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Protein

Cystatin-A

Gene

CSTA

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

Functioni

This is an intracellular thiol proteinase inhibitor. Has an important role in desmosome-mediated cell-cell adhesion in the lower levels of the epidermis.1 Publication

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sitei4 – 41Reactive site

GO - Molecular functioni

  1. cysteine-type endopeptidase inhibitor activity Source: UniProtKB
  2. protease binding Source: BHF-UCL
  3. protein binding, bridging Source: UniProtKB
  4. structural molecule activity Source: UniProtKB

GO - Biological processi

  1. keratinocyte differentiation Source: UniProtKB
  2. negative regulation of endopeptidase activity Source: GOC
  3. negative regulation of peptidase activity Source: BHF-UCL
  4. negative regulation of proteolysis Source: UniProtKB
  5. peptide cross-linking Source: UniProtKB
  6. single organismal cell-cell adhesion Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Protease inhibitor, Thiol protease inhibitor

Keywords - Biological processi

Cell adhesion

Protein family/group databases

MEROPSiI25.001.

Names & Taxonomyi

Protein namesi
Recommended name:
Cystatin-A
Alternative name(s):
Cystatin-AS
Stefin-A
Cleaved into the following chain:
Gene namesi
Name:CSTA
Synonyms:STF1, STFA
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 3

Organism-specific databases

HGNCiHGNC:2481. CSTA.

Subcellular locationi

Cytoplasm 1 Publication

GO - Cellular componenti

  1. cornified envelope Source: UniProtKB
  2. cytoplasm Source: UniProtKB
  3. extracellular space Source: UniProtKB
  4. extracellular vesicular exosome Source: UniProtKB
  5. nucleoplasm Source: HPA
  6. nucleus Source: HPA
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm

Pathology & Biotechi

Involvement in diseasei

Ichthyosis, exfoliative, autosomal recessive, ichthyosis bullosa of Siemens-like1 Publication

The disease is caused by mutations affecting the gene represented in this entry.

Disease descriptionA form of congenital exfoliative ichthyosis, sharing some features with ichthyosis bullosa of Siemens and annular epidermolytic ichthyosis. AREI presents shortly after birth as dry, scaly skin over most of the body with coarse peeling of non-erythematous skin on the palms and soles, which is exacerbated by excessive moisture and minor trauma. Electron microscopy analysis of skin biopsies, reveals mostly normal-appearing upper layers of the epidermis, but prominent intercellular edema of the basal and suprabasal cell layers with aggregates of tonofilaments in the basal keratinocytes.

See also OMIM:607936

Keywords - Diseasei

Ichthyosis

Organism-specific databases

MIMi607936. phenotype.
Orphaneti289586. Exfoliative ichthyosis.
PharmGKBiPA26983.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 9898Cystatin-APRO_0000423202Add
BLAST
Initiator methioninei1 – 11Removed; alternate1 Publication
Chaini2 – 9897Cystatin-A, N-terminally processedPRO_0000207128Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei1 – 11N-acetylmethionineBy similarity

Keywords - PTMi

Acetylation

Proteomic databases

MaxQBiP01040.
PaxDbiP01040.
PeptideAtlasiP01040.
PRIDEiP01040.

PTM databases

PhosphoSiteiP01040.

Expressioni

Tissue specificityi

Expressed in the skin throughout the epidermis.1 Publication

Gene expression databases

BgeeiP01040.
CleanExiHS_CSTA.
ExpressionAtlasiP01040. baseline and differential.
GenevestigatoriP01040.

Organism-specific databases

HPAiCAB000469.
CAB047315.
HPA001031.

Interactioni

Protein-protein interaction databases

BioGridi107857. 21 interactions.
IntActiP01040. 9 interactions.
MINTiMINT-1428155.
STRINGi9606.ENSP00000264474.

Structurei

Secondary structure

1
98
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi7 – 126Combined sources
Helixi14 – 3118Combined sources
Beta strandi34 – 363Combined sources
Beta strandi39 – 5820Combined sources
Helixi60 – 623Combined sources
Beta strandi64 – 718Combined sources
Helixi74 – 763Combined sources
Helixi77 – 793Combined sources
Beta strandi80 – 8910Combined sources
Beta strandi91 – 933Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1CYUNMR-A1-98[»]
1CYVNMR-A1-98[»]
1DVCNMR-A1-98[»]
1DVDNMR-A1-98[»]
1GD3NMR-A1-98[»]
1GD4NMR-A1-98[»]
1N9JNMR-A/B1-98[»]
1NB3X-ray2.80I/J/K/L1-98[»]
1NB5X-ray2.40I/J/K/L1-98[»]
3K9MX-ray2.61C/D1-98[»]
3KFQX-ray1.99C/D1-98[»]
3KSEX-ray1.71D/E/F1-98[»]
ProteinModelPortaliP01040.
SMRiP01040. Positions 1-98.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP01040.

Family & Domainsi

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi46 – 505Secondary area of contact

Sequence similaritiesi

Belongs to the cystatin family.Curated

Phylogenomic databases

eggNOGiNOG119299.
GeneTreeiENSGT00390000015607.
HOGENOMiHOG000294175.
HOVERGENiHBG002292.
InParanoidiP01040.
KOiK13907.
OMAiIEYKTQV.
OrthoDBiEOG7FR7JX.
PhylomeDBiP01040.
TreeFamiTF333174.

Family and domain databases

InterProiIPR000010. Prot_inh_cystat.
IPR018073. Prot_inh_cystat_CS.
IPR001713. Prot_inh_stefinA.
[Graphical view]
PfamiPF00031. Cystatin. 1 hit.
[Graphical view]
PRINTSiPR00295. STEFINA.
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.

P01040-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MIPGGLSEAK PATPEIQEIV DKVKPQLEEK TNETYGKLEA VQYKTQVVAG
60 70 80 90
TNYYIKVRAG DNKYMHLKVF KSLPGQNEDL VLTGYQVDKN KDDELTGF
Length:98
Mass (Da):11,006
Last modified:July 21, 1986 - v1
Checksum:i2F5F0D61C91305EE
GO

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti96 – 961T → M.
Corresponds to variant rs34173813 [ dbSNP | Ensembl ].
VAR_048851

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X05978 mRNA. Translation: CAA29398.1.
D88422 Genomic DNA. Translation: BAA13609.1.
AB007774 Genomic DNA. Translation: BAA87858.1.
AK291308 mRNA. Translation: BAF83997.1.
CR456914 mRNA. Translation: CAG33195.1.
CH471052 Genomic DNA. Translation: EAW79489.1.
BC010379 mRNA. Translation: AAH10379.1.
CCDSiCCDS3011.1.
PIRiA29139. UDHUS.
RefSeqiNP_005204.1. NM_005213.3.
UniGeneiHs.518198.

Genome annotation databases

EnsembliENST00000264474; ENSP00000264474; ENSG00000121552.
GeneIDi1475.
KEGGihsa:1475.
UCSCiuc003eex.3. human.

Polymorphism databases

DMDMi118177.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Web resourcesi

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X05978 mRNA. Translation: CAA29398.1.
D88422 Genomic DNA. Translation: BAA13609.1.
AB007774 Genomic DNA. Translation: BAA87858.1.
AK291308 mRNA. Translation: BAF83997.1.
CR456914 mRNA. Translation: CAG33195.1.
CH471052 Genomic DNA. Translation: EAW79489.1.
BC010379 mRNA. Translation: AAH10379.1.
CCDSiCCDS3011.1.
PIRiA29139. UDHUS.
RefSeqiNP_005204.1. NM_005213.3.
UniGeneiHs.518198.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1CYUNMR-A1-98[»]
1CYVNMR-A1-98[»]
1DVCNMR-A1-98[»]
1DVDNMR-A1-98[»]
1GD3NMR-A1-98[»]
1GD4NMR-A1-98[»]
1N9JNMR-A/B1-98[»]
1NB3X-ray2.80I/J/K/L1-98[»]
1NB5X-ray2.40I/J/K/L1-98[»]
3K9MX-ray2.61C/D1-98[»]
3KFQX-ray1.99C/D1-98[»]
3KSEX-ray1.71D/E/F1-98[»]
ProteinModelPortaliP01040.
SMRiP01040. Positions 1-98.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi107857. 21 interactions.
IntActiP01040. 9 interactions.
MINTiMINT-1428155.
STRINGi9606.ENSP00000264474.

Protein family/group databases

MEROPSiI25.001.

PTM databases

PhosphoSiteiP01040.

Polymorphism databases

DMDMi118177.

Proteomic databases

MaxQBiP01040.
PaxDbiP01040.
PeptideAtlasiP01040.
PRIDEiP01040.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000264474; ENSP00000264474; ENSG00000121552.
GeneIDi1475.
KEGGihsa:1475.
UCSCiuc003eex.3. human.

Organism-specific databases

CTDi1475.
GeneCardsiGC03P122044.
HGNCiHGNC:2481. CSTA.
HPAiCAB000469.
CAB047315.
HPA001031.
MIMi184600. gene.
607936. phenotype.
neXtProtiNX_P01040.
Orphaneti289586. Exfoliative ichthyosis.
PharmGKBiPA26983.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiNOG119299.
GeneTreeiENSGT00390000015607.
HOGENOMiHOG000294175.
HOVERGENiHBG002292.
InParanoidiP01040.
KOiK13907.
OMAiIEYKTQV.
OrthoDBiEOG7FR7JX.
PhylomeDBiP01040.
TreeFamiTF333174.

Miscellaneous databases

ChiTaRSiCSTA. human.
EvolutionaryTraceiP01040.
GeneWikiiCystatin_A.
GenomeRNAii1475.
NextBioi6057.
PROiP01040.
SOURCEiSearch...

Gene expression databases

BgeeiP01040.
CleanExiHS_CSTA.
ExpressionAtlasiP01040. baseline and differential.
GenevestigatoriP01040.

Family and domain databases

InterProiIPR000010. Prot_inh_cystat.
IPR018073. Prot_inh_cystat_CS.
IPR001713. Prot_inh_stefinA.
[Graphical view]
PfamiPF00031. Cystatin. 1 hit.
[Graphical view]
PRINTSiPR00295. STEFINA.
SMARTiSM00043. CY. 1 hit.
[Graphical view]
PROSITEiPS00287. CYSTATIN. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Protein inhibitors of cysteine proteinases. II. Primary structure of stefin, a cytosolic protein inhibitor of cysteine proteinases from human polymorphonuclear granulocytes."
    Machleidt W., Borchart U., Fritz H., Brzin J., Ritonja A., Turk V.
    Hoppe-Seyler's Z. Physiol. Chem. 364:1481-1486(1983) [PubMed] [Europe PMC] [Abstract]
    Cited for: PROTEIN SEQUENCE.
  2. "Comparative studies on the primary structure of human cystatin as from epidermis, liver, spleen, and leukocytes."
    Takeda A., Kaji H., Nakaya K., Nakmura Y., Samejima T.
    J. Biochem. 105:986-991(1989) [PubMed] [Europe PMC] [Abstract]
    Cited for: PROTEIN SEQUENCE.
  3. "Effects of UV, 4-NQO and TPA on gene expression in cultured human epidermal keratinocytes."
    Kartasova T., Cornelissen B.J.C., Belt P., van de Putte P.
    Nucleic Acids Res. 15:5945-5962(1987) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
  4. "Genomic structure of human cystatin A."
    Yamazaki M., Ishidoh K., Eiki K., Ogawa H.
    DNA Seq. 8:71-76(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
  5. "Structure and transcriptional regulation of the human cystatin A gene. The 12-o-tetradecanoylphorbol-13-acetate (tpa) responsive element-2 site (-272 to -278) on cystatin a gene is critical for tpa-dependent regulation."
    Takahashi H., Asano K., Kinouchi M., Ishida-Yamamoto A., Wuepper K.D., Iizuka H.
    J. Biol. Chem. 273:17375-17380(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
  6. "Complete sequencing and characterization of 21,243 full-length human cDNAs."
    Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.
    , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
    Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Tissue: Tongue.
  7. "Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)."
    Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.
    Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
  8. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  9. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Tissue: Bone marrow.
  10. Bienvenut W.V., Gao M., Leug H.
    Submitted (JUN-2009) to UniProtKB
    Cited for: PROTEIN SEQUENCE OF 2-22; 31-56 AND 72-98, CLEAVAGE OF INITIATOR METHIONINE, IDENTIFICATION BY MASS SPECTROMETRY.
    Tissue: Prostatic carcinoma.
  11. "Molecular cloning, occurrence, and expression of a novel partially secreted protein 'psoriasin' that is highly up-regulated in psoriatic skin."
    Madsen P., Rasmussen H.H., Leffers H., Honore B., Dejgaard K., Olsen E., Kiil J., Walbum E., Andersen A.H., Basse B., Lauridsen J.B., Ratz G.P., Celis A., Vandekerckhove J., Celis J.E.
    J. Invest. Dermatol. 97:701-712(1991) [PubMed] [Europe PMC] [Abstract]
    Cited for: PROTEIN SEQUENCE OF 72-85.
    Tissue: Keratinocyte.
  12. "Microsequences of 145 proteins recorded in the two-dimensional gel protein database of normal human epidermal keratinocytes."
    Rasmussen H.H., van Damme J., Puype M., Gesser B., Celis J.E., Vandekerckhove J.
    Electrophoresis 13:960-969(1992) [PubMed] [Europe PMC] [Abstract]
    Cited for: PROTEIN SEQUENCE OF 72-85.
    Tissue: Keratinocyte.
  13. "Mutations in CSTA, encoding Cystatin A, underlie exfoliative ichthyosis and reveal a role for this protease inhibitor in cell-cell adhesion."
    Blaydon D.C., Nitoiu D., Eckl K.M., Cabral R.M., Bland P., Hausser I., van Heel D.A., Rajpopat S., Fischer J., Oji V., Zvulunov A., Traupe H., Hennies H.C., Kelsell D.P.
    Am. J. Hum. Genet. 89:564-571(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, TISSUE SPECIFICITY, SUBCELLULAR LOCATION, INVOLVEMENT IN AREI.
  14. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
  15. "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome."
    Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., Ye M., Zou H.
    J. Proteomics 96:253-262(2014) [PubMed] [Europe PMC] [Abstract]
    Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Liver.
  16. Cited for: STRUCTURE BY NMR.
  17. "Solution structure of a human cystatin A variant, cystatin A2-98 M65L, by NMR spectroscopy. A possible role of the interactions between the N- and C-termini to maintain the inhibitory active form of cystatin A."
    Tate S., Ushioda T., Utsunomiya-Tate N., Shibuya K., Ohyama Y., Nakano Y., Kaji H., Inagaki F., Samejima T., Kainosho M.
    Biochemistry 34:14637-14648(1995) [PubMed] [Europe PMC] [Abstract]
    Cited for: STRUCTURE BY NMR.

Entry informationi

Entry nameiCYTA_HUMAN
AccessioniPrimary (citable) accession number: P01040
Secondary accession number(s): Q6IB90
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 21, 1986
Last sequence update: July 21, 1986
Last modified: March 4, 2015
This is version 163 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

Keywords - Technical termi

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

Documents

  1. Human chromosome 3
    Human chromosome 3: 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

External Data

Dasty 3

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 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.