UniProt functional annotation for Q92876



	UniProt functional annotation for Q92876

UniProt code: Q92876.

Organism: Homo sapiens (Human).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.

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}.

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}.

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};

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. {ECO:0000269|PubMed:10997858, ECO:0000269|PubMed:11018688, ECO:0000269|PubMed:11668196, ECO:0000269|PubMed:12928483, ECO:0000269|PubMed:16800739}.

Induction: By spinal cord injury. This effect is particularly prominent in macrophages, microglia and reactive astrocytes. {ECO:0000269|PubMed:16987227}.

Ptm: Inactivated by autolytic cleavage after Arg-80.

Mass spectrometry: Mass=25866; Method=MALDI; Evidence={ECO:0000269|PubMed:11983703};

Similarity: Belongs to the peptidase S1 family. Kallikrein subfamily. {ECO:0000255|PROSITE-ProRule:PRU00274}.

Annotations taken from UniProtKB at the EBI.


Organism:		Homo sapiens (Human).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.



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}.


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}.
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};
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. {ECO:0000269\|PubMed:10997858, ECO:0000269\|PubMed:11018688, ECO:0000269\|PubMed:11668196, ECO:0000269\|PubMed:12928483, ECO:0000269\|PubMed:16800739}.
Induction:		By spinal cord injury. This effect is particularly prominent in macrophages, microglia and reactive astrocytes. {ECO:0000269\|PubMed:16987227}.
Ptm:		Inactivated by autolytic cleavage after Arg-80.
Mass spectrometry:		Mass=25866; Method=MALDI; Evidence={ECO:0000269\|PubMed:11983703};
Similarity:		Belongs to the peptidase S1 family. Kallikrein subfamily. {ECO:0000255\|PROSITE-ProRule:PRU00274}.