NHR6_CAEEL
ID NHR6_CAEEL Reviewed; 619 AA.
AC P41829; B2MZB4; Q9GTI7; Q9XYB6;
DT 01-NOV-1995, integrated into UniProtKB/Swiss-Prot.
DT 11-JUL-2001, sequence version 3.
DT 03-AUG-2022, entry version 182.
DE RecName: Full=Nuclear hormone receptor family member nhr-6;
DE AltName: Full=Nuclear receptor subfamily 4 group A member 5;
DE AltName: Full=Steroid hormone receptor family member cnr8;
GN Name=nhr-6; Synonyms=cnr-8, nr4a5; ORFNames=C48D5.1;
OS Caenorhabditis elegans.
OC Eukaryota; Metazoa; Ecdysozoa; Nematoda; Chromadorea; Rhabditida;
OC Rhabditina; Rhabditomorpha; Rhabditoidea; Rhabditidae; Peloderinae;
OC Caenorhabditis.
OX NCBI_TaxID=6239;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Bristol N2;
RX PubMed=10022975;
RA Sluder A.E., Mathews S.W., Hough D., Yin V.P., Maina C.V.;
RT "The nuclear receptor superfamily has undergone extensive proliferation and
RT diversification in nematodes.";
RL Genome Res. 9:103-120(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=15983867; DOI=10.1007/s00239-004-0175-8;
RA Robinson-Rechavi M., Maina C.V., Gissendanner C.R., Laudet V., Sluder A.;
RT "Explosive lineage-specific expansion of the orphan nuclear receptor HNF4
RT in nematodes.";
RL J. Mol. Evol. 60:577-586(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Bristol N2;
RX PubMed=9851916; DOI=10.1126/science.282.5396.2012;
RG The C. elegans sequencing consortium;
RT "Genome sequence of the nematode C. elegans: a platform for investigating
RT biology.";
RL Science 282:2012-2018(1998).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 157-619, AND DEVELOPMENTAL STAGE.
RC STRAIN=Bristol N2;
RX PubMed=7816808; DOI=10.1073/pnas.92.1.156;
RA Kostrouch Z., Kostrouchova M., Rall J.E.;
RT "Steroid/thyroid hormone receptor genes in Caenorhabditis elegans.";
RL Proc. Natl. Acad. Sci. U.S.A. 92:156-159(1995).
RN [5]
RP FUNCTION, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, AND DISRUPTION
RP PHENOTYPE.
RX PubMed=18096150; DOI=10.1016/j.ydbio.2007.11.014;
RA Gissendanner C.R., Kelley K., Nguyen T.Q., Hoener M.C., Sluder A.E.,
RA Maina C.V.;
RT "The Caenorhabditis elegans NR4A nuclear receptor is required for
RT spermatheca morphogenesis.";
RL Dev. Biol. 313:767-786(2008).
RN [6]
RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE,
RP DOMAIN, DISRUPTION PHENOTYPE, AND MUTAGENESIS OF CYS-288.
RX PubMed=20506374; DOI=10.1002/dvg.20646;
RA Heard M., Maina C.V., Morehead B.E., Hoener M.C., Nguyen T.Q.,
RA Williams C.C., Rowan B.G., Gissendanner C.R.;
RT "A functional NR4A nuclear receptor DNA-binding domain is required for
RT organ development in Caenorhabditis elegans.";
RL Genesis 48:485-491(2010).
RN [7]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=25529479; DOI=10.1002/dvdy.24244;
RA Praslicka B., Gissendanner C.R.;
RT "The C. elegans NR4A nuclear receptor gene nhr-6 promotes cell cycle
RT progression in the spermatheca lineage.";
RL Dev. Dyn. 244:417-430(2015).
CC -!- FUNCTION: Transcriptional activator that induces gene expression by
CC binding to the NGFI-B response element (NBRE) 5'-AAAGGTCA-3'
CC (PubMed:20506374). Required for proper morphogenesis of the spermatheca
CC and the spermatheca-uterine valve formation (PubMed:18096150,
CC PubMed:25529479). Promotes cell proliferation and differentiation of
CC the spermatheca precursor cells during spermatheca development in
CC larval stage L4 (PubMed:18096150, PubMed:25529479). Might play a role
CC in promoting G1/S phase progression in the spermatheca precursor cell
CC lineage (PubMed:25529479). Also required for the differentiation of the
CC spermatheca-uterine junction core (sujc) cells which are generating the
CC spermatheca-uterine valve (PubMed:18096150).
CC {ECO:0000269|PubMed:18096150, ECO:0000269|PubMed:20506374,
CC ECO:0000269|PubMed:25529479}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:20506374}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=a;
CC IsoId=P41829-1; Sequence=Displayed;
CC Name=b;
CC IsoId=P41829-2; Sequence=VSP_059846;
CC -!- TISSUE SPECIFICITY: In hermaphrodites, expressed in the developing
CC spermatheca and dorsal uterus (PubMed:18096150, PubMed:20506374).
CC Expression includes the 8 cells of the dorsal somatic gonad primordium
CC and the sujc cells that form the core of the spermatheca-uterine valve
CC (PubMed:18096150). Expressed in the precursor cells of the spermatheca-
CC sheath lineages (SS cells) and in the precursors and descendents of the
CC dorsal-uterine lineage (DU cells) (PubMed:20506374). In both
CC hermaphroditic and male animals, expressed in a pair of head
CC chemosensory neurons (PubMed:18096150). {ECO:0000269|PubMed:18096150,
CC ECO:0000269|PubMed:20506374}.
CC -!- DEVELOPMENTAL STAGE: Most abundant in larval stage L3 (PubMed:7816808).
CC Expressed in larval stages L3 and L4 (PubMed:18096150,
CC PubMed:20506374). Weakly expressed in adult animals (PubMed:18096150).
CC {ECO:0000269|PubMed:18096150, ECO:0000269|PubMed:20506374,
CC ECO:0000269|PubMed:7816808}.
CC -!- DOMAIN: The NR LBD domain and the nuclear receptor DNA binding domain
CC are sufficient for binding to the NGFI-B response element (NBRE) 5'-
CC AAAGGTCA-3'. {ECO:0000269|PubMed:20506374}.
CC -!- DISRUPTION PHENOTYPE: Reduced brood size, abnormal egg morphology and
CC arrested egg development. Defects in ovulation with fragmentation of
CC the proximal oocyte and endomitosis. Misplacement of ovulated oocytes
CC into the gonad arms due to a lack of spermatheca-uterine valve
CC formation. Degeneration of gonad tissue. Decreased spermatheca organ
CC size due to decreased spermatheca cell number. Disorganized actin
CC microfilaments in the spermatheca, lack of distal constriction and
CC defects in spermathecal cell differentiation. Misexpression of let-502
CC in all cells of the spermatheca instead of restricted expression to the
CC distal and proximal regions of the spermatheca. Abnormal
CC differentiation and morphology of the sujc cells that form the core of
CC the spermatheca-uterine valve (PubMed:18096150). Lack of cell divisions
CC of the proximal spermatheca precursor daughter cells due to a failure
CC of progressing to S phase during larval stage L4 (PubMed:25529479). In
CC a fzr-1(ku298) mutant background, increase in spermatheca nuclei number
CC as compared to the nhr-6 single mutant (PubMed:25529479). In a fog-
CC 2(q71) mutant background, a large mass of fragmented oocytes in the
CC spermatheca and uterus (PubMed:18096150). RNAi-mediated knockdown leads
CC to reduced brood size and abnormal egg morphology (PubMed:20506374). In
CC a vab-1(e2), vab-1(e699), vab-2(ju1) or vab-2(e96) mutant background,
CC enhanced reduction in brood size (PubMed:25529479). In a vab-2(ju1)
CC mutant background, reduced spermatheca cell number and abnormal
CC spermatheca morphology (PubMed:25529479). In a RNAi-sensitive rrf-
CC 3(pk1426) mutant background, defects in spermatheca morphology,
CC including decreased organ size, decreased spermatheca cell number and
CC misplaced spermatheca nuclei. In a RNAi-sensitive eri-1(mg366) mutant
CC background, reduced brood size, abnormal egg morphology and arrested
CC eggs (PubMed:18096150). {ECO:0000269|PubMed:18096150,
CC ECO:0000269|PubMed:20506374, ECO:0000269|PubMed:25529479}.
CC -!- SIMILARITY: Belongs to the nuclear hormone receptor family. NR4
CC subfamily. {ECO:0000305}.
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DR EMBL; AF083224; AAD03682.1; -; mRNA.
DR EMBL; AF273770; AAG15119.1; -; mRNA.
DR EMBL; AY204167; AAO39171.1; -; mRNA.
DR EMBL; Z36237; CAA85271.2; -; Genomic_DNA.
DR EMBL; BX284603; CAQ48391.1; -; Genomic_DNA.
DR EMBL; U13076; AAA96984.1; -; mRNA.
DR PIR; G88408; G88408.
DR PIR; T43348; T43348.
DR RefSeq; NP_001129836.1; NM_001136364.2. [P41829-2]
DR RefSeq; NP_497731.1; NM_065330.5. [P41829-1]
DR AlphaFoldDB; P41829; -.
DR SMR; P41829; -.
DR BioGRID; 40702; 29.
DR DIP; DIP-26405N; -.
DR IntAct; P41829; 22.
DR STRING; 6239.C48D5.1a; -.
DR PaxDb; P41829; -.
DR PRIDE; P41829; -.
DR EnsemblMetazoa; C48D5.1a.1; C48D5.1a.1; WBGene00003605. [P41829-1]
DR EnsemblMetazoa; C48D5.1b.1; C48D5.1b.1; WBGene00003605. [P41829-2]
DR EnsemblMetazoa; C48D5.1b.2; C48D5.1b.2; WBGene00003605. [P41829-2]
DR GeneID; 175462; -.
DR KEGG; cel:CELE_C48D5.1; -.
DR UCSC; C48D5.1; c. elegans. [P41829-1]
DR CTD; 175462; -.
DR WormBase; C48D5.1a; CE24859; WBGene00003605; nhr-6. [P41829-1]
DR WormBase; C48D5.1b; CE42591; WBGene00003605; nhr-6. [P41829-2]
DR eggNOG; KOG4217; Eukaryota.
DR GeneTree; ENSGT00950000183038; -.
DR HOGENOM; CLU_510231_0_0_1; -.
DR InParanoid; P41829; -.
DR OMA; MCAVCND; -.
DR OrthoDB; 454476at2759; -.
DR PhylomeDB; P41829; -.
DR Reactome; R-CEL-198693; AKT phosphorylates targets in the nucleus.
DR SignaLink; P41829; -.
DR PRO; PR:P41829; -.
DR Proteomes; UP000001940; Chromosome III.
DR Bgee; WBGene00003605; Expressed in larva and 3 other tissues.
DR GO; GO:0005634; C:nucleus; IDA:WormBase.
DR GO; GO:0005667; C:transcription regulator complex; IBA:GO_Central.
DR GO; GO:0003700; F:DNA-binding transcription factor activity; IDA:WormBase.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; IBA:GO_Central.
DR GO; GO:0035259; F:nuclear glucocorticoid receptor binding; IBA:GO_Central.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IBA:GO_Central.
DR GO; GO:0043565; F:sequence-specific DNA binding; IDA:WormBase.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0071376; P:cellular response to corticotropin-releasing hormone stimulus; IBA:GO_Central.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:WormBase.
DR GO; GO:0060278; P:regulation of ovulation; IMP:WormBase.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0035211; P:spermathecum morphogenesis; IMP:WormBase.
DR Gene3D; 1.10.565.10; -; 1.
DR Gene3D; 3.30.50.10; -; 1.
DR InterPro; IPR035500; NHR-like_dom_sf.
DR InterPro; IPR000536; Nucl_hrmn_rcpt_lig-bd.
DR InterPro; IPR001628; Znf_hrmn_rcpt.
DR InterPro; IPR013088; Znf_NHR/GATA.
DR Pfam; PF00105; zf-C4; 1.
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 1: Evidence at protein level;
KW Alternative splicing; DNA-binding; Metal-binding; Nucleus; Receptor;
KW Reference proteome; Transcription; Transcription regulation; Zinc;
KW Zinc-finger.
FT CHAIN 1..619
FT /note="Nuclear hormone receptor family member nhr-6"
FT /id="PRO_0000053727"
FT DOMAIN 365..600
FT /note="NR LBD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01189"
FT DNA_BIND 265..340
FT /note="Nuclear receptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00407"
FT ZN_FING 268..288
FT /note="NR C4-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00407"
FT ZN_FING 304..328
FT /note="NR C4-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00407"
FT REGION 1..29
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 58..86
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 103..134
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 196..232
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 345..365
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 589..600
FT /note="AF-2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01189"
FT COMPBIAS 59..83
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VAR_SEQ 1..136
FT /note="Missing (in isoform b)"
FT /id="VSP_059846"
FT MUTAGEN 288
FT /note="C->S: Abolishes binding to the NGFI-B response
FT element (NBRE) 5'-AAAGGTCA-3'. Fails to activate
FT transcription. Abnormal spermatheca development with
FT abnormal egg morphology, lack of the spermatheca-uterine
FT valve and lack of distal constriction."
FT /evidence="ECO:0000269|PubMed:20506374"
FT CONFLICT 188
FT /note="S -> T (in Ref. 4; AAA96984)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 619 AA; 68623 MW; 43D3DBA751F3737F CRC64;
MEQLSIQTDE LQDQFSNCSP ASVDSSYSSC SSVEDEIEIY TRLVRNEEPL RRDFFREMSK
NSSCSSSFDY GEFGPSSSSR KGSKTTDADL DSLFHSLVET SDQVNTVPKP TKTEVESIPE
EFEQKPSSSS HRLPSEMNAS ITHIKSELDP TMQAFQMPHN DLFLATAAPH YNPFALSNDF
MPNPLMPSFT SPFYPQHFPV SDSRRGSQGT TSSSNNTGGT PSPHSSSLPT SPPQLQGFLR
SFLNPDNLST PTSFGVPSET ALDADKMCAV CNDRAVCLHY GARTCEGCKG FFKRTVQKNS
KYTCAGNKTC PIDKRYRSRC QYCRYQKCLE VGMVKEIVRH GSLSGRRGRL SSKTKLARSE
DQPSPPLPLL ALMGKAIEDH TNMTVVRQFM QPFDETIALR ILHGELHATK KLLMAMPQIS
EIQPADFQIL LSRSFFAIMA IRVANRCGNS TDTIMFESGE LFSLNAFPAC FQQIIRFMVD
KARTFSSLVD WEPQAFAAFI ALQFLAGNTE HNVLGLTNKP LVDQVQSTII NALKDHCSGS
QNKLAKIVRL TQEFDVFHAL GLQALDILYP SHQLPEEFMF LINLTRAPLR STDAPPACGS
PVAPSGSSLF NFQMGPAAF
