| IED ID | IndEnz0002006644 |
| Enzyme Type ID | protease006644 |
| Protein Name |
Kallikrein-6 EC 3.4.21.- Neurosin Protease M SP59 Serine protease 18 Serine protease 9 Zyme |
| Gene Name | KLK6 PRSS18 PRSS9 |
| Organism | Homo sapiens (Human) |
| Taxonomic Lineage | cellular organisms Eukaryota Opisthokonta Metazoa Eumetazoa Bilateria Deuterostomia Chordata Craniata Vertebrata Gnathostomata (jawed vertebrates) Teleostomi Euteleostomi Sarcopterygii Dipnotetrapodomorpha Tetrapoda Amniota Mammalia Theria Eutheria Boreoeutheria Euarchontoglires Primates Haplorrhini Simiiformes Catarrhini Hominoidea (apes) Hominidae (great apes) Homininae Homo Homo sapiens (Human) |
| Enzyme Sequence | MKKLMVVLSLIAAAWAEEQNKLVHGGPCDKTSHPYQAALYTSGHLLCGGVLIHPLWVLTAAHCKKPNLQVFLGKHNLRQRESSQEQSSVVRAVIHPDYDAASHDQDIMLLRLARPAKLSELIQPLPLERDCSANTTSCHILGWGKTADGDFPDTIQCAYIHLVSREECEHAYPGQITQNMLCAGDEKYGKDSCQGDSGGPLVCGDHLRGLVSWGNIPCGSKEKPGVYTNVCRYTNWIQKTIQAK |
| Enzyme Length | 244 |
| Uniprot Accession Number | Q92876 |
| Absorption | |
| Active Site | ACT_SITE 62; /note=Charge relay system; /evidence=ECO:0000269|PubMed:12016211; ACT_SITE 106; /note=Charge relay system; /evidence=ECO:0000269|PubMed:12016211; ACT_SITE 197; /note=Charge relay system; /evidence=ECO:0000269|PubMed:12016211 |
| Activity Regulation | ACTIVITY REGULATION: Inhibited by a range of serine protease inhibitors including soybean trypsin inhibitor, benzamidine and serpins. Activated by a range of glycosaminoglycans including chondroitin sulfate, dermatan sulfate, heparan sulfate and heparin. {ECO:0000269|PubMed:12878203, ECO:0000269|PubMed:16321973}. |
| Binding Site | |
| Calcium Binding | |
| catalytic Activity | |
| DNA Binding | |
| EC Number | 3.4.21.- |
| Enzyme Function | FUNCTION: Serine protease which exhibits a preference for Arg over Lys in the substrate P1 position and for Ser or Pro in the P2 position. Shows activity against amyloid precursor protein, myelin basic protein, gelatin, casein and extracellular matrix proteins such as fibronectin, laminin, vitronectin and collagen. Degrades alpha-synuclein and prevents its polymerization, indicating that it may be involved in the pathogenesis of Parkinson disease and other synucleinopathies. May be involved in regulation of axon outgrowth following spinal cord injury. Tumor cells treated with a neutralizing KLK6 antibody migrate less than control cells, suggesting a role in invasion and metastasis. {ECO:0000269|PubMed:11983703, ECO:0000269|PubMed:12878203, ECO:0000269|PubMed:12928483, ECO:0000269|PubMed:15557757, ECO:0000269|PubMed:16321973, ECO:0000269|PubMed:16987227}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | |
| nucleotide Binding | |
| Features | Active site (3); Alternative sequence (3); Beta strand (17); Chain (1); Disulfide bond (6); Domain (1); Glycosylation (1); Helix (5); Natural variant (1); Propeptide (1); Signal peptide (1); Site (1); Turn (4) |
| Keywords | 3D-structure;Alternative splicing;Autocatalytic cleavage;Cleavage on pair of basic residues;Cytoplasm;Direct protein sequencing;Disulfide bond;Endoplasmic reticulum;Glycoprotein;Hydrolase;Microsome;Mitochondrion;Nucleus;Protease;Reference proteome;Secreted;Serine protease;Signal;Zymogen |
| Interact With | Q8NC06-3; P11117; Q53FZ2-2; Q96BT7-2; P05067; Q9NP61; Q5H9R4-2; Q8WXK3-2; Q12797-6; Q9Y6H3; P27449; O95817; Q8TBE0; Q9UQB8-3; Q9UQB8-6; P51572; O15155-2; Q9BXY8; Q7L1Q6-2; Q9H0W9-3; Q9H257-2; Q86XM0; O75309; P49336-2; Q9Y281; Q8NE62; O75508; Q9BT09; P20849; Q86WV2; P68400; P09668; P09172; P61962; Q9BTE7; Q6ZPD9-2; P63167; Q8N6R0; Q13144; P23588; P16452; Q5RHP9-3; Q6NXG1; Q6NXG1-3; Q7L5A8; Q6NZ36-4; Q14296; P31994; Q7L622; P24522; P15976-2; Q9NXC2; B2RAF7; P52790; Q9P0W2; Q4VB01; Q7LGA3-3; Q96D96-2; Q8IYA8; Q14005-2; Q0VD86; Q9BT40; Q9Y283-3; P57682; Q9Y2M5; O60259; P08727; Q14533; Q3LI72; Q3SYF9; Q8IUC2; Q92615; Q14847-2; Q6DKI2; Q8TE12-2; O95332; Q96JB6; Q99683; Q15759; P42679; Q14728; A0A0A0MR05; Q9BRA0; Q92886; P48645; Q9Y239; P06748; Q6P4D5-2; Q8WW12; Q16549; Q13371; Q9NZ53-2; Q9GZS1; P19388; Q6ZMI0-5; Q96QH2; Q86UA1; P61289; P21246; P53801; Q9NWB1-5; Q9BWF3; P52756; P47804-3; Q9H0X6; Q969K3; Q9BY12-3; Q86SQ7-2; Q9NTN9-3; Q8IUQ4-2; Q9H2B4-2; Q99717; P37840; Q5T0L3; Q496A3; Q9BUD6; Q9C004; Q99469; O75558; Q9UMX1; O43463; O60506-4; Q8TDR4; Q96A09; Q01664; Q6YHU6; Q9H808; Q8IU80-2; Q8IUR5-4; Q8WVP5; Q96KP6; O14787-2; O94900; P06753-2; Q9NX07; O60636; Q86UF1; Q5VYS8-5; Q9GZX9; Q13404; Q9H9P5-5; Q9NVA1; P61964; Q9NZC7-5; O00308; Q9HAV4; Q8N0Y2-2; Q7Z783; Q96EJ4 |
| Induction | INDUCTION: By spinal cord injury. This effect is particularly prominent in macrophages, microglia and reactive astrocytes. {ECO:0000269|PubMed:16987227}. |
| Subcellular Location | SUBCELLULAR LOCATION: Secreted. Nucleus, nucleolus. Cytoplasm. Mitochondrion. Microsome. Note=In brain, detected in the nucleus of glial cells and in the nucleus and cytoplasm of neurons. Detected in the mitochondrial and microsomal fractions of HEK-293 cells and released into the cytoplasm following cell stress. |
| Modified Residue | |
| Post Translational Modification | PTM: Inactivated by autolytic cleavage after Arg-80. |
| Signal Peptide | SIGNAL 1..16; /evidence=ECO:0000255 |
| Structure 3D | X-ray crystallography (17) |
| Cross Reference PDB | 1GVL; 1L2E; 1LO6; 3VFE; 4D8N; 5NX1; 5NX3; 6QFF; 6QFG; 6QFH; 6QH9; 6QHA; 6QHB; 6QHC; 6SKB; 6SKC; 6SKD; |
| Mapped Pubmed ID | 12023317; 12074831; 12232761; 12480753; 14696124; 15255184; 15584920; 15837738; 15867230; 16203767; 17158887; 18359858; 18627290; 18854834; 18957059; 18992199; 19088065; 19383923; 19426157; 19558318; 19560453; 19707197; 19950700; 20403393; 20406964; 20424135; 20438785; 20680316; 20836755; 20846516; 21193224; 21464892; 21656738; 21741862; 21753781; 22102857; 22285222; 22373580; 22386244; 22477710; 22505518; 22505521; 22508489; 22699826; 22874102; 23049835; 23136250; 24430362; 24643912; 24669031; 24979321; 25153389; 25153391; 25476568; 25477184; 25640309; 25649006; 25990935; 26172508; 26231762; 27093921; 27168011; 27283773; 27483364; 27844409; 27863404; 28254587; 28376164; 28431272; 29224812; 29435805; 29934309; 29993134; 30015976; 30137206; 30691925; 30980596; 31045568; 31521475; 31682009; 32155135; 33171469; 33249398; 34065672; |
| Motif | |
| Gene Encoded By | |
| Mass | 26,856 |
| Kinetics | BIOPHYSICOCHEMICAL PROPERTIES: Kinetic parameters: KM=1562 uM for Tosyl-Gly-Pro-Arg-AMC {ECO:0000269|PubMed:11983703, ECO:0000269|PubMed:12878203}; KM=777 uM for Tosyl-Gly-Pro-Lys-AMC {ECO:0000269|PubMed:11983703, ECO:0000269|PubMed:12878203}; KM=0.410 mM for Phe-Ser-Arg-AMC {ECO:0000269|PubMed:11983703, ECO:0000269|PubMed:12878203}; KM=0.455 mM for Gly-Gly-Arg-AMC {ECO:0000269|PubMed:11983703, ECO:0000269|PubMed:12878203}; KM=0.335 mM for Asp-Pro-Arg-AMC {ECO:0000269|PubMed:11983703, ECO:0000269|PubMed:12878203}; KM=0.758 mM for Gln-Gly-Arg-AMC {ECO:0000269|PubMed:11983703, ECO:0000269|PubMed:12878203}; KM=0.625 mM for Pro-Phe-Arg-AMC {ECO:0000269|PubMed:11983703, ECO:0000269|PubMed:12878203}; KM=0.271 mM for Val-Pro-Arg-AMC {ECO:0000269|PubMed:11983703, ECO:0000269|PubMed:12878203}; KM=1.72 mM for Val-Leu-Lys-AMC {ECO:0000269|PubMed:11983703, ECO:0000269|PubMed:12878203}; |
| Metal Binding | |
| Rhea ID | |
| Cross Reference Brenda | 3.4.21.104;3.4.21.34;3.4.21.B10; |