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 27-MAR-2024, entry version 209. 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}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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 CCDS; CCDS94481.1; -. [Q15406-4] 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. DR AlphaFoldDB; Q15406; -. DR SMR; Q15406; -. DR BioGRID; 108919; 7. DR IntAct; Q15406; 1. DR STRING; 9606.ENSP00000420267; -. DR BindingDB; Q15406; -. 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; 9606-ENSP00000420267; -. DR PeptideAtlas; 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; 374 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 AGR; HGNC:7985; -. 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; LVEMDCL; -. DR OrthoDB; 5397661at2759; -. 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; 13 hits in 1174 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 primordial germ cell in gonad and 136 other cell types or tissues. DR ExpressionAtlas; Q15406; baseline and differential. 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:0034056; F:estrogen response element binding; IBA:GO_Central. DR GO; GO:0004879; F:nuclear receptor activity; IBA:GO_Central. DR GO; GO:0042803; F:protein homodimerization activity; ISS:UniProtKB. 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 CDD; cd07169; NR_DBD_GCNF_like; 1. DR CDD; cd06953; NR_LBD_DHR4_like; 1. DR Gene3D; 3.30.50.10; Erythroid Transcription Factor GATA-1, subunit A; 1. DR Gene3D; 1.10.565.10; Retinoid X Receptor; 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 PANTHER; PTHR48092; KNIRPS-RELATED PROTEIN-RELATED; 1. DR PANTHER; PTHR48092:SF18; NUCLEAR RECEPTOR SUBFAMILY 6 GROUP A MEMBER 1; 1. 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; SSF57716; Glucocorticoid receptor-like (DNA-binding domain); 1. DR SUPFAM; SSF48508; Nuclear receptor ligand-binding domain; 1. DR PROSITE; PS51843; NR_LBD; 1. DR PROSITE; PS00031; NUCLEAR_REC_DBD_1; 1. DR PROSITE; PS51030; NUCLEAR_REC_DBD_2; 1. DR Genevisible; Q15406; HS. 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 //