Nuclear receptor subfamily 0 group B member 1

NameNuclear receptor subfamily 0 group B member 1
Synonyms
  • AHC
  • DAX1
  • DSS-AHC critical region on the X chromosome protein 1
  • Nuclear receptor DAX-1
Gene NameNR0B1
OrganismHuman
Amino acid sequence
>lcl|BSEQ0000148|Nuclear receptor subfamily 0 group B member 1
MAGENHQWQGSILYNMLMSAKQTRAAPEAPETRLVDQCWGCSCGDEPGVGREGLLGGRNV
ALLYRCCFCGKDHPRQGSILYSMLTSAKQTYAAPKAPEATLGPCWGCSCGSDPGVGRAGL
PGGRPVALLYRCCFCGEDHPRQGSILYSLLTSSKQTHVAPAAPEARPGGAWWDRSYFAQR
PGGKEALPGGRATALLYRCCFCGEDHPQQGSTLYCVPTSTNQAQAAPEERPRAPWWDTSS
GALRPVALKSPQVVCEAASAGLLKTLRFVKYLPCFQVLPLDQQLVLVRNCWASLLMLELA
QDRLQFETVEVSEPSMLQKILTTRRRETGGNEPLPVPTLQHHLAPPAEARKVPSASQVQA
IKCFLSKCWSLNISTKEYAYLKGTVLFNPDVPGLQCVKYIQGLQWGTQQILSEHTRMTHQ
GPHDRFIELNSTLFLLRFINANVIAELFFRPIIGTVSMDDMMLEMLCTKI
Number of residues470
Molecular Weight51717.185
Theoretical pI8.12
GO Classification
Functions
  • RNA polymerase II transcription factor activity, ligand-activated sequence-specific DNA binding
  • steroid hormone receptor binding
  • protein homodimerization activity
  • transcription corepressor activity
  • RNA binding
  • steroid hormone receptor activity
  • DNA binding
  • transcription factor binding
  • protein domain specific binding
  • AF-2 domain binding
  • sequence-specific DNA binding
  • DNA hairpin binding
Processes
  • transcription initiation from RNA polymerase II promoter
  • steroid biosynthetic process
  • gonad development
  • hypothalamus development
  • Leydig cell differentiation
  • male sex determination
  • negative regulation of transcription from RNA polymerase II promoter
  • negative regulation of intracellular steroid hormone receptor signaling pathway
  • negative regulation of cell differentiation
  • negative regulation of transcription, DNA-templated
  • response to immobilization stress
  • adrenal gland development
  • pituitary gland development
  • male gonad development
  • protein localization
  • intracellular receptor signaling pathway
  • Sertoli cell differentiation
  • spermatogenesis
  • negative regulation of sequence-specific DNA binding transcription factor activity
  • gene expression
Components
  • nucleoplasm
  • cytoplasm
  • membrane
  • nucleus
  • polysomal ribosome
General FunctionTranscription factor binding
Specific FunctionOrphan nuclear receptor. Component of a cascade required for the development of the hypothalamic-pituitary-adrenal-gonadal axis. Acts as a coregulatory protein that inhibits the transcriptional activity of other nuclear receptors through heterodimeric interactions. May also have a role in the development of the embryo and in the maintenance of embryonic stem cell pluripotency (By similarity).
Pfam Domain Function
Transmembrane RegionsNot Available
GenBank Protein ID786532
UniProtKB IDP51843
UniProtKB Entry NameNR0B1_HUMAN
Cellular LocationNucleus
Gene sequence
>lcl|BSEQ0010151|Nuclear receptor subfamily 0 group B member 1 (NR0B1)
ATGGCGGGCGAGAACCACCAGTGGCAGGGCAGCATCCTCTACAACATGCTTATGAGCGCG
AAGCAAACGCGCGCGGCTCCTGAGGCTCCAGAGACGCGGCTGGTGGATCAGTGCTGGGGC
TGTTCGTGCGGCGATGAGCCCGGGGTGGGCAGAGAGGGGCTGCTGGGCGGGCGGAACGTG
GCGCTCCTGTACCGCTGCTGCTTTTGCGGTAAAGACCACCCACGGCAGGGCAGCATCCTC
TACAGCATGCTGACGAGCGCAAAGCAAACGTACGCGGCACCGAAGGCGCCCGAGGCGACG
CTGGGTCCGTGCTGGGGCTGTTCGTGCGGCTCTGATCCCGGGGTGGGCAGAGCGGGGCTT
CCGGGTGGGCGGCCCGTGGCACTCCTGTACCGCTGCTGCTTTTGTGGTGAAGACCACCCG
CGGCAGGGCAGCATCCTCTACAGCTTGCTCACTAGCTCAAAGCAAACGCACGTGGCTCCG
GCAGCGCCCGAGGCACGGCCAGGGGGCGCGTGGTGGGACCGCTCCTACTTCGCGCAGAGG
CCAGGGGGTAAAGAGGCGCTACCAGGCGGGCGGGCCACGGCGCTTCTGTACCGCTGCTGC
TTTTGCGGTGAAGACCACCCGCAGCAGGGCAGCACCCTCTACTGCGTGCCCACGAGCACA
AATCAAGCGCAGGCGGCTCCGGAGGAGCGGCCGAGGGCCCCCTGGTGGGACACCTCCTCT
GGTGCGCTGCGGCCGGTGGCGCTCAAGAGTCCACAGGTGGTCTGCGAGGCAGCCTCAGCG
GGCCTGTTGAAGACGCTGCGCTTCGTCAAGTACTTGCCCTGCTTCCAGGTGCTGCCCCTG
GACCAGCAGCTGGTGCTGGTGCGCAACTGCTGGGCGTCCCTGCTCATGCTTGAGCTGGCC
CAGGACCGCTTGCAGTTCGAGACTGTGGAAGTCTCGGAGCCCAGCATGCTGCAGAAGATC
CTCACCACCAGGCGGCGGGAGACCGGGGGCAACGAGCCACTGCCCGTGCCCACGCTGCAG
CACCATTTGGCACCGCCGGCGGAGGCCAGGAAGGTGCCCTCCGCCTCCCAGGTCCAAGCC
ATCAAGTGCTTTCTTTCCAAATGCTGGAGTCTGAACATCAGTACCAAGGAGTACGCCTAC
CTCAAGGGGACCGTGCTCTTTAACCCGGACGTGCCGGGCCTGCAGTGCGTGAAGTACATT
CAGGGACTCCAGTGGGGAACTCAGCAAATACTCAGTGAACACACCAGGATGACGCACCAA
GGGCCCCATGACAGATTCATCGAACTTAATAGTACCCTTTTCCTGCTGAGATTCATCAAT
GCCAATGTCATTGCTGAACTGTTCTTCAGGCCCATCATCGGCACAGTCAGCATGGATGAT
ATGATGCTGGAAATGCTCTGTACAAAGATATAA
GenBank Gene IDU31929
GeneCard IDNot Available
GenAtlas IDNR0B1
HGNC IDHGNC:7960
Chromosome LocationX
LocusXp21.3-p21.2
References
  1. Zanaria E, Muscatelli F, Bardoni B, Strom TM, Guioli S, Guo W, Lalli E, Moser C, Walker AP, McCabe ER, et al.: An unusual member of the nuclear hormone receptor superfamily responsible for X-linked adrenal hypoplasia congenita. Nature. 1994 Dec 15;372(6507):635-41. 7990953
  2. Guo W, Burris TP, Zhang YH, Huang BL, Mason J, Copeland KC, Kupfer SR, Pagon RA, McCabe ER: Genomic sequence of the DAX1 gene: an orphan nuclear receptor responsible for X-linked adrenal hypoplasia congenita and hypogonadotropic hypogonadism. J Clin Endocrinol Metab. 1996 Jul;81(7):2481-6. 8675564
  3. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. 15489334
  4. Altincicek B, Tenbaum SP, Dressel U, Thormeyer D, Renkawitz R, Baniahmad A: Interaction of the corepressor Alien with DAX-1 is abrogated by mutations of DAX-1 involved in adrenal hypoplasia congenita. J Biol Chem. 2000 Mar 17;275(11):7662-7. 10713076
  5. Suzuki T, Kasahara M, Yoshioka H, Morohashi K, Umesono K: LXXLL-related motifs in Dax-1 have target specificity for the orphan nuclear receptors Ad4BP/SF-1 and LRH-1. Mol Cell Biol. 2003 Jan;23(1):238-49. 12482977
  6. Ho J, Zhang YH, Huang BL, McCabe ER: NR0B1A: an alternatively spliced form of NR0B1. Mol Genet Metab. 2004 Dec;83(4):330-6. 15589120
  7. Niakan KK, McCabe ER: DAX1 origin, function, and novel role. Mol Genet Metab. 2005 Sep-Oct;86(1-2):70-83. 16146703
  8. Iyer AK, Zhang YH, McCabe ER: Dosage-sensitive sex reversal adrenal hypoplasia congenita critical region on the X chromosome, gene 1 (DAX1) (NR0B1) and small heterodimer partner (SHP) (NR0B2) form homodimers individually, as well as DAX1-SHP heterodimers. Mol Endocrinol. 2006 Oct;20(10):2326-42. Epub 2006 May 18. 16709599
  9. Muscatelli F, Strom TM, Walker AP, Zanaria E, Recan D, Meindl A, Bardoni B, Guioli S, Zehetner G, Rabl W, et al.: Mutations in the DAX-1 gene give rise to both X-linked adrenal hypoplasia congenita and hypogonadotropic hypogonadism. Nature. 1994 Dec 15;372(6507):672-6. 7990958
  10. Schwartz M, Blichfeldt S, Muller J: X-linked adrenal hypoplasia in a large Greenlandic family. Detection of a missense mutation (N4401) in the DAX-1 gene; implication for genetic counselling and carrier diagnosis. Hum Genet. 1997 Jan;99(1):83-7. 9003500
  11. Nakae J, Abe S, Tajima T, Shinohara N, Murashita M, Igarashi Y, Kusuda S, Suzuki J, Fujieda K: Three novel mutations and a de novo deletion mutation of the DAX-1 gene in patients with X-linked adrenal hypoplasia congenita. J Clin Endocrinol Metab. 1997 Nov;82(11):3835-41. 9360549
  12. Takahashi T, Shoji Y, Shoji Y, Haraguchi N, Takahashi I, Takada G: Active hypothalamic-pituitary-gonadal axis in an infant with X-linked adrenal hypoplasia congenita. J Pediatr. 1997 Mar;130(3):485-8. 9063431
  13. Lalli E, Bardoni B, Zazopoulos E, Wurtz JM, Strom TM, Moras D, Sassone-Corsi P: A transcriptional silencing domain in DAX-1 whose mutation causes adrenal hypoplasia congenita. Mol Endocrinol. 1997 Dec;11(13):1950-60. 9415399
  14. Zhang YH, Guo W, Wagner RL, Huang BL, McCabe L, Vilain E, Burris TP, Anyane-Yeboa K, Burghes AH, Chitayat D, Chudley AE, Genel M, Gertner JM, Klingensmith GJ, Levine SN, Nakamoto J, New MI, Pagon RA, Pappas JG, Quigley CA, Rosenthal IM, Baxter JD, Fletterick RJ, McCabe ER: DAX1 mutations map to putative structural domains in a deduced three-dimensional model. Am J Hum Genet. 1998 Apr;62(4):855-64. 9529340
  15. Swain A, Narvaez V, Burgoyne P, Camerino G, Lovell-Badge R: Dax1 antagonizes Sry action in mammalian sex determination. Nature. 1998 Feb 19;391(6669):761-7. 9486644
  16. Abe S, Nakae J, Yasoshima K, Tajima T, Shinohara N, Murashita M, Satoh K, Koike A, Takahashi Y, Fujieda K: Novel missense mutation (Leu466Arg) of the DAX1 gene in a patient with X-linked congenital adrenal hypoplasia. Am J Med Genet. 1999 May 21;84(2):87-9. 10323730
  17. Bassett JH, O'Halloran DJ, Williams GR, Beardwell CG, Shalet SM, Thakker RV: Novel DAX1 mutations in X-linked adrenal hypoplasia congenita and hypogonadotrophic hypogonadism. Clin Endocrinol (Oxf). 1999 Jan;50(1):69-75. 10341858
  18. Tabarin A, Achermann JC, Recan D, Bex V, Bertagna X, Christin-Maitre S, Ito M, Jameson JL, Bouchard P: A novel mutation in DAX1 causes delayed-onset adrenal insufficiency and incomplete hypogonadotropic hypogonadism. J Clin Invest. 2000 Feb;105(3):321-8. 10675358
  19. Achermann JC, Silverman BL, Habiby RL, Jameson JL: Presymptomatic diagnosis of X-linked adrenal hypoplasia congenita by analysis of DAX1. J Pediatr. 2000 Dec;137(6):878-81. 11113848
  20. Lalli E, Ohe K, Hindelang C, Sassone-Corsi P: Orphan receptor DAX-1 is a shuttling RNA binding protein associated with polyribosomes via mRNA. Mol Cell Biol. 2000 Jul;20(13):4910-21. 10848616
  21. Zhang YH, Huang BL, Anyane-Yeboa K, Carvalho JA, Clemons RD, Cole T, De Figueiredo BC, Lubinsky M, Metzger DL, Quadrelli R, Repaske DR, Reyno S, Seaver LH, Vaglio A, Van Vliet G, McCabe LL, McCabe ER, Phelan JK: Nine novel mutations in NR0B1 (DAX1) causing adrenal hypoplasia congenita. Hum Mutat. 2001 Dec;18(6):547. 11748852
  22. Achermann JC, Ito M, Silverman BL, Habiby RL, Pang S, Rosler A, Jameson JL: Missense mutations cluster within the carboxyl-terminal region of DAX-1 and impair transcriptional repression. J Clin Endocrinol Metab. 2001 Jul;86(7):3171-5. 11443184
  23. Mantovani G, Ozisik G, Achermann JC, Romoli R, Borretta G, Persani L, Spada A, Jameson JL, Beck-Peccoz P: Hypogonadotropic hypogonadism as a presenting feature of late-onset X-linked adrenal hypoplasia congenita. J Clin Endocrinol Metab. 2002 Jan;87(1):44-8. 11788621
  24. Brown P, Scobie GA, Townsend J, Bayne RA, Seckl JR, Saunders PT, Anderson RA: Identification of a novel missense mutation that is as damaging to DAX-1 repressor function as a nonsense mutation. J Clin Endocrinol Metab. 2003 Mar;88(3):1341-9. 12629128
  25. Franzese A, Brunetti-Pierri N, Spagnuolo MI, Spadaro R, Giugliano M, Mukai T, Valerio G: Inappropriate tall stature and renal ectopy in a male patient with X-linked congenital adrenal hypoplasia due to a novel missense mutation in the DAX-1 gene. Am J Med Genet A. 2005 May 15;135(1):72-4. 15800903