O00482 (NR5A2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

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 names

Name:	NR5A2
Synonyms:	B1F, CPF, FTF

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

General annotation (Comments)

Function	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.
Subunit structure	Binds DNA as a monomer By similarity. Interacts with GRIP1, NCOA2 and NR0B2.
Subcellular location	Nucleus Probable.
Tissue specificity	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.
Sequence similarities	Belongs to the nuclear hormone receptor family. NR5 subfamily. Contains 1 nuclear receptor DNA-binding domain.

Ontologies

Keywords
Biological process	Transcription Transcription regulation
Cellular component	Nucleus
Coding sequence diversity	Alternative splicing
Domain	Zinc-finger
Ligand	DNA-binding Lipid-binding Metal-binding Zinc
Molecular function	Receptor
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	bile acid metabolic process Inferred from electronic annotation. Source: Compara cholesterol homeostasis Inferred from electronic annotation. Source: Compara embryo development Traceable author statement Ref.9. Source: UniProtKB homeostatic process Non-traceable author statement Ref.9. Source: UniProtKB positive regulation of transcription from RNA polymerase II promoter Inferred from electronic annotation. Source: Compara positive regulation of transcription, DNA-dependent Inferred from direct assay PubMed 15143342. Source: BHF-UCL positive regulation of viral genome replication Inferred from direct assay PubMed 19264593. Source: BHF-UCL regulation of cell proliferation 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 PubMed 15205472. Source: BHF-UCL nucleoplasm Traceable author statement. Source: Reactome
Molecular_function	RNA polymerase II distal enhancer sequence-specific DNA binding transcription factor activity Traceable author statement Ref.1. Source: ProtInc double-stranded DNA binding Inferred from electronic annotation. Source: Compara ligand-activated sequence-specific DNA binding RNA polymerase II transcription factor activity Traceable author statement PubMed 16271724. Source: UniProtKB phospholipid binding Inferred from direct assay Ref.10. Source: UniProtKB sequence-specific DNA binding Inferred from direct assay Ref.9. Source: UniProtKB steroid hormone receptor activity Inferred from electronic annotation. Source: InterPro transcription regulatory region DNA binding Inferred from direct assay PubMed 15205472. Source: BHF-UCL zinc ion binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
EDF1	O60869	2	EBI-781320,EBI-781301

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Isoform 2 (identifier: O00482-1)

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.

Isoform 1 (identifier: O00482-2)

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

Isoform 3 (identifier: O00482-3)

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

Note: Does not induce CYP7A promoter activity.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 541

541

Nuclear receptor subfamily 5 group A member 2

PRO_0000053735

Regions

DNA binding

83 – 154

72

Nuclear receptor

Zinc finger

86 – 106

21

NR C4-type

Zinc finger

122 – 146

25

NR C4-type

Region

342 – 390

49

Ligand-binding

Region

419 – 424

6

Lipid binding

Motif

155 – 184

30

FTZ-F1 box

Sites

Binding site

516

1

Lipid headgroup

Binding site

520

1

Lipid headgroup

Natural variations

Alternative sequence

22 – 67

46

Missing in isoform 1.

VSP_003716

Alternative sequence

199 – 370

172

Missing in isoform 3.

VSP_003717

Experimental info

Mutagenesis

96

1

Y → A: Slightly reduced DNA binding. Strongly reduced transactivation; when associated with A-168 and A-172. Ref.9

Mutagenesis

168

1

F → A: Slightly reduced DNA binding. Strongly reduced transactivation; when associated with A-96 and A-172. Ref.9

Mutagenesis

169 – 170

2

GP → VA: Reduced DNA binding. Loss of transactivation.

Mutagenesis

172

1

Y → A: Slightly reduced DNA binding. Strongly reduced transactivation; when associated with A-96 and A-168. Ref.9

Mutagenesis

342

1

F → W: Reduced phospholipid binding. Strongly reduced transactivation; when associated with W-416. Ref.10

Mutagenesis

416

1

I → W: Reduced phospholipid binding. Strongly reduced transactivation; when associated with W-342. Ref.10

Sequence conflict

250 – 251

2

PP → L in AAD03155. Ref.7

Sequence conflict

353

1

L → V in AAD03155. Ref.7

Secondary structure

1

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541

Helix Strand Turn

Details...

Turn

87 – 89

3

Beta strand

92 – 97

6

Beta strand

100 – 103

4

Helix

104 – 115

12

Turn

132 – 137

6

Helix

139 – 148

10

Helix

153 – 155

3

Helix

169 – 177

9

Helix

303 – 310

8

Helix

315 – 328

14

Helix

335 – 337

3

Helix

341 – 362

22

Helix

366 – 368

3

Helix

371 – 397

27

Beta strand

402 – 404

3

Beta strand

410 – 412

3

Helix

413 – 417

5

Helix

422 – 440

19

Helix

445 – 456

12

Helix

467 – 488

22

Helix

495 – 500

6

Helix

502 – 522

21

Helix

531 – 536

6

Sequences

	Sequence		Length	Mass (Da)
	Isoform 2 (B1F2) [UniParc]. Last modified May 30, 2000. Version 2. Checksum: 7B07170C075490FE	FASTA	541	61,331
	10 20 30 40 50 60 MSSNSDTGDL QESLKHGLTP IGAGLPDRHG SPIPARGRLV MLPKVETEAL GLARSHGEQG 70 80 90 100 110 120 QMPENMQVSQ FKMVNYSYDE DLEELCPVCG DKVSGYHYGL LTCESCKGFF KRTVQNNKRY 130 140 150 160 170 180 TCIENQNCQI DKTQRKRCPY CRFQKCLSVG MKLEAVRADR MRGGRNKFGP MYKRDRALKQ 190 200 210 220 230 240 QKKALIRANG LKLEAMSQVI QAMPSDLTIS SAIQNIHSAS KGLPLNHAAL PPTDYDRSPF 250 260 270 280 290 300 VTSPISMTMP PHGSLQGYQT YGHFPSRAIK SEYPDPYTSS PESIMGYSYM DSYQTSSPAS 310 320 330 340 350 360 IPHLILELLK CEPDEPQVQA KIMAYLQQEQ ANRSKHEKLS TFGLMCKMAD QTLFSIVEWA 370 380 390 400 410 420 RSSIFFRELK VDDQMKLLQN CWSELLILDH IYRQVVHGKE GSIFLVTGQQ VDYSIIASQA 430 440 450 460 470 480 GATLNNLMSH AQELVAKLRS LQFDQREFVC LKFLVLFSLD VKNLENFQLV EGVQEQVNAA 490 500 510 520 530 540 LLDYTMCNYP QQTEKFGQLL LRLPEIRAIS MQAEEYLYYK HLNGDVPYNN LLIEMLHAKR A
	Isoform 1 [UniParc]. Checksum: E73E60DCE9880855	FASTA	495	56,459
	10 20 30 40 50 60 MSSNSDTGDL QESLKHGLTP IVSQFKMVNY SYDEDLEELC PVCGDKVSGY HYGLLTCESC 70 80 90 100 110 120 KGFFKRTVQN NKRYTCIENQ NCQIDKTQRK RCPYCRFQKC LSVGMKLEAV RADRMRGGRN 130 140 150 160 170 180 KFGPMYKRDR ALKQQKKALI RANGLKLEAM SQVIQAMPSD LTISSAIQNI HSASKGLPLN 190 200 210 220 230 240 HAALPPTDYD RSPFVTSPIS MTMPPHGSLQ GYQTYGHFPS RAIKSEYPDP YTSSPESIMG 250 260 270 280 290 300 YSYMDSYQTS SPASIPHLIL ELLKCEPDEP QVQAKIMAYL QQEQANRSKH EKLSTFGLMC 310 320 330 340 350 360 KMADQTLFSI VEWARSSIFF RELKVDDQMK LLQNCWSELL ILDHIYRQVV HGKEGSIFLV 370 380 390 400 410 420 TGQQVDYSII ASQAGATLNN LMSHAQELVA KLRSLQFDQR EFVCLKFLVL FSLDVKNLEN 430 440 450 460 470 480 FQLVEGVQEQ VNAALLDYTM CNYPQQTEKF GQLLLRLPEI RAISMQAEEY LYYKHLNGDV 490 PYNNLLIEML HAKRA
	Isoform 3 [UniParc]. Checksum: 1357C2AAEFB4E46B	FASTA	369	42,102
	10 20 30 40 50 60 MSSNSDTGDL QESLKHGLTP IGAGLPDRHG SPIPARGRLV MLPKVETEAL GLARSHGEQG 70 80 90 100 110 120 QMPENMQVSQ FKMVNYSYDE DLEELCPVCG DKVSGYHYGL LTCESCKGFF KRTVQNNKRY 130 140 150 160 170 180 TCIENQNCQI DKTQRKRCPY CRFQKCLSVG MKLEAVRADR MRGGRNKFGP MYKRDRALKQ 190 200 210 220 230 240 QKKALIRANG LKLEAMSQVD DQMKLLQNCW SELLILDHIY RQVVHGKEGS IFLVTGQQVD 250 260 270 280 290 300 YSIIASQAGA TLNNLMSHAQ ELVAKLRSLQ FDQREFVCLK FLVLFSLDVK NLENFQLVEG 310 320 330 340 350 360 VQEQVNAALL DYTMCNYPQQ TEKFGQLLLR LPEIRAISMQ AEEYLYYKHL NGDVPYNNLL IEMLHAKRA

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning and characterization of a novel human hepatocyte transcription factor, hB1F, which binds and activates enhancer II of hepatitis B virus." Li M., Xie Y.-H., Kong Y.-Y., Wu X., Zhu L., Wang Y. J. Biol. Chem. 273:29022-29031(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), ALTERNATIVE SPLICING. Tissue: Liver.
[2]	Li M., Xie Y.-H., Wang Y. Submitted (JAN-1999) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2). Tissue: Hepatoma.
[3]	"CPF: an orphan nuclear receptor that regulates liver-specific expression of the human cholesterol 7alpha-hydroxylase gene." Nitta M., Ku S., Brown C., Okamoto A.Y., Shan B. Proc. Natl. Acad. Sci. U.S.A. 96:6660-6665(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2 AND 3). Tissue: Liver.
[4]	"Characterization of the genomic structure and tissue-specific promoter of the human nuclear receptor NR5A2 (hB1F) gene." Zhang C.K., Lin W., Cai Y.N., Xu P.L., Dong H., Li M., Kong Y.Y., Fu G., Xie Y.H., Huang G.M., Wang Y. Gene 273:239-249(2001) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], ALTERNATIVE SPLICING.
[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. , 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 1).
[7]	"Assignment of the fetoprotein transcription factor gene (FTF) to human chromosome band 1q32.11 by in situ hybridization." Galarneau L., Drouin R., Belanger L. Cytogenet. Cell Genet. 82:269-270(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 41-541.
[8]	"Structural analyses reveal phosphatidyl inositols as ligands for the NR5 orphan receptors SF-1 and LRH-1." Krylova I.N., Sablin E.P., Moore J., Xu R.X., Waitt G.M., MacKay J.A., Juzumiene D., Bynum J.M., Madauss K., Montana V., Lebedeva L., Suzawa M., Williams J.D., Williams S.P., Guy R.K., Thornton J.W., Fletterick R.J., Willson T.M., Ingraham H.A. Cell 120:343-355(2005) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 300-541 IN COMPLEX WITH NCOA2 AND PHOSPHOLIPIDS.
[9]	"Crystal structure of the human LRH-1 DBD-DNA complex reveals Ftz-F1 domain positioning is required for receptor activity." Solomon I.H., Hager J.M., Safi R., McDonnell D.P., Redinbo M.R., Ortlund E.A. J. Mol. Biol. 354:1091-1102(2005) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 79-187 IN COMPLEX WITH DNA, MUTAGENESIS OF TYR-96; PHE-168; 169-GLY-PRO-170 AND TYR-172.
[10]	"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 290-541 IN COMPLEX WITH NR0B2 AND PHOSPHOLIPID, MUTAGENESIS OF PHE-342 AND ILE-416.
[11]	"The crystal structures of human steroidogenic factor-1 and liver receptor homologue-1." Wang W., Zhang C., Marimuthu A., Krupka H.I., Tabrizizad M., Shelloe R., Mehra U., Eng K., Nguyen H., Settachatgul C., Powell B., Milburn M.V., West B.L. Proc. Natl. Acad. Sci. U.S.A. 102:7505-7510(2005) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 297-541 IN COMPLEX WITH NCOA2 AND PHOSPHOLIPID.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

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.
CH471067 Genomic DNA. Translation: EAW91306.1.
BC118571 mRNA. Translation: AAI18572.1.
BC118652 mRNA. Translation: AAI18653.1.
U93553 mRNA. Translation: AAD03155.1.

IPI

IPI00011769.
IPI00217284.
IPI00217285.

RefSeq

NP_003813.1. NM_003822.4.
NP_995582.1. NM_205860.2.

UniGene

Hs.33446.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1YOK	X-ray	2.50	A	300-541	[»]
1YUC	X-ray	1.90	A/B	290-541	[»]
1ZDU	X-ray	2.50	A	297-541	[»]
2A66	X-ray	2.20	A	79-187	[»]
3PLZ	X-ray	1.75	A/B	300-541	[»]
3TX7	X-ray	2.76	B	191-541	[»]
4DOR	X-ray	1.90	A/B	290-541	[»]
4DOS	X-ray	2.00	A	299-538	[»]

ProteinModelPortal

O00482.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-37952N.

IntAct

O00482. 1 interaction.

MINT

MINT-2997724.

STRING

9606.ENSP00000356331.

PTM databases

PhosphoSite

O00482.

Proteomic databases

PaxDb

O00482.

PRIDE

O00482.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000236914; ENSP00000236914; ENSG00000116833.
ENST00000367362; ENSP00000356331; ENSG00000116833.

GeneID

2494.

KEGG

hsa:2494.

UCSC

uc001gvb.3. human.

Organism-specific databases

CTD

2494.

GeneCards

GC01P199996.

HGNC

HGNC:7984. NR5A2.

HPA

HPA005455.
HPA017067.

MIM

604453. gene.

neXtProt

NX_O00482.

PharmGKB

PA31765.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG240365.

HOGENOM

HOG000063718.

HOVERGEN

HBG106677.

InParanoid

O00482.

KO

K08027.

OMA

NTFGLMC.

OrthoDB

EOG470TH1.

PhylomeDB

O00482.

Enzyme and pathway databases

Reactome

REACT_111045. Developmental Biology.
REACT_71. Gene Expression.

Gene expression databases

ArrayExpress

O00482.

Bgee

O00482.

CleanEx

HS_NR5A2.

Genevestigator

O00482.

GermOnline

ENSG00000116833. Homo sapiens.

Family and domain databases

Gene3D

1.10.565.10. 1 hit.
3.30.50.10. 1 hit.

InterPro

IPR008946. Nucl_hormone_rcpt_ligand-bd.
IPR000536. Nucl_hrmn_rcpt_lig-bd_core.
IPR016355. Steroidogenic_factor_1.
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]

PIRSF

PIRSF002530. Nuc_orph_FTZ-F1. 1 hit.

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

O00482.

ChEMBL

CHEMBL3544.

EvolutionaryTrace

O00482.

GenomeRNAi

2494.

NextBio

9851.

SOURCE

Search...

Entry information

Entry name

NR5A2_HUMAN

Accession

Primary (citable) accession number: O00482
Secondary accession number(s): O95642, Q147U3

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 15, 1998
Last sequence update:	May 30, 2000
Last modified:	May 1, 2013
This is version 132 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.