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UniProtKB - Q15596 (NCOA2_HUMAN)

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Protein

Nuclear receptor coactivator 2

Gene

NCOA2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

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. Critical regulator of glucose metabolism regulation, acts as RORA coactivator to specifically modulate G6PC expression. Involved in the positive regulation of the transcriptional activity of the glucocorticoid receptor NR3C1 by sumoylation enhancer RWDD3. Positively regulates the circadian clock by acting as a transcriptional coactivator for the CLOCK-ARNTL/BMAL1 heterodimer (By similarity).By similarity2 Publications

GO - Molecular functioni

View the complete GO annotation on QuickGO ...

GO - Biological processi

View the complete GO annotation on QuickGO ...

Keywordsi

Molecular functionActivator
Biological processBiological rhythms, Transcription, Transcription regulation

Enzyme and pathway databases

ReactomeiR-HSA-1368082 RORA activates gene expression
R-HSA-1368108 BMAL1:CLOCK,NPAS2 activates circadian gene expression
R-HSA-159418 Recycling of bile acids and salts
R-HSA-192105 Synthesis of bile acids and bile salts
R-HSA-193368 Synthesis of bile acids and bile salts via 7alpha-hydroxycholesterol
R-HSA-193807 Synthesis of bile acids and bile salts via 27-hydroxycholesterol
R-HSA-1989781 PPARA activates gene expression
R-HSA-211976 Endogenous sterols
R-HSA-2151201 Transcriptional activation of mitochondrial biogenesis
R-HSA-2426168 Activation of gene expression by SREBF (SREBP)
R-HSA-3214847 HATs acetylate histones
R-HSA-381340 Transcriptional regulation of white adipocyte differentiation
R-HSA-400206 Regulation of lipid metabolism by Peroxisome proliferator-activated receptor alpha (PPARalpha)
R-HSA-400253 Circadian Clock
R-HSA-5625886 Activated PKN1 stimulates transcription of AR (androgen receptor) regulated genes KLK2 and KLK3
R-HSA-9018519 Estrogen-dependent gene expression
SignaLinkiQ15596
SIGNORiQ15596

Names & Taxonomyi

Protein namesi
Recommended name:
Nuclear receptor coactivator 2
Short name:
NCoA-2
Alternative name(s):
Class E basic helix-loop-helix protein 75
Short name:
bHLHe75
Transcriptional intermediary factor 2
Short name:
hTIF2
Gene namesi
Name:NCOA2
Synonyms:BHLHE75, SRC2, TIF2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo
Proteomesi
  • UP000005640 Componenti: Chromosome 8

Organism-specific databases

EuPathDBiHostDB:ENSG00000140396.12
HGNCiHGNC:7669 NCOA2
MIMi601993 gene
neXtProtiNX_Q15596

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

Involvement in diseasei

Chromosomal aberrations involving NCOA2 may be a cause of acute myeloid leukemias. Inversion inv(8)(p11;q13) generates the KAT6A-NCOA2 oncogene, which consists of the N-terminal part of KAT6A and the C-terminal part of NCOA2/TIF2. KAT6A-NCOA2 binds to CREBBP and disrupts its function in transcription activation.3 Publications

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi644 – 645LL → AA: By itself, does not affect nuclear receptor binding or transcriptional coactivation. Abrogates ligand-induced nuclear receptor binding and transactivation; when associated with 693-A-A-694 and 748-A-A-749. 1 Publication2
Mutagenesisi693 – 694LL → AA: By itself, does not affect nuclear receptor binding or transcriptional coactivation. Abrogates ligand-induced nuclear receptor binding and transactivation; when associated with 644-A-A-665 and 748-A-A-749. 1 Publication2
Mutagenesisi748 – 749LL → AA: By itself, does not affect nuclear receptor binding or transcriptional coactivation. Abrogates ligand-induced nuclear receptor binding and transactivation; when associated with 644-A-A-665 and 693-A-A-694. 1 Publication2
Mutagenesisi1079 – 1083LLDQL → AADQA: Reduces transcriptional coactivation and disrupts interaction with CREBBP/CBP. 1 Publication5
Mutagenesisi1081 – 1082DQ → AA: Has little effect on transcriptional coactivation. 1 Publication2

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei869 – 870Breakpoint for translocation to form KAT6A-NCOA23 Publications2

Organism-specific databases

DisGeNETi10499
OpenTargetsiENSG00000140396
PharmGKBiPA31471

Chemistry databases

DrugBankiDB06871 17-METHYL-17-ALPHA-DIHYDROEQUILENIN
DB07863 2-chloro-5-nitro-N-phenylbenzamide
DB07708 3-CHLORO-2-(4-HYDROXYPHENYL)-2H-INDAZOL-5-OL
DB07712 3-ETHYL-2-(4-HYDROXYPHENYL)-2H-INDAZOL-5-OL
DB01645 Genistein
DB02998 Methyltrienolone
DB08773 RALOXIFENE CORE
DB08601 tributylstannanyl

Polymorphism and mutation databases

BioMutaiNCOA2
DMDMi13626594

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedCombined sources
ChainiPRO_00000944022 – 1464Nuclear receptor coactivator 2Add BLAST1463

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylserineCombined sources1
Modified residuei29PhosphoserineCombined sources1
Cross-linki239Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Modified residuei338Asymmetric dimethylarginineBy similarity1
Modified residuei487PhosphoserineCombined sources1
Modified residuei493PhosphoserineCombined sources1
Modified residuei499PhosphoserineCombined sources1
Modified residuei554PhosphoserineCombined sources1
Modified residuei565PhosphoserineCombined sources1
Modified residuei636N6-acetyllysineBy similarity1
Modified residuei640N6-acetyllysineCombined sources1
Cross-linki648Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Modified residuei682PhosphoserineCombined sources1
Modified residuei699PhosphoserineCombined sources1
Cross-linki705Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Cross-linki731Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Modified residuei736PhosphoserineCombined sources1
Modified residuei771PhosphoserineCombined sources1
Modified residuei780N6-acetyllysineCombined sources1
Modified residuei785N6-acetyllysine; alternateCombined sources1
Cross-linki785Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2); alternateCombined sources
Modified residuei864Asymmetric dimethylarginineBy similarity1
Modified residuei874Asymmetric dimethylarginineBy similarity1
Modified residuei1173Asymmetric dimethylarginineCombined sources1
Modified residuei1177Asymmetric dimethylarginineCombined sources1
Modified residuei1190Asymmetric dimethylarginineCombined sources1
Modified residuei1196Asymmetric dimethylarginineCombined sources1
Modified residuei1203Asymmetric dimethylarginineCombined sources1
Modified residuei1221Asymmetric dimethylarginineCombined sources1
Modified residuei1240Asymmetric dimethylarginineBy similarity1
Modified residuei1261Omega-N-methylarginineCombined sources1
Modified residuei1266Asymmetric dimethylarginineCombined sources1
Cross-linki1454Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources

Keywords - PTMi

Acetylation, Isopeptide bond, Methylation, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiQ15596
MaxQBiQ15596
PaxDbiQ15596
PeptideAtlasiQ15596
PRIDEiQ15596
ProteomicsDBi60649

PTM databases

iPTMnetiQ15596
PhosphoSitePlusiQ15596

Expressioni

Gene expression databases

BgeeiENSG00000140396
CleanExiHS_NCOA2
ExpressionAtlasiQ15596 baseline and differential
GenevisibleiQ15596 HS

Organism-specific databases

HPAiHPA060243

Interactioni

Subunit structurei

Present in a complex containing NCOA3, IKKA, IKKB, IKBKG and CREBBP. Interacts (via C-terminus) with CREBBP. Interacts with ESR1, HIF1A, NCOA1, APEX, NR3C1, NR3C2, CARM1, RARA, and RXRA. Present in a complex containing CARM1 and EP300/P300. Interacts with CASP8AP2 and TTLL5/STAMP. Interacts with PSMB9 and DDX5. Interacts (via LXXLL 1, 2 and 3 motifs) with RORA and RORC (via AF-2 motif). Interacts with RWDD3. Interacts with CLOCK and ARNTL/BMAL1 (By similarity). Interacts with NR4A3; potentiates the activity of the NR4A3 (By similarity). Interacts with NR1H3 (PubMed:19481530).By similarity10 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

  • aryl hydrocarbon receptor binding Source: CAFA
  • ligand-dependent nuclear receptor binding Source: UniProtKB
  • nuclear hormone receptor binding Source: UniProtKB
  • protein dimerization activity Source: InterPro
  • protein domain specific binding Source: CAFA
View the complete GO annotation on QuickGO ...

Protein-protein interaction databases

BioGridi115761, 76 interactors
ComplexPortaliCPX-702 PPARgamma-NCOA2 activated nuclear receptor complex
CPX-816 RXRalpha-RARalpha-NCOA2 retinoic acid receptor complex
CORUMiQ15596
DIPiDIP-5997N
ELMiQ15596
IntActiQ15596, 27 interactors
MINTiQ15596
STRINGi9606.ENSP00000399968

Chemistry databases

BindingDBiQ15596

Structurei

Secondary structure

11464
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi685 – 687Combined sources3
Helixi689 – 693Combined sources5
Beta strandi739 – 741Combined sources3
Helixi743 – 750Combined sources8

3D structure databases

ProteinModelPortaliQ15596
SMRiQ15596
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ15596

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini26 – 83bHLHPROSITE-ProRule annotationAdd BLAST58
Domaini119 – 183PASPROSITE-ProRule annotationAdd BLAST65

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni691 – 743CASP8AP2-bindingBy similarityAdd BLAST53
Regioni730 – 1121Interaction with ARNTLBy similarityAdd BLAST392

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi641 – 645LXXLL motif 15
Motifi690 – 694LXXLL motif 25
Motifi745 – 749LXXLL motif 35
Motifi878 – 882LXXLL motif 45
Motifi1079 – 1087LLXXLXXXL motif9

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi1254 – 1260Poly-Gln7

Domaini

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.1 Publication
The LLXXLXXXL motif is involved in transcriptional coactivation and CREBBP/CBP binding.1 Publication
Contains 2 C-terminal transcription activation domains (AD1 and AD2) that can function independently.1 Publication

Sequence similaritiesi

Belongs to the SRC/p160 nuclear receptor coactivator family.Curated

Keywords - Domaini

Repeat

Phylogenomic databases

eggNOGiENOG410IQ5S Eukaryota
ENOG410XPF9 LUCA
GeneTreeiENSGT00530000063109
HOGENOMiHOG000230947
HOVERGENiHBG052583
InParanoidiQ15596
KOiK11255
OMAiPSDMNGW
OrthoDBiEOG091G00US
PhylomeDBiQ15596
TreeFamiTF332652

Family and domain databases

CDDicd00083 HLH, 1 hit
cd00130 PAS, 1 hit
Gene3Di1.10.287.1070, 1 hit
4.10.280.10, 1 hit
InterProiView protein in InterPro
IPR011598 bHLH_dom
IPR010011 DUF1518
IPR032565 DUF4927
IPR036638 HLH_DNA-bd_sf
IPR028822 NCOA2
IPR009110 Nuc_rcpt_coact
IPR014920 Nuc_rcpt_coact_Ncoa-typ
IPR037077 Nuc_rcpt_coact_Ncoa_int_sf
IPR017426 Nuclear_rcpt_coactivator
IPR000014 PAS
IPR035965 PAS-like_dom_sf
IPR013767 PAS_fold
IPR014935 SRC/p160_LXXLL
PANTHERiPTHR10684 PTHR10684, 1 hit
PTHR10684:SF2 PTHR10684:SF2, 1 hit
PfamiView protein in Pfam
PF07469 DUF1518, 1 hit
PF16279 DUF4927, 1 hit
PF08815 Nuc_rec_co-act, 1 hit
PF00989 PAS, 1 hit
PF08832 SRC-1, 1 hit
PIRSFiPIRSF038181 Nuclear_receptor_coactivator, 1 hit
SMARTiView protein in SMART
SM01151 DUF1518, 1 hit
SM00353 HLH, 1 hit
SM00091 PAS, 1 hit
SUPFAMiSSF47459 SSF47459, 1 hit
SSF55785 SSF55785, 2 hits
SSF69125 SSF69125, 1 hit
PROSITEiView protein in PROSITE
PS50888 BHLH, 1 hit
PS50112 PAS, 1 hit

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

Q15596-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MSGMGENTSD PSRAETRKRK ECPDQLGPSP KRNTEKRNRE QENKYIEELA 
        60         70         80         90        100
ELIFANFNDI DNFNFKPDKC AILKETVKQI RQIKEQEKAA AANIDEVQKS 
       110        120        130        140        150
DVSSTGQGVI DKDALGPMML EALDGFFFVV NLEGNVVFVS ENVTQYLRYN 
       160        170        180        190        200
QEELMNKSVY SILHVGDHTE FVKNLLPKSI VNGGSWSGEP PRRNSHTFNC 
       210        220        230        240        250
RMLVKPLPDS EEEGHDNQEA HQKYETMQCF AVSQPKSIKE EGEDLQSCLI 
       260        270        280        290        300
CVARRVPMKE RPVLPSSESF TTRQDLQGKI TSLDTSTMRA AMKPGWEDLV 
       310        320        330        340        350
RRCIQKFHAQ HEGESVSYAK RHHHEVLRQG LAFSQIYRFS LSDGTLVAAQ 
       360        370        380        390        400
TKSKLIRSQT TNEPQLVISL HMLHREQNVC VMNPDLTGQT MGKPLNPISS 
       410        420        430        440        450
NSPAHQALCS GNPGQDMTLS SNINFPINGP KEQMGMPMGR FGGSGGMNHV 
       460        470        480        490        500
SGMQATTPQG SNYALKMNSP SQSSPGMNPG QPTSMLSPRH RMSPGVAGSP 
       510        520        530        540        550
RIPPSQFSPA GSLHSPVGVC SSTGNSHSYT NSSLNALQAL SEGHGVSLGS 
       560        570        580        590        600
SLASPDLKMG NLQNSPVNMN PPPLSKMGSL DSKDCFGLYG EPSEGTTGQA 
       610        620        630        640        650
ESSCHPGEQK ETNDPNLPPA VSSERADGQS RLHDSKGQTK LLQLLTTKSD 
       660        670        680        690        700
QMEPSPLASS LSDTNKDSTG SLPGSGSTHG TSLKEKHKIL HRLLQDSSSP 
       710        720        730        740        750
VDLAKLTAEA TGKDLSQESS STAPGSEVTI KQEPVSPKKK ENALLRYLLD 
       760        770        780        790        800
KDDTKDIGLP EITPKLERLD SKTDPASNTK LIAMKTEKEE MSFEPGDQPG 
       810        820        830        840        850
SELDNLEEIL DDLQNSQLPQ LFPDTRPGAP AGSVDKQAII NDLMQLTAEN 
       860        870        880        890        900
SPVTPVGAQK TALRISQSTF NNPRPGQLGR LLPNQNLPLD ITLQSPTGAG 
       910        920        930        940        950
PFPPIRNSSP YSVIPQPGMM GNQGMIGNQG NLGNSSTGMI GNSASRPTMP 
       960        970        980        990       1000
SGEWAPQSSA VRVTCAATTS AMNRPVQGGM IRNPAASIPM RPSSQPGQRQ 
      1010       1020       1030       1040       1050
TLQSQVMNIG PSELEMNMGG PQYSQQQAPP NQTAPWPESI LPIDQASFAS 
      1060       1070       1080       1090       1100
QNRQPFGSSP DDLLCPHPAA ESPSDEGALL DQLYLALRNF DGLEEIDRAL 
      1110       1120       1130       1140       1150
GIPELVSQSQ AVDPEQFSSQ DSNIMLEQKA PVFPQQYASQ AQMAQGSYSP 
      1160       1170       1180       1190       1200
MQDPNFHTMG QRPSYATLRM QPRPGLRPTG LVQNQPNQLR LQLQHRLQAQ 
      1210       1220       1230       1240       1250
QNRQPLMNQI SNVSNVNLTL RPGVPTQAPI NAQMLAQRQR EILNQHLRQR 
      1260       1270       1280       1290       1300
QMHQQQQVQQ RTLMMRGQGL NMTPSMVAPS GMPATMSNPR IPQANAQQFP 
      1310       1320       1330       1340       1350
FPPNYGISQQ PDPGFTGATT PQSPLMSPRM AHTQSPMMQQ SQANPAYQAP 
      1360       1370       1380       1390       1400
SDINGWAQGN MGGNSMFSQQ SPPHFGQQAN TSMYSNNMNI NVSMATNTGG 
      1410       1420       1430       1440       1450
MSSMNQMTGQ ISMTSVTSVP TSGLSSMGPE QVNDPALRGG NLFPNQLPGM 
      1460 
DMIKQEGDTT RKYC
Length:1,464
Mass (Da):159,157
Last modified:May 1, 1997 - v2
Checksum:i0A61AA5D1878304B
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_0245461282M → I1 PublicationCorresponds to variant dbSNP:rs2228591Ensembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X97674 mRNA Translation: CAA66263.1
BC114383 mRNA Translation: AAI14384.1
CCDSiCCDS47872.1
RefSeqiNP_001308632.1, NM_001321703.1
NP_001308636.1, NM_001321707.1
NP_001308640.1, NM_001321711.1
NP_001308641.1, NM_001321712.1
NP_001308642.1, NM_001321713.1
NP_006531.1, NM_006540.3
UniGeneiHs.446678
Hs.595378

Genome annotation databases

EnsembliENST00000452400; ENSP00000399968; ENSG00000140396
GeneIDi10499
KEGGihsa:10499
UCSCiuc003xyn.2 human

Keywords - Coding sequence diversityi

Polymorphism

Similar proteinsi

Entry informationi

Entry nameiNCOA2_HUMAN
AccessioniPrimary (citable) accession number: Q15596
Secondary accession number(s): Q14CD2
Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 21, 2001
Last sequence update: May 1, 1997
Last modified: July 18, 2018
This is version 206 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 8
    Human chromosome 8: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

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