CST3

Protein identityUniProt · HPA

UniProt accession

P01034

Gene

CST3

Ensembl

ENSG00000101439

Chromosome

20

Canonical length

146 aa

Protein class

Cancer-related genes, Disease related genes, Human disease related genes, Plasma proteins, Predicted secreted proteins

Subcellular location

Golgi apparatus,Vesicles

Secretome location

Secreted to blood

Quaternary structure

Homodimer

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 the kininogens. The type 2 cystatin proteins are a class of cysteine proteinase inhibitors found in a variety of human fluids and secretions, where they appear to provide protective functions. The cystatin locus on chromosome 20 contains the majority of the type 2 cystatin genes and pseudogenes. This gene is located in the cystatin locus and encodes the most abundant extracellular inhibitor of cysteine proteases, which is found in high concentrations in biological fluids and is expressed in virtually all organs of the body. A mutation in this gene has been associated with amyloid angiopathy. Expression of this protein in vascular wall smooth muscle cells is severely reduced in both atherosclerotic and aneurysmal aortic lesions, establishing its role in vascular disease. In addition, this protein has been shown to have an antimicrobial function, inhibiting the replication of herpes simplex virus. Alternative splicing results in multiple transcript variants encoding a single protein. [provided by RefSeq, Nov 2014]

Canonical amino-acid sequenceUniProt

146 residues, UniProt reviewed canonical sequence.

>P01034|CST3
     1  MAGPLRAPLL LLAILAVALA VSPAAGSSPG KPPRLVGGPM DASVEEEGVR RALDFAVGEY
    61  NKASNDMYHS RALQVVRARK QIVAGVNYFL DVELGRTTCT KTQPNLDNCP FHDQPHLKRK
   121  AFCSFQIYAV PWQGTMTLSK STCQDA

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against CST3 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

Secreted

Secreted

Yes

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.4

Highest tissue expression

4,699 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about CST3.

Disease | AllUniProt

Conditions CST3 is implicated in, by any mechanism.

• Cerebral amyloid angiopathy, CST3-related (CAA-CST3) MIM:105150
• Macular degeneration, age-related, 11 (ARMD11) MIM:611953
• Leukodystrophy, adult-onset, autosomal dominant, without amyloid angiopathy (ADLDWA) MIM:621214

Disease | GeneticClinVar

1 pathogenic / likely-pathogenic of 73 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Hereditary cerebral amyloid angiopathy, Icelandic type

ReferencesPubMed · IEDB

Publications for CST3 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. IEDB — curated epitope assays from the Immune Epitope Database (Vita et al., Nucleic Acids Research 2019). 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)

1.6

gnomAD pLI

0

gnomAD missense Z

-0.5

DepMap mean gene effect

-0.06

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 7% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• defense response
• immune response
• negative regulation of blood vessel remodeling
• negative regulation of extracellular matrix disassembly
• negative regulation of proteolysis
• regulation of tissue remodeling
• supramolecular fiber organization
• negative regulation of collagen catabolic process
• negative regulation of elastin catabolic process

Molecular functions

• amyloid-beta binding
• cysteine-type endopeptidase inhibitor activity
• endopeptidase inhibitor activity
• identical protein binding
• peptidase inhibitor activity
• protease binding

Cellular components

• cytoplasm
• endoplasmic reticulum
• endoplasmic reticulum lumen
• extracellular exosome
• extracellular region
• extracellular space
• ficolin-1-rich granule lumen
• Golgi apparatus
• plasma membrane
• tertiary granule lumen
• vesicle

Protein domainsUniProt · Pfam · InterPro

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

KeywordsUniProt

• Age-related macular degeneration
• Amyloid
• Amyloidosis
• Disulfide bond
• Glycoprotein
• Leukodystrophy
• Phosphoprotein
• Protease inhibitor
• Secreted
• Signal
• Thiol protease inhibitor

InteractionsUniProt · HPA

Protein binding partners of CST3 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• LRP2
• CTSB