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Protein

Nuclear receptor subfamily 5 group A member 2

Gene

NR5A2

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

Functioni

Nuclear receptor that acts as a key metabolic sensor by regulating the expression of genes involved in bile acid synthesis, cholesterol homeostasis and triglyceride synthesis. Together with the oxysterol receptors NR1H3/LXR-alpha and NR1H2/LXR-beta, acts as an essential transcriptional regulator of lipid metabolism. Plays an anti-inflammatory role during the hepatic acute phase response by acting as a corepressor: inhibits the hepatic acute phase response by preventing dissociation of the N-Cor corepressor complex (PubMed:20159957). Binds to the sequence element 5'-AACGACCGACCTTGAG-3' of the enhancer II of hepatitis B virus genes, a critical cis-element of their expression and regulation. May be responsible for the liver-specific activity of enhancer II, probably in combination with other hepatocyte transcription factors. Key regulator of cholesterol 7-alpha-hydroxylase gene (CYP7A) expression in liver. May also contribute to the regulation of pancreas-specific genes and play important roles in embryonic development.5 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei516Lipid headgroup1
Binding sitei520Lipid headgroup1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
DNA bindingi83 – 154Nuclear receptorPROSITE-ProRule annotationAdd BLAST72
Zinc fingeri86 – 106NR C4-typePROSITE-ProRule annotationAdd BLAST21
Zinc fingeri122 – 146NR C4-typePROSITE-ProRule annotationAdd BLAST25

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionDNA-binding, Receptor
Biological processTranscription, Transcription regulation
LigandLipid-binding, Metal-binding, Zinc

Enzyme and pathway databases

ReactomeiR-HSA-210747 Regulation of gene expression in early pancreatic precursor cells
R-HSA-383280 Nuclear Receptor transcription pathway
R-HSA-9018519 Estrogen-dependent gene expression
SignaLinkiO00482
SIGNORiO00482

Chemistry databases

SwissLipidsiSLP:000001542

Names & Taxonomyi

Protein namesi
Recommended name:
Nuclear receptor subfamily 5 group A member 2
Alternative name(s):
Alpha-1-fetoprotein transcription factor
B1-binding factor
Short name:
hB1F
CYP7A promoter-binding factor
Hepatocytic transcription factor
Liver receptor homolog 1
Short name:
LRH-1
Gene namesi
Name:NR5A2
Synonyms:B1F, CPF, FTF
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 1

Organism-specific databases

EuPathDBiHostDB:ENSG00000116833.13
HGNCiHGNC:7984 NR5A2
MIMi604453 gene
neXtProtiNX_O00482

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi96Y → A: Slightly reduced DNA binding. Strongly reduced transactivation; when associated with A-168 and A-172. 1 Publication1
Mutagenesisi168F → A: Slightly reduced DNA binding. Strongly reduced transactivation; when associated with A-96 and A-172. 1 Publication1
Mutagenesisi169 – 170GP → VA: Reduced DNA binding. Loss of transactivation. 1 Publication2
Mutagenesisi172Y → A: Slightly reduced DNA binding. Strongly reduced transactivation; when associated with A-96 and A-168. 1 Publication1
Mutagenesisi270K → R: Impaired ability to act as an anti-inflammatory role during the hepatic acute phase response. 1 Publication1
Mutagenesisi342F → W: Reduced phospholipid binding. Strongly reduced transactivation; when associated with W-416. 1 Publication1
Mutagenesisi416I → W: Reduced phospholipid binding. Strongly reduced transactivation; when associated with W-342. 1 Publication1

Organism-specific databases

DisGeNETi2494
OpenTargetsiENSG00000116833
PharmGKBiPA31765

Chemistry databases

ChEMBLiCHEMBL3544

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000537351 – 541Nuclear receptor subfamily 5 group A member 2Add BLAST541

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Cross-linki270Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO1)1 Publication

Post-translational modificationi

Sumoylated by SUMO1 at Lys-270 during the hepatic acute phase response, leading to promote interaction with GPS2 and prevent N-Cor corepressor complex dissociation.1 Publication

Keywords - PTMi

Isopeptide bond, Ubl conjugation

Proteomic databases

PaxDbiO00482
PeptideAtlasiO00482
PRIDEiO00482

PTM databases

iPTMnetiO00482
PhosphoSitePlusiO00482

Expressioni

Tissue specificityi

Abundantly expressed in pancreas, less in liver, very low levels in heart and lung. Expressed in the Hep-G2 cell line. Isoform 1 and isoform 2 seem to be present in fetal and adult liver and Hep-G2 cells.

Gene expression databases

BgeeiENSG00000116833
CleanExiHS_NR5A2
ExpressionAtlasiO00482 baseline and differential
GenevisibleiO00482 HS

Organism-specific databases

HPAiHPA005455
HPA017067

Interactioni

Subunit structurei

Binds DNA as a monomer (By similarity). Interacts with GRIP1, NCOA2 and NR0B2 (PubMed:15707893, PubMed:15723037, PubMed:15897460, PubMed:16289203). Interacts (when sumoylated) with GPS2; interaction with GPS2 onto hepatic acute phase protein promoters prevents N-Cor corepressor complex dissociation (PubMed:20159957).By similarity5 Publications

Binary interactionsi

Show more details

Protein-protein interaction databases

BioGridi108772, 21 interactors
CORUMiO00482
DIPiDIP-37952N
IntActiO00482, 9 interactors
MINTiO00482
STRINGi9606.ENSP00000356331

Chemistry databases

BindingDBiO00482

Structurei

Secondary structure

1541
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Turni87 – 89Combined sources3
Beta strandi95 – 97Combined sources3
Beta strandi100 – 102Combined sources3
Helixi104 – 115Combined sources12
Turni132 – 137Combined sources6
Helixi139 – 148Combined sources10
Helixi153 – 155Combined sources3
Turni167 – 170Combined sources4
Helixi171 – 175Combined sources5
Helixi303 – 310Combined sources8
Helixi315 – 328Combined sources14
Helixi335 – 337Combined sources3
Helixi341 – 362Combined sources22
Helixi366 – 368Combined sources3
Helixi371 – 397Combined sources27
Beta strandi402 – 404Combined sources3
Beta strandi410 – 412Combined sources3
Helixi413 – 417Combined sources5
Helixi422 – 440Combined sources19
Helixi445 – 456Combined sources12
Helixi467 – 488Combined sources22
Beta strandi490 – 492Combined sources3
Helixi495 – 500Combined sources6
Helixi502 – 522Combined sources21
Helixi531 – 536Combined sources6

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1YOKX-ray2.50A300-541[»]
1YUCX-ray1.90A/B290-541[»]
1ZDUX-ray2.50A297-541[»]
2A66X-ray2.20A79-187[»]
3PLZX-ray1.75A/B300-541[»]
3TX7X-ray2.76B191-541[»]
4DORX-ray1.90A/B290-541[»]
4DOSX-ray2.00A299-538[»]
4IS8X-ray2.78A/B300-538[»]
4ONIX-ray1.80A/B291-541[»]
4PLDX-ray1.75A301-541[»]
4PLEX-ray1.75A/C/E/G301-541[»]
4RWVX-ray1.86A294-541[»]
5L0MX-ray2.20A79-187[»]
5L11X-ray1.85A299-541[»]
5SYZX-ray1.93A297-538[»]
5UNJX-ray1.96A299-541[»]
ProteinModelPortaliO00482
SMRiO00482
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiO00482

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini300 – 539NR LBDPROSITE-ProRule annotationAdd BLAST240

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni419 – 424Lipid binding6

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi155 – 184FTZ-F1 boxAdd BLAST30

Sequence similaritiesi

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri86 – 106NR C4-typePROSITE-ProRule annotationAdd BLAST21
Zinc fingeri122 – 146NR C4-typePROSITE-ProRule annotationAdd BLAST25

Keywords - Domaini

Zinc-finger

Phylogenomic databases

eggNOGiKOG4218 Eukaryota
ENOG410YWC2 LUCA
GeneTreeiENSGT00870000136388
HOGENOMiHOG000063718
HOVERGENiHBG106677
InParanoidiO00482
KOiK08027
OMAiTQVIQAM
OrthoDBiEOG091G06RK
PhylomeDBiO00482
TreeFamiTF350737

Family and domain databases

Gene3Di3.30.50.10, 1 hit
InterProiView protein in InterPro
IPR035500 NHR_like_dom_sf
IPR016355 NR5_fam
IPR000536 Nucl_hrmn_rcpt_lig-bd
IPR001723 Nuclear_hrmn_rcpt
IPR001628 Znf_hrmn_rcpt
IPR013088 Znf_NHR/GATA
PANTHERiPTHR24086 PTHR24086, 1 hit
PfamiView protein in Pfam
PF00104 Hormone_recep, 1 hit
PF00105 zf-C4, 1 hit
PIRSFiPIRSF002530 Nuc_orph_FTZ-F1, 1 hit
PRINTSiPR00398 STRDHORMONER
PR00047 STROIDFINGER
SMARTiView protein in SMART
SM00430 HOLI, 1 hit
SM00399 ZnF_C4, 1 hit
SUPFAMiSSF48508 SSF48508, 2 hits
PROSITEiView protein in PROSITE
PS51843 NR_LBD, 1 hit
PS00031 NUCLEAR_REC_DBD_1, 1 hit
PS51030 NUCLEAR_REC_DBD_2, 1 hit

Sequences (4)i

Sequence statusi: Complete.

This entry describes 4 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 2 (identifier: O00482-1) [UniParc]FASTAAdd to basket
Also known as: B1F2

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
MSSNSDTGDL QESLKHGLTP IGAGLPDRHG SPIPARGRLV MLPKVETEAL
60 70 80 90 100
GLARSHGEQG QMPENMQVSQ FKMVNYSYDE DLEELCPVCG DKVSGYHYGL
110 120 130 140 150
LTCESCKGFF KRTVQNNKRY TCIENQNCQI DKTQRKRCPY CRFQKCLSVG
160 170 180 190 200
MKLEAVRADR MRGGRNKFGP MYKRDRALKQ QKKALIRANG LKLEAMSQVI
210 220 230 240 250
QAMPSDLTIS SAIQNIHSAS KGLPLNHAAL PPTDYDRSPF VTSPISMTMP
260 270 280 290 300
PHGSLQGYQT YGHFPSRAIK SEYPDPYTSS PESIMGYSYM DSYQTSSPAS
310 320 330 340 350
IPHLILELLK CEPDEPQVQA KIMAYLQQEQ ANRSKHEKLS TFGLMCKMAD
360 370 380 390 400
QTLFSIVEWA RSSIFFRELK VDDQMKLLQN CWSELLILDH IYRQVVHGKE
410 420 430 440 450
GSIFLVTGQQ VDYSIIASQA GATLNNLMSH AQELVAKLRS LQFDQREFVC
460 470 480 490 500
LKFLVLFSLD VKNLENFQLV EGVQEQVNAA LLDYTMCNYP QQTEKFGQLL
510 520 530 540
LRLPEIRAIS MQAEEYLYYK HLNGDVPYNN LLIEMLHAKR A
Length:541
Mass (Da):61,331
Last modified:May 30, 2000 - v2
Checksum:i7B07170C075490FE
GO
Isoform 1 (identifier: O00482-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     22-67: Missing.

Show »
Length:495
Mass (Da):56,459
Checksum:iE73E60DCE9880855
GO
Isoform 3 (identifier: O00482-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     199-370: Missing.

Note: Does not induce CYP7A promoter activity.
Show »
Length:369
Mass (Da):42,102
Checksum:i1357C2AAEFB4E46B
GO
Isoform 4 (identifier: O00482-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-72: Missing.

Note: No experimental confirmation available.
Show »
Length:469
Mass (Da):53,657
Checksum:i49F21C2F09CF0AB4
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti250 – 251PP → L in AAD03155 (PubMed:9858833).Curated2
Sequence conflicti353L → V in AAD03155 (PubMed:9858833).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0545481 – 72Missing in isoform 4. 1 PublicationAdd BLAST72
Alternative sequenceiVSP_00371622 – 67Missing in isoform 1. 3 PublicationsAdd BLAST46
Alternative sequenceiVSP_003717199 – 370Missing in isoform 3. 1 PublicationAdd BLAST172

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U80251 mRNA Translation: AAC78727.1
AF146343 mRNA Translation: AAD37378.1
AF124247 mRNA Translation: AAD26565.1
AF190464 Genomic DNA Translation: AAG17124.1
AF190464 Genomic DNA Translation: AAG17125.1
AK304365 mRNA Translation: BAG65205.1
AK316513 mRNA Translation: BAH14884.1
AC096633 Genomic DNA No translation available.
CH471067 Genomic DNA Translation: EAW91306.1
BC118571 mRNA Translation: AAI18572.1
BC118652 mRNA Translation: AAI18653.1
U93553 mRNA Translation: AAD03155.1
CCDSiCCDS1400.1 [O00482-2]
CCDS1401.1 [O00482-1]
CCDS60383.1 [O00482-4]
RefSeqiNP_001263393.1, NM_001276464.1 [O00482-4]
NP_003813.1, NM_003822.4 [O00482-2]
NP_995582.1, NM_205860.2 [O00482-1]
XP_005245119.1, XM_005245062.3 [O00482-4]
XP_011507684.1, XM_011509382.1 [O00482-4]
UniGeneiHs.33446

Genome annotation databases

EnsembliENST00000236914; ENSP00000236914; ENSG00000116833 [O00482-2]
ENST00000367362; ENSP00000356331; ENSG00000116833 [O00482-1]
ENST00000544748; ENSP00000439116; ENSG00000116833 [O00482-4]
GeneIDi2494
KEGGihsa:2494
UCSCiuc001gvb.5 human [O00482-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiNR5A2_HUMAN
AccessioniPrimary (citable) accession number: O00482
Secondary accession number(s): B4E2P3, O95642, Q147U3
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 15, 1998
Last sequence update: May 30, 2000
Last modified: May 23, 2018
This is version 185 of the entry and version 2 of the sequence. See 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

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