Full text data of CSTA
CSTA
(STF1, STFA)
[Confidence: low (only semi-automatic identification from reviews)]
Cystatin-A (Cystatin-AS; Stefin-A; Cystatin-A, N-terminally processed)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
Cystatin-A (Cystatin-AS; Stefin-A; Cystatin-A, N-terminally processed)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
UniProt
P01040
ID CYTA_HUMAN Reviewed; 98 AA.
AC P01040;
DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
read moreDT 21-JUL-1986, sequence version 1.
DT 22-JAN-2014, entry version 150.
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;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP PROTEIN SEQUENCE.
RX PubMed=6689312;
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
RT human polymorphonuclear granulocytes.";
RL Hoppe-Seyler's Z. Physiol. Chem. 364:1481-1486(1983).
RN [2]
RP PROTEIN SEQUENCE.
RX PubMed=2768224;
RA Takeda A., Kaji H., Nakaya K., Nakmura Y., Samejima T.;
RT "Comparative studies on the primary structure of human cystatin as
RT from 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;
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
RT gene. The 12-o-tetradecanoylphorbol-13-acetate (tpa) responsive
RT element-2 site (-272 to -278) on cystatin a gene is critical for tpa-
RT dependent regulation.";
RL J. Biol. Chem. 273:17375-17380(1998).
RN [6]
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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [7]
RP PROTEIN SEQUENCE OF 2-22; 31-56 AND 72-98, CLEAVAGE OF INITIATOR
RP METHIONINE, LACK OF N-TERMINAL ACETYLATION, AND MASS SPECTROMETRY.
RC TISSUE=Prostatic carcinoma;
RA Bienvenut W.V., Gao M., Leug H.;
RL Submitted (JUN-2009) to UniProtKB.
RN [8]
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.,
RA Olsen E., Kiil J., Walbum E., Andersen A.H., Basse B., Lauridsen J.B.,
RA Ratz G.P., 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 [9]
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
RT protein database of normal human epidermal keratinocytes.";
RL Electrophoresis 13:960-969(1992).
RN [10]
RP FUNCTION, TISSUE SPECIFICITY, SUBCELLULAR LOCATION, AND INVOLVEMENT IN
RP AREI.
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.,
RA Traupe H., Hennies H.C., Kelsell D.P.;
RT "Mutations in CSTA, encoding Cystatin A, underlie exfoliative
RT ichthyosis and reveal a role for this protease inhibitor in cell-cell
RT adhesion.";
RL Am. J. Hum. Genet. 89:564-571(2011).
RN [11]
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.,
RA Buerckstuemmer T., 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 [12]
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.,
RA Turk V., Waltho J.P.;
RT "The three-dimensional solution structure of human stefin A.";
RL J. Mol. Biol. 246:331-343(1995).
RN [13]
RP STRUCTURE BY NMR.
RX PubMed=7578072; DOI=10.1021/bi00045a004;
RA Tate S., Ushioda T., Utsunomiya-Tate N., Shibuya K., Ohyama Y.,
RA Nakano Y., Kaji H., Inagaki F., Samejima T., Kainosho M.;
RT "Solution structure of a human cystatin A variant, cystatin A2-98
RT M65L, by NMR spectroscopy. A possible role of the interactions between
RT the N- and C-termini to maintain the inhibitory active form of
RT cystatin A.";
RL Biochemistry 34:14637-14648(1995).
CC -!- FUNCTION: This is an intracellular thiol proteinase inhibitor. Has
CC an important role in desmosome-mediated cell-cell adhesion in the
CC lower levels of the epidermis.
CC -!- SUBCELLULAR LOCATION: Cytoplasm.
CC -!- TISSUE SPECIFICITY: Expressed in the skin throughout the
CC epidermis.
CC -!- DISEASE: Ichthyosis, exfoliative, autosomal recessive, ichthyosis
CC bullosa of Siemens-like (AREI) [MIM:607936]: A form of congenital
CC exfoliative ichthyosis, sharing some features with ichthyosis
CC bullosa of Siemens and annular epidermolytic ichthyosis. AREI
CC presents shortly after birth as dry, scaly skin over most of the
CC body with coarse peeling of non-erythematous skin on the palms and
CC soles, which is exacerbated by excessive moisture and minor
CC trauma. Electron microscopy analysis of skin biopsies, reveals
CC mostly normal-appearing upper layers of the epidermis, but
CC prominent intercellular edema of the basal and suprabasal cell
CC layers with aggregates of tonofilaments in the basal
CC keratinocytes. Note=The disease is caused by mutations affecting
CC the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the cystatin family.
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology
CC and Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/CSTAID40180ch3q21.html";
CC -----------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution-NoDerivs License
CC -----------------------------------------------------------------------
DR EMBL; X05978; CAA29398.1; -; mRNA.
DR EMBL; D88422; BAA13609.1; -; Genomic_DNA.
DR EMBL; AB007774; BAA87858.1; -; Genomic_DNA.
DR EMBL; BC010379; AAH10379.1; -; mRNA.
DR PIR; A29139; UDHUS.
DR RefSeq; NP_005204.1; NM_005213.3.
DR UniGene; Hs.518198; -.
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 ProteinModelPortal; P01040; -.
DR SMR; P01040; 1-98.
DR IntAct; P01040; 6.
DR MINT; MINT-1428155; -.
DR STRING; 9606.ENSP00000264474; -.
DR MEROPS; I25.001; -.
DR PhosphoSite; P01040; -.
DR DMDM; 118177; -.
DR PaxDb; P01040; -.
DR PeptideAtlas; P01040; -.
DR PRIDE; P01040; -.
DR Ensembl; ENST00000264474; ENSP00000264474; ENSG00000121552.
DR GeneID; 1475; -.
DR KEGG; hsa:1475; -.
DR UCSC; uc003eex.3; human.
DR CTD; 1475; -.
DR GeneCards; GC03P122044; -.
DR HGNC; HGNC:2481; CSTA.
DR HPA; CAB000469; -.
DR HPA; CAB047315; -.
DR HPA; HPA001031; -.
DR MIM; 184600; gene.
DR MIM; 607936; phenotype.
DR neXtProt; NX_P01040; -.
DR Orphanet; 289586; Exfoliative ichthyosis.
DR PharmGKB; PA26983; -.
DR eggNOG; NOG119299; -.
DR HOGENOM; HOG000294175; -.
DR HOVERGEN; HBG002292; -.
DR InParanoid; P01040; -.
DR KO; K13907; -.
DR OMA; YEKLEAV; -.
DR OrthoDB; EOG7FR7JX; -.
DR PhylomeDB; P01040; -.
DR EvolutionaryTrace; P01040; -.
DR GeneWiki; Cystatin_A; -.
DR GenomeRNAi; 1475; -.
DR NextBio; 6057; -.
DR PRO; PR:P01040; -.
DR ArrayExpress; P01040; -.
DR Bgee; P01040; -.
DR CleanEx; HS_CSTA; -.
DR Genevestigator; P01040; -.
DR GO; GO:0001533; C:cornified envelope; IDA:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005634; C:nucleus; IDA:HPA.
DR GO; GO:0004869; F:cysteine-type endopeptidase inhibitor activity; IDA:BHF-UCL.
DR GO; GO:0030674; F:protein binding, bridging; IDA:UniProtKB.
DR GO; GO:0005198; F:structural molecule activity; IDA:UniProtKB.
DR GO; GO:0016337; P:cell-cell adhesion; IMP:UniProtKB.
DR GO; GO:0030216; P:keratinocyte differentiation; IDA:UniProtKB.
DR GO; GO:0018149; P:peptide cross-linking; IDA:UniProtKB.
DR InterPro; IPR000010; Prot_inh_cystat.
DR InterPro; IPR018073; Prot_inh_cystat_CS.
DR InterPro; IPR001713; Prot_inh_stefinA.
DR Pfam; PF00031; Cystatin; 1.
DR PRINTS; PR00295; STEFINA.
DR SMART; SM00043; CY; 1.
DR PROSITE; PS00287; CYSTATIN; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Cell adhesion; Complete proteome;
KW Cytoplasm; Direct protein sequencing; Ichthyosis; Polymorphism;
KW Protease inhibitor; Reference proteome; Thiol protease inhibitor.
FT CHAIN 1 98 Cystatin-A.
FT /FTId=PRO_0000423202.
FT INIT_MET 1 1 Removed; alternate.
FT CHAIN 2 98 Cystatin-A, N-terminally processed.
FT /FTId=PRO_0000207128.
FT MOTIF 46 50 Secondary area of contact.
FT SITE 2 2 Not acetylated.
FT SITE 4 4 Reactive site.
FT MOD_RES 1 1 N-acetylmethionine (By similarity).
FT VARIANT 96 96 T -> M (in dbSNP:rs34173813).
FT /FTId=VAR_048851.
FT STRAND 7 12
FT HELIX 14 31
FT STRAND 34 36
FT STRAND 39 58
FT HELIX 60 62
FT STRAND 64 71
FT HELIX 74 76
FT HELIX 77 79
FT STRAND 80 89
FT STRAND 91 93
SQ SEQUENCE 98 AA; 11006 MW; 2F5F0D61C91305EE CRC64;
MIPGGLSEAK PATPEIQEIV DKVKPQLEEK TNETYGKLEA VQYKTQVVAG TNYYIKVRAG
DNKYMHLKVF KSLPGQNEDL VLTGYQVDKN KDDELTGF
//
ID CYTA_HUMAN Reviewed; 98 AA.
AC P01040;
DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
read moreDT 21-JUL-1986, sequence version 1.
DT 22-JAN-2014, entry version 150.
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;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP PROTEIN SEQUENCE.
RX PubMed=6689312;
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
RT human polymorphonuclear granulocytes.";
RL Hoppe-Seyler's Z. Physiol. Chem. 364:1481-1486(1983).
RN [2]
RP PROTEIN SEQUENCE.
RX PubMed=2768224;
RA Takeda A., Kaji H., Nakaya K., Nakmura Y., Samejima T.;
RT "Comparative studies on the primary structure of human cystatin as
RT from 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;
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
RT gene. The 12-o-tetradecanoylphorbol-13-acetate (tpa) responsive
RT element-2 site (-272 to -278) on cystatin a gene is critical for tpa-
RT dependent regulation.";
RL J. Biol. Chem. 273:17375-17380(1998).
RN [6]
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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [7]
RP PROTEIN SEQUENCE OF 2-22; 31-56 AND 72-98, CLEAVAGE OF INITIATOR
RP METHIONINE, LACK OF N-TERMINAL ACETYLATION, AND MASS SPECTROMETRY.
RC TISSUE=Prostatic carcinoma;
RA Bienvenut W.V., Gao M., Leug H.;
RL Submitted (JUN-2009) to UniProtKB.
RN [8]
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.,
RA Olsen E., Kiil J., Walbum E., Andersen A.H., Basse B., Lauridsen J.B.,
RA Ratz G.P., 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 [9]
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
RT protein database of normal human epidermal keratinocytes.";
RL Electrophoresis 13:960-969(1992).
RN [10]
RP FUNCTION, TISSUE SPECIFICITY, SUBCELLULAR LOCATION, AND INVOLVEMENT IN
RP AREI.
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.,
RA Traupe H., Hennies H.C., Kelsell D.P.;
RT "Mutations in CSTA, encoding Cystatin A, underlie exfoliative
RT ichthyosis and reveal a role for this protease inhibitor in cell-cell
RT adhesion.";
RL Am. J. Hum. Genet. 89:564-571(2011).
RN [11]
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.,
RA Buerckstuemmer T., 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 [12]
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.,
RA Turk V., Waltho J.P.;
RT "The three-dimensional solution structure of human stefin A.";
RL J. Mol. Biol. 246:331-343(1995).
RN [13]
RP STRUCTURE BY NMR.
RX PubMed=7578072; DOI=10.1021/bi00045a004;
RA Tate S., Ushioda T., Utsunomiya-Tate N., Shibuya K., Ohyama Y.,
RA Nakano Y., Kaji H., Inagaki F., Samejima T., Kainosho M.;
RT "Solution structure of a human cystatin A variant, cystatin A2-98
RT M65L, by NMR spectroscopy. A possible role of the interactions between
RT the N- and C-termini to maintain the inhibitory active form of
RT cystatin A.";
RL Biochemistry 34:14637-14648(1995).
CC -!- FUNCTION: This is an intracellular thiol proteinase inhibitor. Has
CC an important role in desmosome-mediated cell-cell adhesion in the
CC lower levels of the epidermis.
CC -!- SUBCELLULAR LOCATION: Cytoplasm.
CC -!- TISSUE SPECIFICITY: Expressed in the skin throughout the
CC epidermis.
CC -!- DISEASE: Ichthyosis, exfoliative, autosomal recessive, ichthyosis
CC bullosa of Siemens-like (AREI) [MIM:607936]: A form of congenital
CC exfoliative ichthyosis, sharing some features with ichthyosis
CC bullosa of Siemens and annular epidermolytic ichthyosis. AREI
CC presents shortly after birth as dry, scaly skin over most of the
CC body with coarse peeling of non-erythematous skin on the palms and
CC soles, which is exacerbated by excessive moisture and minor
CC trauma. Electron microscopy analysis of skin biopsies, reveals
CC mostly normal-appearing upper layers of the epidermis, but
CC prominent intercellular edema of the basal and suprabasal cell
CC layers with aggregates of tonofilaments in the basal
CC keratinocytes. Note=The disease is caused by mutations affecting
CC the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the cystatin family.
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology
CC and Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/CSTAID40180ch3q21.html";
CC -----------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution-NoDerivs License
CC -----------------------------------------------------------------------
DR EMBL; X05978; CAA29398.1; -; mRNA.
DR EMBL; D88422; BAA13609.1; -; Genomic_DNA.
DR EMBL; AB007774; BAA87858.1; -; Genomic_DNA.
DR EMBL; BC010379; AAH10379.1; -; mRNA.
DR PIR; A29139; UDHUS.
DR RefSeq; NP_005204.1; NM_005213.3.
DR UniGene; Hs.518198; -.
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 ProteinModelPortal; P01040; -.
DR SMR; P01040; 1-98.
DR IntAct; P01040; 6.
DR MINT; MINT-1428155; -.
DR STRING; 9606.ENSP00000264474; -.
DR MEROPS; I25.001; -.
DR PhosphoSite; P01040; -.
DR DMDM; 118177; -.
DR PaxDb; P01040; -.
DR PeptideAtlas; P01040; -.
DR PRIDE; P01040; -.
DR Ensembl; ENST00000264474; ENSP00000264474; ENSG00000121552.
DR GeneID; 1475; -.
DR KEGG; hsa:1475; -.
DR UCSC; uc003eex.3; human.
DR CTD; 1475; -.
DR GeneCards; GC03P122044; -.
DR HGNC; HGNC:2481; CSTA.
DR HPA; CAB000469; -.
DR HPA; CAB047315; -.
DR HPA; HPA001031; -.
DR MIM; 184600; gene.
DR MIM; 607936; phenotype.
DR neXtProt; NX_P01040; -.
DR Orphanet; 289586; Exfoliative ichthyosis.
DR PharmGKB; PA26983; -.
DR eggNOG; NOG119299; -.
DR HOGENOM; HOG000294175; -.
DR HOVERGEN; HBG002292; -.
DR InParanoid; P01040; -.
DR KO; K13907; -.
DR OMA; YEKLEAV; -.
DR OrthoDB; EOG7FR7JX; -.
DR PhylomeDB; P01040; -.
DR EvolutionaryTrace; P01040; -.
DR GeneWiki; Cystatin_A; -.
DR GenomeRNAi; 1475; -.
DR NextBio; 6057; -.
DR PRO; PR:P01040; -.
DR ArrayExpress; P01040; -.
DR Bgee; P01040; -.
DR CleanEx; HS_CSTA; -.
DR Genevestigator; P01040; -.
DR GO; GO:0001533; C:cornified envelope; IDA:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005634; C:nucleus; IDA:HPA.
DR GO; GO:0004869; F:cysteine-type endopeptidase inhibitor activity; IDA:BHF-UCL.
DR GO; GO:0030674; F:protein binding, bridging; IDA:UniProtKB.
DR GO; GO:0005198; F:structural molecule activity; IDA:UniProtKB.
DR GO; GO:0016337; P:cell-cell adhesion; IMP:UniProtKB.
DR GO; GO:0030216; P:keratinocyte differentiation; IDA:UniProtKB.
DR GO; GO:0018149; P:peptide cross-linking; IDA:UniProtKB.
DR InterPro; IPR000010; Prot_inh_cystat.
DR InterPro; IPR018073; Prot_inh_cystat_CS.
DR InterPro; IPR001713; Prot_inh_stefinA.
DR Pfam; PF00031; Cystatin; 1.
DR PRINTS; PR00295; STEFINA.
DR SMART; SM00043; CY; 1.
DR PROSITE; PS00287; CYSTATIN; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Cell adhesion; Complete proteome;
KW Cytoplasm; Direct protein sequencing; Ichthyosis; Polymorphism;
KW Protease inhibitor; Reference proteome; Thiol protease inhibitor.
FT CHAIN 1 98 Cystatin-A.
FT /FTId=PRO_0000423202.
FT INIT_MET 1 1 Removed; alternate.
FT CHAIN 2 98 Cystatin-A, N-terminally processed.
FT /FTId=PRO_0000207128.
FT MOTIF 46 50 Secondary area of contact.
FT SITE 2 2 Not acetylated.
FT SITE 4 4 Reactive site.
FT MOD_RES 1 1 N-acetylmethionine (By similarity).
FT VARIANT 96 96 T -> M (in dbSNP:rs34173813).
FT /FTId=VAR_048851.
FT STRAND 7 12
FT HELIX 14 31
FT STRAND 34 36
FT STRAND 39 58
FT HELIX 60 62
FT STRAND 64 71
FT HELIX 74 76
FT HELIX 77 79
FT STRAND 80 89
FT STRAND 91 93
SQ SEQUENCE 98 AA; 11006 MW; 2F5F0D61C91305EE CRC64;
MIPGGLSEAK PATPEIQEIV DKVKPQLEEK TNETYGKLEA VQYKTQVVAG TNYYIKVRAG
DNKYMHLKVF KSLPGQNEDL VLTGYQVDKN KDDELTGF
//
MIM
184600
*RECORD*
*FIELD* NO
184600
*FIELD* TI
*184600 CYSTATIN A; CSTA
;;STEFIN A; STFA;;
STF1
*FIELD* TX
DESCRIPTION
Cystatin A is a cysteine proteinase inhibitor that belongs to family 1
read moreof the cystatin superfamily. It was originally derived from the cytosol
of human polymorphonuclear granulocytes (Strauss et al., 1988) but has
also been isolated from the spleen, liver, and epidermis. Cystatin A is
identical to keratolinin, one of the precursor proteins of the cornified
cell envelope of keratinocytes (Takahashi et al., 1998).
CLONING
Strauss et al. (1988) isolated a DNA containing the coding sequence for
human stefin A by enzymic ligation of chemically synthesized
deoxyoligonucleotides, using the Khorana ligation method. The deduced
98-residue protein has a molecular mass of 11 kDa. It forms tight
complexes with papain and the cathepsins B, H, and L. Expression in E.
coli resulted in secretion of a protein exhibiting biologic properties
similar to those of the native protein isolated from human plasma.
By immunostaining normal skin sections, Blaydon et al. (2011)
demonstrated localization of cystatin A throughout all suprabasal layers
of the epidermis with a diffuse cytoplasmic distribution and the
strongest synthesis in the granular layer.
GENE STRUCTURE
Takahashi et al. (1998) determined that the CSTA gene contains 3 exons.
MAPPING
Hsieh et al. (1991) used PCR to amplify the human stefin A sequence in a
panel of rodent-human somatic cell hybrid DNAs. They identified STF1
sequences on chromosome 3. Sublocalization to human 3q21 was
accomplished using a deletion mapping panel for human chromosome 3.
GENE FAMILY
Tsui et al. (1993) studied 3 members of the murine stefin gene family.
Southern analysis suggested that the family comprises at least 6 and
possibly 10 to 20 members, all of which appear to be clustered in the
proximal region of mouse chromosome 16 in an area of conserved homology
of synteny with human chromosome 3q.
GENE FUNCTION
Takahashi et al. (1992) demonstrated that phosphorylated cystatin A is a
component of the cornified envelope proteins in newborn rat skin.
Incubation of both phosphorylated cystatin A and nonphosphorylated
cystatin A with epidermal transglutaminase (TGM1; 190195) resulted in
production of polymerized proteins formed by crosslinking peptide bonds
between lysine residues of cystatin A and glutamine residues of the
substrate protein. Inhibition of protein kinase C inhibited
incorporation of cystatin A into keratohyaline granules, indicating that
phosphorylation of cystatin A is necessary to target the polymerized
protein to the cornified envelope.
Blaydon et al. (2011) knocked down cystatin A in the HaCaT human
keratinocyte cell line and studied the effects of mechanical stress on
these cells. Upon intense stretching, thickening of keratin filaments
was observed in both knockdown and control cells; however, in the
knockdown cells, the monolayer of cells split into many fragments,
whereas the monolayer was intact in control cells. At higher
magnification, breakage of keratin filaments and widened intercellular
spaces could be seen in the CSTA knockdown cells. In contrast, there
were no obvious cell-cell adhesion defects in the stretched control cell
monolayer. Knockdown cell monolayers subjected to agitation by inversion
showed a high increase in the number of fragments, compared to the very
few fragments obtained for the control monolayers. In an organotypic 3D
culture model, Blaydon et al. (2011) demonstrated that there is no gross
barrier defect associated with CSTA knockdown. Blaydon et al. (2011)
concluded that cystatin A plays an important role in desmosome-mediated
cell-cell adhesion in the lower levels of the epidermis.
MOLECULAR GENETICS
- Autosomal Recessive Ichthyosis Bullosa of Siemens-Like Exfoliative
Ichthyosis
In a consanguineous Bedouin kindred with autosomal recessive exfoliative
ichthyosis mapping to chromosome 3q21 (607936), Blaydon et al. (2011)
identified homozygosity for a splice site mutation in the candidate gene
CSTA (184600.0001) that segregated with disease in the family and was
not detected in 300 control chromosomes. In affected members of a
Turkish family with a very similar phenotype of exfoliative ichthyosis,
Blaydon et al. (2011) identified homozygosity for a nonsense mutation in
CSTA (184600.0002).
- Association with Psoriasis
Samuelsson et al. (2004) found no association between 2 SNPs in the CSTA
gene and psoriasis among 11 Swedish patients with the disorder from
families showing linkage to chromosome 3q21 (PSORS5; 604316).
Among 107 unrelated patients with psoriasis and 216 controls,
Vasilopoulos et al. (2008) observed an association between a synonymous
162T-C SNP in the CSTA gene and disease (OR = 3.45, p = 0.001). Analysis
of a 3-SNP haplotype showed a significant association between psoriasis
and CSTA -190T/+162C/+344C (CSTA TCC; p = 10(-6)). An independent study
of 126 families with psoriasis confirmed overtransmission of the TCC
haplotype (p = 0.0001). However, the TCC haplotype was only associated
with psoriasis in individuals carrying the risk allele at the HLA-Cw6
locus (142840.0001) (OR = 2.23, p = 0.0002). The findings suggested an
interaction between PSORS5 and PSORS1 (177900).
- Association with Atopic Dermatitis
Among 100 patients with atopic dermatitis (ATOD1; 603165) and 264
controls, Vasilopoulos et al. (2007) observed an association between
risk for ATOD and a 344C-T SNP in the CSTA gene (OR = 2.13, p = 0.006).
The C allele was more common among patients, indicating that the T
allele may offer a protective effect. In vitro functional expression
studies showed that the 344C allele produced mRNA that was 2.2-fold less
stable than the 344T mRNA. Vasilopoulos et al. (2007) noted that since
CSTA is a cysteine protease inhibitor of dust mite proteases that breaks
down epidermal barriers, a decrease in CSTA mRNA may contribute to a
defective epidermal barrier among patients with atopic dermatitis.
*FIELD* AV
.0001
EXFOLIATIVE ICHTHYOSIS, AUTOSOMAL RECESSIVE, ICHTHYOSIS BULLOSA OF
SIEMENS-LIKE
CSTA, IVS1, A-T, -2
In affected members of a consanguineous Bedouin kindred with ichthyosis
bullosa of Siemens-like exfoliative ichthyosis (607936), Blaydon et al.
(2011) identified homozygosity for an A-to-T transversion in intron 1
(67-2A-T) of the CSTA gene. The mutation segregated with disease in the
family and was not found in 300 control chromosomes.
.0002
EXFOLIATIVE ICHTHYOSIS, AUTOSOMAL RECESSIVE, ICHTHYOSIS BULLOSA OF
SIEMENS-LIKE
CSTA, GLN86TER
In affected members of a Turkish family with ichthyosis bullosa of
Siemens-like exfoliative ichthyosis (607936), Blaydon et al. (2011)
identified homozygosity for a 256C-T transition in the CSTA gene,
resulting in a gln86-to-ter (Q86X) substitution at a highly conserved
residue within the conserved cystatin domain.
*FIELD* RF
1. 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.: Mutations
in CSTA, encoding cystatin A, underlie exfoliative ichthyosis and
reveal a role for this protease inhibitor in cell-cell adhesion. Am.
J. Hum. Genet. 89: 564-571, 2011.
2. Hsieh, W.-T.; Fong, D.; Sloane, B. F.; Golembieski, W.; Smith,
D. I.: Mapping of the gene for human cysteine proteinase inhibitor
stefin A, STF1, to chromosome 3cen-q21. Genomics 9: 207-209, 1991.
3. Samuelsson, L.; Stiller, C.; Friberg, C.; Nilsson, C.; Inerot,
A.; Wahlstrom, J.: Association analysis of cystatin A and zinc finger
protein 148, two genes located at the psoriasis susceptibility locus
PSORS5. J. Invest. Derm. 122: 1399-1400, 2004.
4. Strauss, M.; Stollwerk, J.; Lenarcic, B.; Turk, V.; Jany, K.-D.;
Gassen, H. G.: Chemical synthesis of a gene for human stefin A and
its expression in E. coli. Biol. Chem. Hoppe Seyler 369: 1019-1030,
1988.
5. Takahashi, H.; Asano, K.; Kinouchi, M.; Ishida-Yamamoto, A.; Wueppers,
K. D.; Iizuka, H.: 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. J. Biol. Chem. 273: 17375-17380, 1998.
6. Takahashi, M.; Tezuka, T.; Katunuma, N.: Phosphorylated cystatin-alpha
is a natural substrate of epidermal transglutaminase for formation
of skin cornified envelope. FEBS Lett. 308: 79-82, 1992.
7. Tsui, F. W. L.; Tsui, H.-W.; Mok, S.; Mlinaric, I.; Copeland, N.
G.; Gilbert, D. J.; Jenkins, N. A.; Siminovitch, K. A.: Molecular
characterization and mapping of murine genes encoding three members
of the stefin family of cysteine proteinase inhibitors. Genomics 15:
507-514, 1993.
8. Vasilopoulos, Y.; Cork, M. J.; Teare, D.; Marinou, I.; Ward, S.
J.; Duff, G. W.; Tazi-Ahnini, R.: A nonsynonymous substitution of
cystatin A, a cysteine protease inhibitor of house dust mite protease,
leads to decreased mRNA stability and shows a significant association
with atopic dermatitis. Allergy 62: 514-519, 2007.
9. Vasilopoulos, Y.; Walters, J.; Cork, M. J.; Duff, G. W.; Sagoo,
G. S.; Tazi-Ahnini, R.: Association analysis of the skin barrier
gene cystatin A at the PSORS5 locus in psoriatic patients: evidence
for interaction between PSORS1 and PSORS5. Europ. J. Hum. Genet. 16:
1002-1009, 2008.
*FIELD* CN
Marla J. F. O'Neill - updated: 10/28/2011
Cassandra L. Kniffin - updated: 10/23/2008
Cassandra L. Kniffin - updated: 8/20/2008
*FIELD* CD
Victor A. McKusick: 7/11/1990
*FIELD* ED
carol: 05/25/2012
alopez: 11/2/2011
terry: 10/28/2011
terry: 9/17/2010
wwang: 10/24/2008
ckniffin: 10/23/2008
wwang: 8/29/2008
ckniffin: 8/20/2008
carol: 8/18/1998
mark: 3/31/1997
mark: 11/27/1996
carol: 4/30/1993
carol: 3/19/1993
carol: 3/9/1993
supermim: 3/16/1992
carol: 1/16/1991
carol: 9/21/1990
*RECORD*
*FIELD* NO
184600
*FIELD* TI
*184600 CYSTATIN A; CSTA
;;STEFIN A; STFA;;
STF1
*FIELD* TX
DESCRIPTION
Cystatin A is a cysteine proteinase inhibitor that belongs to family 1
read moreof the cystatin superfamily. It was originally derived from the cytosol
of human polymorphonuclear granulocytes (Strauss et al., 1988) but has
also been isolated from the spleen, liver, and epidermis. Cystatin A is
identical to keratolinin, one of the precursor proteins of the cornified
cell envelope of keratinocytes (Takahashi et al., 1998).
CLONING
Strauss et al. (1988) isolated a DNA containing the coding sequence for
human stefin A by enzymic ligation of chemically synthesized
deoxyoligonucleotides, using the Khorana ligation method. The deduced
98-residue protein has a molecular mass of 11 kDa. It forms tight
complexes with papain and the cathepsins B, H, and L. Expression in E.
coli resulted in secretion of a protein exhibiting biologic properties
similar to those of the native protein isolated from human plasma.
By immunostaining normal skin sections, Blaydon et al. (2011)
demonstrated localization of cystatin A throughout all suprabasal layers
of the epidermis with a diffuse cytoplasmic distribution and the
strongest synthesis in the granular layer.
GENE STRUCTURE
Takahashi et al. (1998) determined that the CSTA gene contains 3 exons.
MAPPING
Hsieh et al. (1991) used PCR to amplify the human stefin A sequence in a
panel of rodent-human somatic cell hybrid DNAs. They identified STF1
sequences on chromosome 3. Sublocalization to human 3q21 was
accomplished using a deletion mapping panel for human chromosome 3.
GENE FAMILY
Tsui et al. (1993) studied 3 members of the murine stefin gene family.
Southern analysis suggested that the family comprises at least 6 and
possibly 10 to 20 members, all of which appear to be clustered in the
proximal region of mouse chromosome 16 in an area of conserved homology
of synteny with human chromosome 3q.
GENE FUNCTION
Takahashi et al. (1992) demonstrated that phosphorylated cystatin A is a
component of the cornified envelope proteins in newborn rat skin.
Incubation of both phosphorylated cystatin A and nonphosphorylated
cystatin A with epidermal transglutaminase (TGM1; 190195) resulted in
production of polymerized proteins formed by crosslinking peptide bonds
between lysine residues of cystatin A and glutamine residues of the
substrate protein. Inhibition of protein kinase C inhibited
incorporation of cystatin A into keratohyaline granules, indicating that
phosphorylation of cystatin A is necessary to target the polymerized
protein to the cornified envelope.
Blaydon et al. (2011) knocked down cystatin A in the HaCaT human
keratinocyte cell line and studied the effects of mechanical stress on
these cells. Upon intense stretching, thickening of keratin filaments
was observed in both knockdown and control cells; however, in the
knockdown cells, the monolayer of cells split into many fragments,
whereas the monolayer was intact in control cells. At higher
magnification, breakage of keratin filaments and widened intercellular
spaces could be seen in the CSTA knockdown cells. In contrast, there
were no obvious cell-cell adhesion defects in the stretched control cell
monolayer. Knockdown cell monolayers subjected to agitation by inversion
showed a high increase in the number of fragments, compared to the very
few fragments obtained for the control monolayers. In an organotypic 3D
culture model, Blaydon et al. (2011) demonstrated that there is no gross
barrier defect associated with CSTA knockdown. Blaydon et al. (2011)
concluded that cystatin A plays an important role in desmosome-mediated
cell-cell adhesion in the lower levels of the epidermis.
MOLECULAR GENETICS
- Autosomal Recessive Ichthyosis Bullosa of Siemens-Like Exfoliative
Ichthyosis
In a consanguineous Bedouin kindred with autosomal recessive exfoliative
ichthyosis mapping to chromosome 3q21 (607936), Blaydon et al. (2011)
identified homozygosity for a splice site mutation in the candidate gene
CSTA (184600.0001) that segregated with disease in the family and was
not detected in 300 control chromosomes. In affected members of a
Turkish family with a very similar phenotype of exfoliative ichthyosis,
Blaydon et al. (2011) identified homozygosity for a nonsense mutation in
CSTA (184600.0002).
- Association with Psoriasis
Samuelsson et al. (2004) found no association between 2 SNPs in the CSTA
gene and psoriasis among 11 Swedish patients with the disorder from
families showing linkage to chromosome 3q21 (PSORS5; 604316).
Among 107 unrelated patients with psoriasis and 216 controls,
Vasilopoulos et al. (2008) observed an association between a synonymous
162T-C SNP in the CSTA gene and disease (OR = 3.45, p = 0.001). Analysis
of a 3-SNP haplotype showed a significant association between psoriasis
and CSTA -190T/+162C/+344C (CSTA TCC; p = 10(-6)). An independent study
of 126 families with psoriasis confirmed overtransmission of the TCC
haplotype (p = 0.0001). However, the TCC haplotype was only associated
with psoriasis in individuals carrying the risk allele at the HLA-Cw6
locus (142840.0001) (OR = 2.23, p = 0.0002). The findings suggested an
interaction between PSORS5 and PSORS1 (177900).
- Association with Atopic Dermatitis
Among 100 patients with atopic dermatitis (ATOD1; 603165) and 264
controls, Vasilopoulos et al. (2007) observed an association between
risk for ATOD and a 344C-T SNP in the CSTA gene (OR = 2.13, p = 0.006).
The C allele was more common among patients, indicating that the T
allele may offer a protective effect. In vitro functional expression
studies showed that the 344C allele produced mRNA that was 2.2-fold less
stable than the 344T mRNA. Vasilopoulos et al. (2007) noted that since
CSTA is a cysteine protease inhibitor of dust mite proteases that breaks
down epidermal barriers, a decrease in CSTA mRNA may contribute to a
defective epidermal barrier among patients with atopic dermatitis.
*FIELD* AV
.0001
EXFOLIATIVE ICHTHYOSIS, AUTOSOMAL RECESSIVE, ICHTHYOSIS BULLOSA OF
SIEMENS-LIKE
CSTA, IVS1, A-T, -2
In affected members of a consanguineous Bedouin kindred with ichthyosis
bullosa of Siemens-like exfoliative ichthyosis (607936), Blaydon et al.
(2011) identified homozygosity for an A-to-T transversion in intron 1
(67-2A-T) of the CSTA gene. The mutation segregated with disease in the
family and was not found in 300 control chromosomes.
.0002
EXFOLIATIVE ICHTHYOSIS, AUTOSOMAL RECESSIVE, ICHTHYOSIS BULLOSA OF
SIEMENS-LIKE
CSTA, GLN86TER
In affected members of a Turkish family with ichthyosis bullosa of
Siemens-like exfoliative ichthyosis (607936), Blaydon et al. (2011)
identified homozygosity for a 256C-T transition in the CSTA gene,
resulting in a gln86-to-ter (Q86X) substitution at a highly conserved
residue within the conserved cystatin domain.
*FIELD* RF
1. 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.: Mutations
in CSTA, encoding cystatin A, underlie exfoliative ichthyosis and
reveal a role for this protease inhibitor in cell-cell adhesion. Am.
J. Hum. Genet. 89: 564-571, 2011.
2. Hsieh, W.-T.; Fong, D.; Sloane, B. F.; Golembieski, W.; Smith,
D. I.: Mapping of the gene for human cysteine proteinase inhibitor
stefin A, STF1, to chromosome 3cen-q21. Genomics 9: 207-209, 1991.
3. Samuelsson, L.; Stiller, C.; Friberg, C.; Nilsson, C.; Inerot,
A.; Wahlstrom, J.: Association analysis of cystatin A and zinc finger
protein 148, two genes located at the psoriasis susceptibility locus
PSORS5. J. Invest. Derm. 122: 1399-1400, 2004.
4. Strauss, M.; Stollwerk, J.; Lenarcic, B.; Turk, V.; Jany, K.-D.;
Gassen, H. G.: Chemical synthesis of a gene for human stefin A and
its expression in E. coli. Biol. Chem. Hoppe Seyler 369: 1019-1030,
1988.
5. Takahashi, H.; Asano, K.; Kinouchi, M.; Ishida-Yamamoto, A.; Wueppers,
K. D.; Iizuka, H.: 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. J. Biol. Chem. 273: 17375-17380, 1998.
6. Takahashi, M.; Tezuka, T.; Katunuma, N.: Phosphorylated cystatin-alpha
is a natural substrate of epidermal transglutaminase for formation
of skin cornified envelope. FEBS Lett. 308: 79-82, 1992.
7. Tsui, F. W. L.; Tsui, H.-W.; Mok, S.; Mlinaric, I.; Copeland, N.
G.; Gilbert, D. J.; Jenkins, N. A.; Siminovitch, K. A.: Molecular
characterization and mapping of murine genes encoding three members
of the stefin family of cysteine proteinase inhibitors. Genomics 15:
507-514, 1993.
8. Vasilopoulos, Y.; Cork, M. J.; Teare, D.; Marinou, I.; Ward, S.
J.; Duff, G. W.; Tazi-Ahnini, R.: A nonsynonymous substitution of
cystatin A, a cysteine protease inhibitor of house dust mite protease,
leads to decreased mRNA stability and shows a significant association
with atopic dermatitis. Allergy 62: 514-519, 2007.
9. Vasilopoulos, Y.; Walters, J.; Cork, M. J.; Duff, G. W.; Sagoo,
G. S.; Tazi-Ahnini, R.: Association analysis of the skin barrier
gene cystatin A at the PSORS5 locus in psoriatic patients: evidence
for interaction between PSORS1 and PSORS5. Europ. J. Hum. Genet. 16:
1002-1009, 2008.
*FIELD* CN
Marla J. F. O'Neill - updated: 10/28/2011
Cassandra L. Kniffin - updated: 10/23/2008
Cassandra L. Kniffin - updated: 8/20/2008
*FIELD* CD
Victor A. McKusick: 7/11/1990
*FIELD* ED
carol: 05/25/2012
alopez: 11/2/2011
terry: 10/28/2011
terry: 9/17/2010
wwang: 10/24/2008
ckniffin: 10/23/2008
wwang: 8/29/2008
ckniffin: 8/20/2008
carol: 8/18/1998
mark: 3/31/1997
mark: 11/27/1996
carol: 4/30/1993
carol: 3/19/1993
carol: 3/9/1993
supermim: 3/16/1992
carol: 1/16/1991
carol: 9/21/1990
MIM
607936
*RECORD*
*FIELD* NO
607936
*FIELD* TI
#607936 EXFOLIATIVE ICHTHYOSIS, AUTOSOMAL RECESSIVE, ICHTHYOSIS BULLOSA OF
SIEMENS-LIKE
read more;;EXFOLIATIVE ICHTHYOSIS, AUTOSOMAL RECESSIVE, IBS-LIKE;;
AREI
*FIELD* TX
A number sign (#) is used with this entry because this form of
exfoliative ichthyosis is caused by homozygous mutation in the CSTA gene
(184600) on chromosome 3q21.1.
CLINICAL FEATURES
Hatsell et al. (2003) reported a new variant of congenital exfoliative
ichthyosis in 2 related Bedouin families. The phenotype shared some
features with ichthyosis bullosa of Siemens (IBS; 146800) and annular
epidermolytic ichthyosis (607602), and clinical distinction seemed
difficult. However, the histologic, ultrastructural, and genetic
features in the affected members distinguished the ichthyosis in the
presented family from previously reported ichthyoses. Ichthyosis
appeared shortly after birth as a fine peeling of nonerythematous skin
on the palms and soles. The prominent well-demarcated areas of denuded
skin in moist and traumatized regions resembled the 'mauserung'
phenomenon of IBS. Unlike IBS, this disorder lacked epidermolysis on
histologic examination. Electron microscopy revealed a prominent
intercellular edema and numerous aggregates of keratin filaments in
basal keratinocytes. Abnormal keratin-1 (K1; 139350) expression was seen
in the affected epidermis; however, all other keratins, including K2e
(600194), had a distribution comparable to that seen in normal controls.
The mode of inheritance was consistent with autosomal recessive
transmission.
Blaydon et al. (2011) studied the Bedouin kindred with exfoliative
ichthyosis originally reported by Hatsell et al. (2003), as well as a
Turkish family with a similar phenotype. Affected individuals in both
families presented shortly after birth with dry, scaly skin over most of
the body and coarse peeling of nonerythematous skin on the palms and
soles, which was exacerbated by excessive moisture and minor trauma.
Electron microscopy of skin biopsies from both families revealed 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, indicating that
skin peeling initiated due to weakness in keratinocyte attachment at the
basal and lower suprabasal level in affected individuals. A detailed
view of cell-cell contacts showed a loss in number and tightness of the
desmosomes in the basal layer compared to the upper epidermal layers and
a partial loosening of their intercellular interaction.
MAPPING
In linkage analysis of a large Bedouin pedigree with congenital
exfoliative ichthyosis, Hatsell et al. (2003) found suggestive linkage
to chromosome 12q13. Blaydon et al. (2011) performed high-resolution
homozygosity mapping in 2 affected individuals from the same Bedouin
pedigree and identified a large block of homozygosity on chromosome 3q21
between dbSNP rs6783609 and dbSNP rs6438966. Analysis of the SNP data
revealed no significant blocks of shared homozygosity on chromosomal
region 12q13; linkage to 3q21 was confirmed by genotyping microsatellite
markers across the region.
MOLECULAR GENETICS
In a consanguineous Bedouin kindred with autosomal recessive exfoliative
ichthyosis mapping to chromosome 3q21, Blaydon et al. (2011) identified
homozygosity for a splice site mutation in the candidate gene CSTA
(184600.0001) that segregated with disease in the family and was not
detected in 300 control chromosomes. In affected members of a Turkish
family with a very similar phenotype of exfoliative ichthyosis, Blaydon
et al. (2011) identified homozygosity for a nonsense mutation in CSTA
(184600.0002).
*FIELD* RF
1. 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.: Mutations
in CSTA, encoding cystatin A, underlie exfoliative ichthyosis and
reveal a role for this protease inhibitor in cell-cell adhesion. Am.
J. Hum. Genet. 89: 564-571, 2011.
2. Hatsell, S. J.; Stevens, H.; Jackson, A. P.; Kelsell, D. P.; Zvulunov,
A.: An autosomal recessive exfoliative ichthyosis with linkage to
chromosome 12q13. Brit. J. Derm. 149: 174-180, 2003.
*FIELD* CS
INHERITANCE:
Autosomal recessive
SKIN, NAILS, HAIR:
[Skin];
Well-circumscribed peeling of the skin on the hands, feet and neck
(easily elicited by moisture and minor trauma);
Generalized dry skin with fine scaling but without erythema or blisters.
(sparing of face);
Hyperkeratosis;
Lichenification;
Well-circumscribed areas of nontender denuded skin on extremities
HISTOLOGY:;
Orthokeratosis, nonspecific basket-weave;
Acanthosis;
Thickened granular zone;
Mild spongiosis;
Mild perivascular lymphocytic infiltrate in the upper dermis;
Keratin-1 (K1) staining restricted to the spinous layer;
ELECTRON MICROSCOPY:;
Markedly widened intercellular spaces;
Electron-dense aggregates of keratin filaments in basal keratinocytes;
[Nails];
Onychodystrophy, mild, of the toenails (occasional);
[Hair];
Normal
MOLECULAR BASIS:
Caused by mutation in the cystatin A gene (CSTA, 184600.0001)
*FIELD* CD
Gary A. Bellus: 8/29/2003
*FIELD* ED
joanna: 05/15/2012
joanna: 9/2/2003
joanna: 8/29/2003
*FIELD* CN
Marla J. F. O'Neill - updated: 10/28/2011
*FIELD* CD
Gary A. Bellus: 8/28/2003
*FIELD* ED
alopez: 11/02/2011
terry: 10/28/2011
joanna: 11/1/2005
carol: 3/17/2004
alopez: 8/28/2003
*RECORD*
*FIELD* NO
607936
*FIELD* TI
#607936 EXFOLIATIVE ICHTHYOSIS, AUTOSOMAL RECESSIVE, ICHTHYOSIS BULLOSA OF
SIEMENS-LIKE
read more;;EXFOLIATIVE ICHTHYOSIS, AUTOSOMAL RECESSIVE, IBS-LIKE;;
AREI
*FIELD* TX
A number sign (#) is used with this entry because this form of
exfoliative ichthyosis is caused by homozygous mutation in the CSTA gene
(184600) on chromosome 3q21.1.
CLINICAL FEATURES
Hatsell et al. (2003) reported a new variant of congenital exfoliative
ichthyosis in 2 related Bedouin families. The phenotype shared some
features with ichthyosis bullosa of Siemens (IBS; 146800) and annular
epidermolytic ichthyosis (607602), and clinical distinction seemed
difficult. However, the histologic, ultrastructural, and genetic
features in the affected members distinguished the ichthyosis in the
presented family from previously reported ichthyoses. Ichthyosis
appeared shortly after birth as a fine peeling of nonerythematous skin
on the palms and soles. The prominent well-demarcated areas of denuded
skin in moist and traumatized regions resembled the 'mauserung'
phenomenon of IBS. Unlike IBS, this disorder lacked epidermolysis on
histologic examination. Electron microscopy revealed a prominent
intercellular edema and numerous aggregates of keratin filaments in
basal keratinocytes. Abnormal keratin-1 (K1; 139350) expression was seen
in the affected epidermis; however, all other keratins, including K2e
(600194), had a distribution comparable to that seen in normal controls.
The mode of inheritance was consistent with autosomal recessive
transmission.
Blaydon et al. (2011) studied the Bedouin kindred with exfoliative
ichthyosis originally reported by Hatsell et al. (2003), as well as a
Turkish family with a similar phenotype. Affected individuals in both
families presented shortly after birth with dry, scaly skin over most of
the body and coarse peeling of nonerythematous skin on the palms and
soles, which was exacerbated by excessive moisture and minor trauma.
Electron microscopy of skin biopsies from both families revealed 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, indicating that
skin peeling initiated due to weakness in keratinocyte attachment at the
basal and lower suprabasal level in affected individuals. A detailed
view of cell-cell contacts showed a loss in number and tightness of the
desmosomes in the basal layer compared to the upper epidermal layers and
a partial loosening of their intercellular interaction.
MAPPING
In linkage analysis of a large Bedouin pedigree with congenital
exfoliative ichthyosis, Hatsell et al. (2003) found suggestive linkage
to chromosome 12q13. Blaydon et al. (2011) performed high-resolution
homozygosity mapping in 2 affected individuals from the same Bedouin
pedigree and identified a large block of homozygosity on chromosome 3q21
between dbSNP rs6783609 and dbSNP rs6438966. Analysis of the SNP data
revealed no significant blocks of shared homozygosity on chromosomal
region 12q13; linkage to 3q21 was confirmed by genotyping microsatellite
markers across the region.
MOLECULAR GENETICS
In a consanguineous Bedouin kindred with autosomal recessive exfoliative
ichthyosis mapping to chromosome 3q21, Blaydon et al. (2011) identified
homozygosity for a splice site mutation in the candidate gene CSTA
(184600.0001) that segregated with disease in the family and was not
detected in 300 control chromosomes. In affected members of a Turkish
family with a very similar phenotype of exfoliative ichthyosis, Blaydon
et al. (2011) identified homozygosity for a nonsense mutation in CSTA
(184600.0002).
*FIELD* RF
1. 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.: Mutations
in CSTA, encoding cystatin A, underlie exfoliative ichthyosis and
reveal a role for this protease inhibitor in cell-cell adhesion. Am.
J. Hum. Genet. 89: 564-571, 2011.
2. Hatsell, S. J.; Stevens, H.; Jackson, A. P.; Kelsell, D. P.; Zvulunov,
A.: An autosomal recessive exfoliative ichthyosis with linkage to
chromosome 12q13. Brit. J. Derm. 149: 174-180, 2003.
*FIELD* CS
INHERITANCE:
Autosomal recessive
SKIN, NAILS, HAIR:
[Skin];
Well-circumscribed peeling of the skin on the hands, feet and neck
(easily elicited by moisture and minor trauma);
Generalized dry skin with fine scaling but without erythema or blisters.
(sparing of face);
Hyperkeratosis;
Lichenification;
Well-circumscribed areas of nontender denuded skin on extremities
HISTOLOGY:;
Orthokeratosis, nonspecific basket-weave;
Acanthosis;
Thickened granular zone;
Mild spongiosis;
Mild perivascular lymphocytic infiltrate in the upper dermis;
Keratin-1 (K1) staining restricted to the spinous layer;
ELECTRON MICROSCOPY:;
Markedly widened intercellular spaces;
Electron-dense aggregates of keratin filaments in basal keratinocytes;
[Nails];
Onychodystrophy, mild, of the toenails (occasional);
[Hair];
Normal
MOLECULAR BASIS:
Caused by mutation in the cystatin A gene (CSTA, 184600.0001)
*FIELD* CD
Gary A. Bellus: 8/29/2003
*FIELD* ED
joanna: 05/15/2012
joanna: 9/2/2003
joanna: 8/29/2003
*FIELD* CN
Marla J. F. O'Neill - updated: 10/28/2011
*FIELD* CD
Gary A. Bellus: 8/28/2003
*FIELD* ED
alopez: 11/02/2011
terry: 10/28/2011
joanna: 11/1/2005
carol: 3/17/2004
alopez: 8/28/2003