DP00565: Calcineurin subunit B type 1FASTA viewXML view

General information
DisProt:DP00565
Name:Calcineurin subunit B type 1
Synonym(s):CANB1_HUMAN
Calcineurin B
CaNB
Protein phosphatase 2B regulatory subunit 1
Protein phosphatase 3 regulatory subunit B alpha isoform 1
PPP3R1
First appeared in release:Release 6.01 (10/15/2012)
UniProt:P63098
UniGene:Hs.280604
SwissProt: CANB1_HUMAN
TrEMBL:  
NCBI (GI): 52000904
Source organism:Homo sapiens (Human)
Sequence length:170
Percent disordered:31%
Homologues: 


Native sequence

        10         20         30         40         50         60
         |          |          |          |          |          |
MGNEASYPLE MCSHFDADEI KRLGKRFKKL DLDNSGSLSV EEFMSLPELQ QNPLVQRVID - 60
IFDTDGNGEV DFKEFIEGVS QFSVKGDKEQ KLRFAFRIYD MDKDGYISNG ELFQVLKMMV - 120
GNNLKDTQLQ QIVDKTIINA DKDGDGRISF EEFCAVVGGL DIHKKMVVDV



Functional narrative    

Function: Regulatory subunit of calcineurin, a calcium-dependent, calmodulin stimulated protein phosphatase. Confers calcium sensitivity.
Subunit structure: Composed of a catalytic subunit (A) [DP00092] and a regulatory subunit (B) [DP00565].
Miscellaneous: This protein has four functional calcium-binding sites.
Sequence similarities: Belongs to the calcineurin regulatory subunit family. Contains 4 EF-hand domains.
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Region 1: 1-16 Region 2: 44-53 Region 3: 82-87 Region 4: 120-128 Region 5: 159-170

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:N-terminal region
Location:1 - 16
Length:16
Region sequence:

MGNEASYPLEMCSHFD

Modification type: Complex
Native
PDB: 1AUI:B
Structural/functional type: Function arises from the disordered state
Functional classes: Modification site
Functional subclasses: Fatty acylation (myristolation and palmitoylation)
Detection methods:
  1. Nuclear magnetic resonance (NMR) (310 K; pH: 4.95; Calcineurin B 2.3 mM; CHAPS 25 mM; Ca2+ 20 mM; 95%H2O/5%D2O)

  2. Hydrogen-deuterium exchange (303 K; pH: 7.8; CaCl2 4 mM; Calcineurin B 0.4 mM; CHAPS 5 mM; D2O 0.7 mL; NaN3 0.01 %)

  3. Nuclear magnetic resonance (NMR) (320 K; pH: 5.9; CnB protein/CnA peptide(P2465) 1.5 mM; KCl 200 mM)

  4. X-ray crystallography (pH: 7.5; CaCl2 0.1 M; CaN A and B subunits (PDB 1AUI); DTT 1 mM; PEG 6000 8 %; TES 0.1 M)

  5. High relative B-factor

  6. Sensitivity to proteolysis

References:
  1. Anglister J, Grzesiek S, Wang AC, Ren H, Klee CB, Bax A. "1H, 13C, 15N nuclear magnetic resonance backbone assignments and secondary structure of human calcineurin B." Biochemistry. 1994; 33(12): 3540-7. PubMed: 8142351

  2. Anglister J, Ren H, Klee CB, Bax A. "NMR identification of calcineurin B residues affected by binding of a calcineurin A peptide." FEBS Lett.. 1995; 375(1-2): 108-12. PubMed: 7498455

  3. Jin L, Harrison SC. "Crystal structure of human calcineurin complexed with cyclosporin A and human cyclophilin." Proc Natl Acad Sci U S A. 2002; 99(21): 13522-6. PubMed: 12357034

  4. Kissinger CR, Parge HE, Knighton DR, Lewis CT, Pelletier LA, Tempczyk A, Kalish VJ, Tucker KD, Showalter RE, Moomaw EW, et al. "Crystal structures of human calcineurin and the human FKBP12-FK506-calcineurin complex." Nature. 1995; 378(6557): 641-4. PubMed: 8524402

  5. Li H, Zhang L, Rao A, Harrison SC, Hogan PG. "Structure of calcineurin in complex with PVIVIT peptide: portrait of a low-affinity signalling interaction." J. Mol. Biol.. 2007; 369(5): 1296-306. PubMed: 17498738

Comments:
 



Region 2
Type:Disordered
Name:Loop 2-3
Location:44 - 53
Length:10
Region sequence:

MSLPELQQNP

Modification type: Complex
Native
PDB:  
Structural/functional type: Function arises from the disordered state
Functional classes: Molecular recognition effectors
Functional subclasses: Flexible linkers/spacers
Detection methods:
  1. Nuclear magnetic resonance (NMR) (320 K; pH: 5.9; CnB protein/CnA peptide(P2465) 1.5 mM; KCl 200 mM)

References:
  1. Anglister J, Ren H, Klee CB, Bax A. "NMR identification of calcineurin B residues affected by binding of a calcineurin A peptide." FEBS Lett.. 1995; 375(1-2): 108-12. PubMed: 7498455

Comments:
 



Region 3
Type:Disordered
Name:domain linker (Loop 4-5)
Location:82 - 87
Length:6
Region sequence:

FSVKGD

Modification type: Complex
Native
PDB: 2P6B:B
Structural/functional type: Function arises from the disordered state
Functional classes: Molecular recognition effectors
Molecular assembly
Functional subclasses: Flexible linkers/spacers
Protein-protein binding
Detection methods:
  1. Nuclear magnetic resonance (NMR) (310 K; pH: 4.95; 95%H2O/5%D2O; Ca2+ 20 mM; Calcineurin B 2.3 mM; CHAPS 25 mM)

  2. Hydrogen-deuterium exchange (303 K; pH: 7.8; CaCl2 4 mM; Calcineurin B 0.4 mM; CHAPS 5 mM; D2O 0.7 mL; NaN3 0.01 %)

  3. Nuclear magnetic resonance (NMR) (320 K; pH: 5.9; CnB protein/CnA peptide(P2465) 1.5 mM; KCl 200 mM)

  4. X-ray crystallography (295 K; pH: 8; CaCl2 0.1 M; CNA (1-380)-CNB (16-170)-PVIVIT complex (PDB 2P6B) 7 mg/mL; DTT 0.001 M; PEG 4000 12 %; TES 0.1 M)

References:
  1. Anglister J, Grzesiek S, Wang AC, Ren H, Klee CB, Bax A. "1H, 13C, 15N nuclear magnetic resonance backbone assignments and secondary structure of human calcineurin B." Biochemistry. 1994; 33(12): 3540-7. PubMed: 8142351

  2. Anglister J, Ren H, Klee CB, Bax A. "NMR identification of calcineurin B residues affected by binding of a calcineurin A peptide." FEBS Lett.. 1995; 375(1-2): 108-12. PubMed: 7498455

  3. Li H, Zhang L, Rao A, Harrison SC, Hogan PG. "Structure of calcineurin in complex with PVIVIT peptide: portrait of a low-affinity signalling interaction." J. Mol. Biol.. 2007; 369(5): 1296-306. PubMed: 17498738

Comments:
 



Region 4
Type:Disordered
Name:Loop 6-7 (Loop F-G)
Location:120 - 128
Length:9
Region sequence:

VGNNLKDTQ

Modification type: Native
PDB:  
Structural/functional type: Function arises via a disorder to order transition
Functional classes: Molecular assembly
Functional subclasses: Flexible linkers/spacers
Detection methods:
  1. Nuclear magnetic resonance (NMR) (310 K; pH: 4.95; 95%H2O/5%D2O; Ca2+ 20 mM; Calcineurin B 2.3 mM; CHAPS 25 mM)

  2. Hydrogen-deuterium exchange (303 K; pH: 7.8; CaCl2 4 mM; Calcineurin B 0.4 mM; CHAPS 5 mM; D2O 0.7 mL; NaN3 0.01 %)

References:
  1. Anglister J, Grzesiek S, Wang AC, Ren H, Klee CB, Bax A. "1H, 13C, 15N nuclear magnetic resonance backbone assignments and secondary structure of human calcineurin B." Biochemistry. 1994; 33(12): 3540-7. PubMed: 8142351

Comments:
Anglister et al (1994) describe fast H/D exchange for this region (loop V120-K125 plus the first 3 residues of helix 7, D126-Q128), and this region is visible in crystal structures, suggesting a disorder-to-order transition.




Region 5
Type:Disordered
Name:C-terminal region
Location:159 - 170
Length:12
Region sequence:

GLDIHKKMVVDV

Modification type: Complex
Native
PDB: 1AUI:B, 1MF8:B, 2P6B:B
Structural/functional type: Function arises from the disordered state
Functional classes: Unknown
Functional subclasses: Unknown
Detection methods:
  1. Nuclear magnetic resonance (NMR) (303 K; pH: 4.95; 95%H2O/5%D2O; Ca2+ 20 mM; Calcineurin B 2.3 mM; CHAPS 25 mM)

  2. Hydrogen-deuterium exchange (303 K; pH: 7.8; CaCl2 4 mM; Calcineurin B 0.4 mM; CHAPS 5 mM; D2O 0.7 mL; NaN3 0.01 %)

  3. Nuclear magnetic resonance (NMR) (320 K; pH: 5.9; CnB protein/CnA peptide(P2465) 1.5 mM; KCl 200 mM)

  4. X-ray crystallography (pH: 7.5; CaCl2 0.1 M; CaN A and B subunits (PDB 1AUI); DTT 1 mM; PEG 6000 8 %; TES 0.1 M)

  5. X-ray crystallography (292 K; pH: 4.6; Cyp/CsA/Cn complex (PDB 1MF8); glycerol 15 %; potassoium phosphate 5 mM; sodium citrate 75 mM; Tris 5 mM)

  6. X-ray crystallography (295 K; pH: 8; CaCl2 0.1 M; CNA (1-380)-CNB (16-170)-PVIVIT complex (PDB 2P6B) 7 mg/mL; DTT 0.001 M; PEG 4000 12 %; TES 0.1 M)

  7. High relative B-factor

  8. Sensitivity to proteolysis

References:
  1. Anglister J, Grzesiek S, Wang AC, Ren H, Klee CB, Bax A. "1H, 13C, 15N nuclear magnetic resonance backbone assignments and secondary structure of human calcineurin B." Biochemistry. 1994; 33(12): 3540-7. PubMed: 8142351

  2. Anglister J, Ren H, Klee CB, Bax A. "NMR identification of calcineurin B residues affected by binding of a calcineurin A peptide." FEBS Lett.. 1995; 375(1-2): 108-12. PubMed: 7498455

  3. Jin L, Harrison SC. "Crystal structure of human calcineurin complexed with cyclosporin A and human cyclophilin." Proc Natl Acad Sci U S A. 2002; 99(21): 13522-6. PubMed: 12357034

  4. Kissinger CR, Parge HE, Knighton DR, Lewis CT, Pelletier LA, Tempczyk A, Kalish VJ, Tucker KD, Showalter RE, Moomaw EW, et al. "Crystal structures of human calcineurin and the human FKBP12-FK506-calcineurin complex." Nature. 1995; 378(6557): 641-4. PubMed: 8524402

  5. Li H, Zhang L, Rao A, Harrison SC, Hogan PG. "Structure of calcineurin in complex with PVIVIT peptide: portrait of a low-affinity signalling interaction." J. Mol. Biol.. 2007; 369(5): 1296-306. PubMed: 17498738

Comments:
 



References

  1. Manalan AS, Klee CB. "Activation of calcineurin by limited proteolysis." Proc. Natl. Acad. Sci. U.S.A.. 1983; 80(14): 4291-5. PubMed: 6576338



Comments


The entry DP00092_A001 has been replaced by DP00565. The protein Calcineurin subunit B type 1 is not an alternatively-spliced version of DP00092:Serine/threonine-protein phosphatase 2B catalytic subunit alpha isoform, and therefore receives its own DisProt record, DP00565. The two proteins are interacting subunits of calcineurin.



Manalan and Klee (1983) conducted proteolysis experiments on bovine calcineurin.


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