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Q96HS1 (PGAM5_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 94. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (4) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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 names
Name:PGAM5
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length289 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.5 Ref.6 Ref.10

Catalytic activity

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

Subunit structure

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. Ref.1 Ref.5 Ref.6 Ref.10

Subcellular location

Mitochondrion outer membrane; Single-pass membrane protein. 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. Ref.5

Domain

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 (Ref.5).

Post-translational modification

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

Sequence similarities

Belongs to the phosphoglycerate mutase family. BPG-dependent PGAM subfamily.

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q96HS1-1)

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.
Isoform 2 (identifier: Q96HS1-2)

Also known as: PGAM5-S;

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

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 289289Serine/threonine-protein phosphatase PGAM5, mitochondrial
PRO_0000288782

Regions

Transmembrane7 – 2923Helical; Potential
Region77 – 826Interaction with KEAP1

Amino acid modifications

Modified residue801Phosphoserine Ref.9
Modified residue1161N6-acetyllysine Ref.7
Modified residue1441N6-acetyllysine Ref.7
Modified residue1911N6-acetyllysine Ref.7

Natural variations

Alternative sequence240 – 28950RALQF…KITRS → SIPPLLSAGDFVLLGS in isoform 2.
VSP_025761

Experimental info

Mutagenesis791E → A: Loss of interaction with KEAP1; when associated with A-80. Ref.1
Mutagenesis801S → A: Loss of interaction with KEAP1; when associated with A-79. Ref.1
Mutagenesis1051H → A: Loss of phosphatase activity. Ref.6
Sequence conflict1241G → C in AAK60627. Ref.3
Isoform 2:
Sequence conflict2521L → V in AAH08196. Ref.2

Secondary structure

........................... 289
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 (PGAM5-L) [UniParc].

Last modified May 29, 2007. Version 2.
Checksum: EE20D2F0A99FCD83

FASTA28932,004
        10         20         30         40         50         60 
MAFRQALQLA ACGLAGGSAA VLFSAVAVGK PRAGGDAEPR PAEPPAWAGG ARPGPGVWDP 

        70         80         90        100        110        120 
NWDRREPLSL INVRKRNVES GEEELASKLD HYKAKATRHI FLIRHSQYHV DGSLEKDRTL 

       130        140        150        160        170        180 
TPLGREQAEL TGLRLASLGL KFNKIVHSSM TRAIETTDII SRHLPGVCKV STDLLREGAP 

       190        200        210        220        230        240 
IEPDPPVSHW KPEAVQYYED GARIEAAFRN YIHRADARQE EDSYEIFICH ANVIRYIVCR 

       250        260        270        280 
ALQFPPEGWL RLSLNNGSIT HLVIRPNGRV ALRTLGDTGF MPPDKITRS 

« Hide

Isoform 2 (PGAM5-S) [UniParc].

Checksum: 07B881D6D8BE033C
Show »

FASTA25528,020

References

« Hide 'large scale' references
[1]"PGAM5, a Bcl-XL-interacting protein, is a novel substrate for the redox-regulated Keap1-dependent ubiquitin ligase complex."
Lo S.-C., Hannink M.
J. Biol. Chem. 281:37893-37903(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], IDENTIFICATION BY MASS SPECTROMETRY, ALTERNATIVE SPLICING, SUBUNIT, INTERACTION WITH BCL2L1 AND KEAP1, MUTAGENESIS OF GLU-79 AND SER-80.
[2]"The finished DNA sequence of human chromosome 12."
Scherer S.E., Muzny D.M., Buhay C.J., Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J., Jackson A., Khan Z.M., Kovar-Smith C., Lewis L.R. expand/collapse author list , Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., Montgomery K.T., Morgan M.B., Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D., Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z., Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H., Draper H., Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S., Kelly S.H., Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H., Santibanez J., Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q., Williams G.A., Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V., Bailey M., Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E., Burkett C.E., Burrell K.L., Calderon E., Cardenas V., Carter K., Casias K., Cavazos I., Cavazos S.R., Ceasar H., Chacko J., Chan S.N., Chavez D., Christopoulos C., Chu J., Cockrell R., Cox C.D., Dang M., Dathorne S.R., David R., Davis C.M., Davy-Carroll L., Deshazo D.R., Donlin J.E., D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J., Escotto M., Flagg N., Forbes L.D., Gabisi A.M., Garza M., Hamilton C., Henderson N., Hernandez O., Hines S., Hogues M.E., Huang M., Idlebird D.G., Johnson R., Jolivet A., Jones S., Kagan R., King L.M., Leal B., Lebow H., Lee S., LeVan J.M., Lewis L.C., London P., Lorensuhewa L.M., Loulseged H., Lovett D.A., Lucier A., Lucier R.L., Ma J., Madu R.C., Mapua P., Martindale A.D., Martinez E., Massey E., Mawhiney S., Meador M.G., Mendez S., Mercado C., Mercado I.C., Merritt C.E., Miner Z.L., Minja E., Mitchell T., Mohabbat F., Mohabbat K., Montgomery B., Moore N., Morris S., Munidasa M., Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O., Nwokenkwo S., Obregon M., Oguh M., Oragunye N., Oviedo R.J., Parish B.J., Parker D.N., Parrish J., Parks K.L., Paul H.A., Payton B.A., Perez A., Perrin W., Pickens A., Primus E.L., Pu L.-L., Puazo M., Quiles M.M., Quiroz J.B., Rabata D., Reeves K., Ruiz S.J., Shao H., Sisson I., Sonaike T., Sorelle R.P., Sutton A.E., Svatek A.F., Svetz L.A., Tamerisa K.S., Taylor T.R., Teague B., Thomas N., Thorn R.D., Trejos Z.Y., Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I., Vera V.A., Villasana D.M., Wang L., Ward-Moore S., Warren J.T., Wei X., White F., Williamson A.L., Wleczyk R., Wooden H.S., Wooden S.H., Yen J., Yoon L., Yoon V., Zorrilla S.E., Nelson D., Kucherlapati R., Weinstock G., Gibbs R.A.
Nature 440:346-351(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
Tissue: Cervix.
[4]"In vitro selection and characterization of Bcl-X(L)-binding proteins from a mix of tissue-specific mRNA display libraries."
Hammond P.W., Alpin J., Rise C.E., Wright M., Kreider B.L.
J. Biol. Chem. 276:20898-20906(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 124-157.
Tissue: Kidney.
[5]"PGAM5 tethers a ternary complex containing Keap1 and Nrf2 to mitochondria."
Lo S.-C., Hannink M.
Exp. Cell Res. 314:1789-1803(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY, SUBUNIT, INTERACTION WITH NFE2L2 AND KEAP1, FUNCTION, SUBCELLULAR LOCATION.
[6]"Mitochondrial phosphoglycerate mutase 5 uses alternate catalytic activity as a protein serine/threonine phosphatase to activate ASK1."
Takeda K., Komuro Y., Hayakawa T., Oguchi H., Ishida Y., Murakami S., Noguchi T., Kinoshita H., Sekine Y., Iemura S., Natsume T., Ichijo H.
Proc. Natl. Acad. Sci. U.S.A. 106:12301-12305(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH MAP3K5, MUTAGENESIS OF HIS-105.
[7]"Lysine acetylation targets protein complexes and co-regulates major cellular functions."
Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C., Olsen J.V., Mann M.
Science 325:834-840(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-116; LYS-144 AND LYS-191, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[8]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[9]"System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation."
Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.
Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-80, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[10]"The mitochondrial phosphatase PGAM5 functions at the convergence point of multiple necrotic death pathways."
Wang Z., Jiang H., Chen S., Du F., Wang X.
Cell 148:228-243(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, IDENTIFICATION IN COMPLEX WITH RIPK1; RIPK3 AND MLKL, INTERACTION WITH DNM1L.
[11]"Crystal structure of human phosphoglycerate mutase family member 5 (PGAM5)."
Structural genomics consortium (SGC)
Submitted (SEP-2010) to the PDB data bank
Cited for: X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) OF 90-289.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
EU249757 mRNA. Translation: ABX39494.1.
AC135586 Genomic DNA. No translation available.
BC008196 mRNA. Translation: AAH08196.1.
AF357523 mRNA. Translation: AAK60627.1.
RefSeqNP_001164014.1. NM_001170543.1.
NP_612642.2. NM_138575.3.
UniGeneHs.102558.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
3MXOX-ray1.70A/B90-289[»]
3O0TX-ray1.90A/B90-289[»]
ProteinModelPortalQ96HS1.
SMRQ96HS1. Positions 89-289.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid128154. 52 interactions.
IntActQ96HS1. 28 interactions.
MINTMINT-1385191.

PTM databases

PhosphoSiteQ96HS1.

Polymorphism databases

DMDM150417955.

Proteomic databases

PaxDbQ96HS1.
PRIDEQ96HS1.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000317555; ENSP00000321503; ENSG00000247077. [Q96HS1-2]
ENST00000498926; ENSP00000438465; ENSG00000247077. [Q96HS1-1]
GeneID192111.
KEGGhsa:192111.
UCSCuc001uku.3. human. [Q96HS1-2]
uc009zyv.3. human. [Q96HS1-1]

Organism-specific databases

CTD192111.
GeneCardsGC12P133287.
H-InvDBHIX0017319.
HGNCHGNC:28763. PGAM5.
HPAHPA036978.
HPA036979.
MIM614939. gene.
neXtProtNX_Q96HS1.
PharmGKBPA143485574.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG71348.
HOGENOMHOG000261217.
HOVERGENHBG105576.
InParanoidQ96HS1.
KOK15637.
OMAWLRMSLN.
OrthoDBEOG7966H1.
PhylomeDBQ96HS1.
TreeFamTF314977.

Gene expression databases

ArrayExpressQ96HS1.
BgeeQ96HS1.
CleanExHS_PGAM5.
GenevestigatorQ96HS1.

Family and domain databases

InterProIPR013078. His_Pase_superF_clade-1.
[Graphical view]
PfamPF00300. His_Phos_1. 1 hit.
[Graphical view]
SMARTSM00855. PGAM. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceQ96HS1.
GenomeRNAi192111.
NextBio89319.
PROQ96HS1.
SOURCESearch...

Entry information

Entry namePGAM5_HUMAN
AccessionPrimary (citable) accession number: Q96HS1
Secondary accession number(s): A9LN06, C9IZY7, Q96JB0
Entry history
Integrated into UniProtKB/Swiss-Prot: May 29, 2007
Last sequence update: May 29, 2007
Last modified: April 16, 2014
This is version 94 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human chromosome 12

Human chromosome 12: entries, gene names and cross-references to MIM