Tbio CST3 Cystatin-C

Protein Summary

Description

As an inhibitor of cysteine proteinases, this protein is thought to serve an important physiological role as a local regulator of this enzyme activity. 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]

Uniprot Accession IDs

• P01034
• B2R5J9
• D3DW42
• Q6FGW9

Gene Name

• CST3

Ensembl ID

• ENST00000376925
• ENSP00000366124
• ENSG00000101439
• ENST00000398409
• ENSP00000381446
• ENST00000398411
• ENSP00000381448

Symbol

• ARMD11
• HEL-S-2

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
biological term	1
PubMedID	0.98
disease perturbation	0.9
kinase perturbation	0.88
gene perturbation	0.78

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GENEVA

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ARCHS4 provides access to gene-function predictions based on RNA-seq co-expression, and gene expression levels across cell and tissues.

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IDG Development Level Summary

Tdark

These are targets about which virtually nothing is known. They do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 4624.48   (req: < 5)

Gene RIFs: 430   (req: <= 3)

Antibodies: 1243   (req: <= 50)

Tbio

These targets do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 4624.48   (req: >= 5)

Gene RIFs: 430   (req: > 3)

Antibodies: 1243   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 17

Tchem

Target has at least one ChEMBL compound with an activity cutoff of < 30 nM - AND - satisfies the preceding conditions

Active Ligand: 0

Tclin

Target has at least one approved drug - AND - satisfies the preceding conditions

Active Drug: 0

GWAS Traits (1)

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GWAS Trait	EFO ID	Study Count	SNP Count	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
acute coronary syndrome	EFO_0005672	1	1	1		88.2

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GWAS Trait	EFO ID	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
acute coronary syndrome	EFO_0005672	1		88.2

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Orthologs (6)

1 – 5 of 6

Species	Name	Source ID	Gene ID	OMA	EggNOG	Inparanoid
Mouse	cystatin C	MGI:102519	13010
Rat	cystatin C	RGD:2432	25307
Dog	cystatin-C-like		607874
Horse	cystatin C [Source:HGNC Symbol;Acc:HGNC:2475]
Cow	cystatin C		281102

Species	Name	OMA	EggNOG	Inparanoid
Mouse	cystatin C
Rat	cystatin C
Dog	cystatin-C-like
Horse	cystatin C [Source:HGNC Symbol;Acc:HGNC:2475]
Cow	cystatin C

Protein Structure (9 Structures, 1 AlphaFold Model)

Representation

  axes   backbone   ball+stick   cartoon   rocket   rope   spacefill

Color Scheme

  target   atomindex   bfactor   chainname   electrostatic   element   hydrophobicity   resname   sstruc

Click on a row in the table to change the structure displayed.
More information can be found at RCSB PDB

AF-P01034-F1-model_v1

AlphaFold Structures Developed by DeepMind and EMBL-EBI

1 – 5 of 9

PDB Structure Id	Ligand	Method	Resolution (Å)	Residues	Fraction of Total Protein	Pub Year	Title

PDB Structure Id	Fraction of Total Protein	Resolution	Pub Year

Pathways (69)

Reactome (8)

KEGG (1)

WikiPathways (60)

Amyloid fiber formation (R-HSA-977225)

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Data Source	Name	Explore in Pharos	Explore in Source
Reactome	Amyloid fiber formation	79 targets	R-HSA-977225
Reactome	Immune System	2246 targets	R-HSA-168256
Reactome	Innate Immune System	1188 targets	R-HSA-168249
Reactome	Metabolism of proteins	2050 targets	R-HSA-392499
Reactome	Neutrophil degranulation	543 targets	R-HSA-6798695

Name	Explore in Pharos	Explore in Source
Amyloid fiber formation	79 targets	R-HSA-977225
Immune System	2246 targets	R-HSA-168256
Innate Immune System	1188 targets	R-HSA-168249
Metabolism of proteins	2050 targets	R-HSA-392499
Neutrophil degranulation	543 targets	R-HSA-6798695

Gene Ontology Terms (23)

Functions (5)

Components (6)

Processes (12)

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GO Term	Evidence	Assigned by
cysteine-type endopeptidase inhibitor activity	Inferred from Direct Assay (IDA)	UniProtKB
endopeptidase inhibitor activity	Inferred from Direct Assay (IDA)	UniProtKB
amyloid-beta binding	Inferred from Physical Interaction (IPI)	BHF-UCL
identical protein binding	Inferred from Physical Interaction (IPI)	IntAct
protease binding	Inferred from Physical Interaction (IPI)	BHF-UCL

Protein-Protein Interactions (235)

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1 – 10 of 235

• See Interactions on String-DB

DDX31

Tbio

Family: Enzyme

Novelty: 2.84646195

p_int: 0.950121091

p_ni: 0.049878896

p_wrong: 1.2e-8

Score: 0.189

Data Source: BioPlex,STRINGDB

CSTB

Tbio

Novelty: 0.00311198

Score: 0.979

Data Source: STRINGDB

ALB

Tchem

Novelty: 0.00000616

Score: 0.978

Data Source: STRINGDB

B2M

Tbio

Novelty: 0.00011248

Score: 0.973

Data Source: STRINGDB

CTSD

Tchem

Family: Enzyme

Novelty: 0.00029823

Score: 0.972

Data Source: STRINGDB

CTSS

Tchem

Family: Enzyme

Novelty: 0.00786042

Score: 0.96

Data Source: STRINGDB

APOE

Tbio

Novelty: 0.00005049

Score: 0.959

Data Source: STRINGDB

IL6

Tclin

Novelty: 0.00001819

Score: 0.956

Data Source: STRINGDB

APP

Tchem

Novelty: 0.00008964

Score: 0.956

Data Source: STRINGDB

CTSH

Tchem

Family: Enzyme

Novelty: 0.00336694

Score: 0.955

Data Source: STRINGDB

Publication Statistics

PubMed Score  4624.48

PubMed score by year

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PubTator Score  3557.03

PubTator score by year

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Amino Acid Sequence

Residue Counts

Protein Sequence

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UniProt Keyword Find Similar Targets

3D-structure
Age-related macular degeneration
Amyloid
Amyloidosis
Complete proteome
Direct protein sequencing
Disease mutation
Disulfide bond
Glycoprotein
Phosphoprotein

GWAS Trait Find Similar Targets

acute coronary syndrome

MGI Phenotype Find Similar Targets

cellular phenotype
endocrine/exocrine gland phenotype
homeostasis/metabolism phenotype
mortality/aging
neoplasm
nervous system phenotype
reproductive system phenotype