Q9UBK2 (PRGC1_HUMAN) 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

Alternative name(s):
Ligand effect modulator 6

Gene names

Name:	PPARGC1A
Synonyms:	LEM6, PGC1, PGC1A, PPARGC1

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	798 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.3 Ref.8 Ref.9
Subunit structure	Binds MYBBP1A, which inhibits transcriptional activation by this protein By similarity. Interacts with PRDM16 By similarity. Interacts with LRPPRC. Homooligomer. Interacts with LPIN1 By similarity. Interacts with PML By similarity. Ref.3 Ref.7
Subcellular location	Nucleus. Nucleus › PML body By similarity Ref.3.
Tissue specificity	Heart, skeletal muscle, liver and kidney. Expressed at lower levels in brain and pancreas and at very low levels in the intestine and white adipose tissue. In skeletal muscle, levels were lower in obese than in lean subjects and fasting induced a 2-fold increase in levels in the skeletal muscle in obese subjects. Ref.1 Ref.2 Ref.3
Induction	Transcription is repressed by ZNF746 which binds to 'insulin response sequences' its promoter. Ref.8 Ref.9
Post-translational modification	Phosphorylation by AMPK in skeletal muscle increases activation of its own promoter By similarity. Phosphorylated by CLK2 By similarity. 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
Coding sequence diversity	Polymorphism
Ligand	RNA-binding
Molecular function	Activator
PTM	Acetylation Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	RNA splicing Traceable author statement PubMed 12588810. Source: UniProtKB androgen receptor signaling pathway Non-traceable author statement PubMed 15572661. Source: UniProtKB brown fat cell differentiation Traceable author statement PubMed 12588810. Source: UniProtKB cellular glucose homeostasis Non-traceable author statement PubMed 11854298. Source: UniProtKB cellular response to oxidative stress Inferred from sequence or structural similarity. Source: UniProtKB digestion Traceable author statement Ref.1. Source: UniProtKB fatty acid oxidation Non-traceable author statement PubMed 11854298. Source: UniProtKB gluconeogenesis Non-traceable author statement PubMed 11854298. Source: UniProtKB mRNA processing Traceable author statement PubMed 12588810. Source: UniProtKB mitochondrion organization Non-traceable author statement PubMed 11854298. Source: UniProtKB negative regulation of neuron apoptotic process Inferred from sequence or structural similarity. Source: UniProtKB neuron death Inferred from direct assay Ref.9. Source: UniProtKB positive regulation of ATP biosynthetic process Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of energy homeostasis Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of fatty acid oxidation Traceable author statement PubMed 12588810. Source: UniProtKB positive regulation of gluconeogenesis Traceable author statement PubMed 12588810. Source: UniProtKB positive regulation of histone acetylation Traceable author statement PubMed 14636573. Source: UniProtKB positive regulation of mitochondrion organization Inferred from sequence or structural similarity. 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 sequence or structural similarity. Source: BHF-UCL protein complex assembly Traceable author statement PubMed 14636573. Source: UniProtKB protein stabilization Traceable author statement PubMed 14636573. Source: UniProtKB regulation of N-methyl-D-aspartate selective glutamate receptor activity Inferred from electronic annotation. Source: Compara respiratory electron transport chain Inferred from sequence or structural similarity. Source: UniProtKB response to hypoxia Inferred from electronic annotation. Source: Compara response to muscle activity Inferred from sequence or structural similarity. Source: BHF-UCL response to starvation Non-traceable author statement PubMed 11854298. Source: UniProtKB temperature homeostasis Traceable author statement PubMed 1258810. Source: UniProtKB transcription initiation from RNA polymerase II promoter Traceable author statement PubMed 14636573. Source: UniProtKB
Cellular_component	DNA-directed RNA polymerase II, core complex Traceable author statement PubMed 12588810. Source: UniProtKB cytosol Inferred from electronic annotation. Source: Compara
Molecular_function	RNA binding Traceable author statement PubMed 12588810. Source: UniProtKB RNA polymerase II transcription cofactor activity Traceable author statement PubMed 14636573. Source: UniProtKB androgen receptor binding Non-traceable author statement PubMed 15572661. Source: UniProtKB chromatin DNA binding Inferred from sequence or structural similarity. Source: UniProtKB ligand-dependent nuclear receptor transcription coactivator activity Inferred from direct assay PubMed 16488887. Source: BHF-UCL nucleotide binding Inferred from electronic annotation. Source: InterPro transcription factor binding Traceable author statement PubMed 12588810. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
LRPPRC	P42704	2	EBI-765486,EBI-1050853

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 798

798

Peroxisome proliferator-activated receptor gamma coactivator 1-alpha

PRO_0000081732

Regions

Domain

677 – 753

77

RRM

Region

293 – 339

47

Interaction with PPARG

Motif

144 – 148

5

LXXLL motif

Compositional bias

566 – 599

34

Arg/Ser-rich

Compositional bias

621 – 633

13

Arg/Ser-rich

Amino acid modifications

Modified residue

79

1

N6-acetyllysine By similarity

Modified residue

146

1

N6-acetyllysine By similarity

Modified residue

178

1

Phosphothreonine; by AMPK By similarity

Modified residue

184

1

N6-acetyllysine By similarity

Modified residue

254

1

N6-acetyllysine By similarity

Modified residue

271

1

N6-acetyllysine By similarity

Modified residue

278

1

N6-acetyllysine By similarity

Modified residue

321

1

N6-acetyllysine By similarity

Modified residue

347

1

N6-acetyllysine By similarity

Modified residue

413

1

N6-acetyllysine By similarity

Modified residue

442

1

N6-acetyllysine By similarity

Modified residue

451

1

N6-acetyllysine By similarity

Modified residue

539

1

Phosphoserine; by AMPK By similarity

Modified residue

758

1

N6-acetyllysine By similarity

Modified residue

779

1

N6-acetyllysine By similarity

Natural variations

Natural variant

482

1

G → S. Ref.2
Corresponds to variant rs8192678 [ dbSNP | Ensembl ].

VAR_018450

Natural variant

612

1

T → M.
Corresponds to variant rs3736265 [ dbSNP | Ensembl ].

VAR_018451

Secondary structure

1

.

.

.

.

.

798

Helix Strand Turn

Details...

Helix

143 – 149

7

Helix

208 – 214

7

Sequences

	Sequence		Length	Mass (Da)
	Q9UBK2 [UniParc]. Last modified May 1, 2000. Version 1. Checksum: 97DDD3643051A5F1	FASTA	798	91,027
	10 20 30 40 50 60 MAWDMCNQDS ESVWSDIECA ALVGEDQPLC PDLPELDLSE LDVNDLDTDS FLGGLKWCSD 70 80 90 100 110 120 QSEIISNQYN NEPSNIFEKI DEENEANLLA VLTETLDSLP VDEDGLPSFD ALTDGDVTTD 130 140 150 160 170 180 NEASPSSMPD GTPPPQEAEE PSLLKKLLLA PANTQLSYNE CSGLSTQNHA NHNHRIRTNP 190 200 210 220 230 240 AIVKTENSWS NKAKSICQQQ KPQRRPCSEL LKYLTTNDDP PHTKPTENRN SSRDKCTSKK 250 260 270 280 290 300 KSHTQSQSQH LQAKPTTLSL PLTPESPNDP KGSPFENKTI ERTLSVELSG TAGLTPPTTP 310 320 330 340 350 360 PHKANQDNPF RASPKLKSSC KTVVPPPSKK PRYSESSGTQ GNNSTKKGPE QSELYAQLSK 370 380 390 400 410 420 SSVLTGGHEE RKTKRPSLRL FGDHDYCQSI NSKTEILINI SQELQDSRQL ENKDVSSDWQ 430 440 450 460 470 480 GQICSSTDSD QCYLRETLEA SKQVSPCSTR KQLQDQEIRA ELNKHFGHPS QAVFDDEADK 490 500 510 520 530 540 TGELRDSDFS NEQFSKLPMF INSGLAMDGL FDDSEDESDK LSYPWDGTQS YSLFNVSPSC 550 560 570 580 590 600 SSFNSPCRDS VSPPKSLFSQ RPQRMRSRSR SFSRHRSCSR SPYSRSRSRS PGSRSSSRSC 610 620 630 640 650 660 YYYESSHYRH RTHRNSPLYV RSRSRSPYSR RPRYDSYEEY QHERLKREEY RREYEKRESE 670 680 690 700 710 720 RAKQRERQRQ KAIEERRVIY VGKIRPDTTR TELRDRFEVF GEIEECTVNL RDDGDSYGFI 730 740 750 760 770 780 TYRYTCDAFA ALENGYTLRR SNETDFELYF CGRKQFFKSN YADLDSNSDD FDPASTKSKY 790 DSLDFDSLLK EAQRSLRR

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Human peroxisome proliferator activated receptor gamma coactivator 1 (PPARGC1) gene: cDNA sequence, genomic organization, chromosomal localization, and tissue expression." Esterbauer H., Oberkofler H., Krempler F., Patsch W. Genomics 62:98-102(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA], TISSUE SPECIFICITY.
[2]	"Cloning and mRNA tissue distribution of human PPARgamma coactivator-1." Larrouy D., Vidal H., Andreelli F., Laville M., Langin D. Int. J. Obes. Relat. Metab. Disord. 23:1327-1332(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, VARIANT SER-482. Tissue: Skeletal muscle.
[3]	"A tissue-specific coactivator of steroid receptors, identified in a functional genetic screen." Knutti D., Kaul A., Kralli A. Mol. Cell. Biol. 20:2411-2422(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBUNIT, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
[4]	Rieder M.J., Johanson E.J., da Ponte S.H., Stanaway I.B., Ahearn M.O., Bertucci C.B., Wong M.W., Yi Q., Nickerson D.A. Submitted (NOV-2007) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[5]	"Generation and annotation of the DNA sequences of human chromosomes 2 and 4." Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H. , Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., Wilson R.K. Nature 434:724-731(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]	"Defects in energy homeostasis in Leigh syndrome French Canadian variant through PGC-1alpha/LRP130 complex." Cooper M.P., Qu L., Rohas L.M., Lin J., Yang W., Erdjument-Bromage H., Tempst P., Spiegelman B.M. Genes Dev. 20:2996-3009(2006) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH LRPPRC.
[8]	"Nutrient-dependent regulation of PGC-1alpha's acetylation state and metabolic function through the enzymatic activities of Sirt1/GCN5." Dominy J.E. Jr., Lee Y., Gerhart-Hines Z., Puigserver P. Biochim. Biophys. Acta 1804:1676-1683(2010) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, REGULATION BY ACETYLATION.
[9]	"PARIS (ZNF746) repression of PGC-1alpha contributes to neurodegeneration in Parkinson's disease." Shin J.H., Ko H.S., Kang H., Lee Y., Lee Y.I., Pletinkova O., Troconso J.C., Dawson V.L., Dawson T.M. Cell 144:689-702(2011) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INDUCTION.
+	Additional computationally mapped references.

Web resources

SeattleSNPs

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AF108205 , AF108193, AF108194, AF108195, AF108196, AF108197, AF108198, AF108199, AF108200, AF108201, AF108202, AF108203, AF108204 Genomic DNA. Translation: AAF19083.1.
AF106698 mRNA. Translation: AAF18573.1.
AF159714 mRNA. Translation: AAD51615.1.
AF186379 mRNA. Translation: AAD56250.1.
EU280319 Genomic DNA. Translation: ABX44665.1.
AC092834 Genomic DNA. Translation: AAY41058.1.
CH471069 Genomic DNA. Translation: EAW92811.1.

IPI

IPI00033138.

RefSeq

NP_037393.1. NM_013261.3.

UniGene

Hs.527078.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1XB7	X-ray	2.50	P	205-216	[»]
3B1M	X-ray	1.60	B	136-154	[»]
3CS8	X-ray	2.30	B	141-152	[»]
3D24	X-ray	2.11	B/D	198-219	[»]
3U9Q	X-ray	1.52	B	142-150	[»]
3V9T	X-ray	1.65	C	136-154	[»]
3V9V	X-ray	1.60	C	136-154	[»]

ProteinModelPortal

Q9UBK2.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-38449N.

IntAct

Q9UBK2. 5 interactions.

MINT

MINT-6824612.

STRING

9606.ENSP00000264867.

PTM databases

PhosphoSite

Q9UBK2.

Polymorphism databases

DMDM

47117335.

Proteomic databases

PaxDb

Q9UBK2.

PRIDE

Q9UBK2.

Protocols and materials databases

DNASU

10891.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000264867; ENSP00000264867; ENSG00000109819.

GeneID

10891.

KEGG

hsa:10891.

UCSC

uc003gqs.3. human.

Organism-specific databases

CTD

10891.

GeneCards

GC04M023793.

HGNC

HGNC:9237. PPARGC1A.

MIM

604517. gene.

neXtProt

NX_Q9UBK2.

PharmGKB

PA33558.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG78353.

HOGENOM

HOG000037431.

HOVERGEN

HBG053678.

InParanoid

Q9UBK2.

KO

K07202.

OMA

RLFGDHD.

OrthoDB

EOG4T782R.

PhylomeDB

Q9UBK2.

Enzyme and pathway databases

Pathway_Interaction_DB

hdac_classiii_pathway. Signaling events mediated by HDAC Class III.
p38alphabetadownstreampathway. Signaling mediated by p38-alpha and p38-beta.

Reactome

REACT_111045. Developmental Biology.
REACT_24941. Circadian Clock.

Gene expression databases

ArrayExpress

Q9UBK2.

Bgee

Q9UBK2.

CleanEx

HS_PPARGC1A.

Genevestigator

Q9UBK2.

GermOnline

ENSG00000109819. Homo sapiens.

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

ChEMBL

CHEMBL6116.

EvolutionaryTrace

Q9UBK2.

GenomeRNAi

10891.

NextBio

41353.

SOURCE

Search...

Entry information

Entry name

PRGC1_HUMAN

Accession

Primary (citable) accession number: Q9UBK2
Secondary accession number(s): Q4W5M7, Q9UN32

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 10, 2004
Last sequence update:	May 1, 2000
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

Disclaimer

Any 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.