Q61026 (NCOA2_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Nuclear receptor coactivator 2
Short name=NCoA-2

Alternative name(s):
Glucocorticoid receptor-interacting protein 1
Short name=GRIP-1
Transcriptional intermediary factor 2

Gene names

Name:	Ncoa2
Synonyms:	Grip1, Tif2

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	1462 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Transcriptional coactivator for steroid receptors and nuclear receptors. Coactivator of the steroid binding domain (AF-2) but not of the modulating N-terminal domain (AF-1). Required with NCOA1 to control energy balance between white and brown adipose tissues. Ref.6 Ref.7
Subunit structure	Interacts with NR3C1. Present in a complex containing NCOA3, IKKA, IKKB, IKBKG and CREBBP. Interacts (via C-terminus) with CREBBP. Interacts with ESR1, RARA and RXRA By similarity. Interacts with HIF1A, NCOA1, APEX, NR3C2, and CARM1. Present in a complex containing CARM1 and EP300/P300. Interacts with CASP8AP2 and TTLL5/STAMP. Interacts with PSMB9 and DDX5 By similarity. Ref.1 Ref.5 Ref.7 Ref.8
Subcellular location	Nucleus.
Tissue specificity	Ubiquitous.
Domain	Contains four Leu-Xaa-Xaa-Leu-Leu (LXXLL) motifs. The LXXLL motifs are essential for the association with nuclear receptors and are, at least in part, functionally redundant By similarity. The LLXXLXXXL motif is involved in transcriptional coactivation and CREBBP/CBP binding By similarity. Contains 2 C-terminal transcription activation domains (AD1 and AD2) that can function independently By similarity.
Sequence similarities	Belongs to the SRC/p160 nuclear receptor coactivator family. Contains 1 bHLH (basic helix-loop-helix) domain. Contains 1 PAS (PER-ARNT-SIM) domain.
Sequence caution	The sequence AAB61575.1 differs from that shown. Reason: Frameshift at positions 251, 256, 302, 321, 959, 964 and 983.

Ontologies

Keywords
Biological process	Transcription Transcription regulation
Cellular component	Nucleus
Domain	Repeat
Molecular function	Activator
PTM	Acetylation Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	histone acetylation Inferred from electronic annotation. Source: GOC negative regulation of transcription from RNA polymerase II promoter Inferred from direct assay Ref.4. Source: MGI positive regulation of transcription from RNA polymerase II promoter Inferred from genetic interaction PubMed 15383530. Source: MGI transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	cytoplasm Inferred from direct assay PubMed 11675124. Source: MGI nucleoplasm Traceable author statement. Source: Reactome
Molecular_function	chromatin binding Inferred from direct assay PubMed 16109736. Source: MGI histone acetyltransferase activity Inferred from electronic annotation. Source: InterPro receptor binding Inferred from direct assay Ref.4. Source: MGI signal transducer activity Inferred from electronic annotation. Source: InterPro thyroid hormone receptor coactivator activity Inferred from direct assay PubMed 15072553. Source: MGI
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 1462

1462

Nuclear receptor coactivator 2

PRO_0000094403

Regions

Domain

26 – 83

58

bHLH

Domain

119 – 183

65

PAS

Region

691 – 743

53

CASP8AP2-binding

Motif

641 – 645

5

LXXLL motif 1

Motif

690 – 694

5

LXXLL motif 2

Motif

745 – 749

5

LXXLL motif 3

Motif

878 – 882

5

LXXLL motif 4

Motif

1079 – 1087

9

LLXXLXXXL motif

Amino acid modifications

Modified residue

487

1

Phosphoserine By similarity

Modified residue

493

1

Phosphoserine Ref.11

Modified residue

499

1

Phosphoserine By similarity

Modified residue

640

1

N6-acetyllysine By similarity

Modified residue

699

1

Phosphoserine Ref.9

Modified residue

716

1

Phosphoserine Ref.10

Modified residue

780

1

N6-acetyllysine By similarity

Modified residue

785

1

N6-acetyllysine By similarity

Modified residue

851

1

Phosphoserine By similarity

Experimental info

Sequence conflict

51

1

E → D in AAC53151. Ref.1

Sequence conflict

140 – 141

2

SE → FR in AAB61575. Ref.2

Sequence conflict

194

1

S → T in AAC53151. Ref.1

Sequence conflict

256

1

V → I in AAB61575. Ref.2

Sequence conflict

286

1

S → T in AAB61575. Ref.2

Sequence conflict

420

1

G → S in AAB61575. Ref.2

Sequence conflict

512

1

S → N in AAB61575. Ref.2

Sequence conflict

594

1

E → K in AAB61575. Ref.2

Sequence conflict

607 – 608

2

EE → KK in AAB61575. Ref.2

Sequence conflict

864

1

R → C in AAB61575. Ref.2

Sequence conflict

869

1

T → S in AAB61575. Ref.2

Sequence conflict

884

1

N → Y in AAB61575. Ref.2

Sequence conflict

972

1

M → K in AAB61575. Ref.2

Sequence conflict

980

1

M → K in AAB61575. Ref.2

Sequence conflict

991

1

R → G in AAB61575. Ref.2

Sequence conflict

996

1

P → L in AAB61575. Ref.2

Sequence conflict

1407

1

G → C in AAC53151. Ref.1

Sequence conflict

1446

1

P → L in AAB61575. Ref.2

Secondary structure

1

.

.

.

.

.

1462

Helix Strand Turn

Details...

Helix

689 – 694

6

Helix

743 – 749

7

Sequences

	Sequence		Length	Mass (Da)
	Q61026 [UniParc]. Last modified July 27, 2011. Version 3. Checksum: 619462FF1ACC6067	FASTA	1,462	158,466
	10 20 30 40 50 60 MSGMGENTSD PSRAETRKRK ECPDQLGPSP KRSTEKRNRE QENKYIEELA ELIFANFNDI 70 80 90 100 110 120 DNFNFKPDKC AILKETVKQI RQIKEQEKAA AANIDEVQKS DVSSTGQGVI DKDALGPMML 130 140 150 160 170 180 EALDGFFFVV NLEGSVVFVS ENVTQYLRYN QEELMNKSVY SILHVGDHTE FVKNLLPKSM 190 200 210 220 230 240 VNGGSWSGEP PRRSSHTFNC RMLVKPLPDS EEEGHDSQEA HQKYEAMQCF AVSQPKSIKE 250 260 270 280 290 300 EGEDLQSCLI CVARRVPMKE RPTLPSSESF TTRQDLQGKI TSLDTSTMRA AMKPGWEDLV 310 320 330 340 350 360 RRCIQKFHTQ HEGESLSYAK RHHHEVLRQG LAFSQIYRFS LSDGTLVAAQ TKSKLIRSQT 370 380 390 400 410 420 TNEPQLVISL HMLHREQNVC VMNPDLTGQA MGKPLNPISS SSPAHQALCS GNPGQDMTLG 430 440 450 460 470 480 SNINFPMNGP KEQMGMPMGR FGGSGGMNHV SGMQATTPQG SNYALKMNSP SQSSPGMNPG 490 500 510 520 530 540 QASSVLSPRQ RMSPGVAGSP RIPPSQFSPA GSLHSPVGVC SSTGNSHSYT NSSLNALQAL 550 560 570 580 590 600 SEGHGVSLGS SLASPDLKMG NLQNSPVNMN PPPLSKMGSL DSKDCFGLYG EPSEGTTGQA 610 620 630 640 650 660 EASCHPEEQK GPNDSSMPQA ASGDRAEGHS RLHDSKGQTK LLQLLTTKSD QMEPSPLPSS 670 680 690 700 710 720 LSDTNKDSTG SLPGPGSTHG TSLKEKHKIL HRLLQDSSSP VDLAKLTAEA TGKELSQESS 730 740 750 760 770 780 STAPGSEVTV KQEPASPKKK ENALLRYLLD KDDTKDIGLP EITPKLERLD SKTDPASNTK 790 800 810 820 830 840 LIAMKTVKEE VSFEPSDQPG SELDNLEEIL DDLQNSQLPQ LFPDTRPGAP TGSVDKQAII 850 860 870 880 890 900 NDLMQLTADS SPVPPAGAQK AALRMSQSTF NNPRPGQLGR LLPNQNLPLD ITLQSPTGAG 910 920 930 940 950 960 PFPPIRNSSP YSVIPQPGMM GNQGMLGSQG NLGNNSTGMI GSSTSRPSMP SGEWAPQSPA 970 980 990 1000 1010 1020 VRVTCAATTG AMNRPVQGGM IRNPTASIPM RANSQPGQRQ MLQSQVMNIG PSELEMNMGG 1030 1040 1050 1060 1070 1080 PQYNQQQAPP NQTAPWPESI LPIDQASFAS QNRQPFGSSP DDLLCPHPAA ESPSDEGALL 1090 1100 1110 1120 1130 1140 DQLYLALRNF DGLEEIDRAL GIPELVSQSQ AVDAEQFSSQ ESSIMLEQKP PVFPQQYASQ 1150 1160 1170 1180 1190 1200 AQMAQGGYNP MQDPNFHTMG QRPNYTTLRM QPRPGLRPTG IVQNQPNQLR LQLQHRLQAQ 1210 1220 1230 1240 1250 1260 QNRQPLMNQI SSVSNVNLTL RPGVPTQAPI NAQMLAQRQR EILNQHLRQR QMQQQVQQRT 1270 1280 1290 1300 1310 1320 LMMRGQGLNV TPSMVAPAGL PAAMSNPRIP QANAQQFPFP PNYGISQQPD PGFTGATTPQ 1330 1340 1350 1360 1370 1380 SPLMSPRMAH TQSPMMQQSQ ANPAYQPTSD MNGWAQGSMG GNSMFSQQSP PHFGQQANTS 1390 1400 1410 1420 1430 1440 MYSNNMNISV SMATNTGGLS SMNQMTGQMS MTSVTSVPTS GLPSMGPEQV NDPALRGGNL 1450 1460 FPNQLPGMDM IKQEGDASRK YC

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"GRIP1, a transcriptional coactivator for the AF-2 transactivation domain of steroid, thyroid, retinoid, and vitamin D receptors." Hong H., Kohli K., Garabedian M.J., Stallcup M.R. Mol. Cell. Biol. 17:2735-2744(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], INTERACTION WITH NR3C2. Strain: ICR. Tissue: Brain.
[2]	"The transcriptional co-activator p/CIP binds CBP and mediates nuclear-receptor function." Torchia J., Rose D.W., Inostroza J., Kamei Y., Westin S., Glass C.K., Rosenfeld M.G. Nature 387:677-684(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]	"Lineage-specific biology revealed by a finished genome assembly of the mouse." Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X., Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y., Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S. , Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R., Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K., Eichler E.E., Ponting C.P. PLoS Biol. 7:E1000112-E1000112(2009) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: C57BL/6J.
[4]	"GRIP1, a novel mouse protein that serves as a transcriptional coactivator in yeast for the hormone binding domains of steroid receptors." Hong H., Kohli K., Trivedi A., Johnson D.L., Stallcup M.R. Proc. Natl. Acad. Sci. U.S.A. 93:4948-4952(1996) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 322-1119. Strain: ICR. Tissue: Embryo.
[5]	"Regulation of transcription by a protein methyltransferase." Chen D., Ma H., Hong H., Koh S.S., Huang S.-M., Schurter B.T., Aswad D.W., Stallcup M.R. Science 284:2174-2177(1999) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH CARM1.
[6]	"SRC-1 and TIF2 control energy balance between white and brown adipose tissues." Picard F., Gehin M., Annicotte J.-S., Rocchi S., Champy M.-F., O'Malley B.W., Chambon P., Auwerx J. Cell 111:931-941(2002) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[7]	"Synergy among nuclear receptor coactivators: selective requirement for protein methyltransferase and acetyltransferase activities." Lee Y.-H., Koh S.S., Zhang X., Cheng X., Stallcup M.R. Mol. Cell. Biol. 22:3621-3632(2002) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, IDENTIFICATION IN A COMPLEX WITH EP300 AND NCOA2.
[8]	"Tumor necrosis factor alpha receptor- and Fas-associated FLASH inhibit transcriptional activity of the glucocorticoid receptor by binding to and interfering with its interaction with p160 type nuclear receptor coactivators." Kino T., Chrousos G.P. J. Biol. Chem. 278:3023-3029(2003) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH CASP8AP2.
[9]	"Large-scale phosphorylation analysis of mouse liver." Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-699, MASS SPECTROMETRY. Tissue: Liver.
[10]	"ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage." Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III, Hurov K.E., Luo J., Bakalarski C.E., Zhao Z., Solimini N., Lerenthal Y., Shiloh Y., Gygi S.P., Elledge S.J. Science 316:1160-1166(2007) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-716, MASS SPECTROMETRY. Tissue: Embryonic kidney.
[11]	"The phagosomal proteome in interferon-gamma-activated macrophages." Trost M., English L., Lemieux S., Courcelles M., Desjardins M., Thibault P. Immunity 30:143-154(2009) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-493, MASS SPECTROMETRY. Tissue: Macrophage.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

U39060 mRNA. Translation: AAC53151.1.
AF000582 mRNA. Translation: AAB61575.1. Frameshift.
AC091248 Genomic DNA. No translation available.
AC121538 Genomic DNA. No translation available.

IPI

IPI00116968.

PIR

T30193.
T42639.

RefSeq

NP_032704.2. NM_008678.2.

UniGene

Mm.2537.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1L2I	X-ray	1.95	C/D	686-698	[»]
1OSV	X-ray	2.50	C/D/E	741-752	[»]
1WM0	X-ray	2.90	Y	684-697	[»]
2Q6J	X-ray	2.70	C/D	686-698	[»]
2QA6	X-ray	2.60	C/D	686-698	[»]
2QA8	X-ray	1.85	C/D	686-698	[»]
2QAB	X-ray	1.89	C/D	686-698	[»]
2QGT	X-ray	2.15	C/D	686-698	[»]
2QGW	X-ray	2.39	C/D	686-698	[»]
2QH6	X-ray	2.70	C/D	686-698	[»]
2QPY	X-ray	2.50	B	744-753	[»]
2QR9	X-ray	2.00	C/D	686-698	[»]
2QSE	X-ray	1.85	C/D	686-698	[»]
2QXM	X-ray	2.30	C/D	686-698	[»]
2QZO	X-ray	1.72	C/D	686-698	[»]
3MNE	X-ray	1.96	B	740-752	[»]
3MNO	X-ray	1.55	B	740-752	[»]
3MNP	X-ray	1.50	B	740-752	[»]

ProteinModelPortal

Q61026.

SMR

Q61026. Positions 34-376, 1071-1113.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-5979N.

MINT

MINT-236676.

PTM databases

PhosphoSite

Q61026.

Proteomic databases

PaxDb

Q61026.

PRIDE

Q61026.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENSMUST00000006037; ENSMUSP00000006037; ENSMUSG00000005886.

GeneID

17978.

KEGG

mmu:17978.

UCSC

uc007aim.1. mouse.

Organism-specific databases

CTD

10499.

MGI

MGI:1276533. Ncoa2.

Phylogenomic databases

eggNOG

NOG315556.

GeneTree

ENSGT00530000063109.

HOGENOM

HOG000230947.

HOVERGEN

HBG052583.

InParanoid

Q61026.

KO

K11255.

OMA

TAPWPDS.

Enzyme and pathway databases

Reactome

REACT_127416. Developmental Biology.
REACT_27166. Transcriptional Regulation of Adipocyte Differentiation in 3T3-L1 Pre-adipocytes.

Gene expression databases

ArrayExpress

Q61026.

Bgee

Q61026.

CleanEx

MM_GRIP1.
MM_NCOA2.

Genevestigator

Q61026.

GermOnline

ENSMUSG00000005886. Mus musculus.

Family and domain databases

Gene3D

4.10.280.10. 1 hit.
4.10.630.10. 2 hits.

InterPro

IPR011598. bHLH_dom.
IPR010011. DUF1518.
IPR009110. Nuc_rcpt_coact.
IPR014920. Nuc_rcpt_coact_Ncoa-typ.
IPR017426. Nuclear_rcpt_coactivator.
IPR001610. PAC.
IPR000014. PAS.
IPR013767. PAS_fold.
IPR014935. SRC-1.
IPR008955. Src1_rcpt_coact.
[Graphical view]

Pfam

PF07469. DUF1518. 1 hit.
PF08815. Nuc_rec_co-act. 1 hit.
PF00989. PAS. 1 hit.
PF08832. SRC-1. 1 hit.
[Graphical view]

PIRSF

PIRSF038181. Nuclear_receptor_coactivator. 1 hit.

SMART

SM00353. HLH. 1 hit.
SM00086. PAC. 1 hit.
SM00091. PAS. 1 hit.
[Graphical view]

SUPFAM

SSF47459. HLH_basic. 1 hit.
SSF69125. Nuc_recept_coact. 1 hit.

PROSITE

PS50888. BHLH. 1 hit.
PS50112. PAS. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

ChiTaRS

NCOA2. mouse.

EvolutionaryTrace

Q61026.

NextBio

292941.

SOURCE

Search...

Entry information

Entry name

NCOA2_MOUSE

Accession

Primary (citable) accession number: Q61026
Secondary accession number(s): E9QMH9, O09001, P97759

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 21, 2001
Last sequence update:	July 27, 2011
Last modified:	May 1, 2013
This is version 133 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program