Annotations for this protein have been verified by the authors of the corresponding papers


DP00623: Homeotic protein ultrabithorax [Isoform IB (A)]FASTA viewXML view

General information
DisProt:DP00623
Name:Homeotic protein ultrabithorax [Isoform IB (A)]
Synonym(s):UBX_DROME
Ultrabithorax Homeotic protein IV
First appeared in release:Release 5.1 (05/28/2010)
UniProt:P83949-1
UniGene:Dm.21668
SwissProt: UBX_DROME
TrEMBL:  
NCBI (GI): 48428932
Source organism:Drosophila melanogaster (Fruit fly)
Sequence length:389
Percent disordered:69%
Homologues: 


Native sequence

        10         20         30         40         50         60
         |          |          |          |          |          |
MNSYFEQASG FYGHPHQATG MAMGSGGHHD QTASAAAAAY RGFPLSLGMS PYANHHLQRT - 60
TQDSPYDASI TAACNKIYGD GAGAYKQDCL NIKADAVNGY KDIWNTGGSN GGGGGGGGGG - 120
GGGAGGTGGA GNANGGNAAN ANGQNNPAGG MPVRPSACTP DSRVGGYLDT SGGSPVSHRG - 180
GSAGGNVSVS GGNGNAGGVQ SGVGVAGAGT AWNANCTISG AAAQTAAASS LHQASNHTFY - 240
PWMAIAGECP EDPTKSKIRS DLTQYGGIST DMGKRYSESL AGSLLPDWLG TNGLRRRGRQ - 300
TYTRYQTLEL EKEFHTNHYL TRRRRIEMAH ALCLTERQIK IWFQNRRMKL KKEIQAIKEL - 360
NEQEKQAQAQ KAAAAAAAAA AVQGGHLDQ



Functional narrative    

Sequence-specific transcription factor which is part of a developmental regulatory system that provides cells with specific positional identities on the anterior-posterior axis. Binds the consensus region 5'-TTAAT[GT][GA]-3'. This homeotic protein controls development of the cells in the posterior thoracic and first abdominal segments. It activates the synthesis of the decapentaplegic (DPP) growth factor. Modifies homeodomain-DNA interactions in a pH-dependent manner.

Region 1: 1-174 Region 2: 174-216 Region 3: 235-286

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:R
Location:1 - 174
Length:174
Region sequence:

MNSYFEQASGFYGHPHQATGMAMGSGGHHDQTASAAAAAYRGFPLSLGMSPYANHHLQRT
TQDSPYDASITAACNKIYGDGAGAYKQDCLNIKADAVNGYKDIWNTGGSNGGGGGGGGGG
GGGAGGTGGAGNANGGNAANANGQNNPAGGMPVRPSACTPDSRVGGYLDTSGGS

Modification type: Monomeric
Mutant
PDB:  
Structural/functional type: Function arises from the disordered state
Functional classes: Molecular recognition effectors
Functional subclasses: Intraprotein interaction
Detection methods:
  1. Sensitivity to proteolysis (295 K; pH: 6.8; Proteinase K (protease) 0.2 ng/uL; HEPES (buffer) 50 mM; Protein (substrate) 0.2 ug/uL)

  2. Sensitivity to proteolysis (295 K; pH: 8; Protein (substrate) 0.2 ug/uL; Tris base (buffer) 50 mM; Trypsin (protease) 0.2 ng/uL)

  3. Sensitivity to proteolysis (295 K; pH: 7.5; Chymotrypsin (protease) 0.2 ng/uL; Protein (substrate) 0.2 ug/uL; Tris-HCL (buffer) 50 mM)

  4. Circular dichroism (CD) spectroscopy, far-UV (277 K; pH: 7.5; Dithiothreitol (DTT) (buffer) 0.3 mM; NaCl (buffer) 300 mM; NaH2PO4 (buffer) 50 mM; UbxIb 10.4 uM)
References:
  1. Gavis ER, Hogness DS. "Phosphorylation, expression and function of the Ultrabithorax protein family in Drosophila melanogaster." Development. 1991; 112(4): 1077-93. PubMed: 1682129

  2. Liu Y, Matthews KS, Bondos SE. "Multiple intrinsically disordered sequences alter DNA binding by the homeodomain of the Drosophila hox protein ultrabithorax." J Biol Chem. 2008; 283(30): 20874-87. PubMed: 18508761

  3. Tan XX, Bondos S, Li L, Matthews KS. "Transcription activation by ultrabithorax Ib protein requires a predicted alpha-helical region." Biochemistry. 2002; 41(8): 2774-85. PubMed: 11851425
Comments:
The R region contains part of the transcription activation domain and is phosphorylated in vivo. The R region restores DNA binding affinity inhibited by I2 region. Liu et al., hypothesize an intramolecular interaction with I2 (or a part of I2) that restricts the flexibility of I2 and/or alters pH response of DNA binding to the homeodomain.


Region 2
Type:Disordered
Name:I2
Location:174 - 216
Length:43
Region sequence:

SPVSHRGGSAGGNVSVSGGNGNAGGVQSGVGVAGAGTAWNANC

Modification type:  
PDB:  
Structural/functional type: Function arises via a disorder to order transition
Functional classes: Molecular recognition effectors
Functional subclasses:  
Detection methods:
  1. Sensitivity to proteolysis (295 K; pH: 6.8; HEPES (buffer) 50 mM; Protein (substrate) 0.2 ug/uL; Proteinase K (protease) 0.2 ng/uL)

  2. Sensitivity to proteolysis (295 K; pH: 8; Protein (substrate) 0.2 ug/uL; Tris base (buffer) 50 mM; Trypsin (protease) 0.2 ng/uL)

  3. Sensitivity to proteolysis (295 K; pH: 7.5; Chymotrypsin (protease) 0.2 ng/uL; Protein (substrate) 0.2 ug/uL; Tris-HCL (buffer) 50 mM)

  4. Circular dichroism (CD) spectroscopy, far-UV (277 K; pH: 7.5; Dithiothreitol (DTT) (buffer) 0.3 mM; NaCl (buffer) 300 mM; NaH2PO4 (buffer) 50 mM; UbxIb 10.4 uM)
References:
  1. Liu Y, Matthews KS, Bondos SE. "Multiple intrinsically disordered sequences alter DNA binding by the homeodomain of the Drosophila hox protein ultrabithorax." J Biol Chem. 2008; 283(30): 20874-87. PubMed: 18508761

  2. Tan XX, Bondos S, Li L, Matthews KS. "Transcription activation by ultrabithorax Ib protein requires a predicted alpha-helical region." Biochemistry. 2002; 41(8): 2774-85. PubMed: 11851425
Comments:
The I2 region contains part of the transcription activation domain and inhibits DNA binding. Liu et al., hypothesize that I2 undergoes rapid structural fluctuations thus sterically hindering DNA binding to the homeodomain.


Region 3
Type:Disordered
Name:I1
Location:235 - 286
Length:52
Region sequence:

SNHTFYPWMAIAGECPEDPTKSKIRSDLTQYGGISTDMGKRYSESLAGSLLP

Modification type:  
PDB:  
Structural/functional type:  
Functional classes: Molecular recognition effectors
Functional subclasses:  
Detection methods:
  1. Sensitivity to proteolysis (295 K; pH: 6.8; HEPES (buffer) 50 mM; Protein (substrate) 0.2 ug/uL; Proteinase K (protease) 0.2 ng/uL)

  2. Sensitivity to proteolysis (295 K; pH: 8; Protein (substrate) 0.2 ug/uL; Tris base (buffer) 50 mM; Trypsin (protease) 0.2 ng/uL)

  3. Sensitivity to proteolysis (295 K; pH: 7.5; Chymotrypsin (protease) 0.2 ng/uL; Protein (substrate) 0.2 ug/uL; Tris-HCL (buffer) 50 mM)

  4. Circular dichroism (CD) spectroscopy, far-UV (277 K; pH: 7.5; Dithiothreitol (DTT) (buffer) 0.3 mM; NaCl (buffer) 300 mM; NaH2PO4 (buffer) 50 mM; UbxIb 10.4 uM)
References:
  1. Gavis ER, Hogness DS. "Phosphorylation, expression and function of the Ultrabithorax protein family in Drosophila melanogaster." Development. 1991; 112(4): 1077-93. PubMed: 1682129

  2. Johnson FB, Parker E, Krasnow MA. "Extradenticle protein is a selective cofactor for the Drosophila homeotics: role of the homeodomain and YPWM amino acid motif in the interaction." Proc Natl Acad Sci U S A. 1995; 92(3): 739-43. PubMed: 7846045

  3. Krasnow MA, Saffman EE, Kornfeld K, Hogness DS. "Transcriptional activation and repression by Ultrabithorax proteins in cultured Drosophila cells." Cell. 1989; 57(6): 1031-43. PubMed: 2567632

  4. Liu Y, Matthews KS, Bondos SE. "Multiple intrinsically disordered sequences alter DNA binding by the homeodomain of the Drosophila hox protein ultrabithorax." J Biol Chem. 2008; 283(30): 20874-87. PubMed: 18508761

  5. Liu Y, Matthews KS, Bondos SE. "Internal regulatory interactions determine DNA binding specificity by a Hox transcription factor." J Mol Biol. 2009; 390(4): 760-64. PubMed: 19481089
Comments:
The I1 region contains alternatively spliced microexons. The I1 regions inhibits DNA binding to an optimal sequence. Liu et al. hypothesize that I1 inhibits DNA binding by "propagating disorder along hte backbone of the N-terminal arm" of the DNA-binding homeodomain. The I1 regionn also modulates DNA binding specificity by the homeodomain and mitigates the pH sensitivity of the homeodomain. The I1 region contains theh YPWM (or hexapeptide) motif used to bind the general Hox cofactor Extradenticle. Finally, alternative splicing within I1 alters transcription activation, transcription repression, and interactions with the Exd cofactor.




References

  1. Tan XX, Bondos S, Li L, Matthews KS. "Transcription activation by ultrabithorax Ib protein requires a predicted alpha-helical region." Biochemistry. 2002; 41(8): 2774-85. PubMed: 11851425



Comments


[PMID18508761 AV 05/03/10]


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