Q14995 (NR1D2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Nuclear receptor subfamily 1 group D member 2

Alternative name(s):
Orphan nuclear hormone receptor BD73
Rev-erb-beta
V-erbA-related protein 1-related
Short name=EAR-1R

Gene names

Name:

NR1D2

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

General annotation (Comments)

Function	Binds to the sequences 5'-AATGTAGGTCA-3' and 5'-ATAACTAGGTCA-3'. Acts as a potent competitive repressor of ROR alpha function By similarity.
Subunit structure	Interacts with NCOA5 coactivator, leading to a strong increase of transcription of target genes. Ref.6
Subcellular location	Nucleus By similarity.
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
Coding sequence diversity	Polymorphism
Domain	Zinc-finger
Ligand	DNA-binding Metal-binding Zinc
Molecular function	Receptor Repressor
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	transcription initiation from RNA polymerase II promoter Traceable author statement. Source: Reactome
Cellular_component	nucleoplasm Traceable author statement. Source: Reactome
Molecular_function	ligand-activated sequence-specific DNA binding RNA polymerase II transcription factor activity Traceable author statement Ref.5. Source: UniProtKB sequence-specific DNA binding Inferred from electronic annotation. Source: InterPro steroid hormone receptor activity Inferred from electronic annotation. Source: InterPro zinc ion binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
Clock	O08785	2	EBI-6144053,EBI-79859	From a different organism.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 579

579

Nuclear receptor subfamily 1 group D member 2

PRO_0000053501

Regions

DNA binding

100 – 176

77

Nuclear receptor

Zinc finger

103 – 123

21

NR C4-type

Zinc finger

140 – 164

25

NR C4-type

Compositional bias

13 – 20

8

Poly-Ser

Compositional bias

35 – 39

5

Poly-Ser

Natural variations

Natural variant

21

1

P → H. Ref.4
Corresponds to variant rs17854365 [ dbSNP | Ensembl ].

VAR_047377

Natural variant

282

1

Q → K. Ref.4
Corresponds to variant rs17857305 [ dbSNP | Ensembl ].

VAR_047378

Natural variant

288

1

P → R. Ref.4
Corresponds to variant rs17857306 [ dbSNP | Ensembl ].

VAR_047379

Natural variant

386

1

L → M. Ref.1 Ref.4 Ref.5
Corresponds to variant rs4858097 [ dbSNP | Ensembl ].

VAR_047380

Experimental info

Sequence conflict

519 – 520

2

IE → NRK in AAA65937. Ref.5

Secondary structure

1

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579

Helix Strand Turn

Details...

Helix

398 – 421

24

Helix

424 – 428

5

Helix

431 – 449

19

Helix

451 – 453

3

Turn

456 – 459

4

Beta strand

460 – 462

3

Beta strand

468 – 470

3

Helix

471 – 476

6

Helix

481 – 494

14

Helix

500 – 512

13

Helix

516 – 518

3

Helix

522 – 543

22

Helix

549 – 573

25

Sequences

	Sequence		Length	Mass (Da)
	Q14995 [UniParc]. Last modified November 25, 2008. Version 3. Checksum: 39BDDCD323BD14BF	FASTA	579	64,625
	10 20 30 40 50 60 MEVNAGGVIA YISSSSSASS PASCHSEGSE NSFQSSSSSV PSSPNSSNSD TNGNPKNGDL 70 80 90 100 110 120 ANIEGILKND RIDCSMKTSK SSAPGMTKSH SGVTKFSGMV LLCKVCGDVA SGFHYGVHAC 130 140 150 160 170 180 EGCKGFFRRS IQQNIQYKKC LKNENCSIMR MNRNRCQQCR FKKCLSVGMS RDAVRFGRIP 190 200 210 220 230 240 KREKQRMLIE MQSAMKTMMN SQFSGHLQND TLVEHHEQTA LPAQEQLRPK PQLEQENIKS 250 260 270 280 290 300 SSPPSSDFAK EEVIGMVTRA HKDTFMYNQE QQENSAESMQ PQRGERIPKN MEQYNLNHDH 310 320 330 340 350 360 CGNGLSSHFP CSESQQHLNG QFKGRNIMHY PNGHAICIAN GHCMNFSNAY TQRVCDRVPI 370 380 390 400 410 420 DGFSQNENKN SYLCNTGGRM HLVCPLSKSP YVDPHKSGHE IWEEFSMSFT PAVKEVVEFA 430 440 450 460 470 480 KRIPGFRDLS QHDQVNLLKA GTFEVLMVRF ASLFDAKERT VTFLSGKKYS VDDLHSMGAG 490 500 510 520 530 540 DLLNSMFEFS EKLNALQLSD EEMSLFTAVV LVSADRSGIE NVNSVEALQE TLIRALRTLI 550 560 570 MKNHPNEASI FTKLLLKLPD LRSLNNMHSE ELLAFKVHP

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Isolation of a novel member of the thyroid/steroid hormone receptor superfamily from human osteoblastic osteosarcoma HOS cell." Kamizono A., Shuichiro K., Kohei U. Submitted (JUL-1993) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT MET-386.
[2]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Hippocampus.
[3]	"The DNA sequence, annotation and analysis of human chromosome 3." Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R., Buhay C.J., Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J. , Jackson A., Khan Z.M., Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., Morgan M.B., Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D., Wei S., Wheeler D.A., Wright M.W., Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z., Clendenning J., Clerc-Blankenburg K.P., Chen R., Chen Z., Davis C., Delgado O., Dinh H.H., Dong W., Draper H., Ernst S., Fu G., Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J., Hao B., Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W., Jackson L.R., Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B., Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., Palmeiri A., Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B., Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H., Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J., Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J., Zhang X., Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H., Reinhardt R., Naylor S.L., Yang H., Olson M., Weinstock G., Gibbs R.A. Nature 440:1194-1198(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	"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], VARIANTS HIS-21; LYS-282; ARG-288 AND MET-386. Tissue: Brain.
[5]	"A new orphan member of the nuclear hormone receptor superfamily closely related to Rev-Erb." Dumas B., Harding H.P., Choi H.-S., Lehmann K.A., Chung M., Lazar M.A., Moore D.D. Mol. Endocrinol. 8:996-1005(1994) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 2-579, VARIANT MET-386. Tissue: Peripheral blood lymphocyte.
[6]	"CIA, a novel estrogen receptor coactivator with a bifunctional nuclear receptor interacting determinant." Sauve F., McBroom L.D.B., Gallant J., Moraitis A.N., Labrie F., Giguere V. Mol. Cell. Biol. 21:343-353(2001) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH NCOA5.
[7]	"Structural insight into the constitutive repression function of the nuclear receptor Rev-erbbeta." Woo E.-J., Jeong D.G., Lim M.-Y., Jun Kim S., Kim K.-J., Yoon S.-M., Park B.-C., Eon Ryu S. J. Mol. Biol. 373:735-744(2007) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 386-579.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

D16815 mRNA. Translation: BAA20088.1.
AK313464 mRNA. Translation: BAG36250.1.
AC124914 Genomic DNA. No translation available.
BC045613 mRNA. Translation: AAH45613.1.
L31785 mRNA. Translation: AAA65937.1.

IPI

IPI00788022.

PIR

A57057.

RefSeq

NP_005117.3. NM_005126.4.

UniGene

Hs.37288.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2V0V	X-ray	2.40	A/B/C/D	387-579	[»]
2V7C	X-ray	2.40	A/B	387-579	[»]
3CQV	X-ray	1.90	A	381-579	[»]

ProteinModelPortal

Q14995.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q14995. 6 interactions.

STRING

9606.ENSP00000310006.

PTM databases

PhosphoSite

Q14995.

Polymorphism databases

DMDM

215274122.

Proteomic databases

PaxDb

Q14995.

PRIDE

Q14995.

Protocols and materials databases

DNASU

9975.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000312521; ENSP00000310006; ENSG00000174738.
ENST00000396676; ENSP00000379909; ENSG00000174738.

GeneID

9975.

KEGG

hsa:9975.

Organism-specific databases

CTD

9975.

GeneCards

GC03P023961.

HGNC

HGNC:7963. NR1D2.

HPA

HPA054798.

MIM

602304. gene.

neXtProt

NX_Q14995.

PharmGKB

PA31749.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG324222.

HOGENOM

HOG000261691.

HOVERGEN

HBG106790.

InParanoid

Q14995.

KO

K08531.

OMA

MMNSQFS.

OrthoDB

EOG4V170J.

Enzyme and pathway databases

Reactome

REACT_71. Gene Expression.

Gene expression databases

ArrayExpress

Q14995.

Bgee

Q14995.

CleanEx

HS_NR1D2.

Genevestigator

Q14995.

GermOnline

ENSG00000174738. Homo sapiens.

Family and domain databases

Gene3D

1.10.565.10. 3 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

Q14995.

ChEMBL

CHEMBL1961784.

EvolutionaryTrace

Q14995.

GenomeRNAi

9975.

NextBio

37672.

SOURCE

Search...

Entry information

Entry name

NR1D2_HUMAN

Accession

Primary (citable) accession number: Q14995
Secondary accession number(s): B2R8Q3, O00402, Q86XD4

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 15, 1999
Last sequence update:	November 25, 2008
Last modified:	May 1, 2013
This is version 128 of the entry and version 3 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.