UCHL1

Protein identityUniProt · HPA

UniProt accession

P09936

Gene

UCHL1

Ensembl

ENSG00000154277

Chromosome

4

Canonical length

223 aa

Protein class

Disease related genes, Enzymes, Human disease related genes, Plasma proteins, Potential drug targets, Predicted intracellular proteins

Subcellular location

Nucleoplasm,Cytosol

Quaternary structure

Homodimer

OverviewNCBI Gene

The protein encoded by this gene belongs to the peptidase C12 family. This enzyme is a thiol protease that hydrolyzes a peptide bond at the C-terminal glycine of ubiquitin. This gene is specifically expressed in the neurons and in cells of the diffuse neuroendocrine system. Mutations in this gene may be associated with Parkinson disease.[provided by RefSeq, Sep 2009]

Canonical amino-acid sequenceUniProt

223 residues, UniProt reviewed canonical sequence.

>P09936|UCHL1
     1  MQLKPMEINP EMLNKVLSRL GVAGQWRFVD VLGLEEESLG SVPAPACALL LLFPLTAQHE
    61  NFRKKQIEEL KGQEVSPKVY FMKQTIGNSC GTIGLIHAVA NNQDKLGFED GSVLKQFLSE
   121  TEKMSPEDRA KCFEKNEAIQ AAHDAVAQEG QCRVDDKVNF HFILFNNVDG HLYELDGRMP
   181  FPVNHGASSE DTLLKDAAKV CREFTEREQG EVRFSAVALC KAA

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against UCHL1 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Other membrane

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.26

Highest tissue expression

1,038 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about UCHL1.

Disease | AllUniProt

Conditions UCHL1 is implicated in, by any mechanism.

• Parkinson disease 5 (PARK5) MIM:613643
• Spastic paraplegia 79A, autosomal dominant, with ataxia (SPG79A) MIM:620221
• Spastic paraplegia 79B, autosomal recessive (SPG79B) MIM:615491

Disease | GeneticClinVar

23 pathogenic / likely-pathogenic of 234 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Spastic paraplegia 79A, autosomal dominant, with ataxia
• Early-onset progressive neurodegeneration-blindness-ataxia-spasticity syndrome
• Parkinson disease 5, autosomal dominant, susceptibility to
• UCHL1-related disorder
• Optic neuropathy

ReferencesPubMed · IEDB

Publications for UCHL1 from three distinct lines of evidence, kept separate because they answer different questions: whether antibodies are directed at the protein, whether a B-cell epitope has been mapped on it, and whether a T-cell epitope has. Each is labelled with its source.

Sources: PubMed — antigen-level antibody evidence from a custom retrieval. Records matching a controlled set of autoantibody terms (the MeSH descriptors Autoantibodies and Autoantigens, with title and abstract term variants) were obtained through NCBI E-utilities, and their titles and abstracts parsed for constructions that direct an antibody at a named protein rather than for co-occurrence. Captured names were resolved against UniProt nomenclature and each antigen adjudicated individually against the source text. Bibliographic records from PubMed and MeSH, U.S. National Library of Medicine; citation metrics from NIH iCite (Hutchins et al., PLoS Biology 2016). Titles link to PubMed; abstracts are not reproduced here. The NLM does not endorse this analysis.

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.21

gnomAD pLI

0.99

gnomAD missense Z

0.7

DepMap mean gene effect

0.04

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• adult walking behavior
• axon target recognition
• axonal transport of mitochondrion
• cellular response to xenobiotic stimulus
• eating behavior
• male germ cell proliferation
• muscle cell development
• negative regulation of MAPK cascade
• neuromuscular process
• positive regulation of glycolytic process
• proteasome-mediated ubiquitin-dependent protein catabolic process
• protein catabolic process
• protein deubiquitination
• regulation of macroautophagy
• response to ischemia

Molecular functions

• alpha-2A adrenergic receptor binding
• cysteine-type deubiquitinase activity
• cysteine-type endopeptidase activity
• omega peptidase activity
• ribosome binding
• signaling receptor inhibitor activity
• ubiquitin binding
• ubiquitin protein ligase binding

Cellular components

• axon cytoplasm
• cytoplasm
• cytosol
• endoplasmic reticulum membrane
• neuron projection terminus
• neuronal cell body
• nucleoplasm

Protein domainsUniProt · Pfam · InterPro

• Peptidase C12, ubiquitin carboxyl-terminal hydrolase
• Peptidase C12, ubiquitin carboxyl-terminal hydrolase superfamily
• Papain-like cysteine peptidase superfamily
• Ubiquitin carboxyl-terminal hydrolase family 1, cysteine active-site
• Ubiquitin carboxyl-terminal hydrolase, family 1

KeywordsUniProt

• Acetylation
• Alternative initiation
• Cytoplasm
• Endoplasmic reticulum
• Glycoprotein
• Hereditary spastic paraplegia
• Hydrolase
• Lipoprotein
• Membrane
• Neurodegeneration
• Oxidation
• Parkinson disease
• Parkinsonism
• Phosphoprotein
• Prenylation
• Protease
• Thiol protease
• Ubl conjugation pathway

InteractionsUniProt · HPA

Protein binding partners of UCHL1 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• COPS5
• SNCA
• EGFR
• TERF2IP
• TP53
• USP21