P09668 (CATH_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Pro-cathepsin H

Cleaved into the following 4 chains:

1. Cathepsin H mini chain
2. Cathepsin H
   EC=3.4.22.16
3. Cathepsin H heavy chain
4. Cathepsin H light chain

Gene names

Name:	CTSH
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	335 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	Important for the overall degradation of proteins in lysosomes.
Catalytic activity	Hydrolysis of proteins, acting as an aminopeptidase (notably, cleaving Arg-|-Xaa bonds) as well as an endopeptidase.
Subunit structure	Composed of a mini chain and a large chain. The large chain may be split into heavy and light chain. All chains are held together by disulfide bonds.
Subcellular location	Lysosome.
Sequence similarities	Belongs to the peptidase C1 family.

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 Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	ERK1 and ERK2 cascade Inferred from direct assay PubMed 21217776. Source: UniProtKB T cell mediated cytotoxicity Inferred from sequence or structural similarity. Source: UniProtKB antigen processing and presentation Traceable author statement PubMed 15196205. Source: UniProtKB bradykinin catabolic process Inferred from direct assay PubMed 15127951. Source: UniProtKB cellular response to thyroid hormone stimulus Inferred from expression pattern PubMed 21217776. Source: UniProtKB dichotomous subdivision of terminal units involved in lung branching Inferred from sequence or structural similarity. Source: UniProtKB immune response-regulating signaling pathway Inferred from direct assay PubMed 16822283. Source: UniProtKB membrane protein proteolysis Inferred from direct assay PubMed 14766755. Source: UniProtKB metanephros development Inferred from sequence or structural similarity. Source: UniProtKB negative regulation of apoptotic process Inferred from sequence or structural similarity. Source: UniProtKB neuropeptide catabolic process Inferred from direct assay PubMed 15127951. Source: UniProtKB positive regulation of angiogenesis Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of cell proliferation Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of epithelial cell migration Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of gene expression Inferred from direct assay PubMed 21217776. Source: UniProtKB protein destabilization Inferred from mutant phenotype PubMed 17500053. Source: UniProtKB response to retinoic acid Inferred from sequence or structural similarity. Source: UniProtKB spermatogenesis Inferred from electronic annotation. Source: Compara surfactant homeostasis Inferred from direct assay PubMed 18216060. Source: UniProtKB zymogen activation Inferred from direct assay PubMed 20435891. Source: UniProtKB
Cellular_component	acrosomal vesicle Inferred from electronic annotation. Source: Compara alveolar lamellar body Inferred from direct assay PubMed 18216060. Source: UniProtKB cytosol Inferred from direct assay PubMed 9050938. Source: UniProtKB extracellular space Inferred from direct assay PubMed 18216060PubMed 21217776PubMed 9050938. Source: UniProtKB lysosome Inferred from direct assay PubMed 15196205PubMed 16822283PubMed 1837142. Source: UniProtKB outer dense fiber Inferred from electronic annotation. Source: Compara
Molecular_function	HLA-A specific activating MHC class I receptor activity Inferred from direct assay PubMed 16822283. Source: UniProtKB aminopeptidase activity Inferred from direct assay PubMed 15127951. Source: UniProtKB apoptotic protease activator activity Inferred from direct assay PubMed 20435891. Source: UniProtKB cysteine-type endopeptidase activity Traceable author statement Ref.6. Source: UniProtKB serine-type endopeptidase activity Inferred from sequence or structural similarity. Source: UniProtKB thyroid hormone binding Inferred from direct assay PubMed 21217776. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 22

22

Propeptide

23 – 97

75

Activation peptide

PRO_0000026206

Peptide

98 – 105

8

Cathepsin H mini chain Ref.7

PRO_0000026207

Propeptide

106 – 115

10

PRO_0000026208

Chain

116 – 335

220

Cathepsin H

PRO_0000026209

Chain

116 – 292

177

Cathepsin H heavy chain

PRO_0000026210

Chain

293 – 335

43

Cathepsin H light chain

PRO_0000026211

Sites

Active site

141

1

By similarity

Active site

281

1

By similarity

Active site

301

1

By similarity

Amino acid modifications

Glycosylation

101

1

N-linked (GlcNAc...) Ref.7

Glycosylation

230

1

N-linked (GlcNAc...) Ref.7 Ref.9

Disulfide bond

102 ↔ 327

By similarity

Disulfide bond

138 ↔ 181

By similarity

Disulfide bond

172 ↔ 214

By similarity

Disulfide bond

272 ↔ 322

By similarity

Natural variations

Natural variant

11

1

G → R.
Corresponds to variant rs2289702 [ dbSNP | Ensembl ].

VAR_057038

Natural variant

23

1

A → T.
Corresponds to variant rs35001431 [ dbSNP | Ensembl ].

VAR_057039

Natural variant

26

1

C → S. Ref.1 Ref.3 Ref.5
Corresponds to variant rs1036938 [ dbSNP | Ensembl ].

VAR_060368

Natural variant

126

1

G → R in a colorectal cancer sample; somatic mutation. Ref.11

VAR_036478

Natural variant

179

1

H → Y. Ref.1 Ref.2 Ref.6
Corresponds to variant rs1130856 [ dbSNP | Ensembl ].

VAR_067717

Experimental info

Sequence conflict

306

1

Q → E AA sequence Ref.7

Sequence conflict

306

1

Q → E AA sequence Ref.8

Secondary structure

1

.

.

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.

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335

Helix Strand Turn

Details...

Helix

123 – 126

4

Helix

141 – 158

18

Helix

166 – 172

7

Helix

180 – 182

3

Turn

186 – 188

3

Helix

189 – 196

8

Turn

202 – 204

3

Helix

237 – 245

9

Beta strand

249 – 252

4

Helix

258 – 261

4

Beta strand

273 – 275

3

Beta strand

283 – 291

9

Beta strand

294 – 300

7

Turn

304 – 310

7

Beta strand

326 – 329

4

Sequences

	Sequence		Length	Mass (Da)
	P09668 [UniParc]. Last modified February 9, 2010. Version 4. Checksum: E2CF3A5EEA59C1D1	FASTA	335	37,394
	10 20 30 40 50 60 MWATLPLLCA GAWLLGVPVC GAAELCVNSL EKFHFKSWMS KHRKTYSTEE YHHRLQTFAS 70 80 90 100 110 120 NWRKINAHNN GNHTFKMALN QFSDMSFAEI KHKYLWSEPQ NCSATKSNYL RGTGPYPPSV 130 140 150 160 170 180 DWRKKGNFVS PVKNQGACGS CWTFSTTGAL ESAIAIATGK MLSLAEQQLV DCAQDFNNHG 190 200 210 220 230 240 CQGGLPSQAF EYILYNKGIM GEDTYPYQGK DGYCKFQPGK AIGFVKDVAN ITIYDEEAMV 250 260 270 280 290 300 EAVALYNPVS FAFEVTQDFM MYRTGIYSST SCHKTPDKVN HAVLAVGYGE KNGIPYWIVK 310 320 330 NSWGPQWGMN GYFLIERGKN MCGLAACASY PIPLV

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Nucleotide sequence of human preprocathepsin H, a lysosomal cysteine proteinase." Fuchs R., Gassen H.G. Nucleic Acids Res. 17:9471-9471(1989) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANTS SER-26 AND TYR-179. Tissue: Liver.
[2]	"Analysis of a truncated form of cathepsin H in human prostate tumor cells." Waghray A., Keppler D., Sloane B.F., Schuger L., Chen Y.Q. J. Biol. Chem. 277:11533-11538(2002) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT TYR-179.
[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 SER-26. Tissue: Lung.
[4]	"Analysis of the DNA sequence and duplication history of human chromosome 15." Zody M.C., Garber M., Sharpe T., Young S.K., Rowen L., O'Neill K., Whittaker C.A., Kamal M., Chang J.L., Cuomo C.A., Dewar K., FitzGerald M.G., Kodira C.D., Madan A., Qin S., Yang X., Abbasi N., Abouelleil A. , Arachchi H.M., Baradarani L., Birditt B., Bloom S., Bloom T., Borowsky M.L., Burke J., Butler J., Cook A., DeArellano K., DeCaprio D., Dorris L. III, Dors M., Eichler E.E., Engels R., Fahey J., Fleetwood P., Friedman C., Gearin G., Hall J.L., Hensley G., Johnson E., Jones C., Kamat A., Kaur A., Locke D.P., Madan A., Munson G., Jaffe D.B., Lui A., Macdonald P., Mauceli E., Naylor J.W., Nesbitt R., Nicol R., O'Leary S.B., Ratcliffe A., Rounsley S., She X., Sneddon K.M.B., Stewart S., Sougnez C., Stone S.M., Topham K., Vincent D., Wang S., Zimmer A.R., Birren B.W., Hood L., Lander E.S., Nusbaum C. Nature 440:671-675(2006) [PubMed] [Europe PMC] [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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT SER-26. Tissue: Eye.
[6]	"Molecular cloning and sequencing of a cDNA coding for mature human kidney cathepsin H." Fuchs R., Machleidt W., Gassen H.G. Biol. Chem. Hoppe-Seyler 369:469-475(1988) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 88-335, VARIANT TYR-179. Tissue: Kidney.
[7]	"Amino acid sequences of the human kidney cathepsins H and L." Ritonja A., Popovic T., Kotnik M., Machleidt W., Turk V. FEBS Lett. 228:341-345(1988) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 98-105 AND 114-335, GLYCOSYLATION AT ASN-101 AND ASN-230. Tissue: Kidney.
[8]	"Human cathepsins B, H and L: characterization by amino acid sequences and some kinetics of inhibition by the kininogens." Machleidt W., Ritonja A., Popovic T., Kotnik M., Brzin J., Turk V., Machleidt I., Mueller-Esterl W. (In) Turk V. (eds.); Cysteine proteinases and their inhibitors, pp.3-18, Walter de Gruyter, Berlin and New York (1986) Cited for: PROTEIN SEQUENCE OF 99-105; 116-159 AND 294-335.
[9]	"Glycoproteomics analysis of human liver tissue by combination of multiple enzyme digestion and hydrazide chemistry." Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H. J. Proteome Res. 8:651-661(2009) [PubMed] [Europe PMC] [Abstract] Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-230, MASS SPECTROMETRY. Tissue: Liver.
[10]	"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].
[11]	"The consensus coding sequences of human breast and colorectal cancers." Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V. , Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., Velculescu V.E. Science 314:268-274(2006) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT [LARGE SCALE ANALYSIS] ARG-126.
+	Additional computationally mapped references.

Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

X16832 mRNA. Translation: CAA34734.1.
AF426247 mRNA. Translation: AAL23961.1.
AK314698 mRNA. Translation: BAG37247.1.
AC011944 Genomic DNA. No translation available.
BC002479 mRNA. Translation: AAH02479.1.
X07549 mRNA. Translation: CAA30428.1.
X07549 mRNA. Translation: CAA30429.1.

IPI

IPI00297487.

PIR

KHHUH. S12486.

RefSeq

NP_004381.2. NM_004390.3.

UniGene

Hs.148641.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1BZN	model	-	B	116-335	[»]

ProteinModelPortal

P09668.

SMR

P09668. Positions 34-335.

ModBase

Search...

Protein-protein interaction databases

IntAct

P09668. 1 interaction.

STRING

9606.ENSP00000220166.

Protein family/group databases

MEROPS

C01.040.

PTM databases

PhosphoSite

P09668.

Polymorphism databases

DMDM

288558851.

Proteomic databases

PaxDb

P09668.

PRIDE

P09668.

Protocols and materials databases

DNASU

1512.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000220166; ENSP00000220166; ENSG00000103811.

GeneID

1512.

KEGG

hsa:1512.

UCSC

uc021srk.1. human.

Organism-specific databases

CTD

1512.

GeneCards

GC15M079213.

H-InvDB

HIX0012481.

HGNC

HGNC:2535. CTSH.

HPA

CAB000458.
HPA003524.

MIM

116820. gene.

neXtProt

NX_P09668.

PharmGKB

PA27033.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG4870.

HOGENOM

HOG000230774.

HOVERGEN

HBG011513.

InParanoid

P09668.

KO

K01366.

OMA

STSCHKT.

OrthoDB

EOG4W9J43.

PhylomeDB

P09668.

Enzyme and pathway databases

BRENDA

3.4.22.16. 2681.

Reactome

REACT_6900. Immune System.

Gene expression databases

ArrayExpress

P09668.

Bgee

P09668.

CleanEx

HS_CTSH.

Genevestigator

P09668.

GermOnline

ENSG00000103811. 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.
IPR013201. Prot_inhib_I29.
[Graphical view]

PANTHER

PTHR12411. PTHR12411. 1 hit.

Pfam

PF08246. Inhibitor_I29. 1 hit.
PF00112. Peptidase_C1. 1 hit.
[Graphical view]

PRINTS

PR00705. PAPAIN.

SMART

SM00848. Inhibitor_I29. 1 hit.
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

ChEMBL

CHEMBL2225.

GenomeRNAi

1512.

NextBio

6261.

SOURCE

Search...

Entry information

Entry name

CATH_HUMAN

Accession

Primary (citable) accession number: P09668
Secondary accession number(s): B2RBK0, Q96NY6, Q9BUM7

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 1, 1989
Last sequence update:	February 9, 2010
Last modified:	May 1, 2013
This is version 146 of the entry and version 4 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.