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P01040 (CYTA_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 156. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Cystatin-A
Alternative name(s):
Cystatin-AS
Stefin-A

Cleaved into the following chain:

  1. Cystatin-A, N-terminally processed
Gene names
Name:CSTA
Synonyms:STF1, STFA
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length98 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

This is an intracellular thiol proteinase inhibitor. Has an important role in desmosome-mediated cell-cell adhesion in the lower levels of the epidermis. Ref.13

Subcellular location

Cytoplasm Ref.13.

Tissue specificity

Expressed in the skin throughout the epidermis. Ref.13

Involvement in disease

Ichthyosis, exfoliative, autosomal recessive, ichthyosis bullosa of Siemens-like (AREI) [MIM:607936]: A 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.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.13

Sequence similarities

Belongs to the cystatin family.

Ontologies

Keywords
   Biological processCell adhesion
   Cellular componentCytoplasm
   Coding sequence diversityPolymorphism
   DiseaseIchthyosis
   Molecular functionProtease inhibitor
Thiol protease inhibitor
   PTMAcetylation
   Technical term3D-structure
Complete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processkeratinocyte differentiation

Inferred from direct assay PubMed 10908733. Source: UniProtKB

negative regulation of endopeptidase activity

Inferred from direct assay PubMed 3488317PubMed 6203523. Source: GOC

negative regulation of peptidase activity

Inferred from direct assay PubMed 6203523. Source: BHF-UCL

negative regulation of proteolysis

Inferred from direct assay PubMed 3488317. Source: UniProt

peptide cross-linking

Inferred from direct assay PubMed 10908733. Source: UniProtKB

single organismal cell-cell adhesion

Inferred from mutant phenotype Ref.13. Source: UniProtKB

   Cellular_componentcornified envelope

Inferred from direct assay PubMed 10908733. Source: UniProtKB

cytoplasm

Inferred from direct assay Ref.13. Source: UniProtKB

extracellular space

Inferred from direct assay PubMed 3488317. Source: UniProt

nucleus

Inferred from direct assay. Source: HPA

   Molecular_functioncysteine-type endopeptidase inhibitor activity

Inferred from direct assay PubMed 6203523. Source: BHF-UCL

protease binding

Inferred from physical interaction PubMed 6203523. Source: BHF-UCL

protein binding, bridging

Inferred from direct assay PubMed 10908733. Source: UniProtKB

structural molecule activity

Inferred from direct assay PubMed 10908733. Source: UniProtKB

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 9898Cystatin-A
PRO_0000423202
Initiator methionine11Removed; alternate Ref.10
Chain2 – 9897Cystatin-A, N-terminally processed
PRO_0000207128

Regions

Motif46 – 505Secondary area of contact

Sites

Site41Reactive site

Amino acid modifications

Modified residue11N-acetylmethionine By similarity

Natural variations

Natural variant961T → M.
Corresponds to variant rs34173813 [ dbSNP | Ensembl ].
VAR_048851

Secondary structure

................... 98
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P01040 [UniParc].

Last modified July 21, 1986. Version 1.
Checksum: 2F5F0D61C91305EE

FASTA9811,006
        10         20         30         40         50         60 
MIPGGLSEAK PATPEIQEIV DKVKPQLEEK TNETYGKLEA VQYKTQVVAG TNYYIKVRAG 

        70         80         90 
DNKYMHLKVF KSLPGQNEDL VLTGYQVDKN KDDELTGF 

« Hide

References

« Hide 'large scale' references
[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. expand/collapse author list , 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]Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
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]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[15]"The three-dimensional solution structure of human stefin A."
Martin J.R., Craven C.J., Jerala R., Kroon-Zitko L., Zerovnik E., Turk V., Waltho J.P.
J. Mol. Biol. 246:331-343(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: STRUCTURE BY NMR.
[16]"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.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
CCDSCCDS3011.1.
PIRUDHUS. A29139.
RefSeqNP_005204.1. NM_005213.3.
UniGeneHs.518198.

3D structure databases

PDBe
RCSB-PDB
PDBj
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[»]
ProteinModelPortalP01040.
SMRP01040. Positions 1-98.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid107857. 18 interactions.
IntActP01040. 9 interactions.
MINTMINT-1428155.
STRING9606.ENSP00000264474.

Protein family/group databases

MEROPSI25.001.

PTM databases

PhosphoSiteP01040.

Polymorphism databases

DMDM118177.

Proteomic databases

MaxQBP01040.
PaxDbP01040.
PeptideAtlasP01040.
PRIDEP01040.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000264474; ENSP00000264474; ENSG00000121552.
GeneID1475.
KEGGhsa:1475.
UCSCuc003eex.3. human.

Organism-specific databases

CTD1475.
GeneCardsGC03P122044.
HGNCHGNC:2481. CSTA.
HPACAB000469.
CAB047315.
HPA001031.
MIM184600. gene.
607936. phenotype.
neXtProtNX_P01040.
Orphanet289586. Exfoliative ichthyosis.
PharmGKBPA26983.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG119299.
HOGENOMHOG000294175.
HOVERGENHBG002292.
InParanoidP01040.
KOK13907.
OMAIEYKTQV.
OrthoDBEOG7FR7JX.
PhylomeDBP01040.
TreeFamTF333174.

Gene expression databases

ArrayExpressP01040.
BgeeP01040.
CleanExHS_CSTA.
GenevestigatorP01040.

Family and domain databases

InterProIPR000010. Prot_inh_cystat.
IPR018073. Prot_inh_cystat_CS.
IPR001713. Prot_inh_stefinA.
[Graphical view]
PfamPF00031. Cystatin. 1 hit.
[Graphical view]
PRINTSPR00295. STEFINA.
SMARTSM00043. CY. 1 hit.
[Graphical view]
PROSITEPS00287. CYSTATIN. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceP01040.
GeneWikiCystatin_A.
GenomeRNAi1475.
NextBio6057.
PROP01040.
SOURCESearch...

Entry information

Entry nameCYTA_HUMAN
AccessionPrimary (citable) accession number: P01040
Secondary accession number(s): Q6IB90
Entry history
Integrated into UniProtKB/Swiss-Prot: July 21, 1986
Last sequence update: July 21, 1986
Last modified: July 9, 2014
This is version 156 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 3

Human chromosome 3: entries, gene names and cross-references to MIM