CSTB

Protein identityUniProt · HPA

UniProt accession

P04080

Gene

CSTB

Ensembl

ENSG00000160213

Chromosome

21

Canonical length

98 aa

Protein class

Cancer-related genes, Disease related genes, Human disease related genes, Plasma proteins, Potential drug targets, Predicted intracellular proteins, Transporters

Subcellular location

Nucleoli,Cytosol

OverviewNCBI Gene

The cystatin superfamily encompasses proteins that contain multiple cystatin-like sequences. Some of the members are active cysteine protease inhibitors, while others have lost or perhaps never acquired this inhibitory activity. There are three inhibitory families in the superfamily, including the type 1 cystatins (stefins), type 2 cystatins and kininogens. This gene encodes a stefin that functions as an intracellular thiol protease inhibitor. The protein is able to form a dimer stabilized by noncovalent forces, inhibiting papain and cathepsins l, h and b. The protein is thought to play a role in protecting against the proteases leaking from lysosomes. Evidence indicates that mutations in this gene are responsible for the primary defects in patients with progressive myoclonic epilepsy (EPM1). One type of mutation responsible for EPM1 is the expansion in the promoter region of this gene of a CCCCGCCCCGCG repeat from 2-3 copies to 30-78 copies. [provided by RefSeq, Jul 2016]

Canonical amino-acid sequenceUniProt

98 residues, UniProt reviewed canonical sequence.

>P04080|CSTB
     1  MMCGAPSATQ PATAETQHIA DQVRSQLEEK ENKKFPVFKA VSFKSQVVAG TNYFIKVHVG
    61  DEDFVHLRVF QSLPHENKPL TLSNYQTNKA KHDELTYF

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against CSTB 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

Intracellular

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.33

Highest tissue expression

20,478 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about CSTB.

Disease | AllUniProt

Conditions CSTB is implicated in, by any mechanism.

• Epilepsy, progressive myoclonic 1 (EPM1) MIM:254800

Disease | GeneticClinVar

21 pathogenic / likely-pathogenic of 180 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Unverricht-Lundborg syndrome
• Progressive myoclonic epilepsy
• Inborn genetic diseases
• Dyskinesia
• Chorea

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)

1.85

gnomAD pLI

0.01

gnomAD missense Z

0.02

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 locomotory behavior
• negative regulation of proteolysis

Molecular functions

• cysteine-type endopeptidase inhibitor activity
• endopeptidase inhibitor activity
• protease binding
• RNA binding

Cellular components

• cytoplasm
• cytosol
• extracellular exosome
• extracellular matrix
• extracellular region
• extracellular space
• ficolin-1-rich granule lumen
• nucleolus
• nucleus
• secretory granule lumen
• tertiary granule lumen

Protein domainsUniProt · Pfam · InterPro

• Cystatin domain
• Proteinase inhibitor I25A, stefin
• Proteinase inhibitor I25, cystatin, conserved site
• Cystatin superfamily
• Cystatin domain

KeywordsUniProt

• Acetylation
• Cytoplasm
• Epilepsy
• Neurodegeneration
• Nucleus
• Protease inhibitor
• Thiol protease inhibitor

InteractionsUniProt · HPA

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

• MRFAP1