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Protein

Nuclear receptor subfamily 0 group B member 1

Gene

NR0B1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Orphan 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).By similarity

GO - Molecular functioni

  • AF-2 domain binding Source: UniProtKB
  • DNA binding Source: HGNC
  • DNA hairpin binding Source: HGNC
  • protein domain specific binding Source: UniProtKB
  • protein homodimerization activity Source: UniProtKB
  • RNA binding Source: HGNC
  • RNA polymerase II transcription factor activity, ligand-activated sequence-specific DNA binding Source: UniProtKB
  • sequence-specific DNA binding Source: HGNC
  • steroid hormone receptor activity Source: InterPro
  • steroid hormone receptor binding Source: UniProtKB
  • transcription corepressor activity Source: BHF-UCL
  • transcription factor binding Source: BHF-UCL

GO - Biological processi

  • adrenal gland development Source: HGNC
  • gonad development Source: HGNC
  • hypothalamus development Source: UniProtKB
  • Leydig cell differentiation Source: Ensembl
  • male gonad development Source: UniProtKB
  • male sex determination Source: Ensembl
  • negative regulation of cell differentiation Source: Ensembl
  • negative regulation of intracellular steroid hormone receptor signaling pathway Source: UniProtKB
  • negative regulation of sequence-specific DNA binding transcription factor activity Source: BHF-UCL
  • negative regulation of transcription, DNA-templated Source: HGNC
  • negative regulation of transcription from RNA polymerase II promoter Source: GO_Central
  • pituitary gland development Source: UniProtKB
  • protein localization Source: UniProtKB
  • response to immobilization stress Source: Ensembl
  • Sertoli cell differentiation Source: Ensembl
  • spermatogenesis Source: Ensembl
  • steroid biosynthetic process Source: HGNC
  • transcription initiation from RNA polymerase II promoter Source: Reactome
Complete GO annotation...

Keywords - Molecular functioni

Receptor, Repressor

Keywords - Biological processi

Transcription, Transcription regulation

Enzyme and pathway databases

BioCyciZFISH:ENSG00000169297-MONOMER.
ReactomeiR-HSA-383280. Nuclear Receptor transcription pathway.
SignaLinkiP51843.
SIGNORiP51843.

Names & Taxonomyi

Protein namesi
Recommended name:
Nuclear receptor subfamily 0 group B member 1
Alternative name(s):
DSS-AHC critical region on the X chromosome protein 1
Nuclear receptor DAX-1
Gene namesi
Name:NR0B1
Synonyms:AHC, DAX1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome X

Organism-specific databases

HGNCiHGNC:7960. NR0B1.

Subcellular locationi

  • Nucleus 1 Publication
  • Cytoplasm 1 Publication

  • Note: Shuttles between the cytoplasm and nucleus. Homodimers exits in the cytoplasm and in the nucleus.

GO - Cellular componenti

  • cytoplasm Source: UniProtKB
  • membrane Source: BHF-UCL
  • nucleoplasm Source: HPA
  • nucleus Source: UniProtKB
  • polysomal ribosome Source: HGNC
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Involvement in diseasei

Adrenal hypoplasia, congenital (AHC)14 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA disorder of adrenal gland development characterized by absence of the permanent zone of the adrenal cortex, structural disorganization of the adrenal glands, adrenal insufficiency and profound hormonal deficiencies. AHC patients manifest primary adrenal failure usually in early infancy, and hypogonadotropic hypogonadism leading to absent or incomplete sexual maturation. AHC can be inherited in an X-linked or autosomal recessive pattern.
See also OMIM:300200
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_004738267R → P in AHC; impairs transcriptional silencing of the StAR promoter. 3 PublicationsCorresponds to variant rs104894888dbSNPEnsembl.1
Natural variantiVAR_004739269Missing in AHC; impairs transcriptional silencing of the StAR promoter. 3 Publications1
Natural variantiVAR_031079278L → P in AHC. 1 Publication1
Natural variantiVAR_004740287V → G in AHC; the patient presents an inappropriate tall stature and renal ectopy. 1 Publication1
Natural variantiVAR_031080291W → C in AHC. 1 PublicationCorresponds to variant rs28935482dbSNPEnsembl.1
Natural variantiVAR_018303295L → P in AHC. 1 Publication1
Natural variantiVAR_031081297L → P in AHC; results in a severe loss of repressor activity. 1 PublicationCorresponds to variant rs104894907dbSNPEnsembl.1
Natural variantiVAR_018304300A → P in AHC. 1 Publication1
Natural variantiVAR_004741300A → V in AHC. 1 Publication1
Natural variantiVAR_004742377E → K in AHC. 2 Publications1
Natural variantiVAR_018300380Y → D in AHC. 1 PublicationCorresponds to variant rs104894900dbSNPEnsembl.1
Natural variantiVAR_018301381L → H in AHC. 1 PublicationCorresponds to variant rs104894899dbSNPEnsembl.1
Natural variantiVAR_004743382K → N in AHC. 1 PublicationCorresponds to variant rs28935180dbSNPEnsembl.1
Natural variantiVAR_004744385V → G in AHC. 1 Publication1
Natural variantiVAR_004745425R → G in AHC. 1 Publication1
Natural variantiVAR_018305425R → T in AHC. 1 Publication1
Natural variantiVAR_018302439I → S in AHC; mild phenotype. 1 PublicationCorresponds to variant rs104894897dbSNPEnsembl.1
Natural variantiVAR_004746440N → I in AHC; impairs RNA-binding activity. 2 PublicationsCorresponds to variant rs28935481dbSNPEnsembl.1
Natural variantiVAR_018306466L → R in AHC. 1 Publication1
46,XY sex reversal 2 (SRXY2)1 Publication
The disease is caused by mutations affecting the gene represented in this entry. XY individuals with a duplication of part of the short arm of the X chromosome and an intact SRY gene develop as females. The single X chromosome in these individuals does not undergo X-chromosome inactivation; therefore, these individuals presumably carry 2 active copies of genes, including the NR0B1 gene, in the duplicated region. Individuals with deletion of this region develop as males. Genes within the dosage-sensitive sex reversal region are, therefore, not essential for testis development, but, when present in a double dose, interfere with testis formation.
Disease descriptionA condition characterized by male-to-female sex reversal in the presence of a normal 46,XY karyotype.
See also OMIM:300018

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi16 – 17ML → AA: Strongly reduces homodimerization and interaction with NR0B2. 1 Publication2
Mutagenesisi83 – 84ML → AA: Strongly reduces homodimerization and interaction with NR0B2. 1 Publication2
Mutagenesisi149 – 150LL → AA: Strongly reduces homodimerization and interaction with NR0B2. 1 Publication2
Mutagenesisi461 – 462MM → AA: Strongly reduces homodimerization and interaction with NR0B2. 1 Publication2

Keywords - Diseasei

Disease mutation

Organism-specific databases

DisGeNETi190.
MalaCardsiNR0B1.
MIMi300018. phenotype.
300200. phenotype.
OpenTargetsiENSG00000169297.
Orphaneti242. 46,XY complete gonadal dysgenesis.
251510. 46,XY partial gonadal dysgenesis.
95702. Cytomegalic congenital adrenal hypoplasia.
PharmGKBiPA31746.

Chemistry databases

ChEMBLiCHEMBL1795094.
DrugBankiDB01234. Dexamethasone.
DB00755. Tretinoin.

Polymorphism and mutation databases

BioMutaiNR0B1.
DMDMi20532385.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000537481 – 470Nuclear receptor subfamily 0 group B member 1Add BLAST470

Proteomic databases

EPDiP51843.
MaxQBiP51843.
PaxDbiP51843.
PeptideAtlasiP51843.
PRIDEiP51843.

PTM databases

iPTMnetiP51843.
PhosphoSitePlusiP51843.

Expressioni

Gene expression databases

BgeeiENSG00000169297.
CleanExiHS_NR0B1.
ExpressionAtlasiP51843. baseline and differential.
GenevisibleiP51843. HS.

Organism-specific databases

HPAiHPA070839.

Interactioni

Subunit structurei

Homodimer. Interacts with NR5A1, NR5A2, NR0B2 and with COPS2.2 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
ESRRGP625083EBI-946109,EBI-2834260
NR5A1Q132853EBI-946109,EBI-874629
RORAP353982EBI-946109,EBI-748689

GO - Molecular functioni

  • AF-2 domain binding Source: UniProtKB
  • protein domain specific binding Source: UniProtKB
  • protein homodimerization activity Source: UniProtKB
  • steroid hormone receptor binding Source: UniProtKB
  • transcription factor binding Source: BHF-UCL

Protein-protein interaction databases

BioGridi106695. 14 interactors.
IntActiP51843. 3 interactors.
MINTiMINT-2855705.
STRINGi9606.ENSP00000368253.

Chemistry databases

BindingDBiP51843.

Structurei

Secondary structure

1470
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi145 – 151Combined sources7

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4RWVX-ray1.86B140-154[»]
ProteinModelPortaliP51843.
SMRiP51843.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Repeati1 – 671Add BLAST67
Repeati68 – 1332Add BLAST66
Repeati134 – 2003Add BLAST67
Repeati201 – 2534; truncatedAdd BLAST53

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 2534 X 67 AA tandem repeatsAdd BLAST253
Regioni254 – 470Ligand-bindingBy similarityAdd BLAST217

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi13 – 17LXXLL motif 15
Motifi80 – 84LXXLL motif 25
Motifi146 – 150LXXLL motif 35
Motifi461 – 466AF-2 motif6

Domaini

Homodimerization involved an interaction between amino and carboxy termini involving LXXLL motifs and steroid binding domain (AF-2 motif). Heterodimerizes with NR5A1 and NROB2 through its N-terminal LXXLL motifs.

Sequence similaritiesi

Keywords - Domaini

Repeat

Phylogenomic databases

eggNOGiKOG3575. Eukaryota.
ENOG410XRZC. LUCA.
GeneTreeiENSGT00390000015719.
HOGENOMiHOG000231151.
HOVERGENiHBG005453.
InParanoidiP51843.
KOiK08562.
OMAiGPCWGCS.
OrthoDBiEOG091G0FGK.
PhylomeDBiP51843.
TreeFamiTF332386.

Family and domain databases

Gene3Di1.10.565.10. 1 hit.
InterProiIPR033544. NR0B1.
IPR000536. Nucl_hrmn_rcpt_lig-bd.
IPR001723. Nuclear_hrmn_rcpt.
IPR025900. Nuclear_receptor_repeat.
[Graphical view]
PANTHERiPTHR24081:SF1. PTHR24081:SF1. 3 hits.
PfamiPF00104. Hormone_recep. 1 hit.
PF14046. NR_Repeat. 4 hits.
[Graphical view]
PRINTSiPR00398. STRDHORMONER.
SMARTiSM00430. HOLI. 1 hit.
[Graphical view]
SUPFAMiSSF48508. SSF48508. 1 hit.

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P51843-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MAGENHQWQG SILYNMLMSA KQTRAAPEAP ETRLVDQCWG CSCGDEPGVG
60 70 80 90 100
REGLLGGRNV ALLYRCCFCG KDHPRQGSIL YSMLTSAKQT YAAPKAPEAT
110 120 130 140 150
LGPCWGCSCG SDPGVGRAGL PGGRPVALLY RCCFCGEDHP RQGSILYSLL
160 170 180 190 200
TSSKQTHVAP AAPEARPGGA WWDRSYFAQR PGGKEALPGG RATALLYRCC
210 220 230 240 250
FCGEDHPQQG STLYCVPTST NQAQAAPEER PRAPWWDTSS GALRPVALKS
260 270 280 290 300
PQVVCEAASA GLLKTLRFVK YLPCFQVLPL DQQLVLVRNC WASLLMLELA
310 320 330 340 350
QDRLQFETVE VSEPSMLQKI LTTRRRETGG NEPLPVPTLQ HHLAPPAEAR
360 370 380 390 400
KVPSASQVQA IKCFLSKCWS LNISTKEYAY LKGTVLFNPD VPGLQCVKYI
410 420 430 440 450
QGLQWGTQQI LSEHTRMTHQ GPHDRFIELN STLFLLRFIN ANVIAELFFR
460 470
PIIGTVSMDD MMLEMLCTKI
Length:470
Mass (Da):51,718
Last modified:May 10, 2002 - v2
Checksum:i214E237097DF9786
GO
Isoform 2 (identifier: P51843-2) [UniParc]FASTAAdd to basket
Also known as: NR0B1A

The sequence of this isoform differs from the canonical sequence as follows:
     390-400: DVPGLQCVKYI → GKGKENDCNHH
     401-470: Missing.

Note: More abundant than isoform 1 in all tissues tested except testis where they are nearly equal.
Show »
Length:400
Mass (Da):43,590
Checksum:i368BB8D21A210658
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti4E → Q in AAC13875 (PubMed:8675564).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_004738267R → P in AHC; impairs transcriptional silencing of the StAR promoter. 3 PublicationsCorresponds to variant rs104894888dbSNPEnsembl.1
Natural variantiVAR_004739269Missing in AHC; impairs transcriptional silencing of the StAR promoter. 3 Publications1
Natural variantiVAR_031079278L → P in AHC. 1 Publication1
Natural variantiVAR_004740287V → G in AHC; the patient presents an inappropriate tall stature and renal ectopy. 1 Publication1
Natural variantiVAR_031080291W → C in AHC. 1 PublicationCorresponds to variant rs28935482dbSNPEnsembl.1
Natural variantiVAR_018303295L → P in AHC. 1 Publication1
Natural variantiVAR_031081297L → P in AHC; results in a severe loss of repressor activity. 1 PublicationCorresponds to variant rs104894907dbSNPEnsembl.1
Natural variantiVAR_018304300A → P in AHC. 1 Publication1
Natural variantiVAR_004741300A → V in AHC. 1 Publication1
Natural variantiVAR_004742377E → K in AHC. 2 Publications1
Natural variantiVAR_018300380Y → D in AHC. 1 PublicationCorresponds to variant rs104894900dbSNPEnsembl.1
Natural variantiVAR_018301381L → H in AHC. 1 PublicationCorresponds to variant rs104894899dbSNPEnsembl.1
Natural variantiVAR_004743382K → N in AHC. 1 PublicationCorresponds to variant rs28935180dbSNPEnsembl.1
Natural variantiVAR_004744385V → G in AHC. 1 Publication1
Natural variantiVAR_004745425R → G in AHC. 1 Publication1
Natural variantiVAR_018305425R → T in AHC. 1 Publication1
Natural variantiVAR_018302439I → S in AHC; mild phenotype. 1 PublicationCorresponds to variant rs104894897dbSNPEnsembl.1
Natural variantiVAR_004746440N → I in AHC; impairs RNA-binding activity. 2 PublicationsCorresponds to variant rs28935481dbSNPEnsembl.1
Natural variantiVAR_018306466L → R in AHC. 1 Publication1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_023557390 – 400DVPGLQCVKYI → GKGKENDCNHH in isoform 2. CuratedAdd BLAST11
Alternative sequenceiVSP_023558401 – 470Missing in isoform 2. CuratedAdd BLAST70

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
S74720 mRNA. Translation: AAB32751.1.
U31929 Genomic DNA. Translation: AAC13875.1.
BC011564 mRNA. Translation: AAH11564.1.
CCDSiCCDS14223.1. [P51843-1]
PIRiS50854.
RefSeqiNP_000466.2. NM_000475.4. [P51843-1]
XP_016884827.1. XM_017029338.1. [P51843-2]
UniGeneiHs.268490.

Genome annotation databases

EnsembliENST00000378970; ENSP00000368253; ENSG00000169297. [P51843-1]
GeneIDi190.
KEGGihsa:190.
UCSCiuc004dcf.5. human. [P51843-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
S74720 mRNA. Translation: AAB32751.1.
U31929 Genomic DNA. Translation: AAC13875.1.
BC011564 mRNA. Translation: AAH11564.1.
CCDSiCCDS14223.1. [P51843-1]
PIRiS50854.
RefSeqiNP_000466.2. NM_000475.4. [P51843-1]
XP_016884827.1. XM_017029338.1. [P51843-2]
UniGeneiHs.268490.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4RWVX-ray1.86B140-154[»]
ProteinModelPortaliP51843.
SMRiP51843.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi106695. 14 interactors.
IntActiP51843. 3 interactors.
MINTiMINT-2855705.
STRINGi9606.ENSP00000368253.

Chemistry databases

BindingDBiP51843.
ChEMBLiCHEMBL1795094.
DrugBankiDB01234. Dexamethasone.
DB00755. Tretinoin.

PTM databases

iPTMnetiP51843.
PhosphoSitePlusiP51843.

Polymorphism and mutation databases

BioMutaiNR0B1.
DMDMi20532385.

Proteomic databases

EPDiP51843.
MaxQBiP51843.
PaxDbiP51843.
PeptideAtlasiP51843.
PRIDEiP51843.

Protocols and materials databases

DNASUi190.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000378970; ENSP00000368253; ENSG00000169297. [P51843-1]
GeneIDi190.
KEGGihsa:190.
UCSCiuc004dcf.5. human. [P51843-1]

Organism-specific databases

CTDi190.
DisGeNETi190.
GeneCardsiNR0B1.
GeneReviewsiNR0B1.
HGNCiHGNC:7960. NR0B1.
HPAiHPA070839.
MalaCardsiNR0B1.
MIMi300018. phenotype.
300200. phenotype.
300473. gene.
neXtProtiNX_P51843.
OpenTargetsiENSG00000169297.
Orphaneti242. 46,XY complete gonadal dysgenesis.
251510. 46,XY partial gonadal dysgenesis.
95702. Cytomegalic congenital adrenal hypoplasia.
PharmGKBiPA31746.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG3575. Eukaryota.
ENOG410XRZC. LUCA.
GeneTreeiENSGT00390000015719.
HOGENOMiHOG000231151.
HOVERGENiHBG005453.
InParanoidiP51843.
KOiK08562.
OMAiGPCWGCS.
OrthoDBiEOG091G0FGK.
PhylomeDBiP51843.
TreeFamiTF332386.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000169297-MONOMER.
ReactomeiR-HSA-383280. Nuclear Receptor transcription pathway.
SignaLinkiP51843.
SIGNORiP51843.

Miscellaneous databases

GeneWikiiDAX1.
GenomeRNAii190.
PROiP51843.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000169297.
CleanExiHS_NR0B1.
ExpressionAtlasiP51843. baseline and differential.
GenevisibleiP51843. HS.

Family and domain databases

Gene3Di1.10.565.10. 1 hit.
InterProiIPR033544. NR0B1.
IPR000536. Nucl_hrmn_rcpt_lig-bd.
IPR001723. Nuclear_hrmn_rcpt.
IPR025900. Nuclear_receptor_repeat.
[Graphical view]
PANTHERiPTHR24081:SF1. PTHR24081:SF1. 3 hits.
PfamiPF00104. Hormone_recep. 1 hit.
PF14046. NR_Repeat. 4 hits.
[Graphical view]
PRINTSiPR00398. STRDHORMONER.
SMARTiSM00430. HOLI. 1 hit.
[Graphical view]
SUPFAMiSSF48508. SSF48508. 1 hit.
ProtoNetiSearch...

Entry informationi

Entry nameiNR0B1_HUMAN
AccessioniPrimary (citable) accession number: P51843
Secondary accession number(s): Q96F69
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: May 10, 2002
Last modified: November 2, 2016
This is version 171 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome X
    Human chromosome X: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.