBI-9089805;
CC Q92876; Q8IUQ4-2: SIAH1; NbExp=3; IntAct=EBI-2432309, EBI-11522811;
CC Q92876; Q9H2B4-2: SLC26A1; NbExp=3; IntAct=EBI-2432309, EBI-12908340;
CC Q92876; Q99717: SMAD5; NbExp=3; IntAct=EBI-2432309, EBI-6391136;
CC Q92876; P37840: SNCA; NbExp=3; IntAct=EBI-2432309, EBI-985879;
CC Q92876; Q5T0L3: SPATA46; NbExp=3; IntAct=EBI-2432309, EBI-750105;
CC Q92876; Q496A3: SPATS1; NbExp=3; IntAct=EBI-2432309, EBI-3923692;
CC Q92876; Q9BUD6: SPON2; NbExp=3; IntAct=EBI-2432309, EBI-10298801;
CC Q92876; Q9C004: SPRY4; NbExp=3; IntAct=EBI-2432309, EBI-354861;
CC Q92876; Q99469: STAC; NbExp=3; IntAct=EBI-2432309, EBI-2652799;
CC Q92876; O75558: STX11; NbExp=3; IntAct=EBI-2432309, EBI-714135;
CC Q92876; Q9UMX1: SUFU; NbExp=3; IntAct=EBI-2432309, EBI-740595;
CC Q92876; O43463: SUV39H1; NbExp=3; IntAct=EBI-2432309, EBI-349968;
CC Q92876; O60506-4: SYNCRIP; NbExp=3; IntAct=EBI-2432309, EBI-11123832;
CC Q92876; Q8TDR4: TCP10L; NbExp=3; IntAct=EBI-2432309, EBI-3923210;
CC Q92876; Q96A09: TENT5B; NbExp=3; IntAct=EBI-2432309, EBI-752030;
CC Q92876; Q01664: TFAP4; NbExp=3; IntAct=EBI-2432309, EBI-2514218;
CC Q92876; Q6YHU6: THADA; NbExp=3; IntAct=EBI-2432309, EBI-2824523;
CC Q92876; Q9H808: TLE6; NbExp=3; IntAct=EBI-2432309, EBI-3921684;
CC Q92876; Q8IU80-2: TMPRSS6; NbExp=3; IntAct=EBI-2432309, EBI-25839648;
CC Q92876; Q8IUR5-4: TMTC1; NbExp=3; IntAct=EBI-2432309, EBI-9089156;
CC Q92876; Q8WVP5: TNFAIP8L1; NbExp=3; IntAct=EBI-2432309, EBI-752102;
CC Q92876; Q96KP6: TNIP3; NbExp=3; IntAct=EBI-2432309, EBI-2509913;
CC Q92876; O14787-2: TNPO2; NbExp=3; IntAct=EBI-2432309, EBI-12076664;
CC Q92876; O94900: TOX; NbExp=3; IntAct=EBI-2432309, EBI-9088321;
CC Q92876; P06753-2: TPM3; NbExp=3; IntAct=EBI-2432309, EBI-10977875;
CC Q92876; Q9NX07: TRNAU1AP; NbExp=3; IntAct=EBI-2432309, EBI-12581310;
CC Q92876; O60636: TSPAN2; NbExp=3; IntAct=EBI-2432309, EBI-3914288;
CC Q92876; Q86UF1: TSPAN33; NbExp=3; IntAct=EBI-2432309, EBI-12045841;
CC Q92876; Q5VYS8-5: TUT7; NbExp=3; IntAct=EBI-2432309, EBI-9088812;
CC Q92876; Q9GZX9: TWSG1; NbExp=3; IntAct=EBI-2432309, EBI-10304067;
CC Q92876; Q13404: UBE2V1; NbExp=3; IntAct=EBI-2432309, EBI-1050671;
CC Q92876; Q9H9P5-5: UNKL; NbExp=3; IntAct=EBI-2432309, EBI-12817837;
CC Q92876; Q9NVA1: UQCC1; NbExp=3; IntAct=EBI-2432309, EBI-11911675;
CC Q92876; P61964: WDR5; NbExp=3; IntAct=EBI-2432309, EBI-540834;
CC Q92876; Q9NZC7-5: WWOX; NbExp=3; IntAct=EBI-2432309, EBI-12040603;
CC Q92876; O00308: WWP2; NbExp=3; IntAct=EBI-2432309, EBI-743923;
CC Q92876; Q9HAV4: XPO5; NbExp=3; IntAct=EBI-2432309, EBI-517949;
CC Q92876; Q8N0Y2-2: ZNF444; NbExp=3; IntAct=EBI-2432309, EBI-12010736;
CC Q92876; Q7Z783; NbExp=3; IntAct=EBI-2432309, EBI-9088990;
CC Q92876; Q96EJ4; NbExp=3; IntAct=EBI-2432309, EBI-750454;
CC -!- SUBCELLULAR LOCATION: Secreted. Nucleus, nucleolus. Cytoplasm.
CC Mitochondrion. Microsome. Note=In brain, detected in the nucleus of
CC glial cells and in the nucleus and cytoplasm of neurons. Detected in
CC the mitochondrial and microsomal fractions of HEK-293 cells and
CC released into the cytoplasm following cell stress.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q92876-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q92876-2; Sequence=VSP_034403;
CC Name=3;
CC IsoId=Q92876-3; Sequence=VSP_034404, VSP_034405;
CC -!- TISSUE SPECIFICITY: In fluids, highest levels found in milk of
CC lactating women followed by cerebrospinal fluid, nipple aspirate fluid
CC and breast cyst fluid. Also found in serum, seminal plasma and some
CC amniotic fluids and breast tumor cytosolic extracts. Not detected in
CC urine. At the tissue level, highest concentrations found in glandular
CC tissues such as salivary glands followed by lung, colon, fallopian
CC tube, placenta, breast, pituitary and kidney. Not detected in skin,
CC spleen, bone, thyroid, heart, ureter, liver, muscle, endometrium,
CC testis, pancreas, seminal vesicle, ovary, adrenals and prostate. In
CC brain, detected in gray matter neurons (at protein level). Colocalizes
CC with pathological inclusions such as Lewy bodies and glial cytoplasmic
CC inclusions. Overexpressed in primary breast tumors but not expressed in
CC metastatic tumors. {ECO:0000269|PubMed:10997858,
CC ECO:0000269|PubMed:11018688, ECO:0000269|PubMed:11668196,
CC ECO:0000269|PubMed:12928483, ECO:0000269|PubMed:16800739}.
CC -!- INDUCTION: By spinal cord injury. This effect is particularly prominent
CC in macrophages, microglia and reactive astrocytes.
CC {ECO:0000269|PubMed:16987227}.
CC -!- PTM: Inactivated by autolytic cleavage after Arg-80.
CC -!- MASS SPECTROMETRY: Mass=25866; Method=MALDI;
CC Evidence={ECO:0000269|PubMed:11983703};
CC -!- SIMILARITY: Belongs to the peptidase S1 family. Kallikrein subfamily.
CC {ECO:0000255|PROSITE-ProRule:PRU00274}.
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DR EMBL; U62801; AAB07113.1; -; mRNA.
DR EMBL; D78203; BAA11306.1; -; mRNA.
DR EMBL; AF013988; AAB66483.1; -; mRNA.
DR EMBL; AF149289; AAD51475.1; -; Genomic_DNA.
DR EMBL; AF243527; AAG33359.1; -; Genomic_DNA.
DR EMBL; AY318867; AAP82446.1; -; mRNA.
DR EMBL; AY318868; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; AY318869; AAP82448.1; -; mRNA.
DR EMBL; AY318870; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; DQ223012; ABB04464.1; -; mRNA.
DR EMBL; AK314897; BAG37411.1; -; mRNA.
DR EMBL; BT006852; AAP35498.1; -; mRNA.
DR EMBL; AC011483; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471135; EAW71953.1; -; Genomic_DNA.
DR EMBL; CH471135; EAW71954.1; -; Genomic_DNA.
DR EMBL; BC015525; AAH15525.1; -; mRNA.
DR CCDS; CCDS12811.1; -. [Q92876-1]
DR CCDS; CCDS42599.1; -. [Q92876-2]
DR RefSeq; NP_001012982.1; NM_001012964.2. [Q92876-1]
DR RefSeq; NP_001012983.1; NM_001012965.2. [Q92876-2]
DR RefSeq; NP_001306877.1; NM_001319948.1. [Q92876-2]
DR RefSeq; NP_001306878.1; NM_001319949.1. [Q92876-2]
DR RefSeq; NP_002765.1; NM_002774.3. [Q92876-1]
DR PDB; 1GVL; X-ray; 1.80 A; A=21-243.
DR PDB; 1L2E; X-ray; 1.75 A; A=22-244.
DR PDB; 1LO6; X-ray; 1.56 A; A=22-244.
DR PDB; 3VFE; X-ray; 1.88 A; A=22-244.
DR PDB; 4D8N; X-ray; 1.68 A; A=22-244.
DR PDB; 5NX1; X-ray; 1.85 A; A=22-244.
DR PDB; 5NX3; X-ray; 2.30 A; A=22-244.
DR PDB; 6QFF; X-ray; 1.64 A; A/B=22-243.
DR PDB; 6QFG; X-ray; 1.68 A; A/B=22-244.
DR PDB; 6QFH; X-ray; 1.65 A; A/B=22-243.
DR PDB; 6QH9; X-ray; 2.27 A; A/B=22-244.
DR PDB; 6QHA; X-ray; 1.82 A; A/B=22-244.
DR PDB; 6QHB; X-ray; 1.84 A; A/B=22-244.
DR PDB; 6QHC; X-ray; 1.87 A; A/B=22-244.
DR PDB; 6SKB; X-ray; 1.84 A; A/B/C=12-244.
DR PDB; 6SKC; X-ray; 2.18 A; A/B=22-244.
DR PDB; 6SKD; X-ray; 2.26 A; A/B=22-244.
DR PDBsum; 1GVL; -.
DR PDBsum; 1L2E; -.
DR PDBsum; 1LO6; -.
DR PDBsum; 3VFE; -.
DR PDBsum; 4D8N; -.
DR PDBsum; 5NX1; -.
DR PDBsum; 5NX3; -.
DR PDBsum; 6QFF; -.
DR PDBsum; 6QFG; -.
DR PDBsum; 6QFH; -.
DR PDBsum; 6QH9; -.
DR PDBsum; 6QHA; -.
DR PDBsum; 6QHB; -.
DR PDBsum; 6QHC; -.
DR PDBsum; 6SKB; -.
DR PDBsum; 6SKC; -.
DR PDBsum; 6SKD; -.
DR AlphaFoldDB; Q92876; -.
DR SMR; Q92876; -.
DR BioGRID; 111634; 63.
DR IntAct; Q92876; 169.
DR MINT; Q92876; -.
DR STRING; 9606.ENSP00000366047; -.
DR BindingDB; Q92876; -.
DR ChEMBL; CHEMBL4448; -.
DR DrugBank; DB03127; Benzamidine.
DR GuidetoPHARMACOLOGY; 2376; -.
DR MEROPS; S01.236; -.
DR GlyConnect; 2937; 2 N-Linked glycans (1 site).
DR GlyGen; Q92876; 1 site, 17 N-linked glycans (1 site).
DR PhosphoSitePlus; Q92876; -.
DR BioMuta; KLK6; -.
DR DMDM; 3914480; -.
DR EPD; Q92876; -.
DR jPOST; Q92876; -.
DR MassIVE; Q92876; -.
DR MaxQB; Q92876; -.
DR PaxDb; Q92876; -.
DR PeptideAtlas; Q92876; -.
DR PRIDE; Q92876; -.
DR ProteomicsDB; 75559; -. [Q92876-1]
DR ProteomicsDB; 75560; -. [Q92876-2]
DR Antibodypedia; 32402; 361 antibodies from 34 providers.
DR DNASU; 5653; -.
DR Ensembl; ENST00000310157.7; ENSP00000309148.1; ENSG00000167755.15. [Q92876-1]
DR Ensembl; ENST00000376851.7; ENSP00000366047.2; ENSG00000167755.15. [Q92876-1]
DR Ensembl; ENST00000391808.5; ENSP00000375684.1; ENSG00000167755.15. [Q92876-2]
DR Ensembl; ENST00000594641.1; ENSP00000470482.1; ENSG00000167755.15. [Q92876-1]
DR Ensembl; ENST00000597379.5; ENSP00000469630.1; ENSG00000167755.15. [Q92876-3]
DR Ensembl; ENST00000599881.5; ENSP00000471948.1; ENSG00000167755.15. [Q92876-3]
DR GeneID; 5653; -.
DR KEGG; hsa:5653; -.
DR MANE-Select; ENST00000310157.7; ENSP00000309148.1; NM_002774.4; NP_002765.1.
DR UCSC; uc002pui.4; human. [Q92876-1]
DR CTD; 5653; -.
DR DisGeNET; 5653; -.
DR GeneCards; KLK6; -.
DR HGNC; HGNC:6367; KLK6.
DR HPA; ENSG00000167755; Tissue enhanced (brain, esophagus).
DR MIM; 602652; gene.
DR neXtProt; NX_Q92876; -.
DR OpenTargets; ENSG00000167755; -.
DR PharmGKB; PA30156; -.
DR VEuPathDB; HostDB:ENSG00000167755; -.
DR eggNOG; KOG3627; Eukaryota.
DR GeneTree; ENSGT01030000234551; -.
DR HOGENOM; CLU_006842_1_1_1; -.
DR InParanoid; Q92876; -.
DR OMA; DFPNTIQ; -.
DR PhylomeDB; Q92876; -.
DR TreeFam; TF331065; -.
DR BRENDA; 3.4.21.104; 2681.
DR BRENDA; 3.4.21.34; 2681.
DR BRENDA; 3.4.21.B10; 2681.
DR PathwayCommons; Q92876; -.
DR SABIO-RK; Q92876; -.
DR SignaLink; Q92876; -.
DR BioGRID-ORCS; 5653; 20 hits in 1081 CRISPR screens.
DR ChiTaRS; KLK6; human.
DR EvolutionaryTrace; Q92876; -.
DR GeneWiki; KLK6; -.
DR GenomeRNAi; 5653; -.
DR Pharos; Q92876; Tchem.
DR PRO; PR:Q92876; -.
DR Proteomes; UP000005640; Chromosome 19.
DR RNAct; Q92876; protein.
DR Bgee; ENSG00000167755; Expressed in C1 segment of cervical spinal cord and 144 other tissues.
DR ExpressionAtlas; Q92876; baseline and differential.
DR Genevisible; Q92876; HS.
DR GO; GO:0001533; C:cornified envelope; IEA:Ensembl.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005783; C:endoplasmic reticulum; IEA:UniProtKB-KW.
DR GO; GO:0005576; C:extracellular region; IDA:UniProtKB.
DR GO; GO:0005615; C:extracellular space; HDA:UniProtKB.
DR GO; GO:0005739; C:mitochondrion; IEA:UniProtKB-SubCell.
DR GO; GO:0005730; C:nucleolus; IEA:UniProtKB-SubCell.
DR GO; GO:0030141; C:secretory granule; IBA:GO_Central.
DR GO; GO:0004252; F:serine-type endopeptidase activity; IDA:UniProtKB.
DR GO; GO:0042982; P:amyloid precursor protein metabolic process; NAS:UniProtKB.
DR GO; GO:0007417; P:central nervous system development; NAS:UniProtKB.
DR GO; GO:0030574; P:collagen catabolic process; NAS:UniProtKB.
DR GO; GO:0042445; P:hormone metabolic process; NAS:UniProtKB.
DR GO; GO:0042552; P:myelination; NAS:UniProtKB.
DR GO; GO:0045745; P:positive regulation of G protein-coupled receptor signaling pathway; IDA:UniProtKB.
DR GO; GO:0016540; P:protein autoprocessing; NAS:UniProtKB.
DR GO; GO:0045595; P:regulation of cell differentiation; NAS:UniProtKB.
DR GO; GO:0010975; P:regulation of neuron projection development; IEA:Ensembl.
DR GO; GO:0009611; P:response to wounding; NAS:UniProtKB.
DR GO; GO:0042246; P:tissue regeneration; NAS:UniProtKB.
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; Alternative splicing; Autocatalytic cleavage;
KW Cleavage on pair of basic residues; Cytoplasm; Direct protein sequencing;
KW Disulfide bond; Endoplasmic reticulum; Glycoprotein; Hydrolase; Microsome;
KW Mitochondrion; Nucleus; Protease; Reference proteome; Secreted;
KW Serine protease; Signal; Zymogen.
FT SIGNAL 1..16
FT /evidence="ECO:0000255"
FT PROPEP 17..21
FT /note="Activation peptide"
FT /evidence="ECO:0000255"
FT /id="PRO_0000027940"
FT CHAIN 22..244
FT /note="Kallikrein-6"
FT /id="PRO_0000027941"
FT DOMAIN 22..242
FT /note="Peptidase S1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT ACT_SITE 62
FT /note="Charge relay system"
FT /evidence="ECO:0000269|PubMed:12016211"
FT ACT_SITE 106
FT /note="Charge relay system"
FT /evidence="ECO:0000269|PubMed:12016211"
FT ACT_SITE 197
FT /note="Charge relay system"
FT /evidence="ECO:0000269|PubMed:12016211"
FT SITE 80..81
FT /note="Cleavage; by autolysis"
FT CARBOHYD 134
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 28..157
FT DISULFID 47..63
FT DISULFID 131..231
FT DISULFID 138..203
FT DISULFID 168..182
FT DISULFID 193..218
FT VAR_SEQ 1..107
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15207701"
FT /id="VSP_034403"
FT VAR_SEQ 14..40
FT /note="AWAEEQNKLVHGGPCDKTSHPYQAALY -> GIFRSSWGSITFGKGRVPRSR
FT VLLSGL (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15207701"
FT /id="VSP_034404"
FT VAR_SEQ 41..244
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15207701"
FT /id="VSP_034405"
FT VARIANT 78
FT /note="R -> W (in dbSNP:rs61469141)"
FT /id="VAR_061776"
FT HELIX 27..29
FT /evidence="ECO:0007829|PDB:1GVL"
FT STRAND 36..41
FT /evidence="ECO:0007829|PDB:1LO6"
FT STRAND 44..53
FT /evidence="ECO:0007829|PDB:1LO6"
FT STRAND 56..59
FT /evidence="ECO:0007829|PDB:1LO6"
FT HELIX 61..63
FT /evidence="ECO:0007829|PDB:1LO6"
FT STRAND 69..73
FT /evidence="ECO:0007829|PDB:1LO6"
FT STRAND 75..77
FT /evidence="ECO:0007829|PDB:1GVL"
FT STRAND 85..94
FT /evidence="ECO:0007829|PDB:1LO6"
FT TURN 100..102
FT /evidence="ECO:0007829|PDB:1LO6"
FT STRAND 108..114
FT /evidence="ECO:0007829|PDB:1LO6"
FT STRAND 120..122
FT /evidence="ECO:0007829|PDB:6SKD"
FT STRAND 137..144
FT /evidence="ECO:0007829|PDB:1LO6"
FT STRAND 146..149
FT /evidence="ECO:0007829|PDB:1GVL"
FT STRAND 156..163
FT /evidence="ECO:0007829|PDB:1LO6"
FT HELIX 165..171
FT /evidence="ECO:0007829|PDB:1LO6"
FT TURN 173..175
FT /evidence="ECO:0007829|PDB:1LO6"
FT STRAND 180..184
FT /evidence="ECO:0007829|PDB:1LO6"
FT TURN 186..188
FT /evidence="ECO:0007829|PDB:1LO6"
FT TURN 194..198
FT /evidence="ECO:0007829|PDB:1LO6"
FT STRAND 200..203
FT /evidence="ECO:0007829|PDB:1LO6"
FT STRAND 206..213
FT /evidence="ECO:0007829|PDB:1LO6"
FT STRAND 216..218
FT /evidence="ECO:0007829|PDB:6QFF"
FT STRAND 221..223
FT /evidence="ECO:0007829|PDB:1LO6"
FT STRAND 225..229
FT /evidence="ECO:0007829|PDB:1LO6"
FT HELIX 230..233
FT /evidence="ECO:0007829|PDB:1LO6"
FT HELIX 234..241
FT /evidence="ECO:0007829|PDB:1LO6"
SQ SEQUENCE 244 AA; 26856 MW; AEA03F9145D87AAB CRC64;
MKKLMVVLSL IAAAWAEEQN KLVHGGPCDK TSHPYQAALY TSGHLLCGGV LIHPLWVLTA
AHCKKPNLQV FLGKHNLRQR ESSQEQSSVV RAVIHPDYDA ASHDQDIMLL RLARPAKLSE
LIQPLPLERD CSANTTSCHI LGWGKTADGD FPDTIQCAYI HLVSREECEH AYPGQITQNM
LCAGDEKYGK DSCQGDSGGP LVCGDHLRGL VSWGNIPCGS KEKPGVYTNV CRYTNWIQKT
IQAK
