The Eukaryote Linear Motif resource for Functional Sites in Proteins
Accession:
Functional site class:
Nuclear receptor box
Functional site description:
The NR box confers binding to nuclear receptors (NRs), and are found primarily in co-activators of NRs.
ELM Description:
The nuclear receptor box motif (LXXLL) confers binding to nuclear receptors. It must therefore be exposed and reside in natively disordered polypeptide. However, as this motif is hydrophobic, it is particularly prone to false positives buried in globular domains.
Pattern: [^P]L[^P][^P]LL[^P]
Pattern Probability: 0.0002628
Present in taxon: Metazoa
Interaction Domain:
Hormone_recep (PF00104) Ligand-binding domain of nuclear hormone receptor (Stochiometry: 1 : 1)
PDB Structure: 1GWQ
<a href="http://www.rcsb.org/pdb/cgi/explore.cgi?pdbId=1GWQ" title="" target="_blank"><img src="/media/pdb.ico.png"/>1GWQ</a>
o See 24 Instances for LIG_NRBOX
o Abstract
The NR (nuclear receptor) box allows for specific interaction with NRs and is primarily found in co-activators of NRs (Leo,2000). The consensus sequence of the NR box is LXXLL (Heery,1997). Several structures with NR box peptides bound to different NRs have been solved. The structures reveal that the NR box forms an alpha-helix that interacts with a hydrophobic groove in the AF-2 domain. The three leucines form a hydrophobic face that interacts with the AF-2 domain groove, and the helix is positioned by the so-called 'charge clamp', where a conserved glutamate and lysin residue forms hydrogen bonds with the backbone of the N- and C-terminal end of the helix respectively.
Several NR box containing proteins have more than one NR box, such as the steroid receptor co-activator (SRC) family of proteins which have three (TIF2/GRIP) or four (SRC-1). The structure of a 88 peptide from SRC-1, containing two NR boxes, bound to a dimer of the ligand binding domain of PPARgamma shows that each NR box binds to one monomer (Nolte,1998), suggesting that two NR boxes can work in consort. Variants of the LxxLL motif has been reported, but has not yet been incorporated into the ELM resource. The related Corepressor nuclear receptor box (LIG_CORNRBOX) mediates binding of co-repressors to nuclear receptors.
o 3 selected references:

o 6 GO-Terms:

o 24 Instances for LIG_NRBOX
(click table headers for sorting; Notes column: =Number of Switches, =Number of Interactions)
Acc., Gene-, NameStartEndSubsequenceLogic#Ev.OrganismNotes
Q90ZL7 prox1
Q90ZL7_DANRE
69 75 DGEKSNVLRKLLKRANSYED TP 1 Danio rerio (Zebrafish)
P48552 NRIP1
NRIP1_HUMAN
499 505 NSHQKVTLLQLLLGHKNEEN TP 1 Homo sapiens (Human)
2 
Q9JL19 Ncoa6
NCOA6_MOUSE
1494 1500 MREAPTSLSQLLDNSGAPNV TP 1 Mus musculus (House mouse)
1 
Q9UQ80 PA2G4
PA2G4_HUMAN
353 359 MEVQDAELKALLQSSASRKT TP 1 Homo sapiens (Human)
P48552 NRIP1
NRIP1_HUMAN
132 138 GKQDSTLLASLLQSFSSRLQ TP 2 Homo sapiens (Human)
1 
P48552 NRIP1
NRIP1_HUMAN
184 190 YGVASSHLKTLLKKSKVKDQ TP 2 Homo sapiens (Human)
1 
P48552 NRIP1
NRIP1_HUMAN
20 26 DSIVLTYLEGLLMHQAAGGS TP 2 Homo sapiens (Human)
1 
P48552 NRIP1
NRIP1_HUMAN
265 271 PSVACSQLALLLSSEAHLQQ TP 2 Homo sapiens (Human)
1 
P48552 NRIP1
NRIP1_HUMAN
712 718 LLERRTVLQLLLGNPNKGKS TP 2 Homo sapiens (Human)
1 
P48552 NRIP1
NRIP1_HUMAN
500 506 SHQKVTLLQLLLGHKNEENV TP 2 Homo sapiens (Human)
2 
P48552 NRIP1
NRIP1_HUMAN
818 824 SFSKNGLLSRLLRQNQDSYL TP 2 Homo sapiens (Human)
1 
P48552 NRIP1
NRIP1_HUMAN
935 941 ESKSFNVLKQLLLSENCVRD TP 3 Homo sapiens (Human)
1 
Q15596 NCOA2
NCOA2_HUMAN
689 695 LKEKHKILHRLLQDSSSPVD TP 4 Homo sapiens (Human)
1 
P48552 NRIP1
NRIP1_HUMAN
379 385 QAANNSLLLHLLKSQTIPKP TP 3 Homo sapiens (Human)
1 
Q9UBK2 PPARGC1A
PRGC1_HUMAN
143 149 EAEEPSLLKKLLLAPANTQL TP 2 Homo sapiens (Human)
Q15596 NCOA2
NCOA2_HUMAN
744 750 KKKENALLRYLLDKDDTKDI TP 1 Homo sapiens (Human)
1 
O43593 HR
HAIR_HUMAN
565 571 LSGLGDRLCRLLRREREALA TP 1 Homo sapiens (Human)
O43593 HR
HAIR_HUMAN
757 763 GPLPCPSLCELLASTAVKLC TP 1 Homo sapiens (Human)
Q15648 MED1
MED1_HUMAN
603 609 KVSQNPILTSLLQITGNGGS TP 1 Homo sapiens (Human)
1 
Q92793 CREBBP
CBP_HUMAN
357 363 RKLIQQQLVLLLHAHKCQRR FP 2 Homo sapiens (Human)
Q92793 CREBBP
CBP_HUMAN
69 75 AASKHKQLSELLRGGSGSSI TP 2 Homo sapiens (Human)
Q15596 NCOA2
NCOA2_HUMAN
640 646 DSKGQTKLLQLLTTKSDQME TP 3 Homo sapiens (Human)
1 
Q15648 MED1
MED1_HUMAN
644 650 NTKNHPMLMNLLKDNPAQDF TP 2 Homo sapiens (Human)
1 
Q16881-4 TXNRD1
TRXR1_HUMAN
46 52 KAYQEGRLQKLLKMNGPEDL TP 3 Homo sapiens (Human)
2 
2 
Please cite: The Eukaryotic Linear Motif Resource ELM: 10 Years and Counting (PMID:24214962)

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