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Protein

Serine/threonine-protein phosphatase PGAM5, mitochondrial

Gene

PGAM5

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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 complex binding Source: UniProtKB
  • receptor signaling protein serine/threonine phosphatase activity Source: CACAO

GO - Biological processi

  • necroptotic process Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Hydrolase

Keywords - Biological processi

Necrosis

Enzyme and pathway databases

BioCyciZFISH:ENSG00000176894-MONOMER.

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

HGNCiHGNC:28763. PGAM5.

Subcellular locationi

  • Mitochondrion outer membrane 1 Publication; Single-pass membrane protein 1 Publication

  • Note: Isoform 2 overexpression results in the formation of disconnected punctuate mitochondria distributed throughout the cytoplasm. Isoform 1 overexpression results in the clustering of mitochondria around the nucleus.

Topology

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

GO - Cellular componenti

Complete GO annotation...

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.
TopDownProteomicsiQ96HS1-1. [Q96HS1-1]
Q96HS1-2. [Q96HS1-2]

PTM databases

DEPODiQ96HS1.
iPTMnetiQ96HS1.
PhosphoSitePlusiQ96HS1.
SwissPalmiQ96HS1.

Expressioni

Gene expression databases

BgeeiENSG00000247077.
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

GO - Molecular functioni

  • protein complex binding Source: UniProtKB

Protein-protein interaction databases

BioGridi128154. 60 interactors.
DIPiDIP-50735N.
IntActiQ96HS1. 41 interactors.
MINTiMINT-1385191.
STRINGi9606.ENSP00000438465.

Structurei

Secondary structure

1289
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi98 – 104Combined sources7
Helixi115 – 117Combined sources3
Helixi122 – 136Combined sources15
Beta strandi143 – 150Combined sources8
Helixi151 – 162Combined sources12
Beta strandi169 – 172Combined sources4
Helixi173 – 175Combined sources3
Helixi197 – 211Combined sources15
Beta strandi223 – 229Combined sources7
Helixi231 – 241Combined sources11
Helixi246 – 251Combined sources6
Beta strandi259 – 264Combined sources6
Beta strandi270 – 277Combined sources8
Helixi283 – 285Combined sources3

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[»]
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.
OMAiKEDSYEI.
OrthoDBiEOG091G0DEJ.
PhylomeDBiQ96HS1.
TreeFamiTF314977.

Family and domain databases

CDDicd07067. HP_PGM_like. 1 hit.
Gene3Di3.40.50.1240. 1 hit.
InterProiIPR013078. His_Pase_superF_clade-1.
IPR029033. His_PPase_superfam.
[Graphical view]
PfamiPF00300. His_Phos_1. 1 hit.
[Graphical view]
SMARTiSM00855. PGAM. 1 hit.
[Graphical view]
SUPFAMiSSF53254. SSF53254. 1 hit.

Sequences (2)i

Sequence statusi: Complete.

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

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

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

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[»]
ProteinModelPortaliQ96HS1.
SMRiQ96HS1.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi128154. 60 interactors.
DIPiDIP-50735N.
IntActiQ96HS1. 41 interactors.
MINTiMINT-1385191.
STRINGi9606.ENSP00000438465.

PTM databases

DEPODiQ96HS1.
iPTMnetiQ96HS1.
PhosphoSitePlusiQ96HS1.
SwissPalmiQ96HS1.

Polymorphism and mutation databases

BioMutaiPGAM5.
DMDMi150417955.

Proteomic databases

EPDiQ96HS1.
MaxQBiQ96HS1.
PaxDbiQ96HS1.
PeptideAtlasiQ96HS1.
PRIDEiQ96HS1.
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.
GeneCardsiPGAM5.
H-InvDBHIX0017319.
HGNCiHGNC:28763. PGAM5.
HPAiCAB068215.
HPA036978.
HPA036979.
MIMi614939. gene.
neXtProtiNX_Q96HS1.
OpenTargetsiENSG00000247077.
PharmGKBiPA143485574.
GenAtlasiSearch...

Phylogenomic databases

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

Enzyme and pathway databases

BioCyciZFISH:ENSG00000176894-MONOMER.

Miscellaneous databases

ChiTaRSiPGAM5. human.
EvolutionaryTraceiQ96HS1.
GenomeRNAii192111.
PROiQ96HS1.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000247077.
CleanExiHS_PGAM5.
ExpressionAtlasiQ96HS1. baseline and differential.
GenevisibleiQ96HS1. HS.

Family and domain databases

CDDicd07067. HP_PGM_like. 1 hit.
Gene3Di3.40.50.1240. 1 hit.
InterProiIPR013078. His_Pase_superF_clade-1.
IPR029033. His_PPase_superfam.
[Graphical view]
PfamiPF00300. His_Phos_1. 1 hit.
[Graphical view]
SMARTiSM00855. PGAM. 1 hit.
[Graphical view]
SUPFAMiSSF53254. SSF53254. 1 hit.
ProtoNetiSearch...

Entry informationi

Entry nameiPGAM5_HUMAN
AccessioniPrimary (citable) accession number: Q96HS1
Secondary accession number(s): A9LN06, C9IZY7, Q96JB0
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 29, 2007
Last sequence update: May 29, 2007
Last modified: November 30, 2016
This is version 121 of the entry and version 2 of the sequence. [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. Human chromosome 12
    Human chromosome 12: entries, gene names and cross-references to MIM
  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. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.