P20393 (NR1D1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Nuclear receptor subfamily 1 group D member 1

Alternative name(s):
Rev-erbA-alpha
V-erbA-related protein 1
Short name=EAR-1

Gene names

Name:	NR1D1
Synonyms:	EAR1, HREV, THRAL

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	614 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Functions as a constitutive transcriptional repressor. In collaboration with SP1, activates GJA1 transcription By similarity. Possible receptor for triiodothyronine. Ref.1 Ref.2
Subunit structure	Interacts with C1D and NR2E3 By similarity. Interacts with SP1 By similarity.
Subcellular location	Nucleus Potential.
Tissue specificity	Expressed in all tissues and cell lines examined. Expressed at high levels in some squamous carcinoma cell lines. Ref.1
Domain	Composed of three domains: a modulating N-terminal domain, a DNA-binding domain and a C-terminal ligand-binding domain.
Sequence similarities	Belongs to the nuclear hormone receptor family. NR1 subfamily. Contains 1 nuclear receptor DNA-binding domain.

Ontologies

Keywords
Biological process	Transcription Transcription regulation
Cellular component	Nucleus
Domain	Zinc-finger
Ligand	DNA-binding Metal-binding Zinc
Molecular function	Activator Receptor Repressor
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	cellular response to lipopolysaccharide Inferred from mutant phenotype PubMed 18511497. Source: BHF-UCL circadian rhythm Inferred from electronic annotation. Source: Compara negative regulation of receptor biosynthetic process Inferred from mutant phenotype PubMed 18511497. Source: BHF-UCL negative regulation of toll-like receptor 4 signaling pathway Inferred from mutant phenotype PubMed 18511497. Source: BHF-UCL negative regulation of transcription from RNA polymerase II promoter Inferred from mutant phenotype PubMed 18511497. Source: BHF-UCL transcription initiation from RNA polymerase II promoter Traceable author statement. Source: Reactome
Cellular_component	nuclear chromatin Inferred from direct assay PubMed 18511497. Source: BHF-UCL nucleoplasm Traceable author statement. Source: Reactome
Molecular_function	ligand-activated sequence-specific DNA binding RNA polymerase II transcription factor activity Traceable author statement PubMed 8622974. Source: ProtInc sequence-specific DNA binding Inferred from electronic annotation. Source: InterPro steroid hormone receptor activity Traceable author statement Ref.2. Source: ProtInc transcription corepressor activity Traceable author statement PubMed 8622974. Source: ProtInc transcription regulatory region DNA binding Inferred from direct assay PubMed 18511497. Source: BHF-UCL zinc ion binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 614

614

Nuclear receptor subfamily 1 group D member 1

PRO_0000053499

Regions

DNA binding

129 – 205

77

Nuclear receptor

Zinc finger

132 – 152

21

NR C4-type

Zinc finger

169 – 193

25

NR C4-type

Compositional bias

82 – 93

12

Poly-Ser

Experimental info

Sequence conflict

147

1

H → L in CAB53540. Ref.2

Sequence conflict

564

1

E → Q Ref.2

Secondary structure

1

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614

Helix Strand Turn

Details...

Turn

133 – 135

3

Beta strand

136 – 138

3

Beta strand

141 – 143

3

Beta strand

146 – 148

3

Helix

150 – 160

11

Beta strand

170 – 173

4

Turn

179 – 183

5

Helix

186 – 193

8

Turn

194 – 197

4

Helix

200 – 202

3

Helix

285 – 299

15

Helix

434 – 456

23

Helix

460 – 462

3

Helix

465 – 486

22

Helix

509 – 511

3

Helix

514 – 529

16

Helix

534 – 546

13

Helix

556 – 577

22

Helix

584 – 589

6

Helix

591 – 602

12

Beta strand

606 – 610

5

Sequences

	Sequence		Length	Mass (Da)
	P20393 [UniParc]. Last modified February 1, 1991. Version 1. Checksum: 67C71758E166508A	FASTA	614	66,805
	10 20 30 40 50 60 MTTLDSNNNT GGVITYIGSS GSSPSRTSPE SLYSDNSNGS FQSLTQGCPT YFPPSPTGSL 70 80 90 100 110 120 TQDPARSFGS IPPSLSDDGS PSSSSSSSSS SSSFYNGSPP GSLQVAMEDS SRVSPSKSTS 130 140 150 160 170 180 NITKLNGMVL LCKVCGDVAS GFHYGVHACE GCKGFFRRSI QQNIQYKRCL KNENCSIVRI 190 200 210 220 230 240 NRNRCQQCRF KKCLSVGMSR DAVRFGRIPK REKQRMLAEM QSAMNLANNQ LSSQCPLETS 250 260 270 280 290 300 PTQHPTPGPM GPSPPPAPVP SPLVGFSQFP QQLTPPRSPS PEPTVEDVIS QVARAHREIF 310 320 330 340 350 360 TYAHDKLGSS PGNFNANHAS GSPPATTPHR WENQGCPPAP NDNNTLAAQR HNEALNGLRQ 370 380 390 400 410 420 APSSYPPTWP PGPAHHSCHQ SNSNGHRLCP THVYAAPEGK APANSPRQGN SKNVLLACPM 430 440 450 460 470 480 NMYPHGRSGR TVQEIWEDFS MSFTPAVREV VEFAKHIPGF RDLSQHDQVT LLKAGTFEVL 490 500 510 520 530 540 MVRFASLFNV KDQTVMFLSR TTYSLQELGA MGMGDLLSAM FDFSEKLNSL ALTEEELGLF 550 560 570 580 590 600 TAVVLVSADR SGMENSASVE QLQETLLRAL RALVLKNRPL ETSRFTKLLL KLPDLRTLNN 610 MHSEKLLSFR VDAQ

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Two erbA homologs encoding proteins with different T3 binding capacities are transcribed from opposite DNA strands of the same genetic locus." Miyajima N., Horiuchi R., Shibuya Y., Fukushige S., Matsubara K., Toyoshima K., Yamamoto T. Cell 57:31-39(1989) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, TISSUE SPECIFICITY. Tissue: Placenta.
[2]	"Isolation of a cDNA encoding human Rev-ErbA alpha: transcription from the noncoding DNA strand of a thyroid hormone receptor gene results in a related protein that does not bind thyroid hormone." Lazar M.A., Jones K.E., Chin W.W. DNA Cell Biol. 9:77-83(1990) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION. Tissue: Fetal skeletal muscle.
[3]	"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: PNS.
[4]	"Genomic organization of the human thyroid hormone receptor alpha (c-erbA-1) gene." Laudet V., Begue A., Henry C., Joubel A., Martin P., Stehelin D., Saule S. Nucleic Acids Res. 19:1105-1112(1991) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 549-614.
[5]	"Structural elements of an orphan nuclear receptor-DNA complex." Zhao Q., Khorasanizadeh S., Miyoshi Y., Lazar M.A., Rastinejad F. Mol. Cell 1:849-861(1998) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 123-215.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

M24898 mRNA. Translation: AAA52335.1.
M24900 mRNA. Translation: AAA52332.1.
X55066 Genomic DNA. No translation available.
X55067 Genomic DNA. No translation available.
X72631 mRNA. Translation: CAB53540.1.
BC047875 mRNA. Translation: AAH47875.1.
BC056148 mRNA. Translation: AAH56148.1.
M34339 mRNA. Translation: AAA36561.1.
M34340 mRNA. Translation: AAA36562.2.

IPI

IPI00023603.

PIR

A32608. A32286.

RefSeq

NP_068370.1. NM_021724.4.

UniGene

Hs.592130.
Hs.724.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1A6Y	X-ray	2.30	A/B	123-216	[»]
1EF6	model	-	A	281-301	[»]
			B	430-614	[»]
1GA5	X-ray	2.40	A/B/E/F	123-216	[»]
1HLZ	X-ray	2.80	A/B	123-216	[»]
3N00	X-ray	2.60	A	281-614	[»]

ProteinModelPortal

P20393.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-48396N.

IntAct

P20393. 1 interaction.

STRING

9606.ENSP00000246672.

PTM databases

PhosphoSite

P20393.

Polymorphism databases

DMDM

119100.

Proteomic databases

PaxDb

P20393.

PRIDE

P20393.

Protocols and materials databases

DNASU

9572.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000246672; ENSP00000246672; ENSG00000126368.

GeneID

9572.

KEGG

hsa:9572.

UCSC

uc002htz.2. human.

Organism-specific databases

CTD

9572.

GeneCards

GC17M038249.

HGNC

HGNC:7962. NR1D1.

HPA

HPA007935.

MIM

602408. gene.

neXtProt

NX_P20393.

PharmGKB

PA31748.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG324222.

HOGENOM

HOG000261691.

HOVERGEN

HBG106790.

InParanoid

P20393.

KO

K03728.

OMA

SCHQPNS.

OrthoDB

EOG4DV5KZ.

Enzyme and pathway databases

Pathway_Interaction_DB

circadianpathway. Circadian rhythm pathway.

Reactome

REACT_24941. Circadian Clock.
REACT_71. Gene Expression.

Gene expression databases

ArrayExpress

P20393.

Bgee

P20393.

CleanEx

HS_NR1D1.

Genevestigator

P20393.

GermOnline

ENSG00000126368. Homo sapiens.

Family and domain databases

Gene3D

1.10.565.10. 2 hits.
3.30.50.10. 1 hit.

InterPro

IPR008946. Nucl_hormone_rcpt_ligand-bd.
IPR000536. Nucl_hrmn_rcpt_lig-bd_core.
IPR001723. Str_hrmn_rcpt.
IPR001628. Znf_hrmn_rcpt.
IPR013088. Znf_NHR/GATA.
[Graphical view]

Pfam

PF00104. Hormone_recep. 1 hit.
PF00105. zf-C4. 1 hit.
[Graphical view]

PRINTS

PR00398. STRDHORMONER.
PR00047. STROIDFINGER.

SMART

SM00430. HOLI. 1 hit.
SM00399. ZnF_C4. 1 hit.
[Graphical view]

SUPFAM

SSF48508. Str_ncl_receptor. 1 hit.

PROSITE

PS00031. NUCLEAR_REC_DBD_1. 1 hit.
PS51030. NUCLEAR_REC_DBD_2. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

BindingDB

P20393.

ChEMBL

CHEMBL1961783.

ChiTaRS

NR1D1. human.

EvolutionaryTrace

P20393.

GenomeRNAi

9572.

NextBio

35899.

SOURCE

Search...

Entry information

Entry name

NR1D1_HUMAN

Accession

Primary (citable) accession number: P20393
Secondary accession number(s): Q0P5Z4, Q15304

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 1, 1991
Last sequence update:	February 1, 1991
Last modified:	May 1, 2013
This is version 152 of the entry and version 1 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.