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. Defects in HNF1A are a cause of susceptibility to insulin-dependent diabetes mellitus (IDDM) [MIM:222100].
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
Cellular component	nucleus Inferred from electronic annotation. Source: InterPro protein complex Inferred from direct assay. Source: UniProtKB
Molecular function	RNA polymerase II transcription factor activity Inferred from direct assay. Source: UniProtKB protein binding Inferred from physical interaction. Source: UniProtKB sequence-specific DNA binding Inferred from electronic annotation. Source: InterPro 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.

VAR_010537

Natural variant

20

1

G → R in MODY3.

VAR_012483

Natural variant

27

1

I → L: dbSNP rs1169288.

VAR_007905

Natural variant

31

1

G → D in MODY3.

VAR_010538

Natural variant

48

1

E → K in IDDM.

VAR_010539

Natural variant

98

1

A → V: dbSNP rs1800574.

VAR_010540

Natural variant

107

1

L → R in MODY3.

VAR_010541

Natural variant

117

1

K → E in MODY3.

VAR_010542

Natural variant

122

1

Y → C in MODY3.

VAR_003756

Natural variant

127

1

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

VAR_033088

Natural variant

128

1

I → N in MODY3.

VAR_010543

Natural variant

129

1

P → T in MODY3.

VAR_010544

Natural variant

131

1

R → Q in MODY3.

VAR_010545

Natural variant

131

1

R → W in MODY3.

VAR_010546

Natural variant

133

1

V → M in MODY3.

VAR_010547

Natural variant

142

1

S → F in MODY3.

VAR_003757

Natural variant

143

1

H → Y in MODY3.

VAR_010548

Natural variant

158

1

K → N in MODY3.

VAR_010549

Natural variant

159

1

R → Q in MODY3.

VAR_003758

Natural variant

159

1

R → W in MODY3.

VAR_010550

Natural variant

161

1

A → T in MODY3.

VAR_010551

Natural variant

165

1

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

VAR_033089

Natural variant

191

1

G → D in late-onset NIDDM.

VAR_010552

Natural variant

200

1

R → W in MODY3.

VAR_010553

Natural variant

203

1

R → C in MODY3.

VAR_010554

Natural variant

203

1

R → H in MODY3.

VAR_012484

Natural variant

205

1

K → Q in MODY3.

VAR_010555

Natural variant

206

1

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

VAR_033090

Natural variant

206

1

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

VAR_033091

Natural variant

229

1

R → Q in MODY3.

VAR_010556

Natural variant

237

1

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

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.

VAR_033093

Natural variant

250

1

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

VAR_033094

Natural variant

254

1

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

VAR_010558

Natural variant

259

1

V → D in MODY3.

VAR_010559

Natural variant

260

1

T → M in MODY3.

VAR_010560

Natural variant

263

1

R → C in MODY3.

VAR_010561

Natural variant

268

1

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

VAR_033095

Natural variant

271

1

R → W in MODY3.

VAR_010562

Natural variant

272

1

R → C in NIDDM.

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.

VAR_033096

Natural variant

319

1

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

VAR_010564

Natural variant

415

1

G → R in IDDM; loss of function.

VAR_010565

Natural variant

432

1

S → C in MODY3.

VAR_012485

Natural variant

447

1

P → L in MODY3.

VAR_003760

Natural variant

487

1

S → N: dbSNP rs2464196.

VAR_007906

Natural variant

514

1

H → R

VAR_010566

Natural variant

519

1

P → L in MODY3.

VAR_010567

Natural variant

537

1

T → R in MODY3; incomplete penetrance.

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.

VAR_010569

Natural variant

583

1

R → G in IDDM.

VAR_003761

Natural variant

583

1

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

VAR_010570

Natural variant

594

1

S → I in MODY3.

VAR_010571

Natural variant

618

1

I → M in MODY3.

VAR_012486

Natural variant

619

1

E → K in MODY3.

VAR_010572

Natural variant

620

1

T → I in MODY3; incomplete penetrance.

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