Cystatin A

Cystatin-A is a protein that in humans is encoded by the CSTA gene.^[5][6]

CSTA
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1CYU, 1CYV, 1DVC, 1DVD, 1GD3, 1GD4, 1N9J, 1NB3, 1NB5, 3K9M, 3KFQ, 3KSE
Identifiers
Aliases	CSTA, AREI, STF1, STFA, Cystatin A, PSS4
External IDs	OMIM: 184600; MGI: 1924020; HomoloGene: 3819; GeneCards: CSTA; OMA:CSTA - orthologs
Gene location (Human) Chr. Chromosome 3 (human)[1] Band 3q21.1 Start 122,325,248 bp[1] End 122,341,969 bp[1]
Gene location (Mouse) Chr. Chromosome 16 (mouse)[2] Band 16|16 B3 Start 36,041,838 bp[2] End 36,077,810 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in mucosa of pharynx oral cavity gums gingival epithelium body of tongue human penis vulva superior surface of tongue epithelium of nasopharynx skin of thigh Top expressed in granulocyte zygote morula blastocyst blood right kidney proximal tubule suprachiasmatic nucleus secondary oocyte primary oocyte More reference expression data BioGPS More reference expression data
Gene ontology Molecular function peptidase inhibitor activity protease binding protein-macromolecule adaptor activity endopeptidase inhibitor activity structural molecule activity cysteine-type endopeptidase inhibitor activity Cellular component cytoplasm intracellular anatomical structure cornified envelope extracellular space nucleus cytosol Biological process negative regulation of proteolysis peptide cross-linking negative regulation of peptidase activity cell adhesion keratinocyte differentiation negative regulation of endopeptidase activity cornification cell-cell adhesion Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 1475 76770 Ensembl ENSG00000121552 ENSMUSG00000095620 UniProt P01040 Q9D8D6 RefSeq (mRNA) NM_005213 NM_029733 NM_001384090 RefSeq (protein) NP_005204 NP_084009 NP_001371019 Location (UCSC) Chr 3: 122.33 – 122.34 Mb Chr 16: 36.04 – 36.08 Mb PubMed search [3] [4]
Wikidata
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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 a cysteine protease inhibitor, forming tight complexes with papain and the cathepsins B, H, and L. The protein is one of the precursor proteins of cornified cell envelope in keratinocytes and plays a role in epidermal development and maintenance. Stefins have been proposed as prognostic and diagnostic tools for cancer.^[6]

Structure and Inhibatory Mechanism

The structure of cystatin A features a wedge-like shape that's typical of cysteine protease inhibitors. This shape is critical for how it blocks protease activity.^[7] The protein has three main functional regions:

• An N-terminal region with a conserved glycine^[7]
• Two β-hairpin loops (the first loop contains the important QVVAG sequence shown in blue in the image)^[7]
• A C-terminal region that helps stabilize the structure^[7]

These three regions work together to form the functional core that fits into the catalytic cleft of target proteases. The inhibitory mechanism depends on specific structural features:

• Leu73 in the second binding loop plays a crucial role in the inhibitory activity^[8]
• The N-terminal domain contributes about 40% of the overall binding energy^[9]
• Pro-3 and Ile-2 are particularly important for energy binding^[9]

Function

Cystatin A mainly works as an inhibitor of cysteine proteases, with strong binding to papain and cathepsins B, H, and L. It also serves as a building block for the cornified cell envelope in skin cells and helps with skin growth and maintenance.^[10]

In tissues, cystatin A helps regulate protein breakdown by controlling the activity of these proteases. This regulation is important for normal cell function and can be disrupted in certain diseases.

Interactions

Cystatin A has been shown to interact with Cathepsin B^[11][12] and CTSL1.^[12][13]

Clinical Significance

Altered levels of cystatin A have been observed in several disease states, particularly in skin disorders and certain cancers.^[14] Its role as a protease inhibitor makes it potentially valuable as both a diagnostic marker and therapeutic target.^[15]

See also

• Peptide Transporter Carbon Starvation (cstA) Family