ID KLK8_HUMAN Reviewed; 260 AA. AC O60259; Q5V9X1; Q5V9X2; Q8IW69; Q9HCB3; Q9NR68; Q9NR69; Q9UIL9; Q9UQ47; DT 15-JUL-1999, integrated into UniProtKB/Swiss-Prot. DT 01-AUG-1998, sequence version 1. DT 27-MAR-2024, entry version 196. DE RecName: Full=Kallikrein-8; DE Short=hK8; DE EC=3.4.21.118; DE AltName: Full=Neuropsin; DE Short=NP; DE AltName: Full=Ovasin; DE AltName: Full=Serine protease 19; DE AltName: Full=Serine protease TADG-14; DE AltName: Full=Tumor-associated differentially expressed gene 14 protein; DE Flags: Precursor; GN Name=KLK8; Synonyms=NRPN, PRSS19, TADG14; ORFNames=UNQ283/PRO322; 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 [GENOMIC DNA / MRNA] (ISOFORM 1). RC TISSUE=Hippocampus; RX PubMed=9714609; DOI=10.1016/s0378-1119(98)00232-7; RA Yoshida S., Taniguchi M., Hirata A., Shiosaka S.; RT "Sequence analysis and expression of human neuropsin cDNA and gene."; RL Gene 213:9-16(1998). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RC TISSUE=Ovary; RX PubMed=10485494; RA Underwood L.J., Tanimoto H., Wang Y., Shigemasa K., Parmley T.H., RA O'Brien T.J.; RT "Cloning of tumor-associated differentially expressed gene-14, a novel RT serine protease overexpressed by ovarian carcinoma."; RL Cancer Res. 59:4435-4439(1999). RN [3] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORMS 1 AND 2). RC TISSUE=Brain; RX PubMed=10102990; DOI=10.1046/j.1432-1327.1999.00213.x; RA Mitsui S., Tsuruoka N., Yamashiro K., Nakazato H., Yamaguchi N.; RT "A novel form of human neuropsin, a brain-related serine protease, is RT generated by alternative splicing and is expressed preferentially in human RT adult brain."; RL Eur. J. Biochem. 260:627-634(1999). RN [4] 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 [5] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORMS 3 AND 4), AND TISSUE RP SPECIFICITY. RX PubMed=11309326; RA Magklara A., Scorilas A., Katsaros D., Massobrio M., Yousef G.M., RA Fracchioli S., Danese S., Diamandis E.P.; RT "The human KLK8 (neuropsin/ovasin) gene: identification of two novel splice RT variants and its prognostic value in ovarian cancer."; RL Clin. Cancer Res. 7:806-811(2001). RN [6] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 1). RA Gan L., Gelinas R., Gown A.M., Moss P., Smith R., Wang K.; RT "Molecular cloning and characterization of a novel serine protease, ovasin, RT a potential molecular marker for ovarian carcinomas."; RL Submitted (SEP-1998) to the EMBL/GenBank/DDBJ databases. RN [7] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3). RA Michael I.P., Diamandis E.P.; RT "Human kallikrein 8 and human kallikrein 9 are organized as a bicistronic RT operon."; RL Submitted (OCT-2005) to the EMBL/GenBank/DDBJ databases. RN [8] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). 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 [9] 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 [10] 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 [11] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Brain; 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 [12] RP PARTIAL NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORMS 1 AND 2). RX PubMed=15282331; DOI=10.1093/molbev/msh220; RA Li Y., Qian Y.-P., Yu X.-J., Wang Y.-Q., Dong D.-G., Sun W., Ma R.-M., RA Su B.; RT "Recent origin of a hominoid-specific splice form of neuropsin, a gene RT involved in learning and memory."; RL Mol. Biol. Evol. 21:2111-2115(2004). RN [13] RP TISSUE SPECIFICITY. RX PubMed=11522960; DOI=10.1097/00001756-200108280-00031; RA Shimizu-Okabe C., Yousef G.M., Diamandis E.P., Yoshida S., Shiosaka S., RA Fahnestock M.; RT "Expression of the kallikrein gene family in normal and Alzheimer's disease RT brain."; RL NeuroReport 12:2747-2751(2001). RN [14] RP TISSUE SPECIFICITY. RX PubMed=12147714; DOI=10.1136/mp.55.4.235; RA Kuwae K., Matsumoto-Miyai K., Yoshida S., Sadayama T., Yoshikawa K., RA Hosokawa K., Shiosaka S.; RT "Epidermal expression of serine protease, neuropsin (KLK8) in normal and RT pathological skin samples."; RL Mol. Pathol. 55:235-241(2002). RN [15] RP USE AS A MARKER FOR OVARIAN CANCER. RX PubMed=12782581; RA Kishi T., Grass L., Soosaipillai A., Scorilas A., Harbeck N., RA Schmalfeldt B., Dorn J., Mysliwiec M., Schmitt M., Diamandis E.P.; RT "Human kallikrein 8, a novel biomarker for ovarian carcinoma."; RL Cancer Res. 63:2771-2774(2003). RN [16] RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, AND BIOPHYSICOCHEMICAL RP PROPERTIES. RX PubMed=16337200; DOI=10.1016/j.febslet.2005.11.039; RA Rajapakse S., Ogiwara K., Takano N., Moriyama A., Takahashi T.; RT "Biochemical characterization of human kallikrein 8 and its possible RT involvement in the degradation of extracellular matrix proteins."; RL FEBS Lett. 579:6879-6884(2005). RN [17] RP ALTERNATIVE SPLICING (ISOFORM 2). RX PubMed=17487847; DOI=10.1002/humu.20547; RA Lu Z.-X., Peng J., Su B.; RT "A human-specific mutation leads to the origin of a novel splice form of RT neuropsin (KLK8), a gene involved in learning and memory."; RL Hum. Mutat. 28:978-984(2007). RN [18] RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY. RX PubMed=17761692; DOI=10.1093/jb/mvm156; RA Scott F.L., Sun J., Whisstock J.C., Kato K., Bird P.I.; RT "SerpinB6 is an inhibitor of kallikrein-8 in keratinocytes."; RL J. Biochem. 142:435-442(2007). RN [19] 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). CC -!- FUNCTION: Serine protease which is capable of degrading a number of CC proteins such as casein, fibrinogen, kininogen, fibronectin and CC collagen type IV. Also cleaves L1CAM in response to increased neural CC activity. Induces neurite outgrowth and fasciculation of cultured CC hippocampal neurons. Plays a role in the formation and maturation of CC orphan and small synaptic boutons in the Schaffer-collateral pathway, CC regulates Schaffer-collateral long-term potentiation in the hippocampus CC and is required for memory acquisition and synaptic plasticity. CC Involved in skin desquamation and keratinocyte proliferation. Plays a CC role in the secondary phase of pathogenesis following spinal cord CC injury. {ECO:0000269|PubMed:16337200}. CC -!- CATALYTIC ACTIVITY: CC Reaction=Cleavage of amide substrates following the basic amino acids CC Arg or Lys at the P1 position, with a preference for Arg over Lys.; CC EC=3.4.21.118; Evidence={ECO:0000269|PubMed:16337200}; CC -!- ACTIVITY REGULATION: Inhibited by a range of serine protease inhibitors CC including antipain, aprotinin, leupeptin, benzamidine and soybean CC trypsin inhibitor. {ECO:0000269|PubMed:16337200}. CC -!- BIOPHYSICOCHEMICAL PROPERTIES: CC Kinetic parameters: CC KM=0.07 mM for Pro-Phe-Arg-MCA {ECO:0000269|PubMed:16337200}; CC KM=0.07 mM for Z-Val-Val-Arg-MCA {ECO:0000269|PubMed:16337200}; CC KM=0.07 mM for Boc-Val-Pro-Arg-MCA {ECO:0000269|PubMed:16337200}; CC KM=0.1 mM for Boc-Leu-Lys-Arg-MCA {ECO:0000269|PubMed:16337200}; CC KM=0.1 mM for Boc-Val-Leu-Lys-MCA {ECO:0000269|PubMed:16337200}; CC KM=0.07 mM for Boc-Phe-Ser-Arg-MCA {ECO:0000269|PubMed:16337200}; CC Vmax=7.1 umol/min/mg enzyme toward Pro-Phe-Arg-MCA CC {ECO:0000269|PubMed:16337200}; CC Vmax=5.4 umol/min/mg enzyme toward Z-Val-Val-Arg-MCA CC {ECO:0000269|PubMed:16337200}; CC Vmax=3.9 umol/min/mg enzyme toward Boc-Val-Pro-Arg-MCA CC {ECO:0000269|PubMed:16337200}; CC Vmax=2.6 umol/min/mg enzyme toward Boc-Leu-Lys-Arg-MCA CC {ECO:0000269|PubMed:16337200}; CC Vmax=1.9 umol/min/mg enzyme toward Boc-Val-Leu-Lys-MCA CC {ECO:0000269|PubMed:16337200}; CC Vmax=1.6 umol/min/mg enzyme toward Boc-Phe-Ser-Arg-MCA CC {ECO:0000269|PubMed:16337200}; CC pH dependence: CC Optimum pH is 8.5. Active from pH 7-10. CC {ECO:0000269|PubMed:16337200}; CC -!- SUBUNIT: Interacts with SPINK9. {ECO:0000269|PubMed:19194479}. CC -!- INTERACTION: CC O60259; A8MQ03: CYSRT1; NbExp=3; IntAct=EBI-3915857, EBI-3867333; CC O60259; P42858: HTT; NbExp=3; IntAct=EBI-3915857, EBI-466029; CC O60259; Q92876: KLK6; NbExp=3; IntAct=EBI-3915857, EBI-2432309; CC O60259; Q15323: KRT31; NbExp=3; IntAct=EBI-3915857, EBI-948001; CC O60259; O76011: KRT34; NbExp=3; IntAct=EBI-3915857, EBI-1047093; CC O60259; Q07627: KRTAP1-1; NbExp=3; IntAct=EBI-3915857, EBI-11959885; CC O60259; P60410: KRTAP10-8; NbExp=3; IntAct=EBI-3915857, EBI-10171774; CC O60259; P26371: KRTAP5-9; NbExp=3; IntAct=EBI-3915857, EBI-3958099; CC O60259; Q7Z3S9: NOTCH2NLA; NbExp=3; IntAct=EBI-3915857, EBI-945833; CC O60259; P0DPK4: NOTCH2NLC; NbExp=3; IntAct=EBI-3915857, EBI-22310682; CC O60259; P50454: SERPINH1; NbExp=3; IntAct=EBI-3915857, EBI-350723; CC O60259; P37173: TGFBR2; NbExp=3; IntAct=EBI-3915857, EBI-296151; CC O60259; Q8IUH5: ZDHHC17; NbExp=3; IntAct=EBI-3915857, EBI-524753; CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:17761692}. Cytoplasm CC {ECO:0000269|PubMed:17761692}. Note=Shows a cytoplasmic distribution in CC the keratinocytes. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=4; CC Name=1; CC IsoId=O60259-1; Sequence=Displayed; CC Name=2; CC IsoId=O60259-2; Sequence=VSP_005401; CC Name=3; CC IsoId=O60259-3; Sequence=VSP_030350; CC Name=4; CC IsoId=O60259-4; Sequence=VSP_030351, VSP_030352; CC -!- TISSUE SPECIFICITY: Isoform 1 is predominantly expressed in the CC pancreas. Isoform 2 is expressed in adult brain and hippocampus. CC Isoform 1 and isoform 2 are found in fetal brain and placenta. Detected CC in salivary gland, uterus, thymus, breast, testis and kidney but not in CC spleen, liver, lung or normal ovarian tissue. Displays an 11.5-fold CC increase in Alzheimer disease hippocampus compared to controls and is CC overexpressed in some ovarian carcinomas. Expressed at low levels in CC normal skin while high levels are found in psoriasis vulgaris, CC seborrheic keratosis, lichen planus and squamous cell carcinoma skin CC samples. Expressed in the keratinocytes. {ECO:0000269|PubMed:11309326, CC ECO:0000269|PubMed:11522960, ECO:0000269|PubMed:12147714, CC ECO:0000269|PubMed:17761692}. CC -!- MISCELLANEOUS: Expressed at high levels in serum, ascites fluid and CC tumor cytosol of advanced stage ovarian cancer patients and may serve CC as a marker of ovarian cancer. CC -!- MISCELLANEOUS: [Isoform 2]: Produced as a result of a human-specific CC mutation which is not found in other primates. {ECO:0000305}. CC -!- SIMILARITY: Belongs to the peptidase S1 family. Kallikrein subfamily. CC {ECO:0000255|PROSITE-ProRule:PRU00274}. CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and CC Haematology; CC URL="https://atlasgeneticsoncology.org/gene/41088/KLK8"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AB009849; BAA28673.1; -; mRNA. DR EMBL; AB012761; BAA28676.1; -; Genomic_DNA. DR EMBL; AF055982; AAD56050.1; -; mRNA. DR EMBL; AB008390; BAA82665.1; -; mRNA. DR EMBL; AB008927; BAA82666.1; -; mRNA. DR EMBL; AB010780; BAA88684.1; -; Genomic_DNA. DR EMBL; AF243527; AAG33361.1; -; Genomic_DNA. DR EMBL; AF251125; AAF79144.1; -; Genomic_DNA. DR EMBL; AF251125; AAF79145.1; -; Genomic_DNA. DR EMBL; AF095742; AAD25979.1; -; mRNA. DR EMBL; AF095743; AAD29574.1; -; Genomic_DNA. DR EMBL; DQ267420; ABB83339.1; -; mRNA. DR EMBL; AY359036; AAQ89395.1; -; mRNA. DR EMBL; AC011473; AAG23254.1; -; Genomic_DNA. DR EMBL; AC011483; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471135; EAW71962.1; -; Genomic_DNA. DR EMBL; BC040887; AAH40887.1; -; mRNA. DR EMBL; AY563055; AAT76913.1; -; Genomic_DNA. DR EMBL; AY563055; AAT76914.1; -; Genomic_DNA. DR EMBL; AY563056; AAT76915.1; -; Genomic_DNA. DR EMBL; AY563056; AAT76916.1; -; Genomic_DNA. DR EMBL; AY563057; AAT76917.1; -; Genomic_DNA. DR EMBL; AY563057; AAT76918.1; -; Genomic_DNA. DR EMBL; AY563058; AAT76919.1; -; Genomic_DNA. DR EMBL; AY563058; AAT76920.1; -; Genomic_DNA. DR EMBL; AY563059; AAT76921.1; -; Genomic_DNA. DR EMBL; AY563059; AAT76922.1; -; Genomic_DNA. DR EMBL; AY563060; AAT76923.1; -; Genomic_DNA. DR EMBL; AY563060; AAT76924.1; -; Genomic_DNA. DR EMBL; AY563061; AAT76925.1; -; Genomic_DNA. DR EMBL; AY563061; AAT76926.1; -; Genomic_DNA. DR EMBL; AY563062; AAT76927.1; -; Genomic_DNA. DR EMBL; AY563062; AAT76928.1; -; Genomic_DNA. DR EMBL; AY563063; AAT76929.1; -; Genomic_DNA. DR EMBL; AY563063; AAT76930.1; -; Genomic_DNA. DR EMBL; AY563064; AAT76931.1; -; Genomic_DNA. DR EMBL; AY563064; AAT76932.1; -; Genomic_DNA. DR EMBL; AY563065; AAT76933.1; -; Genomic_DNA. DR EMBL; AY563065; AAT76934.1; -; Genomic_DNA. DR EMBL; AY563066; AAT76935.1; -; Genomic_DNA. DR EMBL; AY563066; AAT76936.1; -; Genomic_DNA. DR EMBL; AY563067; AAT76937.1; -; Genomic_DNA. DR EMBL; AY563067; AAT76938.1; -; Genomic_DNA. DR CCDS; CCDS12813.1; -. [O60259-1] DR CCDS; CCDS12814.1; -. [O60259-3] DR CCDS; CCDS12815.1; -. [O60259-4] DR CCDS; CCDS42600.1; -. [O60259-2] DR RefSeq; NP_001268360.1; NM_001281431.1. DR RefSeq; NP_009127.1; NM_007196.3. [O60259-1] DR RefSeq; NP_653088.1; NM_144505.2. [O60259-2] DR RefSeq; NP_653089.1; NM_144506.2. [O60259-3] DR RefSeq; NP_653090.1; NM_144507.2. [O60259-4] DR PDB; 5MS3; X-ray; 2.30 A; A=33-260. DR PDB; 5MS4; X-ray; 2.10 A; A/B/C/D=33-260. DR PDBsum; 5MS3; -. DR PDBsum; 5MS4; -. DR AlphaFoldDB; O60259; -. DR SMR; O60259; -. DR BioGRID; 116371; 44. DR IntAct; O60259; 20. DR STRING; 9606.ENSP00000375682; -. DR BindingDB; O60259; -. DR ChEMBL; CHEMBL4812; -. DR GuidetoPHARMACOLOGY; 2378; -. DR MEROPS; S01.244; -. DR GlyCosmos; O60259; 1 site, No reported glycans. DR GlyGen; O60259; 2 sites, 1 O-linked glycan (1 site). DR PhosphoSitePlus; O60259; -. DR BioMuta; KLK8; -. DR EPD; O60259; -. DR MassIVE; O60259; -. DR PeptideAtlas; O60259; -. DR ProteomicsDB; 49286; -. [O60259-1] DR ProteomicsDB; 49287; -. [O60259-2] DR ProteomicsDB; 49288; -. [O60259-3] DR Pumba; O60259; -. DR Antibodypedia; 32417; 1500 antibodies from 32 providers. DR DNASU; 11202; -. DR Ensembl; ENST00000320838.9; ENSP00000325072.5; ENSG00000129455.16. [O60259-4] DR Ensembl; ENST00000347619.8; ENSP00000341555.3; ENSG00000129455.16. [O60259-3] DR Ensembl; ENST00000391806.6; ENSP00000375682.1; ENSG00000129455.16. [O60259-2] DR Ensembl; ENST00000593490.1; ENSP00000469278.1; ENSG00000129455.16. [O60259-4] DR Ensembl; ENST00000600767.5; ENSP00000472016.1; ENSG00000129455.16. [O60259-1] DR Ensembl; ENST00000695909.1; ENSP00000512260.1; ENSG00000129455.16. [O60259-1] DR GeneID; 11202; -. DR KEGG; hsa:11202; -. DR MANE-Select; ENST00000695909.1; ENSP00000512260.1; NM_007196.4; NP_009127.1. DR UCSC; uc002puq.2; human. [O60259-1] DR AGR; HGNC:6369; -. DR CTD; 11202; -. DR DisGeNET; 11202; -. DR GeneCards; KLK8; -. DR HGNC; HGNC:6369; KLK8. DR HPA; ENSG00000129455; Tissue enhanced (esophagus, skin, vagina). DR MIM; 605644; gene. DR neXtProt; NX_O60259; -. DR OpenTargets; ENSG00000129455; -. DR PharmGKB; PA30158; -. DR VEuPathDB; HostDB:ENSG00000129455; -. DR GeneTree; ENSGT01020000230389; -. DR HOGENOM; CLU_006842_1_1_1; -. DR InParanoid; O60259; -. DR OMA; GMTCYSG; -. DR OrthoDB; 4629979at2759; -. DR PhylomeDB; O60259; -. DR TreeFam; TF331065; -. DR BRENDA; 3.4.21.118; 2681. DR PathwayCommons; O60259; -. DR Reactome; R-HSA-6809371; Formation of the cornified envelope. DR SignaLink; O60259; -. DR BioGRID-ORCS; 11202; 10 hits in 1144 CRISPR screens. DR GeneWiki; KLK8; -. DR GenomeRNAi; 11202; -. DR Pharos; O60259; Tchem. DR PRO; PR:O60259; -. DR Proteomes; UP000005640; Chromosome 19. DR RNAct; O60259; Protein. DR Bgee; ENSG00000129455; Expressed in lower esophagus mucosa and 104 other cell types or tissues. DR ExpressionAtlas; O60259; baseline and differential. DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB. DR GO; GO:0005576; C:extracellular region; TAS:Reactome. DR GO; GO:0005615; C:extracellular space; ISS:UniProtKB. DR GO; GO:0030141; C:secretory granule; IBA:GO_Central. DR GO; GO:0097180; C:serine protease inhibitor complex; IDA:BHF-UCL. DR GO; GO:0004252; F:serine-type endopeptidase activity; IDA:UniProtKB. DR GO; GO:0043616; P:keratinocyte proliferation; ISS:UniProtKB. DR GO; GO:0007613; P:memory; ISS:UniProtKB. DR GO; GO:0048812; P:neuron projection morphogenesis; ISS:UniProtKB. DR GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW. DR GO; GO:0050807; P:regulation of synapse organization; ISS:UniProtKB. DR GO; GO:0009611; P:response to wounding; ISS:UniProtKB. DR GO; GO:0050808; P:synapse organization; IEA:Ensembl. DR CDD; cd00190; Tryp_SPc; 1. DR Gene3D; 2.40.10.10; Trypsin-like serine proteases; 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 PANTHER; PTHR24271:SF62; KALLIKREIN-8; 1. DR PANTHER; PTHR24271; KALLIKREIN-RELATED; 1. DR Pfam; PF00089; Trypsin; 1. DR PRINTS; PR00722; CHYMOTRYPSIN. DR SMART; SM00020; Tryp_SPc; 1. DR SUPFAM; SSF50494; Trypsin-like serine proteases; 1. DR PROSITE; PS50240; TRYPSIN_DOM; 1. DR PROSITE; PS00134; TRYPSIN_HIS; 1. DR PROSITE; PS00135; TRYPSIN_SER; 1. DR Genevisible; O60259; HS. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Cytoplasm; Disulfide bond; KW Glycoprotein; Hydrolase; Protease; Reference proteome; Secreted; KW Serine protease; Signal; Zymogen. FT SIGNAL 1..28 FT /evidence="ECO:0000255" FT PROPEP 29..32 FT /evidence="ECO:0000250" FT /id="PRO_0000027946" FT CHAIN 33..260 FT /note="Kallikrein-8" FT /id="PRO_0000027947" FT DOMAIN 33..257 FT /note="Peptidase S1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274" FT ACT_SITE 73 FT /note="Charge relay system" FT /evidence="ECO:0000250" FT ACT_SITE 120 FT /note="Charge relay system" FT /evidence="ECO:0000250" FT ACT_SITE 212 FT /note="Charge relay system" FT /evidence="ECO:0000250" FT CARBOHYD 110 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT DISULFID 39..173 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274" FT DISULFID 58..74 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274" FT DISULFID 145..246 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274" FT DISULFID 152..218 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274" FT DISULFID 184..198 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274" FT DISULFID 208..233 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274" FT VAR_SEQ 23 FT /note="A -> AACGSLDLLTKLYAENLPCVHLNPQWPSQPSHCPRGWRSNPLPPAA FT (in isoform 2)" FT /evidence="ECO:0000303|PubMed:10102990" FT /id="VSP_005401" FT VAR_SEQ 24..164 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000303|Ref.7" FT /id="VSP_030350" FT VAR_SEQ 25..32 FT /note="HSRAQEDK -> RFWRPPGV (in isoform 4)" FT /evidence="ECO:0000305" FT /id="VSP_030351" FT VAR_SEQ 33..260 FT /note="Missing (in isoform 4)" FT /evidence="ECO:0000305" FT /id="VSP_030352" FT VARIANT 154 FT /note="V -> I (in dbSNP:rs16988799)" FT /id="VAR_051855" FT CONFLICT 195 FT /note="G -> V (in Ref. 11; AAH40887)" FT /evidence="ECO:0000305" FT STRAND 47..54 FT /evidence="ECO:0007829|PDB:5MS4" FT STRAND 56..64 FT /evidence="ECO:0007829|PDB:5MS4" FT STRAND 67..70 FT /evidence="ECO:0007829|PDB:5MS4" FT HELIX 72..74 FT /evidence="ECO:0007829|PDB:5MS4" FT STRAND 80..84 FT /evidence="ECO:0007829|PDB:5MS4" FT STRAND 86..90 FT /evidence="ECO:0007829|PDB:5MS4" FT STRAND 96..105 FT /evidence="ECO:0007829|PDB:5MS4" FT STRAND 111..113 FT /evidence="ECO:0007829|PDB:5MS3" FT STRAND 122..128 FT /evidence="ECO:0007829|PDB:5MS4" FT STRAND 133..136 FT /evidence="ECO:0007829|PDB:5MS4" FT STRAND 151..158 FT /evidence="ECO:0007829|PDB:5MS4" FT STRAND 160..164 FT /evidence="ECO:0007829|PDB:5MS4" FT STRAND 172..178 FT /evidence="ECO:0007829|PDB:5MS4" FT HELIX 181..187 FT /evidence="ECO:0007829|PDB:5MS4" FT TURN 189..191 FT /evidence="ECO:0007829|PDB:5MS4" FT STRAND 196..200 FT /evidence="ECO:0007829|PDB:5MS4" FT STRAND 215..228 FT /evidence="ECO:0007829|PDB:5MS4" FT STRAND 231..234 FT /evidence="ECO:0007829|PDB:5MS3" FT STRAND 236..238 FT /evidence="ECO:0007829|PDB:5MS4" FT STRAND 240..244 FT /evidence="ECO:0007829|PDB:5MS4" FT HELIX 245..247 FT /evidence="ECO:0007829|PDB:5MS4" FT HELIX 249..257 FT /evidence="ECO:0007829|PDB:5MS4" SQ SEQUENCE 260 AA; 28048 MW; EF439E5B8C83E660 CRC64; MGRPRPRAAK TWMFLLLLGG AWAGHSRAQE DKVLGGHECQ PHSQPWQAAL FQGQQLLCGG VLVGGNWVLT AAHCKKPKYT VRLGDHSLQN KDGPEQEIPV VQSIPHPCYN SSDVEDHNHD LMLLQLRDQA SLGSKVKPIS LADHCTQPGQ KCTVSGWGTV TSPRENFPDT LNCAEVKIFP QKKCEDAYPG QITDGMVCAG SSKGADTCQG DSGGPLVCDG ALQGITSWGS DPCGRSDKPG VYTNICRYLD WIKKIIGSKG //