CYTB_HUMAN
ID CYTB_HUMAN Reviewed; 98 AA.
AC P04080;
DT 01-NOV-1986, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1996, sequence version 2.
DT 03-AUG-2022, entry version 226.
DE RecName: Full=Cystatin-B;
DE AltName: Full=CPI-B;
DE AltName: Full=Liver thiol proteinase inhibitor;
DE AltName: Full=Stefin-B;
GN Name=CSTB; Synonyms=CST6, STFB;
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=3902020; DOI=10.1016/0006-291x(85)90216-5;
RA Ritonja A., Machleidt W., Barrett A.J.;
RT "Amino acid sequence of the intracellular cysteine proteinase inhibitor
RT cystatin B from human liver.";
RL Biochem. Biophys. Res. Commun. 131:1187-1192(1985).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA].
RX PubMed=8596935; DOI=10.1126/science.271.5256.1731;
RA Pennacchio L.A., Lehesjoki A.-E., Stone N.E., Willour V.L., Virteneva K.,
RA Miao J., D'Amato E., Ramirez L., Faham J., Koskiniemi M., Warringtion J.A.,
RA Norio R., la Chapelle A., Cox D.R., Myers R.M.;
RT "Mutations in the gene encoding cystatin B in progressive myoclonus
RT epilepsy (EPM1).";
RL Science 271:1731-1734(1996).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Bhat K.S.;
RL Submitted (MAY-1993) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=10830953; DOI=10.1038/35012518;
RA Hattori M., Fujiyama A., Taylor T.D., Watanabe H., Yada T., Park H.-S.,
RA Toyoda A., Ishii K., Totoki Y., Choi D.-K., Groner Y., Soeda E., Ohki M.,
RA Takagi T., Sakaki Y., Taudien S., Blechschmidt K., Polley A., Menzel U.,
RA Delabar J., Kumpf K., Lehmann R., Patterson D., Reichwald K., Rump A.,
RA Schillhabel M., Schudy A., Zimmermann W., Rosenthal A., Kudoh J.,
RA Shibuya K., Kawasaki K., Asakawa S., Shintani A., Sasaki T., Nagamine K.,
RA Mitsuyama S., Antonarakis S.E., Minoshima S., Shimizu N., Nordsiek G.,
RA Hornischer K., Brandt P., Scharfe M., Schoen O., Desario A., Reichelt J.,
RA Kauer G., Bloecker H., Ramser J., Beck A., Klages S., Hennig S.,
RA Riesselmann L., Dagand E., Wehrmeyer S., Borzym K., Gardiner K.,
RA Nizetic D., Francis F., Lehrach H., Reinhardt R., Yaspo M.-L.;
RT "The DNA sequence of human chromosome 21.";
RL Nature 405:311-319(2000).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Placenta;
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 [6]
RP SUBCELLULAR LOCATION.
RX PubMed=11139332; DOI=10.1006/excr.2000.5085;
RA Riccio M., Di Giaimo R., Pianetti S., Palmieri P.P., Melli M., Santi S.;
RT "Nuclear localization of cystatin B, the cathepsin inhibitor implicated in
RT myoclonus epilepsy (EPM1).";
RL Exp. Cell Res. 262:84-94(2001).
RN [7]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a
RT refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [8]
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 [9]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22223895; DOI=10.1074/mcp.m111.015131;
RA Bienvenut W.V., Sumpton D., Martinez A., Lilla S., Espagne C., Meinnel T.,
RA Giglione C.;
RT "Comparative large-scale characterisation of plant vs. mammal proteins
RT reveals similar and idiosyncratic N-alpha acetylation features.";
RL Mol. Cell. Proteomics 11:M111.015131-M111.015131(2012).
RN [10]
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 [11]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25944712; DOI=10.1002/pmic.201400617;
RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT "N-terminome analysis of the human mitochondrial proteome.";
RL Proteomics 15:2519-2524(2015).
RN [12]
RP X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS).
RX PubMed=2347312; DOI=10.1002/j.1460-2075.1990.tb08321.x;
RA Stubbs M.T., Laber B., Bode W., Huber R., Jerala R., Lenarcic B., Turk V.;
RT "The refined 2.4 A X-ray crystal structure of recombinant human stefin B in
RT complex with the cysteine proteinase papain: a novel type of proteinase
RT inhibitor interaction.";
RL EMBO J. 9:1939-1947(1990).
RN [13]
RP VARIANT EPM1 ARG-4.
RX PubMed=9012407;
RA Lalioti M.D., Mirotsou M., Buresi C., Peitsch M.C., Rossier C.,
RA Ouazzani R., Baldy-Moulinier M., Bottani A., Malafosse A.,
RA Antonarakis S.E.;
RT "Identification of mutations in cystatin B, the gene responsible for the
RT Unverricht-Lundborg type of progressive myoclonus epilepsy (EPM1).";
RL Am. J. Hum. Genet. 60:342-351(1997).
CC -!- FUNCTION: This is an intracellular thiol proteinase inhibitor. Tightly
CC binding reversible inhibitor of cathepsins L, H and B.
CC -!- SUBUNIT: Able to form dimers stabilized by noncovalent forces.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:11139332}. Nucleus
CC {ECO:0000269|PubMed:11139332}.
CC -!- DISEASE: Epilepsy, progressive myoclonic 1 (EPM1) [MIM:254800]: A form
CC of progressive myoclonic epilepsy, a clinically and genetically
CC heterogeneous group of disorders defined by the combination of action
CC and reflex myoclonus, other types of epileptic seizures, and
CC progressive neurodegeneration and neurocognitive impairment. EPM1 is an
CC autosomal recessive form characterized by severe, stimulus-sensitive
CC myoclonus and tonic-clonic seizures. The onset, occurring between 6 and
CC 13 years of age, is characterized by convulsions. Myoclonus begins 1 to
CC 5 years later. The twitchings occur predominantly in the proximal
CC muscles of the extremities and are bilaterally symmetrical, although
CC asynchronous. At first small, they become late in the clinical course
CC so violent that the victim is thrown to the floor. Mental deterioration
CC and eventually dementia develop. {ECO:0000269|PubMed:9012407}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC 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/CSTBID40181ch21q22.html";
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DR EMBL; U46692; AAA99014.1; -; Genomic_DNA.
DR EMBL; L03558; AAA35727.1; -; mRNA.
DR EMBL; AF208234; AAF44059.1; -; Genomic_DNA.
DR EMBL; AP001752; BAA95541.1; -; Genomic_DNA.
DR EMBL; BC003370; AAH03370.1; -; mRNA.
DR EMBL; BC010532; AAH10532.1; -; mRNA.
DR CCDS; CCDS13701.1; -.
DR PIR; A01278; UDHUB.
DR RefSeq; NP_000091.1; NM_000100.3.
DR PDB; 1STF; X-ray; 2.37 A; I=1-98.
DR PDB; 2OCT; X-ray; 1.40 A; A/B=1-98.
DR PDB; 4N6V; X-ray; 1.80 A; 0/1/2/3/4/5/6/7/8/9=8-98.
DR PDBsum; 1STF; -.
DR PDBsum; 2OCT; -.
DR PDBsum; 4N6V; -.
DR AlphaFoldDB; P04080; -.
DR BMRB; P04080; -.
DR SMR; P04080; -.
DR BioGRID; 107858; 57.
DR IntAct; P04080; 18.
DR MINT; P04080; -.
DR STRING; 9606.ENSP00000291568; -.
DR DrugBank; DB09131; Cupric Chloride.
DR MEROPS; I25.003; -.
DR TCDB; 1.C.91.1.1; the stefin b pore-forming protein (stefin b) family.
DR GlyGen; P04080; 5 sites, 1 O-linked glycan (5 sites).
DR iPTMnet; P04080; -.
DR PhosphoSitePlus; P04080; -.
DR SwissPalm; P04080; -.
DR BioMuta; CSTB; -.
DR DMDM; 1706278; -.
DR CPTAC; CPTAC-184; -.
DR CPTAC; CPTAC-185; -.
DR EPD; P04080; -.
DR jPOST; P04080; -.
DR MassIVE; P04080; -.
DR PaxDb; P04080; -.
DR PeptideAtlas; P04080; -.
DR PRIDE; P04080; -.
DR ProteomicsDB; 51648; -.
DR TopDownProteomics; P04080; -.
DR Antibodypedia; 4378; 820 antibodies from 38 providers.
DR CPTC; P04080; 3 antibodies.
DR DNASU; 1476; -.
DR Ensembl; ENST00000291568.7; ENSP00000291568.6; ENSG00000160213.9.
DR GeneID; 1476; -.
DR KEGG; hsa:1476; -.
DR MANE-Select; ENST00000291568.7; ENSP00000291568.6; NM_000100.4; NP_000091.1.
DR CTD; 1476; -.
DR DisGeNET; 1476; -.
DR GeneCards; CSTB; -.
DR GeneReviews; CSTB; -.
DR HGNC; HGNC:2482; CSTB.
DR HPA; ENSG00000160213; Tissue enriched (esophagus).
DR MalaCards; CSTB; -.
DR MIM; 254800; phenotype.
DR MIM; 601145; gene.
DR neXtProt; NX_P04080; -.
DR OpenTargets; ENSG00000160213; -.
DR Orphanet; 248; Autosomal recessive hypohidrotic ectodermal dysplasia.
DR Orphanet; 308; Progressive myoclonic epilepsy type 1.
DR PharmGKB; PA26984; -.
DR VEuPathDB; HostDB:ENSG00000160213; -.
DR eggNOG; ENOG502SF2X; Eukaryota.
DR GeneTree; ENSGT00940000154826; -.
DR HOGENOM; CLU_150234_2_0_1; -.
DR InParanoid; P04080; -.
DR OMA; AAYQTNK; -.
DR OrthoDB; 1647595at2759; -.
DR PhylomeDB; P04080; -.
DR TreeFam; TF333174; -.
DR PathwayCommons; P04080; -.
DR Reactome; R-HSA-6798695; Neutrophil degranulation.
DR SignaLink; P04080; -.
DR BioGRID-ORCS; 1476; 25 hits in 1089 CRISPR screens.
DR ChiTaRS; CSTB; human.
DR EvolutionaryTrace; P04080; -.
DR GeneWiki; Cystatin_B; -.
DR GenomeRNAi; 1476; -.
DR Pharos; P04080; Tbio.
DR PRO; PR:P04080; -.
DR Proteomes; UP000005640; Chromosome 21.
DR RNAct; P04080; protein.
DR Bgee; ENSG00000160213; Expressed in lower esophagus mucosa and 200 other tissues.
DR ExpressionAtlas; P04080; baseline and differential.
DR Genevisible; P04080; HS.
DR GO; GO:0062023; C:collagen-containing extracellular matrix; HDA:BHF-UCL.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:0005615; C:extracellular space; IDA:UniProtKB.
DR GO; GO:1904813; C:ficolin-1-rich granule lumen; TAS:Reactome.
DR GO; GO:0005730; C:nucleolus; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:MGI.
DR GO; GO:0034774; C:secretory granule lumen; TAS:Reactome.
DR GO; GO:1904724; C:tertiary granule lumen; TAS:Reactome.
DR GO; GO:0004869; F:cysteine-type endopeptidase inhibitor activity; IDA:UniProtKB.
DR GO; GO:0004866; F:endopeptidase inhibitor activity; IDA:MGI.
DR GO; GO:0002020; F:protease binding; IDA:MGI.
DR GO; GO:0003723; F:RNA binding; HDA:UniProtKB.
DR GO; GO:0008344; P:adult locomotory behavior; IEA:Ensembl.
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 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; Cytoplasm; Direct protein sequencing;
KW Disease variant; Epilepsy; Neurodegeneration; Nucleus; Protease inhibitor;
KW Reference proteome; Thiol protease inhibitor.
FT CHAIN 1..98
FT /note="Cystatin-B"
FT /id="PRO_0000207136"
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:0007744|PubMed:19413330,
FT ECO:0007744|PubMed:22223895"
FT VARIANT 4
FT /note="G -> R (in EPM1; dbSNP:rs74315443)"
FT /evidence="ECO:0000269|PubMed:9012407"
FT /id="VAR_002206"
FT CONFLICT 31
FT /note="E -> Y (in Ref. 1; AA sequence)"
FT /evidence="ECO:0000305"
FT HELIX 14..31
FT /evidence="ECO:0007829|PDB:2OCT"
FT STRAND 39..58
FT /evidence="ECO:0007829|PDB:2OCT"
FT STRAND 60..62
FT /evidence="ECO:0007829|PDB:1STF"
FT STRAND 64..74
FT /evidence="ECO:0007829|PDB:2OCT"
FT STRAND 80..89
FT /evidence="ECO:0007829|PDB:2OCT"
SQ SEQUENCE 98 AA; 11140 MW; B8076220E19D0483 CRC64;
MMCGAPSATQ PATAETQHIA DQVRSQLEEK ENKKFPVFKA VSFKSQVVAG TNYFIKVHVG
DEDFVHLRVF QSLPHENKPL TLSNYQTNKA KHDELTYF
