Reviewed, UniProtKB/Swiss-Prot P11416 (RARA_MOUSE)

Names and origin

Protein names

Recommended name:
    Retinoic acid receptor alpha
      Short name=RAR-alpha
Alternative name(s):
    Nuclear receptor subfamily 1 group B member 1

Gene names

Name:	Rara
Synonyms:	Nr1b1

Organism

Mus musculus (Mouse)

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus

Protein attributes

Sequence length	462 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	This is a receptor for retinoic acid. This metabolite has profound effects on vertebrate development. Retinoic acid is a morphogen and is a powerful teratogen. This receptor controls cell function by directly regulating gene expression.
Subunit structure	Interacts with NOCA7 in a ligand-inducible manner By similarity. Interacts with NCOA3 and NCOA6 coactivators, leading to a strong increase of transcription of target genes. Interacts with CDK7.
Subcellular location	Nucleus.
Domain	Composed of three domains: a modulating N-terminal domain, a DNA-binding domain and a C-terminal steroid-binding domain.
Post-translational modification	Phosphorylated. Phosphorylation does not change during cell cycle. Phosphorylation on Ser-77 is crucial for transcriptional activity.
Sequence similarities	Belongs to the nuclear hormone receptor family. NR1 subfamily. Contains 1 nuclear receptor DNA-binding domain.

Ontologies

Keywords
Biological process	Transcription Transcription regulation
Cellular component	Nucleus
Coding sequence diversity	Alternative splicing
Domain	Zinc-finger
Ligand	DNA-binding Metal-binding Zinc
Molecular function	Receptor
PTM	Methylation Phosphoprotein
Technical term	Direct protein sequencing
Gene Ontology (GO)
Biological process	negative regulation of transcription from RNA polymerase II promoter Inferred from direct assay. Source: MGI positive regulation of transcription from RNA polymerase II promoter Inferred from genetic interaction. Source: MGI ureteric bud development Inferred from mutant phenotype. Source: MGI ventricular cardiac muscle cell differentiation Inferred from mutant phenotype. Source: MGI
Cellular component	cytoplasm Inferred from direct assay. Source: MGI nucleus Inferred from direct assay. Source: MGI
Molecular function	protein binding Inferred from physical interaction. Source: UniProtKB retinoic acid receptor activity Inferred from direct assay. Source: MGI sequence-specific DNA binding Inferred from direct assay. Source: MGI transcription factor activity Inferred from direct assay. Source: MGI transcription repressor activity Inferred from direct assay. Source: MGI
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform Alpha-1 (identifier: P11416-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform Alpha-2 (identifier: P11416-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-60: MASNSSSCPT...SGYSTPSPAT → MYESVEVGGL...TPLWNGSNHS

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view
Molecule processing
	Chain	1 – 462	462	Retinoic acid receptor alpha
Regions
	DNA binding	88 – 153	66	Nuclear receptor
	Zinc finger	88 – 108	21	NR C4-type
	Zinc finger	124 – 148	25	NR C4-type
	Region	1 – 87	87	Modulating
	Region	154 – 199	46	Hinge
	Region	200 – 419	220	Ligand-binding
Amino acid modifications
	Modified residue	77	1	Phosphoserine; by CDK7
	Modified residue	347	1	N6,N6,N6-trimethyllysine
	Modified residue	449	1	Phosphoserine Probable
	Modified residue	456	1	Phosphoserine Probable
	Modified residue	461	1	Phosphoserine Probable
Natural variations
	Alternative sequence	1 – 60	60	MASNS…PSPAT → MYESVEVGGLTPAPNPFLVV DFYNQNRACLLQEKGLPAPG PYSTPLRTPLWNGSNHS in isoform Alpha-2.
	Natural variant	391	1	G → A in embryonal carcinoma cell line RAC65.
	Natural variant	392 – 462	71	Missing in embryonal carcinoma cell line RAC65.
Experimental info
	Mutagenesis	74	1	S → A: No effect on phosphorylation, no effect on transcriptional activity
	Mutagenesis	77	1	S → A: Decreases phosphorylation; no effect on interaction with CDK7. Strongly reduces transcriptional activity
	Mutagenesis	449	1	S → A: Changes phosphopeptide pattern, but no effect on transcriptional activity
	Mutagenesis	456	1	S → A: Changes phosphopeptide pattern, but no effect on transcriptional activity
	Mutagenesis	461	1	S → A: Changes phosphopeptide pattern, but no effect on transcriptional activity
	Sequence conflict	163	1	N → K in AAA40031. Ref.5
	Sequence conflict	179	1	T → S in AAA40031. Ref.5
	Sequence conflict	284	1	M → L in AAA40031. Ref.5

Sequences

	Sequence		Length	Mass (Da)
	Isoform Alpha-1 [UniParc]. Last modified October 1, 1989. Version 1. Checksum: 726F7799633A85AD	FASTA	462	50,735
	10 20 30 40 50 60 MASNSSSCPT PGGGHLNGYP VPPYAFFFPP MLGGLSPPGA LTSLQHQLPV SGYSTPSPAT 70 80 90 100 110 120 IETQSSSSEE IVPSPPSPPP LPRIYKPCFV CQDKSSGYHY GVSACEGCKG FFRRSIQKNM 130 140 150 160 170 180 VYTCHRDKNC IINKVTRNRC QYCRLQKCFD VGMSKESVRN DRNKKKKEAP KPECSESYTL 190 200 210 220 230 240 TPEVGELIEK VRKAHQETFP ALCQLGKYTT NNSSEQRVSL DIDLWDKFSE LSTKCIIKTV 250 260 270 280 290 300 EFAKQLPGFT TLTIADQITL LKAACLDILI LRICTRYTPE QDTMTFSDGL TLNRTQMHNA 310 320 330 340 350 360 GFGPLTDLVF AFANQLLPLE MDDAETGLLS AICLICGDRQ DLEQPDKVDM LQEPLLEALK 370 380 390 400 410 420 VYVRKRRPSR PHMFPKMLMK ITDLRSISAK GAERVITLKM EIPGSMPPLI QEMLENSEGL 430 440 450 460 DTLSGQSGGG TRDGGGLAPP PGSCSPSLSP SSHRSSPATQ SP
	Isoform Alpha-2 [UniParc]. Checksum: 15096242FF09896E		459	50,935
	10 20 30 40 50 60 MYESVEVGGL TPAPNPFLVV DFYNQNRACL LQEKGLPAPG PYSTPLRTPL WNGSNHSIET 70 80 90 100 110 120 QSSSSEEIVP SPPSPPPLPR IYKPCFVCQD KSSGYHYGVS ACEGCKGFFR RSIQKNMVYT 130 140 150 160 170 180 CHRDKNCIIN KVTRNRCQYC RLQKCFDVGM SKESVRNDRN KKKKEAPKPE CSESYTLTPE 190 200 210 220 230 240 VGELIEKVRK AHQETFPALC QLGKYTTNNS SEQRVSLDID LWDKFSELST KCIIKTVEFA 250 260 270 280 290 300 KQLPGFTTLT IADQITLLKA ACLDILILRI CTRYTPEQDT MTFSDGLTLN RTQMHNAGFG 310 320 330 340 350 360 PLTDLVFAFA NQLLPLEMDD AETGLLSAIC LICGDRQDLE QPDKVDMLQE PLLEALKVYV 370 380 390 400 410 420 RKRRPSRPHM FPKMLMKITD LRSISAKGAE RVITLKMEIP GSMPPLIQEM LENSEGLDTL 430 440 450 SGQSGGGTRD GGGLAPPPGS CSPSLSPSSH RSSPATQSP

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning of murine alpha and beta retinoic acid receptors and a novel receptor gamma predominantly expressed in skin." Zelent A., Krust A., Petkovich M., Kastner P., Chambon P. Nature 339:714-717(1989) [PubMed: 2544807] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM ALPHA-1).
[2]	"Cloning of several genes coding for retinoic acid nuclear receptors in the mouse embryonal carcinoma cell line PCC7-MZ1." Heiermann R., Rentrop M., Lang E., Maelicke A. J. Recept. Res. 13:693-709(1993) [PubMed: 8383767] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM ALPHA-1).
[3]	"Multiple isoforms of the mouse retinoic acid receptor alpha are generated by alternative splicing and differential induction by retinoic acid." Leroy P., Krust A., Zelent A., Mendelsohn C., Garnier J.-M., Kastner P., Dierich A., Chambon P. EMBO J. 10:59-69(1991) [PubMed: 1846598] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS ALPHA-1 AND ALPHA-2).
[4]	"Retinoic acid resistance of the variant embryonal carcinoma cell line RAC65 is caused by expression of a truncated RAR alpha." Kruyt F.A.E., van der Veer L., Mader S., van den Brink C.E., Feijen A., Jonk L.J., Kruijer W., van der Saag P.T. Differentiation 49:27-37(1992) [PubMed: 1320576] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (VARIANT IN EMBRYONAL CARCINOMA CELL LINE RAC65).
[5]	"A dominant negative mutation of the alpha retinoic acid receptor gene in a retinoic acid-nonresponsive embryonal carcinoma cell." Pratt M.A.C., Kralova J., McBurney M.W. Mol. Cell. Biol. 10:6445-6453(1990) [PubMed: 2174108] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (VARIANT IN EMBRYONAL CARCINOMA CELL LINE RAC65).
[6]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM ALPHA-1). Strain: FVB/N. Tissue: Mammary gland.
[7]	"Lysine trimethylation of retinoic acid receptor-alpha: a novel means to regulate receptor function." Huq M.D., Tsai N.-P., Khan S.A., Wei L.-N. Mol. Cell. Proteomics 6:677-688(2007) [PubMed: 17205979] [Abstract] Cited for: PROTEIN SEQUENCE OF 340-359, METHYLATION AT LYS-347, MASS SPECTROMETRY.
[8]	"Stimulation of RAR alpha activation function AF-1 through binding to the general transcription factor TFIIH and phosphorylation by CDK7." Rochette-Egly C., Adam S., Rossignol M., Egly J.-M., Chambon P. Cell 90:97-107(1997) [PubMed: 9230306] [Abstract] Cited for: INTERACTION WITH CDK7, PHOSPHORYLATION AT SER-77, MUTAGENESIS OF SER-74; SER-77; SER-449; SER-456 AND SER-461.
[9]	"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: 9192892] [Abstract] Cited for: INTERACTION WITH NCOA3.
[10]	"Isolation and characterization of peroxisome proliferator-activated receptor (PPAR) interacting protein (PRIP) as a coactivator for PPAR." Zhu Y.-J., Kan L., Qi C., Kanwar Y.S., Yeldandi A.V., Rao M.S., Reddy J.K. J. Biol. Chem. 275:13510-13516(2000) [PubMed: 10788465] [Abstract] Cited for: INTERACTION WITH NCOA6.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBLGenBankDDBJ	X56572 mRNA. Translation: CAA39919.1. X56565 mRNA. Translation: CAA39917.1. S56656 mRNA. Translation: AAB25783.1. X57528 mRNA. Translation: CAA40749.1. M60909 mRNA. Translation: AAA40031.1. BC010216 mRNA. Translation: AAH10216.1.
PIR	S05050.
RefSeq	NP_033050.2.
UniGene	Mm.439744
3D structure databases
HSSP	HSSP built from PDB template 1DKF based on UniProtKB P10276.
SMR	P11416. Positions 87-161, 182-416.
ModBase	Search...
PTM databases
PhosphoSite	P11416.
Genome annotation databases
Ensembl	ENSMUSG00000037992. Mus musculus. [Contig view]
GeneID	19401.
KEGG	mmu:19401.
Organism-specific databases
MGI	MGI:97856. Rara.
Phylogenomic databases
HOGENOM	P11416.
HOVERGEN	P11416.
Gene expression databases
ArrayExpress	P11416.
CleanEx	MM_RARA.
GermOnline	ENSMUSG00000037992. Mus musculus.
Family and domain databases
InterPro	IPR008946. Nucl_hormone_rcpt_ligand-bd. IPR000536. Nucl_hrmn_rcpt_lig-bd_core. IPR003078. Retinoic_acid_rcpt. IPR001723. Str_hrmn_rcpt. IPR001628. Znf_hrmn_rcpt. IPR013088. Znf_NHR/GATA. [Graphical view]
Gene3D	G3DSA:1.10.565.10. Nucl_hrmn_rcpt_lig_bd. 1 hit. G3DSA:3.30.50.10. Znf_NHR/GATA. 1 hit.
PANTHER	PTHR11865:SF169. Rtnoid_rcpt. 1 hit.
Pfam	PF00104. Hormone_recep. 1 hit. PF00105. zf-C4. 1 hit. [Graphical view]
PRINTS	PR01292. RETNOICACIDR. PR00398. STRDHORMONER. PR00047. STROIDFINGER.
ProDom	PD000035. Znf_C4steroid. 1 hit. [Graphical view] [Entries sharing at least one domain]
SMART	SM00430. HOLI. 1 hit. SM00399. ZnF_C4. 1 hit. [Graphical view]
PROSITE	PS00031. NUCLEAR_REC_DBD_1. 1 hit. PS51030. NUCLEAR_REC_DBD_2. 1 hit. [Graphical view]
BLOCKS	Search...
Other Resources
SOURCE	Search...
ProtoNet	Search...

Entry information

Entry name

RARA_MOUSE

Accession

Primary (citable) accession number: P11416
Secondary accession number(s): P22603

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1989
Last sequence update:	October 1, 1989
Last modified:	July 22, 2008
This is version 101 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)