Q6XLJ0 (GCR_CALJA) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Glucocorticoid receptor
Short name=GR

Alternative name(s):
Nuclear receptor subfamily 3 group C member 1

Gene names

Name:	NR3C1
Synonyms:	GRL

Organism

Callithrix jacchus (White-tufted-ear marmoset) [Reference proteome]

Taxonomic identifier

9483 [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 › Platyrrhini › Cebidae › Callitrichinae › Callithrix

Protein attributes

Sequence length	777 AA.
Sequence status	Complete.
Protein existence	Evidence at transcript level

General annotation (Comments)

Function	Receptor for glucocorticoids (GC). Has a dual mode of action: as a transcription factor that binds to glucocorticoid response elements (GRE), both for nuclear and mitochondrial DNA, and as a modulator of other transcription factors. Affects inflammatory responses, cellular proliferation and differentiation in target tissues. Could act as a coactivator for STAT5-dependent transcription upon growth hormone (GH) stimulation and could reveal an essential role of hepatic GR in the control of body growth. Involved in chromatin remodeling. Plays a significant role in transactivation By similarity.
Subunit structure	Heteromultimeric cytoplasmic complex with HSP90, HSP70, and an immunophilin. Directly interacts with UNC45A. Upon ligand binding the complex undergoes a conformation change and moves to the nucleus, where it dissociates. Binds to DNA as a homodimer, and as a heterodimer with NR3C2 or the retinoid X receptor. Interacts with the coactivator NCOA6, leading to a strong increase in transcription of target genes. Interaction with numerous other transcription factors modulates transcription activation. Interacts with TRIM28. Interacts with HEXIM1, PELP1 and TGFB1I1. Interacts with NCOA1, NCOA3, SMARCA4, SMARCC1, SMARCD1, and SMARCE1 By similarity.
Subcellular location	Cytoplasm By similarity. Mitochondrion By similarity. Nucleus By similarity. Note: Cytoplasmic in the absence of ligand, nuclear after ligand-binding By similarity.
Tissue specificity	Within the infant and adult hippocampal formation, highest expression observed in the DG granule cell layer with moderate levels in the DG hilus, the CA2-CA4 pyramidal cell layer and the proximal part of the CA1 pyramidal cell layer. Moderate to high expression levels found in the presubiculum and in its' superficial layers. Weak but specific expression detected throughout the entire corticle mantle. In the amygdala, moderate levels were detected in the lateral, central and medial nuclei. Moderate expression levels were present in the PVNh alongside the third ventricle. Ref.1
Domain	Composed of three domains: a modulating N-terminal domain, a DNA-binding domain and a C-terminal ligand-binding domain.
Post-translational modification	Increased proteasome-mediated degradation in response to glucocorticoids By similarity. Phosphorylated in the absence of hormone; becomes hyperphosphorylated in the presence of glucocorticoids By similarity. Ubiquitinated; restricts glucocorticoid-mediated transcriptional signaling By similarity. Sumoylated; this reduces transcription transactivation By similarity.
Sequence similarities	Belongs to the nuclear hormone receptor family. NR3 subfamily. Contains 1 nuclear receptor DNA-binding domain.

Ontologies

Keywords
Biological process	Transcription Transcription regulation
Cellular component	Cytoplasm Mitochondrion Nucleus
Domain	Zinc-finger
Ligand	DNA-binding Lipid-binding Metal-binding Steroid-binding Zinc
Molecular function	Chromatin regulator Receptor
PTM	Isopeptide bond Phosphoprotein Ubl conjugation
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	adrenal gland development Inferred from electronic annotation. Source: Compara chromatin modification Inferred from electronic annotation. Source: UniProtKB-KW glucocorticoid metabolic process Inferred from electronic annotation. Source: Compara mammary gland duct morphogenesis Inferred from electronic annotation. Source: Compara positive regulation of neuron apoptotic process Inferred from electronic annotation. Source: Compara regulation of glucocorticoid biosynthetic process Inferred from electronic annotation. Source: Compara regulation of gluconeogenesis Inferred from electronic annotation. Source: Compara transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	cytosol Inferred from electronic annotation. Source: Compara membrane Inferred from electronic annotation. Source: Compara mitochondrion Inferred from electronic annotation. Source: UniProtKB-SubCell nucleus Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	glucocorticoid receptor activity Inferred from electronic annotation. Source: Compara sequence-specific DNA binding Inferred from electronic annotation. Source: Compara sequence-specific DNA binding transcription factor activity Inferred from electronic annotation. Source: InterPro steroid binding Inferred from electronic annotation. Source: UniProtKB-KW zinc ion binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 777	777	Glucocorticoid receptor		PRO_0000250494
Regions
	DNA binding	421 – 486	66	Nuclear receptor
	Zinc finger	421 – 441	21	NR C4-type
	Zinc finger	457 – 481	25	NR C4-type
	Region	1 – 420	420	Modulating
	Region	487 – 527	41	Hinge
	Region	528 – 777	250	Steroid-binding
	Compositional bias	399 – 418	20	Glu/Pro/Ser/Thr-rich (PEST region)
Amino acid modifications
	Modified residue	113	1	Phosphoserine By similarity
	Modified residue	134	1	Phosphoserine By similarity
	Modified residue	141	1	Phosphoserine By similarity
	Modified residue	203	1	Phosphoserine By similarity
	Modified residue	211	1	Phosphoserine By similarity
	Modified residue	226	1	Phosphoserine By similarity
	Modified residue	267	1	Phosphoserine By similarity
	Cross-link	277		Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO) By similarity
	Cross-link	293		Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO) By similarity
	Cross-link	419		Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) Probable

Sequences

	Sequence		Length	Mass (Da)
	Q6XLJ0 [UniParc]. Last modified July 5, 2004. Version 1. Checksum: B47368C57C4360E5	FASTA	777	85,747
	10 20 30 40 50 60 MDSKESLTPG KEENPSSVLT QERGNVMDFC KILRGGATLK VSVSSTSLAA ASQSDPKQQR 70 80 90 100 110 120 LLVDFPKGSV SNVQQPDLSK AVSLSMGLYM GETETKVMGN DLGFPQQGQI SLSSGETDLQ 130 140 150 160 170 180 LLEESIANLN RSTSVPENPK SSASSSVSAA PKEKEFPKTH SDVSSEQQNL KGQTGTNGGN 190 200 210 220 230 240 VKLYTADQST FDILQDLEFS SGSPGKERNQ SPWRSDLLID ENCLLSPLAG EEDSFLLEGN 250 260 270 280 290 300 SNEDCKPLIL PDTKPKIKDN GDLVLSSSSN VTLPQVKTEK EDFIELCTPG VIKQEKLSTV 310 320 330 340 350 360 YCQASFPGAN IIGNKMSAIS IHGVSTSGGQ MYHYDMNTAS LSQQQDQKPI FNVIPPIPVG 370 380 390 400 410 420 SENWNRCQGS GDDNLTSLGT LNFPGRTVFS NGYSSPSMRP DVSSPPSSSS TATTGPPPKL 430 440 450 460 470 480 CLVCSDEASG CHYGVLTCGS CKVFFKRAVE GQHNYLCAGR NDCIIDKIRR KNCPACRYRK 490 500 510 520 530 540 CLQAGMNLEA RKTKKKIKGI QQATTGVSQE TSENPANKTI VPATLPQLTP TLVSLLEVIE 550 560 570 580 590 600 PEVLYAGYDS TVPDSTWRIM TTLNMLGGRQ VIAAVKWAKA IPGFRNLHLD DQMTLLQYSW 610 620 630 640 650 660 MFLMAFALGW RSYRQASSNL LCFAPDLIIN EQRMTLPCMY DQCKHMLYVS SELHRLQVSY 670 680 690 700 710 720 EEYLCMKTLL LLSSVPKDGL KSQELFDEIR MTYIKELGKA IVKREGNSSQ NWQRFYQLTK 730 740 750 760 770 LLDSMHEVVE NLLNYCFQTF LDKTMSIEFP EMLAEIITNQ LPKYSNGNIK KLLFHQK

References

[1]

"Postnatal ontogeny of hippocampal expression of the mineralocorticoid and glucocorticoid receptors in the common marmoset monkey." Pryce C.R., Feldon J., Fuchs E., Knuesel I., Oertle T., Sengstag C., Spengler M., Weber E., Weston A., Jongen-Relo A. Eur. J. Neurosci. 21:1521-1535(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY. Tissue: Hippocampus.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AY225975 mRNA. Translation: AAP48589.1.
RefSeq	NP_001244179.1. NM_001257250.2.
3D structure databases
HSSP	HSSP built from PDB template 1GDC based on UniProtKB P06536.
ProteinModelPortal	Q6XLJ0.
SMR	Q6XLJ0. Positions 420-491, 523-777.
ModBase	Search...
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSCJAT00000035893; ENSCJAP00000033976; ENSCJAG00000018337. ENSCJAT00000035946; ENSCJAP00000034025; ENSCJAG00000018337.
GeneID	100394916.
Organism-specific databases
CTD	2908.
Phylogenomic databases
GeneTree	ENSGT00700000104072.
HOGENOM	HOG000037950.
HOVERGEN	HBG007583.
OrthoDB	EOG402WRW.
Family and domain databases
Gene3D	1.10.565.10. 1 hit. 3.30.50.10. 1 hit.
InterPro	IPR001409. Glcrtcd_rcpt. IPR008946. Nucl_hormone_rcpt_ligand-bd. IPR000536. Nucl_hrmn_rcpt_lig-bd_core. IPR001723. Str_hrmn_rcpt. IPR001628. Znf_hrmn_rcpt. IPR013088. Znf_NHR/GATA. [Graphical view]
Pfam	PF02155. GCR. 1 hit. PF00104. Hormone_recep. 1 hit. PF00105. zf-C4. 1 hit. [Graphical view]
PRINTS	PR00528. GLCORTICOIDR. PR00398. STRDHORMONER. PR00047. STROIDFINGER.
SMART	SM00430. HOLI. 1 hit. SM00399. ZnF_C4. 1 hit. [Graphical view]
SUPFAM	SSF48508. Str_ncl_receptor. 1 hit.
PROSITE	PS00031. NUCLEAR_REC_DBD_1. 1 hit. PS51030. NUCLEAR_REC_DBD_2. 1 hit. [Graphical view]
ProtoNet	Search...

Entry information

Entry name

GCR_CALJA

Accession

Primary (citable) accession number: Q6XLJ0

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 3, 2006
Last sequence update:	July 5, 2004
Last modified:	April 3, 2013
This is version 70 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program