ID   PGAM5_RAT               Reviewed;         288 AA.
AC   Q562B5;
DT   29-MAY-2007, integrated into UniProtKB/Swiss-Prot.
DT   10-MAY-2005, sequence version 1.
DT   27-MAR-2024, entry version 96.
DE   RecName: Full=Serine/threonine-protein phosphatase PGAM5, mitochondrial;
DE            EC=3.1.3.16;
DE   AltName: Full=Phosphoglycerate mutase family member 5;
GN   Name=Pgam5;
OS   Rattus norvegicus (Rat).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Rattus.
OX   NCBI_TaxID=10116;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Ovary;
RX   PubMed=15489334; DOI=10.1101/gr.2596504;
RG   The MGC Project Team;
RT   "The status, quality, and expansion of the NIH full-length cDNA project:
RT   the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [2]
RP   FUNCTION.
RX   PubMed=22265414; DOI=10.1016/j.cell.2011.11.030;
RA   Wang Z., Jiang H., Chen S., Du F., Wang X.;
RT   "The mitochondrial phosphatase PGAM5 functions at the convergence point of
RT   multiple necrotic death pathways.";
RL   Cell 148:228-243(2012).
CC   -!- FUNCTION: Mitochondrial serine/threonine phosphatase that
CC       dephosphorylates various substrates and thus plays a role in different
CC       biological processes including cellular senescence or mitophagy.
CC       Modulates cellular senescence by regulating mitochondrial dynamics.
CC       Mechanistically, participates in mitochondrial fission through
CC       dephosphorylating DNM1L/DRP1. Additionally, dephosphorylates MFN2 in a
CC       stress-sensitive manner and consequently protects it from
CC       ubiquitination and degradation to promote mitochondrial network
CC       formation. Regulates mitophagy independent of PARKIN by interacting
CC       with and dephosphorylating FUNDC1, which interacts with LC3. Regulates
CC       anti-oxidative response by forming a tertiary complex with KEAP1 and
CC       NRF2 (By similarity). Regulates necroptosis by acting as a RIPK3 target
CC       and recruiting the RIPK1-RIPK3-MLKL necrosis 'attack' complex to
CC       mitochondria (PubMed:22265414). {ECO:0000250|UniProtKB:Q96HS1,
CC       ECO:0000269|PubMed:22265414}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=H2O + O-phospho-L-seryl-[protein] = L-seryl-[protein] +
CC         phosphate; Xref=Rhea:RHEA:20629, Rhea:RHEA-COMP:9863, Rhea:RHEA-
CC         COMP:11604, ChEBI:CHEBI:15377, ChEBI:CHEBI:29999, ChEBI:CHEBI:43474,
CC         ChEBI:CHEBI:83421; EC=3.1.3.16;
CC         Evidence={ECO:0000250|UniProtKB:Q96HS1};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=H2O + O-phospho-L-threonyl-[protein] = L-threonyl-[protein] +
CC         phosphate; Xref=Rhea:RHEA:47004, Rhea:RHEA-COMP:11060, Rhea:RHEA-
CC         COMP:11605, ChEBI:CHEBI:15377, ChEBI:CHEBI:30013, ChEBI:CHEBI:43474,
CC         ChEBI:CHEBI:61977; EC=3.1.3.16;
CC         Evidence={ECO:0000250|UniProtKB:Q96HS1};
CC   -!- SUBUNIT: Dimer. Forms a ternary complex with NFE2L2 and KEAP1.
CC       Interacts with BCL2L1 and MAP3K5. Upon TNF-induced necrosis, forms in
CC       complex with RIPK1, RIPK3 and MLKL; the formation of this complex leads
CC       to PGAM5 phosphorylation. Isoform 2, but not isoform 1, interacts with
CC       DNM1L; this interaction leads to DNM1L dephosphorylation and activation
CC       and eventually to mitochondria fragmentation.
CC       {ECO:0000250|UniProtKB:Q96HS1}.
CC   -!- SUBCELLULAR LOCATION: Mitochondrion outer membrane
CC       {ECO:0000250|UniProtKB:Q96HS1}; Single-pass membrane protein
CC       {ECO:0000255}. Mitochondrion inner membrane
CC       {ECO:0000250|UniProtKB:Q96HS1}; Single-pass membrane protein
CC       {ECO:0000255}.
CC   -!- DOMAIN: The N-terminal 35 amino acids, including the potential
CC       transmembrane alpha-helix, function as a non-cleaved mitochondrial
CC       targeting sequence that targets the protein to the cytosolic side of
CC       the outer mitochondrial membrane. {ECO:0000250}.
CC   -!- PTM: Phosphorylated by the RIPK1/RIPK3 complex under necrotic
CC       conditions. This phosphorylation increases PGAM5 phosphatase activity
CC       (By similarity). {ECO:0000250}.
CC   -!- PTM: Proteolytically cleaved by PARL in response to loss of
CC       mitochondrial membrane potential. {ECO:0000250|UniProtKB:Q96HS1}.
CC   -!- SIMILARITY: Belongs to the phosphoglycerate mutase family. BPG-
CC       dependent PGAM subfamily. {ECO:0000305}.
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DR   EMBL; BC092607; AAH92607.1; -; mRNA.
DR   RefSeq; NP_001020443.1; NM_001025272.1.
DR   AlphaFoldDB; Q562B5; -.
DR   SMR; Q562B5; -.
DR   BioGRID; 252666; 2.
DR   IntAct; Q562B5; 1.
DR   MINT; Q562B5; -.
DR   STRING; 10116.ENSRNOP00000053513; -.
DR   iPTMnet; Q562B5; -.
DR   PhosphoSitePlus; Q562B5; -.
DR   jPOST; Q562B5; -.
DR   PaxDb; 10116-ENSRNOP00000053513; -.
DR   GeneID; 288731; -.
DR   KEGG; rno:288731; -.
DR   UCSC; RGD:1312028; rat.
DR   AGR; RGD:1312028; -.
DR   CTD; 192111; -.
DR   RGD; 1312028; Pgam5.
DR   eggNOG; KOG4609; Eukaryota.
DR   InParanoid; Q562B5; -.
DR   OrthoDB; 2994603at2759; -.
DR   PhylomeDB; Q562B5; -.
DR   Reactome; R-RNO-8934903; Receptor Mediated Mitophagy.
DR   PRO; PR:Q562B5; -.
DR   Proteomes; UP000002494; Unplaced.
DR   GO; GO:0005743; C:mitochondrial inner membrane; ISS:UniProtKB.
DR   GO; GO:0005741; C:mitochondrial outer membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0005739; C:mitochondrion; IBA:GO_Central.
DR   GO; GO:0005096; F:GTPase activator activity; ISS:UniProtKB.
DR   GO; GO:0017018; F:myosin phosphatase activity; IEA:UniProtKB-EC.
DR   GO; GO:0016791; F:phosphatase activity; ISS:UniProtKB.
DR   GO; GO:0004722; F:protein serine/threonine phosphatase activity; ISO:RGD.
DR   GO; GO:0044877; F:protein-containing complex binding; ISO:RGD.
DR   GO; GO:0016311; P:dephosphorylation; ISS:UniProtKB.
DR   GO; GO:0070266; P:necroptotic process; ISS:UniProtKB.
DR   GO; GO:0120163; P:negative regulation of cold-induced thermogenesis; ISS:YuBioLab.
DR   GO; GO:0090141; P:positive regulation of mitochondrial fission; IBA:GO_Central.
DR   CDD; cd07067; HP_PGM_like; 1.
DR   Gene3D; 3.40.50.1240; Phosphoglycerate mutase-like; 1.
DR   InterPro; IPR013078; His_Pase_superF_clade-1.
DR   InterPro; IPR029033; His_PPase_superfam.
DR   PANTHER; PTHR20935; PHOSPHOGLYCERATE MUTASE-RELATED; 1.
DR   PANTHER; PTHR20935:SF0; SERINE_THREONINE-PROTEIN PHOSPHATASE PGAM5, MITOCHONDRIAL; 1.
DR   Pfam; PF00300; His_Phos_1; 1.
DR   SMART; SM00855; PGAM; 1.
DR   SUPFAM; SSF53254; Phosphoglycerate mutase-like; 1.
PE   2: Evidence at transcript level;
KW   Acetylation; Hydrolase; Membrane; Mitochondrion;
KW   Mitochondrion inner membrane; Mitochondrion outer membrane; Necrosis;
KW   Phosphoprotein; Reference proteome; Transmembrane; Transmembrane helix.
FT   CHAIN           1..288
FT                   /note="Serine/threonine-protein phosphatase PGAM5,
FT                   mitochondrial"
FT                   /id="PRO_0000288784"
FT   TOPO_DOM        1..6
FT                   /note="Mitochondrial matrix"
FT                   /evidence="ECO:0000250|UniProtKB:Q96HS1"
FT   TRANSMEM        7..29
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        30..288
FT                   /note="Mitochondrial intermembrane"
FT                   /evidence="ECO:0000250|UniProtKB:Q96HS1"
FT   REGION          76..81
FT                   /note="Interaction with KEAP1"
FT                   /evidence="ECO:0000250"
FT   SITE            24..25
FT                   /note="Cleavage; by PARL"
FT                   /evidence="ECO:0000250|UniProtKB:Q96HS1"
FT   MOD_RES         86
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q96HS1"
FT   MOD_RES         115
FT                   /note="N6-acetyllysine"
FT                   /evidence="ECO:0000250|UniProtKB:Q96HS1"
FT   MOD_RES         143
FT                   /note="N6-acetyllysine"
FT                   /evidence="ECO:0000250|UniProtKB:Q96HS1"
FT   MOD_RES         190
FT                   /note="N6-acetyllysine"
FT                   /evidence="ECO:0000250|UniProtKB:Q96HS1"
SQ   SEQUENCE   288 AA;  32060 MW;  B4DD3F3D276A61C5 CRC64;
     MAFRQALQLA ACGLAGGSAA VLFSAVAVGK PRAGGDADTR TTEPLAWTGA RPGHGVWDSN
     WDRREPLSLI NLKKRNVEFG EDELASRLDH YKAKATRHIF LIRHSQYNVD GSMEKDRTLT
     PLGREQAELT GIRLASLGLK FNKIVHSSMT RAVETTDIIS KHLPGVCRVS TDLLREGAPI
     EPDPPVSHWK PEAVQYYEDG ARIEAAFRNY IHRADAKQEE DSYEIFICHA NVIRYIVCRA
     LQFPPEGWLR LSLNNGSITH LVIRPNGRVA LRTLGDTGFM PPDKITRS
//