The Eukaryote Linear Motif resource for Functional Sites in Proteins
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 with this model: LIG_NRBOX 
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: 1RJK
<a style="white-space:nowrap;" href="http://www.rcsb.org/pdb/cgi/explore.cgi?pdbId=1RJK" target="_blank"><img src="/media/pdb.ico.png"/>1RJK</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)
Protein NameGene NameStartEndSubsequenceLogic#Ev.OrganismNotes
Q90ZL7_DANRE prox1 69 75 DGEKSNVLRKLLKRANSYED TP 1 Danio rerio (Zebrafish)
NRIP1_HUMAN NRIP1 499 505 NSHQKVTLLQLLLGHKNEEN TP 1 Homo sapiens (Human)
2 
NCOA6_MOUSE Ncoa6 1494 1500 MREAPTSLSQLLDNSGAPNV TP 1 Mus musculus (House mouse)
1 
PA2G4_HUMAN PA2G4 353 359 MEVQDAELKALLQSSASRKT TP 1 Homo sapiens (Human)
NRIP1_HUMAN NRIP1 132 138 GKQDSTLLASLLQSFSSRLQ TP 2 Homo sapiens (Human)
1 
NRIP1_HUMAN NRIP1 184 190 YGVASSHLKTLLKKSKVKDQ TP 2 Homo sapiens (Human)
1 
NRIP1_HUMAN NRIP1 20 26 DSIVLTYLEGLLMHQAAGGS TP 2 Homo sapiens (Human)
1 
NRIP1_HUMAN NRIP1 265 271 PSVACSQLALLLSSEAHLQQ TP 2 Homo sapiens (Human)
1 
NRIP1_HUMAN NRIP1 712 718 LLERRTVLQLLLGNPNKGKS TP 2 Homo sapiens (Human)
1 
NRIP1_HUMAN NRIP1 500 506 SHQKVTLLQLLLGHKNEENV TP 2 Homo sapiens (Human)
2 
NRIP1_HUMAN NRIP1 818 824 SFSKNGLLSRLLRQNQDSYL TP 2 Homo sapiens (Human)
1 
NRIP1_HUMAN NRIP1 935 941 ESKSFNVLKQLLLSENCVRD TP 3 Homo sapiens (Human)
1 
NCOA2_HUMAN NCOA2 689 695 LKEKHKILHRLLQDSSSPVD TP 4 Homo sapiens (Human)
1 
NRIP1_HUMAN NRIP1 379 385 QAANNSLLLHLLKSQTIPKP TP 3 Homo sapiens (Human)
1 
PRGC1_HUMAN PPARGC1A 143 149 EAEEPSLLKKLLLAPANTQL TP 2 Homo sapiens (Human)
NCOA2_HUMAN NCOA2 744 750 KKKENALLRYLLDKDDTKDI TP 1 Homo sapiens (Human)
1 
HAIR_HUMAN HR 565 571 LSGLGDRLCRLLRREREALA TP 1 Homo sapiens (Human)
HAIR_HUMAN HR 757 763 GPLPCPSLCELLASTAVKLC TP 1 Homo sapiens (Human)
MED1_HUMAN MED1 603 609 KVSQNPILTSLLQITGNGGS TP 1 Homo sapiens (Human)
1 
CBP_HUMAN CREBBP 357 363 RKLIQQQLVLLLHAHKCQRR FP 2 Homo sapiens (Human)
CBP_HUMAN CREBBP 69 75 AASKHKQLSELLRGGSGSSI TP 2 Homo sapiens (Human)
NCOA2_HUMAN NCOA2 640 646 DSKGQTKLLQLLTTKSDQME TP 3 Homo sapiens (Human)
1 
MED1_HUMAN MED1 644 650 NTKNHPMLMNLLKDNPAQDF TP 2 Homo sapiens (Human)
1 
TRXR1_HUMAN TXNRD1 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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