Reviewed,
UniProtKB/Swiss-Prot P20823 (HNF1A_HUMAN)
Last modified
November 25, 2008.
Version 115.
History...
Clusters with 100%,
90%,
50% identity |
Documents (6) |
Third-party data |
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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 |
| ||||
| 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 | |
| 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
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 | ||||||||||||||||||||||||||||||
Helix Strand Turn | ||||||||||||||||||||||||||||||
| 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 | ||||||||||||||||||||||||||||

Clusters with