Processing of SMDT1 (Homo sapiens)

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Bibliography

1. Mallilankaraman K, Cárdenas C, Doonan PJ, Chandramoorthy HC, Irrinki KM, Golenár T, Csordás G, Madireddi P, Yang J, Müller M, Miller R, Kolesar JE, Molgó J, Kaufman B, Hajnóczky G, Foskett JK, Madesh M.; ''MCUR1 is an essential component of mitochondrial Ca2+ uptake that regulates cellular metabolism.''; PubMed Europe PMC Scholia
2. Paupe V, Prudent J, Dassa EP, Rendon OZ, Shoubridge EA.; ''CCDC90A (MCUR1) is a cytochrome c oxidase assembly factor and not a regulator of the mitochondrial calcium uniporter.''; PubMed Europe PMC Scholia
3. Tomar D, Dong Z, Shanmughapriya S, Koch DA, Thomas T, Hoffman NE, Timbalia SA, Goldman SJ, Breves SL, Corbally DP, Nemani N, Fairweather JP, Cutri AR, Zhang X, Song J, Jaña F, Huang J, Barrero C, Rabinowitz JE, Luongo TS, Schumacher SM, Rockman ME, Dietrich A, Merali S, Caplan J, Stathopulos P, Ahima RS, Cheung JY, Houser SR, Koch WJ, Patel V, Gohil VM, Elrod JW, Rajan S, Madesh M.; ''MCUR1 Is a Scaffold Factor for the MCU Complex Function and Promotes Mitochondrial Bioenergetics.''; PubMed Europe PMC Scholia
4. Plovanich M, Bogorad RL, Sancak Y, Kamer KJ, Strittmatter L, Li AA, Girgis HS, Kuchimanchi S, De Groot J, Speciner L, Taneja N, Oshea J, Koteliansky V, Mootha VK.; ''MICU2, a paralog of MICU1, resides within the mitochondrial uniporter complex to regulate calcium handling.''; PubMed Europe PMC Scholia
5. Baughman JM, Perocchi F, Girgis HS, Plovanich M, Belcher-Timme CA, Sancak Y, Bao XR, Strittmatter L, Goldberger O, Bogorad RL, Koteliansky V, Mootha VK.; ''Integrative genomics identifies MCU as an essential component of the mitochondrial calcium uniporter.''; PubMed Europe PMC Scholia
6. De Stefani D, Raffaello A, Teardo E, Szabò I, Rizzuto R.; ''A forty-kilodalton protein of the inner membrane is the mitochondrial calcium uniporter.''; PubMed Europe PMC Scholia
7. König T, Tröder SE, Bakka K, Korwitz A, Richter-Dennerlein R, Lampe PA, Patron M, Mühlmeister M, Guerrero-Castillo S, Brandt U, Decker T, Lauria I, Paggio A, Rizzuto R, Rugarli EI, De Stefani D, Langer T.; ''The m-AAA Protease Associated with Neurodegeneration Limits MCU Activity in Mitochondria.''; PubMed Europe PMC Scholia
8. Wai T, Saita S, Nolte H, Müller S, König T, Richter-Dennerlein R, Sprenger HG, Madrenas J, Mühlmeister M, Brandt U, Krüger M, Langer T.; ''The membrane scaffold SLP2 anchors a proteolytic hub in mitochondria containing PARL and the i-AAA protease YME1L.''; PubMed Europe PMC Scholia

History

External references

DataNodes

Name	Type	Database reference	Comment
AFG3L2	Protein	Q9Y4W6 (Uniprot-TrEMBL)
C2orf47	Protein	Q8WWC4 (Uniprot-TrEMBL)
C2orf47:AFG3L2:SPG7:PHB:PHB2	Complex	R-HSA-8949645 (Reactome)
MCU	Protein	Q8NE86 (Uniprot-TrEMBL)
MCU complex	Complex	R-HSA-8949151 (Reactome)
MCUB	Protein	Q9NWR8 (Uniprot-TrEMBL)
MCUB	Protein	Q9NWR8 (Uniprot-TrEMBL)
MCU	Protein	Q8NE86 (Uniprot-TrEMBL)
MICU1	Protein	Q9BPX6 (Uniprot-TrEMBL)
MICU1	Protein	Q9BPX6 (Uniprot-TrEMBL)
MICU2	Protein	Q8IYU8 (Uniprot-TrEMBL)
MICU2,3	Complex	R-HSA-8956344 (Reactome)
MICU3	Protein	Q86XE3 (Uniprot-TrEMBL)
Mitochondrial processing peptidase	Complex	R-HSA-1299458 (Reactome)
PARL	Protein	Q9H300 (Uniprot-TrEMBL)
PHB	Protein	P35232 (Uniprot-TrEMBL)
PHB2	Protein	Q99623 (Uniprot-TrEMBL)
PMPCA	Protein	Q10713 (Uniprot-TrEMBL)
PMPCB	Protein	O75439 (Uniprot-TrEMBL)
SMDT1	Protein	Q9H4I9 (Uniprot-TrEMBL)
SMDT1 transit peptide	Protein	Q9H4I9 (Uniprot-TrEMBL)
SMDT1	Protein	Q9H4I9 (Uniprot-TrEMBL)
SPG7	Protein	Q9UQ90 (Uniprot-TrEMBL)
STOML2	Protein	Q9UJZ1 (Uniprot-TrEMBL)
STOML2:PARL:YME1L	Complex	R-HSA-8953745 (Reactome)
YME1L1	Protein	Q96TA2 (Uniprot-TrEMBL)
Zn2+	Metabolite	CHEBI:29105 (ChEBI)
proSMDT1	Protein	Q9H4I9 (Uniprot-TrEMBL)
proSMDT1:C2orf47:AFG3L2:SPG7:PHB:PHB2	Complex	R-HSA-8949643 (Reactome)
proSMDT1	Protein	Q9H4I9 (Uniprot-TrEMBL)

Annotated Interactions

Source	Target	Type	Database reference	Comment
	C2orf47:AFG3L2:SPG7:PHB:PHB2	Arrow	R-HSA-8949649 (Reactome)
C2orf47:AFG3L2:SPG7:PHB:PHB2			R-HSA-8949661 (Reactome)
C2orf47:AFG3L2:SPG7:PHB:PHB2		mim-catalysis	R-HSA-8949659 (Reactome)
	MCU complex	Arrow	R-HSA-8953461 (Reactome)
MCUB			R-HSA-8953461 (Reactome)
MCU			R-HSA-8953461 (Reactome)
MICU1			R-HSA-8953461 (Reactome)
MICU2,3			R-HSA-8953461 (Reactome)
Mitochondrial processing peptidase		mim-catalysis	R-HSA-8949649 (Reactome)
			R-HSA-8949649 (Reactome)	The mitochondrial endopeptidase PMPCA:PMPCB cleaves the transit peptide of proSMDT1 (proEMRE) yielding SMDT1 (Konig et al. 2016). Mature SMDT1 is assembled into the MCU complex where it serves to bridge the MCU pore and the MCU regulators MICU1 and MICU2 (or MICU3 in neurons).
			R-HSA-8949659 (Reactome)	Free SMDT1 (EMRE) that is not complexed with MICU1 and MICU2 (or MICU3) is degraded by AFG3L2 (m-AAA protease) (Konig et al. 2016). This degradation appears to prevent the formation of MCU complexes that contain MCU and SMDT1 but lack MICU1 and MICU2 (or MICU3) and are therefore unregulated.
			R-HSA-8949661 (Reactome)	C2orf47 exists in a large complex containing AFG3L2 and SPG7, which exist in a large complex containing SPG7 (Paraplegin) in the mitochondrial matrix and binds the transit peptide of proSMDT1 (proEMRE). The binding stabilizes SMDT1 perhaps by preventing backsliding of SMDT1 into the intermembrane space (Konig et al. 2016).
			R-HSA-8949668 (Reactome)	ProSMDT1 (proEMRE) that is not bound by C2orf47:AFG3L2 and processed by PMPCA,B is proteolyzed by YME1L1 (Konig et al. 2016) in a large complex containing STOML2 (SLP2) and PARL (Wai et al. 2016). Thus YME1L1 appears to prevent accumulation of proSMDT1.
			R-HSA-8953461 (Reactome)	During or after processing of the transit peptide of proSMDT1 (proEMRE), the mature SMDT1 is incorporated with MCU, MCUB, MICU1, and MICU2 (or MICU3 in neurons) into the mitochondrial calcium uniporter (MCU) complex (Konig et al. 2016). MCUR1 may also be a member of the MCU complex, however this is controversial.
	SMDT1 transit peptide	Arrow	R-HSA-8949649 (Reactome)
	SMDT1	Arrow	R-HSA-8949649 (Reactome)
SMDT1			R-HSA-8949659 (Reactome)
SMDT1			R-HSA-8953461 (Reactome)
STOML2:PARL:YME1L		mim-catalysis	R-HSA-8949668 (Reactome)
	proSMDT1:C2orf47:AFG3L2:SPG7:PHB:PHB2	Arrow	R-HSA-8949661 (Reactome)
proSMDT1:C2orf47:AFG3L2:SPG7:PHB:PHB2			R-HSA-8949649 (Reactome)
proSMDT1			R-HSA-8949661 (Reactome)
proSMDT1			R-HSA-8949668 (Reactome)