Reviewed, UniProtKB/Swiss-Prot P20823 (HNF1A_HUMAN)

Names and origin

Protein names

Recommended name:
    Hepatocyte nuclear factor 1-alpha
      Short name=HNF-1A
Alternative name(s):
    Liver-specific transcription factor LF-B1
      Short name=LFB1
      Short name=Transcription factor 1
      Short name=TCF-1

Gene names

Name:	HNF1A
Synonyms:	TCF1

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

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

Protein attributes

Sequence length	631 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Required for the expression of several liver specific genes. Binds to the inverted palindrome 5'-GTTAATNATTAAC-3'.
Subunit structure	Binds DNA as a dimer.
Subcellular location	Nucleus.
Tissue specificity	Liver.
Polymorphism	The Ala-98/Val-98 polymorphism is associated with a reduction in glucose-induced serum C-peptide and insulin responses.
Involvement in disease	Defects in HNF1A may predispose to hepatic adenomas [MIM:142330]. Hepatic adenomas are benign tumors at risk of malignant transformation. Bi-allelic inactivation of HNF1A, whether sporadic or associated with MODY3, may be an early step in the developmant of some hepatocellular carcinomas. Defects in HNF1A are the cause of maturity onset diabetes of the young type 3 (MODY3) [MIM:600496]; also symbolized MODY-3. MODY [MIM:606391] is a form of diabetes characterized by an autosomal dominant mode of inheritance, age of onset of 25 years or younger and a primary defect in insulin secretion. The clinical phenotype of MODY3 is characterized by severe insulin secretory defects, and by major hyperglycemia associated with microvascular complications. Ref.3 Ref.5 Ref.6 Ref.9 Ref.10 Ref.11 Ref.12 Ref.15 Ref.17 Ref.19 Ref.21 Ref.22 Ref.24 Ref.25 Defects in HNF1A are a cause of susceptibility to insulin-dependent diabetes mellitus (IDDM) [MIM:222100]. Ref.8 Ref.18 Ref.23
Sequence similarities	Belongs to the HNF1 homeobox family. Contains 1 homeobox DNA-binding domain.

Ontologies

Keywords
Biological process	Transcription Transcription regulation
Cellular component	Nucleus
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Diabetes mellitus Disease mutation
Domain	Homeobox
Ligand	DNA-binding
Molecular function	Activator
PTM	Phosphoprotein
Technical term	3D-structure
Gene Ontology (GO)
Biological process	glucose homeostasis Inferred from mutant phenotype. Source: UniProtKB positive regulation of transcription, DNA-dependent Inferred from direct assay. Source: UniProtKB regulation of specific transcription from RNA polymerase II promoter Inferred from direct assay. Source: UniProtKB transcription Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	nucleus Inferred from electronic annotation. Source: UniProtKB-SubCell protein complex Inferred from direct assay. Source: UniProtKB
Molecular function	RNA polymerase II transcription factor activity Inferred from direct assay. Source: UniProtKB promoter binding Inferred from direct assay. Source: UniProtKB protein binding Inferred from physical interaction. Source: UniProtKB transcription activator activity Inferred from electronic annotation. Source: InterPro transcription factor activity Inferred from direct assay. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
CALM1	P62158	1	EBI-636034,EBI-397435
DYRK1B	Q9Y463	3	EBI-636034,EBI-634187
PCBD1	P61457	1	EBI-636034,EBI-740475
PCBD2	Q9H0N5	1	EBI-636034,EBI-634289
RHPN2	Q8IUC4	1	EBI-636034,EBI-1043535
SNRPA1	P09661	1	EBI-636034,EBI-876439

Alternative products

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

Isoform A (identifier: P20823-1)

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 B (identifier: P20823-2)

The sequence of this isoform differs from the canonical sequence as follows:
     501-542: ALYSHKPEVA...LASLTPTKQV → GEHPVPHTAG...ACVSGTSVFP
     543-601: Missing.

Isoform C (identifier: P20823-3)

The sequence of this isoform differs from the canonical sequence as follows:
     438-494: LASTQAQSVP...TQSPFMATMA → KLVGMGGHLG...SHCATSVIPG
     495-601: Missing.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 631

631

Hepatocyte nuclear factor 1-alpha

PRO_0000049115

Regions

DNA binding

199 – 279

81

Homeobox; HNF1-type

Region

1 – 31

31

Dimerization

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 By similarity

Modified residue

247

1

Phosphoserine By similarity

Natural variations

Alternative sequence

438 – 494

57

LASTQ…MATMA → KLVGMGGHLGGRLMGQPQNP GAGRATGTHSFIHSFIQHVF IQCLLWTSHCATSVIPG in isoform C.

VSP_002252

Alternative sequence

495 – 601

107

Missing in isoform C.

VSP_002253

Alternative sequence

501 – 542

42

ALYSH…PTKQV → GEHPVPHTAGDDDRGWLSMD AGERGAWQALQSACVSGTSV FP in isoform B.

VSP_002250

Alternative sequence

543 – 601

59

Missing in isoform B.

VSP_002251

Natural variant

12

1

L → H in MODY3. Ref.6 Ref.21

VAR_010537

Natural variant

20

1

G → R in MODY3. Ref.24

VAR_012483

Natural variant

27

1

I → L: dbSNP rs1169288. Ref.4 Ref.7 Ref.13 Ref.14 Ref.16 Ref.20

VAR_007905

Natural variant

31

1

G → D in MODY3. Ref.17

VAR_010538

Natural variant

48

1

E → K in IDDM. Ref.18

VAR_010539

Natural variant

98

1

A → V: dbSNP rs1800574. Ref.13 Ref.14

VAR_010540

Natural variant

107

1

L → R in MODY3. Ref.5

VAR_010541

Natural variant

117

1

K → E in MODY3. Ref.22

VAR_010542

Natural variant

122

1

Y → C in MODY3. Ref.15

VAR_003756

Natural variant

127

1

N → Y in a hepatocellular carcinoma sample; somatic mutation. Ref.27

VAR_033088

Natural variant

128

1

I → N in MODY3. Ref.12

VAR_010543

Natural variant

129

1

P → T in MODY3. Ref.11

VAR_010544

Natural variant

131

1

R → Q in MODY3. Ref.5 Ref.6 Ref.10 Ref.11

VAR_010545

Natural variant

131

1

R → W in MODY3. Ref.5 Ref.6 Ref.10 Ref.11

VAR_010546

Natural variant

133

1

V → M in MODY3.

VAR_010547

Natural variant

142

1

S → F in MODY3. Ref.15

VAR_003757

Natural variant

143

1

H → Y in MODY3. Ref.12 Ref.22

VAR_010548

Natural variant

158

1

K → N in MODY3. Ref.21

VAR_010549

Natural variant

159

1

R → Q in MODY3. Ref.11 Ref.15 Ref.17 Ref.21

VAR_003758

Natural variant

159

1

R → W in MODY3. Ref.11 Ref.15 Ref.17 Ref.21

VAR_010550

Natural variant

161

1

A → T in MODY3. Ref.17

VAR_010551

Natural variant

165

1

W → C in a hepatocellular carcinoma sample; somatic mutation. Ref.27

VAR_033089

Natural variant

191

1

G → D in late-onset NIDDM. Ref.6

VAR_010552

Natural variant

200

1

R → W in MODY3. Ref.17

VAR_010553

Natural variant

203

1

R → C in MODY3. Ref.21 Ref.24

VAR_010554

Natural variant

203

1

R → H in MODY3. Ref.21 Ref.24

VAR_012484

Natural variant

205

1

K → Q in MODY3. Ref.6

VAR_010555

Natural variant

206

1

W → C in a hepatic adenoma sample; somatic mutation. Ref.27

VAR_033090

Natural variant

206

1

W → L in a hepatic adenoma sample; somatic mutation. Ref.27

VAR_033091

Natural variant

229

1

R → Q in MODY3. Ref.10

VAR_010556

Natural variant

237

1

N → S in a hepatic multiple adenoma sample; somatic mutation. Ref.27

VAR_033092

Natural variant

241

1

C → G in MODY3 and IDDM.

VAR_010557

Natural variant

244

1

R → G in a hepatic adenoma sample; somatic mutation. Ref.27

VAR_033093

Natural variant

250

1

Q → P in a hepatocellular carcinoma sample; somatic mutation. Ref.27

VAR_033094

Natural variant

254

1

L → M in late-onset NIDDM; low penetrance; could be a rare polymorphism. Ref.7

VAR_010558

Natural variant

259

1

V → D in MODY3.

VAR_010559

Natural variant

260

1

T → M in MODY3. Ref.5

VAR_010560

Natural variant

263

1

R → C in MODY3. Ref.6

VAR_010561

Natural variant

268

1

F → C in a hepatic adenoma sample; somatic mutation. Ref.27

VAR_033095

Natural variant

271

1

R → W in MODY3. Ref.17

VAR_010562

Natural variant

272

1

R → C in NIDDM. Ref.23

VAR_010563

Natural variant

272

1

R → H in IDDM and MODY3.

VAR_003759

Natural variant

273

1

K → E in a hepatic adenoma sample; somatic mutation. Ref.27 Ref.28

VAR_033096

Natural variant

319

1

G → S Strong association with NIDDM susceptibility; unique to the Canadian Oji-Cree population. Ref.26

VAR_010564

Natural variant

415

1

G → R in IDDM; loss of function. Ref.23

VAR_010565

Natural variant

432

1

S → C in MODY3. Ref.24

VAR_012485

Natural variant

447

1

P → L in MODY3. Ref.3 Ref.12

VAR_003760

Natural variant

487

1

S → N: dbSNP rs2464196. Ref.7 Ref.13 Ref.14 Ref.16 Ref.20

VAR_007906

Natural variant

514

1

H → R Ref.16

VAR_010566

Natural variant

519

1

P → L in MODY3. Ref.11

VAR_010567

Natural variant

537

1

T → R in MODY3; incomplete penetrance. Ref.19

VAR_010568

Natural variant

574

1

G → S in a black African with an atypical form of diabetes; also in an individual with hepatic adenoma and familial early-onset diabetes. dbSNP rs1169305. Ref.9 Ref.27

VAR_010569

Natural variant

583

1

R → G in IDDM. Ref.8

VAR_003761

Natural variant

583

1

R → Q in late-onset NIDDM; also in an individual with hepatic hyperplasia and familial early-onset diabetes. Ref.8 Ref.14 Ref.27

VAR_010570

Natural variant

594

1

S → I in MODY3.

VAR_010571

Natural variant

618

1

I → M in MODY3. Ref.24

VAR_012486

Natural variant

619

1

E → K in MODY3. Ref.19

VAR_010572

Natural variant

620

1

T → I in MODY3; incomplete penetrance. Ref.11 Ref.25

VAR_010573

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

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631

Helix Strand Turn

Details...

Helix

94 – 107

14

Helix

112 – 125

14

Helix

130 – 137

8

Helix

141 – 149

9

Helix

156 – 169

14

Turn

170 – 173

4

Helix

174 – 177

4

Helix

208 – 221

14

Turn

226 – 229

4

Helix

230 – 243

14

Helix

255 – 257

3

Helix

261 – 274

14

Sequences

	Sequence		Length	Mass (Da)
	Isoform A [UniParc]. Last modified August 16, 2004. Version 2. Checksum: 8327CD4FDC39254A	FASTA	631	67,356
	10 20 30 40 50 60 MVSKLSQLQT ELLAALLESG LSKEALIQAL GEPGPYLLAG EGPLDKGESC GGGRGELAEL 70 80 90 100 110 120 PNGLGETRGS EDETDDDGED FTPPILKELE NLSPEEAAHQ KAVVETLLQE 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 LAMDTYSGPP PGPGPGPALP 310 320 330 340 350 360 AHSSPGLPPP ALSPSKVHGV RYGQPATSET AEVPSSSGGP LVTVSTPLHQ VSPTGLEPSH 370 380 390 400 410 420 SLLSTEAKLV SAAGGPLPPV STLTALHSLE QTSPGLNQQP QNLIMASLPG VMTIGPGEPA 430 440 450 460 470 480 SLGPTFTNTG ASTLVIGLAS TQAQSVPVIN SMGSSLTTLQ PVQFSQPLHP SYQQPLMPPV 490 500 510 520 530 540 QSHVTQSPFM ATMAQLQSPH ALYSHKPEVA QYTHTGLLPQ TMLITDTTNL SALASLTPTK 550 560 570 580 590 600 QVFTSDTEAS SESGLHTPAS QATTLHVPSQ DPAGIQHLQP AHRLSASPTV SSSSLVLYQS 610 620 630 SDSSNGQSHL LPSNHSVIET FISTQMASSS Q
	Isoform B. Checksum: E9BD79E885C2E3C0	FASTA	572	61,112
	10 20 30 40 50 60 MVSKLSQLQT ELLAALLESG LSKEALIQAL GEPGPYLLAG EGPLDKGESC GGGRGELAEL 70 80 90 100 110 120 PNGLGETRGS EDETDDDGED FTPPILKELE NLSPEEAAHQ KAVVETLLQE 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 LAMDTYSGPP PGPGPGPALP 310 320 330 340 350 360 AHSSPGLPPP ALSPSKVHGV RYGQPATSET AEVPSSSGGP LVTVSTPLHQ VSPTGLEPSH 370 380 390 400 410 420 SLLSTEAKLV SAAGGPLPPV STLTALHSLE QTSPGLNQQP QNLIMASLPG VMTIGPGEPA 430 440 450 460 470 480 SLGPTFTNTG ASTLVIGLAS TQAQSVPVIN SMGSSLTTLQ PVQFSQPLHP SYQQPLMPPV 490 500 510 520 530 540 QSHVTQSPFM ATMAQLQSPH GEHPVPHTAG DDDRGWLSMD AGERGAWQAL QSACVSGTSV 550 560 570 FPDSSNGQSH LLPSNHSVIE TFISTQMASS SQ
	Isoform C. Checksum: F6855702DE665780	FASTA	524	55,930
	10 20 30 40 50 60 MVSKLSQLQT ELLAALLESG LSKEALIQAL GEPGPYLLAG EGPLDKGESC GGGRGELAEL 70 80 90 100 110 120 PNGLGETRGS EDETDDDGED FTPPILKELE NLSPEEAAHQ KAVVETLLQE 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 LAMDTYSGPP PGPGPGPALP 310 320 330 340 350 360 AHSSPGLPPP ALSPSKVHGV RYGQPATSET AEVPSSSGGP LVTVSTPLHQ VSPTGLEPSH 370 380 390 400 410 420 SLLSTEAKLV SAAGGPLPPV STLTALHSLE QTSPGLNQQP QNLIMASLPG VMTIGPGEPA 430 440 450 460 470 480 SLGPTFTNTG ASTLVIGKLV GMGGHLGGRL MGQPQNPGAG RATGTHSFIH SFIQHVFIQC 490 500 510 520 LLWTSHCATS VIPGDSSNGQ SHLLPSNHSV IETFISTQMA SSSQ

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning of human hepatic nuclear factor 1 (HNF1) and chromosomal localization of its gene in man and mouse." Bach I., Galcheva-Gargova Z., Mattei M.-G., Simon-Chazottes D., Guenet J.-L., Cereghini S., Yaniv M. Genomics 8:155-164(1990) [PubMed: 1707031] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Liver.
[2]	"More potent transcriptional activators or a transdominant inhibitor of the HNF1 homeoprotein family are generated by alternative RNA processing." Bach I., Yaniv M. EMBO J. 12:4229-4242(1993) [PubMed: 7900999] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Liver.
[3]	"Mutations in the hepatocyte nuclear factor-1alpha gene in maturity-onset diabetes of the young (MODY3)." Yamagata K., Oda N., Kaisaki P.J., Menzel S., Furuta H., Vaxillaire M., Southam L., Cox R.D., Lathrop G.M., Boriraj V.V., Chen X., Cox N.J., Oda Y., Yano H., le Beau M.M., Yamada S., Nishigori H., Takeda J. , Fajans S.S., Hattersley A.T., Iwasaki N., Hansen T., Pedersen O., Polonsky K.S., Turner R.C., Velho G., Chevre J.-C., Froguel P., Bell G.I. Nature 384:455-458(1996) [PubMed: 8945470] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT MODY3 LEU-447.
[4]	"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], VARIANT LEU-27. Tissue: Liver.
[5]	"Novel mutations and a mutational hotspot in the MODY3 gene." Glucksmann M.A., Lehto M., Tayber O., Scotti S., Berkemeier L., Pulido J.C., Wu Y., Nir W.-J., Fang L., Markel P., Munnelly K.D., Goranson J., Orho M., Young B.M., Whitacre J.L., McMenimen C., Wantman M., Tuomi T. , Warram J., Forsblom C.M., Carlsson M., Rosenzweig J., Kennedy G., Duyk G.M., Krolewski A.S., Groop L.C., Thomas J.D. Diabetes 46:1081-1086(1997) [PubMed: 9166684] [Abstract] Cited for: VARIANTS MODY3 ARG-107; TRP-131; MET-260 AND HIS-272.
[6]	"Mutations in the hepatocyte nuclear factor-1alpha/MODY3 gene in Japanese subjects with early- and late-onset NIDDM." Iwasaki N., Oda N., Ogata M., Hara M., Hinokio Y., Oda Y., Yamagata K., Kanematsu S., Ohgawara H., Omori Y., Bell G.I. Diabetes 46:1504-1508(1997) [PubMed: 9287053] [Abstract] Cited for: VARIANTS MODY3 HIS-12; GLN-131; GLN-205 AND CYS-263, VARIANT NIDDM ASP-191.
[7]	"Mutations in the hepatocyte nuclear factor-1alpha gene (MODY3) are not a major cause of late-onset NIDDM in Japanese subjects." Yamada S., Nishigori H., Onda H., Takahashi K., Kitano N., Morikawa A., Takeuchi T., Takeda J. Diabetes 46:1512-1513(1997) [PubMed: 9287055] [Abstract] Cited for: VARIANT NIDDM MET-254, VARIANTS LEU-27 AND ASN-487.
[8]	"Identification of mutations in the hepatocyte nuclear factor (HNF)-1-alpha gene in Japanese subjects with IDDM." Yamada S., Nishigori H., Onda H., Utsugi T., Yanagawa T., Maruyama T., Onigata K., Nagashima K., Nagai R., Morikawa A., Takeuchi T., Takeda J. Diabetes 46:1643-1647(1997) [PubMed: 9313763] [Abstract] Cited for: VARIANTS IDDM HIS-272 AND GLY-583.
[9]	"An automated fluorescent single-strand conformation polymorphism technique for screening mutations in the hepatocyte nuclear factor-1alpha gene (maturity-onset diabetes of the young)." Boutin P., Chevre J.-C., Hani E.H., Gomis R., Pardini V.C., Guillausseau P.-J., Vaxillaire M., Velho G., Froguel P. Diabetes 46:2108-2109(1997) [PubMed: 9392505] [Abstract] Cited for: VARIANTS MODY3, VARIANT ATYPICAL DIABETES SER-574.
[10]	"Mutations in the hepatocyte nuclear factor-1alpha gene in MODY and early-onset NIDDM: evidence for a mutational hotspot in exon 4." Kaisaki P.J., Menzel S., Lindner T., Oda N., Rjasanowski I., Sahm J., Meincke G., Schulze J., Schmechel H., Petzold C., Ledermann H.M., Sachse G., Boriraj V.V., Menzel R., Kerner W., Turner R.C., Yamagata K., Bell G.I. Diabetes 46:528-535(1997) [PubMed: 9032114] [Abstract] Cited for: VARIANTS MODY3 GLN-131; GLN-229; GLY-241 AND HIS-272.
[11]	"Mutations in the hepatocyte nuclear factor-1alpha gene are a common cause of maturity-onset diabetes of the young in the U.K." Frayling T.M., Bulman M.P., Ellard S., Appleton M., Dronsfield M.J., Mackie A.D., Baird J.D., Kaisaki P.J., Yamagata K., Bell G.I., Bain S.C., Hattersley A.T. Diabetes 46:720-725(1997) [PubMed: 9075818] [Abstract] Cited for: VARIANTS MODY3 THR-129; TRP-131; TRP-159; LEU-519 AND ILE-620.
[12]	"Novel MODY3 mutations in the hepatocyte nuclear factor-1alpha gene: evidence for a hyperexcitability of pancreatic beta-cells to intravenous secretagogues in a glucose-tolerant carrier of a P447L mutation." Hansen T., Eiberg H., Rouard M., Vaxillaire M., Moeller A.M., Rasmussen S.K., Fridberg M., Urhammer S.A., Holst J.J., Almind K., Echwald S.M., Hansen L., Bell G.I., Pedersen O. Diabetes 46:726-730(1997) [PubMed: 9075819] [Abstract] Cited for: VARIANTS MODY3 ASN-128; TYR-143 AND LEU-447.
[13]	"A prevalent amino acid polymorphism at codon 98 in the hepatocyte nuclear factor-1alpha gene is associated with reduced serum C-peptide and insulin responses to an oral glucose challenge." Urhammer S.A., Fridberg M., Hansen T., Rasmussen S.K., Moeller A.M., Clausen J.O., Pedersen O. Diabetes 46:912-916(1997) [PubMed: 9133564] [Abstract] Cited for: VARIANTS LEU-27; VAL-98 AND ASN-487.
[14]	"Genetic variation in the hepatocyte nuclear factor-1 alpha gene in Danish Caucasians with late-onset NIDDM." Urhammer S.A., Rasmussen S.K., Kaisaki P.J., Oda N., Yamagata K., Moeller A.M., Fridberg M., Hansen L., Hansen T., Bell G.I., Pedersen O. Diabetologia 40:473-475(1997) [PubMed: 9112026] [Abstract] Cited for: VARIANT NIDDM GLN-583, VARIANTS LEU-27; VAL-98 AND ASN-487.
[15]	"Identification of nine novel mutations in the hepatocyte nuclear factor 1 alpha gene associated with maturity-onset diabetes of the young (MODY3)." Vaxillaire M., Rouard M., Yamagata K., Oda N., Kaisaki P.J., Boriraj V.V., Chevre J.-C., Boccio V., Cox R.D., Lathrop G.M., Dussoix P., Philippe J., Timsit J., Charpentier G., Velho G., Bell G.I., Froguel P. Hum. Mol. Genet. 6:583-586(1997) [PubMed: 9097962] [Abstract] Cited for: VARIANTS MODY3 CYS-122; PHE-142 AND GLN-159.
[16]	"Hepatocyte nuclear factor 1alpha coding mutations are an uncommon contributor to early-onset type 2 diabetes in Ashkenazi Jews." Behn P.S., Wasson J., Chayen S., Smolovitch I., Thomas J.D., Glaser B., Permutt M.A. Diabetes 47:967-969(1998) [PubMed: 9604876] [Abstract] Cited for: VARIANTS LEU-27; ASN-487 AND ARG-514.
[17]	"Mutation screening in 18 Caucasian families suggest the existence of other MODY genes." Chevre J.-C., Hani E.H., Boutin P., Vaxillaire M., Blanche H., Vionnet N., Pardini V.C., Timsit J., Larger E., Charpentier G., Beckers D., Maes M., Bellanne-Chantelot C., Velho G., Froguel P. Diabetologia 41:1017-1023(1998) [PubMed: 9754819] [Abstract] Cited for: VARIANTS MODY3 ASP-31; TRP-159; THR-161; TRP-200 AND TRP-271.
[18]	"Mutations in the hepatocyte nuclear factor-1alpha gene in Caucasian families originally classified as having type I diabetes." Moeller A.M., Dalgaard L.T., Pociot F., Nerup J., Hansen T., Pedersen O. Diabetologia 41:1528-1531(1998) [PubMed: 9867222] [Abstract] Cited for: VARIANTS IDDM LYS-48 AND GLY-241.
[19]	"Linkage and molecular scanning analyses of MODY3/hepatocyte nuclear factor-1 alpha gene in typical familial type 2 diabetes: evidence for novel mutations in exons 8 and 10." Elbein S.C., Teng K., Yount P., Scroggin E. J. Clin. Endocrinol. Metab. 83:2059-2065(1998) [PubMed: 9626139] [Abstract] Cited for: VARIANTS MODY3 ARG-537 AND LYS-619.
[20]	"Mutations in the hepatocyte nuclear factor-1 alpha gene 'MODY3' are not a major cause of early-onset non-insulin-dependent 'type 2' diabetes mellitus in Japanese." Nishigori H., Yamada S., Kohama T., Utsugi T., Shimizu H., Takeuchi T., Takeda J. J. Hum. Genet. 43:107-110(1998) [PubMed: 9621514] [Abstract] Cited for: VARIANTS LEU-27 AND ASN-487.
[21]	"Identification of mutations in the hepatocyte nuclear factor-1alpha gene in Japanese subjects with early-onset NIDDM and functional analysis of the mutant proteins." Yamada S., Tomura H., Nishigori H., Sho K., Mabe H., Iwatani N., Takumi T., Kito Y., Moriya N., Muroya K., Ogata T., Onigata K., Morikawa A., Inoue I., Takeda J. Diabetes 48:645-648(1999) [PubMed: 10078571] [Abstract] Cited for: VARIANTS MODY3 HIS-12; ASN-158; GLN-159 AND CYS-203.
[22]	"Allelic drop-out in exon 2 of the hepatocyte nuclear factor-1alpha gene hinders the identification of mutations in three families with maturity-onset diabetes of the young." Ellard S., Bulman M.P., Frayling T.M., Allen L.I.S., Dronsfield M.J., Tack C.J., Hattersley A.T. Diabetes 48:921-923(1999) [PubMed: 10102714] [Abstract] Cited for: VARIANTS MODY3 GLU-117 AND TYR-143.
[23]	"Three new mutations in the hepatocyte nuclear factor-1alpha gene in Japanese subjects with diabetes mellitus: clinical features and functional characterization." Yoshiuchi I., Yamagata K., Yang Q., Iwahashi H., Okita K., Yamamoto K., Oue T., Imagawa A., Hamaguchi T., Yamasaki T., Horikawa Y., Satoh T., Nakajima H., Miyazaki J., Higashiyama S., Miyagawa J., Namba M., Hanafusa T., Matsuzawa Y. Diabetologia 42:621-626(1999) [PubMed: 10333057] [Abstract] Cited for: VARIANT NIDDM CYS-272, VARIANT IDDM ARG-415.
[24]	"Molecular genetics of diabetes mellitus in Chinese subjects: identification of mutations in glucokinase and hepatocyte nuclear factor-1alpha genes in patients with early-onset type 2 diabetes mellitus/MODY." Ng M.C.Y., Cockburn B.N., Lindner T.H., Yeung V.T.F., Chow C.-C., So W.-Y., Li J.K.Y., Lo Y.M.D., Lee Z.S.K., Cockram C.S., Critchley J.A.J.H., Bell G.I., Chan J.C.N. Diabet. Med. 16:956-963(1999) [PubMed: 10588527] [Abstract] Cited for: VARIANTS MODY3 ARG-20; HIS-203; CYS-432 AND MET-618.
[25]	"Non-penetrance in a MODY 3 family with a mutation in the hepatic nuclear factor 1alpha gene: implications for predictive testing." Miedzybrodzka Z., Hattersley A.T., Ellard S., Pearson D., de Silva D., Harvey R., Haites N. Eur. J. Hum. Genet. 7:729-732(1999) [PubMed: 10482964] [Abstract] Cited for: VARIANT MODY3 ILE-620.
[26]	"The hepatic nuclear factor-1alpha G319S variant is associated with early-onset type 2 diabetes in Canadian Oji-Cree." Hegele R.A., Cao H., Harris S.B., Hanley A.J.G., Zinman B. J. Clin. Endocrinol. Metab. 84:1077-1082(1999) [PubMed: 10084598] [Abstract] Cited for: VARIANT SER-319.
[27]	"Bi-allelic inactivation of TCF1 in hepatic adenomas." Bluteau O., Jeannot E., Bioulac-Sage P., Marques J.M., Blanc J.-F., Bui H., Beaudoin J.-C., Franco D., Balabaud C., Laurent-Puig P., Zucman-Rossi J. Nat. Genet. 32:312-315(2002) [PubMed: 12355088] [Abstract] Cited for: INVOLVEMENT IN HEPATIC ADENOMAS, VARIANTS TYR-127; CYS-165; CYS-206; LEU-206; SER-237; GLY-244; PRO-250; CYS-268; GLU-273; SER-574 AND GLN-583.
[28]	"The consensus coding sequences of human breast and colorectal cancers." Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V. , Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., Velculescu V.E. Science 314:268-274(2006) [PubMed: 16959974] [Abstract] Cited for: VARIANT [LARGE SCALE ANALYSIS] GLU-273.
+	Additional computationally mapped references.

Web resources

GeneReviews

Wikipedia

Hepatocyte nuclear factors entry

Cross-references

Sequence databases

EMBLGenBankDDBJ

M57732 mRNA. Translation: AAA88077.1.
X71346 mRNA. Translation: CAB59201.1.
U72618 , U72612, U72613, U72614, U72615, U72616, U72617 Genomic DNA. Translation: AAC51137.1.
BC104908 mRNA. Translation: AAI04909.1.
BC104910 mRNA. Translation: AAI04911.1.

IPI

IPI00025839.
IPI00219056.
IPI00411416.

PIR

A36749.

RefSeq

NP_000536.4.

UniGene

Hs.654455

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1IC8	X-ray	2.60	A/B	85-278	[»]
2GYP	X-ray	1.40	A/B	2-32	[»]

ModBase

Search...

Protein-protein interaction databases

IntAct

P20823. 10 interactions.

PTM databases

PhosphoSite

P20823.

Proteomic databases

PRIDE

P20823.

Genome annotation databases

Ensembl

ENSG00000135100. Homo sapiens. [Contig view]

GeneID

6927.

KEGG

hsa:6927.

Organism-specific databases

GeneCards

GC12P119900.

H-InvDB

HIX0036847.

HGNC

HGNC:11621. HNF1A.

HPA

CAB010430.

MIM

142330. phenotype.
142410. gene.
222100. phenotype.
600496. phenotype.
606391. phenotype.

Orphanet

552. MODY syndrome.
98802. MODY3.

PharmGKB

PA36380.

GenAtlas

Search...

Phylogenomic databases

HOGENOM

P20823.

HOVERGEN

P20823.

Enzyme and pathway databases

Pathway_Interaction_DB

wnt_canonical_pathway. Canonical Wnt signaling pathway.
hnf3bpathway. FOXA2 and FOXA3 transcription factor networks.
ps1pathway. Presenilin action in Notch and Wnt signaling.

Gene expression databases

Bgee

P20823.

CleanEx

HS_HNF1A.

GermOnline

ENSG00000135100. Homo sapiens.

Family and domain databases

InterPro

IPR006899. HNF-1_N.
IPR006898. HNF1a_C.
IPR006897. HNF1b_C.
IPR001356. Homeobox.
IPR017970. Homeobox_CS.
IPR012287. Homeodomain-rel.
[Graphical view]

Gene3D

G3DSA:1.10.10.60. Homeodomain-rel. 1 hit.

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]

ProDom

PD000010. Homeobox. 1 hit.
[Graphical view] [Entries sharing at least one domain]

SMART

SM00389. HOX. 1 hit.
[Graphical view]

PROSITE

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

ProtoNet

Search...

Other Resources

NextBio

27105.

SOURCE

Search...

Entry information

Entry name

HNF1A_HUMAN

Accession

Primary (citable) accession number: P20823
Secondary accession number(s): Q2M3H2, Q99861

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 1, 1991
Last sequence update:	August 16, 2004
Last modified:	June 16, 2009
This is version 123 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)