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Nuclear receptor subfamily 2 group C member 2 (Orphan nuclear receptor TAK1) (Orphan nuclear receptor TR4) (Testicular receptor 4)

 NR2C2_MOUSE             Reviewed;         596 AA.
P49117; P55093;
01-FEB-1996, integrated into UniProtKB/Swiss-Prot.
01-FEB-1996, sequence version 1.
12-SEP-2018, entry version 162.
RecName: Full=Nuclear receptor subfamily 2 group C member 2;
AltName: Full=Orphan nuclear receptor TAK1;
AltName: Full=Orphan nuclear receptor TR4;
AltName: Full=Testicular receptor 4;
Name=Nr2c2; Synonyms=Mtr2r1, Tak1, Tr4;
Mus musculus (Mouse).
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha;
Muroidea; Muridae; Murinae; Mus; Mus.
NCBI_TaxID=10090;
[1]
NUCLEOTIDE SEQUENCE [MRNA].
STRAIN=CD-1;
PubMed=7590273; DOI=10.1016/0378-1119(95)00414-2;
Hirose T., O'Brien D.A., Jetten A.M.;
"Cloning of the gene encoding the murine orphan receptor TAK1 and
cell-type-specific expression in testis.";
Gene 163:239-242(1995).
[2]
NUCLEOTIDE SEQUENCE [MRNA].
PubMed=7841789;
Law S.W., Conneely O.M., O'Malley B.W.;
"Molecular cloning of a novel member of the nuclear receptor
superfamily related to the orphan receptor, TR2.";
Gene Expr. 4:77-84(1994).
[3]
NUCLEOTIDE SEQUENCE [MRNA].
STRAIN=C57BL/6J; TISSUE=Testis;
Young W.J., Smith S., Chang C.;
Submitted (JAN-1996) to the EMBL/GenBank/DDBJ databases.
[4]
TISSUE SPECIFICITY.
PubMed=10347174; DOI=10.1074/jbc.274.23.16198;
Lee Y.F., Young W.J., Lin W.J., Shyr C.R., Chang C.;
"Differential regulation of direct repeat 3 vitamin D3 and direct
repeat 4 thyroid hormone signaling pathways by the human TR4 orphan
receptor.";
J. Biol. Chem. 274:16198-16205(1999).
[5]
IDENTIFICATION BY MASS SPECTROMETRY AS A COMPONENT OF THE DRED
COMPLEX, FUNCTION, SUBCELLULAR LOCATION, HETERODIMERIZATION, AND
DEVELOPMENTAL STAGE.
PubMed=12093744; DOI=10.1093/emboj/cdf340;
Tanabe O., Katsuoka F., Campbell A.D., Song W., Yamamoto M.,
Tanimoto K., Engel J.D.;
"An embryonic/fetal beta-type globin gene repressor contains a nuclear
receptor TR2/TR4 heterodimer.";
EMBO J. 21:3434-3442(2002).
[6]
DISRUPTION PHENOTYPE, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, AND
FUNCTION.
PubMed=15199144; DOI=10.1128/MCB.24.13.5887-5899.2004;
Mu X., Lee Y.F., Liu N.C., Chen Y.T., Kim E., Shyr C.R., Chang C.;
"Targeted inactivation of testicular nuclear orphan receptor 4 delays
and disrupts late meiotic prophase and subsequent meiotic divisions of
spermatogenesis.";
Mol. Cell. Biol. 24:5887-5899(2004).
[7]
PHOSPHORYLATION AT SER-19; SER-55 AND SER-68, FUNCTION, IDENTIFICATION
BY MASS SPECTROMETRY, INTERACTION WITH NRIP1 AND PCAF, AND MUTAGENESIS
OF SER-19; SER-55 AND SER-68.
PubMed=16887930; DOI=10.1074/mcp.M600180-MCP200;
Huq M.D., Gupta P., Tsai N.P., Wei L.N.;
"Modulation of testicular receptor 4 activity by mitogen-activated
protein kinase-mediated phosphorylation.";
Mol. Cell. Proteomics 5:2072-2082(2006).
[8]
DISRUPTION PHENOTYPE, TISSUE SPECIFICITY, AND FUNCTION.
PubMed=17706948; DOI=10.1016/j.brainres.2007.06.069;
Chen Y.T., Collins L.L., Uno H., Chou S.M., Meshul C.K., Chang S.S.,
Chang C.;
"Abnormal cerebellar cytoarchitecture and impaired inhibitory
signaling in adult mice lacking TR4 orphan nuclear receptor.";
Brain Res. 1168:72-82(2007).
[9]
HETERODIMERIZATION, AND FUNCTION.
PubMed=17974920; DOI=10.1101/gad.1593307;
Tanabe O., Shen Y., Liu Q., Campbell A.D., Kuroha T., Yamamoto M.,
Engel J.D.;
"The TR2 and TR4 orphan nuclear receptors repress Gata1
transcription.";
Genes Dev. 21:2832-2844(2007).
[10]
DISRUPTION PHENOTYPE, INDUCTION, AND FUNCTION.
PubMed=19131575; DOI=10.1210/en.2008-1165;
Shyr C.R., Kang H.Y., Tsai M.Y., Liu N.C., Ku P.Y., Huang K.E.,
Chang C.;
"Roles of testicular orphan nuclear receptors 2 and 4 in early
embryonic development and embryonic stem cells.";
Endocrinology 150:2454-2462(2009).
[11]
DISRUPTION PHENOTYPE, AND FUNCTION.
PubMed=20393820; DOI=10.1007/s12311-010-0163-z;
Kim Y.S., Harry G.J., Kang H.S., Goulding D., Wine R.N.,
Kissling G.E., Liao G., Jetten A.M.;
"Altered cerebellar development in nuclear receptor TAK1/ TR4 null
mice is associated with deficits in GLAST(+) glia, alterations in
social behavior, motor learning, startle reactivity, and microglia.";
Cerebellum 9:310-323(2010).
[12]
ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-231, AND IDENTIFICATION BY
MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
TISSUE=Embryonic fibroblast;
PubMed=23806337; DOI=10.1016/j.molcel.2013.06.001;
Park J., Chen Y., Tishkoff D.X., Peng C., Tan M., Dai L., Xie Z.,
Zhang Y., Zwaans B.M., Skinner M.E., Lombard D.B., Zhao Y.;
"SIRT5-mediated lysine desuccinylation impacts diverse metabolic
pathways.";
Mol. Cell 50:919-930(2013).
-!- FUNCTION: Orphan nuclear receptor that can act as a repressor or
activator of transcription. An important repressor of nuclear
receptor signaling pathways such as retinoic acid receptor,
retinoid X, vitamin D3 receptor, thyroid hormone receptor and
estrogen receptor pathways. May regulate gene expression during
the late phase of spermatogenesis. Activates transcriptional
activity of LHCG and is antagonist of PPARA-mediated
transactivation (By similarity). Together with NR2C1, forms the
core of the DRED (direct repeat erythroid-definitive) complex that
represses embryonic and fetal globin transcription including that
of GATA1. Binds to hormone response elements (HREs) consisting of
two 5'-AGGTCA-3' half site direct repeat consensus sequences.
Plays a fundamental role in early embryonic development and
embryonic stem cells. Required for normal spermatogenesis and
cerebellum development. Appears to be important for
neurodevelopmentally regulated behavior. {ECO:0000250,
ECO:0000269|PubMed:12093744, ECO:0000269|PubMed:15199144,
ECO:0000269|PubMed:16887930, ECO:0000269|PubMed:17706948,
ECO:0000269|PubMed:17974920, ECO:0000269|PubMed:19131575,
ECO:0000269|PubMed:20393820}.
-!- SUBUNIT: Homodimer; can bind DNA as homodimer (By similarity).
Heterodimer; binds DNA as a heterodimer with NR2C1 required for
chromatin remodeling and for binding to promoter regions such as
globin DR1 repeats. Interacts with NR2C2AP; the interaction
represses selective NR2C2-mediated transcriptional activity (By
similarity). Interacts with PCAF; the interaction preferentially
occurs on the non-phosphorylated form and induces NR2C2-mediated
transactivation activity and does not require the ligand-binding
domain (PubMed:16887930). Interacts (MAPK-mediated phosphorylated
form) with NRIP1; the interaction promotes repression of NR2C2-
mediated activity (PubMed:16887930). Interacts with NLRP10.
Interacts (via ligand-binding region) with transcriptional
corepressor JAZF1; the interaction promotes NR2C2-mediated
transcriptional repression (By similarity).
{ECO:0000250|UniProtKB:P49116, ECO:0000269|PubMed:16887930}.
-!- SUBCELLULAR LOCATION: Nucleus {ECO:0000255|PROSITE-
ProRule:PRU00407}.
-!- TISSUE SPECIFICITY: Expressed, during embryogenesis, in
perichondrium, developing glomeruli structures and tubules of
kidney, as well as in intestiinal villi. Also expressed in lung
and hair follicles. {ECO:0000269|PubMed:10347174,
ECO:0000269|PubMed:15199144, ECO:0000269|PubMed:17706948}.
-!- INDUCTION: Induced by retinoic acid.
{ECO:0000269|PubMed:19131575}.
-!- PTM: Phosphorylation on Ser-19 and Ser-68 is an important
regulator of NR2C2-mediated transcriptional activity.
Phosphorylation on these residues recruits the corepressor, NRIP1,
leading to transcripional repression, whereas the non-
phosphorylated form preferentially recruits the coactivator, PCAF.
{ECO:0000269|PubMed:16887930}.
-!- DISRUPTION PHENOTYPE: Impaired spermatogenesis. Mutant animals
have smaller cerebellums with disruption of lobes VI-VII. They
exhibit a delay in monolayer maturation of dysmorphic calbindin
28K-positive Purkinje cells 7 days after birth. Deficiencies in
acoustic startle response, prepulse startle inhibition, and social
interactions were observed. Also responses to novel environmental
situations are inhibited. NR2C1 and NR2C2 double knockout results
in embryonic lethality around 7.5 dpc and increased apoptosis.
{ECO:0000269|PubMed:15199144, ECO:0000269|PubMed:17706948,
ECO:0000269|PubMed:19131575, ECO:0000269|PubMed:20393820}.
-!- SIMILARITY: Belongs to the nuclear hormone receptor family. NR2
subfamily. {ECO:0000305}.
-!- SEQUENCE CAUTION:
Sequence=AAB33314.1; Type=Erroneous initiation; Note=Translation N-terminally shortened.; Evidence={ECO:0000305};
Sequence=AAC18408.1; Type=Erroneous initiation; Note=Translation N-terminally shortened.; Evidence={ECO:0000305};
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EMBL; U11688; AAA93150.1; -; mRNA.
EMBL; S75970; AAB33314.1; ALT_INIT; mRNA.
EMBL; U32939; AAC18408.1; ALT_INIT; mRNA.
CCDS; CCDS20372.1; -.
PIR; I54075; I54075.
PIR; JC4299; JC4299.
RefSeq; NP_001334271.1; NM_001347342.1.
RefSeq; NP_035760.1; NM_011630.3.
RefSeq; XP_006505967.1; XM_006505904.3.
RefSeq; XP_006505968.1; XM_006505905.3.
RefSeq; XP_006505969.1; XM_006505906.3.
UniGene; Mm.442385; -.
UniGene; Mm.87062; -.
ProteinModelPortal; P49117; -.
IntAct; P49117; 1.
MINT; P49117; -.
STRING; 10090.ENSMUSP00000109087; -.
iPTMnet; P49117; -.
PhosphoSitePlus; P49117; -.
EPD; P49117; -.
PaxDb; P49117; -.
PRIDE; P49117; -.
Ensembl; ENSMUST00000113460; ENSMUSP00000109087; ENSMUSG00000005893.
GeneID; 22026; -.
KEGG; mmu:22026; -.
UCSC; uc009cyp.2; mouse.
CTD; 7182; -.
MGI; MGI:1352466; Nr2c2.
eggNOG; KOG3575; Eukaryota.
eggNOG; ENOG410XRZC; LUCA.
GeneTree; ENSGT00760000118948; -.
HOGENOM; HOG000013058; -.
HOVERGEN; HBG008596; -.
InParanoid; P49117; -.
KO; K08544; -.
PhylomeDB; P49117; -.
TreeFam; TF316650; -.
Reactome; R-MMU-383280; Nuclear Receptor transcription pathway.
ChiTaRS; Nr2c2; mouse.
PRO; PR:P49117; -.
Proteomes; UP000000589; Chromosome 6.
Bgee; ENSMUSG00000005893; Expressed in 274 organ(s), highest expression level in rostral migratory stream.
CleanEx; MM_NR2C2; -.
ExpressionAtlas; P49117; baseline and differential.
Genevisible; P49117; MM.
GO; GO:0005654; C:nucleoplasm; ISO:MGI.
GO; GO:0003700; F:DNA-binding transcription factor activity; ISO:MGI.
GO; GO:0046982; F:protein heterodimerization activity; ISO:MGI.
GO; GO:0000978; F:RNA polymerase II proximal promoter sequence-specific DNA binding; ISO:MGI.
GO; GO:0000977; F:RNA polymerase II regulatory region sequence-specific DNA binding; ISO:MGI.
GO; GO:0043565; F:sequence-specific DNA binding; ISO:MGI.
GO; GO:0003707; F:steroid hormone receptor activity; IEA:InterPro.
GO; GO:0001077; F:transcriptional activator activity, RNA polymerase II proximal promoter sequence-specific DNA binding; ISO:MGI.
GO; GO:0001228; F:transcriptional activator activity, RNA polymerase II transcription regulatory region sequence-specific DNA binding; ISO:MGI.
GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
GO; GO:0030154; P:cell differentiation; IEA:UniProtKB-KW.
GO; GO:0021549; P:cerebellum development; IMP:UniProtKB.
GO; GO:0051321; P:meiotic cell cycle; IMP:MGI.
GO; GO:0038066; P:p38MAPK cascade; IEP:CACAO.
GO; GO:0048520; P:positive regulation of behavior; IMP:UniProtKB.
GO; GO:0040019; P:positive regulation of embryonic development; IMP:UniProtKB.
GO; GO:0045663; P:positive regulation of myoblast differentiation; IDA:CACAO.
GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISO:MGI.
GO; GO:0007283; P:spermatogenesis; IMP:MGI.
Gene3D; 3.30.50.10; -; 1.
InterPro; IPR035500; NHR_like_dom_sf.
InterPro; IPR000536; Nucl_hrmn_rcpt_lig-bd.
InterPro; IPR001723; Nuclear_hrmn_rcpt.
InterPro; IPR001628; Znf_hrmn_rcpt.
InterPro; IPR013088; Znf_NHR/GATA.
Pfam; PF00104; Hormone_recep; 1.
Pfam; PF00105; zf-C4; 1.
PRINTS; PR00398; STRDHORMONER.
PRINTS; PR00047; STROIDFINGER.
SMART; SM00430; HOLI; 1.
SMART; SM00399; ZnF_C4; 1.
SUPFAM; SSF48508; SSF48508; 2.
PROSITE; PS51843; NR_LBD; 1.
PROSITE; PS00031; NUCLEAR_REC_DBD_1; 1.
PROSITE; PS51030; NUCLEAR_REC_DBD_2; 1.
1: Evidence at protein level;
Acetylation; Activator; Complete proteome; Differentiation;
DNA-binding; Isopeptide bond; Metal-binding; Nucleus; Phosphoprotein;
Receptor; Reference proteome; Repressor; Spermatogenesis;
Transcription; Transcription regulation; Ubl conjugation; Zinc;
Zinc-finger.
CHAIN 1 596 Nuclear receptor subfamily 2 group C
member 2.
/FTId=PRO_0000053589.
DOMAIN 341 583 NR LBD. {ECO:0000255|PROSITE-
ProRule:PRU01189}.
DNA_BIND 114 189 Nuclear receptor. {ECO:0000255|PROSITE-
ProRule:PRU00407}.
ZN_FING 117 137 NR C4-type. {ECO:0000255|PROSITE-
ProRule:PRU00407}.
ZN_FING 153 177 NR C4-type. {ECO:0000255|PROSITE-
ProRule:PRU00407}.
MOD_RES 19 19 Phosphoserine; by MAPK.
{ECO:0000269|PubMed:16887930}.
MOD_RES 46 46 Phosphoserine.
{ECO:0000250|UniProtKB:P49116}.
MOD_RES 55 55 Phosphoserine; by MAPK.
{ECO:0000269|PubMed:16887930}.
MOD_RES 68 68 Phosphoserine; by MAPK.
{ECO:0000269|PubMed:16887930}.
MOD_RES 98 98 Phosphoserine.
{ECO:0000250|UniProtKB:P49116}.
MOD_RES 219 219 Phosphoserine.
{ECO:0000250|UniProtKB:P49116}.
MOD_RES 231 231 N6-acetyllysine.
{ECO:0000244|PubMed:23806337}.
CROSSLNK 192 192 Glycyl lysine isopeptide (Lys-Gly)
(interchain with G-Cter in SUMO2).
{ECO:0000250|UniProtKB:P49116}.
MUTAGEN 15 15 S->A: Enhanced transcriptional
activation; Greatly enhanced
transcriptional activation; when
associated with A-68.
MUTAGEN 19 19 S->E: Some repression of transcriptional
activation; Repressed transcriptional
activity by about 10-fold; when
associated with E-68.
{ECO:0000269|PubMed:16887930}.
MUTAGEN 55 55 S->A: No effect on transcriptional
activation.
{ECO:0000269|PubMed:16887930}.
MUTAGEN 68 68 S->A: Enhanced transcriptional
activation; Greatly enhanced
transcriptional activation; when
associated with A-15.
{ECO:0000269|PubMed:16887930}.
MUTAGEN 68 68 S->E: Some repression of transcriptional
activation; Repressed transcriptional
activity by about 10-fold; when
associated with E-19.
{ECO:0000269|PubMed:16887930}.
CONFLICT 60 60 G -> E (in Ref. 2; AAC18408).
{ECO:0000305}.
CONFLICT 106 106 A -> Q (in Ref. 2; AAC18408).
{ECO:0000305}.
CONFLICT 122 122 D -> V (in Ref. 2; AAC18408).
{ECO:0000305}.
CONFLICT 247 247 N -> K (in Ref. 2; AAC18408).
{ECO:0000305}.
CONFLICT 263 263 A -> T (in Ref. 2; AAC18408).
{ECO:0000305}.
CONFLICT 323 323 T -> I (in Ref. 2; AAC18408).
{ECO:0000305}.
CONFLICT 327 328 SP -> CF (in Ref. 2; AAC18408).
{ECO:0000305}.
CONFLICT 337 337 A -> T (in Ref. 2; AAC18408).
{ECO:0000305}.
CONFLICT 484 485 KL -> NW (in Ref. 2; AAC18408).
{ECO:0000305}.
CONFLICT 510 510 G -> S (in Ref. 2; AAC18408).
{ECO:0000305}.
SEQUENCE 596 AA; 65239 MW; DE93C438A9CF1ED7 CRC64;
MTSPSPRIQI ISTDSAVASP QRIQIVTDQQ TGQKIQIVTA VDASGSSKQQ FILTSPDGAG
TGKVILASPE TSSAKQLIFT TSDNLVPGRI QIVTDSASVE RLLGKADVQR PQVVEYCVVC
GDKASGRHYG AVSCEGCKGF FKRSVRKNLT YSCRSSQDCI INKHHRNRCQ FCRLKKCLEM
GMKMESVQSE RKPFDVQREK PSNCAASTEK IYIRKDLRSP LIATPTFVAD KDGARQTGLL
DPGMLVNIQQ PLIREDGTVL LAADSKAETS QGALGTLANV VTSLANLSES LNNGDASEMQ
PEDQSASEIT RAFDTLAKAL NTTDSASPPS LADGIDASGG GSIHVISRDQ STPIIEVEGP
LLSDTHVTFK LTMPSPMPEY LNVHYICESA SRLLFLSMHW ARSIPAFQAL GQDCNTSLVR
ACWNELFTLG LAQCAQVMSL STILAAIVNH LQNSIQEDKL SGDRIKQVME HIWKLQEFCN
SMAKLDIDGY EYAYLKAIVL FSPDHPGLTG TSQIEKFQEK AQMELQDYVQ KTYSEDTYRL
ARILVRLPAL RLMSSNITEE LFFTGLIGNV SIDSIIPYIL KMETAEYNGQ ITGASL


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