P22361 (HNF1A_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Hepatocyte nuclear factor 1-alpha
Short name=HNF-1-alpha
Short name=HNF-1A

Alternative name(s):
Liver-specific transcription factor LF-B1
Short name=LFB1
Transcription factor 1
Short name=TCF-1

Gene names

Name:	Hnf1a
Synonyms:	Hnf-1, Hnf-1a, Tcf1

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	628 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Transcriptional activator that regulates the tissue specific expression of multiple genes, especially in pancreatic islet cells and in liver. Required for the expression of several liver specific genes. Binds to the inverted palindrome 5'-GTTAATNATTAAC-3'. Ref.7 Ref.9
Subunit structure	Binds DNA as a dimer. Interacts with PCBD1. Heterotetramer with PCBD1; formed by a dimer of dimers. Ref.8 Ref.9 Ref.10
Subcellular location	Nucleus.
Tissue specificity	Liver.
Disruption phenotype	Mice are born at less than half of the expected frequency. Neonates are slightly smaller than normal and do not grow normally. After 5 weeks mice weigh only 50 to 60% as much as their littermates. Mice develop non-insulin-dependent diabetes mellitus (NIDDM) 2 weeks after birth. Mice exhibit elevated levels of blood glucose, combined with reduced blood levels of insulin and insulin-like growth factor I (IGFI). Males and females are sterile. Ref.4
Sequence similarities	Belongs to the HNF1 homeobox family. Contains 1 homeobox DNA-binding domain.

Ontologies

Keywords
Biological process	Transcription Transcription regulation
Cellular component	Nucleus
Domain	Homeobox
Ligand	DNA-binding
Molecular function	Activator
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	SMAD protein signal transduction Inferred from direct assay PubMed 9420335. Source: MGI bile acid and bile salt transport Inferred from mutant phenotype PubMed 11279518. Source: MGI bile acid biosynthetic process Inferred from mutant phenotype PubMed 11279518. Source: MGI blastocyst development Inferred from mutant phenotype PubMed 16880268. Source: MGI bone resorption Inferred from genetic interaction PubMed 15866165. Source: MGI cholesterol metabolic process Inferred from mutant phenotype PubMed 11279518. Source: MGI chromatin remodeling Inferred from mutant phenotype PubMed 12367519. Source: UniProtKB embryonic limb morphogenesis Inferred from genetic interaction PubMed 10090727. Source: MGI endocrine pancreas development Inferred from mutant phenotype PubMed 9609100. Source: MGI fatty acid biosynthetic process Inferred from mutant phenotype PubMed 10852923. Source: MGI fatty acid transport Inferred from mutant phenotype PubMed 10852923. Source: MGI glucose homeostasis Inferred from direct assay PubMed 11269503. Source: UniProtKB glucose import Inferred from direct assay PubMed 11269503. Source: UniProtKB heme biosynthetic process Inferred from mutant phenotype PubMed 10617683. Source: MGI insulin secretion Inferred from mutant phenotype PubMed 15142986PubMed 9593777PubMed 9733737. Source: MGI liver development Inferred from mutant phenotype Ref.4. Source: MGI negative regulation of transcription from RNA polymerase II promoter Inferred from electronic annotation. Source: Compara paraxial mesoderm formation Inferred from genetic interaction PubMed 10090727. Source: MGI placenta development Inferred from genetic interaction PubMed 10090727. Source: MGI positive regulation of transcription from RNA polymerase II promoter Inferred from direct assay PubMed 15581617. Source: MGI positive regulation of transcription initiation from RNA polymerase II promoter Inferred from electronic annotation. Source: Compara protein localization Inferred from mutant phenotype PubMed 16880268. Source: MGI regulation of Wnt receptor signaling pathway Inferred from genetic interaction PubMed 10090727. Source: MGI regulation of insulin secretion Inferred from mutant phenotype Ref.4. Source: MGI renal glucose absorption Inferred from direct assay PubMed 11269503. Source: UniProtKB reproductive structure development Inferred from mutant phenotype Ref.4. Source: MGI response to glucose stimulus Inferred from mutant phenotype PubMed 9733737. Source: MGI response to oxidative stress Inferred from mutant phenotype PubMed 10617683. Source: MGI reverse cholesterol transport Inferred from mutant phenotype PubMed 15793583. Source: MGI
Cellular_component	cytoplasm Inferred from direct assay PubMed 16880268. Source: MGI photoreceptor outer segment Inferred from genetic interaction PubMed 10090727. Source: MGI pronucleus Inferred from direct assay PubMed 16880268. Source: MGI transcription factor complex Inferred from physical interaction PubMed 14570708. Source: MGI
Molecular_function	RNA polymerase II core promoter proximal region sequence-specific DNA binding transcription factor activity involved in positive regulation of transcription Inferred from electronic annotation. Source: Compara double-stranded DNA binding Inferred from electronic annotation. Source: Compara sequence-specific DNA binding Inferred from electronic annotation. Source: Compara sequence-specific DNA binding transcription factor activity Inferred from direct assay PubMed 12367519. Source: UniProtKB transcription regulatory region DNA binding Inferred from sequence or structural similarity. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
Sirt1	Q923E4	5	EBI-5272860,EBI-1802585

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 628

628

Hepatocyte nuclear factor 1-alpha

PRO_0000049116

Regions

DNA binding

199 – 279

81

Homeobox; HNF1-type

Region

1 – 31

31

Dimerization

Region

130 – 132

3

Interaction with DNA By similarity

Region

143 – 149

7

Interaction with DNA By similarity

Region

155 – 158

4

Interaction with DNA By similarity

Region

203 – 206

4

Interaction with DNA By similarity

Region

263 – 265

3

Interaction with DNA By similarity

Region

270 – 273

4

Interaction with DNA By similarity

Motif

197 – 205

9

Nuclear localization signal Potential

Compositional bias

71 – 80

10

Asp/Glu-rich (acidic; potential involvement with transcription)

Amino acid modifications

Modified residue

74

1

Phosphothreonine Ref.5

Modified residue

247

1

Phosphoserine Ref.6

Experimental info

Sequence conflict

89

1

L → P in AAA37821. Ref.1

Secondary structure

1

.

.

.

.

.

628

Helix Strand Turn

Details...

Helix

4 – 18

15

Helix

23 – 30

8

Sequences

	Sequence		Length	Mass (Da)
	P22361 [UniParc]. Last modified July 27, 2011. Version 2. Checksum: 737920D47BA1F081	FASTA	628	67,253
	10 20 30 40 50 60 MVSKLSQLQT ELLAALLESG LSKEALIQAL GEPGPYLMVG EGPLDKGESC GGSRGDLTEL 70 80 90 100 110 120 PNGLGETRGS EDDTDDDGED FAPPILKELE NLSPEEAAHQ KAVVESLLQE DPWRVAKMVK 130 140 150 160 170 180 SYLQQHNIPQ REVVDTTGLN QSHLSQHLNK GTPMKTQKRA ALYTWYVRKQ REVAQQFTHA 190 200 210 220 230 240 GQGGLIEEPT GDELPTKKGR RNRFKWGPAS QQILFQAYER QKNPSKEERE TLVEECNRAE 250 260 270 280 290 300 CIQRGVSPSQ AQGLGSNLVT EVRVYNWFAN RRKEEAFRHK LAMDTYNGPP PGPGPGPALP 310 320 330 340 350 360 AHSSPGLPTT TLSPSKVHGV RYGQSATSEA AEVPSSSGGP LVTVSAALHQ VSPTGLEPSS 370 380 390 400 410 420 LLSTEAKLVS ATGGPLPPVS TLTALHSLEQ TSPGLNQQPQ NLIMASLPGV MTIGPGEPAS 430 440 450 460 470 480 LGPTFTNTGA STLVIGLAST QAQSVPVINS MGSSLTTLQP VQFSQPLHPS YQQPLMPPVQ 490 500 510 520 530 540 SHVAQSPFMA TMAQLQSPHA LYSHKPEVAQ YTHTSLLPQT MLITDTNLST LASLTPTKQV 550 560 570 580 590 600 FTSDTEASSE PGLHEPPSPA TTIHIPSQDP SNIQHLQPAH RLSTSPTVSS SSLVLYQSSD 610 620 SNGHSHLLPS NHSVIETFIS TQMASSSQ

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Molecular cloning, functional expression, and chromosomal localization of mouse hepatocyte nuclear factor 1." Kuo C.J., Conley P.B., Hsieh C.L., Francke U., Crabtree G.R. Proc. Natl. Acad. Sci. U.S.A. 87:9838-9842(1990) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: C57BL/6J.
[3]	"Structure of the gene encoding hepatocyte nuclear factor 1 (HNF1)." Bach I., Pontoglio M., Yaniv M. Nucleic Acids Res. 20:4199-4204(1992) [PubMed] [Europe PMC] [Abstract] Cited for: GENE STRUCTURE.
[4]	"Laron dwarfism and non-insulin-dependent diabetes mellitus in the Hnf-1alpha knockout mouse." Lee Y.H., Sauer B., Gonzalez F.J. Mol. Cell. Biol. 18:3059-3068(1998) [PubMed] [Europe PMC] [Abstract] Cited for: DISRUPTION PHENOTYPE.
[5]	"Protein phosphorylation and expression profiling by Yin-yang multidimensional liquid chromatography (Yin-yang MDLC) mass spectrometry." Dai J., Jin W.-H., Sheng Q.-H., Shieh C.-H., Wu J.-R., Zeng R. J. Proteome Res. 6:250-262(2007) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-74, MASS SPECTROMETRY. Tissue: Liver.
[6]	"Specific phosphopeptide enrichment with immobilized titanium ion affinity chromatography adsorbent for phosphoproteome analysis." Zhou H., Ye M., Dong J., Han G., Jiang X., Wu R., Zou H. J. Proteome Res. 7:3957-3967(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-247, MASS SPECTROMETRY. Tissue: Liver.
[7]	"Hnf1alpha (MODY3) controls tissue-specific transcriptional programs and exerts opposed effects on cell growth in pancreatic islets and liver." Servitja J.M., Pignatelli M., Maestro M.A., Cardalda C., Boj S.F., Lozano J., Blanco E., Lafuente A., McCarthy M.I., Sumoy L., Guigo R., Ferrer J. Mol. Cell. Biol. 29:2945-2959(2009) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[8]	"High-resolution structure of the HNF-1alpha dimerization domain." Rose R.B., Endrizzi J.A., Cronk J.D., Holton J., Alber T. Biochemistry 39:15062-15070(2000) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.0 ANGSTROMS) OF 1-32, SUBUNIT.
[9]	"Structural basis of dimerization, coactivator recognition and MODY3 mutations in HNF-1alpha." Rose R.B., Bayle J.H., Endrizzi J.A., Cronk J.D., Crabtree G.R., Alber T. Nat. Struct. Biol. 7:744-748(2000) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 1-32 IN COMPLEX WITH PCBD1, SUBUNIT, FUNCTION.
[10]	"The dimerization domain of HNF-1alpha: structure and plasticity of an intertwined four-helix bundle with application to diabetes mellitus." Narayana N., Hua Q., Weiss M.A. J. Mol. Biol. 310:635-658(2001) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) OF 2-32, SUBUNIT.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

M57966 mRNA. Translation: AAA37821.1.
AC116500 Genomic DNA. No translation available.

IPI

IPI00127366.

PIR

A39262.

RefSeq

NP_033353.2. NM_009327.3.

UniGene

Mm.332607.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1F93	X-ray	2.60	E/F/G/H	1-32	[»]
1G2Y	X-ray	1.00	A/B/C/D	1-32	[»]
1G2Z	X-ray	1.15	A/B	1-32	[»]
1G39	X-ray	1.22	A/B/C/D	1-32	[»]
1JB6	X-ray	1.70	A/B	2-32	[»]

ProteinModelPortal

P22361.

SMR

P22361. Positions 2-31, 85-286.

ModBase

Search...

Protein-protein interaction databases

IntAct

P22361. 1 interaction.

STRING

10090.ENSMUSP00000031535.

PTM databases

PhosphoSite

P22361.

Proteomic databases

PaxDb

P22361.

PRIDE

P22361.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENSMUST00000031535; ENSMUSP00000031535; ENSMUSG00000029556.

GeneID

21405.

KEGG

mmu:21405.

Organism-specific databases

CTD

6927.

MGI

MGI:98504. Hnf1a.

Phylogenomic databases

eggNOG

NOG79356.

GeneTree

ENSGT00530000063140.

HOGENOM

HOG000015305.

HOVERGEN

HBG005980.

InParanoid

P22361.

KO

K08036.

OMA

TTIHIPS.

OrthoDB

EOG4WH8M1.

Gene expression databases

ArrayExpress

P22361.

Bgee

P22361.

CleanEx

MM_HNF1A.

Genevestigator

P22361.

GermOnline

ENSMUSG00000029556. Mus musculus.

Family and domain databases

Gene3D

1.10.10.60. 1 hit.
1.10.260.40. 1 hit.

InterPro

IPR006899. HNF-1_N.
IPR023219. HNF1_dimer_dom.
IPR006898. HNF1a_C.
IPR006897. HNF1b_C.
IPR001356. Homeodomain.
IPR009057. Homeodomain-like.
IPR010982. Lambda_DNA-bd_dom.
[Graphical view]

Pfam

PF04814. HNF-1_N. 1 hit.
PF04813. HNF-1A_C. 1 hit.
PF04812. HNF-1B_C. 1 hit.
PF00046. Homeobox. 1 hit.
[Graphical view]

SMART

SM00389. HOX. 1 hit.
[Graphical view]

SUPFAM

SSF100957. HNF1_dimer_dom. 1 hit.
SSF46689. Homeodomain_like. 1 hit.
SSF47413. Lambda_like_DNA. 1 hit.

PROSITE

PS00027. HOMEOBOX_1. 1 hit.
PS50071. HOMEOBOX_2. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

P22361.

NextBio

300672.

SOURCE

Search...

Entry information

Entry name

HNF1A_MOUSE

Accession

Primary (citable) accession number: P22361
Secondary accession number(s): E9QP86

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 1, 1991
Last sequence update:	July 27, 2011
Last modified:	May 1, 2013
This is version 136 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program