Reviewed, UniProtKB/Swiss-Prot P04080 (CYTB_HUMAN)

Names and origin

Protein names

Recommended name:
    Cystatin-B
Alternative name(s):
    Stefin-B
    Liver thiol proteinase inhibitor
    CPI-B

Gene names

Name:	CSTB
Synonyms:	CST6, STFB

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	98 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	This is an intracellular thiol proteinase inhibitor. Tightly binding reversible inhibitor of cathepsins L, H and B.
Subunit structure	Able to form dimers stabilized by noncovalent forces.
Subcellular location	Cytoplasm. Nucleus. Ref.6
Involvement in disease	Defects in CSTB are the cause of progressive myoclonic epilepsy type 1 (EPM1) [MIM:254800]. EPM1 is an autosomal recessive disorder characterized by severe, stimulus-sensitive myoclonus and tonic-clonic seizures. The onset, occurring between 6 and 13 years of age, is characterized by convulsions. Myoclonus begins 1 to 5 years later. The twitchings occur predominantly in the proximal muscles of the extremities and are bilaterally symmetrical, although asynchronous. At first small, they become late in the clinical course so violent that the victim is thrown to the floor. Mental deterioration and eventually dementia develop. Ref.9
Sequence similarities	Belongs to the cystatin family.

Ontologies

Keywords
Cellular component	Cytoplasm Nucleus
Disease	Disease mutation Epilepsy
Molecular function	Protease inhibitor Thiol protease inhibitor
PTM	Acetylation
Technical term	3D-structure Direct protein sequencing
Gene Ontology (GO)
Biological process	negative regulation of peptidase activity Inferred from direct assay. Source: UniProtKB
Cellular component	cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell nucleus Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	cysteine-type endopeptidase inhibitor activity Inferred from direct assay. Source: UniProtKB protease binding Inferred from physical interaction. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
VHL	P40337	1	EBI-1051966,EBI-301246

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 98

98

Cystatin-B

PRO_0000207136

Regions

Motif

46 – 50

5

Secondary area of contact

Sites

Site

4

1

Reactive site

Amino acid modifications

Modified residue

1

1

N-acetylmethionine Probable

Natural variations

Natural variant

4

1

G → R in EPM1. Ref.9

VAR_002206

Experimental info

Sequence conflict

31

1

E → Y AA sequence Ref.1

Secondary structure

1

.

.

.

.

.

.

.

.

.

98

Helix Strand Turn

Details...

Helix

14 – 31

18

Beta strand

39 – 58

20

Beta strand

64 – 74

11

Beta strand

80 – 89

10

Sequences

	Sequence		Length	Mass (Da)
	P04080-1 [UniParc]. Last modified October 1, 1996. Version 2. Checksum: B8076220E19D0483	FASTA	98	11,140
	10 20 30 40 50 60 MMCGAPSATQ PATAETQHIA DQVRSQLEEK ENKKFPVFKA VSFKSQVVAG TNYFIKVHVG 70 80 90 DEDFVHLRVF QSLPHENKPL TLSNYQTNKA KHDELTYF

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Amino acid sequence of the intracellular cysteine proteinase inhibitor cystatin B from human liver." Ritonja A., Machleidt W., Barrett A.J. Biochem. Biophys. Res. Commun. 131:1187-1192(1985) [PubMed: 3902020] [Abstract] Cited for: PROTEIN SEQUENCE.
[2]	"Mutations in the gene encoding cystatin B in progressive myoclonus epilepsy (EPM1)." Pennacchio L.A., Lehesjoki A.-E., Stone N.E., Willour V.L., Virteneva K., Miao J., D'Amato E., Ramirez L., Faham J., Koskiniemi M., Warringtion J.A., Norio R., la Chapelle A., Cox D.R., Myers R.M. Science 271:1731-1734(1996) [PubMed: 8596935] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA].
[3]	Bhat K.S. Submitted (MAY-1993) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[4]	"The DNA sequence of human chromosome 21." Hattori M., Fujiyama A., Taylor T.D., Watanabe H., Yada T., Park H.-S., Toyoda A., Ishii K., Totoki Y., Choi D.-K., Groner Y., Soeda E., Ohki M., Takagi T., Sakaki Y., Taudien S., Blechschmidt K., Polley A. , Menzel U., Delabar J., Kumpf K., Lehmann R., Patterson D., Reichwald K., Rump A., Schillhabel M., Schudy A., Zimmermann W., Rosenthal A., Kudoh J., Shibuya K., Kawasaki K., Asakawa S., Shintani A., Sasaki T., Nagamine K., Mitsuyama S., Antonarakis S.E., Minoshima S., Shimizu N., Nordsiek G., Hornischer K., Brandt P., Scharfe M., Schoen O., Desario A., Reichelt J., Kauer G., Bloecker H., Ramser J., Beck A., Klages S., Hennig S., Riesselmann L., Dagand E., Wehrmeyer S., Borzym K., Gardiner K., Nizetic D., Francis F., Lehrach H., Reinhardt R., Yaspo M.-L. Nature 405:311-319(2000) [PubMed: 10830953] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	"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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Placenta.
[6]	"Nuclear localization of cystatin B, the cathepsin inhibitor implicated in myoclonus epilepsy (EPM1)." Riccio M., Di Giaimo R., Pianetti S., Palmieri P.P., Melli M., Santi S. Exp. Cell Res. 262:84-94(2001) [PubMed: 11139332] [Abstract] Cited for: SUBCELLULAR LOCATION.
[7]	Colinge J., Superti-Furga G., Bennett K.L. Submitted (OCT-2008) to UniProtKB Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
[8]	"The refined 2.4 A X-ray crystal structure of recombinant human stefin B in complex with the cysteine proteinase papain: a novel type of proteinase inhibitor interaction." Stubbs M.T., Laber B., Bode W., Huber R., Jerala R., Lenarcic B., Turk V. EMBO J. 9:1939-1947(1990) [PubMed: 2347312] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS).
[9]	"Identification of mutations in cystatin B, the gene responsible for the Unverricht-Lundborg type of progressive myoclonus epilepsy (EPM1)." Lalioti M.D., Mirotsou M., Buresi C., Peitsch M.C., Rossier C., Ouazzani R., Baldy-Moulinier M., Bottani A., Malafosse A., Antonarakis S.E. Am. J. Hum. Genet. 60:342-351(1997) [PubMed: 9012407] [Abstract] Cited for: VARIANT EPM1 ARG-4.
+	Additional computationally mapped references.

Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

GeneReviews

Cross-references

Sequence databases

EMBLGenBankDDBJ

U46692 Genomic DNA. Translation: AAA99014.1.
L03558 mRNA. Translation: AAA35727.1.
AF208234 Genomic DNA. Translation: AAF44059.1.
AP001752 Genomic DNA. Translation: BAA95541.1.
BC003370 mRNA. Translation: AAH03370.1.
BC010532 mRNA. Translation: AAH10532.1.

IPI

IPI00021828.

PIR

UDHUB. A01278.

RefSeq

NP_000091.1.

UniGene

Hs.695

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1STF	X-ray	2.37	I	1-98	[»]
2OCT	X-ray	1.40	A/B	1-98	[»]

ModBase

Search...

Protein-protein interaction databases

IntAct

P04080. 6 interactions.

Protein family/group databases

MEROPS

I25.003.

PTM databases

PhosphoSite

P04080.

Proteomic databases

PeptideAtlas

P04080.

PRIDE

P04080.

Genome annotation databases

Ensembl

ENSG00000160213. Homo sapiens. [Contig view]

GeneID

1476.

KEGG

hsa:1476.

Organism-specific databases

GeneCards

GC21M044018.

H-InvDB

HIX0016156.

HGNC

HGNC:2482. CSTB.

HPA

CAB000470.
HPA017380.

MIM

254800. phenotype.
601145. gene.

Orphanet

308. Unverricht-Lundborg disease.

PharmGKB

PA26984.

GenAtlas

Search...

Phylogenomic databases

HOGENOM

P04080.

HOVERGEN

P04080.

OMA

P04080. KAVEFKS.

Gene expression databases

ArrayExpress

P04080.

Bgee

P04080.

CleanEx

HS_CST6.
HS_CSTB.

GermOnline

ENSG00000160213. 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 Resources

NextBio

6061.

SOURCE

Search...

Entry information

Entry name

CYTB_HUMAN

Accession

Primary (citable) accession number: P04080

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1986
Last sequence update:	October 1, 1996
Last modified:	June 16, 2009
This is version 119 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)