Cathepsin B precursor - Homo sapiens (Human)

Names and origin

Protein names

Recommended name:
    Cathepsin B
    EC=3.4.22.1
Alternative name(s):
    Cathepsin B1
    APP secretase
      Short name=APPS
Cleaved into the following 2 chains:
    1- Recommended name:
            Cathepsin B light chain
    2- Recommended name:
            Cathepsin B heavy chain

Gene names

Name:	CTSB
Synonyms:	CPSB

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

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

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Protein attributes

Sequence length	339 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level.

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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.
Subcellular location	Lysosome. Melanosome. Note: Identified by mass spectrometry in melanosome fractions from stage I to stage IV. Ref.8 Ref.9
Sequence similarities	Belongs to the peptidase C1 family.

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Ontologies

Keywords
Cellular component	Lysosome
Coding sequence diversity	Polymorphism
Domain	Signal
Molecular function	Hydrolase Protease Thiol protease
PTM	Disulfide bond Glycoprotein Zymogen
Technical term	3D-structure Direct protein sequencing
Gene Ontology (GO)
Biological process	proteolysis Ref.1 Inferred from direct assay. Source: UniProtKB regulation of apoptosis Traceable author statement. Source: UniProtKB regulation of catalytic activity Inferred from electronic annotation. Source: InterPro
Cellular component	lysosome Inferred from electronic annotation. Source: UniProtKB-SubCell melanosome Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	cysteine-type endopeptidase activity Inferred from direct assay. Source: UniProtKB
Complete GO annotation...

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Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 17

17

Potential

Propeptide

18 – 79

62

Activation peptide Ref.5 Ref.6

PRO_0000026143

Chain

80 – 333

254

Cathepsin B

PRO_0000026144

Chain

80 – 126

47

Cathepsin B light chain

PRO_0000026145

Chain

129 – 333

205

Cathepsin B heavy chain

PRO_0000026146

Propeptide

334 – 339

6

PRO_0000026147

Sites

Active site

108

1

Active site

278

1

Active site

298

1

Amino acid modifications

Glycosylation

192

1

N-linked (GlcNAc...) Ref.1

Disulfide bond

Disulfide bond

Disulfide bond

Disulfide bond

Disulfide bond

Disulfide bond

Natural variations

Natural variant

26

1

L → V: dbSNP rs12338. Ref.1 Ref.3 Ref.4

VAR_006724

Natural variant

53

1

S → G: dbSNP rs1803250. Ref.4

VAR_051511

Natural variant

91

1

P → L: dbSNP rs11548596.

VAR_051512

Natural variant

235

1

S → N: dbSNP rs17573.

VAR_014696

Experimental info

Sequence conflict

228

1

N → D AA sequence Ref.5

Secondary structure

1

.

339

Helix Strand Turn

Details...

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Sequences

Sequence

Length

Mass (Da)

Tools

P07858-1 [UniParc].

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

339

37,822

        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

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References

	« Hide 'large scale' referencesShow '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: 3463996] [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: 8112600] [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. Sugano S. Nat. Genet. 36:40-45(2004) [PubMed: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT VAL-26. Tissue: Oesophagus.
[4]	"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], VARIANTS VAL-26 AND GLY-53. Tissue: Brain and Placenta.
[5]	"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: 3972105] [Abstract] Cited for: PROTEIN SEQUENCE OF 80-126 AND 129-333. Tissue: Liver.
[6]	"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: 1637335] [Abstract] Cited for: PROTEIN SEQUENCE OF 80-91 AND 129-139. Tissue: Liver.
[7]	"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: 3010323] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 131-339.
[8]	"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: 12643545] [Abstract] Cited for: SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
[9]	"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: 17081065] [Abstract] Cited for: SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
[10]	Colinge J., Superti-Furga G., Bennett K.L. Submitted (OCT-2008) to UniProtKB Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
[11]	"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: 1868826] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.15 ANGSTROMS).
[12]	"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: 8617355] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (3.2 ANGSTROMS).
[13]	"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: 9299326] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS).
+	Additional computationally mapped references.

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Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

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Cross-references

Sequence databases

M14221 mRNA. Translation: AAA52129.1.
L16510 mRNA. Translation: AAC37547.1.
AK092070 mRNA. Translation: BAG52477.1.
BC010240 mRNA. Translation: AAH10240.1.
BC095408 mRNA. Translation: AAH95408.1.
M13230 mRNA. Translation: AAA52125.1.

IPI

IPI00295741.

PIR

KHHUB. A26498.

RefSeq

NP_001899.1.
NP_680090.1.
NP_680091.1.
NP_680092.1.
NP_680093.1.

UniGene

Hs.520898

3D structure databases

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1CSB	X-ray	2.00	A/D	80-126	[»]
			B/E	129-333	[»]
1GMY	X-ray	1.90	A/B/C	79-339	[»]
1HUC	X-ray	2.10	A/C	80-126	[»]
			B/D	129-333	[»]
1PBH	X-ray	3.20	A	18-333	[»]
2IPP	X-ray	2.15	A	80-126	[»]
			B	129-333	[»]
2PBH	X-ray	3.30	A	18-333	[»]
3CBJ	X-ray	1.80	A	74-339	[»]
3CBK	X-ray	2.67	A	74-339	[»]
3PBH	X-ray	2.50	A	18-333	[»]

SMR

P07858. Positions 18-333.

ModBase

Search...

Protein-protein interaction databases

IntAct

P07858. 2 interactions.

Protein family/group databases

MEROPS

C01.060.

PTM databases

PhosphoSite

P07858.

2-D gel databases

SWISS-2DPAGE

P07858.

Proteomic databases

PeptideAtlas

P07858.

PRIDE

P07858.

Genome annotation databases

Ensembl

ENSG00000164733. Homo sapiens. [Contig view]

GeneID

1508.

KEGG

hsa:1508.

Organism-specific databases

GeneCards

GC08M011737.

H-InvDB

HIX0007320.

HGNC

HGNC:2527. CTSB.

HPA

CAB000457.
HPA018156.

MIM

116810. gene.

PharmGKB

PA27027.

GenAtlas

Search...

Phylogenomic databases

HOGENOM

P07858.

HOVERGEN

P07858.

OMA

P07858. TFLGGPK.

Enzyme and pathway databases

BRENDA

3.4.22.1. 247.

Gene expression databases

ArrayExpress

P07858.

Bgee

P07858.

CleanEx

HS_CTSB.

GermOnline

ENSG00000164733. Homo sapiens.

Family and domain databases

InterPro

IPR000169. Pept_cys_AS.
IPR013128. Peptidase_C1A.
IPR000668. Peptidase_C1A_C.
IPR015643. Peptidase_C1A_cathepsin-B.
IPR012599. Propeptide_C1A.
[Graphical view]

PANTHER

PTHR12411:SF16. CathepsinB_like. 1 hit.
PTHR12411. Peptidase_C1A. 1 hit.

Pfam

PF00112. Peptidase_C1. 1 hit.
PF08127. Propeptide_C1. 1 hit.
[Graphical view]

PRINTS

PR00705. PAPAIN.

ProDom

PD000158. Peptidase_C1. 1 hit.
[Graphical view] [Entries sharing at least one domain]

SMART

SM00645. Pept_C1. 1 hit.
[Graphical view]

PROSITE

PS00640. THIOL_PROTEASE_ASN. 1 hit.
PS00139. THIOL_PROTEASE_CYS. 1 hit.
PS00639. THIOL_PROTEASE_HIS. 1 hit.
[Graphical view]

ProtoNet

Search...

Other Resources

NextBio

6235.

PMAP-CutDB

P07858.

SOURCE

Search...

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Entry information

Entry name

CATB_HUMAN

Accession

Primary (citable) accession number: P07858
Secondary accession number(s): B3KRR5, Q503A6, Q96D87

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 1, 1988
Last sequence update:	June 21, 2005
Last modified:	June 16, 2009
This is version 120 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

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