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P07858 (CATB_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 172. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Cathepsin B

EC=3.4.22.1
Alternative name(s):
APP secretase
Short name=APPS
Cathepsin B1

Cleaved into the following 2 chains:

  1. Cathepsin B light chain
  2. Cathepsin B heavy chain
Gene names
Name:CTSB
Synonyms:CPSB
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length339 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Thiol protease which is believed to participate in intracellular degradation and turnover of proteins. Has also been implicated in tumor invasion and metastasis.

Catalytic activity

Hydrolysis of proteins with broad specificity for peptide bonds. Preferentially cleaves -Arg-Arg-|-Xaa bonds in small molecule substrates (thus differing from cathepsin L). In addition to being an endopeptidase, shows peptidyl-dipeptidase activity, liberating C-terminal dipeptides.

Subunit structure

Dimer of a heavy chain and a light chain cross-linked by a disulfide bond. Interacts with SRPX2. Ref.12

Subcellular location

Lysosome. Melanosome. Secretedextracellular space By similarity. Note: Identified by mass spectrometry in melanosome fractions from stage I to stage IV. Ref.10 Ref.11

Sequence similarities

Belongs to the peptidase C1 family.

Ontologies

Keywords
   Cellular componentLysosome
Secreted
   Coding sequence diversityPolymorphism
   DomainSignal
   Molecular functionHydrolase
Protease
Thiol protease
   PTMAcetylation
Disulfide bond
Glycoprotein
Zymogen
   Technical term3D-structure
Complete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processcellular response to thyroid hormone stimulus

Inferred from expression pattern PubMed 21217776. Source: UniProtKB

collagen catabolic process

Inferred from direct assay PubMed 22952693. Source: BHF-UCL

epithelial cell differentiation

Inferred from expression pattern PubMed 21492153. Source: UniProt

extracellular matrix disassembly

Traceable author statement. Source: Reactome

extracellular matrix organization

Traceable author statement. Source: Reactome

innate immune response

Traceable author statement. Source: Reactome

proteolysis

Inferred from direct assay PubMed 8811434. Source: UniProtKB

proteolysis involved in cellular protein catabolic process

Inferred from direct assay PubMed 22952693. Source: BHF-UCL

regulation of apoptotic process

Traceable author statement PubMed 16130169. Source: UniProtKB

regulation of catalytic activity

Inferred from electronic annotation. Source: InterPro

toll-like receptor signaling pathway

Traceable author statement. Source: Reactome

   Cellular_componentendolysosome lumen

Traceable author statement. Source: Reactome

extracellular region

Traceable author statement. Source: Reactome

extracellular space

Inferred from direct assay PubMed 22952693. Source: BHF-UCL

extracellular vesicular exosome

Inferred from direct assay PubMed 19199708. Source: UniProt

intracellular

Traceable author statement PubMed 1645961. Source: ProtInc

intracellular membrane-bounded organelle

Inferred from direct assay. Source: HPA

lysosome

Inferred from direct assay PubMed 1837142. Source: UniProtKB

melanosome

Inferred from electronic annotation. Source: UniProtKB-SubCell

mitochondrion

Inferred from electronic annotation. Source: Ensembl

nucleolus

Inferred from direct assay. Source: HPA

perinuclear region of cytoplasm

Inferred from direct assay PubMed 15614436. Source: UniProtKB

   Molecular_functioncollagen binding

Inferred from direct assay PubMed 22952693. Source: BHF-UCL

cysteine-type endopeptidase activity

Inferred from direct assay PubMed 22952693PubMed 6203523. Source: BHF-UCL

cysteine-type peptidase activity

Inferred from direct assay PubMed 8811434. Source: UniProtKB

peptidase activity

Inferred from direct assay PubMed 7890620. Source: BHF-UCL

proteoglycan binding

Inferred from physical interaction PubMed 22952693. Source: BHF-UCL

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 1717 Potential
Propeptide18 – 7962Activation peptide
PRO_0000026143
Chain80 – 333254Cathepsin B
PRO_0000026144
Chain80 – 12647Cathepsin B light chain
PRO_0000026145
Chain129 – 333205Cathepsin B heavy chain
PRO_0000026146
Propeptide334 – 3396
PRO_0000026147

Sites

Active site1081
Active site2781
Active site2981

Amino acid modifications

Modified residue2201N6-acetyllysine By similarity
Glycosylation1921N-linked (GlcNAc...) Ref.1
Disulfide bond93 ↔ 122 Ref.14
Disulfide bond105 ↔ 150 Ref.14
Disulfide bond141 ↔ 207 Ref.14
Disulfide bond142 ↔ 146 Ref.14
Disulfide bond179 ↔ 211 Ref.14
Disulfide bond187 ↔ 198 Ref.14

Natural variations

Natural variant261L → V. Ref.1 Ref.3 Ref.6
Corresponds to variant rs12338 [ dbSNP | Ensembl ].
VAR_006724
Natural variant531S → G. Ref.6
Corresponds to variant rs1803250 [ dbSNP | Ensembl ].
VAR_051511
Natural variant911P → L.
Corresponds to variant rs11548596 [ dbSNP | Ensembl ].
VAR_051512
Natural variant2351S → N.
Corresponds to variant rs17573 [ dbSNP | Ensembl ].
VAR_014696

Experimental info

Sequence conflict2281N → D AA sequence Ref.7

Secondary structure

....................................................... 339
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P07858 [UniParc].

Last modified June 21, 2005. Version 3.
Checksum: 0FC818EA4C1F6D90

FASTA33937,822
        10         20         30         40         50         60 
MWQLWASLCC LLVLANARSR PSFHPLSDEL VNYVNKRNTT WQAGHNFYNV DMSYLKRLCG 

        70         80         90        100        110        120 
TFLGGPKPPQ RVMFTEDLKL PASFDAREQW PQCPTIKEIR DQGSCGSCWA FGAVEAISDR 

       130        140        150        160        170        180 
ICIHTNAHVS VEVSAEDLLT CCGSMCGDGC NGGYPAEAWN FWTRKGLVSG GLYESHVGCR 

       190        200        210        220        230        240 
PYSIPPCEHH VNGSRPPCTG EGDTPKCSKI CEPGYSPTYK QDKHYGYNSY SVSNSEKDIM 

       250        260        270        280        290        300 
AEIYKNGPVE GAFSVYSDFL LYKSGVYQHV TGEMMGGHAI RILGWGVENG TPYWLVANSW 

       310        320        330 
NTDWGDNGFF KILRGQDHCG IESEVVAGIP RTDQYWEKI 

« Hide

References

« Hide 'large scale' references
[1]"Nucleotide and predicted amino acid sequences of cloned human and mouse preprocathepsin B cDNAs."
Chan S.J., San Segundo B., McCormick M.B., Steiner D.F.
Proc. Natl. Acad. Sci. U.S.A. 83:7721-7725(1986) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT VAL-26.
[2]"Human gastric adenocarcinoma cathepsin B: isolation and sequencing of full-length cDNAs and polymorphisms of the gene."
Cao L., Taggart R.T., Berquin I.M., Moin K., Fong D., Sloane B.F.
Gene 139:163-169(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Gastric carcinoma.
[3]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT VAL-26.
Tissue: Esophagus.
[4]"Signal sequence and keyword trap in silico for selection of full-length human cDNAs encoding secretion or membrane proteins from oligo-capped cDNA libraries."
Otsuki T., Ota T., Nishikawa T., Hayashi K., Suzuki Y., Yamamoto J., Wakamatsu A., Kimura K., Sakamoto K., Hatano N., Kawai Y., Ishii S., Saito K., Kojima S., Sugiyama T., Ono T., Okano K., Yoshikawa Y. expand/collapse author list , Aotsuka S., Sasaki N., Hattori A., Okumura K., Nagai K., Sugano S., Isogai T.
DNA Res. 12:117-126(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[5]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE 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], VARIANTS VAL-26 AND GLY-53.
Tissue: Brain and Placenta.
[7]"Amino acid sequence of human liver cathepsin B."
Ritonja A., Popovic T., Turk V., Wiedenmann K., Machleidt W.
FEBS Lett. 181:169-172(1985) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 80-126 AND 129-333.
Tissue: Liver.
[8]"Human tumour cathepsin B. Comparison with normal liver cathepsin B."
Moin K., Day N.A., Sameni M., Hasnain S., Hirama T., Sloane B.F.
Biochem. J. 285:427-434(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 80-91 AND 129-139.
Tissue: Liver.
[9]"Isolation of a cDNA clone for the human lysosomal proteinase cathepsin B."
Fong D., Calhoun D.H., Hsieh W.-T., Lee B., Wells R.D.
Proc. Natl. Acad. Sci. U.S.A. 83:2909-2913(1986) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 131-339.
[10]"Proteomic analysis of early melanosomes: identification of novel melanosomal proteins."
Basrur V., Yang F., Kushimoto T., Higashimoto Y., Yasumoto K., Valencia J., Muller J., Vieira W.D., Watabe H., Shabanowitz J., Hearing V.J., Hunt D.F., Appella E.
J. Proteome Res. 2:69-79(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS].
Tissue: Melanoma.
[11]"Proteomic and bioinformatic characterization of the biogenesis and function of melanosomes."
Chi A., Valencia J.C., Hu Z.-Z., Watabe H., Yamaguchi H., Mangini N.J., Huang H., Canfield V.A., Cheng K.C., Yang F., Abe R., Yamagishi S., Shabanowitz J., Hearing V.J., Wu C., Appella E., Hunt D.F.
J. Proteome Res. 5:3135-3144(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS].
Tissue: Melanoma.
[12]"Epileptic and developmental disorders of the speech cortex: ligand/receptor interaction of wild-type and mutant SRPX2 with the plasminogen activator receptor uPAR."
Royer-Zemmour B., Ponsole-Lenfant M., Gara H., Roll P., Leveque C., Massacrier A., Ferracci G., Cillario J., Robaglia-Schlupp A., Vincentelli R., Cau P., Szepetowski P.
Hum. Mol. Genet. 17:3617-3630(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH SRPX2.
[13]"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].
[14]"The refined 2.15 A X-ray crystal structure of human liver cathepsin B: the structural basis for its specificity."
Musil D., Zucic D., Turk D., Engh R.A., Mayr I., Huber R., Popovic T., Turk V., Towatari T., Katunuma N., Bode W.
EMBO J. 10:2321-2330(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.15 ANGSTROMS).
[15]"Crystal structures of human procathepsin B at 3.2- and 3.3-A resolution reveal an interaction motif between a papain-like cysteine protease and its propeptide."
Turk D., Podobnik M., Kuhelj R., Dolinar M., Turk V.
FEBS Lett. 384:211-214(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (3.2 ANGSTROMS).
[16]"Crystal structure of the wild-type human procathepsin B at 2.5-A resolution reveals the native active site of a papain-like cysteine protease zymogen."
Podobnik M., Kuhelj R., Turk V., Turk D.
J. Mol. Biol. 271:774-788(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS).
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
M14221 mRNA. Translation: AAA52129.1.
L16510 mRNA. Translation: AAC37547.1.
AK092070 mRNA. Translation: BAG52477.1.
AK075393 mRNA. Translation: BAG52127.1.
CH471157 Genomic DNA. Translation: EAW65630.1.
BC010240 mRNA. Translation: AAH10240.1.
BC095408 mRNA. Translation: AAH95408.1.
M13230 mRNA. Translation: AAA52125.1.
PIRKHHUB. A26498.
RefSeqNP_001899.1. NM_001908.3.
NP_680090.1. NM_147780.2.
NP_680091.1. NM_147781.2.
NP_680092.1. NM_147782.2.
NP_680093.1. NM_147783.2.
UniGeneHs.520898.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1CSBX-ray2.00A/D80-126[»]
B/E129-333[»]
1GMYX-ray1.90A/B/C79-339[»]
1HUCX-ray2.10A/C80-126[»]
B/D129-333[»]
1PBHX-ray3.20A18-333[»]
2IPPX-ray2.15A80-126[»]
B129-333[»]
2PBHX-ray3.30A18-333[»]
3AI8X-ray2.11A/B78-333[»]
3CBJX-ray1.80A74-339[»]
3CBKX-ray2.67A74-339[»]
3K9MX-ray2.61A/B80-333[»]
3PBHX-ray2.50A18-333[»]
ProteinModelPortalP07858.
SMRP07858. Positions 18-333.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid107888. 28 interactions.
DIPDIP-42785N.
IntActP07858. 22 interactions.
MINTMINT-1397666.
STRING9606.ENSP00000342070.

Chemistry

BindingDBP07858.
ChEMBLCHEMBL2111396.
GuidetoPHARMACOLOGY2343.

Protein family/group databases

MEROPSC01.060.

PTM databases

PhosphoSiteP07858.

Polymorphism databases

DMDM68067549.

2D gel databases

SWISS-2DPAGEP07858.
UCD-2DPAGEP07858.

Proteomic databases

PaxDbP07858.
PeptideAtlasP07858.
PRIDEP07858.

Protocols and materials databases

DNASU1508.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000345125; ENSP00000342070; ENSG00000164733.
ENST00000353047; ENSP00000345672; ENSG00000164733.
ENST00000434271; ENSP00000415889; ENSG00000164733.
ENST00000453527; ENSP00000409917; ENSG00000164733.
ENST00000530640; ENSP00000435105; ENSG00000164733.
ENST00000531089; ENSP00000433215; ENSG00000164733.
ENST00000533455; ENSP00000432244; ENSG00000164733.
ENST00000534510; ENSP00000434217; ENSG00000164733.
GeneID1508.
KEGGhsa:1508.
UCSCuc003wum.3. human.

Organism-specific databases

CTD1508.
GeneCardsGC08M011700.
H-InvDBHIX0007320.
HGNCHGNC:2527. CTSB.
HPACAB000457.
HPA018156.
MIM116810. gene.
neXtProtNX_P07858.
PharmGKBPA27027.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG4870.
HOGENOMHOG000241341.
HOVERGENHBG003480.
InParanoidP07858.
KOK01363.
OMACTGEGDT.
OrthoDBEOG7034HR.
PhylomeDBP07858.
TreeFamTF314576.

Enzyme and pathway databases

BRENDA3.4.22.1. 2681.
ReactomeREACT_118779. Extracellular matrix organization.
REACT_6900. Immune System.

Gene expression databases

ArrayExpressP07858.
BgeeP07858.
CleanExHS_CTSB.
GenevestigatorP07858.

Family and domain databases

InterProIPR025661. Pept_asp_AS.
IPR000169. Pept_cys_AS.
IPR025660. Pept_his_AS.
IPR013128. Peptidase_C1A.
IPR000668. Peptidase_C1A_C.
IPR012599. Propeptide_C1A.
[Graphical view]
PANTHERPTHR12411. PTHR12411. 1 hit.
PfamPF00112. Peptidase_C1. 1 hit.
PF08127. Propeptide_C1. 1 hit.
[Graphical view]
PRINTSPR00705. PAPAIN.
SMARTSM00645. Pept_C1. 1 hit.
[Graphical view]
PROSITEPS00640. THIOL_PROTEASE_ASN. 1 hit.
PS00139. THIOL_PROTEASE_CYS. 1 hit.
PS00639. THIOL_PROTEASE_HIS. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSCTSB. human.
EvolutionaryTraceP07858.
GeneWikiCathepsin_B.
GenomeRNAi1508.
NextBio6235.
PMAP-CutDBP07858.
PROP07858.
SOURCESearch...

Entry information

Entry nameCATB_HUMAN
AccessionPrimary (citable) accession number: P07858
Secondary accession number(s): B3KQR5 expand/collapse secondary AC list , B3KRR5, Q503A6, Q96D87
Entry history
Integrated into UniProtKB/Swiss-Prot: August 1, 1988
Last sequence update: June 21, 2005
Last modified: April 16, 2014
This is version 172 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

Peptidase families

Classification of peptidase families and list of entries

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 8

Human chromosome 8: entries, gene names and cross-references to MIM