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Overview

Uniprot ID	Q96HS1
Protein Name	Serine/threonine-protein phosphatase PGAM5, mitochondrial
Gene Name	PGAM5
Organism	Homo sapiens

Kla Sites from experimental identification

Position	Flanking peptide
141	RLASLGLKFNKIVHS
88	GEEELASKLDHYKAK

Function

Mitochondrial serine/threonine phosphatase that dephosphorylates various substrates and thus plays a role in different biological processes including cellular senescence or mitophagy (PubMed:24746696, PubMed:32439975). Modulates cellular senescence by regulating mitochondrial dynamics. Mechanistically, participates in mitochondrial fission through dephosphorylating DNM1L/DRP1 (PubMed:32439975). Additionally, dephosphorylates MFN2 in a stress-sensitive manner and consequently protects it from ubiquitination and degradation to promote mitochondrial network formation (PubMed:37498743). Regulates mitophagy independent of PARKIN by interacting with and dephosphorylating FUNDC1, which interacts with LC3 (PubMed:24746696). Regulates anti-oxidative response by forming a tertiary complex with KEAP1 and NRF2 (PubMed:18387606). Regulates necroptosis by acting as a RIPK3 target and recruiting the RIPK1-RIPK3-MLKL necrosis 'attack' complex to mitochondria (PubMed:22265414)

Protein Sequence

10 MAFRQALQLA 20 ACGLAGGSAA 30 VLFSAVAVGK 40 PRAGGDAEPR 50 PAEPPAWAGG 60 ARPGPGVWDP 70 NWDRREPLSL 80 INVRKRNVES 90 GEEELASKLD 100 HYKAKATRHI 110 FLIRHSQYHV 120 DGSLEKDRTL 130 TPLGREQAEL 140 TGLRLASLGL 150 KFNKIVHSSM 160 TRAIETTDII 170 SRHLPGVCKV 180 STDLLREGAP 190 IEPDPPVSHW 200 KPEAVQYYED 210 GARIEAAFRN 220 YIHRADARQE 230 EDSYEIFICH 240 ANVIRYIVCR 250 ALQFPPEGWL 260 RLSLNNGSIT 270 HLVIRPNGRV 280 ALRTLGDTGF MPPDKITRS

Gene Ontology

Classification	GO ID	Description
Cellular Component	GO:0005743	mitochondrial inner membrane
Cellular Component	GO:0005741	mitochondrial outer membrane
Cellular Component	GO:0005739	mitochondrion
Molecular Function	GO:0004722	protein serine/threonine phosphatase activity
Biological Process	GO:0016236	macroautophagy
Biological Process	GO:0070266	necroptotic process
Biological Process	GO:0120163	negative regulation of cold-induced thermogenesis
Biological Process	GO:0090141	positive regulation of mitochondrial fission

Reference

[1] Yang Z, Yan C, Ma J, Peng P, Ren X et al.. Lactylome analysis suggests lactylation-dependent mechanisms of metabolic adaptation in hepatocellular carcinoma.. Nat Metab 5(1):61-79. 2023 Jan. PMID: 36593272.

[2] He C, Zhang J, Bai X, Lu C, Zhang K. Lysine lactylation-based insight to understanding the characterization of cervical cancer.. Biochim Biophys Acta Mol Basis Dis 1870(7):167356. 2024 Oct. PMID: 39025375.