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Protein

Hepatocyte nuclear factor 1-alpha

Gene

HNF1A

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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'.2 Publications

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
DNA bindingi199 – 279Homeobox; HNF1-typePROSITE-ProRule annotationAdd BLAST81

GO - Molecular functioni

  • DNA binding Source: UniProtKB
  • protein dimerization activity Source: UniProtKB
  • protein heterodimerization activity Source: UniProtKB
  • protein homodimerization activity Source: UniProtKB
  • RNA polymerase II regulatory region sequence-specific DNA binding Source: GO_Central
  • transcriptional activator activity, RNA polymerase II core promoter proximal region sequence-specific binding Source: BHF-UCL
  • transcription factor activity, sequence-specific DNA binding Source: UniProtKB
  • transcription regulatory region DNA binding Source: UniProtKB

GO - Biological processi

  • glucose homeostasis Source: UniProtKB
  • glucose import Source: UniProtKB
  • insulin secretion Source: UniProtKB
  • positive regulation of transcription, DNA-templated Source: UniProtKB
  • positive regulation of transcription from RNA polymerase II promoter Source: BHF-UCL
  • positive regulation of transcription initiation from RNA polymerase II promoter Source: UniProtKB
  • regulation of transcription from RNA polymerase II promoter Source: BHF-UCL
  • renal glucose absorption Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Activator

Keywords - Biological processi

Transcription, Transcription regulation

Keywords - Ligandi

DNA-binding

Enzyme and pathway databases

BioCyciZFISH:ENSG00000135100-MONOMER.
ReactomeiR-HSA-210745. Regulation of gene expression in beta cells.
SignaLinkiP20823.
SIGNORiP20823.

Names & Taxonomyi

Protein namesi
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 namesi
Name:HNF1A
Synonyms:TCF1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 12

Organism-specific databases

HGNCiHGNC:11621. HNF1A.

Subcellular locationi

  • Nucleus PROSITE-ProRule annotation1 Publication

GO - Cellular componenti

  • cytoplasm Source: UniProtKB
  • nucleus Source: UniProtKB
  • protein complex Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Involvement in diseasei

Hepatic adenomas familial (HEPAF)
The disease is caused by mutations affecting the gene represented in this entry. Bi-allelic inactivation of HNF1A, whether sporadic or associated with MODY3, may be an early step in the development of some hepatocellular carcinomas.
Disease descriptionRare benign liver tumors of presumable epithelial origin that develop in an otherwise normal liver. Hepatic adenomas may be single or multiple. They consist of sheets of well-differentiated hepatocytes that contain fat and glycogen and can produce bile. Bile ducts or portal areas are absent. Kupffer cells, if present, are reduced in number and are non-functional. Conditions associated with adenomas are insulin-dependent diabetes mellitus and glycogen storage diseases (types 1 and 3).
See also OMIM:142330
Maturity-onset diabetes of the young 3 (MODY3)14 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA 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), a primary defect in insulin secretion and frequent insulin-independence at the beginning of the disease.
See also OMIM:600496
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_01053712L → H in MODY3; abolishes interaction with PCBD1 and DNA. 3 Publications1
Natural variantiVAR_01248320G → R in MODY3; abolishes interaction with PCBD1 and DNA. 2 Publications1
Natural variantiVAR_01053831G → D in MODY3; no effect on interaction with PCBD1 and DNA. 2 Publications1
Natural variantiVAR_010541107L → R in MODY3. 1 Publication1
Natural variantiVAR_010542117K → E in MODY3. 1 Publication1
Natural variantiVAR_003756122Y → C in MODY3. 1 Publication1
Natural variantiVAR_010543128I → N in MODY3. 1 Publication1
Natural variantiVAR_010544129P → T in MODY3. 1 Publication1
Natural variantiVAR_010545131R → Q in MODY3; expected to interfere with DNA binding. 2 Publications1
Natural variantiVAR_010546131R → W in MODY3; expected to interfere with DNA binding. 2 Publications1
Natural variantiVAR_010547133V → M in MODY3. 1
Natural variantiVAR_003757142S → F in MODY3; reduces transcription activation by about 80%. 2 Publications1
Natural variantiVAR_010548143H → Y in MODY3; expected to interfere with DNA binding. 2 Publications1
Natural variantiVAR_010549158K → N in MODY3; expected to interfere with DNA binding. 1 Publication1
Natural variantiVAR_003758159R → Q in MODY3. 2 Publications1
Natural variantiVAR_010550159R → W in MODY3. 2 Publications1
Natural variantiVAR_010551161A → T in MODY3. 1 Publication1
Natural variantiVAR_063069200R → W in MODY3; expected to interfere with nuclear localization. 1 Publication1
Natural variantiVAR_010554203R → C in MODY3; expected to interfere with nuclear localization and DNA binding. 1 Publication1
Natural variantiVAR_012484203R → H in MODY3; expected to interfere with nuclear localization and DNA binding. 1 Publication1
Natural variantiVAR_010555205K → Q in MODY3; reduces transcription activation by about 50%. 2 Publications1
Natural variantiVAR_010556229R → Q in MODY3. 1 Publication1
Natural variantiVAR_010557241C → G in IDDM20 and MODY3. 2 Publications1
Natural variantiVAR_010559259V → D in MODY3. 1
Natural variantiVAR_010560260T → M in MODY3. 1 Publication1
Natural variantiVAR_010561263R → C in MODY3; expected to interfere with DNA binding. 1 Publication1
Natural variantiVAR_010562271R → W in MODY3. 1 Publication1
Natural variantiVAR_003759272R → H in IDDM20 and MODY3. 3 Publications1
Natural variantiVAR_012485432S → C in MODY3. 1 Publication1
Natural variantiVAR_003760447P → L in MODY3. 2 Publications1
Natural variantiVAR_010567519P → L in MODY3. 1 Publication1
Natural variantiVAR_010568537T → R in MODY3; incomplete penetrance. 1 Publication1
Natural variantiVAR_010571594S → I in MODY3. 1
Natural variantiVAR_012486618I → M in MODY3. 1 Publication1
Natural variantiVAR_010572619E → K in MODY3. 1 Publication1
Natural variantiVAR_010573620T → I in MODY3; incomplete penetrance. 2 Publications1
Diabetes mellitus, insulin-dependent, 20 (IDDM20)3 Publications
Disease susceptibility is associated with variations affecting the gene represented in this entry.
Disease descriptionA multifactorial disorder of glucose homeostasis that is characterized by susceptibility to ketoacidosis in the absence of insulin therapy. Clinical features are polydipsia, polyphagia and polyuria which result from hyperglycemia-induced osmotic diuresis and secondary thirst. These derangements result in long-term complications that affect the eyes, kidneys, nerves, and blood vessels.
See also OMIM:612520
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_01053948E → K in IDDM20. 1 Publication1
Natural variantiVAR_010557241C → G in IDDM20 and MODY3. 2 Publications1
Natural variantiVAR_003759272R → H in IDDM20 and MODY3. 3 Publications1
Natural variantiVAR_010565415G → R in IDDM20; loss of function. 1 Publication1
Natural variantiVAR_003761583R → G in IDDM20. 1 Publication1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi127N → W: Abolishes transcription activation. 1 Publication1
Mutagenesisi132E → K: Abolishes transcription activation. 1 Publication1
Mutagenesisi177F → S: No significant effect on transcription activation. 1 Publication1
Mutagenesisi186I → Q: No effect on transcription activation. 1 Publication1
Mutagenesisi190T → Q: No effect on transcription activation. 1 Publication1
Mutagenesisi202N → D: Reduces transcription activation by 70%. 1 Publication1
Mutagenesisi246V → D: Reduces transcription activation by 75%. 1 Publication1
Mutagenesisi257N → W: Reduces transcription activation by 70%. 1 Publication1

Keywords - Diseasei

Diabetes mellitus, Disease mutation

Organism-specific databases

DisGeNETi6927.
MalaCardsiHNF1A.
MIMi142330. phenotype.
600496. phenotype.
606391. phenotype.
612520. phenotype.
OpenTargetsiENSG00000135100.
Orphaneti324575. Hyperinsulinism due to HNF1A deficiency.
552. MODY.
PharmGKBiPA36380.

Polymorphism and mutation databases

BioMutaiHNF1A.
DMDMi51338763.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000491151 – 631Hepatocyte nuclear factor 1-alphaAdd BLAST631

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei70PhosphoserineBy similarity1
Modified residuei74PhosphothreonineBy similarity1
Modified residuei93PhosphoserineCombined sources1
Modified residuei247PhosphoserineCombined sources1
Modified residuei313PhosphoserineBy similarity1

Keywords - PTMi

Phosphoprotein

Proteomic databases

MaxQBiP20823.
PaxDbiP20823.
PeptideAtlasiP20823.
PRIDEiP20823.

PTM databases

iPTMnetiP20823.
PhosphoSitePlusiP20823.

Expressioni

Tissue specificityi

Liver.

Gene expression databases

BgeeiENSG00000135100.
CleanExiHS_HNF1A.
ExpressionAtlasiP20823. baseline and differential.
GenevisibleiP20823. HS.

Organism-specific databases

HPAiHPA035231.

Interactioni

Subunit structurei

Binds DNA as a dimer. Interacts with PCBD1. Heterotetramer with PCBD1; formed by a dimer of dimers.2 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
DYRK1BQ9Y4634EBI-636034,EBI-634187
PROX1Q927863EBI-636034,EBI-3912635

GO - Molecular functioni

  • protein dimerization activity Source: UniProtKB
  • protein heterodimerization activity Source: UniProtKB
  • protein homodimerization activity Source: UniProtKB

Protein-protein interaction databases

BioGridi112789. 39 interactors.
DIPiDIP-33544N.
IntActiP20823. 9 interactors.
STRINGi9606.ENSP00000257555.

Structurei

Secondary structure

1631
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi4 – 19Combined sources16
Helixi23 – 30Combined sources8
Helixi94 – 107Combined sources14
Helixi112 – 125Combined sources14
Helixi130 – 137Combined sources8
Helixi141 – 149Combined sources9
Helixi156 – 169Combined sources14
Turni170 – 173Combined sources4
Helixi174 – 177Combined sources4
Helixi208 – 221Combined sources14
Turni226 – 229Combined sources4
Helixi230 – 243Combined sources14
Helixi255 – 257Combined sources3
Helixi261 – 274Combined sources14

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1IC8X-ray2.60A/B85-278[»]
2GYPX-ray1.40A/B2-32[»]
ProteinModelPortaliP20823.
SMRiP20823.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP20823.

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 31DimerizationAdd BLAST31
Regioni130 – 132Interaction with DNA3
Regioni143 – 149Interaction with DNA7
Regioni155 – 158Interaction with DNA4
Regioni203 – 206Interaction with DNA4
Regioni263 – 265Interaction with DNA3
Regioni270 – 273Interaction with DNA4

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi197 – 205Nuclear localization signalCurated9

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi71 – 80Asp/Glu-rich (acidic; potential involvement with transcription)10

Sequence similaritiesi

Belongs to the HNF1 homeobox family.Curated
Contains 1 homeobox DNA-binding domain.PROSITE-ProRule annotation

Keywords - Domaini

Homeobox

Phylogenomic databases

eggNOGiENOG410IFA0. Eukaryota.
ENOG410ZZZ0. LUCA.
GeneTreeiENSGT00860000133745.
HOGENOMiHOG000015305.
HOVERGENiHBG005980.
InParanoidiP20823.
KOiK08036.
PhylomeDBiP20823.
TreeFamiTF320327.

Family and domain databases

Gene3Di1.10.10.60. 1 hit.
1.10.260.40. 1 hit.
InterProiIPR006899. HNF-1_N.
IPR023219. HNF1_dimer_dom.
IPR006898. HNF1a_C.
IPR006897. HNF1b_C.
IPR001356. Homeobox_dom.
IPR009057. Homeodomain-like.
IPR010982. Lambda_DNA-bd_dom.
[Graphical view]
PfamiPF04814. HNF-1_N. 1 hit.
PF04813. HNF-1A_C. 1 hit.
PF04812. HNF-1B_C. 1 hit.
PF00046. Homeobox. 1 hit.
[Graphical view]
SMARTiSM00389. HOX. 1 hit.
[Graphical view]
SUPFAMiSSF100957. SSF100957. 1 hit.
SSF46689. SSF46689. 1 hit.
SSF47413. SSF47413. 1 hit.
PROSITEiPS00027. HOMEOBOX_1. 1 hit.
PS50071. HOMEOBOX_2. 1 hit.
[Graphical view]

Sequences (8)i

Sequence statusi: Complete.

This entry describes 8 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform A (identifier: P20823-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MVSKLSQLQT ELLAALLESG LSKEALIQAL GEPGPYLLAG EGPLDKGESC
60 70 80 90 100
GGGRGELAEL PNGLGETRGS EDETDDDGED FTPPILKELE NLSPEEAAHQ
110 120 130 140 150
KAVVETLLQE DPWRVAKMVK SYLQQHNIPQ REVVDTTGLN QSHLSQHLNK
160 170 180 190 200
GTPMKTQKRA ALYTWYVRKQ REVAQQFTHA GQGGLIEEPT GDELPTKKGR
210 220 230 240 250
RNRFKWGPAS QQILFQAYER QKNPSKEERE TLVEECNRAE CIQRGVSPSQ
260 270 280 290 300
AQGLGSNLVT EVRVYNWFAN RRKEEAFRHK LAMDTYSGPP PGPGPGPALP
310 320 330 340 350
AHSSPGLPPP ALSPSKVHGV RYGQPATSET AEVPSSSGGP LVTVSTPLHQ
360 370 380 390 400
VSPTGLEPSH SLLSTEAKLV SAAGGPLPPV STLTALHSLE QTSPGLNQQP
410 420 430 440 450
QNLIMASLPG VMTIGPGEPA SLGPTFTNTG ASTLVIGLAS TQAQSVPVIN
460 470 480 490 500
SMGSSLTTLQ PVQFSQPLHP SYQQPLMPPV QSHVTQSPFM ATMAQLQSPH
510 520 530 540 550
ALYSHKPEVA QYTHTGLLPQ TMLITDTTNL SALASLTPTK QVFTSDTEAS
560 570 580 590 600
SESGLHTPAS QATTLHVPSQ DPAGIQHLQP AHRLSASPTV SSSSLVLYQS
610 620 630
SDSSNGQSHL LPSNHSVIET FISTQMASSS Q
Length:631
Mass (Da):67,356
Last modified:August 16, 2004 - v2
Checksum:i8327CD4FDC39254A
GO
Isoform B (identifier: P20823-2) [UniParc]FASTAAdd to basket

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

Show »
Length:572
Mass (Da):61,112
Checksum:iE9BD79E885C2E3C0
GO
Isoform C (identifier: P20823-3) [UniParc]FASTAAdd to basket

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

Show »
Length:524
Mass (Da):55,930
Checksum:iF6855702DE665780
GO
Isoform 4 (identifier: P20823-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     176-278: QFTHAGQGGL...ANRRKEEAFR → RRNASREGCP...QKYPQAAAVP
     279-631: Missing.

Show »
Length:278
Mass (Da):30,407
Checksum:i1AB561D8993D268F
GO
Isoform 5 (identifier: P20823-5) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     239-247: AECIQRGVS → CALWTACDQ
     248-631: Missing.

Show »
Length:247
Mass (Da):27,519
Checksum:i65A8988847FC27DF
GO
Isoform 6 (identifier: P20823-6) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-117: Missing.
     438-520: LASTQAQSVP...QYTHTGLLPQ → KLVGMGGHLG...NTSILWYLRR
     521-631: Missing.

Show »
Length:403
Mass (Da):43,469
Checksum:i5D22409F773364C6
GO
Isoform 7 (identifier: P20823-7) [UniParc]FASTAAdd to basket
Also known as: insIVS8

The sequence of this isoform differs from the canonical sequence as follows:
     540-540: K → KQVRSRPAGPPLACDRAPHPHIPRAQEAALLP

Note: Due to intron retention.Curated
Show »
Length:662
Mass (Da):70,661
Checksum:iFCCE6C78F8F6676F
GO
Isoform 8 (identifier: P20823-8) [UniParc]FASTAAdd to basket
Also known as: delta 2

The sequence of this isoform differs from the canonical sequence as follows:
     110-119: EDPWRVAKMV → VHPCRAGRAD
     120-631: Missing.

Note: No experimental confirmation available.
Show »
Length:119
Mass (Da):12,491
Checksum:i136DC46C438C5BC9
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Isoform 7 (identifier: P20823-7)
Sequence conflicti551L → S in ADK56177 (Ref. 5) Curated1

Polymorphismi

The Ala-98/Val-98 polymorphism is associated with a reduction in glucose-induced serum C-peptide and insulin responses.1 Publication

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_01053712L → H in MODY3; abolishes interaction with PCBD1 and DNA. 3 Publications1
Natural variantiVAR_01248320G → R in MODY3; abolishes interaction with PCBD1 and DNA. 2 Publications1
Natural variantiVAR_00790527I → L.7 PublicationsCorresponds to variant rs1169288dbSNPEnsembl.1
Natural variantiVAR_01053831G → D in MODY3; no effect on interaction with PCBD1 and DNA. 2 Publications1
Natural variantiVAR_01053948E → K in IDDM20. 1 Publication1
Natural variantiVAR_01054098A → V.3 PublicationsCorresponds to variant rs1800574dbSNPEnsembl.1
Natural variantiVAR_010541107L → R in MODY3. 1 Publication1
Natural variantiVAR_010542117K → E in MODY3. 1 Publication1
Natural variantiVAR_003756122Y → C in MODY3. 1 Publication1
Natural variantiVAR_033088127N → Y in a hepatocellular carcinoma sample; somatic mutation. 1 Publication1
Natural variantiVAR_010543128I → N in MODY3. 1 Publication1
Natural variantiVAR_010544129P → T in MODY3. 1 Publication1
Natural variantiVAR_010545131R → Q in MODY3; expected to interfere with DNA binding. 2 Publications1
Natural variantiVAR_010546131R → W in MODY3; expected to interfere with DNA binding. 2 Publications1
Natural variantiVAR_010547133V → M in MODY3. 1
Natural variantiVAR_003757142S → F in MODY3; reduces transcription activation by about 80%. 2 Publications1
Natural variantiVAR_010548143H → Y in MODY3; expected to interfere with DNA binding. 2 Publications1
Natural variantiVAR_010549158K → N in MODY3; expected to interfere with DNA binding. 1 Publication1
Natural variantiVAR_003758159R → Q in MODY3. 2 Publications1
Natural variantiVAR_010550159R → W in MODY3. 2 Publications1
Natural variantiVAR_010551161A → T in MODY3. 1 Publication1
Natural variantiVAR_033089165W → C in a hepatocellular carcinoma sample; somatic mutation. 1 Publication1
Natural variantiVAR_010552191G → D in late-onset NIDDM. 1 Publication1
Natural variantiVAR_063069200R → W in MODY3; expected to interfere with nuclear localization. 1 Publication1
Natural variantiVAR_010554203R → C in MODY3; expected to interfere with nuclear localization and DNA binding. 1 Publication1
Natural variantiVAR_012484203R → H in MODY3; expected to interfere with nuclear localization and DNA binding. 1 Publication1
Natural variantiVAR_010555205K → Q in MODY3; reduces transcription activation by about 50%. 2 Publications1
Natural variantiVAR_033090206W → C in a hepatic adenoma sample; somatic mutation; expected to interfere with DNA binding. 1 Publication1
Natural variantiVAR_033091206W → L in a hepatic adenoma sample; somatic mutation; expected to interfere with DNA binding. 1 Publication1
Natural variantiVAR_010556229R → Q in MODY3. 1 Publication1
Natural variantiVAR_033092237N → S in a hepatic multiple adenoma sample; somatic mutation. 1 Publication1
Natural variantiVAR_010557241C → G in IDDM20 and MODY3. 2 Publications1
Natural variantiVAR_033093244R → G in a hepatic adenoma sample; somatic mutation; expected to interfere with DNA binding. 1 Publication1
Natural variantiVAR_033094250Q → P in a hepatocellular carcinoma sample; somatic mutation. 1 Publication1
Natural variantiVAR_010558254L → M in late-onset NIDDM; low penetrance; unknown pathological significance. 1 Publication1
Natural variantiVAR_010559259V → D in MODY3. 1
Natural variantiVAR_010560260T → M in MODY3. 1 Publication1
Natural variantiVAR_010561263R → C in MODY3; expected to interfere with DNA binding. 1 Publication1
Natural variantiVAR_033095268F → C in a hepatic adenoma sample; somatic mutation. 1 Publication1
Natural variantiVAR_010562271R → W in MODY3. 1 Publication1
Natural variantiVAR_010563272R → C in NIDDM. 1 Publication1
Natural variantiVAR_003759272R → H in IDDM20 and MODY3. 3 Publications1
Natural variantiVAR_033096273K → E in a hepatic adenoma sample; somatic mutation. 2 Publications1
Natural variantiVAR_010564319G → S Strong association with NIDDM susceptibility; unique to the Canadian Oji-Cree population. 1 Publication1
Natural variantiVAR_010565415G → R in IDDM20; loss of function. 1 Publication1
Natural variantiVAR_012485432S → C in MODY3. 1 Publication1
Natural variantiVAR_003760447P → L in MODY3. 2 Publications1
Natural variantiVAR_007906487S → N.6 PublicationsCorresponds to variant rs2464196dbSNPEnsembl.1
Natural variantiVAR_010566514H → R.1 Publication1
Natural variantiVAR_010567519P → L in MODY3. 1 Publication1
Natural variantiVAR_010568537T → R in MODY3; incomplete penetrance. 1 Publication1
Natural variantiVAR_010569574G → S in a black African with an atypical form of diabetes; also in an individual with hepatic adenoma and familial early-onset diabetes. 4 PublicationsCorresponds to variant rs1169305dbSNPEnsembl.1
Natural variantiVAR_003761583R → G in IDDM20. 1 Publication1
Natural variantiVAR_010570583R → Q in late-onset NIDDM; also in an individual with hepatic hyperplasia and familial early-onset diabetes. 2 Publications1
Natural variantiVAR_010571594S → I in MODY3. 1
Natural variantiVAR_012486618I → M in MODY3. 1 Publication1
Natural variantiVAR_010572619E → K in MODY3. 1 Publication1
Natural variantiVAR_010573620T → I in MODY3; incomplete penetrance. 2 Publications1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0533241 – 117Missing in isoform 6. 1 PublicationAdd BLAST117
Alternative sequenceiVSP_054300110 – 119EDPWRVAKMV → VHPCRAGRAD in isoform 8. Curated10
Alternative sequenceiVSP_054301120 – 631Missing in isoform 8. CuratedAdd BLAST512
Alternative sequenceiVSP_047736176 – 278QFTHA…EEAFR → RRNASREGCPHHRHRGWAPT SSRRCVSTTGLPTGAKKKPS GTSWPWTRTAGPPQGQARDL RCPLTAPLACLHLPSPPVRS TVCAMDSLRPVRLQKYPQAA AVP in isoform 4. 1 PublicationAdd BLAST103
Alternative sequenceiVSP_047737239 – 247AECIQRGVS → CALWTACDQ in isoform 5. 1 Publication9
Alternative sequenceiVSP_047738248 – 631Missing in isoform 5. 1 PublicationAdd BLAST384
Alternative sequenceiVSP_047739279 – 631Missing in isoform 4. 1 PublicationAdd BLAST353
Alternative sequenceiVSP_053325438 – 520LASTQ…GLLPQ → KLVGMGGHLGGRLMGQPQNP GAGRATGTHSFIHTTCIYPV PTLDQSLCYISDTWVNQTDQ NLSNSSREAGTKHNTSILWY LRR in isoform 6. 1 PublicationAdd BLAST83
Alternative sequenceiVSP_002252438 – 494LASTQ…MATMA → KLVGMGGHLGGRLMGQPQNP GAGRATGTHSFIHSFIQHVF IQCLLWTSHCATSVIPG in isoform C. CuratedAdd BLAST57
Alternative sequenceiVSP_002253495 – 601Missing in isoform C. CuratedAdd BLAST107
Alternative sequenceiVSP_002250501 – 542ALYSH…PTKQV → GEHPVPHTAGDDDRGWLSMD AGERGAWQALQSACVSGTSV FP in isoform B. CuratedAdd BLAST42
Alternative sequenceiVSP_053326521 – 631Missing in isoform 6. 1 PublicationAdd BLAST111
Alternative sequenceiVSP_054302540K → KQVRSRPAGPPLACDRAPHP HIPRAQEAALLP in isoform 7. 1 Publication1
Alternative sequenceiVSP_002251543 – 601Missing in isoform B. CuratedAdd BLAST59

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M57732 mRNA. Translation: AAA88077.1.
X71346 mRNA. Translation: CAB59201.1.
U72618
, U72612, U72613, U72614, U72615, U72616, U72617 Genomic DNA. Translation: AAC51137.1.
HM116552 mRNA. Translation: ADM43489.1.
HM116557 mRNA. Translation: ADM43494.1.
HM116558 mRNA. Translation: ADM43495.1.
HM449088 mRNA. Translation: ADK56177.1.
HM449089 mRNA. Translation: ADK56178.1.
EF641294 Genomic DNA. Translation: ABR09270.1.
AC079602 Genomic DNA. No translation available.
CH471054 Genomic DNA. Translation: EAW98226.1.
BC104908 mRNA. Translation: AAI04909.1.
BC104910 mRNA. Translation: AAI04911.1.
CCDSiCCDS9209.1. [P20823-1]
PIRiA36749.
RefSeqiNP_000536.5. NM_000545.6. [P20823-1]
NP_001293108.1. NM_001306179.1.
UniGeneiHs.654455.

Genome annotation databases

EnsembliENST00000538646; ENSP00000443964; ENSG00000135100. [P20823-4]
ENST00000540108; ENSP00000445445; ENSG00000135100. [P20823-8]
ENST00000541924; ENSP00000440361; ENSG00000135100. [P20823-5]
GeneIDi6927.
KEGGihsa:6927.
UCSCiuc021rfb.2. human. [P20823-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Web resourcesi

Wikipedia

Hepatocyte nuclear factors entry

SeattleSNPs

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M57732 mRNA. Translation: AAA88077.1.
X71346 mRNA. Translation: CAB59201.1.
U72618
, U72612, U72613, U72614, U72615, U72616, U72617 Genomic DNA. Translation: AAC51137.1.
HM116552 mRNA. Translation: ADM43489.1.
HM116557 mRNA. Translation: ADM43494.1.
HM116558 mRNA. Translation: ADM43495.1.
HM449088 mRNA. Translation: ADK56177.1.
HM449089 mRNA. Translation: ADK56178.1.
EF641294 Genomic DNA. Translation: ABR09270.1.
AC079602 Genomic DNA. No translation available.
CH471054 Genomic DNA. Translation: EAW98226.1.
BC104908 mRNA. Translation: AAI04909.1.
BC104910 mRNA. Translation: AAI04911.1.
CCDSiCCDS9209.1. [P20823-1]
PIRiA36749.
RefSeqiNP_000536.5. NM_000545.6. [P20823-1]
NP_001293108.1. NM_001306179.1.
UniGeneiHs.654455.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1IC8X-ray2.60A/B85-278[»]
2GYPX-ray1.40A/B2-32[»]
ProteinModelPortaliP20823.
SMRiP20823.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi112789. 39 interactors.
DIPiDIP-33544N.
IntActiP20823. 9 interactors.
STRINGi9606.ENSP00000257555.

PTM databases

iPTMnetiP20823.
PhosphoSitePlusiP20823.

Polymorphism and mutation databases

BioMutaiHNF1A.
DMDMi51338763.

Proteomic databases

MaxQBiP20823.
PaxDbiP20823.
PeptideAtlasiP20823.
PRIDEiP20823.

Protocols and materials databases

DNASUi6927.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000538646; ENSP00000443964; ENSG00000135100. [P20823-4]
ENST00000540108; ENSP00000445445; ENSG00000135100. [P20823-8]
ENST00000541924; ENSP00000440361; ENSG00000135100. [P20823-5]
GeneIDi6927.
KEGGihsa:6927.
UCSCiuc021rfb.2. human. [P20823-1]

Organism-specific databases

CTDi6927.
DisGeNETi6927.
GeneCardsiHNF1A.
H-InvDBHIX0036847.
HGNCiHGNC:11621. HNF1A.
HPAiHPA035231.
MalaCardsiHNF1A.
MIMi142330. phenotype.
142410. gene.
600496. phenotype.
606391. phenotype.
612520. phenotype.
neXtProtiNX_P20823.
OpenTargetsiENSG00000135100.
Orphaneti324575. Hyperinsulinism due to HNF1A deficiency.
552. MODY.
PharmGKBiPA36380.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IFA0. Eukaryota.
ENOG410ZZZ0. LUCA.
GeneTreeiENSGT00860000133745.
HOGENOMiHOG000015305.
HOVERGENiHBG005980.
InParanoidiP20823.
KOiK08036.
PhylomeDBiP20823.
TreeFamiTF320327.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000135100-MONOMER.
ReactomeiR-HSA-210745. Regulation of gene expression in beta cells.
SignaLinkiP20823.
SIGNORiP20823.

Miscellaneous databases

EvolutionaryTraceiP20823.
GeneWikiiHNF1A.
GenomeRNAii6927.
PROiP20823.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000135100.
CleanExiHS_HNF1A.
ExpressionAtlasiP20823. baseline and differential.
GenevisibleiP20823. HS.

Family and domain databases

Gene3Di1.10.10.60. 1 hit.
1.10.260.40. 1 hit.
InterProiIPR006899. HNF-1_N.
IPR023219. HNF1_dimer_dom.
IPR006898. HNF1a_C.
IPR006897. HNF1b_C.
IPR001356. Homeobox_dom.
IPR009057. Homeodomain-like.
IPR010982. Lambda_DNA-bd_dom.
[Graphical view]
PfamiPF04814. HNF-1_N. 1 hit.
PF04813. HNF-1A_C. 1 hit.
PF04812. HNF-1B_C. 1 hit.
PF00046. Homeobox. 1 hit.
[Graphical view]
SMARTiSM00389. HOX. 1 hit.
[Graphical view]
SUPFAMiSSF100957. SSF100957. 1 hit.
SSF46689. SSF46689. 1 hit.
SSF47413. SSF47413. 1 hit.
PROSITEiPS00027. HOMEOBOX_1. 1 hit.
PS50071. HOMEOBOX_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiHNF1A_HUMAN
AccessioniPrimary (citable) accession number: P20823
Secondary accession number(s): A5Z2R8
, E0YMJ5, E0YMK0, E0YMK1, E2I9R4, E2I9R5, F5H5U3, Q2M3H2, Q99861
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 1, 1991
Last sequence update: August 16, 2004
Last modified: November 30, 2016
This is version 205 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 12
    Human chromosome 12: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.