UniProt functional annotation for P09936



	UniProt functional annotation for P09936

UniProt code: P09936.

Organism: Homo sapiens (Human).

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

Function: Ubiquitin-protein hydrolase involved both in the processing of ubiquitin precursors and of ubiquitinated proteins (Probable). This enzyme is a thiol protease that recognizes and hydrolyzes a peptide bond at the C-terminal glycine of ubiquitin (PubMed:9774100, PubMed:8639624, PubMed:12408865, PubMed:23359680). Also binds to free monoubiquitin and may prevent its degradation in lysosomes (By similarity). The homodimer may have ATP-independent ubiquitin ligase activity (PubMed:12408865). {ECO:0000250|UniProtKB:Q9R0P9, ECO:0000269|PubMed:12408865, ECO:0000269|PubMed:23359680, ECO:0000269|PubMed:8639624, ECO:0000269|PubMed:9774100, ECO:0000305|PubMed:12408865, ECO:0000305|PubMed:23359680, ECO:0000305|PubMed:8639624, ECO:0000305|PubMed:9774100}.

Catalytic activity: Reaction=Thiol-dependent hydrolysis of ester, thioester, amide, peptide and isopeptide bonds formed by the C-terminal Gly of ubiquitin (a 76- residue protein attached to proteins as an intracellular targeting signal).; EC=3.4.19.12; Evidence={ECO:0000269|PubMed:12408865, ECO:0000269|PubMed:12705903, ECO:0000269|PubMed:16475834, ECO:0000269|PubMed:20439756, ECO:0000269|PubMed:23359680, ECO:0000269|PubMed:8639624, ECO:0000269|PubMed:9774100};

Biophysicochemical properties: Kinetic parameters: KM=122 nM for Ub-AMC {ECO:0000269|PubMed:12705903, ECO:0000269|PubMed:8639624, ECO:0000269|PubMed:9774100}; KM=1.20 uM for ubiquitin ethyl ester {ECO:0000269|PubMed:12705903, ECO:0000269|PubMed:8639624, ECO:0000269|PubMed:9774100}; Vmax=0.47 umol/min/mg enzyme toward Ub-AMC {ECO:0000269|PubMed:12705903, ECO:0000269|PubMed:8639624, ECO:0000269|PubMed:9774100}; Vmax=25 umol/min/mg enzyme toward ubiquitin ethyl ester {ECO:0000269|PubMed:12705903, ECO:0000269|PubMed:8639624, ECO:0000269|PubMed:9774100};

Subunit: Monomer. Homodimer. Interacts with SNCA (By similarity). Interacts with COPS5. {ECO:0000250, ECO:0000269|PubMed:12082530, ECO:0000269|PubMed:16537382, ECO:0000269|PubMed:20439756}.

Subcellular location: Cytoplasm {ECO:0000269|PubMed:19261853}. Endoplasmic reticulum membrane {ECO:0000269|PubMed:19261853}; Lipid- anchor {ECO:0000269|PubMed:19261853}. Note=About 30% of total UCHL1 is associated with membranes in brain.

Tissue specificity: Found in neuronal cell bodies and processes throughout the neocortex (at protein level). Expressed in neurons and cells of the diffuse neuroendocrine system and their tumors. Weakly expressed in ovary. Down-regulated in brains from Parkinson disease and Alzheimer disease patients. {ECO:0000269|PubMed:14722078, ECO:0000269|PubMed:9790970}.

Ptm: O-glycosylated. {ECO:0000250}.

Disease: Parkinson disease 5 (PARK5) [MIM:613643]: A complex neurodegenerative disorder with manifestations ranging from typical Parkinson disease to dementia with Lewy bodies. Clinical features include parkinsonian symptoms (resting tremor, rigidity, postural instability and bradykinesia), dementia, diffuse Lewy body pathology, autonomic dysfunction, hallucinations and paranoia. {ECO:0000269|PubMed:12408865, ECO:0000269|PubMed:12705903, ECO:0000269|PubMed:9774100}. Note=The disease is caused by variants affecting the gene represented in this entry.

Disease: Spastic paraplegia 79, autosomal recessive (SPG79) [MIM:615491]: A form of spastic paraplegia, a neurodegenerative disorder characterized by a slow, gradual, progressive weakness and spasticity of the lower limbs. Rate of progression and the severity of symptoms are quite variable. Initial symptoms may include difficulty with balance, weakness and stiffness in the legs, muscle spasms, and dragging the toes when walking. In some forms of the disorder, bladder symptoms (such as incontinence) may appear, or the weakness and stiffness may spread to other parts of the body. SPG79 is characterized by childhood onset blindness, cerebellar ataxia, nystagmus, dorsal column dysfunction, and spasticity with upper motor neuron dysfunction. {ECO:0000269|PubMed:23359680, ECO:0000269|PubMed:28007905}. Note=The disease is caused by variants affecting the gene represented in this entry.

Miscellaneous: Oxidation of Met-1, Met-6, Met-12, Met-124 and Met-179 to methionine sulfoxide, and oxidation of Cys-220 to cysteine sulfonic acid have been observed in brains from Alzheimer disease (AD) and Parkinson disease (PD) patients. In AD, UCHL1 was found to be associated with neurofibrillary tangles. In contrast to UCHL3, does not hydrolyze a peptide bond at the C-terminal glycine of NEDD8.

Similarity: Belongs to the peptidase C12 family. {ECO:0000305}.

Sequence caution: Sequence=CAA28443.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};

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:		Ubiquitin-protein hydrolase involved both in the processing of ubiquitin precursors and of ubiquitinated proteins (Probable). This enzyme is a thiol protease that recognizes and hydrolyzes a peptide bond at the C-terminal glycine of ubiquitin (PubMed:9774100, PubMed:8639624, PubMed:12408865, PubMed:23359680). Also binds to free monoubiquitin and may prevent its degradation in lysosomes (By similarity). The homodimer may have ATP-independent ubiquitin ligase activity (PubMed:12408865). {ECO:0000250\|UniProtKB:Q9R0P9, ECO:0000269\|PubMed:12408865, ECO:0000269\|PubMed:23359680, ECO:0000269\|PubMed:8639624, ECO:0000269\|PubMed:9774100, ECO:0000305\|PubMed:12408865, ECO:0000305\|PubMed:23359680, ECO:0000305\|PubMed:8639624, ECO:0000305\|PubMed:9774100}.


Catalytic activity:		Reaction=Thiol-dependent hydrolysis of ester, thioester, amide, peptide and isopeptide bonds formed by the C-terminal Gly of ubiquitin (a 76- residue protein attached to proteins as an intracellular targeting signal).; EC=3.4.19.12; Evidence={ECO:0000269\|PubMed:12408865, ECO:0000269\|PubMed:12705903, ECO:0000269\|PubMed:16475834, ECO:0000269\|PubMed:20439756, ECO:0000269\|PubMed:23359680, ECO:0000269\|PubMed:8639624, ECO:0000269\|PubMed:9774100};
Biophysicochemical properties:		Kinetic parameters: KM=122 nM for Ub-AMC {ECO:0000269\|PubMed:12705903, ECO:0000269\|PubMed:8639624, ECO:0000269\|PubMed:9774100}; KM=1.20 uM for ubiquitin ethyl ester {ECO:0000269\|PubMed:12705903, ECO:0000269\|PubMed:8639624, ECO:0000269\|PubMed:9774100}; Vmax=0.47 umol/min/mg enzyme toward Ub-AMC {ECO:0000269\|PubMed:12705903, ECO:0000269\|PubMed:8639624, ECO:0000269\|PubMed:9774100}; Vmax=25 umol/min/mg enzyme toward ubiquitin ethyl ester {ECO:0000269\|PubMed:12705903, ECO:0000269\|PubMed:8639624, ECO:0000269\|PubMed:9774100};
Subunit:		Monomer. Homodimer. Interacts with SNCA (By similarity). Interacts with COPS5. {ECO:0000250, ECO:0000269\|PubMed:12082530, ECO:0000269\|PubMed:16537382, ECO:0000269\|PubMed:20439756}.
Subcellular location:		Cytoplasm {ECO:0000269\|PubMed:19261853}. Endoplasmic reticulum membrane {ECO:0000269\|PubMed:19261853}; Lipid- anchor {ECO:0000269\|PubMed:19261853}. Note=About 30% of total UCHL1 is associated with membranes in brain.
Tissue specificity:		Found in neuronal cell bodies and processes throughout the neocortex (at protein level). Expressed in neurons and cells of the diffuse neuroendocrine system and their tumors. Weakly expressed in ovary. Down-regulated in brains from Parkinson disease and Alzheimer disease patients. {ECO:0000269\|PubMed:14722078, ECO:0000269\|PubMed:9790970}.
Ptm:		O-glycosylated. {ECO:0000250}.
Disease:		Parkinson disease 5 (PARK5) [MIM:613643]: A complex neurodegenerative disorder with manifestations ranging from typical Parkinson disease to dementia with Lewy bodies. Clinical features include parkinsonian symptoms (resting tremor, rigidity, postural instability and bradykinesia), dementia, diffuse Lewy body pathology, autonomic dysfunction, hallucinations and paranoia. {ECO:0000269\|PubMed:12408865, ECO:0000269\|PubMed:12705903, ECO:0000269\|PubMed:9774100}. Note=The disease is caused by variants affecting the gene represented in this entry.
Disease:		Spastic paraplegia 79, autosomal recessive (SPG79) [MIM:615491]: A form of spastic paraplegia, a neurodegenerative disorder characterized by a slow, gradual, progressive weakness and spasticity of the lower limbs. Rate of progression and the severity of symptoms are quite variable. Initial symptoms may include difficulty with balance, weakness and stiffness in the legs, muscle spasms, and dragging the toes when walking. In some forms of the disorder, bladder symptoms (such as incontinence) may appear, or the weakness and stiffness may spread to other parts of the body. SPG79 is characterized by childhood onset blindness, cerebellar ataxia, nystagmus, dorsal column dysfunction, and spasticity with upper motor neuron dysfunction. {ECO:0000269\|PubMed:23359680, ECO:0000269\|PubMed:28007905}. Note=The disease is caused by variants affecting the gene represented in this entry.
Miscellaneous:		Oxidation of Met-1, Met-6, Met-12, Met-124 and Met-179 to methionine sulfoxide, and oxidation of Cys-220 to cysteine sulfonic acid have been observed in brains from Alzheimer disease (AD) and Parkinson disease (PD) patients. In AD, UCHL1 was found to be associated with neurofibrillary tangles. In contrast to UCHL3, does not hydrolyze a peptide bond at the C-terminal glycine of NEDD8.
Similarity:		Belongs to the peptidase C12 family. {ECO:0000305}.
Sequence caution:		Sequence=CAA28443.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};