Q15466 (NR0B2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Nuclear receptor subfamily 0 group B member 2

Alternative name(s):
Orphan nuclear receptor SHP
Small heterodimer partner

Gene names

Name:	NR0B2
Synonyms:	SHP

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	257 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Acts as a transcriptional regulator. Acts as a negative regulator of receptor-dependent signaling pathways. Specifically inhibits transactivation of the nuclear receptor with whom it interacts. Inhibits transcriptional activity of NEUROD1 on E-box-containing promoter by interfering with the coactivation function of the p300/CBP-mediated trancription complex for NEUROD1. Ref.6
Subunit structure	Interacts with RARA, RXRA, THRB, NR5A1, NR5A2, NR1I3, PPARA, PPARG and EID1. May also interact with HNF4A By similarity. Heterodimer; efficient DNA binding requires dimerization with another bHLH protein. Interacts (via N-terminus) with NEUROD1 (via N-terminus an C-terminus). Interacts with ID2. Ref.6
Subcellular location	Nucleus. Cytoplasm. Note: Colocalizes with NEUROD1 in the nucleus. Ref.6
Tissue specificity	Liver. Low levels of expression were detected in heart and pancreas. Ref.1
Involvement in disease	Obesity (OBESITY) [MIM:601665]: A condition characterized by an increase of body weight beyond the limitation of skeletal and physical requirements, as the result of excessive accumulation of body fat. Note: Disease susceptibility is associated with variations affecting the gene represented in this entry. Ref.3
Sequence similarities	Belongs to the nuclear hormone receptor family. NR0 subfamily.

Ontologies

Keywords
Biological process	Transcription Transcription regulation
Cellular component	Cytoplasm Nucleus
Coding sequence diversity	Polymorphism
Disease	Disease mutation Obesity
Molecular function	Receptor Repressor
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	cholesterol metabolic process Traceable author statement PubMed 11030331. Source: ProtInc negative regulation of sequence-specific DNA binding transcription factor activity Inferred from direct assay Ref.6. Source: UniProtKB negative regulation of transcription from RNA polymerase II promoter Traceable author statement PubMed 11030331. Source: ProtInc organ regeneration Inferred from electronic annotation. Source: Compara positive regulation of insulin secretion Inferred from electronic annotation. Source: Compara response to glucose stimulus Inferred from electronic annotation. Source: Compara transcription initiation from RNA polymerase II promoter Traceable author statement. Source: Reactome
Cellular_component	cytoplasm Inferred from direct assay Ref.6. Source: UniProtKB nucleoplasm Traceable author statement. Source: Reactome protein complex Inferred from electronic annotation. Source: Compara
Molecular_function	DNA binding Inferred from electronic annotation. Source: InterPro sequence-specific DNA binding transcription factor activity Inferred from electronic annotation. Source: InterPro steroid hormone receptor activity Inferred from electronic annotation. Source: InterPro transcription corepressor activity Inferred from direct assay Ref.6. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
SIRT1	Q96EB6	6	EBI-3910729,EBI-1802965

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 257

257

Nuclear receptor subfamily 0 group B member 2

PRO_0000053752

Regions

Region

57 – 228

172

Ligand-binding By similarity

Natural variations

Natural variant

57

1

R → W in early-onset obesity; Japanese population; loss of repressor activity. Ref.3

VAR_026015

Natural variant

171

1

G → A.
Corresponds to variant rs6659176 [ dbSNP | Ensembl ].

VAR_050584

Natural variant

189

1

G → E in early-onset obesity; Japanese population; strong decrease of repressor activity. Ref.3

VAR_026016

Natural variant

195

1

A → S in early-onset obesity; Japanese population; slight decrease of repressor activity. Ref.3

VAR_026017

Natural variant

213

1

R → C in early-onset obesity; Japanese population; loss of repressor activity. Ref.3

VAR_026018

Natural variant

216

1

R → H No effect on repressor activity. Ref.3

VAR_026019

Secondary structure

1

.

.

.

.

.

257

Helix Strand Turn

Details...

Helix

19 – 26

8

Helix

118 – 122

5

Sequences

	Sequence		Length	Mass (Da)
	Q15466 [UniParc]. Last modified December 1, 2000. Version 2. Checksum: 14BEE2B3FF46154A	FASTA	257	28,058
	10 20 30 40 50 60 MSTSQPGACP CQGAASRPAI LYALLSSSLK AVPRPRSRCL CRQHRPVQLC APHRTCREAL 70 80 90 100 110 120 DVLAKTVAFL RNLPSFWQLP PQDQRRLLQG CWGPLFLLGL AQDAVTFEVA EAPVPSILKK 130 140 150 160 170 180 ILLEEPSSSG GSGQLPDRPQ PSLAAVQWLQ CCLESFWSLE LSPKEYACLK GTILFNPDVP 190 200 210 220 230 240 GLQAASHIGH LQQEAHWVLC EVLEPWCPAA QGRLTRVLLT ASTLKSIPTS LLGDLFFRPI 250 IGDVDIAGLL GDMLLLR

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"An orphan nuclear hormone receptor that lacks a DNA binding domain and heterodimerizes with other receptors." Seol W., Choi H.-S., Moore D.D. Science 272:1336-1339(1996) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], TISSUE SPECIFICITY.
[2]	"Structure and expression of the orphan nuclear receptor SHP gene." Lee H.-K., Lee Y.-K., Park S.-H., Kim Y.-S., Park S.H., Lee J.W., Kwon H.-B., Soh J., Moore D.D., Choi H.-S. J. Biol. Chem. 273:14398-14402(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]	"Mutations in the small heterodimer partner gene are associated with mild obesity in Japanese subjects." Nishigori H., Tomura H., Tonooka N., Kanamori M., Yamada S., Sho K., Inoue I., Kikuchi N., Onigata K., Kojima I., Kohama T., Yamagata K., Yang Q., Matsuzawa Y., Miki T., Seino S., Kim M.-Y., Choi H.-S. , Lee Y.-K., Moore D.D., Takeda J. Proc. Natl. Acad. Sci. U.S.A. 98:575-580(2001) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS EARLY-ONSET OBESITY TRP-57; GLU-189; SER-195 AND CYS-213, VARIANT HIS-216, CHARACTERIZATION OF VARIANTS EARLY-ONSET OBESITY TRP-57; GLU-189; SER-195 AND CYS-213, CHARACTERIZATION OF VARIANT HIS-216.
[4]	"The DNA sequence and biological annotation of human chromosome 1." Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K. , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R. Nature 441:315-321(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Pancreas and Spleen.
[6]	"Orphan nuclear receptor small heterodimer partner, a novel corepressor for a basic helix-loop-helix transcription factor BETA2/neuroD." Kim J.Y., Chu K., Kim H.J., Seong H.A., Park K.C., Sanyal S., Takeda J., Ha H., Shong M., Tsai M.J., Choi H.S. Mol. Endocrinol. 18:776-790(2004) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, HETERODIMERIZATION, INTERACTION WITH ID2 AND NEUROD1, SUBCELLULAR LOCATION.
[7]	"Modulation of human nuclear receptor LRH-1 activity by phospholipids and SHP." Ortlund E.A., Lee Y., Solomon I.H., Hager J.M., Safi R., Choi Y., Guan Z., Tripathy A., Raetz C.R.H., McDonnell D.P., Moore D.D., Redinbo M.R. Nat. Struct. Mol. Biol. 12:357-363(2005) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 15-28 IN COMPLEX WITH NR5A2.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

L76571 Genomic DNA. Translation: AAC41998.1.
AB058644 Genomic DNA. Translation: BAB68530.1.
AL356390 Genomic DNA. Translation: CAI13562.1.
BC030207 mRNA. Translation: AAH30207.1.

IPI

IPI00017483.

RefSeq

NP_068804.1. NM_021969.2.

UniGene

Hs.427055.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1YUC	X-ray	1.90	C/D	15-28	[»]
2Q3Y	X-ray	2.40	B	18-27	[»]
2Z4J	X-ray	2.60	B	115-124	[»]
4DOR	X-ray	1.90	C/D	15-28	[»]

ProteinModelPortal

Q15466.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-46313N.

IntAct

Q15466. 14 interactions.

STRING

9606.ENSP00000254227.

PTM databases

PhosphoSite

Q15466.

Polymorphism databases

DMDM

9978744.

Proteomic databases

PaxDb

Q15466.

PRIDE

Q15466.

Protocols and materials databases

DNASU

8431.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000254227; ENSP00000254227; ENSG00000131910.

GeneID

8431.

KEGG

hsa:8431.

UCSC

uc001bnf.3. human.

Organism-specific databases

CTD

8431.

GeneCards

GC01M027237.

HGNC

HGNC:7961. NR0B2.

MIM

601665. phenotype.
604630. gene.

neXtProt

NX_Q15466.

PharmGKB

PA31747.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG235713.

HOGENOM

HOG000231151.

HOVERGEN

HBG008136.

InParanoid

Q15466.

KO

K08563.

OMA

HRTCREA.

OrthoDB

EOG4FXR8J.

PhylomeDB

Q15466.

Enzyme and pathway databases

Reactome

REACT_71. Gene Expression.

Gene expression databases

ArrayExpress

Q15466.

Bgee

Q15466.

CleanEx

HS_NR0B2.

Genevestigator

Q15466.

GermOnline

ENSG00000131910. Homo sapiens.

Family and domain databases

Gene3D

1.10.565.10. 1 hit.

InterPro

IPR008946. Nucl_hormone_rcpt_ligand-bd.
IPR000536. Nucl_hrmn_rcpt_lig-bd_core.
IPR001723. Str_hrmn_rcpt.
[Graphical view]

Pfam

PF00104. Hormone_recep. 1 hit.
[Graphical view]

PRINTS

PR00398. STRDHORMONER.

SMART

SM00430. HOLI. 1 hit.
[Graphical view]

SUPFAM

SSF48508. Str_ncl_receptor. 1 hit.

ProtoNet

Search...

Other

ChEMBL

CHEMBL5603.

EvolutionaryTrace

Q15466.

GenomeRNAi

8431.

NextBio

31546.

SOURCE

Search...

Entry information

Entry name

NR0B2_HUMAN

Accession

Primary (citable) accession number: Q15466
Secondary accession number(s): Q5QP36

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 1, 2000
Last sequence update:	December 1, 2000
Last modified:	May 1, 2013
This is version 122 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.