ID RARA_CANFA Reviewed; 462 AA.
AC Q5FBR4;
DT 26-APR-2005, integrated into UniProtKB/Swiss-Prot.
DT 15-MAR-2005, sequence version 1.
DT 03-APR-2013, entry version 64.
DE RecName: Full=Retinoic acid receptor alpha;
DE Short=RAR-alpha;
DE AltName: Full=Nuclear receptor subfamily 1 group B member 1;
GN Name=RARA; Synonyms=NR1B1;
OS Canis familiaris (Dog) (Canis lupus familiaris).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Laurasiatheria; Carnivora; Caniformia; Canidae;
OC Canis.
OX NCBI_TaxID=9615;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Spleen;
RA Miyajima N., Watanabe M., Sugano S., Sasaki N.;
RT "Molecular cloning of canine highly similar retinoic acid receptor
RT alpha.";
RL Submitted (MAY-2004) to the EMBL/GenBank/DDBJ databases.
CC -!- FUNCTION: Receptor for retinoic acid. Retinoic acid receptors bind
CC as heterodimers to their target response elements in response to
CC their ligands, all-trans or 9-cis retinoic acid, and regulate gene
CC expression in various biological processes. The RXR/RAR
CC heterodimers bind to the retinoic acid response elements (RARE)
CC composed of tandem 5'-AGGTCA-3' sites known as DR1-DR5. In the
CC absence of ligand, the RXR-RAR heterodimers associate with a
CC multiprotein complex containing transcription corepressors that
CC induce histone acetylation, chromatin condensation and
CC transcriptional suppression. On ligand binding, the corepressors
CC dissociate from the receptors and associate with the coactivators
CC leading to transcriptional activation. Regulates expression of
CC target genes in a ligand-dependent manner by recruiting chromatin
CC complexes containing MLL5. Mediates retinoic acid-induced
CC granulopoiesis. RARA plays an essential role in the regulation of
CC retinoic acid-induced germ cell development during
CC spermatogenesis. Has a role in the survival of early spermatocytes
CC at the beginning prophase of meiosis. In Sertoli cells, may
CC promote the survival and development of early meiotic prophase
CC spermatocytes (By similarity).
CC -!- SUBUNIT: Interacts with NCOA7 in a ligand-inducible manner.
CC Interacts with MLL5. Interacts (via the ligand-binding domain)
CC with PRAME; interaction is direct and ligand (retinoic acid)-
CC dependent. Interacts with NCOR1 and NCOR2; the interaction occurs
CC in the absence of ligand and represses transciptional activity.
CC Interacts with NCOA3 and NCOA6 coactivators, leading to a strong
CC increase of transcription of target genes. Interacts with CDK7;
CC the interaction is enhanced by interaction with GTF2H3. Interacts
CC with GTF2H3; the interaction requires prior phosphorylation on
CC Ser-369 which then enhances interaction with CDK7. Interacts with
CC PRKAR1A; the interaction negatively regulates RARA transcriptional
CC activity. Interacts with PRMT2. Interacts with LRIF1. Interacts
CC with ASXL1 and NCOA1 (By similarity).
CC -!- SUBCELLULAR LOCATION: Nucleus (By similarity). Cytoplasm (By
CC similarity). Note=Nuclear localization depends on ligand binding,
CC phosphorylation and sumoylation. Transloaction to the nucleus is
CC dependent on activation of PKC and the downstream MAPK
CC phosphorylation (By similarity).
CC -!- DOMAIN: Composed of three domains: a modulating N-terminal domain,
CC a DNA-binding domain and a C-terminal ligand-binding domain.
CC -!- PTM: Phosphorylated on serine and threonine residues.
CC Phosphorylation does not change during cell cycle. Phosphorylation
CC on Ser-77 is crucial for the N-terminal AF1 transcriptional
CC activity. Under stress conditions, MAPK8 enhances phosphorylation
CC on Thr-181, Ser-445 and Ser-461 leading to RARA ubiquitination and
CC degradation. Phosphorylation by AKT1 inhibits the transactivation
CC activity. On retinoic acid stimulation, phosphorylation on Ser-369
CC by RPS6KA5 promotes interaction with GTF2H3 and the CDK7-mediated
CC phosphorylation of Ser-77 (By similarity).
CC -!- PTM: Sumoylated with SUMO2, mainly on Lys-399 which is also
CC required for SENP6 binding. On all-trans retinoic acid (ATRA)
CC binding, a confromational change may occur that allows sumoylation
CC on two additional site, Lys-166 and Lys-171. Probably desumoylated
CC by SENP6. Sumoylation levels determine nuclear localization and
CC regulate ATRA-mediated transcriptional activity (By similarity).
CC -!- SIMILARITY: Belongs to the nuclear hormone receptor family. NR1
CC subfamily.
CC -!- SIMILARITY: Contains 1 nuclear receptor DNA-binding domain.
CC -----------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution-NoDerivs License
CC -----------------------------------------------------------------------
DR EMBL; AB179779; BAD89859.1; -; mRNA.
DR RefSeq; NP_001012663.1; NM_001012645.1.
DR UniGene; Cfa.45823; -.
DR ProteinModelPortal; Q5FBR4; -.
DR SMR; Q5FBR4; 87-161, 182-416.
DR STRING; 9615.ENSCAFP00000030948; -.
DR GeneID; 480526; -.
DR KEGG; cfa:480526; -.
DR CTD; 5914; -.
DR eggNOG; NOG297448; -.
DR HOGENOM; HOG000010312; -.
DR HOVERGEN; HBG005606; -.
DR KO; K08527; -.
DR NextBio; 20855534; -.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0003708; F:retinoic acid receptor activity; IEA:InterPro.
DR GO; GO:0043565; F:sequence-specific DNA binding; IEA:InterPro.
DR GO; GO:0003707; F:steroid hormone receptor activity; IEA:InterPro.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR Gene3D; 1.10.565.10; -; 1.
DR Gene3D; 3.30.50.10; -; 1.
DR InterPro; IPR008946; Nucl_hormone_rcpt_ligand-bd.
DR InterPro; IPR000536; Nucl_hrmn_rcpt_lig-bd_core.
DR InterPro; IPR003078; Retinoic_acid_rcpt.
DR InterPro; IPR001723; Str_hrmn_rcpt.
DR InterPro; IPR001628; Znf_hrmn_rcpt.
DR InterPro; IPR013088; Znf_NHR/GATA.
DR Pfam; PF00104; Hormone_recep; 1.
DR Pfam; PF00105; zf-C4; 1.
DR PRINTS; PR01292; RETNOICACIDR.
DR PRINTS; PR00398; STRDHORMONER.
DR PRINTS; PR00047; STROIDFINGER.
DR SMART; SM00430; HOLI; 1.
DR SMART; SM00399; ZnF_C4; 1.
DR SUPFAM; SSF48508; Str_ncl_receptor; 1.
DR PROSITE; PS00031; NUCLEAR_REC_DBD_1; 1.
DR PROSITE; PS51030; NUCLEAR_REC_DBD_2; 1.
PE 2: Evidence at transcript level;
KW Complete proteome; Cytoplasm; DNA-binding; Isopeptide bond;
KW Metal-binding; Nucleus; Phosphoprotein; Receptor; Reference proteome;
KW Transcription; Transcription regulation; Ubl conjugation; Zinc;
KW Zinc-finger.
FT CHAIN 1 462 Retinoic acid receptor alpha.
FT /FTId=PRO_0000053460.
FT DNA_BIND 88 153 Nuclear receptor.
FT ZN_FING 88 108 NR C4-type.
FT ZN_FING 124 148 NR C4-type.
FT REGION 1 87 Modulating.
FT REGION 154 199 Hinge.
FT REGION 200 419 Ligand-binding.
FT MOD_RES 77 77 Phosphoserine; by CDK7 (By similarity).
FT MOD_RES 96 96 Phosphoserine; by PKB/AKT1 (By
FT similarity).
FT MOD_RES 219 219 Phosphoserine; by PKA (By similarity).
FT MOD_RES 369 369 Phosphoserine; by PKA (By similarity).
FT CROSSLNK 166 166 Glycyl lysine isopeptide (Lys-Gly)
FT (interchain with G-Cter in SUMO) (By
FT similarity).
FT CROSSLNK 171 171 Glycyl lysine isopeptide (Lys-Gly)
FT (interchain with G-Cter in SUMO) (By
FT similarity).
FT CROSSLNK 399 399 Glycyl lysine isopeptide (Lys-Gly)
FT (interchain with G-Cter in SUMO) (By
FT similarity).
SQ SEQUENCE 462 AA; 50771 MW; 8E63EE98C4E0FB4A CRC64;
MASNSSSCPT PGGGHLNGYP VPPYAFFFPP MLGGLSPPGA LTTLQHQLPV SGYSTPSPAT
IETQSSSSEE IVPSPPSPPP LPRIYKPCFV CQDKSSGYHY GVSACEGCKG FFRRSIQKNM
VYTCHRDKNC IINKVTRNRC QYCRLQKCFE VGMSKESVRN DRNKKKKEAP KPECSESYTL
TPEVGELIEK VRKAHQETFP ALCQLGKYTT NNSSEQRVSL DIDLWDKFSE LSTKCIIKTV
EFAKQLPGFT TLTIADQITL LKAACLDILI LRICTRYTPE QDTMTFSEGL TLNRTQMHKA
GFGPLTDLVF AFANQLLPLE MDDAETGLLS AICLICGDRQ DLEQPDRVDM LQEPLLEALK
VYVRKRRPSR PHMFPKMLMK ITDLRSISAK GAERVITLKM EIPGSMPPLI QEMLENSEGL
DTLSGQPGGG GRDGGGLAPP PGSCSPSLSP SSNRSSPATH SP
//
