Conserved Protein Domain Family
SH3_MPP1-like

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cd12035: SH3_MPP1-like 
Src Homology 3 domain of Membrane Protein, Palmitoylated 1 (or MAGUK p55 subfamily member 1)-like proteins
This subfamily includes MPP1, CASK (Calcium/calmodulin-dependent Serine protein Kinase), Caenorhabditis elegans lin-2, and similar proteins. MPP1 and CASK are scaffolding proteins from the MAGUK (membrane-associated guanylate kinase) protein family, which is characterized by the presence of a core of three domains: PDZ, SH3, and guanylate kinase (GuK). In addition, they also have the Hook (Protein 4.1 Binding) motif in between the SH3 and GuK domains. The GuK domain in MAGUK proteins is enzymatically inactive; instead, the domain mediates protein-protein interactions and associates intramolecularly with the SH3 domain. CASK and lin-2 also contain an N-terminal calmodulin-dependent kinase (CaMK)-like domain and two L27 domains. MPP1 is ubiquitously-expressed and plays roles in regulating neutrophil polarity, cell shape, hair cell development, and neural development and patterning of the retina. CASK is highly expressed in the mammalian nervous system and plays roles in synaptic protein targeting, neural development, and gene expression regulation. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.
Statistics
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PSSM-Id: 212968
Aligned: 8 rows
Threshold Bit Score: 124.467
Created: 2-Jun-2011
Updated: 2-Oct-2020
Structure
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Aligned Rows:
 
peptide ligandGuK domain
Feature 1:peptide ligand binding site [polypeptide binding site]
Evidence:
  • Comment:based on the binding of peptide ligands to the SH3 domains of other superfamily members
  • Comment:SH3 domains typically bind proline-rich ligands, preferentially to PxxP motifs.
  • Citation:PMID 7664083
  • Citation:PMID 7735837
  • Comment:flanking hinge and loops (RT and n-Src) confer sequence specificity for ligand residues outside the core binding motif

Sequence Alignment
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Format: Row Display: Color Bits: Type Selection:
Feature 1              # #  #          #                 ##                              # ## 
1346575       162 FMRAQFDYDPKKDNLIPCKEAGLKFATGDIIQIINKDDSNWWQGRVEgs--------------sKESAGLIPSPEL 223  human
O14936        616 YVRAQFEYDPAKDDLIPCKEAGIRFRVGDIIQIISKDDHNWWQGKLEns--------------kNGTAGLIPSPEL 677  human
XP_001631427  627 FVRALFDYDPRSDDLIPCQRAGMAFHCSEILQVVNKADCYWWQAKKPda--------------nEEFAGLIPSPEL 688  starlet sea anemone
XP_002163427  428 YVRCLFDYDSSLDNLIPCQQAGMSFECGEILEIKCKSDPLWWQATKPg----------------KHMAGLIPSQEL 487  green hydra
P54936        637 FVRAQFDYEPSQDDLIPCPQAGIPFKTGDILQVISKDDHNWWQARFVssfpsignssnaqrsnqQQVAGLIPSPEL 712  nematode
XP_002573209  543 YVRAMFDYNPENDDLIPCTQAGIHFHIGDILQIISKDDHNWWQVRNYc----------------QAPAGLIPSPEL 602  Schistosoma mansoni
AAO83853      608 YVRALFNYDPRDDDLIPCSQAGVPFKVGDVLRIISKDDSDWWQAKKWea-------------ksSGPAGLIPSPEL 670  great pond snail
EFX82008      604 YVRAQFDYDPLGDDTIPCAQAGIAFKTGDILQIISKDDNRWWQARKDga-------------geLAPAGLVPSPEL 666  common water flea

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