DP00709: Protein chibby homolog 1FASTA viewXML view

General information
DisProt:DP00709
Name:Protein chibby homolog 1
Synonym(s):CBY1_HUMAN
ARPP-binding protein
Cytosolic leucine-rich protein
PIGEA-14
PKD2 interactor, Golgi and endoplasmic reticulum-associated 1
Chibby
Cby
First appeared in release:Release 5.7 (02/28/2011)
UniProt:Q9Y3M2
UniGene: 
SwissProt: CBY1_HUMAN
TrEMBL:  
NCBI (GI):  
Source organism:Homo sapiens (Human)
Sequence length:126
Percent disordered:50%
Homologues: 


Native sequence

        10         20         30         40         50         60
         |          |          |          |          |          |
MPFFGNTFSP KKTPPRKSAS LSNLHSLDRS TREVELGLEY GSPTMNLAGQ SLKFENGQWI - 60
AETGVSGGVD RREVQRLRRR NQQLEEENNL LRLKVDILLD MLSESTAESH LMEKELDELR - 120
ISRKRK



Functional narrative    

Function: Inhibits the Wnt/Wingless pathway by binding to beta- catenin and inhibiting beta-catenin-mediated transcriptional activation through competition with TCF/LEF transcription factors. Has also been shown to play a role in regulating the intracellular trafficking of polycystin-2/PKD2 and possibly of other intracellular proteins. Promotes adipocyte and cardiomyocyte differentiation.
SUBUNIT: Homodimer. Interacts with polycystin-2/PKD2 and GM130. Interacts with the C-terminal region of beta-catenin.


Subcellular Location: Nucleus speckle. Golgi apparatus, trans- Golgi network. Note=Nuclear, in a punctate manner. Also found in the trans-Golgi.
TISSUE SPECIFICITY: Widely expressed. Expressed at higher levels in heart, skeletal muscle, kidney and placenta. Also found in brain, lung, liver and testis. Significantly down-regulated in thyroid and metastatic uterine tumors.
MISCELLANEOUS: \'Chibby\' is Japanese for \'small\'; the gene was so named for the RNAi phenotype seen in flies.
SIMILARITY: Belongs to the chibby family.
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Region 1: 1-19 Region 2: 20-50 Region 3: 51-63 Region 4: 64-126

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 w/ Residual Structure
Name:N-terminal segment
Location:1 - 19
Length:19
Region sequence:

MPFFGNTFSPKKTPPRKSA

Modification type: Native
PDB:  
Structural/functional type: Function arises via a disorder to order transition
Functional classes: Molecular recognition effectors
Functional subclasses: Nuclear localization
Protein-protein binding
Phosphorylation
Detection methods:
  1. Nuclear magnetic resonance (NMR) (298 K; pH: 5; Cby (250-300 uM); sodium acetate 10 mM; urea (varying concentrations))

  2. Nuclear magnetic resonance (NMR) (298 K; pH: 7; 14-3-3-zeta (protein interaction partner) 600 uM; DTT 1 mM; EDTA 1 mM; NaOH 50 mM; N-Cby(S20D) (to simulate phoshorylated-Cby) 200 uM; sodium acetate (buffer) 10 mM)

  3. Circular dichroism (CD) spectroscopy, far-UV (298 K; at various pH levels; Cby 40 uM; sodium acetate 10 mM; urea (or various other additives))

  4. Dynamic light scattering (298 K; pH: 5; Cby (concentrations of 50 uM and above) 50 uM; sodium acetate 10 mM)

References:
  1. Mokhtarzada S, Yu C, Brickenden A, Choy WY. "Structural Characterization of Partially Disordered Human Chibby: Insights into Its Function in the Wnt-Signaling Pathway." 2011. PubMed: 21182262

Comments:
Mokhtarzada et al (2010) describe the N-terminal of Chibby (N-Cby) as overall intrinsically disordered with "mild helical propensity" at aa 20-50, while the rest of N-Cby "adopts transient beta-strand structure." Additionally, N-Cby contains a binding motif for 14-3-3 proteins at aa 16-22, and a nuclear export signal at aa 21-29.




Region 2
Type:Disordered w/ Residual Structure
Name:N-terminal segment
Location:20 - 50
Length:31
Region sequence:

SLSNLHSLDRSTREVELGLEYGSPTMNLAGQ

Modification type: Native
PDB:  
Structural/functional type: Function arises via a disorder to order transition
Functional classes: Molecular recognition effectors
Functional subclasses: Nuclear localization
Phosphorylation
Protein-protein binding
Detection methods:
  1. Nuclear magnetic resonance (NMR) (298 K; pH: 5; Cby (250-300 uM); sodium acetate (buffer) 10 mM; urea (varying concentrations))

  2. Nuclear magnetic resonance (NMR) (298 K; pH: 5; 14-3-3-zeta (protein interaction partner) 600 uM; DTT (buffer) 1 mM; EDTA (buffer) 1 mM; NaOH 50 mM; N-Cby(S20D) (to simulate phoshorylated-Cby) 200 uM; sodium acetate (buffer) 10 mM)

  3. Circular dichroism (CD) spectroscopy, far-UV (298 K; at various pH levels; Cby 40 uM; sodium acetate (buffer) 10 mM; urea (or various other additives))

  4. Dynamic light scattering (298 K; pH: 5; Cby (concentrations of 50 uM and above); sodium acetate (buffer))

References:
  1. Mokhtarzada S, Yu C, Brickenden A, Choy WY. "Structural Characterization of Partially Disordered Human Chibby: Insights into Its Function in the Wnt-Signaling Pathway." 2011. PubMed: 21182262

Comments:
Mokhtarzada et al (2010) describe the N-terminal of Chibby (N-Cby) as overall intrinsically disordered with "mild helical propensity" at aa 20-50, while the rest of N-Cby "adopts transient beta-strand structure." Additionally, N-Cby contains a binding motif for 14-3-3 proteins at aa 16-22, and a nuclear export signal at aa 21-29.




Region 3
Type:Disordered w/ Residual Structure
Name:N-terminal segment
Location:51 - 63
Length:13
Region sequence:

SLKFENGQWIAET

Modification type: Native
PDB:  
Structural/functional type: Function arises via a disorder to order transition
Functional classes: Molecular recognition effectors
Functional subclasses: Nuclear localization
Phosphorylation
Protein-protein binding
Detection methods:
  1. Nuclear magnetic resonance (NMR) (298 K; pH: 5; Cby (250-300 uM); sodium acetate 10 mM; urea (varying concentrations))

  2. Circular dichroism (CD) spectroscopy, far-UV (298 K; at various pH levels; Cby 40 uM; sodium acetate 10 mM; urea (or various other additives))

  3. Dynamic light scattering (298 K; pH: 5; Cby (concentrations of 50 uM and above) 50 uM; sodium acetate 10 mM)

  4. Nuclear magnetic resonance (NMR) (298 K; pH: 5; 14-3-3-zeta (protein interaction partner) 600 uM; DTT 1 mM; EDTA 1 mM; NaOH 50 mM; N-Cby(S20D) (to simulate phoshorylated-Cby) 200 uM; sodium acetate (buffer) 10 mM)

References:
  1. Mokhtarzada S, Yu C, Brickenden A, Choy WY. "Structural Characterization of Partially Disordered Human Chibby: Insights into Its Function in the Wnt-Signaling Pathway." 2011. PubMed: 21182262

Comments:
Mokhtarzada et al (2010) describe the N-terminal of Chibby (N-Cby) as overall intrinsically disordered with "mild helical propensity" at aa 20-50, while the rest of N-Cby "adopts transient beta-strand structure." Additionally, N-Cby contains a binding motif for 14-3-3 proteins at aa 16-22, and a nuclear export signal at aa 21-29.




Region 4
Type:Ordered
Name:C-terminal region
Location:64 - 126
Length:63
Region sequence:

GVSGGVDRREVQRLRRRNQQLEEENNLLRLKVDILLDMLSESTAESHLMEKELDELRISR
KRK

Modification type: Native
PDB:  
Structural/functional type: Function arises from the ordered state
Functional classes: Molecular recognition effectors
Functional subclasses: Intraprotein interaction
Nuclear localization
Protein-protein binding
Detection methods:
  1. Nuclear magnetic resonance (NMR) (298 K; pH: 5; Cby (250-300 uM); sodium acetate 10 mM; urea (varying concentrations))

  2. Circular dichroism (CD) spectroscopy, far-UV (298 K; at various pH levels; Cby 40 uM; sodium acetate 10 mM; urea (or various other additives))

  3. Dynamic light scattering (298 K; pH: 5; Cby (concentrations of 50 uM and above) 50 uM; sodium acetate 10 mM)

References:
  1. Mokhtarzada S, Yu C, Brickenden A, Choy WY. "Structural Characterization of Partially Disordered Human Chibby: Insights into Its Function in the Wnt-Signaling Pathway." 2011. PubMed: 21182262

Comments:
According to Mokhtarzada et al (2010), the C-terminal of Chibby is "strongly alpha-helical...with a stable four-heptad repeat coiled-coil" at aa 73-100.




References

  1. Mokhtarzada S, Yu C, Brickenden A, Choy WY. "Structural Characterization of Partially Disordered Human Chibby: Insights into Its Function in the Wnt-Signaling Pathway." 2011. PubMed: 21182262



Comments


Author Verified 1-31-2011 (PubMed: 21182262)


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