CYTA_HUMAN
ID CYTA_HUMAN Reviewed; 98 AA.
AC P01040; Q6IB90;
DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT 21-JUL-1986, sequence version 1.
DT 03-AUG-2022, entry version 218.
DE RecName: Full=Cystatin-A;
DE AltName: Full=Cystatin-AS;
DE AltName: Full=Stefin-A;
DE Contains:
DE RecName: Full=Cystatin-A, N-terminally processed;
GN Name=CSTA; Synonyms=STF1, STFA;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP PROTEIN SEQUENCE.
RX PubMed=6689312; DOI=10.1515/bchm2.1983.364.2.1481;
RA Machleidt W., Borchart U., Fritz H., Brzin J., Ritonja A., Turk V.;
RT "Protein inhibitors of cysteine proteinases. II. Primary structure of
RT stefin, a cytosolic protein inhibitor of cysteine proteinases from human
RT polymorphonuclear granulocytes.";
RL Hoppe-Seyler's Z. Physiol. Chem. 364:1481-1486(1983).
RN [2]
RP PROTEIN SEQUENCE.
RX PubMed=2768224; DOI=10.1093/oxfordjournals.jbchem.a122792;
RA Takeda A., Kaji H., Nakaya K., Nakmura Y., Samejima T.;
RT "Comparative studies on the primary structure of human cystatin as from
RT epidermis, liver, spleen, and leukocytes.";
RL J. Biochem. 105:986-991(1989).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=2442723; DOI=10.1093/nar/15.15.5945;
RA Kartasova T., Cornelissen B.J.C., Belt P., van de Putte P.;
RT "Effects of UV, 4-NQO and TPA on gene expression in cultured human
RT epidermal keratinocytes.";
RL Nucleic Acids Res. 15:5945-5962(1987).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=9522124; DOI=10.3109/10425179709020888;
RA Yamazaki M., Ishidoh K., Eiki K., Ogawa H.;
RT "Genomic structure of human cystatin A.";
RL DNA Seq. 8:71-76(1997).
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=9651321; DOI=10.1074/jbc.273.28.17375;
RA Takahashi H., Asano K., Kinouchi M., Ishida-Yamamoto A., Wuepper K.D.,
RA Iizuka H.;
RT "Structure and transcriptional regulation of the human cystatin A gene. The
RT 12-o-tetradecanoylphorbol-13-acetate (tpa) responsive element-2 site (-272
RT to -278) on cystatin a gene is critical for tpa-dependent regulation.";
RL J. Biol. Chem. 273:17375-17380(1998).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Tongue;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Bone marrow;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [10]
RP PROTEIN SEQUENCE OF 2-22; 31-56 AND 72-98, CLEAVAGE OF INITIATOR
RP METHIONINE, AND IDENTIFICATION BY MASS SPECTROMETRY.
RC TISSUE=Prostatic carcinoma;
RA Bienvenut W.V., Gao M., Leug H.;
RL Submitted (JUN-2009) to UniProtKB.
RN [11]
RP PROTEIN SEQUENCE OF 72-85.
RC TISSUE=Keratinocyte;
RX PubMed=1940442; DOI=10.1111/1523-1747.ep12484041;
RA Madsen P., Rasmussen H.H., Leffers H., Honore B., Dejgaard K., Olsen E.,
RA Kiil J., Walbum E., Andersen A.H., Basse B., Lauridsen J.B., Ratz G.P.,
RA Celis A., Vandekerckhove J., Celis J.E.;
RT "Molecular cloning, occurrence, and expression of a novel partially
RT secreted protein 'psoriasin' that is highly up-regulated in psoriatic
RT skin.";
RL J. Invest. Dermatol. 97:701-712(1991).
RN [12]
RP PROTEIN SEQUENCE OF 72-85.
RC TISSUE=Keratinocyte;
RX PubMed=1286667; DOI=10.1002/elps.11501301199;
RA Rasmussen H.H., van Damme J., Puype M., Gesser B., Celis J.E.,
RA Vandekerckhove J.;
RT "Microsequences of 145 proteins recorded in the two-dimensional gel protein
RT database of normal human epidermal keratinocytes.";
RL Electrophoresis 13:960-969(1992).
RN [13]
RP FUNCTION, TISSUE SPECIFICITY, SUBCELLULAR LOCATION, AND INVOLVEMENT IN
RP PSS4.
RX PubMed=21944047; DOI=10.1016/j.ajhg.2011.09.001;
RA Blaydon D.C., Nitoiu D., Eckl K.M., Cabral R.M., Bland P., Hausser I.,
RA van Heel D.A., Rajpopat S., Fischer J., Oji V., Zvulunov A., Traupe H.,
RA Hennies H.C., Kelsell D.P.;
RT "Mutations in CSTA, encoding Cystatin A, underlie exfoliative ichthyosis
RT and reveal a role for this protease inhibitor in cell-cell adhesion.";
RL Am. J. Hum. Genet. 89:564-571(2011).
RN [14]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [15]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [16]
RP STRUCTURE BY NMR.
RX PubMed=7869384; DOI=10.1006/jmbi.1994.0088;
RA Martin J.R., Craven C.J., Jerala R., Kroon-Zitko L., Zerovnik E., Turk V.,
RA Waltho J.P.;
RT "The three-dimensional solution structure of human stefin A.";
RL J. Mol. Biol. 246:331-343(1995).
RN [17]
RP STRUCTURE BY NMR.
RX PubMed=7578072; DOI=10.1021/bi00045a004;
RA Tate S., Ushioda T., Utsunomiya-Tate N., Shibuya K., Ohyama Y., Nakano Y.,
RA Kaji H., Inagaki F., Samejima T., Kainosho M.;
RT "Solution structure of a human cystatin A variant, cystatin A2-98 M65L, by
RT NMR spectroscopy. A possible role of the interactions between the N- and C-
RT termini to maintain the inhibitory active form of cystatin A.";
RL Biochemistry 34:14637-14648(1995).
CC -!- FUNCTION: This is an intracellular thiol proteinase inhibitor. Has an
CC important role in desmosome-mediated cell-cell adhesion in the lower
CC levels of the epidermis. {ECO:0000269|PubMed:21944047}.
CC -!- INTERACTION:
CC P01040; G5E9A7: DMWD; NbExp=3; IntAct=EBI-724303, EBI-10976677;
CC P01040; P28799: GRN; NbExp=3; IntAct=EBI-724303, EBI-747754;
CC P01040; P04792: HSPB1; NbExp=3; IntAct=EBI-724303, EBI-352682;
CC P01040; Q9Y3C5: RNF11; NbExp=3; IntAct=EBI-724303, EBI-396669;
CC P01040; Q7Z699: SPRED1; NbExp=3; IntAct=EBI-724303, EBI-5235340;
CC P01040; O76024: WFS1; NbExp=3; IntAct=EBI-724303, EBI-720609;
CC P01040; P00784; Xeno; NbExp=2; IntAct=EBI-724303, EBI-8501709;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:21944047}.
CC -!- TISSUE SPECIFICITY: Expressed in the skin throughout the epidermis.
CC {ECO:0000269|PubMed:21944047}.
CC -!- DISEASE: Peeling skin syndrome 4 (PSS4) [MIM:607936]: A genodermatosis
CC characterized by congenital exfoliative ichthyosis, sharing some
CC features with ichthyosis bullosa of Siemens and annular epidermolytic
CC ichthyosis. PSS4 presents shortly after birth as dry, scaly skin over
CC most of the body with coarse peeling of non-erythematous skin on the
CC palms and soles, which is exacerbated by excessive moisture and minor
CC trauma. Electron microscopy analysis of skin biopsies, reveals mostly
CC normal-appearing upper layers of the epidermis, but prominent
CC intercellular edema of the basal and suprabasal cell layers with
CC aggregates of tonofilaments in the basal keratinocytes.
CC {ECO:0000269|PubMed:21944047}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the cystatin family. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/CSTAID40180ch3q21.html";
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; X05978; CAA29398.1; -; mRNA.
DR EMBL; D88422; BAA13609.1; -; Genomic_DNA.
DR EMBL; AB007774; BAA87858.1; -; Genomic_DNA.
DR EMBL; AK291308; BAF83997.1; -; mRNA.
DR EMBL; CR456914; CAG33195.1; -; mRNA.
DR EMBL; CH471052; EAW79489.1; -; Genomic_DNA.
DR EMBL; BC010379; AAH10379.1; -; mRNA.
DR CCDS; CCDS3011.1; -.
DR PIR; A29139; UDHUS.
DR RefSeq; NP_005204.1; NM_005213.3.
DR PDB; 1CYU; NMR; -; A=1-98.
DR PDB; 1CYV; NMR; -; A=1-98.
DR PDB; 1DVC; NMR; -; A=1-98.
DR PDB; 1DVD; NMR; -; A=1-98.
DR PDB; 1GD3; NMR; -; A=1-98.
DR PDB; 1GD4; NMR; -; A=1-98.
DR PDB; 1N9J; NMR; -; A/B=1-98.
DR PDB; 1NB3; X-ray; 2.80 A; I/J/K/L=1-98.
DR PDB; 1NB5; X-ray; 2.40 A; I/J/K/L=1-98.
DR PDB; 3K9M; X-ray; 2.61 A; C/D=1-98.
DR PDB; 3KFQ; X-ray; 1.99 A; C/D=1-98.
DR PDB; 3KSE; X-ray; 1.71 A; D/E/F=1-98.
DR PDBsum; 1CYU; -.
DR PDBsum; 1CYV; -.
DR PDBsum; 1DVC; -.
DR PDBsum; 1DVD; -.
DR PDBsum; 1GD3; -.
DR PDBsum; 1GD4; -.
DR PDBsum; 1N9J; -.
DR PDBsum; 1NB3; -.
DR PDBsum; 1NB5; -.
DR PDBsum; 3K9M; -.
DR PDBsum; 3KFQ; -.
DR PDBsum; 3KSE; -.
DR AlphaFoldDB; P01040; -.
DR BMRB; P01040; -.
DR SMR; P01040; -.
DR BioGRID; 107857; 130.
DR ComplexPortal; CPX-98; Cathepsin-B - cystatin-A complex.
DR IntAct; P01040; 52.
DR MINT; P01040; -.
DR STRING; 9606.ENSP00000264474; -.
DR MEROPS; I25.001; -.
DR GlyGen; P01040; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; P01040; -.
DR PhosphoSitePlus; P01040; -.
DR BioMuta; CSTA; -.
DR DMDM; 118177; -.
DR EPD; P01040; -.
DR jPOST; P01040; -.
DR MassIVE; P01040; -.
DR PaxDb; P01040; -.
DR PeptideAtlas; P01040; -.
DR PRIDE; P01040; -.
DR ProteomicsDB; 51314; -.
DR TopDownProteomics; P01040; -.
DR Antibodypedia; 608; 555 antibodies from 39 providers.
DR CPTC; P01040; 3 antibodies.
DR DNASU; 1475; -.
DR Ensembl; ENST00000264474.4; ENSP00000264474.3; ENSG00000121552.4.
DR GeneID; 1475; -.
DR KEGG; hsa:1475; -.
DR MANE-Select; ENST00000264474.4; ENSP00000264474.3; NM_005213.4; NP_005204.1.
DR UCSC; uc003eex.4; human.
DR CTD; 1475; -.
DR DisGeNET; 1475; -.
DR GeneCards; CSTA; -.
DR HGNC; HGNC:2481; CSTA.
DR HPA; ENSG00000121552; Tissue enhanced (esophagus, vagina).
DR MalaCards; CSTA; -.
DR MIM; 184600; gene.
DR MIM; 607936; phenotype.
DR neXtProt; NX_P01040; -.
DR OpenTargets; ENSG00000121552; -.
DR Orphanet; 263534; Acral peeling skin syndrome.
DR Orphanet; 289586; Exfoliative ichthyosis.
DR PharmGKB; PA26983; -.
DR VEuPathDB; HostDB:ENSG00000121552; -.
DR eggNOG; ENOG502SF2X; Eukaryota.
DR GeneTree; ENSGT00940000155717; -.
DR HOGENOM; CLU_150234_2_1_1; -.
DR InParanoid; P01040; -.
DR OMA; ICDKMKP; -.
DR OrthoDB; 1647595at2759; -.
DR PhylomeDB; P01040; -.
DR TreeFam; TF333174; -.
DR PathwayCommons; P01040; -.
DR Reactome; R-HSA-6809371; Formation of the cornified envelope.
DR SignaLink; P01040; -.
DR BioGRID-ORCS; 1475; 50 hits in 1007 CRISPR screens.
DR ChiTaRS; CSTA; human.
DR EvolutionaryTrace; P01040; -.
DR GeneWiki; Cystatin_A; -.
DR GenomeRNAi; 1475; -.
DR Pharos; P01040; Tbio.
DR PRO; PR:P01040; -.
DR Proteomes; UP000005640; Chromosome 3.
DR RNAct; P01040; protein.
DR Bgee; ENSG00000121552; Expressed in pharyngeal mucosa and 164 other tissues.
DR ExpressionAtlas; P01040; baseline and differential.
DR Genevisible; P01040; HS.
DR GO; GO:0001533; C:cornified envelope; IDA:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0005615; C:extracellular space; IDA:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:1904090; C:peptidase inhibitor complex; IPI:ComplexPortal.
DR GO; GO:0004869; F:cysteine-type endopeptidase inhibitor activity; IDA:UniProtKB.
DR GO; GO:0002020; F:protease binding; IPI:BHF-UCL.
DR GO; GO:0098609; P:cell-cell adhesion; IMP:UniProtKB.
DR GO; GO:0030216; P:keratinocyte differentiation; IDA:UniProtKB.
DR GO; GO:0010466; P:negative regulation of peptidase activity; IDA:BHF-UCL.
DR GO; GO:0045861; P:negative regulation of proteolysis; IDA:UniProtKB.
DR GO; GO:0018149; P:peptide cross-linking; IDA:UniProtKB.
DR CDD; cd00042; CY; 1.
DR InterPro; IPR000010; Cystatin_dom.
DR InterPro; IPR046350; Cystatin_sf.
DR InterPro; IPR018073; Prot_inh_cystat_CS.
DR InterPro; IPR001713; Prot_inh_stefin.
DR PANTHER; PTHR11414; PTHR11414; 1.
DR Pfam; PF00031; Cystatin; 1.
DR PRINTS; PR00295; STEFINA.
DR SMART; SM00043; CY; 1.
DR SUPFAM; SSF54403; SSF54403; 1.
DR PROSITE; PS00287; CYSTATIN; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Cell adhesion; Cytoplasm;
KW Direct protein sequencing; Ichthyosis; Protease inhibitor;
KW Reference proteome; Thiol protease inhibitor.
FT CHAIN 1..98
FT /note="Cystatin-A"
FT /id="PRO_0000423202"
FT INIT_MET 1
FT /note="Removed; alternate"
FT /evidence="ECO:0000269|Ref.10"
FT CHAIN 2..98
FT /note="Cystatin-A, N-terminally processed"
FT /id="PRO_0000207128"
FT MOTIF 46..50
FT /note="Secondary area of contact"
FT SITE 4
FT /note="Reactive site"
FT MOD_RES 1
FT /note="N-acetylmethionine"
FT /evidence="ECO:0000250|UniProtKB:P01039"
FT VARIANT 96
FT /note="T -> M (in dbSNP:rs34173813)"
FT /id="VAR_048851"
FT STRAND 7..12
FT /evidence="ECO:0007829|PDB:1CYU"
FT HELIX 14..31
FT /evidence="ECO:0007829|PDB:3KSE"
FT STRAND 34..36
FT /evidence="ECO:0007829|PDB:1CYU"
FT STRAND 39..58
FT /evidence="ECO:0007829|PDB:3KSE"
FT HELIX 60..62
FT /evidence="ECO:0007829|PDB:3KSE"
FT STRAND 64..71
FT /evidence="ECO:0007829|PDB:3KSE"
FT HELIX 74..76
FT /evidence="ECO:0007829|PDB:3KSE"
FT HELIX 77..79
FT /evidence="ECO:0007829|PDB:1N9J"
FT STRAND 80..89
FT /evidence="ECO:0007829|PDB:3KSE"
FT STRAND 91..93
FT /evidence="ECO:0007829|PDB:1DVC"
SQ SEQUENCE 98 AA; 11006 MW; 2F5F0D61C91305EE CRC64;
MIPGGLSEAK PATPEIQEIV DKVKPQLEEK TNETYGKLEA VQYKTQVVAG TNYYIKVRAG
DNKYMHLKVF KSLPGQNEDL VLTGYQVDKN KDDELTGF
