Reviewed, UniProtKB/Swiss-Prot P41235 (HNF4A_HUMAN)

Names and origin

Protein names

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

Gene names

Name:	HNF4A
Synonyms:	HNF4, NR2A1, TCF14

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	474 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
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.
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. Ref.7
Involvement in disease	Defects in HNF4A are the cause of maturity-onset diabetes of the young type 1 (MODY1) [MIM:125850]; also symbolized MODY-1. MODY [MIM:606391] is a form of diabetes that is characterized by an autosomal dominant mode of inheritance, onset in childhood or early adulthood (usually before 25 years of age) and a primary defect in insulin secretion. The clinical phenotype of MODY1 is characterized by severe insulin secretory defects, and by major hyperglycemia associated with microvascular complications. Ref.9 Ref.10 Ref.12
Miscellaneous	Binds fatty acids.
Sequence similarities	Belongs to the nuclear hormone receptor family. NR2 subfamily. Contains 1 nuclear receptor DNA-binding domain.
Sequence caution	The sequence CAA61133.1 differs from that shown. Reason: Frameshift at positions 2 and 7. The sequence CAA61134.1 differs from that shown. Reason: Frameshift at positions 2 and 7. The sequence CAA61135.1 differs from that shown. Reason: Frameshift at positions 2 and 7.

Ontologies

Keywords
Biological process	Transcription Transcription regulation
Cellular component	Nucleus
Coding sequence diversity	Alternative promoter usage Alternative splicing Polymorphism
Disease	Diabetes mellitus Disease mutation
Domain	Zinc-finger
Ligand	DNA-binding Metal-binding Zinc
Molecular function	Receptor
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome
Gene Ontology (GO)
Biological process	blood coagulation Inferred from direct assay. Source: UniProtKB lipid homeostasis Inferred from mutant phenotype. Source: UniProtKB negative regulation of cell growth Inferred from mutant phenotype. Source: UniProtKB negative regulation of cell proliferation Inferred from mutant phenotype. Source: UniProtKB ornithine metabolic process Inferred from mutant phenotype. Source: UniProtKB positive regulation of gene-specific transcription from RNA polymerase II promoter Inferred from mutant phenotype. Source: UniProtKB regulation of growth hormone receptor signaling pathway Non-traceable author statement. Source: UniProtKB regulation of lipid metabolic process Inferred from direct assay. Source: UniProtKB transcription Inferred from electronic annotation. Source: UniProtKB-KW xenobiotic metabolic process Inferred from mutant phenotype. Source: UniProtKB
Cellular component	cytoplasm Inferred from direct assay. Source: UniProtKB nucleus Inferred from direct assay. Source: UniProtKB
Molecular function	fatty acid binding Inferred from direct assay. Source: UniProtKB promoter binding Inferred from direct assay. Source: UniProtKB protein homodimerization activity Inferred from direct assay. Source: UniProtKB receptor binding Inferred from direct assay. Source: UniProtKB steroid binding Inferred from electronic annotation. Source: InterPro steroid hormone receptor activity Inferred from electronic annotation. Source: InterPro transcription factor activity Inferred from direct assay. Source: UniProtKB zinc ion binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
EXT2	Q93063	1	EBI-1049011,EBI-1047761
PABPC4	Q13310	1	EBI-1049011,EBI-372844
RAD50	Q92878	1	EBI-1049011,EBI-495494
SNCG	O76070	1	EBI-1049011,EBI-1053810
STK16	O75716	1	EBI-1049011,EBI-1046308

Alternative products

This entry describes 7 isoforms produced by alternative promoter usage and alternative splicing. [Align] [Select]

Note: Additional isoforms seem to exist.

Isoform HNF4-Alpha-1 (identifier: P41235-1)

Also known as: HNF-4B;

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.

Note: Produced by alternative promoter usage.

Isoform HNF4-Alpha-2 (identifier: P41235-2)

Also known as: HNF4-A;

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

Note: Produced by alternative splicing of isoform HNF4-Alpha-1.

Isoform HNF4-Alpha-3 (identifier: P41235-3)

Also known as: HNF4-C;

The sequence of this isoform differs from the canonical sequence as follows:
     378-474: SPSDAPHAHH...QPTITKQEVI → PCQAQEGRGW...SPLCRFGQVA

Note: Produced by alternative splicing of isoform HNF4-Alpha-1.

Isoform HNF4-Alpha-4 (identifier: P41235-4)

The sequence of this isoform differs from the canonical sequence as follows:
     38-38: N → NDLLPLRLARLRHPLRHHWSISGGVDSSPQG

Note: Produced by alternative splicing of isoform HNF4-Alpha-1.

Isoform HNF4-Alpha-7 (identifier: P41235-5)

The sequence of this isoform differs from the canonical sequence as follows:
     1-38: MRLSKTLVDMDMADYSAALDPAYTTLEFENVQVLTMGN → MVSVNAPLGAPVESSY

Note: Produced by alternative promoter usage.

Isoform HNF4-Alpha-8 (identifier: P41235-6)

The sequence of this isoform differs from the canonical sequence as follows:
     1-38: MRLSKTLVDMDMADYSAALDPAYTTLEFENVQVLTMGN → MVSVNAPLGAPVESSY
     418-428: CEWPRPRGQAA → S

Note: Produced by alternative splicing of isoform HNF4-Alpha-7.

Isoform HNF4-Alpha-9 (identifier: P41235-7)

The sequence of this isoform differs from the canonical sequence as follows:
     1-38: MRLSKTLVDMDMADYSAALDPAYTTLEFENVQVLTMGN → MVSVNAPLGAPVESSY
     378-474: SPSDAPHAHH...QPTITKQEVI → PCQAQEGRGW...SPLCRFGQVA

Note: Produced by alternative splicing of isoform HNF4-Alpha-7.

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_0000053558

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

429

1

Phosphothreonine By similarity

Modified residue

432

1

Phosphothreonine By similarity

Natural variations

Alternative sequence

1 – 38

38

MRLSK…LTMGN → MVSVNAPLGAPVESSY in isoform HNF4-Alpha-7, isoform HNF4-Alpha-8 and isoform HNF4-Alpha-9.

VSP_026030

Alternative sequence

38

1

N → NDLLPLRLARLRHPLRHHWS ISGGVDSSPQG in isoform HNF4-Alpha-4.

VSP_003673

Alternative sequence

378 – 474

97

SPSDA…KQEVI → PCQAQEGRGWSGDSPGDRPH TVSSPLSSLASPLCRFGQVA in isoform HNF4-Alpha-3 and isoform HNF4-Alpha-9.

VSP_003675

Alternative sequence

418 – 428

11

CEWPRPRGQAA → S in isoform HNF4-Alpha-2 and isoform HNF4-Alpha-8.

VSP_003674

Natural variant

136

1

R → W in MODY1. Ref.9

VAR_004668

Natural variant

139

1

T → I: dbSNP rs1800961. Ref.11

VAR_004669

Natural variant

264

1

V → M in late-onset NIDDM. Ref.11

VAR_010600

Natural variant

285

1

E → Q in MODY1. Ref.10

VAR_010601

Natural variant

402

1

V → I in MODY1; reduced transactivation activity. Ref.12

VAR_004670

Natural variant

445

1

P → S: dbSNP rs1063239. Ref.1

VAR_011785

Experimental info

Sequence conflict

440

1

G → A in CAA54248. Ref.6

Secondary structure

1

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474

Helix Strand Turn

Details...

Helix

149 – 153

5

Helix

155 – 163

9

Turn

176 – 178

3

Helix

184 – 202

19

Helix

206 – 209

4

Helix

213 – 222

10

Helix

224 – 236

13

Beta strand

239 – 244

6

Beta strand

250 – 254

5

Helix

256 – 261

6

Helix

262 – 271

10

Helix

273 – 279

7

Helix

283 – 294

12

Helix

305 – 324

20

Beta strand

325 – 328

4

Helix

333 – 338

6

Helix

340 – 360

21

Helix

368 – 374

7

Sequences

	Sequence		Length	Mass (Da)
	Isoform HNF4-Alpha-1 (HNF-4B) [UniParc]. Last modified May 29, 2007. Version 3. Checksum: 5F1309B89D95DCAF	FASTA	474	52,785
	10 20 30 40 50 60 MRLSKTLVDM DMADYSAALD PAYTTLEFEN VQVLTMGNDT SPSEGTNLNA PNSLGVSALC 70 80 90 100 110 120 AICGDRATGK HYGASSCDGC KGFFRRSVRK NHMYSCRFSR QCVVDKDKRN QCRYCRLKKC 130 140 150 160 170 180 FRAGMKKEAV QNERDRISTR RSSYEDSSLP SINALLQAEV LSRQITSPVS GINGDIRAKK 190 200 210 220 230 240 IASIADVCES MKEQLLVLVE WAKYIPAFCE LPLDDQVALL RAHAGEHLLL GATKRSMVFK 250 260 270 280 290 300 DVLLLGNDYI VPRHCPELAE MSRVSIRILD ELVLPFQELQ IDDNEYAYLK AIIFFDPDAK 310 320 330 340 350 360 GLSDPGKIKR LRSQVQVSLE DYINDRQYDS RGRFGELLLL LPTLQSITWQ MIEQIQFIKL 370 380 390 400 410 420 FGMAKIDNLL QEMLLGGSPS DAPHAHHPLH PHLMQEHMGT NVIVANTMPT HLSNGQMCEW 430 440 450 460 470 PRPRGQAATP ETPQPSPPGG SGSEPYKLLP GAVATIVKPL SAIPQPTITK QEVI
	Isoform HNF4-Alpha-2 (HNF4-A). Checksum: FF0A4FB233ADCC56	FASTA	464	51,619
	10 20 30 40 50 60 MRLSKTLVDM DMADYSAALD PAYTTLEFEN VQVLTMGNDT SPSEGTNLNA PNSLGVSALC 70 80 90 100 110 120 AICGDRATGK HYGASSCDGC KGFFRRSVRK NHMYSCRFSR QCVVDKDKRN QCRYCRLKKC 130 140 150 160 170 180 FRAGMKKEAV QNERDRISTR RSSYEDSSLP SINALLQAEV LSRQITSPVS GINGDIRAKK 190 200 210 220 230 240 IASIADVCES MKEQLLVLVE WAKYIPAFCE LPLDDQVALL RAHAGEHLLL GATKRSMVFK 250 260 270 280 290 300 DVLLLGNDYI VPRHCPELAE MSRVSIRILD ELVLPFQELQ IDDNEYAYLK AIIFFDPDAK 310 320 330 340 350 360 GLSDPGKIKR LRSQVQVSLE DYINDRQYDS RGRFGELLLL LPTLQSITWQ MIEQIQFIKL 370 380 390 400 410 420 FGMAKIDNLL QEMLLGGSPS DAPHAHHPLH PHLMQEHMGT NVIVANTMPT HLSNGQMSTP 430 440 450 460 ETPQPSPPGG SGSEPYKLLP GAVATIVKPL SAIPQPTITK QEVI
	Isoform HNF4-Alpha-3 (HNF4-C). Checksum: DE7D9F4F6436EFE2	FASTA	417	46,623
	10 20 30 40 50 60 MRLSKTLVDM DMADYSAALD PAYTTLEFEN VQVLTMGNDT SPSEGTNLNA PNSLGVSALC 70 80 90 100 110 120 AICGDRATGK HYGASSCDGC KGFFRRSVRK NHMYSCRFSR QCVVDKDKRN QCRYCRLKKC 130 140 150 160 170 180 FRAGMKKEAV QNERDRISTR RSSYEDSSLP SINALLQAEV LSRQITSPVS GINGDIRAKK 190 200 210 220 230 240 IASIADVCES MKEQLLVLVE WAKYIPAFCE LPLDDQVALL RAHAGEHLLL GATKRSMVFK 250 260 270 280 290 300 DVLLLGNDYI VPRHCPELAE MSRVSIRILD ELVLPFQELQ IDDNEYAYLK AIIFFDPDAK 310 320 330 340 350 360 GLSDPGKIKR LRSQVQVSLE DYINDRQYDS RGRFGELLLL LPTLQSITWQ MIEQIQFIKL 370 380 390 400 410 FGMAKIDNLL QEMLLGGPCQ AQEGRGWSGD SPGDRPHTVS SPLSSLASPL CRFGQVA
	Isoform HNF4-Alpha-4. Checksum: F291EFDE331E9338	FASTA	504	56,139
	10 20 30 40 50 60 MRLSKTLVDM DMADYSAALD PAYTTLEFEN VQVLTMGNDL LPLRLARLRH PLRHHWSISG 70 80 90 100 110 120 GVDSSPQGDT SPSEGTNLNA PNSLGVSALC AICGDRATGK HYGASSCDGC KGFFRRSVRK 130 140 150 160 170 180 NHMYSCRFSR QCVVDKDKRN QCRYCRLKKC FRAGMKKEAV QNERDRISTR RSSYEDSSLP 190 200 210 220 230 240 SINALLQAEV LSRQITSPVS GINGDIRAKK IASIADVCES MKEQLLVLVE WAKYIPAFCE 250 260 270 280 290 300 LPLDDQVALL RAHAGEHLLL GATKRSMVFK DVLLLGNDYI VPRHCPELAE MSRVSIRILD 310 320 330 340 350 360 ELVLPFQELQ IDDNEYAYLK AIIFFDPDAK GLSDPGKIKR LRSQVQVSLE DYINDRQYDS 370 380 390 400 410 420 RGRFGELLLL LPTLQSITWQ MIEQIQFIKL FGMAKIDNLL QEMLLGGSPS DAPHAHHPLH 430 440 450 460 470 480 PHLMQEHMGT NVIVANTMPT HLSNGQMCEW PRPRGQAATP ETPQPSPPGG SGSEPYKLLP 490 500 GAVATIVKPL SAIPQPTITK QEVI
	Isoform HNF4-Alpha-7. Checksum: 96854D18F389B0F9	FASTA	452	50,150
	10 20 30 40 50 60 MVSVNAPLGA PVESSYDTSP SEGTNLNAPN SLGVSALCAI CGDRATGKHY GASSCDGCKG 70 80 90 100 110 120 FFRRSVRKNH MYSCRFSRQC VVDKDKRNQC RYCRLKKCFR AGMKKEAVQN ERDRISTRRS 130 140 150 160 170 180 SYEDSSLPSI NALLQAEVLS RQITSPVSGI NGDIRAKKIA SIADVCESMK EQLLVLVEWA 190 200 210 220 230 240 KYIPAFCELP LDDQVALLRA HAGEHLLLGA TKRSMVFKDV LLLGNDYIVP RHCPELAEMS 250 260 270 280 290 300 RVSIRILDEL VLPFQELQID DNEYAYLKAI IFFDPDAKGL SDPGKIKRLR SQVQVSLEDY 310 320 330 340 350 360 INDRQYDSRG RFGELLLLLP TLQSITWQMI EQIQFIKLFG MAKIDNLLQE MLLGGSPSDA 370 380 390 400 410 420 PHAHHPLHPH LMQEHMGTNV IVANTMPTHL SNGQMCEWPR PRGQAATPET PQPSPPGGSG 430 440 450 SEPYKLLPGA VATIVKPLSA IPQPTITKQE VI
	Isoform HNF4-Alpha-8. Checksum: 8FD1619FC51F7217	FASTA	442	48,984
	10 20 30 40 50 60 MVSVNAPLGA PVESSYDTSP SEGTNLNAPN SLGVSALCAI CGDRATGKHY GASSCDGCKG 70 80 90 100 110 120 FFRRSVRKNH MYSCRFSRQC VVDKDKRNQC RYCRLKKCFR AGMKKEAVQN ERDRISTRRS 130 140 150 160 170 180 SYEDSSLPSI NALLQAEVLS RQITSPVSGI NGDIRAKKIA SIADVCESMK EQLLVLVEWA 190 200 210 220 230 240 KYIPAFCELP LDDQVALLRA HAGEHLLLGA TKRSMVFKDV LLLGNDYIVP RHCPELAEMS 250 260 270 280 290 300 RVSIRILDEL VLPFQELQID DNEYAYLKAI IFFDPDAKGL SDPGKIKRLR SQVQVSLEDY 310 320 330 340 350 360 INDRQYDSRG RFGELLLLLP TLQSITWQMI EQIQFIKLFG MAKIDNLLQE MLLGGSPSDA 370 380 390 400 410 420 PHAHHPLHPH LMQEHMGTNV IVANTMPTHL SNGQMSTPET PQPSPPGGSG SEPYKLLPGA 430 440 VATIVKPLSA IPQPTITKQE VI
	Isoform HNF4-Alpha-9. Checksum: DC25511938ED9EF0	FASTA	395	43,988
	10 20 30 40 50 60 MVSVNAPLGA PVESSYDTSP SEGTNLNAPN SLGVSALCAI CGDRATGKHY GASSCDGCKG 70 80 90 100 110 120 FFRRSVRKNH MYSCRFSRQC VVDKDKRNQC RYCRLKKCFR AGMKKEAVQN ERDRISTRRS 130 140 150 160 170 180 SYEDSSLPSI NALLQAEVLS RQITSPVSGI NGDIRAKKIA SIADVCESMK EQLLVLVEWA 190 200 210 220 230 240 KYIPAFCELP LDDQVALLRA HAGEHLLLGA TKRSMVFKDV LLLGNDYIVP RHCPELAEMS 250 260 270 280 290 300 RVSIRILDEL VLPFQELQID DNEYAYLKAI IFFDPDAKGL SDPGKIKRLR SQVQVSLEDY 310 320 330 340 350 360 INDRQYDSRG RFGELLLLLP TLQSITWQMI EQIQFIKLFG MAKIDNLLQE MLLGGPCQAQ 370 380 390 EGRGWSGDSP GDRPHTVSSP LSSLASPLCR FGQVA

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Isolation and characterization of a third isoform of human hepatocyte nuclear factor 4." Kritis A.A., Argyrokastritis A., Moschonas N.K., Power S., Katrakili N., Zannis V.I., Cereghini S., Talianidis I. Gene 173:275-280(1996) [PubMed: 8964514] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS HNF4-ALPHA-1; HNF4-ALPHA-2 AND HNF4-ALPHA-3), VARIANT SER-445. Tissue: Liver.
[2]	"Human hepatocyte nuclear factor 4 isoforms are encoded by distinct and differentially expressed genes." Drewes T., Senkel S., Holewa B., Ryffel G.U. Mol. Cell. Biol. 16:925-931(1996) [PubMed: 8622695] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], ALTERNATIVE SPLICING. Tissue: Kidney.
[3]	"Mutations in the hepatocyte nuclear factor-4alpha gene in maturity-onset diabetes of the young (MODY1)." Yamagata K., Furuta H., Oda N., Kaisaki P.J., Menzel S., Cox N.J., Fajans S.S., Signorini S., Stoffel M., Bell G.I. Nature 384:458-460(1996) [PubMed: 8945471] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[4]	"Variation in P1 and P2 promoter-driven hepatocyte nuclear factor-4a (HNF4a) expression in human tissues: implications for carcinogenesis." Tanaka T., Jiang S., Hotta H., Takano K., Iwanari H., Hirayama Y., Midorikawa Y., Hippo Y., Watanabe A., Yamashita H., Kumakura J., Uchiyama Y., Hasegawa G., Aburatani H., Hamakubo T., Naito M., Sakai J., Kodama T. Submitted (JUL-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA], ALTERNATIVE PROMOTER USAGE (ISOFORMS HNF4-ALPHA-7; HNF4-ALPHA-8 AND HNF4-ALPHA-9).
[5]	"The DNA sequence and comparative analysis of human chromosome 20." Deloukas P., Matthews L.H., Ashurst J.L., Burton J., Gilbert J.G.R., Jones M., Stavrides G., Almeida J.P., Babbage A.K., Bagguley C.L., Bailey J., Barlow K.F., Bates K.N., Beard L.M., Beare D.M., Beasley O.P., Bird C.P., Blakey S.E. , Bridgeman A.M., Brown A.J., Buck D., Burrill W.D., Butler A.P., Carder C., Carter N.P., Chapman J.C., Clamp M., Clark G., Clark L.N., Clark S.Y., Clee C.M., Clegg S., Cobley V.E., Collier R.E., Connor R.E., Corby N.R., Coulson A., Coville G.J., Deadman R., Dhami P.D., Dunn M., Ellington A.G., Frankland J.A., Fraser A., French L., Garner P., Grafham D.V., Griffiths C., Griffiths M.N.D., Gwilliam R., Hall R.E., Hammond S., Harley J.L., Heath P.D., Ho S., Holden J.L., Howden P.J., Huckle E., Hunt A.R., Hunt S.E., Jekosch K., Johnson C.M., Johnson D., Kay M.P., Kimberley A.M., King A., Knights A., Laird G.K., Lawlor S., Lehvaeslaiho M.H., Leversha M.A., Lloyd C., Lloyd D.M., Lovell J.D., Marsh V.L., Martin S.L., McConnachie L.J., McLay K., McMurray A.A., Milne S.A., Mistry D., Moore M.J.F., Mullikin J.C., Nickerson T., Oliver K., Parker A., Patel R., Pearce T.A.V., Peck A.I., Phillimore B.J.C.T., Prathalingam S.R., Plumb R.W., Ramsay H., Rice C.M., Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S., Skuce C.D., Smith M.L., Soderlund C., Steward C.A., Sulston J.E., Swann R.M., Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A., Tracey A., Tromans A.C., Vaudin M., Wall M., Wallis J.M., Whitehead S.L., Whittaker P., Willey D.L., Williams L., Williams S.A., Wilming L., Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S., Rogers J. Nature 414:865-871(2001) [PubMed: 11780052] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	"Cloning and sequencing of cDNAs encoding the human hepatocyte nuclear factor 4 indicate the presence of two isoforms in human liver." Chartier F.L., Bossu J.-P., Laudet V., Fruchart J.-C., Laine B. Gene 147:269-272(1994) [PubMed: 7926813] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 4-474, ALTERNATIVE SPLICING. Tissue: Liver.
[7]	"Recruitment of hepatocyte nuclear factor 4 into specific intranuclear compartments depends on tyrosine phosphorylation that affects its DNA-binding and transactivation potential." Ktistaki E., Ktistakis N.T., Papadogeorgaki E., Talianidis I. Proc. Natl. Acad. Sci. U.S.A. 92:9876-9880(1995) [PubMed: 7568236] [Abstract] Cited for: PHOSPHORYLATION.
[8]	"Structural basis for HNF-4alpha activation by ligand and coactivator binding." Duda K., Chi Y.-I., Shoelson S.E. J. Biol. Chem. 279:23311-23316(2004) [PubMed: 14982928] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 142-378, FATTY ACID BINDING.
[9]	"Organization and partial sequence of the hepatocyte nuclear factor-4-alpha/MODY1 gene and identification of a missense mutation, R127W, in a Japanese family with MODY." Furuta H., Iwasaki N., Oda N., Hinokio Y., Horikawa Y., Yamagata K., Yano N., Sugahiro J., Ogata M., Ohgawara H., Omori Y., Iwamoto Y., Bell G.I. Diabetes 46:1652-1657(1997) [PubMed: 9313765] [Abstract] Cited for: VARIANT MODY1 TRP-136.
[10]	"A missense mutation in the hepatocyte nuclear factor 4 alpha gene in a UK pedigree with maturity-onset diabetes of the young." Bulman M.P., Dronsfield M.J., Frayling T.M., Appleton M., Bain S.C., Ellard S., Hattersley A.T. Diabetologia 40:859-862(1997) [PubMed: 9243109] [Abstract] Cited for: VARIANT MODY1 GLN-285.
[11]	"Studies of the genetic variability of the coding region of the hepatocyte nuclear factor-4alpha in Caucasians with maturity onset NIDDM." Moeller A.M., Urhammer S.A., Dalgaard L.T., Reneland R., Berglund L., Hansen T., Clausen J.O., Lithell H., Pedersen O. Diabetologia 40:980-983(1997) [PubMed: 9267996] [Abstract] Cited for: VARIANT NIDDM MET-264, VARIANT ILE-139.
[12]	"A missense mutation in hepatocyte nuclear factor-4-alpha, resulting in a reduced transactivation activity, in human late-onset non-insulin-dependent diabetes mellitus." Hani E.H., Suaud L., Boutin P., Chevre J.-C., Durand E., Philippi A., Demenais F., Vionnet N., Furuta H., Velho G., Bell G.I., Laine B., Froguel P. J. Clin. Invest. 101:521-526(1998) [PubMed: 9449683] [Abstract] Cited for: VARIANT MODY1 ILE-402.
+	Additional computationally mapped references.

Web resources

GeneReviews

Wikipedia

Hepatocyte nuclear factors entry

Cross-references

Sequence databases

EMBLGenBankDDBJ

X87870 mRNA. Translation: CAA61133.1. Frameshift.
X87871 mRNA. Translation: CAA61134.1. Frameshift.
X87872 mRNA. Translation: CAA61135.1. Frameshift.
Z49825 mRNA. Translation: CAA89989.1.
AY680696 mRNA. Translation: AAT91237.1.
AY680697 mRNA. Translation: AAT91238.1.
AY680698 mRNA. Translation: AAT91239.1.
U72969 , U72959, U72961, U72962, U72963, U72964, U72965, U72966, U72967, U72968 Genomic DNA. Translation: AAB48082.1. Sequence problems.
U72967 , U72959, U72961, U72962, U72963, U72964, U72965, U72966 Genomic DNA. Translation: AAB48083.1.
AL132772 Genomic DNA. Translation: CAC01303.1.
AL132772 Genomic DNA. Translation: CAI18856.1.
X76930 mRNA. Translation: CAA54248.1. Different initiation.

IPI

IPI00013196.
IPI00216080.
IPI00300558.
IPI00412368.
IPI00641248.
IPI00645235.
IPI00847265.

PIR

JC4937.
JC4938.
JC6096.

RefSeq

NP_000448.3.
NP_001025174.1.
NP_001025175.1.
NP_787110.2.
NP_849180.1.
NP_849181.1.

UniGene

Hs.116462

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1PZL	X-ray	2.10	A	142-378	[»]
3CBB	X-ray	2.00	A/B	58-135	[»]

SMR

P41235. Positions 138-369.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP:499N.

IntAct

P41235. 5 interactions.

STRING

P41235.

PTM databases

PhosphoSite

P41235.

Proteomic databases

PRIDE

P41235.

Genome annotation databases

Ensembl

ENST00000316099; ENSP00000312987; ENSG00000101076; Homo sapiens. [Genome view]
ENST00000316673; ENSP00000315180; ENSG00000101076; Homo sapiens. [Genome view]
ENST00000338692; ENSP00000343807; ENSG00000101076; Homo sapiens. [Genome view]
ENST00000372913; ENSP00000362004; ENSG00000101076; Homo sapiens. [Genome view]
ENST00000372920; ENSP00000362011; ENSG00000101076; Homo sapiens. [Genome view]
ENST00000415691; ENSP00000412111; ENSG00000101076; Homo sapiens. [Genome view]
ENST00000430653; ENSP00000400315; ENSG00000101076; Homo sapiens. [Genome view]
ENST00000443598; ENSP00000410911; ENSG00000101076; Homo sapiens. [Genome view]
ENST00000457232; ENSP00000396216; ENSG00000101076; Homo sapiens. [Genome view]

GeneID

3172.

KEGG

hsa:3172.

UCSC

uc002xlt.1. human.
uc002xlu.1. human.
uc002xlv.1. human.
uc002xly.1. human.
uc002xlz.1. human.
uc002xma.1. human.

Organism-specific databases

CTD

3172.

GeneCards

GC20P042463.

H-InvDB

HIX0015837.
HIX0040507.

HGNC

HGNC:5024. HNF4A.

HPA

CAB019417.
HPA004712.

MIM

125850. phenotype.
600281. gene.
606391. phenotype.

Orphanet

552. MODY syndrome.
98800. MODY1.

PharmGKB

PA29349.

GenAtlas

Search...

Phylogenomic databases

HOVERGEN

P41235.

OMA

KIKRMRY.

Enzyme and pathway databases

Pathway_Interaction_DB

hnf3bpathway. FOXA2 and FOXA3 transcription factor networks.
hif1_tfpathway. HIF-1-alpha transcription factor network.
smad2_3nuclearpathway. Regulation of nuclear SMAD2/3 signaling.

Reactome

REACT_13698. Regulation of beta-cell development.

Gene expression databases

ArrayExpress

P41235.

Bgee

P41235.

Genevestigator

P41235.

GermOnline

ENSG00000101076. Homo sapiens.

Family and domain databases

InterPro

IPR008946. Nucl_hormone_rcpt_ligand-bd.
IPR000536. Nucl_hrmn_rcpt_lig-bd_core.
IPR000003. RtnoidX_rcpt.
IPR001723. Str_hrmn_rcpt.
IPR001628. Znf_hrmn_rcpt.
[Graphical view]

Gene3D

G3DSA:1.10.565.10. Nucl_hrmn_rcpt_lig_bd. 1 hit.

Pfam

PF00104. Hormone_recep. 1 hit.
PF00105. zf-C4. 1 hit.
[Graphical view]

PRINTS

PR00545. RETINOIDXR.
PR00398. STRDHORMONER.
PR00047. STROIDFINGER.

ProDom

PD000035. Znf_C4steroid. 1 hit.
[Graphical view] [Entries sharing at least one domain]

SMART

SM00430. HOLI. 1 hit.
SM00399. ZnF_C4. 1 hit.
[Graphical view]

PROSITE

PS00031. NUCLEAR_REC_DBD_1. 1 hit.
PS51030. NUCLEAR_REC_DBD_2. 1 hit.
[Graphical view]

ProtoNet

Search...

Other Resources

NextBio

12578.

SOURCE

Search...

Entry information

Entry name

HNF4A_HUMAN

Accession

Primary (citable) accession number: P41235
Secondary accession number(s): O00659 , O00723, Q14540, Q5QPB8, Q6B4V5, Q6B4V6, Q6B4V7, Q92653, Q92654, Q92655, Q99864, Q9NQH0

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 1, 1995
Last sequence update:	May 29, 2007
Last modified:	November 3, 2009
This is version 120 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

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.