P49698 (HNF4A_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Hepatocyte nuclear factor 4-alpha
Short name=HNF-4-alpha

Alternative name(s):
Nuclear receptor subfamily 2 group A member 1
Transcription factor 14
Short name=TCF-14
Transcription factor HNF-4

Gene names

Name:	Hnf4a
Synonyms:	Hnf-4, Hnf4, Nr2a1, Tcf14

Organism

Mus musculus (Mouse)

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	474 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Transcriptionally controlled transcription factor. Binds to DNA sites required for the transcription of alpha 1-antitrypsin, apolipoprotein CIII, transthyretin genes and HNF1-alpha. May be essential for development of the liver, kidney and intestine.
Subunit structure	Homodimerization is required for HNF4-alpha to bind to its recognition site By similarity.
Subcellular location	Nucleus.
Post-translational modification	Phosphorylated on tyrosine residue(s); phosphorylation is important for its DNA-binding activity. Phosphorylation may directly or indirectly play a regulatory role in the subnuclear distribution. Phosphorylation at Ser-313 by AMPK reduces the ability to form homodimers and bind DNA By similarity. Ref.7
Miscellaneous	Binds fatty acids By similarity.
Sequence similarities	Belongs to the nuclear hormone receptor family. NR2 subfamily. Contains 1 nuclear receptor DNA-binding domain.
Sequence caution	The sequence BAA06101.1 differs from that shown. Reason: Erroneous initiation. The sequence CAM22399.1 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
Biological process	Transcription Transcription regulation
Cellular component	Nucleus
Coding sequence diversity	Alternative splicing
Domain	Zinc-finger
Ligand	DNA-binding Metal-binding Zinc
Molecular function	Receptor
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	SMAD protein signal transduction Inferred from direct assay. Source: MGI endocrine pancreas development Traceable author statement. Source: Reactome glucose homeostasis Inferred from mutant phenotype. Source: BHF-UCL lipid metabolic process Inferred from mutant phenotype. Source: MGI phospholipid homeostasis Inferred from mutant phenotype. Source: BHF-UCL positive regulation of cholesterol homeostasis Inferred from mutant phenotype. Source: BHF-UCL regulation of gastrulation Inferred from mutant phenotype. Source: MGI regulation of insulin secretion Inferred from mutant phenotype. Source: BHF-UCL response to glucose stimulus Inferred from mutant phenotype. Source: BHF-UCL sex differentiation Inferred from mutant phenotype. Source: MGI signal transduction involved in regulation of gene expression Inferred from direct assay. Source: MGI triglyceride homeostasis Inferred from mutant phenotype. Source: BHF-UCL
Cellular component	cytosol Traceable author statement. Source: Reactome
Molecular function	activating transcription factor binding Inferred from physical interaction. Source: BHF-UCL sequence-specific DNA binding Inferred from direct assay. Source: MGI sequence-specific distal enhancer binding RNA polymerase II transcription factor activity Inferred from direct assay. Source: MGI steroid hormone receptor activity Inferred from electronic annotation. Source: InterPro transcription regulatory region DNA binding Inferred from direct assay. Source: BHF-UCL zinc ion binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform Long (identifier: P49698-1)

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 Short (identifier: P49698-2)

The sequence of this isoform differs from the canonical sequence as follows:
     418-428: CEWPRPRGQAA → S

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 474	474	Hepatocyte nuclear factor 4-alpha		PRO_0000053559
Regions
	DNA binding	57 – 132	76	Nuclear receptor
	Zinc finger	60 – 80	21	NR C4-type
	Zinc finger	96 – 120	25	NR C4-type
Amino acid modifications
	Modified residue	313	1	Phosphoserine; by AMPK By similarity
	Modified residue	429	1	Phosphothreonine Ref.7
	Modified residue	432	1	Phosphothreonine Ref.7
Natural variations
	Alternative sequence	418 – 428	11	CEWPRPRGQAA → S in isoform Short.		VSP_003676
Experimental info
	Sequence conflict	55	1	G → S in BAA06101. Ref.1
	Sequence conflict	365	1	K → R in BAE25624. Ref.3
	Sequence conflict	378	1	S → L in ABM69091. Ref.6

Sequences

	Sequence		Length	Mass (Da)
	Isoform Long [UniParc]. Last modified May 29, 2007. Version 2. Checksum: 10843D528EAE87EE	FASTA	474	52,684
	10 20 30 40 50 60 MRLSKTLAGM DMADYSAALD PAYTTLEFEN VQVLTMGNDT SPSEGANLNS SNSLGVSALC 70 80 90 100 110 120 AICGDRATGK HYGASSCDGC KGFFRRSVRK NHMYSCRFSR QCVVDKDKRN QCRYCRLKKC 130 140 150 160 170 180 FRAGMKKEAV QNERDRISTR RSSYEDSSLP SINALLQAEV LSQQITSPIS GINGDIRAKK 190 200 210 220 230 240 IANITDVCES MKEQLLVLVE WAKYIPAFCE LLLDDQVALL RAHAGEHLLL GATKRSMVFK 250 260 270 280 290 300 DVLLLGNDYI VPRHCPELAE MSRVSIRILD ELVLPFQELQ IDDNEYACLK AIIFFDPDAK 310 320 330 340 350 360 GLSDPGKIKR LRSQVQVSLE DYINDRQYDS RGRFGELLLL LPTLQSITWQ MIEQIQFIKL 370 380 390 400 410 420 FGMAKIDNLL QEMLLGGSAS DAPHTHHPLH PHLMQEHMGT NVIVANTMPS HLSNGQMCEW 430 440 450 460 470 PRPRGQAATP ETPQPSPPSG SGSESYKLLP GAITTIVKPP SAIPQPTITK QEAI
	Isoform Short [UniParc]. Checksum: 4C293463C33B2D76	FASTA	464	51,518
	10 20 30 40 50 60 MRLSKTLAGM DMADYSAALD PAYTTLEFEN VQVLTMGNDT SPSEGANLNS SNSLGVSALC 70 80 90 100 110 120 AICGDRATGK HYGASSCDGC KGFFRRSVRK NHMYSCRFSR QCVVDKDKRN QCRYCRLKKC 130 140 150 160 170 180 FRAGMKKEAV QNERDRISTR RSSYEDSSLP SINALLQAEV LSQQITSPIS GINGDIRAKK 190 200 210 220 230 240 IANITDVCES MKEQLLVLVE WAKYIPAFCE LLLDDQVALL RAHAGEHLLL GATKRSMVFK 250 260 270 280 290 300 DVLLLGNDYI VPRHCPELAE MSRVSIRILD ELVLPFQELQ IDDNEYACLK AIIFFDPDAK 310 320 330 340 350 360 GLSDPGKIKR LRSQVQVSLE DYINDRQYDS RGRFGELLLL LPTLQSITWQ MIEQIQFIKL 370 380 390 400 410 420 FGMAKIDNLL QEMLLGGSAS DAPHTHHPLH PHLMQEHMGT NVIVANTMPS HLSNGQMSTP 430 440 450 460 ETPQPSPPSG SGSESYKLLP GAITTIVKPP SAIPQPTITK QEAI

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Identification of two splice isoforms of mRNA for mouse hepatocyte nuclear factor 4 (HNF-4)." Hata S., Inoue T., Kosuga K., Nakashima T., Tsukamoto T., Osumi T. Biochim. Biophys. Acta 1260:55-61(1995) [PubMed: 7999795] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS LONG AND SHORT). Strain: C57BL/6 X CBA. Tissue: Liver.
[2]	"Genome-wide isolation of growth and obesity QTL using mouse speed congenic strains." Farber C.R., Corva P.M., Medrano J.F. BMC Genomics 7:102-102(2006) [PubMed: 16670015] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Strain: CAST/Ei. Tissue: Liver.
[3]	"The transcriptional landscape of the mammalian genome." Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y. Science 309:1559-1563(2005) [PubMed: 16141072] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Strain: C57BL/6J. Tissue: Kidney.
[4]	"Lineage-specific biology revealed by a finished genome assembly of the mouse." Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X., Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y., Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S. , Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R., Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K., Eichler E.E., Ponting C.P. PLoS Biol. 7:E1000112-E1000112(2009) [PubMed: 19468303] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: C57BL/6J.
[5]	"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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Strain: FVB/N. Tissue: Kidney.
[6]	"Expression of HNF4 alpha 3 in pancreatic islets and Ins-1 beta cells." Huang J., Karakucuk V., Levitsky L.L., Rhoads D.B. Submitted (DEC-2006) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 21-378. Strain: C57BL/6. Tissue: Liver.
[7]	"Large-scale phosphorylation analysis of mouse liver." Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007) [PubMed: 17242355] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-429 AND THR-432, MASS SPECTROMETRY. Tissue: Liver.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	D29015 mRNA. Translation: BAA06101.1. Different initiation. AY902317 Genomic DNA. Translation: AAX90602.1. AK143948 mRNA. Translation: BAE25624.1. AL591488 Genomic DNA. Translation: CAM22399.1. Different initiation. BC039220 mRNA. Translation: AAH39220.1. EF193393 mRNA. Translation: ABM69091.1.
IPI	IPI00230333. IPI00321964.
PIR	S52074.
RefSeq	NP_032287.2. NM_008261.2.
UniGene	Mm.202383.
3D structure databases
ProteinModelPortal	P49698.
SMR	P49698. Positions 57-377.
ModBase	Search...
Protein-protein interaction databases
IntAct	P49698. 1 interaction.
STRING	P49698.
PTM databases
PhosphoSite	P49698.
Proteomic databases
PRIDE	P49698.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000018094; ENSMUSP00000018094; ENSMUSG00000017950. ENSMUST00000109411; ENSMUSP00000105038; ENSMUSG00000017950.
GeneID	15378.
KEGG	mmu:15378.
UCSC	uc008nta.2. mouse. uc008ntb.1. mouse.
Organism-specific databases
CTD	3172.
MGI	MGI:109128. Hnf4a.
Phylogenomic databases
GeneTree	ENSGT00580000081371.
HOGENOM	HBG713785.
HOVERGEN	HBG005606.
InParanoid	P49698.
OMA	NDTSPSE.
PhylomeDB	P49698.
Enzyme and pathway databases
Reactome	REACT_115492. Developmental Biology. REACT_13641. Regulation of Beta-Cell Development.
Gene expression databases
ArrayExpress	P49698.
Bgee	P49698.
CleanEx	MM_HNF4A.
Genevestigator	P49698.
GermOnline	ENSMUSG00000017950. Mus musculus.
Family and domain databases
InterPro	IPR003068. COUP_TF. 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]
Gene3D	G3DSA:1.10.565.10. Nucl_hrmn_rcpt_lig_bd. 1 hit. G3DSA:3.30.50.10. Znf_NHR/GATA. 1 hit.
KO	K07292.
Pfam	PF00104. Hormone_recep. 1 hit. PF00105. zf-C4. 1 hit. [Graphical view]
PRINTS	PR01282. COUPTNFACTOR. 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
NextBio	288038.
SOURCE	Search...

Entry information

Entry name

HNF4A_MOUSE

Accession

Primary (citable) accession number: P49698
Secondary accession number(s): A2A5I5 , A2ICH0, Q3UNX3, Q8CFY1

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 1, 1996
Last sequence update:	May 29, 2007
Last modified:	January 25, 2012
This is version 115 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program