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Protein

Serine/threonine-protein phosphatase PGAM5, mitochondrial

Gene

PGAM5

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Displays phosphatase activity for serine/threonine residues, and, dephosphorylates and activates MAP3K5 kinase. Has apparently no phosphoglycerate mutase activity. May be regulator of mitochondrial dynamics. Substrate for a KEAP1-dependent ubiquitin ligase complex. Contributes to the repression of NFE2L2-dependent gene expression. Acts as a central mediator for programmed necrosis induced by TNF, by reactive oxygen species and by calcium ionophore.3 Publications

Catalytic activityi

[a protein]-serine/threonine phosphate + H2O = [a protein]-serine/threonine + phosphate.

GO - Molecular functioni

  • GTPase activator activity Source: UniProtKB
  • phosphatase activity Source: UniProtKB
  • protein-containing complex binding Source: UniProtKB
  • protein serine/threonine phosphatase activity Source: CACAO

GO - Biological processi

  • macroautophagy Source: Reactome
  • necroptotic process Source: UniProtKB
  • negative regulation of cold-induced thermogenesis Source: YuBioLab

Keywordsi

Molecular functionHydrolase
Biological processNecrosis

Enzyme and pathway databases

ReactomeiR-HSA-8934903 Receptor Mediated Mitophagy

Names & Taxonomyi

Protein namesi
Recommended name:
Serine/threonine-protein phosphatase PGAM5, mitochondrial (EC:3.1.3.16)
Alternative name(s):
Bcl-XL-binding protein v68
Phosphoglycerate mutase family member 5
Gene namesi
Name:PGAM5
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 12

Organism-specific databases

EuPathDBiHostDB:ENSG00000247077.6
HGNCiHGNC:28763 PGAM5
MIMi614939 gene
neXtProtiNX_Q96HS1

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Transmembranei7 – 29HelicalSequence analysisAdd BLAST23

Keywords - Cellular componenti

Membrane, Mitochondrion, Mitochondrion outer membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi79E → A: Loss of interaction with KEAP1; when associated with A-80. 1 Publication1
Mutagenesisi80S → A: Loss of interaction with KEAP1; when associated with A-79. 1 Publication1
Mutagenesisi105H → A: Loss of phosphatase activity. 1 Publication1

Organism-specific databases

OpenTargetsiENSG00000247077
PharmGKBiPA143485574

Polymorphism and mutation databases

BioMutaiPGAM5
DMDMi150417955

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002887821 – 289Serine/threonine-protein phosphatase PGAM5, mitochondrialAdd BLAST289

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei80PhosphoserineCombined sources1
Modified residuei87PhosphoserineCombined sources1
Modified residuei116N6-acetyllysineCombined sources1
Modified residuei144N6-acetyllysineCombined sources1
Modified residuei191N6-acetyllysineCombined sources1

Post-translational modificationi

Both isoform 1 and isoform 2 are phosphorylated by the RIPK1/RIPK3 complex under necrotic conditions. This phosphorylation increases PGAM5 phosphatase activity.

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiQ96HS1
MaxQBiQ96HS1
PaxDbiQ96HS1
PeptideAtlasiQ96HS1
PRIDEiQ96HS1
ProteomicsDBi76781
76782 [Q96HS1-2]
TopDownProteomicsiQ96HS1-1 [Q96HS1-1]
Q96HS1-2 [Q96HS1-2]

PTM databases

DEPODiQ96HS1
iPTMnetiQ96HS1
PhosphoSitePlusiQ96HS1
SwissPalmiQ96HS1

Expressioni

Gene expression databases

BgeeiENSG00000247077 Expressed in 106 organ(s), highest expression level in skeletal muscle tissue
CleanExiHS_PGAM5
ExpressionAtlasiQ96HS1 baseline and differential
GenevisibleiQ96HS1 HS

Organism-specific databases

HPAiCAB068215
HPA036978
HPA036979

Interactioni

Subunit structurei

Dimer. Forms a ternary complex with NFE2L2 and KEAP1. Interacts with BCL2L1 and MAP3K5. Upon TNF-induced necrosis, forms in complex with RIPK1, RIPK3 and MLKL; the formation of this complex leads to PGAM5 phosphorylation. Isoform 2, but not isoform 1, interacts with DNM1L; this interaction leads to DNM1L dephosphorylation and activation and eventually to mitochondria fragmentation.4 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
MAP3K5Q996832EBI-713608,EBI-476263

Protein-protein interaction databases

BioGridi128154, 93 interactors
CORUMiQ96HS1
DIPiDIP-50735N
ELMiQ96HS1
IntActiQ96HS1, 52 interactors
MINTiQ96HS1
STRINGi9606.ENSP00000438465

Structurei

Secondary structure

1289
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliQ96HS1
SMRiQ96HS1
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ96HS1

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni77 – 82Interaction with KEAP16

Domaini

The N-terminal 35 amino acids, including the potential transmembrane alpha-helix, function as a non-cleaved mitochondrial targeting sequence that targets the protein to the cytosolic side of the outer mitochondrial membrane.1 Publication

Sequence similaritiesi

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG4609 Eukaryota
ENOG410XXCQ LUCA
GeneTreeiENSGT00390000004796
HOGENOMiHOG000261217
HOVERGENiHBG105576
InParanoidiQ96HS1
KOiK15637
OMAiAVQYHED
OrthoDBiEOG091G0DEJ
PhylomeDBiQ96HS1
TreeFamiTF314977

Family and domain databases

CDDicd07067 HP_PGM_like, 1 hit
Gene3Di3.40.50.1240, 1 hit
InterProiView protein in InterPro
IPR013078 His_Pase_superF_clade-1
IPR029033 His_PPase_superfam
PfamiView protein in Pfam
PF00300 His_Phos_1, 1 hit
SMARTiView protein in SMART
SM00855 PGAM, 1 hit
SUPFAMiSSF53254 SSF53254, 1 hit

Sequences (2+)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 2 described isoforms and 1 potential isoform that is computationally mapped.Show allAlign All

Isoform 1 (identifier: Q96HS1-1) [UniParc]FASTAAdd to basket
Also known as: PGAM5-L

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide
        10         20         30         40         50
MAFRQALQLA ACGLAGGSAA VLFSAVAVGK PRAGGDAEPR PAEPPAWAGG
60 70 80 90 100
ARPGPGVWDP NWDRREPLSL INVRKRNVES GEEELASKLD HYKAKATRHI
110 120 130 140 150
FLIRHSQYHV DGSLEKDRTL TPLGREQAEL TGLRLASLGL KFNKIVHSSM
160 170 180 190 200
TRAIETTDII SRHLPGVCKV STDLLREGAP IEPDPPVSHW KPEAVQYYED
210 220 230 240 250
GARIEAAFRN YIHRADARQE EDSYEIFICH ANVIRYIVCR ALQFPPEGWL
260 270 280
RLSLNNGSIT HLVIRPNGRV ALRTLGDTGF MPPDKITRS
Length:289
Mass (Da):32,004
Last modified:May 29, 2007 - v2
Checksum:iEE20D2F0A99FCD83
GO
Isoform 2 (identifier: Q96HS1-2) [UniParc]FASTAAdd to basket
Also known as: PGAM5-S

The sequence of this isoform differs from the canonical sequence as follows:
     240-289: RALQFPPEGWLRLSLNNGSITHLVIRPNGRVALRTLGDTGFMPPDKITRS → SIPPLLSAGDFVLLGS

Show »
Length:255
Mass (Da):28,020
Checksum:i07B881D6D8BE033C
GO

Computationally mapped potential isoform sequencesi

There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
F5GXG4F5GXG4_HUMAN
Serine/threonine-protein phosphatas...
PGAM5
140Annotation score:

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti124G → C in AAK60627 (PubMed:15489334).Curated1
Isoform 2 (identifier: Q96HS1-2)
Sequence conflicti252L → V in AAH08196 (PubMed:16541075).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_025761240 – 289RALQF…KITRS → SIPPLLSAGDFVLLGS in isoform 2. 1 PublicationAdd BLAST50

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
EU249757 mRNA Translation: ABX39494.1
AC135586 Genomic DNA No translation available.
BC008196 mRNA Translation: AAH08196.1
AF357523 mRNA Translation: AAK60627.1
CCDSiCCDS53845.1 [Q96HS1-1]
CCDS9280.1 [Q96HS1-2]
RefSeqiNP_001164014.1, NM_001170543.1 [Q96HS1-1]
NP_612642.2, NM_138575.3 [Q96HS1-2]
UniGeneiHs.102558

Genome annotation databases

EnsembliENST00000317555; ENSP00000321503; ENSG00000247077 [Q96HS1-2]
ENST00000498926; ENSP00000438465; ENSG00000247077 [Q96HS1-1]
GeneIDi192111
KEGGihsa:192111
UCSCiuc001uku.4 human [Q96HS1-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
EU249757 mRNA Translation: ABX39494.1
AC135586 Genomic DNA No translation available.
BC008196 mRNA Translation: AAH08196.1
AF357523 mRNA Translation: AAK60627.1
CCDSiCCDS53845.1 [Q96HS1-1]
CCDS9280.1 [Q96HS1-2]
RefSeqiNP_001164014.1, NM_001170543.1 [Q96HS1-1]
NP_612642.2, NM_138575.3 [Q96HS1-2]
UniGeneiHs.102558

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3MXOX-ray1.70A/B90-289[»]
3O0TX-ray1.90A/B90-289[»]
5MUFX-ray3.10A/B/C54-289[»]
ProteinModelPortaliQ96HS1
SMRiQ96HS1
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi128154, 93 interactors
CORUMiQ96HS1
DIPiDIP-50735N
ELMiQ96HS1
IntActiQ96HS1, 52 interactors
MINTiQ96HS1
STRINGi9606.ENSP00000438465

PTM databases

DEPODiQ96HS1
iPTMnetiQ96HS1
PhosphoSitePlusiQ96HS1
SwissPalmiQ96HS1

Polymorphism and mutation databases

BioMutaiPGAM5
DMDMi150417955

Proteomic databases

EPDiQ96HS1
MaxQBiQ96HS1
PaxDbiQ96HS1
PeptideAtlasiQ96HS1
PRIDEiQ96HS1
ProteomicsDBi76781
76782 [Q96HS1-2]
TopDownProteomicsiQ96HS1-1 [Q96HS1-1]
Q96HS1-2 [Q96HS1-2]

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000317555; ENSP00000321503; ENSG00000247077 [Q96HS1-2]
ENST00000498926; ENSP00000438465; ENSG00000247077 [Q96HS1-1]
GeneIDi192111
KEGGihsa:192111
UCSCiuc001uku.4 human [Q96HS1-1]

Organism-specific databases

CTDi192111
EuPathDBiHostDB:ENSG00000247077.6
GeneCardsiPGAM5
H-InvDBiHIX0017319
HGNCiHGNC:28763 PGAM5
HPAiCAB068215
HPA036978
HPA036979
MIMi614939 gene
neXtProtiNX_Q96HS1
OpenTargetsiENSG00000247077
PharmGKBiPA143485574
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG4609 Eukaryota
ENOG410XXCQ LUCA
GeneTreeiENSGT00390000004796
HOGENOMiHOG000261217
HOVERGENiHBG105576
InParanoidiQ96HS1
KOiK15637
OMAiAVQYHED
OrthoDBiEOG091G0DEJ
PhylomeDBiQ96HS1
TreeFamiTF314977

Enzyme and pathway databases

ReactomeiR-HSA-8934903 Receptor Mediated Mitophagy

Miscellaneous databases

ChiTaRSiPGAM5 human
EvolutionaryTraceiQ96HS1
GenomeRNAii192111
PROiPR:Q96HS1
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000247077 Expressed in 106 organ(s), highest expression level in skeletal muscle tissue
CleanExiHS_PGAM5
ExpressionAtlasiQ96HS1 baseline and differential
GenevisibleiQ96HS1 HS

Family and domain databases

CDDicd07067 HP_PGM_like, 1 hit
Gene3Di3.40.50.1240, 1 hit
InterProiView protein in InterPro
IPR013078 His_Pase_superF_clade-1
IPR029033 His_PPase_superfam
PfamiView protein in Pfam
PF00300 His_Phos_1, 1 hit
SMARTiView protein in SMART
SM00855 PGAM, 1 hit
SUPFAMiSSF53254 SSF53254, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiPGAM5_HUMAN
AccessioniPrimary (citable) accession number: Q96HS1
Secondary accession number(s): A9LN06, C9IZY7, Q96JB0
Entry historyiIntegrated into UniProtKB/Swiss-Prot: May 29, 2007
Last sequence update: May 29, 2007
Last modified: November 7, 2018
This is version 136 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  4. Human chromosome 12
    Human chromosome 12: entries, gene names and cross-references to MIM
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