Interactions

Uniprot Id	Domain family	Domain Start	Domain End	Affinity Min/Max (µMol)	Notes
(Q15700) DLG2_HUMAN	PF00595 (PDZ) PDZ domain (Also known as DHR or GLGF)				[mitab][xml]
(O75970) MPDZ_HUMAN	PF00595 (PDZ) PDZ domain (Also known as DHR or GLGF)				[mitab][xml]

This ELM instance is part of the following 6 switching mechanisms annotated at the switches.ELM resource:

• SWTI000484:
  
  Alternative splicing removes the PDZ-binding motif of Plasma membrane calcium-transporting ATPase 4 (ATP2B4), abrogating binding to Nitric oxide synthase, brain (NOS1). PMCA4b acts as a negative regulator of Nitric oxide synthase, brain (NOS1), reducing production of nitric oxide in heart tissue. This negative regulation was not dependent on a conformational change due to binding of the PDZ ligand, but on Ca2+ depletion in close proximity of the enzyme. Nitric oxide production by NOS1 is known to be important in the regulation of excitation-contraction (EC) coupling and subsequently contractility.

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• SWTI000485:
  
  Alternative splicing removes the PDZ-binding motif of Plasma membrane calcium-transporting ATPase 4 (ATP2B4), abrogating binding to Disks large homolog 3 (DLG3). Disks large homolog 3 (DLG3) did not bind to \'b\' isoform of PMCA2. There is therefore an interaction selectivity between \'b\' isoforms of ATP2B4 and DLG3 as opposed to the promiscuity of \'b\' isoforms of ATP2B2 and ATP2B4 in interacting with other SAPs. Same study DLG4, DLG2 and DLG1 shown to bind to PDZ-binding motifs in \'b\' isoforms of ATP2B4 and ATP2B2.

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• SWTI000486:
  
  Alternative splicing removes the PDZ-binding motif of Plasma membrane calcium-transporting ATPase 4 (ATP2B4), abrogating binding to Disks large homolog 1 (DLG1). A much lower affinity was recorded for the third PDZ domain of DLG1 (in in the micromolar range (KD = 1.2 microM) compared to nanomolar affinity (KD = 1.6 nM)). PMCA4b and DLG1 are co-expressed in kidney and intestinal epithelial cells as well as in several areas of the brain. Should be noted that the \'b\' isoforms of Plasma membrane calcium-transporting ATPase 2 (ATP2B2) bind much more weakly to all PDZ domains of DLG1

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• SWTI000487:
  
  Alternative splicing removes the PDZ-binding motif of Plasma membrane calcium-transporting ATPase 4 (ATP2B4), abrogating binding to Peripheral plasma membrane protein CASK (CASK). The PDZ domain-containing protein CASK and PMCA4b co-precipitate in kidney and brain. Similar to NOS1, binding to PMCA4b allows Ca2+ dependent regulation. Depletion of local Ca2+ by PMCA4b in close proximity to CASK may inhibit Ca2+/calmodulin binding. This can subsequently inhibit binding to T-box brain protein 1 (TBR1) and/or translocation of CASK or the CASK/TBR1 complex to the nucleus.

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• SWTI000628:
  
  Alternative splicing removes the PDZ-binding motif of Plasma membrane calcium-transporting ATPase 4 (ATP2B4), abrogating binding to Disks large homolog 1 (DLG1). A much lower affinity was recorded for the third PDZ domain of DLG1 (in in the micromolar range (KD = 1.2 microM) compared to nanomolar affinity (KD = 1.6 nM)). PMCA4b and DLG1 are co-expressed in kidney and intestinal epithelial cells as well as in several areas of the brain.

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• SWTI000629:
  
  Alternative splicing removes the PDZ-binding motif of Plasma membrane calcium-transporting ATPase 4 (ATP2B4), abrogating binding to Disks large homolog 3 (DLG3). Disks large homolog 3 (DLG3) did not bind to \'b\' isoform of PMCA2. There is therefore an interaction selectivity between \'b\' isoforms of ATP2B4 and DLG3 as opposed to the promiscuity of \'b\' isoforms of ATP2B2 and ATP2B4 in interacting with other SAPs. Same study DLG4, DLG2 and DLG1 shown to bind to PDZ-binding motifs in \'b\' isoforms of ATP2B4 and ATP2B2.

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