Cystatin C (CST3)

Cystatin C, also known as Cystatin-3 (CST3) is a secreted type 2 cysteine protease inhibitor synthesized in all nucleated cells, has been proposed as a replacement for serum creatinine for the assessment of renal function, particularly to detect small reductions in glomerular filtration rate. The mature, active form of human cystatin C is a single non-glycosylated polypeptide chain consisting of 120 amino acid residues, with a molecular mass of 13,343-13,359 Da, and containing four characteristic disulfide-paired cysteine residues. Cystatin C is a low-molecular-weight protein which has been proposed as a marker of renal function that could replace creatinine. Indeed, the concentration of Cystatin C is mainly determined by glomerular filtration and is particularly of interest in clinical settings where the relationship between creatinine production and muscle mass impairs the clinical performance of creatinine. Since the last decade, numerous studies have evaluated its potential use in measuring renal function in various populations. More recently, other potential developments for its clinical use have emerged. In almost all the clinical studies, Cystatin C demonstrated a better diagnostic accuracy than serum creatinine in discriminating normal from impaired kidney function, but controversial results have been obtained by comparing this protein with other indices of kidney disease, especially serum creatinine-based equations, such as early atherosclerosis, Alzheimer's dementia, vascular aneurysms, hyperhomocysteinaemia and other neurodegenerative diseases. Cystatin C could be a useful clinical tool to identify HIV-infected persons. In addition, its expression is up-regulated in malignance of certain tumor progression.

Cystatin C (CST3) Related Areas

Enzyme>>Protease & Regulator>>Cysteine Protease & Regulator>>Cystatin>>Cystatin C/CST3

Cancer>>Angiogenesis>>Cystatin>>Cystatin C/CST3

Cystatin C (CST3) Alternative Names

Cystatin C, CST3, ARMD11, MGC117328 [Homo sapiens]

Cystatin C, Cst3, CysC, RP23-250M11.9 [Mus musculus]

Summaries for Cystatin C (CST3)

Entrez Gene summary for Cystatin C (CST3):

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.

OMIM - description for Cystatin C (CST3):

Cystatin C, which belongs to the type II cystatin gene family, is a potent inhibitor of lysosomal proteinases

Wikipedia summary for Cystatin C (CST3):

Cystatin C or cystatin 3 (formerly gamma trace, post-gamma-globulin or neuroendocrine basic polypeptide), a protein encoded by the CST3 gene, is mainly used as a biomarker of kidney function. Recently, it has been studied for its role in predicting new-onset or deteriorating cardiovascular disease. It also seems to play a role in brain disorders involving amyloid (a specific type of protein deposition), such as Alzheimer's disease. In humans, all cells with a nucleus (cell core containing the DNA) produce cystatin C as a chain of 120 amino acids. It is found in virtually all tissues and bodily fluids. It is a potent inhibitor of lysosomal proteinases (enzymes from a special subunit of the cell that break down proteins) and probably one of the most important extracellular inhibitors of cysteine proteases (it prevents the breakdown of proteins outside the cell by a specific type of protein degrading enzymes). Cystatin C belongs to the type 2 cystatin gene family.

Human Cystatin C (CST3) Protein General Information

 

• Protein names: Recommended name: Cystatin-C
• Sequence length: 146 AA.
• Domain: Signal
• Sequence similarities: Belongs to the cystatin family.
• Post-translational modification: 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
• Subunit structure: Homodimer.
• Subcellular location: Secreted
• Tissue specificity: 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.
• Involvement in disease: Defects in CST3 are the cause of amyloidosis type 6 (AMYL6) [MIM:105150]; also known as hereditary cerebral hemorrhage with amyloidosis (HCHWA), cerebral amyloid angiopathy (CAA) or cerebroarterial amyloidosis Icelandic type. AMYL6 is a 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. Ref.3 Ref.22 Genetic variations in CST3 are associated with age-related macular degeneration type 11 (ARMD11) [MIM:611953]. ARMD is 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.

General information above from UniProt

Function for Cystatin C (CST3) Protein

UniProtKB:

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

Genatlas:

• Cystatin C (CST3) is the inhibitor of several cysteine proteinases, such as cathepsins S, B, and K
• Cystatin C (CST3) is the inhibitor of cathepsin B, playing an important role of C in coronary artery disease
• Cystatin C (CST3) is a inhibitor of CST6 in retinal pigment epithelium
• Cystatin C (CST3) plays a role in cardiac extracellular matrix remodelling
• Cystatin C (CST3) is a inhibitor for human meprin MEP1A
• CST3 an AHSG are endogenous inhibitors of human meprin metalloproteases
• Cystatin C (CST3) regulates nitric oxide secretion by macrophages and is a TGFbeta antagonist

Homology for human Cystatin C (CST3)

• homolog to murine Cst3

Phenotype Information for Cystatin C (CST3)

• Gene/Locus: CST3, ARMD11
• Phenotype: Cerebral amyloid angiopathy Macular degeneration, age-related, 11

Phenotype Information for Cystatin C (CST3) from OMIM (Online Mendelian Inheritance in Man)