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Showing Protein Kallikrein-6 (HMDBP10708)

IdentificationBiological propertiesGene propertiesProtein propertiesExternal linksReferencesXMLShow 1 metabolite
Identification
HMDB Protein ID HMDBP10708
Secondary Accession Numbers
  • 16969
Name Kallikrein-6
Synonyms
  1. Neurosin
  2. Protease M
  3. SP59
  4. Serine protease 18
  5. Serine protease 9
  6. Zyme
Gene Name KLK6
Protein Type Enzyme
Biological Properties
General Function Involved in serine-type endopeptidase activity
Specific 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
Pathways Not Available
Reactions Not Available
GO Classification
Function
endopeptidase activity
serine-type endopeptidase activity
catalytic activity
hydrolase activity
peptidase activity
peptidase activity, acting on l-amino acid peptides
Process
metabolic process
macromolecule metabolic process
protein metabolic process
proteolysis
Cellular Location
  1. Nucleus
  2. Cytoplasm
  3. Mitochondrion
  4. nucleolus
  5. Secreted
  6. Microsome
Gene Properties
Chromosome Location Chromosome:1
Locus 19q13.3
SNPs KLK6
Gene Sequence 
>735 bp
ATGAAGAAGCTGATGGTGGTGCTGAGTCTGATTGCTGCAGCCTGGGCAGAGGAGCAGAAT
AAGTTGGTGCATGGCGGACCCTGCGACAAGACATCTCACCCCTACCAAGCTGCCCTCTAC
ACCTCGGGCCACTTGCTCTGTGGTGGGGTCCTTATCCATCCACTGTGGGTCCTCACAGCT
GCCCACTGCAAAAAACCGAATCTTCAGGTCTTCCTGGGGAAGCATAACCTTCGGCAAAGG
GAGAGTTCCCAGGAGCAGAGTTCTGTTGTCCGGGCTGTGATCCACCCTGACTATGATGCC
GCCAGCCATGACCAGGACATCATGCTGTTGCGCCTGGCACGCCCAGCCAAACTCTCTGAA
CTCATCCAGCCCCTTCCCCTGGAGAGGGACTGCTCAGCCAACACCACCAGCTGCCACATC
CTGGGCTGGGGCAAGACAGCAGATGGTGATTTCCCTGACACCATCCAGTGTGCATACATC
CACCTGGTGTCCCGTGAGGAGTGTGAGCATGCCTACCCTGGCCAGATCACCCAGAACATG
TTGTGTGCTGGGGATGAGAAGTACGGGAAGGATTCCTGCCAGGGTGATTCTGGGGGTCCG
CTGGTATGTGGAGACCACCTCCGAGGCCTTGTGTCATGGGGTAACATCCCCTGTGGATCA
AAGGAGAAGCCAGGAGTCTACACCAACGTCTGCAGATACACGAACTGGATCCAAAAAACC
ATTCAGGCCAAGTGA
Protein Properties
Number of Residues 244
Molecular Weight 26855.5
Theoretical pI 7.48
Pfam Domain Function
Signals
  • 1-16
Transmembrane Regions
  • None
Protein Sequence 
>Kallikrein-6
MKKLMVVLSLIAAAWAEEQNKLVHGGPCDKTSHPYQAALYTSGHLLCGGVLIHPLWVLTA
AHCKKPNLQVFLGKHNLRQRESSQEQSSVVRAVIHPDYDAASHDQDIMLLRLARPAKLSE
LIQPLPLERDCSANTTSCHILGWGKTADGDFPDTIQCAYIHLVSREECEHAYPGQITQNM
LCAGDEKYGKDSCQGDSGGPLVCGDHLRGLVSWGNIPCGSKEKPGVYTNVCRYTNWIQKT
IQAK
GenBank ID Protein Not Available
UniProtKB/Swiss-Prot ID Q92876
UniProtKB/Swiss-Prot Entry Name KLK6_HUMAN
PDB IDs
GenBank Gene ID U62801
GeneCard ID KLK6
GenAtlas ID KLK6
HGNC ID HGNC:6367
References
General References
  1. Ota T, Suzuki Y, Nishikawa T, Otsuki T, Sugiyama T, Irie R, Wakamatsu A, Hayashi K, Sato H, Nagai K, Kimura K, Makita H, Sekine M, Obayashi M, Nishi T, Shibahara T, Tanaka T, Ishii S, Yamamoto J, Saito K, Kawai Y, Isono Y, Nakamura Y, Nagahari K, Murakami K, Yasuda T, Iwayanagi T, Wagatsuma M, Shiratori A, Sudo H, Hosoiri T, Kaku Y, Kodaira H, Kondo H, Sugawara M, Takahashi M, Kanda K, Yokoi T, Furuya T, Kikkawa E, Omura Y, Abe K, Kamihara K, Katsuta N, Sato K, Tanikawa M, Yamazaki M, Ninomiya K, Ishibashi T, Yamashita H, Murakawa K, Fujimori K, Tanai H, Kimata M, Watanabe M, Hiraoka S, Chiba Y, Ishida S, Ono Y, Takiguchi S, Watanabe S, Yosida M, Hotuta T, Kusano J, Kanehori K, Takahashi-Fujii A, Hara H, Tanase TO, Nomura Y, Togiya S, Komai F, Hara R, Takeuchi K, Arita M, Imose N, Musashino K, Yuuki H, Oshima A, Sasaki N, Aotsuka S, Yoshikawa Y, Matsunawa H, Ichihara T, Shiohata N, Sano S, Moriya S, Momiyama H, Satoh N, Takami S, Terashima Y, Suzuki O, Nakagawa S, Senoh A, Mizoguchi H, Goto Y, Shimizu F, Wakebe H, Hishigaki H, Watanabe T, Sugiyama A, Takemoto M, Kawakami B, Yamazaki M, Watanabe K, Kumagai A, Itakura S, Fukuzumi Y, Fujimori Y, Komiyama M, Tashiro H, Tanigami A, Fujiwara T, Ono T, Yamada K, Fujii Y, Ozaki K, Hirao M, Ohmori Y, Kawabata A, Hikiji T, Kobatake N, Inagaki H, Ikema Y, Okamoto S, Okitani R, Kawakami T, Noguchi S, Itoh T, Shigeta K, Senba T, Matsumura K, Nakajima Y, Mizuno T, Morinaga M, Sasaki M, Togashi T, Oyama M, Hata H, Watanabe M, Komatsu T, Mizushima-Sugano J, Satoh T, Shirai Y, Takahashi Y, Nakagawa K, Okumura K, Nagase T, Nomura N, Kikuchi H, Masuho Y, Yamashita R, Nakai K, Yada T, Nakamura Y, Ohara O, Isogai T, Sugano S: Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat Genet. 2004 Jan;36(1):40-5. Epub 2003 Dec 21. [PubMed:14702039 ]
  2. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [PubMed:15489334 ]
  3. Grimwood J, Gordon LA, Olsen A, Terry A, Schmutz J, Lamerdin J, Hellsten U, Goodstein D, Couronne O, Tran-Gyamfi M, Aerts A, Altherr M, Ashworth L, Bajorek E, Black S, Branscomb E, Caenepeel S, Carrano A, Caoile C, Chan YM, Christensen M, Cleland CA, Copeland A, Dalin E, Dehal P, Denys M, Detter JC, Escobar J, Flowers D, Fotopulos D, Garcia C, Georgescu AM, Glavina T, Gomez M, Gonzales E, Groza M, Hammon N, Hawkins T, Haydu L, Ho I, Huang W, Israni S, Jett J, Kadner K, Kimball H, Kobayashi A, Larionov V, Leem SH, Lopez F, Lou Y, Lowry S, Malfatti S, Martinez D, McCready P, Medina C, Morgan J, Nelson K, Nolan M, Ovcharenko I, Pitluck S, Pollard M, Popkie AP, Predki P, Quan G, Ramirez L, Rash S, Retterer J, Rodriguez A, Rogers S, Salamov A, Salazar A, She X, Smith D, Slezak T, Solovyev V, Thayer N, Tice H, Tsai M, Ustaszewska A, Vo N, Wagner M, Wheeler J, Wu K, Xie G, Yang J, Dubchak I, Furey TS, DeJong P, Dickson M, Gordon D, Eichler EE, Pennacchio LA, Richardson P, Stubbs L, Rokhsar DS, Myers RM, Rubin EM, Lucas SM: The DNA sequence and biology of human chromosome 19. Nature. 2004 Apr 1;428(6982):529-35. [PubMed:15057824 ]
  4. Gan L, Lee I, Smith R, Argonza-Barrett R, Lei H, McCuaig J, Moss P, Paeper B, Wang K: Sequencing and expression analysis of the serine protease gene cluster located in chromosome 19q13 region. Gene. 2000 Oct 17;257(1):119-30. [PubMed:11054574 ]
  5. Anisowicz A, Sotiropoulou G, Stenman G, Mok SC, Sager R: A novel protease homolog differentially expressed in breast and ovarian cancer. Mol Med. 1996 Sep;2(5):624-36. [PubMed:8898378 ]
  6. Yamashiro K, Tsuruoka N, Kodama S, Tsujimoto M, Yamamura Y, Tanaka T, Nakazato H, Yamaguchi N: Molecular cloning of a novel trypsin-like serine protease (neurosin) preferentially expressed in brain. Biochim Biophys Acta. 1997 Jan 3;1350(1):11-4. [PubMed:9003450 ]
  7. Little SP, Dixon EP, Norris F, Buckley W, Becker GW, Johnson M, Dobbins JR, Wyrick T, Miller JR, MacKellar W, Hepburn D, Corvalan J, McClure D, Liu X, Stephenson D, Clemens J, Johnstone EM: Zyme, a novel and potentially amyloidogenic enzyme cDNA isolated from Alzheimer's disease brain. J Biol Chem. 1997 Oct 3;272(40):25135-42. [PubMed:9312124 ]
  8. Yousef GM, Luo LY, Scherer SW, Sotiropoulou G, Diamandis EP: Molecular characterization of zyme/protease M/neurosin (PRSS9), a hormonally regulated kallikrein-like serine protease. Genomics. 1999 Dec 1;62(2):251-9. [PubMed:10610719 ]
  9. Pampalakis G, Kurlender L, Diamandis EP, Sotiropoulou G: Cloning and characterization of novel isoforms of the human kallikrein 6 gene. Biochem Biophys Res Commun. 2004 Jul 16;320(1):54-61. [PubMed:15207701 ]
  10. Pampalakis G, Sotiropoulou G: Multiple mechanisms underlie the aberrant expression of the human kallikrein 6 gene in breast cancer. Biol Chem. 2006 Jun;387(6):773-82. [PubMed:16800739 ]
  11. Diamandis EP, Yousef GM, Soosaipillai AR, Grass L, Porter A, Little S, Sotiropoulou G: Immunofluorometric assay of human kallikrein 6 (zyme/protease M/neurosin) and preliminary clinical applications. Clin Biochem. 2000 Jul;33(5):369-75. [PubMed:11018688 ]
  12. Ogawa K, Yamada T, Tsujioka Y, Taguchi J, Takahashi M, Tsuboi Y, Fujino Y, Nakajima M, Yamamoto T, Akatsu H, Mitsui S, Yamaguchi N: Localization of a novel type trypsin-like serine protease, neurosin, in brain tissues of Alzheimer's disease and Parkinson's disease. Psychiatry Clin Neurosci. 2000 Aug;54(4):419-26. [PubMed:10997858 ]
  13. Petraki CD, Karavana VN, Skoufogiannis PT, Little SP, Howarth DJ, Yousef GM, Diamandis EP: The spectrum of human kallikrein 6 (zyme/protease M/neurosin) expression in human tissues as assessed by immunohistochemistry. J Histochem Cytochem. 2001 Nov;49(11):1431-41. [PubMed:11668196 ]
  14. Magklara A, Mellati AA, Wasney GA, Little SP, Sotiropoulou G, Becker GW, Diamandis EP: Characterization of the enzymatic activity of human kallikrein 6: Autoactivation, substrate specificity, and regulation by inhibitors. Biochem Biophys Res Commun. 2003 Aug 8;307(4):948-55. [PubMed:12878203 ]
  15. Iwata A, Maruyama M, Akagi T, Hashikawa T, Kanazawa I, Tsuji S, Nukina N: Alpha-synuclein degradation by serine protease neurosin: implication for pathogenesis of synucleinopathies. Hum Mol Genet. 2003 Oct 15;12(20):2625-35. Epub 2003 Aug 19. [PubMed:12928483 ]
  16. Ghosh MC, Grass L, Soosaipillai A, Sotiropoulou G, Diamandis EP: Human kallikrein 6 degrades extracellular matrix proteins and may enhance the metastatic potential of tumour cells. Tumour Biol. 2004 Jul-Aug;25(4):193-9. [PubMed:15557757 ]
  17. Scarisbrick IA, Sabharwal P, Cruz H, Larsen N, Vandell AG, Blaber SI, Ameenuddin S, Papke LM, Fehlings MG, Reeves RK, Blaber M, Windebank AJ, Rodriguez M: Dynamic role of kallikrein 6 in traumatic spinal cord injury. Eur J Neurosci. 2006 Sep;24(5):1457-69. [PubMed:16987227 ]
  18. Angelo PF, Lima AR, Alves FM, Blaber SI, Scarisbrick IA, Blaber M, Juliano L, Juliano MA: Substrate specificity of human kallikrein 6: salt and glycosaminoglycan activation effects. J Biol Chem. 2006 Feb 10;281(6):3116-26. Epub 2005 Dec 1. [PubMed:16321973 ]
  19. Blaber SI, Yoon H, Scarisbrick IA, Juliano MA, Blaber M: The autolytic regulation of human kallikrein-related peptidase 6. Biochemistry. 2007 May 1;46(17):5209-17. Epub 2007 Apr 7. [PubMed:17417874 ]
  20. Gomis-Ruth FX, Bayes A, Sotiropoulou G, Pampalakis G, Tsetsenis T, Villegas V, Aviles FX, Coll M: The structure of human prokallikrein 6 reveals a novel activation mechanism for the kallikrein family. J Biol Chem. 2002 Jul 26;277(30):27273-81. Epub 2002 May 16. [PubMed:12016211 ]
  21. Bernett MJ, Blaber SI, Scarisbrick IA, Dhanarajan P, Thompson SM, Blaber M: Crystal structure and biochemical characterization of human kallikrein 6 reveals that a trypsin-like kallikrein is expressed in the central nervous system. J Biol Chem. 2002 Jul 5;277(27):24562-70. Epub 2002 Apr 30. [PubMed:11983703 ]