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Protein

Peroxisome proliferator-activated receptor gamma coactivator 1-alpha

Gene

Ppargc1a

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Transcriptional coactivator for steroid receptors and nuclear receptors. Greatly increases the transcriptional activity of PPARG and thyroid hormone receptor on the uncoupling protein promoter. Can regulate key mitochondrial genes that contribute to the program of adaptive thermogenesis. Plays an essential role in metabolic reprogramming in response to dietary availability through coordination of the expression of a wide array of genes involved in glucose and fatty acid metabolism. Induces the expression of PERM1 in the skeletal muscle in an ESRRA-dependent manner. Also involved in the integration of the circadian rhythms and energy metabolism. Required for oscillatory expression of clock genes, such as ARNTL/BMAL1 and NR1D1, through the coactivation of RORA and RORC, and metabolic genes, such as PDK4 and PEPCK. Isoform 4 specifically activates the expression of IGF1 and suppresses myostatin expression in skeletal muscle leading to muscle fiber hypertrophy.4 Publications

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionActivator, RNA-binding
Biological processBiological rhythms, Transcription, Transcription regulation

Names & Taxonomyi

Protein namesi
Recommended name:
Peroxisome proliferator-activated receptor gamma coactivator 1-alpha
Short name:
PGC-1-alpha
Short name:
PPAR-gamma coactivator 1-alpha
Short name:
PPARGC-1-alpha
Gene namesi
Name:Ppargc1a
Synonyms:Pgc1, Pgc1a, Ppargc1
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 5

Organism-specific databases

MGIiMGI:1342774 Ppargc1a

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

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Disruption phenotypei

Mice show abnormal diurnal rhythms of activity, body temperature and metabolic rate.1 Publication

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi142 – 146LKKLL → AKKAA: Strongly reduces coactivation of RORA activity. 1 Publication5
Mutagenesisi177T → A: Abolishes AMPK-mediated phosphorylation; when associated with A-538. 1 Publication1
Mutagenesisi538S → A: Abolishes AMPK-mediated phosphorylation; when associated with A-177. 1 Publication1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000817331 – 797Peroxisome proliferator-activated receptor gamma coactivator 1-alphaAdd BLAST797

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei77N6-acetyllysine1 Publication1
Modified residuei144N6-acetyllysine1 Publication1
Modified residuei177Phosphothreonine; by AMPK1 Publication1
Modified residuei183N6-acetyllysine1 Publication1
Modified residuei253N6-acetyllysine1 Publication1
Modified residuei270N6-acetyllysine1 Publication1
Modified residuei277N6-acetyllysine1 Publication1
Modified residuei320N6-acetyllysine1 Publication1
Modified residuei346N6-acetyllysine1 Publication1
Modified residuei412N6-acetyllysine1 Publication1
Modified residuei441N6-acetyllysine1 Publication1
Modified residuei450N6-acetyllysine1 Publication1
Modified residuei538Phosphoserine; by AMPK1 Publication1
Modified residuei757N6-acetyllysine1 Publication1
Modified residuei778N6-acetyllysine1 Publication1

Post-translational modificationi

Phosphorylation by AMPK in skeletal muscle increases activation of its own promoter. Phosphorylated by CLK2.2 Publications
Heavily acetylated by GCN5 and biologically inactive under conditions of high nutrients. Deacetylated by SIRT1 in low nutrients/high NAD conditions.1 Publication
Ubiquitinated. Ubiquitination by RNF34 induces proteasomal degradation.By similarity

Keywords - PTMi

Acetylation, Phosphoprotein, Ubl conjugation

Proteomic databases

PaxDbiO70343
PRIDEiO70343

PTM databases

iPTMnetiO70343
PhosphoSitePlusiO70343

Expressioni

Tissue specificityi

White quadriceps and red tibialis anterior (TA) muscles, liver, kidney and brown adipose tissue (at protein level). Skeletal muscle, brown adipose tissue, heart, kidney and brain.3 Publications

Inductioni

Dramatically induced in brown adipose tissue and skeletal muscle by exposure of animals to cold. Up-regulated in brown adipose tissue of obese leptin-deficient (ob/ob) and leptin-unresponsive (db/db) mice. Leptin is required for normal basal and cold-stimulated expression in brown adipose tissue and hyperleptinemia rapidly up-regulates its expression. Induced in muscle by exercise. Oscillates diurnally in liver and skeletal muscle.5 Publications

Gene expression databases

BgeeiENSMUSG00000029167 Expressed in 280 organ(s), highest expression level in diaphragm
ExpressionAtlasiO70343 baseline and differential
GenevisibleiO70343 MM

Interactioni

Subunit structurei

Homooligomer (By similarity). Interacts with MYBBP1A; inhibits MYBBP1A transcriptional activation. Interacts with PRDM16, LPIN1 and PML. Interacts (via LXXLL motif) with RORA and RORC (via AF-2 motif); activates RORA and RORC transcriptional activation. Interacts with LRPPRC (By similarity). Interacts with RNF34 (via RING-type zinc finger) (By similarity).By similarity6 Publications

Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

BioGridi202321, 14 interactors
CORUMiO70343
DIPiDIP-38447N
IntActiO70343, 14 interactors
STRINGi10090.ENSMUSP00000117040

Structurei

Secondary structure

1797
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliO70343
SMRiO70343
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiO70343

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini676 – 752RRMPROSITE-ProRule annotationAdd BLAST77

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni292 – 338Interaction with PPARGBy similarityAdd BLAST47
Regioni349 – 797Mediates interaction with RNF34By similarityAdd BLAST449

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi142 – 146LXXLL motif5

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi565 – 598Arg/Ser-richAdd BLAST34
Compositional biasi620 – 632Arg/Ser-richAdd BLAST13

Phylogenomic databases

eggNOGiENOG410IIVU Eukaryota
ENOG410YQI0 LUCA
GeneTreeiENSGT00530000063196
HOGENOMiHOG000037431
HOVERGENiHBG053678
InParanoidiO70343
KOiK07202
OMAiYESSHCR
OrthoDBiEOG091G029M
PhylomeDBiO70343
TreeFamiTF343068

Family and domain databases

CDDicd12623 RRM_PPARGC1A, 1 hit
Gene3Di3.30.70.330, 1 hit
InterProiView protein in InterPro
IPR012677 Nucleotide-bd_a/b_plait_sf
IPR034605 PGC-1
IPR034625 PGC-1alpha
IPR034833 PPARGC1A_RRM
IPR035979 RBD_domain_sf
IPR000504 RRM_dom
PANTHERiPTHR15528 PTHR15528, 1 hit
PTHR15528:SF10 PTHR15528:SF10, 1 hit
PfamiView protein in Pfam
PF00076 RRM_1, 1 hit
SMARTiView protein in SMART
SM00360 RRM, 1 hit
SUPFAMiSSF54928 SSF54928, 1 hit
PROSITEiView protein in PROSITE
PS50102 RRM, 1 hit

Sequences (4+)i

Sequence statusi: Complete.

This entry describes 4 isoformsi produced by alternative promoter usage and alternative splicing. AlignAdd to basket

This entry has 4 described isoforms and 3 potential isoforms that are computationally mapped.Show allAlign All

Isoform 1 (identifier: O70343-1) [UniParc]FASTAAdd to basket
Also known as: PGC-1a1

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
MAWDMCSQDS VWSDIECAAL VGEDQPLCPD LPELDLSELD VNDLDTDSFL
60 70 80 90 100
GGLKWCSDQS EIISNQYNNE PANIFEKIDE ENEANLLAVL TETLDSLPVD
110 120 130 140 150
EDGLPSFDAL TDGAVTTDNE ASPSSMPDGT PPPQEAEEPS LLKKLLLAPA
160 170 180 190 200
NTQLSYNECS GLSTQNHAAN HTHRIRTNPA IVKTENSWSN KAKSICQQQK
210 220 230 240 250
PQRRPCSELL KYLTTNDDPP HTKPTENRNS SRDKCASKKK SHTQPQSQHA
260 270 280 290 300
QAKPTTLSLP LTPESPNDPK GSPFENKTIE RTLSVELSGT AGLTPPTTPP
310 320 330 340 350
HKANQDNPFK ASPKLKPSCK TVVPPPTKRA RYSECSGTQG SHSTKKGPEQ
360 370 380 390 400
SELYAQLSKS SGLSRGHEER KTKRPSLRLF GDHDYCQSLN SKTDILINIS
410 420 430 440 450
QELQDSRQLD FKDASCDWQG HICSSTDSGQ CYLRETLEAS KQVSPCSTRK
460 470 480 490 500
QLQDQEIRAE LNKHFGHPCQ AVFDDKSDKT SELRDGDFSN EQFSKLPVFI
510 520 530 540 550
NSGLAMDGLF DDSEDESDKL SYPWDGTQPY SLFDVSPSCS SFNSPCRDSV
560 570 580 590 600
SPPKSLFSQR PQRMRSRSRS FSRHRSCSRS PYSRSRSRSP GSRSSSRSCY
610 620 630 640 650
YYESSHYRHR THRNSPLYVR SRSRSPYSRR PRYDSYEAYE HERLKRDEYR
660 670 680 690 700
KEHEKRESER AKQRERQKQK AIEERRVIYV GKIRPDTTRT ELRDRFEVFG
710 720 730 740 750
EIEECTVNLR DDGDSYGFIT YRYTCDAFAA LENGYTLRRS NETDFELYFC
760 770 780 790
GRKQFFKSNY ADLDTNSDDF DPASTKSKYD SLDFDSLLKE AQRSLRR
Length:797
Mass (Da):90,588
Last modified:August 1, 1998 - v1
Checksum:iAE73EE2B3A622B05
GO
Isoform 2 (identifier: O70343-2) [UniParc]FASTAAdd to basket
Also known as: PGC-1a2

The sequence of this isoform differs from the canonical sequence as follows:
     2-16: AWDMCSQDSVWSDIE → LGLSSMDSILK
     108-274: Missing.
     545-680: PCRDSVSPPK...AIEERRVIYV → LNVIIT
     681-797: Missing.

Note: Produced by alternative promoter usage and alternative splicing.
Show »
Length:379
Mass (Da):41,921
Checksum:iF9FC43F94A209D82
GO
Isoform 3 (identifier: O70343-3) [UniParc]FASTAAdd to basket
Also known as: PGC-1a3

The sequence of this isoform differs from the canonical sequence as follows:
     2-16: AWDMCSQDSVWSDIE → LL
     108-274: Missing.
     545-680: PCRDSVSPPK...AIEERRVIYV → LNVIIT
     681-797: Missing.

Note: Produced by alternative promoter usage and alternative splicing.
Show »
Length:370
Mass (Da):41,002
Checksum:iAA98B0425EE8F122
GO
Isoform 4 (identifier: O70343-4) [UniParc]FASTAAdd to basket
Also known as: PGC-1a4

The sequence of this isoform differs from the canonical sequence as follows:
     2-16: AWDMCSQDSVWSDIE → LGLSSMDSILK
     268-500: DPKGSPFENK...EQFSKLPVFI → LFL
     501-797: Missing.

Note: Produced by alternative promoter usage and alternative splicing.
Show »
Length:266
Mass (Da):29,115
Checksum:i317BEC86DF2E9DFB
GO

Computationally mapped potential isoform sequencesi

There are 3 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
A0A0G2JGG3A0A0G2JGG3_MOUSE
Peroxisome proliferator-activated r...
Ppargc1a
696Annotation score:
Q3LIG2Q3LIG2_MOUSE
PPAR gamma coactivator variant form
Ppargc1a PGC-1v
270Annotation score:
D3YZS8D3YZS8_MOUSE
Peroxisome proliferator-activated r...
Ppargc1a
142Annotation score:

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti587S → L in AAH66868 (PubMed:15489334).Curated1
Sequence conflicti629R → C in AAH66868 (PubMed:15489334).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0532752 – 16AWDMC…WSDIE → LGLSSMDSILK in isoform 2 and isoform 4. 1 PublicationAdd BLAST15
Alternative sequenceiVSP_0532762 – 16AWDMC…WSDIE → LL in isoform 3. 1 PublicationAdd BLAST15
Alternative sequenceiVSP_053277108 – 274Missing in isoform 2 and isoform 3. 1 PublicationAdd BLAST167
Alternative sequenceiVSP_053279268 – 500DPKGS…LPVFI → LFL in isoform 4. 1 PublicationAdd BLAST233
Alternative sequenceiVSP_053281501 – 797Missing in isoform 4. 1 PublicationAdd BLAST297
Alternative sequenceiVSP_053278545 – 680PCRDS…RVIYV → LNVIIT in isoform 2 and isoform 3. 1 PublicationAdd BLAST136
Alternative sequenceiVSP_053280681 – 797Missing in isoform 2 and isoform 3. 1 PublicationAdd BLAST117

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF049330 mRNA Translation: AAC13554.1
JX866946 mRNA Translation: AFZ74947.1
JX866947 mRNA Translation: AFZ74948.1
JX866948 mRNA Translation: AFZ74949.1
AK138668 mRNA Translation: BAE23740.1
AK143753 mRNA Translation: BAE25525.1
CH466524 Genomic DNA Translation: EDL37647.1
BC066868 mRNA Translation: AAH66868.1
CCDSiCCDS19282.1 [O70343-1]
RefSeqiNP_032930.1, NM_008904.2 [O70343-1]
UniGeneiMm.259072

Genome annotation databases

EnsembliENSMUST00000132734; ENSMUSP00000117040; ENSMUSG00000029167 [O70343-1]
ENSMUST00000151104; ENSMUSP00000116566; ENSMUSG00000029167 [O70343-4]
GeneIDi19017
KEGGimmu:19017
UCSCiuc008xkc.2 mouse [O70343-1]

Keywords - Coding sequence diversityi

Alternative promoter usage, Alternative splicing

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF049330 mRNA Translation: AAC13554.1
JX866946 mRNA Translation: AFZ74947.1
JX866947 mRNA Translation: AFZ74948.1
JX866948 mRNA Translation: AFZ74949.1
AK138668 mRNA Translation: BAE23740.1
AK143753 mRNA Translation: BAE25525.1
CH466524 Genomic DNA Translation: EDL37647.1
BC066868 mRNA Translation: AAH66868.1
CCDSiCCDS19282.1 [O70343-1]
RefSeqiNP_032930.1, NM_008904.2 [O70343-1]
UniGeneiMm.259072

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3F7DX-ray2.20B137-150[»]
ProteinModelPortaliO70343
SMRiO70343
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi202321, 14 interactors
CORUMiO70343
DIPiDIP-38447N
IntActiO70343, 14 interactors
STRINGi10090.ENSMUSP00000117040

PTM databases

iPTMnetiO70343
PhosphoSitePlusiO70343

Proteomic databases

PaxDbiO70343
PRIDEiO70343

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000132734; ENSMUSP00000117040; ENSMUSG00000029167 [O70343-1]
ENSMUST00000151104; ENSMUSP00000116566; ENSMUSG00000029167 [O70343-4]
GeneIDi19017
KEGGimmu:19017
UCSCiuc008xkc.2 mouse [O70343-1]

Organism-specific databases

CTDi10891
MGIiMGI:1342774 Ppargc1a

Phylogenomic databases

eggNOGiENOG410IIVU Eukaryota
ENOG410YQI0 LUCA
GeneTreeiENSGT00530000063196
HOGENOMiHOG000037431
HOVERGENiHBG053678
InParanoidiO70343
KOiK07202
OMAiYESSHCR
OrthoDBiEOG091G029M
PhylomeDBiO70343
TreeFamiTF343068

Miscellaneous databases

ChiTaRSiPpargc1a mouse
EvolutionaryTraceiO70343
PROiPR:O70343
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000029167 Expressed in 280 organ(s), highest expression level in diaphragm
ExpressionAtlasiO70343 baseline and differential
GenevisibleiO70343 MM

Family and domain databases

CDDicd12623 RRM_PPARGC1A, 1 hit
Gene3Di3.30.70.330, 1 hit
InterProiView protein in InterPro
IPR012677 Nucleotide-bd_a/b_plait_sf
IPR034605 PGC-1
IPR034625 PGC-1alpha
IPR034833 PPARGC1A_RRM
IPR035979 RBD_domain_sf
IPR000504 RRM_dom
PANTHERiPTHR15528 PTHR15528, 1 hit
PTHR15528:SF10 PTHR15528:SF10, 1 hit
PfamiView protein in Pfam
PF00076 RRM_1, 1 hit
SMARTiView protein in SMART
SM00360 RRM, 1 hit
SUPFAMiSSF54928 SSF54928, 1 hit
PROSITEiView protein in PROSITE
PS50102 RRM, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiPRGC1_MOUSE
AccessioniPrimary (citable) accession number: O70343
Secondary accession number(s): L0AM20
, L0AN96, L0APB0, Q3UP72
Entry historyiIntegrated into UniProtKB/Swiss-Prot: May 10, 2004
Last sequence update: August 1, 1998
Last modified: November 7, 2018
This is version 171 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
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Main funding by: National Institutes of Health

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