| General information | | DisProt: | DP00071 | | Name: | Homeobox protein Nkx-2.1 | | Synonym(s): | NKX21_RAT
Thyroid transcription factor 1
TTF-1
Thyroid nuclear factor 1
| | First appeared in release: | Release 1.0 (08/01/2003) | | UniProt: | P23441 | | UniGene: | Rn.34265 | | SwissProt: | NKX21_RAT | | TrEMBL: | | | NCBI (GI): | 136462 | | Source organism: | Rattus norvegicus (Rat) | | Sequence length: | 372 | | Percent disordered: | 47% | | Homologues: | |
| Native sequence |
10 20 30 40 50 60
| | | | | |
MSMSPKHTTP FSVSDILSPL EESYKKVGME GGGLGAPLAA YRQGQAAPPA AAMQQHAVGH - 60
HGAVTAAYHM TAAGVPQLSH SAVGGYCNGN LGNMSELPPY QDTMRNSASG PGWYGANPDP - 120
RFPAISRFMG PASGMNMSGM GGLGSLGDVS KNMAPLPSAP RRKRRVLFSQ AQVYELERRF - 180
KQQKYLSAPE REHLASMIHL TPTQVKIWFQ NHRYKMKRQA KDKAAQQQLQ QDSGGGGGGG - 240
GGAGCPQQQQ AQQQSPRRVA VPVLVKDGKP CQAGAPAPGA ASLQGHAQQQ AQQQAQAAQA - 300
AAAAISVGSG GAGLGAHPGH QPGSAGQSPD LAHHAASPAA LQGQVSSLSH LNSSGSDYGA - 360
MSCSTLLYGR TW
|
| Functional narrative |
Function: Transcription factor that binds and activates the promoter of thyroid specific genes such as thyroglobulin, thyroperoxidase, and thyrotropin receptor. Crucial in the maintenance of the thyroid differentiation phenotype. May play a role in lung development and surfactant homeostasis.
Subunit structure: Interacts with WWTR1 By similarity.
Subcellular location: Nucleus.
Tissue specificity: Thyroid, lung and CNS. Expressed in restricted regions of the developing brain within the diencephalon, in parts of the hypothalamus and neurohypophysis, and in the telencephalon.
Post-translational modification: Phosphorylated on serine residues by STK3/MST2. Ref.3
Sequence similarities: Belongs to the NK-2 homeobox family. Contains 1 homeobox DNA-binding domain (UniProt)
|
| Map of ordered and disordered regions |
Note: 'Mouse' over a region to see the start and stop residues. Click on a region to see detailed information.
|
| Region 1 | | Type: | Disordered | | Name: | TTF-1 N domain | | Location: | 1 - 157 | | Length: | 157 | | Region sequence: |
MSMSPKHTTPFSVSDILSPLEESYKKVGMEGGGLGAPLAAYRQGQAAPPAAAMQQHAVGH
HGAVTAAYHMTAAGVPQLSHSAVGGYCNGNLGNMSELPPYQDTMRNSASGPGWYGANPDP
RFPAISRFMGPASGMNMSGMGGLGSLGDVSKNMAPLP | | Modification type: | Fragment
Native
| | PDB: | | | Structural/functional type: | Function arises via a disorder to order transition
| | Functional classes: | Molecular recognition effectors
| | Functional subclasses: | Transactivation (transcriptional activation)
Protein-protein binding
| Detection methods:
- Circular dichroism (CD) spectroscopy, far-UV (298 K; pH: 4.4; )
| References:
- Tell G, Perrone L, Fabbro D, Pellizzari L, Pucillo C, De Felice M, Acquaviva R, Formisano S, Damante G. "Structural and functional properties of the N transcriptional activation domain of thyroid transcription factor-1: similarities with the acidic activation domains." Biochem J. 1998; 329 ( Pt 2): 395-403. PubMed: 9425125
| Comments:
|
| Region 2 | | Type: | Disordered | | Name: | stable proteolytic fragment | | Location: | 58 - 78 | | Length: | 21 | | Region sequence: |
VGHHGAVTAAYHMTAAGVPQL | | Modification type: | Fragment
Native
| | PDB: | | | Structural/functional type: | Function arises via a disorder to order transition
| | Functional classes: | Molecular recognition effectors
| | Functional subclasses: | Transactivation (transcriptional activation)
Protein-protein binding
| Detection methods:
- Sensitivity to proteolysis (298 K; protease/substrate (1:50); TFE 10 %)
| References:
- Tell G, Perrone L, Fabbro D, Pellizzari L, Pucillo C, De Felice M, Acquaviva R, Formisano S, Damante G. "Structural and functional properties of the N transcriptional activation domain of thyroid transcription factor-1: similarities with the acidic activation domains." Biochem J. 1998; 329 ( Pt 2): 395-403. PubMed: 9425125
| Comments:According to Tell et al (1998), this proteolytic fragment "maps inside the minimal activating region (residues 50-102) of the TTF-1 N domain."
|
| Region 3 | | Type: | Disordered | | Name: | Homeodomain (HD) N-terminal arm | | Location: | 161 - 169 | | Length: | 9 | | Region sequence: |
RRKRRVLFS | | Modification type: | Fragment
Native
| | PDB: | 1FTT:A | | Structural/functional type: | Function arises from the disordered state
| | Functional classes: | | | Functional subclasses: | Intraprotein interaction
| Detection methods:
- Nuclear magnetic resonance (NMR) (287 K; pH: 4; H2O/D2O (90:10) 0.5 mL; HCl (to adjust pH 4.0-4.2) 1 M; NaN3 (0.2-0.5% mass/vol); temps 287K and 289K; TTF-1 homeodomain 5.5 mM)
- Hydrogen-deuterium exchange (284 K; pH: 4; D2O (99.9%) 0.5 mL; DCl (to adjust pH 4.0-4.2) 1 M; TTF-1 homeodomain 5.5 mM)
| References:
- Esposito G, Fogolari F, Damante G, Formisano S, Tell G, Leonardi A, Di Lauro R, Viglino P. "Analysis of the solution structure of the homeodomain of rat thyroid transcription factor 1 by 1H-NMR spectroscopy and restrained molecular mechanics." Eur. J. Biochem.. 1996; 241(1): 101-13. PubMed: 8898894
- Viglino P, Fogolari F, Formisano S, Bortolotti N, Damante G, Di Lauro R, Esposito G. "Structural study of rat thyroid transcription factor 1 homeodomain (TTF-1 HD) by nuclear magnetic resonance." FEBS Lett.. 1993; 336(3): 397-402. PubMed: 8282100
| Comments:Primary reference for PDB structure 1FTT is Esposito et al (1996) whose work is based, in part, on Viglino et al (1993). The structure encompasses aa 161-226 (DP regions 3, 4 and 5).
PDB 1FTT shows characteristic three-helix homeodomain folding (DP region 4). Helices are found at aa Q170-Q182, A188-I198, P202-R218; loop at Q183-S187; tight turn at H199-T201. This fold is flanked by disordered segments at both its N- and C-terminals (DP regions 3 and 5), typical of homeodomains.
|
| Region 4 | | Type: | Ordered | | Name: | Homeodomain (HD) | | Location: | 170 - 219 | | Length: | 50 | | Region sequence: |
QAQVYELERRFKQQKYLSAPEREHLASMIHLTPTQVKIWFQNHRYKMKRQ | | Modification type: | Fragment
Native
| | PDB: | 1FTT:A | | Structural/functional type: | Function arises from the ordered state
| | Functional classes: | | | Functional subclasses: | Protein-DNA binding
| Detection methods:
- Nuclear magnetic resonance (NMR) (287 K; pH: 4; H2O/D2O (90:10) 0.5 mL; HCl (to adjust pH 4.0-4.2) 1 M; NaN3 (0.2-0.5% mass/vol); temps 287K and 289K; TTF-1 homeodomain 5.5 mM)
- Hydrogen-deuterium exchange (284 K; pH: 4; D2O (99.9%) 0.5 mL; DCl (to adjust pH 4.0-4.2) 1 M; TTF-1 homeodomain 5.5 mM)
| References:
- Esposito G, Fogolari F, Damante G, Formisano S, Tell G, Leonardi A, Di Lauro R, Viglino P. "Analysis of the solution structure of the homeodomain of rat thyroid transcription factor 1 by 1H-NMR spectroscopy and restrained molecular mechanics." Eur. J. Biochem.. 1996; 241(1): 101-13. PubMed: 8898894
- Viglino P, Fogolari F, Formisano S, Bortolotti N, Damante G, Di Lauro R, Esposito G. "Structural study of rat thyroid transcription factor 1 homeodomain (TTF-1 HD) by nuclear magnetic resonance." FEBS Lett.. 1993; 336(3): 397-402. PubMed: 8282100
| Comments:Primary reference for PDB structure 1FTT is Esposito et al (1996) whose work is based, in part, on Viglino et al (1993). The structure encompasses aa 161-226 (DP regions 3, 4 and 5).
PDB 1FTT shows characteristic three-helix homeodomain folding (DP region 4). Helices are found at aa Q170-Q182, A188-I198, P202-R218; loop at Q183-S187; tight turn at H199-T201. This fold is flanked by disordered segments at both its N- and C-terminals (DP regions 3 and 5), typical of homeodomains.
|
| Region 5 | | Type: | Disordered | | Name: | Homeodomain (HD) C-terminal arm | | Location: | 220 - 226 | | Length: | 7 | | Region sequence: |
AKDKAAQ | | Modification type: | Fragment
Native
| | PDB: | 1FTT:A | | Structural/functional type: | Function arises from the disordered state
| | Functional classes: | | | Functional subclasses: | | Detection methods:
- Nuclear magnetic resonance (NMR) (287 K; pH: 4; H2O/D2O (90:10) 0.5 mL; HCl (to adjust pH 4.0-4.2) 1 M; NaN3 (0.2-0.5% mass/vol); temps 287K and 289K; TTF-1 homeodomain 5.5 mM)
- Hydrogen-deuterium exchange (284 K; pH: 4; D2O (99.9%) 0.5 mL; DCl (to adjust pH 4.0-4.2) 1 M; TTF-1 homeodomain 5.5 mM)
| References:
- Esposito G, Fogolari F, Damante G, Formisano S, Tell G, Leonardi A, Di Lauro R, Viglino P. "Analysis of the solution structure of the homeodomain of rat thyroid transcription factor 1 by 1H-NMR spectroscopy and restrained molecular mechanics." Eur. J. Biochem.. 1996; 241(1): 101-13. PubMed: 8898894
- Viglino P, Fogolari F, Formisano S, Bortolotti N, Damante G, Di Lauro R, Esposito G. "Structural study of rat thyroid transcription factor 1 homeodomain (TTF-1 HD) by nuclear magnetic resonance." FEBS Lett.. 1993; 336(3): 397-402. PubMed: 8282100
| Comments:Primary reference for PDB structure 1FTT is Esposito et al (1996) whose work is based, in part, on Viglino et al (1993). The structure encompasses aa 161-226 (DP regions 3, 4 and 5).
PDB 1FTT shows characteristic three-helix homeodomain folding (DP region 4). Helices are found at aa Q170-Q182, A188-I198, P202-R218; loop at Q183-S187; tight turn at H199-T201. This fold is flanked by disordered segments at both its N- and C-terminals (DP regions 3 and 5), typical of homeodomains.
|
| If you have any comments or wish to provide additional references to this protein or its disordered region(s), please click here to e-mail us. |
Disprot-footer
|
