Reactome | UniProt:O70343 Ppargc1a

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UniProt:O70343 Ppargc1a Show undefined attributes

chain	chain:1-797
checksum	AE73EE2B3A622B05
comment	FUNCTION Transcriptional coactivator for steroid receptors and nuclear receptors (PubMed:12754525, PubMed:15744310, PubMed:23217713, PubMed:9529258). Greatly increases the transcriptional activity of PPARG and thyroid hormone receptor on the uncoupling protein promoter (PubMed:12754525, PubMed:15744310, PubMed:23217713, PubMed:9529258). Can regulate key mitochondrial genes that contribute to the program of adaptive thermogenesis (PubMed:12754525, PubMed:15744310, PubMed:23217713, PubMed:9529258). 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 (PubMed:12754525, PubMed:15744310, PubMed:23217713, PubMed:9529258). Acts as a key regulator of gluconeogenesis: stimulates hepatic gluconeogenesis by increasing the expression of gluconeogenic enzymes, and acting together with FOXO1 to promote the fasting gluconeogenic program (PubMed:12754525). Induces the expression of PERM1 in the skeletal muscle in an ESRRA-dependent manner (By similarity). Also involved in the integration of the circadian rhythms and energy metabolism (PubMed:17476214). Required for oscillatory expression of clock genes, such as BMAL1 and NR1D1, through the coactivation of RORA and RORC, and metabolic genes, such as PDK4 and PEPCK (PubMed:17476214).SUBUNIT Homooligomer (By similarity). Interacts with MYBBP1A; inhibits MYBBP1A transcriptional activation (PubMed:14744933). Interacts with PRDM16, LPIN1 and PML (PubMed:16950137, PubMed:17618855, PubMed:18483224, PubMed:22886304). Interacts (via LXXLL motif) with RORA and RORC (via AF-2 motif); activates RORA and RORC transcriptional activation (PubMed:17476214). Interacts with LRPPRC (By similarity). Interacts with FOXO1 (PubMed:12754525). Interacts with NR5A2 (By similarity).INTERACTION 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.INDUCTION 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.PTM Phosphorylation by AMPK in skeletal muscle increases activation of its own promoter (PubMed:17609368). Phosphorylated by CLK2 (PubMed:20074525).PTM Heavily acetylated by KAT2A/GCN5 under conditions of high nutrients, leading to inactivation of PPARGC1A (PubMed:15744310). Deacetylated by SIRT1 in low nutrients/high NAD conditions, leading to its activation (PubMed:15716268, PubMed:15744310).PTM Ubiquitinated. Ubiquitination by RNF34 induces proteasomal degradation.DISRUPTION PHENOTYPE Mice show abnormal diurnal rhythms of activity, body temperature and metabolic rate.MISCELLANEOUS Produced by alternative promoter usage and alternative splicing.MISCELLANEOUS Produced by alternative promoter usage and alternative splicing.MISCELLANEOUS Produced by alternative promoter usage and alternative splicing.
created	[InstanceEdit:143527] Schmidt, EE, 2004-11-12 07:45:10
crossReference	[DatabaseIdentifier:12391339] RefSeq:NP_032930.1 [DatabaseIdentifier:12276450] PRO:O70343 [DatabaseIdentifier:12209914] PDB:3F7D [DatabaseIdentifier:11935316] MGI:1342774 [DatabaseIdentifier:11811299] GlyGen:O70343 [DatabaseIdentifier:11707596] ENSEMBL:ENSMUST00000151104 [DatabaseIdentifier:11707597] ENSEMBL:ENSMUST00000132734 [DatabaseIdentifier:11584898] ENSEMBL:ENSMUSP00000117040 [DatabaseIdentifier:11584897] ENSEMBL:ENSMUSP00000116566 [DatabaseIdentifier:11483057] ENSEMBL:ENSMUSG00000029167
databaseName	UniProt
dbId	152384
description	recommendedName: Peroxisome proliferator-activated receptor gamma coactivator 1-alpha shortName: PGC-1-alpha shortName: PPAR-gamma coactivator 1-alpha shortName: PPARGC-1-alpha
displayName	UniProt:O70343 Ppargc1a
geneName	Ppargc1a Pgc1 Pgc1a Ppargc1
identifier	O70343
isSequenceChanged	false
keyword	3D-structure Acetylation Activator Alternative promoter usage Alternative splicing Biological rhythms Nucleus Phosphoprotein Reference proteome RNA-binding Transcription Transcription regulation Ubl conjugation
modified	[InstanceEdit:9939033] Weiser, Joel, 2025-02-21
moleculeType	Protein
name	Ppargc1a
otherIdentifier	102240_at 10529977 10529979 112668_at 1434099_at 1434100_x_at 1437751_at 1456395_at 1460336_at 17448001 19017 4446378 4461324 4486508 4736906 4795709 4804133 4810106 4818704 4822501 4859084 5004480 5005451 5038549 5105145 5106051 5301504 5317514 5420393 5451373 5509536 A_51_P279038 A_52_P5945 A_55_P2011702 A_55_P2745394 GE1562520 GE34249 GO:0000785 GO:0002021 GO:0003676 GO:0003677 GO:0003712 GO:0003713 GO:0003723 GO:0005515 GO:0005634 GO:0005654 GO:0005829 GO:0005975 GO:0006091 GO:0006094 GO:0006355 GO:0007005 GO:0008134 GO:0010628 GO:0014850 GO:0016605 GO:0016922 GO:0022904 GO:0031490 GO:0031625 GO:0032502 GO:0032922 GO:0034599 GO:0042592 GO:0042752 GO:0043524 GO:0043565 GO:0045722 GO:0045893 GO:0045944 GO:0048511 GO:0048662 GO:0048856 GO:0051402 GO:0060612 GO:0061629 GO:0097009 GO:0106222 GO:0120162 ILMN_2710139 ILMN_2763524 mMC014490 mMC014739
physicalEntity	[EntityWithAccessionedSequence:R-MMU-3903008] monoSumo1-K183-Ppargc1a [nucleoplasm] - Mus musculus [EntityWithAccessionedSequence:R-MMU-1605429] p-T177,S538-Ppargc1a [nucleoplasm] - Mus musculus [EntityWithAccessionedSequence:R-MMU-1605518] p-T262,S265,T298-Ppargc1a [nucleoplasm] - Mus musculus [EntityWithAccessionedSequence:R-MMU-556791] Ppargc1a [nucleoplasm] - Mus musculus [EntityWithAccessionedSequence:R-MMU-1592224] phospho-Ppargc1a [nucleoplasm] - Mus musculus [EntityWithAccessionedSequence:R-MMU-1592204] phospho-Ppargc1a [nucleoplasm] - Mus musculus [EntityWithAccessionedSequence:R-MMU-442481] Ppargc1a [nucleoplasm] - Mus musculus
referenceDatabase	[ReferenceDatabase:2] UniProt
referenceGene	[ReferenceDNASequence:12694531] UCSC:O70343 Ppargc1a [ReferenceDNASequence:12062364] NCBI Gene:19017 Ppargc1a [ReferenceDNASequence:11978271] Monarch:19017 Ppargc1a [ReferenceDNASequence:11888452] KEGG:mmu:19017 Ppargc1a [ReferenceDNASequence:11348482] BioGPS Gene:19017 Ppargc1a
referenceTranscript	[ReferenceRNASequence:12573086] RefSeq:NM_008904.3 Ppargc1a
schemaClass	ReferenceGeneProduct
secondaryIdentifier	PRGC1_MOUSE L0AM20 L0AN96 L0APB0 Q3UP72
sequenceLength	797
species	[Species:48892] Mus musculus
stId	uniprot:O70343
url	http://purl.uniprot.org/uniprot/O70343

Referrals

(interactor)	[UndirectedInteraction:11207535] UniProt:O70343 <-> UniProt:Q6GMV2 (IntAct) [UndirectedInteraction:11207531] UniProt:O70343 <-> UniProt:Q64287 (IntAct) [UndirectedInteraction:11207529] UniProt:O70343 <-> UniProt:Q00899 (IntAct) [UndirectedInteraction:11207527] UniProt:O70343 <-> UniProt:Q923E4 (IntAct)
(referenceEntity)	[EntityWithAccessionedSequence:R-MMU-3903008] monoSumo1-K183-Ppargc1a [nucleoplasm] [EntityWithAccessionedSequence:R-MMU-1605429] p-T177,S538-Ppargc1a [nucleoplasm] [EntityWithAccessionedSequence:R-MMU-1605518] p-T262,S265,T298-Ppargc1a [nucleoplasm] [EntityWithAccessionedSequence:R-MMU-556791] Ppargc1a [nucleoplasm] [EntityWithAccessionedSequence:R-MMU-1592224] phospho-Ppargc1a [nucleoplasm] [EntityWithAccessionedSequence:R-MMU-1592204] phospho-Ppargc1a [nucleoplasm] [EntityWithAccessionedSequence:R-MMU-442481] Ppargc1a [nucleoplasm]
(referenceSequence)	[GroupModifiedResidue:3903009] sumoylated lysine (monoSumo1 [nucleoplasm]) at 183 [ModifiedResidue:1605434] O-phospho-L-threonine at 177 [ModifiedResidue:1605513] O-phospho-L-serine at 538 [ModifiedResidue:1605473] O-phospho-L-threonine at 298 [ModifiedResidue:1605440] O-phospho-L-serine at 265 [ModifiedResidue:1605417] O-phospho-L-threonine at 262 [ModifiedResidue:10034416] O-phospho-L-serine at 266 (in Homo sapiens) [ModifiedResidue:10034417] O-phospho-L-threonine at 299 (in Homo sapiens) [ModifiedResidue:10034415] O-phospho-L-threonine at 263 (in Homo sapiens) [ModifiedResidue:10034412] O-phospho-L-serine at 539 (in Homo sapiens) [ModifiedResidue:10034411] O-phospho-L-threonine at 178 (in Homo sapiens)