O70343 (PRGC1_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

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 names

Name:	Ppargc1a
Synonyms:	Pgc1, Pgc1a, Ppargc1

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	797 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	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. Ref.1 Ref.5
Subunit structure	Homooligomer By similarity. Binds MYBBP1A, which inhibits transcriptional activation by this protein. Interacts with LRPPRC By similarity. Interacts with PRDM16. Interacts with LPIN1. Interacts with PML. Ref.4 Ref.6 Ref.7 Ref.9 Ref.11
Subcellular location	Nucleus. Nucleus › PML body Ref.11.
Tissue specificity	Brown adipose tissue, heart, kidney and brain. Ref.1
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. Ref.1 Ref.3 Ref.12
Post-translational modification	Phosphorylation by AMPK in skeletal muscle increases activation of its own promoter. Phosphorylated by CLK2. Ref.8 Ref.10 Heavily acetylated by GCN5 and biologically inactive under conditions of high nutrients. Deacetylated by SIRT1 in low nutrients/high NAD conditions.
Sequence similarities	Contains 1 RRM (RNA recognition motif) domain.

Ontologies

Keywords
Biological process	Transcription Transcription regulation
Cellular component	Nucleus
Ligand	RNA-binding
Molecular function	Activator
PTM	Acetylation Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	cellular response to oxidative stress Inferred from mutant phenotype PubMed 20566846. Source: MGI mitochondrion organization Inferred from electronic annotation. Source: Compara negative regulation of neuron apoptotic process Inferred from mutant phenotype PubMed 20566846. Source: MGI neuron death Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of ATP biosynthetic process Inferred from mutant phenotype PubMed 23150719. Source: UniProtKB positive regulation of cellular respiration Inferred from mutant phenotype PubMed 23150719. Source: UniProtKB positive regulation of energy homeostasis Inferred from mutant phenotype PubMed 23150719. Source: UniProtKB positive regulation of fatty acid oxidation Inferred from electronic annotation. Source: Compara positive regulation of mitochondrial DNA metabolic process Inferred from mutant phenotype PubMed 23150719. Source: UniProtKB positive regulation of mitochondrion organization Inferred from mutant phenotype PubMed 23150719. Source: UniProtKB positive regulation of muscle tissue development Inferred from mutant phenotype PubMed 23150719. Source: UniProtKB positive regulation of sequence-specific DNA binding transcription factor activity Inferred from direct assay PubMed 19651776. Source: BHF-UCL positive regulation of transcription from RNA polymerase II promoter Inferred from mutant phenotype PubMed 21106753. Source: BHF-UCL regulation of N-methyl-D-aspartate selective glutamate receptor activity Inferred from electronic annotation. Source: Compara respiratory electron transport chain Inferred from direct assay Ref.4. Source: MGI response to hypoxia Inferred from electronic annotation. Source: Compara response to muscle activity Inferred from mutant phenotype PubMed 21106753. Source: BHF-UCL transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	cytosol Inferred from electronic annotation. Source: Compara nucleoplasm Traceable author statement. Source: Reactome
Molecular_function	RNA binding Inferred from electronic annotation. Source: UniProtKB-KW chromatin DNA binding Inferred from direct assay PubMed 17952069. Source: MGI ligand-dependent nuclear receptor transcription coactivator activity Inferred from electronic annotation. Source: Compara nucleotide binding Inferred from electronic annotation. Source: InterPro transcription coactivator activity Inferred from mutant phenotype PubMed 16271724. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
Lrpprc	Q6PB66	2	EBI-1371053,EBI-1371262
Sirt1	Q923E4	6	EBI-1371053,EBI-1802585

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 797

797

Peroxisome proliferator-activated receptor gamma coactivator 1-alpha

PRO_0000081733

Regions

Domain

676 – 752

77

RRM

Region

292 – 338

47

Interaction with PPARG By similarity

Motif

142 – 146

5

LXXLL motif

Compositional bias

565 – 598

34

Arg/Ser-rich

Compositional bias

620 – 632

13

Arg/Ser-rich

Amino acid modifications

Modified residue

77

1

N6-acetyllysine Ref.5

Modified residue

144

1

N6-acetyllysine Ref.5

Modified residue

177

1

Phosphothreonine; by AMPK Ref.8

Modified residue

183

1

N6-acetyllysine Ref.5

Modified residue

253

1

N6-acetyllysine Ref.5

Modified residue

270

1

N6-acetyllysine Ref.5

Modified residue

277

1

N6-acetyllysine Ref.5

Modified residue

320

1

N6-acetyllysine Ref.5

Modified residue

346

1

N6-acetyllysine Ref.5

Modified residue

412

1

N6-acetyllysine Ref.5

Modified residue

441

1

N6-acetyllysine Ref.5

Modified residue

450

1

N6-acetyllysine Ref.5

Modified residue

538

1

Phosphoserine; by AMPK Ref.8

Modified residue

757

1

N6-acetyllysine Ref.5

Modified residue

778

1

N6-acetyllysine Ref.5

Experimental info

Mutagenesis

177

1

T → A: Abolishes AMPK-mediated phosphorylation; when associated with A-538. Ref.8

Mutagenesis

538

1

S → A: Abolishes AMPK-mediated phosphorylation; when associated with A-177. Ref.8

Sequence conflict

587

1

S → L in AAH66868. Ref.2

Sequence conflict

629

1

R → C in AAH66868. Ref.2

Secondary structure

1

.

.

.

797

Helix Strand Turn

Details...

Helix

141 – 147

7

Sequences

	Sequence		Length	Mass (Da)
	O70343 [UniParc]. Last modified August 1, 1998. Version 1. Checksum: AE73EE2B3A622B05	FASTA	797	90,588
	10 20 30 40 50 60 MAWDMCSQDS VWSDIECAAL VGEDQPLCPD LPELDLSELD VNDLDTDSFL GGLKWCSDQS 70 80 90 100 110 120 EIISNQYNNE PANIFEKIDE ENEANLLAVL TETLDSLPVD EDGLPSFDAL TDGAVTTDNE 130 140 150 160 170 180 ASPSSMPDGT PPPQEAEEPS LLKKLLLAPA NTQLSYNECS GLSTQNHAAN HTHRIRTNPA 190 200 210 220 230 240 IVKTENSWSN KAKSICQQQK PQRRPCSELL KYLTTNDDPP HTKPTENRNS SRDKCASKKK 250 260 270 280 290 300 SHTQPQSQHA QAKPTTLSLP LTPESPNDPK GSPFENKTIE RTLSVELSGT AGLTPPTTPP 310 320 330 340 350 360 HKANQDNPFK ASPKLKPSCK TVVPPPTKRA RYSECSGTQG SHSTKKGPEQ SELYAQLSKS 370 380 390 400 410 420 SGLSRGHEER KTKRPSLRLF GDHDYCQSLN SKTDILINIS QELQDSRQLD FKDASCDWQG 430 440 450 460 470 480 HICSSTDSGQ CYLRETLEAS KQVSPCSTRK QLQDQEIRAE LNKHFGHPCQ AVFDDKSDKT 490 500 510 520 530 540 SELRDGDFSN EQFSKLPVFI NSGLAMDGLF DDSEDESDKL SYPWDGTQPY SLFDVSPSCS 550 560 570 580 590 600 SFNSPCRDSV SPPKSLFSQR PQRMRSRSRS FSRHRSCSRS PYSRSRSRSP GSRSSSRSCY 610 620 630 640 650 660 YYESSHYRHR THRNSPLYVR SRSRSPYSRR PRYDSYEAYE HERLKRDEYR KEHEKRESER 670 680 690 700 710 720 AKQRERQKQK AIEERRVIYV GKIRPDTTRT ELRDRFEVFG EIEECTVNLR DDGDSYGFIT 730 740 750 760 770 780 YRYTCDAFAA LENGYTLRRS NETDFELYFC GRKQFFKSNY ADLDTNSDDF DPASTKSKYD 790 SLDFDSLLKE AQRSLRR

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"A cold-inducible coactivator of nuclear receptors linked to adaptive thermogenesis." Puigserver P., Wu Z., Park C.W., Graves R., Wright M., Spiegelman B.M. Cell 92:829-839(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, INDUCTION, TISSUE SPECIFICITY. Strain: C57BL/6J. Tissue: Brown adipose tissue.
[2]	"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]. Strain: CD-1. Tissue: Neural stem cell.
[3]	"Role of leptin in peroxisome proliferator-activated receptor gamma coactivator-1 expression." Kakuma T., Wang Z.-W., Pan W., Unger R.H., Zhou Y.-T. Endocrinology 141:4576-4582(2000) [PubMed] [Europe PMC] [Abstract] Cited for: INDUCTION.
[4]	"Suppression of mitochondrial respiration through recruitment of p160 myb binding protein to PGC-1alpha: modulation by p38 MAPK." Fan M., Rhee J., St Pierre J., Handschin C., Puigserver P., Lin J., Jaeger S., Erdjument-Bromage H., Tempst P., Spiegelman B.M. Genes Dev. 18:278-289(2004) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH MYBBP1.
[5]	"Nutrient control of glucose homeostasis through a complex of PGC-1alpha and SIRT1." Rodgers J.T., Lerin C., Haas W., Gygi S.P., Spiegelman B.M., Puigserver P. Nature 434:113-118(2005) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, ACETYLATION AT LYS-77; LYS-144; LYS-183; LYS-253; LYS-270; LYS-277; LYS-320; LYS-346; LYS-412; LYS-441; LYS-450; LYS-757 AND LYS-778, DEACETYLATION BY SIRT1.
[6]	"Lipin 1 is an inducible amplifier of the hepatic PGC-1alpha/PPARalpha regulatory pathway." Finck B.N., Gropler M.C., Chen Z., Leone T.C., Croce M.A., Harris T.E., Lawrence J.C. Jr., Kelly D.P. Cell Metab. 4:199-210(2006) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH LPIN1.
[7]	"Transcriptional control of brown fat determination by PRDM16." Seale P., Kajimura S., Yang W., Chin S., Rohas L.M., Uldry M., Tavernier G., Langin D., Spiegelman B.M. Cell Metab. 6:38-54(2007) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH PRDM16.
[8]	"AMP-activated protein kinase (AMPK) action in skeletal muscle via direct phosphorylation of PGC-1alpha." Jager S., Handschin C., St-Pierre J., Spiegelman B.M. Proc. Natl. Acad. Sci. U.S.A. 104:12017-12022(2007) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION AT THR-177 AND SER-538, MUTAGENESIS OF THR-177 AND SER-538.
[9]	"Regulation of the brown and white fat gene programs through a PRDM16/CtBP transcriptional complex." Kajimura S., Seale P., Tomaru T., Erdjument-Bromage H., Cooper M.P., Ruas J.L., Chin S., Tempst P., Lazar M.A., Spiegelman B.M. Genes Dev. 22:1397-1409(2008) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH PRDM16.
[10]	"Cdc2-like kinase 2 is an insulin-regulated suppressor of hepatic gluconeogenesis." Rodgers J.T., Haas W., Gygi S.P., Puigserver P. Cell Metab. 11:23-34(2010) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION BY CLK2.
[11]	"A metabolic prosurvival role for PML in breast cancer." Carracedo A., Weiss D., Leliaert A.K., Bhasin M., de Boer V.C., Laurent G., Adams A.C., Sundvall M., Song S.J., Ito K., Finley L.S., Egia A., Libermann T., Gerhart-Hines Z., Puigserver P., Haigis M.C., Maratos-Flier E., Richardson A.L., Schafer Z.T., Pandolfi P.P. J. Clin. Invest. 122:3088-3100(2012) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION, INTERACTION WITH PML.
[12]	"A PGC1-alpha-dependent myokine that drives brown-fat-like development of white fat and thermogenesis." Bostrom P., Wu J., Jedrychowski M.P., Korde A., Ye L., Lo J.C., Rasbach K.A., Bostrom E.A., Choi J.H., Long J.Z., Kajimura S., Zingaretti M.C., Vind B.F., Tu H., Cinti S., Hojlund K., Gygi S.P., Spiegelman B.M. Nature 481:463-468(2012) [PubMed] [Europe PMC] [Abstract] Cited for: INDUCTION.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AF049330 mRNA. Translation: AAC13554.1.
BC066868 mRNA. Translation: AAH66868.1.

IPI

IPI00117336.

RefSeq

NP_032930.1. NM_008904.2.

UniGene

Mm.259072.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
3F7D	X-ray	2.20	B	137-150	[»]

ProteinModelPortal

O70343.

SMR

O70343. Positions 674-740.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-38447N.

IntAct

O70343. 7 interactions.

PTM databases

PhosphoSite

O70343.

Proteomic databases

PaxDb

O70343.

PRIDE

O70343.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENSMUST00000132734; ENSMUSP00000117040; ENSMUSG00000029167.

GeneID

19017.

KEGG

mmu:19017.

Organism-specific databases

CTD

10891.

MGI

MGI:1342774. Ppargc1a.

Phylogenomic databases

eggNOG

NOG78353.

HOGENOM

HOG000037431.

HOVERGEN

HBG053678.

InParanoid

O70343.

KO

K07202.

OMA

RLFGDHD.

OrthoDB

EOG4T782R.

Enzyme and pathway databases

Reactome

REACT_109335. Circadian Clock.
REACT_127416. Developmental Biology.
REACT_24972. Circadian Clock (mouse).
REACT_27166. Transcriptional Regulation of Adipocyte Differentiation in 3T3-L1 Pre-adipocytes.

Gene expression databases

ArrayExpress

O70343.

Bgee

O70343.

Genevestigator

O70343.

GermOnline

ENSMUSG00000029167. Mus musculus.

Family and domain databases

Gene3D

3.30.70.330. 1 hit.

InterPro

IPR012677. Nucleotide-bd_a/b_plait.
IPR000504. RRM_dom.
[Graphical view]

Pfam

PF00076. RRM_1. 1 hit.
[Graphical view]

SMART

SM00360. RRM. 1 hit.
[Graphical view]

PROSITE

PS50102. RRM. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

O70343.

NextBio

295448.

SOURCE

Search...

Entry information

Entry name

PRGC1_MOUSE

Accession

Primary (citable) accession number: O70343

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 10, 2004
Last sequence update:	August 1, 1998
Last modified:	May 1, 2013
This is version 116 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program