Description: Homo sapiens kallikrein-related peptidase 6 (KLK6), transcript variant A, mRNA. RefSeq Summary (NM_001012965): This gene encodes a member of the kallikrein subfamily of the peptidase S1 family of serine proteases. Growing evidence suggests that many kallikreins are implicated in carcinogenesis and some have potential as novel cancer and other disease biomarkers. The encoded preproprotein is proteolytically processed to generate the mature protease. Expression of this protease is regulated by steroid hormones and may be elevated in multiple human cancers and in serum from psoriasis patients. The encoded protease may participate in the cleavage of amyloid precursor protein and alpha-synuclein, thus implicating this protease in Alzheimer's and Parkinson's disease, respectively. This gene is located in a gene cluster on chromosome 19. Alternative splicing results in multiple transcript variants, at least one of which encodes an isoform that is proteolytically processed. [provided by RefSeq, Feb 2016]. Transcript (Including UTRs) Position: hg19 chr19:51,461,887-51,471,452 Size: 9,566 Total Exon Count: 5 Strand: - Coding Region Position: hg19 chr19:51,462,420-51,471,387 Size: 8,968 Coding Exon Count: 5
ID:KLK6_HUMAN DESCRIPTION: RecName: Full=Kallikrein-6; EC=3.4.21.-; AltName: Full=Neurosin; AltName: Full=Protease M; AltName: Full=SP59; AltName: Full=Serine protease 18; AltName: Full=Serine protease 9; AltName: Full=Zyme; Flags: Precursor; 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. ENZYME 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. BIOPHYSICOCHEMICAL PROPERTIES: Kinetic parameters: KM=1562 uM for Tosyl-Gly-Pro-Arg-AMC; KM=777 uM for Tosyl-Gly-Pro-Lys-AMC; KM=0.410 mM for Phe-Ser-Arg-AMC; KM=0.455 mM for Gly-Gly-Arg-AMC; KM=0.335 mM for Asp-Pro-Arg-AMC; KM=0.758 mM for Gln-Gly-Arg-AMC; KM=0.625 mM for Pro-Phe-Arg-AMC; KM=0.271 mM for Val-Pro-Arg-AMC; KM=1.72 mM for Val-Leu-Lys-AMC; 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. TISSUE SPECIFICITY: In fluids, highest levels found in milk of lactating women followed by cerebrospinal fluid, nipple aspirate fluid and breast cyst fluid. Also found in serum, seminal plasma and some amniotic fluids and breast tumor cytosolic extracts. Not detected in urine. At the tissue level, highest concentrations found in glandular tissues such as salivary glands followed by lung, colon, fallopian tube, placenta, breast, pituitary and kidney. Not detected in skin, spleen, bone, thyroid, heart, ureter, liver, muscle, endometrium, testis, pancreas, seminal vesicle, ovary, adrenals and prostate. In brain, detected in gray matter neurons (at protein level). Colocalizes with pathological inclusions such as Lewy bodies and glial cytoplasmic inclusions. Overexpressed in primary breast tumors but not expressed in metastatic tumors. INDUCTION: By spinal cord injury. This effect is particularly prominent in macrophages, microglia and reactive astrocytes. PTM: Inactivated by autolytic cleavage after Arg-80. MASS SPECTROMETRY: Mass=25866; Method=MALDI; Range=22-244; Source=PubMed:11983703; SIMILARITY: Belongs to the peptidase S1 family. Kallikrein subfamily. SIMILARITY: Contains 1 peptidase S1 domain.
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on Q92876
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
Biological Process: GO:0006508 proteolysis GO:0007417 central nervous system development GO:0009611 response to wounding GO:0010975 regulation of neuron projection development GO:0016540 protein autoprocessing GO:0030574 collagen catabolic process GO:0042246 tissue regeneration GO:0042445 hormone metabolic process GO:0042552 myelination GO:0042982 amyloid precursor protein metabolic process GO:0045595 regulation of cell differentiation GO:0045745 positive regulation of G-protein coupled receptor protein signaling pathway GO:0070997 neuron death
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