TYSND1 cleaves peroxisomal proteins (Homo sapiens)

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1-33333-53peroxisomal matrixSCP2PHYH(1-30)TYSND1(111-566)H2OPHYHACAA1H2OH2OTYSND1(1-110)SCP2(425-547)PHYH(1-338)H2OACOX1(1-438)ACAA1(1-424)AGPS(1-658)TYSND1H2OSCP2(1-424)ACOX1HSD17B4(1-311)ACAA1(1-26)HSD17B4(1-736)H2OHSD17B4(312-736)ACOX1(439-660)H2OAGPS(1-58)AGPS


Description

After proteins are imported into the peroxisome a subset of proteins are cleaved by the protease TYSND1 (Okumoto et al. 2011). Based onmutagenesis of human TYSND1 (Okumoto et al. 2011) and the homolog in Arabidopsis (Schuhmann et al. 2008), TYSND1 appears to be a trypsin-like serine protease containing a conserved histidine aspartate serine triad essential for catalysis. Mice lacking Tysnd1 have reduced peroxisomal localization of some peroxisomal enzymes and exhibit reduced beta-oxidation of fatty acids and metabolism of phytanic acid (Mizuno et al. 2013). Male mice lacking Tysnd1 are sterile due to sperm that lack acrosomal caps. View original pathway at:Reactome.

Comments

Reactome-Converter 
Pathway is converted from Reactome ID: 9033500
Reactome-version 
Reactome version: 66
Reactome Author 
Reactome Author: May, Bruce

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Ontology Terms

 

Bibliography

  1. Mizuno Y, Ninomiya Y, Nakachi Y, Iseki M, Iwasa H, Akita M, Tsukui T, Shimozawa N, Ito C, Toshimori K, Nishimukai M, Hara H, Maeba R, Okazaki T, Alodaib AN, Al Amoudi M, Jacob M, Alkuraya FS, Horai Y, Watanabe M, Motegi H, Wakana S, Noda T, Kurochkin IV, Mizuno Y, Schönbach C, Okazaki Y.; ''Tysnd1 deficiency in mice interferes with the peroxisomal localization of PTS2 enzymes, causing lipid metabolic abnormalities and male infertility.''; PubMed Europe PMC Scholia
  2. Jiang LL, Miyazawa S, Souri M, Hashimoto T.; ''Structure of D-3-hydroxyacyl-CoA dehydratase/D-3-hydroxyacyl-CoA dehydrogenase bifunctional protein.''; PubMed Europe PMC Scholia
  3. Schuhmann H, Huesgen PF, Gietl C, Adamska I.; ''The DEG15 serine protease cleaves peroxisomal targeting signal 2-containing proteins in Arabidopsis.''; PubMed Europe PMC Scholia
  4. Okumoto K, Kametani Y, Fujiki Y.; ''Two proteases, trypsin domain-containing 1 (Tysnd1) and peroxisomal lon protease (PsLon), cooperatively regulate fatty acid β-oxidation in peroxisomal matrix.''; PubMed Europe PMC Scholia
  5. Huyghe S, Mannaerts GP, Baes M, Van Veldhoven PP.; ''Peroxisomal multifunctional protein-2: the enzyme, the patients and the knockout mouse model.''; PubMed Europe PMC Scholia

History

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CompareRevisionActionTimeUserComment
114820view16:32, 25 January 2021ReactomeTeamReactome version 75
113265view11:33, 2 November 2020ReactomeTeamReactome version 74
112480view15:43, 9 October 2020ReactomeTeamReactome version 73
101702view14:42, 1 November 2018DeSlOntology Term : 'peptide and protein metabolic process' added !
101391view11:28, 1 November 2018ReactomeTeamreactome version 66
100929view21:03, 31 October 2018ReactomeTeamreactome version 65
100721view20:11, 31 October 2018ReactomeTeamNew pathway

External references

DataNodes

View all...
NameTypeDatabase referenceComment
ACAA1(1-26)ProteinP09110 (Uniprot-TrEMBL)
ACAA1(1-424)ProteinP09110 (Uniprot-TrEMBL)
ACAA1ProteinP09110 (Uniprot-TrEMBL)
ACOX1(1-438)ProteinQ15067 (Uniprot-TrEMBL)
ACOX1(439-660)ProteinQ15067 (Uniprot-TrEMBL)
ACOX1ProteinQ15067 (Uniprot-TrEMBL)
AGPS(1-58)ProteinO00116 (Uniprot-TrEMBL)
AGPS(1-658)ProteinO00116 (Uniprot-TrEMBL)
AGPSProteinO00116 (Uniprot-TrEMBL)
H2OMetaboliteCHEBI:15377 (ChEBI)
HSD17B4(1-311)ProteinP51659 (Uniprot-TrEMBL)
HSD17B4(1-736)ProteinP51659 (Uniprot-TrEMBL)
HSD17B4(312-736)ProteinP51659 (Uniprot-TrEMBL)
PHYH(1-30)ProteinO14832 (Uniprot-TrEMBL)
PHYH(1-338)ProteinO14832 (Uniprot-TrEMBL)
PHYHProteinO14832 (Uniprot-TrEMBL)
SCP2(1-424)ProteinP22307 (Uniprot-TrEMBL)
SCP2(425-547)ProteinP22307 (Uniprot-TrEMBL)
SCP2ProteinP22307 (Uniprot-TrEMBL)
TYSND1(1-110)ProteinQ2T9J0 (Uniprot-TrEMBL)
TYSND1(111-566)ProteinQ2T9J0 (Uniprot-TrEMBL)
TYSND1ProteinQ2T9J0 (Uniprot-TrEMBL)

Annotated Interactions

View all...
SourceTargetTypeDatabase referenceComment
ACAA1(1-26)ArrowR-HSA-9033529 (Reactome)
ACAA1(1-424)R-HSA-9033529 (Reactome)
ACAA1ArrowR-HSA-9033529 (Reactome)
ACOX1(1-438)ArrowR-HSA-9033515 (Reactome)
ACOX1(439-660)ArrowR-HSA-9033515 (Reactome)
ACOX1R-HSA-9033515 (Reactome)
AGPS(1-58)ArrowR-HSA-9033506 (Reactome)
AGPS(1-658)R-HSA-9033506 (Reactome)
AGPSArrowR-HSA-9033506 (Reactome)
H2OR-HSA-9033490 (Reactome)
H2OR-HSA-9033506 (Reactome)
H2OR-HSA-9033515 (Reactome)
H2OR-HSA-9033520 (Reactome)
H2OR-HSA-9033524 (Reactome)
H2OR-HSA-9033529 (Reactome)
H2OR-HSA-9033530 (Reactome)
HSD17B4(1-311)ArrowR-HSA-9033530 (Reactome)
HSD17B4(1-736)R-HSA-9033530 (Reactome)
HSD17B4(312-736)ArrowR-HSA-9033530 (Reactome)
PHYH(1-30)ArrowR-HSA-9033490 (Reactome)
PHYH(1-338)R-HSA-9033490 (Reactome)
PHYHArrowR-HSA-9033490 (Reactome)
R-HSA-9033490 (Reactome) The trypsin-like serine-type endopeptidase TYSND1 cleaves PHYH between amino acid residues 30 and 31, yielding PHYH(1-30) and PHYH(31-338). In mice, knockout of Tysnd1 causes reduced localization of Phyh to peroxisomes.
R-HSA-9033506 (Reactome) The trypsin-like serine-type endopeptidase TYSND1 cleaves AGPS between amino acid residues 58 and 59, yielding AGPS(1-58) and AGPS(59-658) (inferred from mouse homologs). In mice, knockout of TYSND1 causes reduced localization of AGPS to the peroxisome.
R-HSA-9033515 (Reactome) The trypsin-like serine-type endopeptidase TYSND1 cleaves ACOX1 between amino acid residues 438 and 439, yielding ACOX1(1-438) and ACOX1(439-660) (Okumoto et al. 2011, also inferred from mouse and rat homologs).
R-HSA-9033520 (Reactome) The trypsin-like serine-type endopeptidase TYSND1 cleaves TYSND1 between amino acid residues 110 and 111, yielding TYSND1(1-110) and TYSND1(111-566) (Okumoto et al. 2011). Self-cleavage of TYSND1 reduces its proteolytic activity.
R-HSA-9033524 (Reactome) The trypsin-like serine-type endopeptidase TYSND1 cleaves SCP2 (also known as SCPX) between amino acid residues 424 and 425, yielding SCP2(1-424) and SCP2(425-547) (Okumoto et al. 2011, also inferred from mouse homologs).
R-HSA-9033529 (Reactome) The trypsin-like serine-type endopeptidase TYSND1 cleaves ACAA1 between amino acid residues 26 and 27, yielding ACAA1(1-26) and ACAA1(27-424) (Okumoto et al. 2011). In mice, knockout of Tysnd1 causes reduced localization of Acaa1 to the peroxisome.
R-HSA-9033530 (Reactome) The trypsin-like serine-type endopeptidase TYSND1 cleaves HSD17B4 (Peroxisomal multifunctional enzyme type 2, MFP-2) between amino acid residues 311 and 312, yielding HSD17B4(1-311) and HSD17B4(312-736) (Okumoto et al. 2011, also inferred from mouse homologs). HSD17B4(1-311) dehydrogenates 3-hydroxyacyl-CoA; HSD17B4(312-736) acts as an enoyl-CoA hydratase (Jiang et al. 1997, reviewed in Huyghe et al. 2006). (In vitro, HSD17B4(312-736) facilitates the transfer of 7-dehydrocholesterol and phosphatidylcholine between membranes.) The uncleaved protein (HSD17B4) also catalyzes these reactions.
SCP2(1-424)ArrowR-HSA-9033524 (Reactome)
SCP2(425-547)ArrowR-HSA-9033524 (Reactome)
SCP2R-HSA-9033524 (Reactome)
TYSND1(1-110)ArrowR-HSA-9033520 (Reactome)
TYSND1(111-566)ArrowR-HSA-9033520 (Reactome)
TYSND1R-HSA-9033520 (Reactome)
TYSND1mim-catalysisR-HSA-9033490 (Reactome)
TYSND1mim-catalysisR-HSA-9033506 (Reactome)
TYSND1mim-catalysisR-HSA-9033515 (Reactome)
TYSND1mim-catalysisR-HSA-9033520 (Reactome)
TYSND1mim-catalysisR-HSA-9033524 (Reactome)
TYSND1mim-catalysisR-HSA-9033529 (Reactome)
TYSND1mim-catalysisR-HSA-9033530 (Reactome)
Retrieved from "https://classic.wikipathways.org/index.php/Pathway:WP4433"
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