Uniprot ID:P35398	Protein name: Nuclear receptor ROR-alpha	Gene : RORA NR1F1 RZRA
Protein Family:"Nuclear hormone receptor family, NR1 subfamily"	Squence Length : 523

Sequnce	>P35398 524 MESAPAAPDPAASEPGSSGADAAAGSRETPLNQESARKSEPPAPVRRQSYSSTSRGISVTKKTHTSQIEIIPCKICGDKSSGIHYGVITCEGCKGFFRRSQQSNATYSCPRQKNCLIDRTSRNRCQHCRLQKCLAVGMSRDAVKFGRMSKKQRDSLYAEVQKHRMQQQQRDHQQQPGEAEPLTPTYNISANGLTELHDDLSNYIDGHTPEGSKADSAVSSFYLDIQPSPDQSGLDINGIKPEPICDYTPASGFFPYCSFTNGETSPTVSMAELEHLAQNISKSHLETCQYLREELQQITWQTFLQEEIENYQNKQREVMWQLCAIKITEAIQYVVEFAKRIDGFMELCQNDQIVLLKAGSLEVVFIRMCRAFDSQNNTVYFDGKYASPDVFKSLGCEDFISFVFEFGKSLCSMHLTEDEIALFSAFVLMSADRSWLQEKVKIEKLQQKIQLALQHVLQKNHREDGILTKLICKVSTLRALCGRHTEKLMAFKAIYPDIVRLHFPPLYKELFTSEFEPAMQIDG
NR C4-type domains repeats	ZN_FING 73 93 NR C4-type ZN_FING 109 133 NR C4-type
Domin repeated regions	73 - 93 CKICGDKSSGIHYGVITCEGC 109 - 133 CPRQKNCLIDRTSRNRCQHCRLQKC
Function	"Nuclear receptor that binds DNA as a monomer to ROR response elements (RORE) containing a single core motif half-site 5'-AGGTCA-3' preceded by a short A-T-rich sequence. Key regulator of embryonic development, cellular differentiation, immunity, circadian rhythm as well as lipid, steroid, xenobiotics and glucose metabolism. Considered to have intrinsic transcriptional activity, have some natural ligands like oxysterols that act as agonists (25-hydroxycholesterol) or inverse agonists (7-oxygenated sterols), enhancing or repressing the transcriptional activity, respectively. Recruits distinct combinations of cofactors to target genes regulatory regions to modulate their transcriptional expression, depending on the tissue, time and promoter contexts. Regulates genes involved in photoreceptor development including OPN1SW, OPN1SM and ARR3 and skeletal muscle development with MYOD1. Required for proper cerebellum development, regulates SHH gene expression, among others, to induce granule cells proliferation as well as expression of genes involved in calcium-mediated signal transduction. Regulates the circadian expression of several clock genes, including CLOCK, ARNTL/BMAL1, NPAS2 and CRY1. Competes with NR1D1 for binding to their shared DNA response element on some clock genes such as ARNTL/BMAL1, CRY1 and NR1D1 itself, resulting in NR1D1-mediated repression or RORA-mediated activation of clock genes expression, leading to the circadian pattern of clock genes expression. Therefore influences the period length and stability of the clock. Regulates genes involved in lipid metabolism such as apolipoproteins APOA1, APOA5, APOC3 and PPARG. In liver, has specific and redundant functions with RORC as positive or negative modulator of expression of genes encoding phase I and phase II proteins involved in the metabolism of lipids, steroids and xenobiotics, such as CYP7B1 and SULT2A1. Induces a rhythmic expression of some of these genes. In addition, interplays functionally with NR1H2 and NR1H3 for the regulation of genes involved in cholesterol metabolism. Also involved in the regulation of hepatic glucose metabolism through the modulation of G6PC and PCK1. In adipose tissue, plays a role as negative regulator of adipocyte differentiation, probably acting through dual mechanisms. May suppress CEBPB-dependent adipogenesis through direct interaction and PPARG-dependent adipogenesis through competition for DNA-binding. Downstream of IL6 and TGFB and synergistically with RORC isoform 2, is implicated in the lineage specification of uncommitted CD4(+) T-helper (T(H)) cells into T(H)17 cells, antagonizing the T(H)1 program. Probably regulates IL17 and IL17F expression on T(H) by binding to the essential enhancer conserved non-coding sequence 2 (CNS2) in the IL17-IL17F locus. Involved in hypoxia signaling by interacting with and activating the transcriptional activity of HIF1A. May inhibit cell growth in response to cellular stress. May exert an anti-inflammatory role by inducing CHUK expression and inhibiting NF-kappa-B signaling"
Motifs	MOTIF 506 523 AF-2
Mutation	"183 183 T->A: Greatly increased transcriptional activity 183 183 T->D,E: Some increase in transcriptional activity 183 183 T->R: Attenuates transcriptional activity 183 183 T->V,I: Some increase in transcriptional activity 240 240 K->R: Loss of sumoylation 288 288 C->Q: Less effect on transcriptional activity with cholesterol sulfate as substrate as compared to cholesterol as substrate 323 323 C->L: About 60% loss of transcriptional activity 330 330 A->L: About 80% loss of transcriptional activity 335 335 V->R: Strongly decreases interaction with NCOA2 and MED1 339 339 K->A: Complete loss of transcriptional activity when associated with A-507 357 357 K->A: Increased transcriptional activity 361 361 L->F: Small reduction in transcriptional activity 364 364 V->G: Greatly reduced transcriptional activity 371 371 A->Q: Almost total loss of transcriptional activity 399 399 F->W: Slight loss of transcriptional activity 441 441 K->R: No effect on sumoylation 484 484 H->W: Almost total loss of transcriptional activity 507 507 Y->A: Complete loss of transcriptional activity when associated with A-339 507 507 Y->F: About 40% loss of transcriptional activity 509 509 E->K: Abolishes transcriptional activity 510 511 LF->AA: Decreases interaction with NCOA2"

P35398 of Proteins NR C4-type domain repeats