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P13056 (NR2C1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 146. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Nuclear receptor subfamily 2 group C member 1
Alternative name(s):
Orphan nuclear receptor TR2
Testicular receptor 2
Gene names
Name:NR2C1
Synonyms:TR2
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length603 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Orphan nuclear receptor. Binds the IR7 element in the promoter of its own gene in an autoregulatory negative feedback mechanism. Primarily repressor of a broad range of genes. Binds to hormone response elements (HREs) consisting of two 5'-AGGTCA-3' half site direct repeat consensus sequences. Together with NR2C2, forms the core of the DRED (direct repeat erythroid-definitive) complex that represses embryonic and fetal globin transcription. Also activator of OCT4 gene expression. May be involved in stem cell proliferation and differentiation. Mediator of retinoic acid-regulated preadipocyte proliferation. Ref.7 Ref.8

Subunit structure

Homodimer By similarity. Heterodimer; binds DNA as a heterodimer with NR2C2 required for chromatin remodeling and for binding to promoter regions such as globin DR1 repeats By similarity. Interacts with NRIP1 (via its LXXLL motifs); the interaction provides corepressor activity. Interacts with HDAC3 (via the DNA-binding domain). Interacts with HDAC4 (via the DNA-binding domain). Interacts with PIAS1; the interaction is required for sumoylation of NR2C1. Interacts with UBE2I; the interaction is required for sumoylation of NR2C1. Interacts with KAT2B; the interaction acts as a corepressor of gene expression By similarity. Interacts with ESR1; the interaction prevents homodimerization of ESR1 and suppresses its transcriptional activity and cell growth. Ref.7

Subcellular location

Nucleus By similarity. NucleusPML body By similarity. Note: Recruited by HDAC3, after all-trans retinoic acid stimulated MAPK1-mediated Thr-223 phosphorylation, to PML bodies for subsequent sumoylation By similarity.

Post-translational modification

Sumoylation requires both PIAS1 and UBE2I. Sumoylation appears to dissociate NR2C1 from the PML nuclear bodies. Enhances the interaction with NRIP1 but inhibits interaction with KAT2B. In proliferating cells, stimulation by all-trans retinoic acid, activation of MAPK1-mediated phosphorylation and recruitment to PML bodies with subsequent sumoylation, suppresses OCT4 expression By similarity.

Phosphorylated on several serine and threonine residues. Phosphorylation on Thr-222, stimulated by all-trans retinoic acid (atRA) mediates PML location and sumoylation in proliferating cells which then modulates its association with effector molecules, KAT2B and NRIP1. Phosphorylation on Ser-581 by PKC is important for protein stability and function as activator of RARB By similarity.

Sequence similarities

Belongs to the nuclear hormone receptor family. NR2 subfamily.

Contains 1 nuclear receptor DNA-binding domain.

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: P13056-1)

Also known as: TR2-11;

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.
Isoform 2 (identifier: P13056-2)

Also known as: TR2-9;

The sequence of this isoform differs from the canonical sequence as follows:
     465-467: DKM → AEG
     468-603: Missing.
Isoform 3 (identifier: P13056-3)

Also known as: TR2-7;

The sequence of this isoform differs from the canonical sequence as follows:
     466-483: KMSTERRKLLMEHIFKLQ → AKVIAALIHFTRRAITDL
     484-603: Missing.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 603603Nuclear receptor subfamily 2 group C member 1
PRO_0000053586

Regions

DNA binding110 – 18576Nuclear receptor
Zinc finger113 – 13321NR C4-type
Zinc finger149 – 17325NR C4-type
Region1 – 178178Required for interaction with KAT2B By similarity
Region584 – 60320Required for interaction with NRIP1 By similarity

Amino acid modifications

Modified residue1971Phosphoserine By similarity
Modified residue2151Phosphoserine Ref.9
Modified residue2201Phosphothreonine Ref.9
Modified residue2221Phosphothreonine; by MAPK1 By similarity
Modified residue5811Phosphoserine; by PKC By similarity
Cross-link250Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO) By similarity

Natural variations

Alternative sequence465 – 4673DKM → AEG in isoform 2.
VSP_036855
Alternative sequence466 – 48318KMSTE…IFKLQ → AKVIAALIHFTRRAITDL in isoform 3.
VSP_036856
Alternative sequence468 – 603136Missing in isoform 2.
VSP_036857
Alternative sequence484 – 603120Missing in isoform 3.
VSP_036858

Experimental info

Sequence conflict2911N → K in BAF84008. Ref.3
Sequence conflict3041D → N in BAF84008. Ref.3
Sequence conflict5201Q → L in AAA36761. Ref.2

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 (TR2-11) [UniParc].

Last modified April 14, 2009. Version 2.
Checksum: 37444D2701B9CA60

FASTA60367,315
        10         20         30         40         50         60 
MATIEEIAHQ IIEQQMGEIV TEQQTGQKIQ IVTALDHNTQ GKQFILTNHD GSTPSKVILA 

        70         80         90        100        110        120 
RQDSTPGKVF LTTPDAAGVN QLFFTTPDLS AQHLQLLTDN SPDQGPNKVF DLCVVCGDKA 

       130        140        150        160        170        180 
SGRHYGAVTC EGCKGFFKRS IRKNLVYSCR GSKDCIINKH HRNRCQYCRL QRCIAFGMKQ 

       190        200        210        220        230        240 
DSVQCERKPI EVSREKSSNC AASTEKIYIR KDLRSPLTAT PTFVTDSEST RSTGLLDSGM 

       250        260        270        280        290        300 
FMNIHPSGVK TESAVLMTSD KAESCQGDLS TLANVVTSLA NLGKTKDLSQ NSNEMSMIES 

       310        320        330        340        350        360 
LSNDDTSLCE FQEMQTNGDV SRAFDTLAKA LNPGESTACQ SSVAGMEGSV HLITGDSSIN 

       370        380        390        400        410        420 
YTEKEGPLLS DSHVAFRLTM PSPMPEYLNV HYIGESASRL LFLSMHWALS IPSFQALGQE 

       430        440        450        460        470        480 
NSISLVKAYW NELFTLGLAQ CWQVMNVATI LATFVNCLHN SLQQDKMSTE RRKLLMEHIF 

       490        500        510        520        530        540 
KLQEFCNSMV KLCIDGYEYA YLKAIVLFSP DHPSLENMEQ IEKFQEKAYV EFQDYITKTY 

       550        560        570        580        590        600 
PDDTYRLSRL LLRLPALRLM NATITEELFF KGLIGNIRID SVIPHILKME PADYNSQIIG 


HSI 

« Hide

Isoform 2 (TR2-9) [UniParc].

Checksum: 012EB168180BC63A
Show »

FASTA46751,193
Isoform 3 (TR2-7) [UniParc].

Checksum: 293E21E317E05814
Show »

FASTA48353,042

References

« Hide 'large scale' references
[1]"Identification of a new member of the steroid receptor super-family by cloning and sequence analysis."
Chang C., Kokontis J.
Biochem. Biophys. Res. Commun. 155:971-977(1988) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3).
Tissue: Testis.
[2]"Molecular cloning of new human TR2 receptors: a class of steroid receptor with multiple ligand-binding domains."
Chang C., Kokontis J., Acakpo-Satchivi L., Liao S., Takeda H., Chang Y.
Biochem. Biophys. Res. Commun. 165:735-741(1989) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2).
[3]"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. expand/collapse author list , 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] (ISOFORM 1).
Tissue: Tongue.
[4]"The finished DNA sequence of human chromosome 12."
Scherer S.E., Muzny D.M., 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. expand/collapse author list , Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., Montgomery K.T., Morgan M.B., Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D., Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z., Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H., Draper H., Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S., Kelly S.H., Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H., Santibanez J., Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q., Williams G.A., Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V., Bailey M., Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E., Burkett C.E., Burrell K.L., Calderon E., Cardenas V., Carter K., Casias K., Cavazos I., Cavazos S.R., Ceasar H., Chacko J., Chan S.N., Chavez D., Christopoulos C., Chu J., Cockrell R., Cox C.D., Dang M., Dathorne S.R., David R., Davis C.M., Davy-Carroll L., Deshazo D.R., Donlin J.E., D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J., Escotto M., Flagg N., Forbes L.D., Gabisi A.M., Garza M., Hamilton C., Henderson N., Hernandez O., Hines S., Hogues M.E., Huang M., Idlebird D.G., Johnson R., Jolivet A., Jones S., Kagan R., King L.M., Leal B., Lebow H., Lee S., LeVan J.M., Lewis L.C., London P., Lorensuhewa L.M., Loulseged H., Lovett D.A., Lucier A., Lucier R.L., Ma J., Madu R.C., Mapua P., Martindale A.D., Martinez E., Massey E., Mawhiney S., Meador M.G., Mendez S., Mercado C., Mercado I.C., Merritt C.E., Miner Z.L., Minja E., Mitchell T., Mohabbat F., Mohabbat K., Montgomery B., Moore N., Morris S., Munidasa M., Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O., Nwokenkwo S., Obregon M., Oguh M., Oragunye N., Oviedo R.J., Parish B.J., Parker D.N., Parrish J., Parks K.L., Paul H.A., Payton B.A., Perez A., Perrin W., Pickens A., Primus E.L., Pu L.-L., Puazo M., Quiles M.M., Quiroz J.B., Rabata D., Reeves K., Ruiz S.J., Shao H., Sisson I., Sonaike T., Sorelle R.P., Sutton A.E., Svatek A.F., Svetz L.A., Tamerisa K.S., Taylor T.R., Teague B., Thomas N., Thorn R.D., Trejos Z.Y., Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I., Vera V.A., Villasana D.M., Wang L., Ward-Moore S., Warren J.T., Wei X., White F., Williamson A.L., Wleczyk R., Wooden H.S., Wooden S.H., Yen J., Yoon L., Yoon V., Zorrilla S.E., Nelson D., Kucherlapati R., Weinstock G., Gibbs R.A.
Nature 440:346-351(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]"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] (ISOFORM 2).
Tissue: Colon.
[7]"Suppression of estrogen receptor-mediated transcription and cell growth by interaction with TR2 orphan receptor."
Hu Y.C., Shyr C.R., Che W., Mu X.M., Kim E., Chang C.
J. Biol. Chem. 277:33571-33579(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH ESR1.
[8]"Transcriptional regulation of the human TR2 orphan receptor gene by nuclear factor 1-A."
Lin Y.L., Wang Y.H., Lee H.J.
Biochem. Biophys. Res. Commun. 350:430-436(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[9]"A quantitative atlas of mitotic phosphorylation."
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-215 AND THR-220, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[10]"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis."
Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.
Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
M21985 mRNA. Translation: AAA36650.1.
M29959 mRNA. Translation: AAA36762.1.
M29960 mRNA. Translation: AAA36761.1.
AK291319 mRNA. Translation: BAF84008.1.
AC011598 Genomic DNA. No translation available.
CH471054 Genomic DNA. Translation: EAW97518.1.
BC040141 mRNA. Translation: AAH40141.1.
PIRA31521.
A36738.
B36738.
RefSeqNP_001027458.1. NM_001032287.2.
NP_001120834.1. NM_001127362.1.
NP_003288.2. NM_003297.3.
UniGeneHs.108301.
Hs.707524.

3D structure databases

ProteinModelPortalP13056.
SMRP13056. Positions 111-589.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid113033. 29 interactions.
IntActP13056. 3 interactions.
MINTMINT-8247579.
STRING9606.ENSP00000333275.

Chemistry

ChEMBLCHEMBL1961787.

PTM databases

PhosphoSiteP13056.

Polymorphism databases

DMDM226693548.

Proteomic databases

PaxDbP13056.
PRIDEP13056.

Protocols and materials databases

DNASU7181.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000330677; ENSP00000328843; ENSG00000120798. [P13056-3]
ENST00000333003; ENSP00000333275; ENSG00000120798. [P13056-1]
ENST00000393101; ENSP00000376813; ENSG00000120798. [P13056-2]
GeneID7181.
KEGGhsa:7181.
UCSCuc001tdm.5. human. [P13056-1]
uc001tdo.4. human. [P13056-3]

Organism-specific databases

CTD7181.
GeneCardsGC12M095414.
HGNCHGNC:7971. NR2C1.
MIM601529. gene.
neXtProtNX_P13056.
PharmGKBPA31754.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG297520.
HOGENOMHOG000013058.
HOVERGENHBG008596.
KOK08543.
OMAEKAYMEF.
OrthoDBEOG7FJH0K.
PhylomeDBP13056.
TreeFamTF316650.

Enzyme and pathway databases

ReactomeREACT_71. Gene Expression.
SignaLinkP13056.

Gene expression databases

ArrayExpressP13056.
BgeeP13056.
CleanExHS_NR2C1.
GenevestigatorP13056.

Family and domain databases

Gene3D1.10.565.10. 3 hits.
3.30.50.10. 1 hit.
InterProIPR008946. 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]
PfamPF00104. Hormone_recep. 1 hit.
PF00105. zf-C4. 1 hit.
[Graphical view]
PRINTSPR00398. STRDHORMONER.
PR00047. STROIDFINGER.
SMARTSM00430. HOLI. 1 hit.
SM00399. ZnF_C4. 1 hit.
[Graphical view]
SUPFAMSSF48508. SSF48508. 3 hits.
PROSITEPS00031. NUCLEAR_REC_DBD_1. 1 hit.
PS51030. NUCLEAR_REC_DBD_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiTesticular_receptor_2.
GenomeRNAi7181.
NextBio28152.
PROP13056.
SOURCESearch...

Entry information

Entry nameNR2C1_HUMAN
AccessionPrimary (citable) accession number: P13056
Secondary accession number(s): A8K5K4, Q15625, Q15626
Entry history
Integrated into UniProtKB/Swiss-Prot: January 1, 1990
Last sequence update: April 14, 2009
Last modified: April 16, 2014
This is version 146 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human chromosome 12

Human chromosome 12: entries, gene names and cross-references to MIM