RORG_PONAB
ID RORG_PONAB Reviewed; 518 AA.
AC Q5RAP4;
DT 23-JAN-2007, integrated into UniProtKB/Swiss-Prot.
DT 21-DEC-2004, sequence version 1.
DT 03-AUG-2022, entry version 101.
DE RecName: Full=Nuclear receptor ROR-gamma;
DE AltName: Full=Nuclear receptor RZR-gamma;
DE AltName: Full=Nuclear receptor subfamily 1 group F member 3;
DE AltName: Full=Retinoid-related orphan receptor-gamma;
GN Name=RORC; Synonyms=NR1F3;
OS Pongo abelii (Sumatran orangutan) (Pongo pygmaeus abelii).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Pongo.
OX NCBI_TaxID=9601;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Kidney;
RG The German cDNA consortium;
RL Submitted (NOV-2004) to the EMBL/GenBank/DDBJ databases.
CC -!- FUNCTION: Nuclear receptor that binds DNA as a monomer to ROR response
CC elements (RORE) containing a single core motif half-site 5'-AGGTCA-3'
CC preceded by a short A-T-rich sequence. Key regulator of cellular
CC differentiation, immunity, peripheral circadian rhythm as well as
CC lipid, steroid, xenobiotics and glucose metabolism. Considered to have
CC intrinsic transcriptional activity, have some natural ligands like
CC oxysterols that act as agonists (25-hydroxycholesterol) or inverse
CC agonists (7-oxygenated sterols), enhancing or repressing the
CC transcriptional activity, respectively. Recruits distinct combinations
CC of cofactors to target gene regulatory regions to modulate their
CC transcriptional expression, depending on the tissue, time and promoter
CC contexts. Regulates the circadian expression of clock genes such as
CC CRY1, ARNTL/BMAL1 and NR1D1 in peripheral tissues and in a tissue-
CC selective manner. Competes with NR1D1 for binding to their shared DNA
CC response element on some clock genes such as ARNTL/BMAL1, CRY1 and
CC NR1D1 itself, resulting in NR1D1-mediated repression or RORC-mediated
CC activation of the expression, leading to the circadian pattern of clock
CC genes expression. Therefore influences the period length and stability
CC of the clock. Involved in the regulation of the rhythmic expression of
CC genes involved in glucose and lipid metabolism, including PLIN2 and
CC AVPR1A. Negative regulator of adipocyte differentiation through the
CC regulation of early phase genes expression, such as MMP3. Controls
CC adipogenesis as well as adipocyte size and modulates insulin
CC sensitivity in obesity. In liver, has specific and redundant functions
CC with RORA as positive or negative modulator of expression of genes
CC encoding phase I and Phase II proteins involved in the metabolism of
CC lipids, steroids and xenobiotics, such as SULT1E1. Also plays a role in
CC the regulation of hepatocyte glucose metabolism through the regulation
CC of G6PC1 and PCK1. Essential for thymopoiesis and the development of
CC several secondary lymphoid tissues, including lymph nodes and Peyer's
CC patches. Required for the generation of LTi (lymphoid tissue inducer)
CC cells. Regulates thymocyte survival through DNA-binding on ROREs of
CC target gene promoter regions and recruitment of coactivaros via the AF-
CC 2. Also plays a key role, downstream of IL6 and TGFB and
CC synergistically with RORA, for lineage specification of uncommitted
CC CD4(+) T-helper (T(H)) cells into T(H)17 cells, antagonizing the T(H)1
CC program. Probably regulates IL17 and IL17F expression on T(H) by
CC binding to the essential enhancer conserved non-coding sequence 2
CC (CNS2) in the IL17-IL17F locus. May also play a role in the pre-TCR
CC activation cascade leading to the maturation of alpha/beta T-cells and
CC may participate in the regulation of DNA accessibility in the TCR-
CC J(alpha) locus. Regulates the rhythmic expression of PROX1 and promotes
CC its nuclear localization. Plays an indispensable role in the induction
CC of IFN-gamma dependent anti-mycobacterial systemic immunity (By
CC similarity). {ECO:0000250|UniProtKB:P51449,
CC ECO:0000250|UniProtKB:P51450}.
CC -!- SUBUNIT: Interacts (via AF-2 motif) with the coactivators NCOA1, NCOA2
CC and PPARGC1A (via LXXLL motif) (By similarity). Interacts with the
CC corepressor NCOR1 (By similarity). Interacts with CRY1 (By similarity).
CC Interacts (via AF-2 motif) with PROX1 (By similarity). Interacts with
CC FOXP3 (By similarity). Interacts with NR0B2 (By similarity).
CC {ECO:0000250|UniProtKB:P51450}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:P51449,
CC ECO:0000255|PROSITE-ProRule:PRU00407}.
CC -!- DOMAIN: The AF-2 (activation function-2) motif is required for
CC recruiting coregulators containing LXXLL motifs such as NCOA1 and
CC NCOA2. {ECO:0000250|UniProtKB:P51450}.
CC -!- SIMILARITY: Belongs to the nuclear hormone receptor family. NR1
CC subfamily. {ECO:0000305}.
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DR EMBL; CR858971; CAH91166.1; -; mRNA.
DR RefSeq; NP_001125682.1; NM_001132210.1.
DR AlphaFoldDB; Q5RAP4; -.
DR SMR; Q5RAP4; -.
DR STRING; 9601.ENSPPYP00000000995; -.
DR PRIDE; Q5RAP4; -.
DR GeneID; 100172603; -.
DR KEGG; pon:100172603; -.
DR CTD; 6097; -.
DR eggNOG; KOG4216; Eukaryota.
DR InParanoid; Q5RAP4; -.
DR OrthoDB; 583704at2759; -.
DR Proteomes; UP000001595; Unplaced.
DR GO; GO:0005654; C:nucleoplasm; IEA:UniProt.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0003700; F:DNA-binding transcription factor activity; ISS:UniProtKB.
DR GO; GO:0004879; F:nuclear receptor activity; IEA:InterPro.
DR GO; GO:0043565; F:sequence-specific DNA binding; IEA:InterPro.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0060612; P:adipose tissue development; ISS:UniProtKB.
DR GO; GO:0032922; P:circadian regulation of gene expression; ISS:UniProtKB.
DR GO; GO:0048535; P:lymph node development; ISS:UniProtKB.
DR GO; GO:0048541; P:Peyer's patch development; ISS:UniProtKB.
DR GO; GO:0042753; P:positive regulation of circadian rhythm; ISS:UniProtKB.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; ISS:UniProtKB.
DR GO; GO:0045598; P:regulation of fat cell differentiation; ISS:UniProtKB.
DR GO; GO:0010906; P:regulation of glucose metabolic process; ISS:UniProtKB.
DR GO; GO:0019218; P:regulation of steroid metabolic process; ISS:UniProtKB.
DR GO; GO:0072539; P:T-helper 17 cell differentiation; ISS:UniProtKB.
DR GO; GO:0042093; P:T-helper cell differentiation; ISS:UniProtKB.
DR GO; GO:0006805; P:xenobiotic metabolic process; ISS:UniProtKB.
DR CDD; cd06968; NR_DBD_ROR; 1.
DR Gene3D; 1.10.565.10; -; 1.
DR Gene3D; 3.30.50.10; -; 1.
DR InterPro; IPR035500; NHR-like_dom_sf.
DR InterPro; IPR044101; NR_DBD_ROR.
DR InterPro; IPR000536; Nucl_hrmn_rcpt_lig-bd.
DR InterPro; IPR001723; Nuclear_hrmn_rcpt.
DR InterPro; IPR003079; ROR_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; PR01293; RORNUCRECPTR.
DR PRINTS; PR00398; STRDHORMONER.
DR PRINTS; PR00047; STROIDFINGER.
DR SMART; SM00430; HOLI; 1.
DR SMART; SM00399; ZnF_C4; 1.
DR SUPFAM; SSF48508; SSF48508; 1.
DR PROSITE; PS51843; NR_LBD; 1.
DR PROSITE; PS00031; NUCLEAR_REC_DBD_1; 1.
DR PROSITE; PS51030; NUCLEAR_REC_DBD_2; 1.
PE 2: Evidence at transcript level;
KW Activator; Biological rhythms; Developmental protein; DNA-binding;
KW Metal-binding; Nucleus; Receptor; Reference proteome; Transcription;
KW Transcription regulation; Zinc; Zinc-finger.
FT CHAIN 1..518
FT /note="Nuclear receptor ROR-gamma"
FT /id="PRO_0000273575"
FT DOMAIN 269..508
FT /note="NR LBD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01189"
FT DNA_BIND 31..96
FT /note="Nuclear receptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00407"
FT ZN_FING 31..51
FT /note="NR C4-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00407"
FT ZN_FING 67..91
FT /note="NR C4-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00407"
FT REGION 1..30
FT /note="Modulating"
FT /evidence="ECO:0000255"
FT REGION 105..183
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 238..258
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 501..506
FT /note="AF-2"
FT COMPBIAS 119..135
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
SQ SEQUENCE 518 AA; 58191 MW; 00ECC2D3FDBE851B CRC64;
MDRAPQRQHQ ASRELLAAKK THTSQIEVIP CKICGDKSSG IHYGVITCEG CKGFFRRSQR
CNAAYSCTRQ QNCPIDRTSR NRCQHCRLQK CLALGMSRDA VKFGRMSKKQ RDSLHAEVQK
QLQQRQQQQQ EPVVKTPPAG AQGADTLTYT LGLPDGQLPL GSSPDLPEAS ACPPGLLKAS
GSGPSYSNNL AKAGLNGASC HLEYSPERGK AEGRESFYST GSQLTPDRCG LRFEEHRHPG
LGELGQGPDS YGSPSFRSTP EAPYASLTEI EHLVQSVCKS YRETCQLRLE DLLRQRSNIF
SREEVTGYQR KSMWEMWERC AHHLTEAIQY VVEFAKRLSG FMELCQNDQI VLLKAGAVEV
VLVRMCRAYN ADNRTVFFEG KYGGMELFRA LGCSELISSI FDFSHSLSAL HFSEDEIALY
TALVLINAYR PGLQEKRKVE QLQYNLELAF HHHLCKTHRQ SILAKLPPKG KLRSLCSQHV
ERLQIFQHLH PIVVQATFPP LYKELFSTET ESPVGLSK
