P01040 (CYTA_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Cystatin-A

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

Gene names

Name:	CSTA
Synonyms:	STF1, STFA

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	98 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence 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.10
Subcellular location	Cytoplasm Ref.10.
Tissue specificity	Expressed in the skin throughout the epidermis. Ref.10
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.10
Sequence similarities	Belongs to the cystatin family.

Ontologies

Keywords
Biological process	Cell adhesion
Cellular component	Cytoplasm
Coding sequence diversity	Polymorphism
Disease	Ichthyosis
Molecular function	Protease inhibitor Thiol protease inhibitor
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	cell-cell adhesion Inferred from mutant phenotype Ref.10. Source: UniProtKB keratinocyte differentiation Inferred from direct assay PubMed 10908733. Source: UniProtKB peptide cross-linking Inferred from direct assay PubMed 10908733. Source: UniProtKB
Cellular_component	cornified envelope Inferred from direct assay PubMed 10908733. Source: UniProtKB cytoplasm Inferred from direct assay Ref.10. Source: UniProtKB nucleus Inferred from direct assay. Source: HPA
Molecular_function	cysteine-type endopeptidase inhibitor activity Inferred from direct assay 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 key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Initiator methionine

1

1

Removed Ref.7

Chain

2 – 98

97

Cystatin-A

PRO_0000207128

Regions

Motif

46 – 50

5

Secondary area of contact

Sites

Site

2

1

Not acetylated

Site

4

1

Reactive site

Natural variations

Natural variant

96

1

T → M.
Corresponds to variant rs34173813 [ dbSNP | Ensembl ].

VAR_048851

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

98

Helix Strand Turn

Details...

Beta strand

7 – 12

6

Helix

14 – 31

18

Beta strand

34 – 36

3

Beta strand

39 – 58

20

Helix

60 – 62

3

Beta strand

64 – 71

8

Helix

74 – 76

3

Helix

77 – 79

3

Beta strand

80 – 89

10

Beta strand

91 – 93

3

Sequences

	Sequence		Length	Mass (Da)
	P01040 [UniParc]. Last modified July 21, 1986. Version 1. Checksum: 2F5F0D61C91305EE	FASTA	98	11,006
	10 20 30 40 50 60 MIPGGLSEAK PATPEIQEIV DKVKPQLEEK TNETYGKLEA VQYKTQVVAG TNYYIKVRAG 70 80 90 DNKYMHLKVF KSLPGQNEDL VLTGYQVDKN KDDELTGF

References

	« Hide 'large scale' referencesShow '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]	"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.
[7]	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, LACK OF N-TERMINAL ACETYLATION, MASS SPECTROMETRY. Tissue: Prostatic carcinoma.
[8]	"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.
[9]	"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.
[10]	"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.
[11]	"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].
[12]	"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.
[13]	"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.

Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

X05978 mRNA. Translation: CAA29398.1.
D88422 Genomic DNA. Translation: BAA13609.1.
AB007774 Genomic DNA. Translation: BAA87858.1.
BC010379 mRNA. Translation: AAH10379.1.

IPI

IPI00032325.

PIR

UDHUS. A29139.

RefSeq

NP_005204.1. NM_005213.3.

UniGene

Hs.518198.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1CYU	NMR	-	A	1-98	[»]
1CYV	NMR	-	A	1-98	[»]
1DVC	NMR	-	A	1-98	[»]
1DVD	NMR	-	A	1-98	[»]
1GD3	NMR	-	A	1-98	[»]
1GD4	NMR	-	A	1-98	[»]
1N9J	NMR	-	A/B	1-98	[»]
1NB3	X-ray	2.80	I/J/K/L	1-98	[»]
1NB5	X-ray	2.40	I/J/K/L	1-98	[»]
3K9M	X-ray	2.61	C/D	1-98	[»]
3KFQ	X-ray	1.99	C/D	1-98	[»]
3KSE	X-ray	1.71	D/E/F	1-98	[»]

ProteinModelPortal

P01040.

ModBase

Search...

Protein-protein interaction databases

IntAct

P01040. 4 interactions.

MINT

MINT-1428155.

STRING

9606.ENSP00000264474.

Protein family/group databases

MEROPS

I25.001.

PTM databases

PhosphoSite

P01040.

Polymorphism databases

DMDM

118177.

Proteomic databases

PaxDb

P01040.

PeptideAtlas

P01040.

PRIDE

P01040.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000264474; ENSP00000264474; ENSG00000121552.

GeneID

1475.

KEGG

hsa:1475.

UCSC

uc003eex.3. human.

Organism-specific databases

CTD

1475.

GeneCards

GC03P122044.

HGNC

HGNC:2481. CSTA.

HPA

CAB000469.
CAB047315.
HPA001031.

MIM

184600. gene.
607936. phenotype.

neXtProt

NX_P01040.

Orphanet

289586. Exfoliative ichthyosis.

PharmGKB

PA26983.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG119299.

HOGENOM

HOG000294175.

HOVERGEN

HBG002292.

InParanoid

P01040.

KO

K13907.

OMA

TGYQTDK.

OrthoDB

EOG42Z4RQ.

PhylomeDB

P01040.

Gene expression databases

ArrayExpress

P01040.

Bgee

P01040.

CleanEx

HS_CSTA.

Genevestigator

P01040.

GermOnline

ENSG00000121552. Homo sapiens.

Family and domain databases

InterPro

IPR000010. Prot_inh_cystat.
IPR018073. Prot_inh_cystat_CS.
IPR001713. Prot_inh_stefinA.
[Graphical view]

Pfam

PF00031. Cystatin. 1 hit.
[Graphical view]

PRINTS

PR00295. STEFINA.

SMART

SM00043. CY. 1 hit.
[Graphical view]

PROSITE

PS00287. CYSTATIN. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

P01040.

GenomeRNAi

1475.

NextBio

6057.

SOURCE

Search...

Entry information

Entry name

CYTA_HUMAN

Accession

Primary (citable) accession number: P01040

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 21, 1986
Last sequence update:	July 21, 1986
Last modified:	May 1, 2013
This is version 145 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.