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Protein

Cystatin-C

Gene

CST3

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei37Reactive site1

GO - Molecular functioni

  • beta-amyloid binding Source: BHF-UCL
  • cysteine-type endopeptidase inhibitor activity Source: UniProtKB
  • endopeptidase inhibitor activity Source: UniProtKB
  • identical protein binding Source: IntAct
  • protease binding Source: BHF-UCL

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Protease inhibitor, Thiol protease inhibitor

Enzyme and pathway databases

BioCyciZFISH:ENSG00000101439-MONOMER.
ReactomeiR-HSA-6798695. Neutrophil degranulation.
R-HSA-977225. Amyloid fiber formation.

Protein family/group databases

MEROPSiI25.004.

Names & Taxonomyi

Protein namesi
Recommended name:
Cystatin-C
Alternative name(s):
Cystatin-3
Gamma-trace
Neuroendocrine basic polypeptide
Post-gamma-globulin
Gene namesi
Name:CST3
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 20

Organism-specific databases

HGNCiHGNC:2475. CST3.

Subcellular locationi

GO - Cellular componenti

  • axon Source: Ensembl
  • basement membrane Source: Ensembl
  • contractile fiber Source: Ensembl
  • endoplasmic reticulum Source: Ensembl
  • extracellular exosome Source: UniProtKB
  • extracellular region Source: BHF-UCL
  • extracellular space Source: UniProtKB
  • lysosome Source: Ensembl
  • multivesicular body Source: Ensembl
  • neuronal cell body Source: Ensembl
  • nuclear membrane Source: Ensembl
  • perinuclear region of cytoplasm Source: Ensembl
Complete GO annotation...

Keywords - Cellular componenti

Amyloid, Secreted

Pathology & Biotechi

Involvement in diseasei

Amyloidosis 6 (AMYL6)2 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA hereditary generalized amyloidosis due to cystatin C amyloid deposition. Cystatin C amyloid accumulates in the walls of arteries, arterioles, and sometimes capillaries and veins of the brain, and in various organs including lymphoid tissue, spleen, salivary glands, and seminal vesicles. Amyloid deposition in the cerebral vessels results in cerebral amyloid angiopathy, cerebral hemorrhage and premature stroke. Cystatin C levels in the cerebrospinal fluid are abnormally low.
See also OMIM:105150
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_00220794L → Q in AMYL6. 2 PublicationsCorresponds to variant rs28939068dbSNPEnsembl.1
Macular degeneration, age-related, 11 (ARMD11)1 Publication
Disease susceptibility is associated with variations affecting the gene represented in this entry.
Disease descriptionA form of age-related macular degeneration, a multifactorial eye disease and the most common cause of irreversible vision loss in the developed world. In most patients, the disease is manifest as ophthalmoscopically visible yellowish accumulations of protein and lipid that lie beneath the retinal pigment epithelium and within an elastin-containing structure known as Bruch membrane.
See also OMIM:611953
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_01189325A → T in ARMD11; alters processing and glycosylation. 2 PublicationsCorresponds to variant rs1064039dbSNPEnsembl.1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi25A → S: Shows a dual distribution to the Golgi apparatus and to the mitochondria. 1 Publication1

Keywords - Diseasei

Age-related macular degeneration, Amyloidosis, Disease mutation

Organism-specific databases

DisGeNETi1471.
MalaCardsiCST3.
MIMi105150. phenotype.
611953. phenotype.
OpenTargetsiENSG00000101439.
Orphaneti100008. Hereditary cerebral hemorrhage with amyloidosis, Icelandic type.
PharmGKBiPA26976.

Polymorphism and mutation databases

BioMutaiCST3.
DMDMi118183.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 264 PublicationsAdd BLAST26
ChainiPRO_000000663927 – 146Cystatin-C2 PublicationsAdd BLAST120

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei43Phosphoserine; by FAM20C1 Publication1
Disulfide bondi99 ↔ 109
Disulfide bondi123 ↔ 143

Post-translational modificationi

The Thr-25 variant is O-glycosylated with a core 1 or possibly core 8 glycan. The signal peptide of the O-glycosylated Thr-25 variant is cleaved between Ala-20 and Val-21.1 Publication

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein

Proteomic databases

EPDiP01034.
MaxQBiP01034.
PaxDbiP01034.
PeptideAtlasiP01034.
PRIDEiP01034.

2D gel databases

DOSAC-COBS-2DPAGEP01034.
UCD-2DPAGEP01034.

PTM databases

iPTMnetiP01034.
PhosphoSitePlusiP01034.

Miscellaneous databases

PMAP-CutDBP01034.

Expressioni

Tissue specificityi

Expressed in submandibular and sublingual saliva but not in parotid saliva (at protein level). Expressed in various body fluids, such as the cerebrospinal fluid and plasma. Expressed in highest levels in the epididymis, vas deferens, brain, thymus, and ovary and the lowest in the submandibular gland.2 Publications

Gene expression databases

BgeeiENSG00000101439.
CleanExiHS_CST3.
ExpressionAtlasiP01034. baseline and differential.
GenevisibleiP01034. HS.

Organism-specific databases

HPAiCAB000118.
HPA013143.

Interactioni

Subunit structurei

Homodimer.

Binary interactionsi

WithEntry#Exp.IntActNotes
itself8EBI-948622,EBI-948622

GO - Molecular functioni

  • identical protein binding Source: IntAct
  • protease binding Source: BHF-UCL

Protein-protein interaction databases

BioGridi107853. 7 interactors.
IntActiP01034. 4 interactors.
MINTiMINT-2857857.
STRINGi9606.ENSP00000366124.

Structurei

Secondary structure

1146
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi40 – 42Combined sources3
Helixi47 – 63Combined sources17
Beta strandi67 – 101Combined sources35
Helixi106 – 108Combined sources3
Helixi115 – 118Combined sources4
Beta strandi121 – 130Combined sources10
Turni131 – 134Combined sources4
Beta strandi135 – 145Combined sources11

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1G96X-ray2.50A27-146[»]
1R4CX-ray2.18A/B/C/D/E/F/G/H37-146[»]
1TIJX-ray3.03A/B27-146[»]
3GAXX-ray1.70A/B27-146[»]
3NX0X-ray2.04A/B27-146[»]
3PS8X-ray2.55A27-146[»]
3QRDX-ray2.19A/B/C/D27-146[»]
3S67X-ray2.26A27-146[»]
3SVAX-ray3.02A27-146[»]
ProteinModelPortaliP01034.
SMRiP01034.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP01034.

Family & Domainsi

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi81 – 85Secondary area of contact5

Sequence similaritiesi

Belongs to the cystatin family.Curated

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiENOG410IZZH. Eukaryota.
ENOG4112CFJ. LUCA.
GeneTreeiENSGT00860000133739.
HOGENOMiHOG000231754.
HOVERGENiHBG009556.
InParanoidiP01034.
KOiK13899.
OMAiYTVPWLG.
OrthoDBiEOG091G0TP1.
PhylomeDBiP01034.

Family and domain databases

CDDicd00042. CY. 1 hit.
InterProiIPR027214. Cystatin.
IPR000010. Cystatin_dom.
IPR018073. Prot_inh_cystat_CS.
[Graphical view]
PANTHERiPTHR11413. PTHR11413. 1 hit.
PfamiPF00031. Cystatin. 1 hit.
[Graphical view]
SMARTiSM00043. CY. 1 hit.
[Graphical view]
PROSITEiPS00287. CYSTATIN. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P01034-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MAGPLRAPLL LLAILAVALA VSPAAGSSPG KPPRLVGGPM DASVEEEGVR
60 70 80 90 100
RALDFAVGEY NKASNDMYHS RALQVVRARK QIVAGVNYFL DVELGRTTCT
110 120 130 140
KTQPNLDNCP FHDQPHLKRK AFCSFQIYAV PWQGTMTLSK STCQDA
Length:146
Mass (Da):15,799
Last modified:August 1, 1988 - v1
Checksum:i75EF049CAE2E8B2B
GO

Mass spectrometryi

Molecular mass is 13334.5829±0.0140 Da from positions 27 - 146. Determined by ESI. 1 Publication

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_01189325A → T in ARMD11; alters processing and glycosylation. 2 PublicationsCorresponds to variant rs1064039dbSNPEnsembl.1
Natural variantiVAR_00220794L → Q in AMYL6. 2 PublicationsCorresponds to variant rs28939068dbSNPEnsembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X05607 mRNA. Translation: CAA29096.1.
M27891, M27889, M27890 Genomic DNA. Translation: AAA52164.1.
X61681, X61682, X61683 Genomic DNA. Translation: CAA43856.2.
X52255 Genomic DNA. Translation: CAA36497.1.
AK312213 mRNA. Translation: BAG35146.1.
BT006839 mRNA. Translation: AAP35485.1.
CR541988 mRNA. Translation: CAG46785.1.
CR542018 mRNA. Translation: CAG46815.1.
AL121894 Genomic DNA. Translation: CAC05424.1.
CH471133 Genomic DNA. Translation: EAX10137.1.
CH471133 Genomic DNA. Translation: EAX10138.1.
BC013083 mRNA. Translation: AAH13083.1.
BC110305 mRNA. Translation: AAI10306.1.
CCDSiCCDS13158.1.
PIRiS10216. UDHU.
RefSeqiNP_000090.1. NM_000099.3.
NP_001275543.1. NM_001288614.1.
UniGeneiHs.304682.

Genome annotation databases

EnsembliENST00000376925; ENSP00000366124; ENSG00000101439.
ENST00000398409; ENSP00000381446; ENSG00000101439.
ENST00000398411; ENSP00000381448; ENSG00000101439.
GeneIDi1471.
KEGGihsa:1471.
UCSCiuc002wtm.5. human.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X05607 mRNA. Translation: CAA29096.1.
M27891, M27889, M27890 Genomic DNA. Translation: AAA52164.1.
X61681, X61682, X61683 Genomic DNA. Translation: CAA43856.2.
X52255 Genomic DNA. Translation: CAA36497.1.
AK312213 mRNA. Translation: BAG35146.1.
BT006839 mRNA. Translation: AAP35485.1.
CR541988 mRNA. Translation: CAG46785.1.
CR542018 mRNA. Translation: CAG46815.1.
AL121894 Genomic DNA. Translation: CAC05424.1.
CH471133 Genomic DNA. Translation: EAX10137.1.
CH471133 Genomic DNA. Translation: EAX10138.1.
BC013083 mRNA. Translation: AAH13083.1.
BC110305 mRNA. Translation: AAI10306.1.
CCDSiCCDS13158.1.
PIRiS10216. UDHU.
RefSeqiNP_000090.1. NM_000099.3.
NP_001275543.1. NM_001288614.1.
UniGeneiHs.304682.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1G96X-ray2.50A27-146[»]
1R4CX-ray2.18A/B/C/D/E/F/G/H37-146[»]
1TIJX-ray3.03A/B27-146[»]
3GAXX-ray1.70A/B27-146[»]
3NX0X-ray2.04A/B27-146[»]
3PS8X-ray2.55A27-146[»]
3QRDX-ray2.19A/B/C/D27-146[»]
3S67X-ray2.26A27-146[»]
3SVAX-ray3.02A27-146[»]
ProteinModelPortaliP01034.
SMRiP01034.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi107853. 7 interactors.
IntActiP01034. 4 interactors.
MINTiMINT-2857857.
STRINGi9606.ENSP00000366124.

Protein family/group databases

MEROPSiI25.004.

PTM databases

iPTMnetiP01034.
PhosphoSitePlusiP01034.

Polymorphism and mutation databases

BioMutaiCST3.
DMDMi118183.

2D gel databases

DOSAC-COBS-2DPAGEP01034.
UCD-2DPAGEP01034.

Proteomic databases

EPDiP01034.
MaxQBiP01034.
PaxDbiP01034.
PeptideAtlasiP01034.
PRIDEiP01034.

Protocols and materials databases

DNASUi1471.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000376925; ENSP00000366124; ENSG00000101439.
ENST00000398409; ENSP00000381446; ENSG00000101439.
ENST00000398411; ENSP00000381448; ENSG00000101439.
GeneIDi1471.
KEGGihsa:1471.
UCSCiuc002wtm.5. human.

Organism-specific databases

CTDi1471.
DisGeNETi1471.
GeneCardsiCST3.
HGNCiHGNC:2475. CST3.
HPAiCAB000118.
HPA013143.
MalaCardsiCST3.
MIMi105150. phenotype.
604312. gene.
611953. phenotype.
neXtProtiNX_P01034.
OpenTargetsiENSG00000101439.
Orphaneti100008. Hereditary cerebral hemorrhage with amyloidosis, Icelandic type.
PharmGKBiPA26976.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IZZH. Eukaryota.
ENOG4112CFJ. LUCA.
GeneTreeiENSGT00860000133739.
HOGENOMiHOG000231754.
HOVERGENiHBG009556.
InParanoidiP01034.
KOiK13899.
OMAiYTVPWLG.
OrthoDBiEOG091G0TP1.
PhylomeDBiP01034.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000101439-MONOMER.
ReactomeiR-HSA-6798695. Neutrophil degranulation.
R-HSA-977225. Amyloid fiber formation.

Miscellaneous databases

ChiTaRSiCST3. human.
EvolutionaryTraceiP01034.
GeneWikiiCystatin_C.
GenomeRNAii1471.
PMAP-CutDBP01034.
PROiP01034.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000101439.
CleanExiHS_CST3.
ExpressionAtlasiP01034. baseline and differential.
GenevisibleiP01034. HS.

Family and domain databases

CDDicd00042. CY. 1 hit.
InterProiIPR027214. Cystatin.
IPR000010. Cystatin_dom.
IPR018073. Prot_inh_cystat_CS.
[Graphical view]
PANTHERiPTHR11413. PTHR11413. 1 hit.
PfamiPF00031. Cystatin. 1 hit.
[Graphical view]
SMARTiSM00043. CY. 1 hit.
[Graphical view]
PROSITEiPS00287. CYSTATIN. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiCYTC_HUMAN
AccessioniPrimary (citable) accession number: P01034
Secondary accession number(s): B2R5J9, D3DW42, Q6FGW9
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 21, 1986
Last sequence update: August 1, 1988
Last modified: November 30, 2016
This is version 196 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Miscellaneous

Potential cerebrospinal fluid marker for the diagnosis of Creutzfeldt-Jakob disease.

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 20
    Human chromosome 20: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.