P07858 (CATB_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

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	339 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	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. Secreted › extracellular 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 component	Lysosome Secreted
Coding sequence diversity	Polymorphism
Domain	Signal
Molecular function	Hydrolase Protease Thiol protease
PTM	Disulfide bond Glycoprotein Zymogen
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	cellular response to thyroid hormone stimulus Inferred from expression pattern PubMed 21217776. Source: UniProtKB innate immune response Traceable author statement. Source: Reactome proteolysis Inferred from direct assay PubMed 8811434. Source: UniProtKB regulation of apoptotic process Traceable author statement PubMed 16130169. Source: UniProtKB regulation of catalytic activity Inferred from electronic annotation. Source: InterPro
Cellular_component	endolysosome lumen Traceable author statement. Source: Reactome extracellular space Inferred from sequence or structural similarity PubMed 22261194. Source: BHF-UCL melanosome Inferred from electronic annotation. Source: UniProtKB-SubCell mitochondrion Inferred from electronic annotation. Source: Compara nucleolus Inferred from direct assay. Source: HPA perinuclear region of cytoplasm Inferred from direct assay PubMed 15614436. Source: UniProtKB
Molecular_function	cysteine-type endopeptidase activity Inferred from direct assay PubMed 6203523. Source: BHF-UCL
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
MLH1	P40692	7	EBI-715062,EBI-744248

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

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

93 ↔ 122

Ref.14

Disulfide bond

105 ↔ 150

Ref.14

Disulfide bond

141 ↔ 207

Ref.14

Disulfide bond

142 ↔ 146

Ref.14

Disulfide bond

179 ↔ 211

Ref.14

Disulfide bond

187 ↔ 198

Ref.14

Natural variations

Natural variant

26

1

L → V. Ref.1 Ref.3 Ref.6
Corresponds to variant rs12338 [ dbSNP | Ensembl ].

VAR_006724

Natural variant

53

1

S → G. Ref.6
Corresponds to variant rs1803250 [ dbSNP | Ensembl ].

VAR_051511

Natural variant

91

1

P → L.
Corresponds to variant rs11548596 [ dbSNP | Ensembl ].

VAR_051512

Natural variant

235

1

S → N.
Corresponds to variant rs17573 [ dbSNP | Ensembl ].

VAR_014696

Experimental info

Sequence conflict

228

1

N → D AA sequence Ref.7

Secondary structure

1

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339

Helix Strand Turn

Details...

Beta strand

20 – 22

3

Helix

28 – 37

10

Beta strand

40 – 43

4

Helix

52 – 57

6

Beta strand

69 – 72

4

Beta strand

82 – 85

4

Helix

86 – 89

4

Helix

94 – 97

4

Beta strand

104 – 106

3

Helix

108 – 124

17

Turn

125 – 127

3

Beta strand

131 – 133

3

Helix

135 – 141

7

Helix

143 – 146

4

Helix

149 – 151

3

Helix

155 – 164

10

Beta strand

167 – 170

4

Turn

173 – 175

3

Beta strand

178 – 180

3

Beta strand

188 – 191

4

Beta strand

192 – 195

4

Helix

220 – 222

3

Beta strand

230 – 232

3

Helix

236 – 246

11

Beta strand

249 – 256

8

Helix

257 – 261

5

Beta strand

264 – 267

4

Beta strand

274 – 288

15

Beta strand

291 – 297

7

Beta strand

302 – 304

3

Beta strand

309 – 313

5

Turn

314 – 317

4

Helix

318 – 320

3

Turn

321 – 323

3

Beta strand

326 – 331

6

Sequences

	Sequence		Length	Mass (Da)
	P07858 [UniParc]. Last modified June 21, 2005. Version 3. Checksum: 0FC818EA4C1F6D90	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

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] [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. , 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. , 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. , 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], MASS SPECTROMETRY. 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], MASS SPECTROMETRY. 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.

Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

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.

IPI

IPI00295741.

PIR

KHHUB. A26498.

RefSeq

NP_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.

UniGene

Hs.520898.

3D structure databases

PDBe
RCSB PDB
PDBj

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	[»]
3AI8	X-ray	2.11	A/B	78-333	[»]
3CBJ	X-ray	1.80	A	74-339	[»]
3CBK	X-ray	2.67	A	74-339	[»]
3K9M	X-ray	2.61	A/B	80-333	[»]
3PBH	X-ray	2.50	A	18-333	[»]

ProteinModelPortal

P07858.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-42785N.

IntAct

P07858. 13 interactions.

MINT

MINT-1397666.

STRING

9606.ENSP00000342070.

Protein family/group databases

MEROPS

C01.060.

PTM databases

PhosphoSite

P07858.

Polymorphism databases

DMDM

68067549.

2D gel databases

SWISS-2DPAGE

P07858.

UCD-2DPAGE

P07858.

Proteomic databases

PaxDb

P07858.

PeptideAtlas

P07858.

PRIDE

P07858.

Protocols and materials databases

DNASU

1508.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000345125; ENSP00000342070; ENSG00000164733.
ENST00000353047; ENSP00000345672; ENSG00000164733.
ENST00000434271; ENSP00000415889; ENSG00000164733.
ENST00000453527; ENSP00000409917; ENSG00000164733.
ENST00000530640; ENSP00000435105; ENSG00000164733.
ENST00000531089; ENSP00000433215; ENSG00000164733.
ENST00000533455; ENSP00000432244; ENSG00000164733.
ENST00000534510; ENSP00000434217; ENSG00000164733.

GeneID

1508.

KEGG

hsa:1508.

UCSC

uc003wum.3. human.

Organism-specific databases

CTD

1508.

GeneCards

GC08M011700.

H-InvDB

HIX0007320.

HGNC

HGNC:2527. CTSB.

HPA

CAB000457.
HPA018156.

MIM

116810. gene.

neXtProt

NX_P07858.

PharmGKB

PA27027.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG4870.

HOGENOM

HOG000241341.

HOVERGEN

HBG003480.

InParanoid

P07858.

KO

K01363.

OMA

GYPSGAW.

OrthoDB

EOG4K6G4C.

PhylomeDB

P07858.

Enzyme and pathway databases

BRENDA

3.4.22.1. 2681.

Reactome

REACT_118779. Extracellular matrix organization.
REACT_6900. Immune System.

Gene expression databases

ArrayExpress

P07858.

Bgee

P07858.

CleanEx

HS_CTSB.

Genevestigator

P07858.

GermOnline

ENSG00000164733. Homo sapiens.

Family and domain databases

InterPro

IPR025661. Pept_asp_AS.
IPR000169. Pept_cys_AS.
IPR025660. Pept_his_AS.
IPR013128. Peptidase_C1A.
IPR000668. Peptidase_C1A_C.
IPR015643. Peptidase_C1A_cathepsin-B.
IPR012599. Propeptide_C1A.
[Graphical view]

PANTHER

PTHR12411. PTHR12411. 1 hit.
PTHR12411:SF16. PTHR12411:SF16. 1 hit.

Pfam

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

PRINTS

PR00705. PAPAIN.

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

BindingDB

P07858.

ChEMBL

CHEMBL4072.

ChiTaRS

CTSB. human.

EvolutionaryTrace

P07858.

GenomeRNAi

1508.

NextBio

6235.

PMAP-CutDB

P07858.

SOURCE

Search...

Entry information

Entry name

CATB_HUMAN

Accession

Primary (citable) accession number: P07858
Secondary accession number(s): B3KQR5 , B3KRR5, Q503A6, Q96D87

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 1, 1988
Last sequence update:	June 21, 2005
Last modified:	May 1, 2013
This is version 161 of the entry and version 3 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.