NR6A1_HUMAN
ID NR6A1_HUMAN Reviewed; 480 AA.
AC Q15406; O00551; O00603; Q5T6F4; Q8NHQ0; Q92898; Q99802;
DT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-2000, sequence version 2.
DT 03-AUG-2022, entry version 200.
DE RecName: Full=Nuclear receptor subfamily 6 group A member 1;
DE AltName: Full=Germ cell nuclear factor;
DE Short=GCNF;
DE Short=hGCNF;
DE AltName: Full=Retinoid receptor-related testis-specific receptor;
DE Short=RTR;
DE Short=hRTR;
GN Name=NR6A1; Synonyms=GCNF;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), AND TISSUE SPECIFICITY.
RC TISSUE=Embryonic carcinoma;
RX PubMed=8982251; DOI=10.1016/s0167-4781(96)00157-1;
RA Suesens U., Borgmeyer U.;
RT "Characterization of the human germ cell nuclear factor gene.";
RL Biochim. Biophys. Acta 1309:179-182(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 4), ALTERNATIVE SPLICING, AND
RP TISSUE SPECIFICITY.
RC TISSUE=Testis;
RX PubMed=9177477; DOI=10.1016/s0167-4781(97)00043-2;
RA Kapelle M., Kraetzschmar J., Husemann M., Schleuning W.-D.;
RT "cDNA cloning of two closely related forms of human germ cell nuclear
RT factor (GCNF).";
RL Biochim. Biophys. Acta 1352:13-17(1997).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND TISSUE SPECIFICITY.
RC TISSUE=Testis;
RX PubMed=9134503; DOI=10.1677/jme.0.0180167;
RA Lei W., Hirose T., Zhang L.-X., Adachi H., Spinella M.J., Dmitrovsky E.,
RA Jetten A.M.;
RT "Cloning of the human orphan receptor germ cell nuclear factor/retinoid
RT receptor-related testis-associated receptor and its differential regulation
RT during embryonal carcinoma cell differentiation.";
RL J. Mol. Endocrinol. 18:167-176(1997).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3), AND TISSUE SPECIFICITY.
RC TISSUE=Testis;
RX PubMed=9537518; DOI=10.1016/s0014-5793(98)00142-2;
RA Agoulnik I.Y., Cho Y., Niederberger C., Kieback D.G., Cooney A.J.;
RT "Cloning, expression analysis and chromosomal localization of the human
RT nuclear receptor gene GCNF.";
RL FEBS Lett. 424:73-78(1998).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND TISSUE SPECIFICITY.
RX PubMed=9493564; DOI=10.3109/10799899809039161;
RA Schneider-Hirsch S., Bauer U.M., Heiermann R., Rentrop M., Maelicke A.;
RT "Cloning of the human NCNF gene.";
RL J. Recept. Signal Transduct. 18:1-13(1998).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15164053; DOI=10.1038/nature02465;
RA Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L.,
RA Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R.,
RA Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S.,
RA Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K.,
RA Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y.,
RA Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C.,
RA Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E.,
RA Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M.,
RA Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J.,
RA Frankish A., Frankland J.A., French L., Fricker D.G., Garner P.,
RA Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S.,
RA Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E.,
RA Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D.,
RA Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E.,
RA Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K.,
RA Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S.,
RA Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J.,
RA Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E.,
RA McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V.,
RA Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S.,
RA Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K.,
RA Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J.,
RA Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M.,
RA West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L.,
RA Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M.,
RA Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J.,
RA Dunham I.;
RT "DNA sequence and analysis of human chromosome 9.";
RL Nature 429:369-374(2004).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 5).
RC TISSUE=Testis;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [8]
RP INTERACTION WITH UIMC1.
RX PubMed=12080054; DOI=10.1074/jbc.m203475200;
RA Yan Z., Kim Y.-S., Jetten A.M.;
RT "RAP80: a novel nuclear protein that interacts with the retinoid-related
RT testis-associated receptor.";
RL J. Biol. Chem. 277:32379-32388(2002).
CC -!- FUNCTION: Orphan nuclear receptor. Binds to a response element
CC containing the sequence 5'-TCAAGGTCA-3'. May be involved in the
CC regulation of gene expression in germ cell development during
CC gametogenesis (By similarity). {ECO:0000250}.
CC -!- SUBUNIT: Homodimer. Interacts with UIMC1 (By similarity).
CC {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000305}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=5;
CC Name=1;
CC IsoId=Q15406-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q15406-2; Sequence=VSP_003721;
CC Name=3;
CC IsoId=Q15406-3; Sequence=VSP_003720, VSP_003721;
CC Name=4;
CC IsoId=Q15406-4; Sequence=VSP_025927;
CC Name=5;
CC IsoId=Q15406-5; Sequence=VSP_003721, VSP_025927;
CC -!- TISSUE SPECIFICITY: Shows highest expression in the germ cells of the
CC adult testis. {ECO:0000269|PubMed:8982251, ECO:0000269|PubMed:9134503,
CC ECO:0000269|PubMed:9177477, ECO:0000269|PubMed:9493564,
CC ECO:0000269|PubMed:9537518}.
CC -!- SIMILARITY: Belongs to the nuclear hormone receptor family. NR6
CC subfamily. {ECO:0000305}.
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DR EMBL; S83309; AAB50876.1; -; mRNA.
DR EMBL; U80802; AAB96828.1; -; mRNA.
DR EMBL; U64876; AAB06335.1; -; mRNA.
DR EMBL; AF004291; AAC52054.1; -; mRNA.
DR EMBL; X99975; CAA68236.1; -; mRNA.
DR EMBL; AL158075; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL354928; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL354979; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC030600; AAH30600.1; -; mRNA.
DR CCDS; CCDS35137.1; -. [Q15406-1]
DR CCDS; CCDS55340.1; -. [Q15406-5]
DR CCDS; CCDS65127.1; -. [Q15406-2]
DR RefSeq; NP_001265475.1; NM_001278546.1. [Q15406-2]
DR RefSeq; NP_001480.3; NM_001489.4. [Q15406-5]
DR RefSeq; NP_201591.2; NM_033334.3. [Q15406-1]
DR RefSeq; XP_005251974.1; XM_005251917.4. [Q15406-4]
DR AlphaFoldDB; Q15406; -.
DR SMR; Q15406; -.
DR BioGRID; 108919; 7.
DR IntAct; Q15406; 1.
DR STRING; 9606.ENSP00000420267; -.
DR ChEMBL; CHEMBL1961793; -.
DR iPTMnet; Q15406; -.
DR PhosphoSitePlus; Q15406; -.
DR BioMuta; NR6A1; -.
DR DMDM; 12643728; -.
DR EPD; Q15406; -.
DR jPOST; Q15406; -.
DR MassIVE; Q15406; -.
DR MaxQB; Q15406; -.
DR PaxDb; Q15406; -.
DR PeptideAtlas; Q15406; -.
DR PRIDE; Q15406; -.
DR ProteomicsDB; 60572; -. [Q15406-1]
DR ProteomicsDB; 60573; -. [Q15406-2]
DR ProteomicsDB; 60574; -. [Q15406-3]
DR ProteomicsDB; 60575; -. [Q15406-4]
DR ProteomicsDB; 60576; -. [Q15406-5]
DR Antibodypedia; 16337; 336 antibodies from 35 providers.
DR DNASU; 2649; -.
DR Ensembl; ENST00000344523.8; ENSP00000341135.4; ENSG00000148200.17. [Q15406-4]
DR Ensembl; ENST00000373584.7; ENSP00000362686.3; ENSG00000148200.17. [Q15406-2]
DR Ensembl; ENST00000416460.6; ENSP00000413701.2; ENSG00000148200.17. [Q15406-5]
DR Ensembl; ENST00000487099.7; ENSP00000420267.1; ENSG00000148200.17. [Q15406-1]
DR GeneID; 2649; -.
DR KEGG; hsa:2649; -.
DR MANE-Select; ENST00000487099.7; ENSP00000420267.1; NM_033334.4; NP_201591.2.
DR UCSC; uc004boq.3; human. [Q15406-1]
DR CTD; 2649; -.
DR DisGeNET; 2649; -.
DR GeneCards; NR6A1; -.
DR HGNC; HGNC:7985; NR6A1.
DR HPA; ENSG00000148200; Tissue enriched (testis).
DR MIM; 602778; gene.
DR neXtProt; NX_Q15406; -.
DR OpenTargets; ENSG00000148200; -.
DR PharmGKB; PA31766; -.
DR VEuPathDB; HostDB:ENSG00000148200; -.
DR eggNOG; KOG3575; Eukaryota.
DR GeneTree; ENSGT00940000157936; -.
DR HOGENOM; CLU_007368_6_1_1; -.
DR InParanoid; Q15406; -.
DR OMA; SPEAYVC; -.
DR PhylomeDB; Q15406; -.
DR TreeFam; TF350737; -.
DR PathwayCommons; Q15406; -.
DR Reactome; R-HSA-2892247; POU5F1 (OCT4), SOX2, NANOG activate genes related to proliferation. [Q15406-1]
DR Reactome; R-HSA-383280; Nuclear Receptor transcription pathway.
DR SignaLink; Q15406; -.
DR BioGRID-ORCS; 2649; 10 hits in 1091 CRISPR screens.
DR ChiTaRS; NR6A1; human.
DR GeneWiki; Germ_cell_nuclear_factor; -.
DR GenomeRNAi; 2649; -.
DR Pharos; Q15406; Tbio.
DR PRO; PR:Q15406; -.
DR Proteomes; UP000005640; Chromosome 9.
DR RNAct; Q15406; protein.
DR Bgee; ENSG00000148200; Expressed in oocyte and 135 other tissues.
DR ExpressionAtlas; Q15406; baseline and differential.
DR Genevisible; Q15406; HS.
DR GO; GO:0000785; C:chromatin; ISA:NTNU_SB.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0005667; C:transcription regulator complex; ISS:UniProtKB.
DR GO; GO:0003677; F:DNA binding; ISS:UniProtKB.
DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; IEA:Ensembl.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; ISA:NTNU_SB.
DR GO; GO:0004879; F:nuclear receptor activity; IBA:GO_Central.
DR GO; GO:0042803; F:protein homodimerization activity; ISS:UniProtKB.
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; ISS:UniProtKB.
DR GO; GO:1990837; F:sequence-specific double-stranded DNA binding; IDA:ARUK-UCL.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0007276; P:gamete generation; ISS:UniProtKB.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; ISS:UniProtKB.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
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; IPR001723; Nuclear_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; 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 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..480
FT /note="Nuclear receptor subfamily 6 group A member 1"
FT /id="PRO_0000053741"
FT DOMAIN 249..480
FT /note="NR LBD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01189"
FT DNA_BIND 57..132
FT /note="Nuclear receptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00407"
FT ZN_FING 60..80
FT /note="NR C4-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00407"
FT ZN_FING 96..120
FT /note="NR C4-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00407"
FT REGION 1..32
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 131..150
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 162..199
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 172..253
FT /note="Sufficient for interaction with UIMC1"
FT /evidence="ECO:0000250"
FT COMPBIAS 173..199
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VAR_SEQ 9..30
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:9537518"
FT /id="VSP_003720"
FT VAR_SEQ 48..52
FT /note="ISVSD -> N (in isoform 2, isoform 3 and isoform 5)"
FT /evidence="ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:8982251, ECO:0000303|PubMed:9537518"
FT /id="VSP_003721"
FT VAR_SEQ 199
FT /note="Missing (in isoform 4 and isoform 5)"
FT /evidence="ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:9177477"
FT /id="VSP_025927"
FT CONFLICT 90
FT /note="N -> K (in Ref. 3; AAB06335)"
FT /evidence="ECO:0000305"
FT CONFLICT 129
FT /note="A -> T (in Ref. 5; CAA68236)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 480 AA; 54383 MW; 0D8578E192581A8E CRC64;
MERDEPPPSG GGGGGGSAGF LEPPAALPPP PRNGFCQDEL AELDPGTISV SDDRAEQRTC
LICGDRATGL HYGIISCEGC KGFFKRSICN KRVYRCSRDK NCVMSRKQRN RCQYCRLLKC
LQMGMNRKAI REDGMPGGRN KSIGPVQISE EEIERIMSGQ EFEEEANHWS NHGDSDHSSP
GNRASESNQP SPGSTLSSSR SVELNGFMAF REQYMGMSVP PHYQYIPHLF SYSGHSPLLP
QQARSLDPQS YSLIHQLLSA EDLEPLGTPM LIEDGYAVTQ AELFALLCRL ADELLFRQIA
WIKKLPFFCE LSIKDYTCLL SSTWQELILL SSLTVYSKQI FGELADVTAK YSPSDEELHR
FSDEGMEVIE RLIYLYHKFH QLKVSNEEYA CMKAINFLNQ DIRGLTSASQ LEQLNKRYWY
ICQDFTEYKY THQPNRFPDL MMCLPEIRYI AGKMVNVPLE QLPLLFKVVL HSCKTSVGKE
