1G9O,2KRG,3NGH,6EZI,4Q2P,2V90,2OCS,2EDZ,2HE4,2D90,4R2Z


Conserved Protein Domain Family
PDZ_NHERF-like

?
cd06768: PDZ_NHERF-like 
PDZ domains of the Na+/H+ exchange regulatory cofactor (NHERF) family (NHERF1-4), and related domains
PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of the Na+/H+ exchange regulatory cofactor (NHERF) family of multi-PDZ-domain-containing scaffolding proteins (NHERF1-4), and related domains. The NHERF family includes NHERF1 (also known as EBP50), NHERF2 (also known as E3KARP; TKA-1; SIP-1), NHERF3 (also known as CAP70; CLAMP; Napi-Cap-1; PDZD1) and NHERF4 (also known as IKEPP; PDZK2; Napi-Cap-2). NHERF1 and NHERF2 have tandem PDZ domains (PDZ1-2); NHERF3 and NHERF4 have four PDZ domains (PDZ1-4). NHERFs are involved in the regulation of multiple receptors or transporters, such as type II sodium-phosphate cotransporter (Npt2a), purinergic P2Y1 receptor P2Y1R, the beta2-adrenergic receptor (beta2-AR), parathyroid hormone receptor type 1 (PTHR), the lysophosphatidic acid receptors (LPARs), sodium-hydrogen exchanger 3 (NHE3), and cystic fibrosis transmembrane conductance regulator (CFTR). NHERF-PDZ1 domain interaction partners include Npt2a, purinergic P2Y1 receptor, beta2-AR, CFTR, PTHR, NH3, G-protein-coupled receptor kinase 6 (GRK6A), platelet-derived growth factor receptor (PDGFR), B1 subunit of the H+ATPase, cholesterol, receptor for activated C-kinase RACK1, aquaporin 9, among others. The NHERF PDZ2 domain interacts with fewer proteins: NHERF1 PDZ2 binds Npt2a, PTHR, beta-catenin, aquaporin 9, and RACK1; NHERF2 PDZ2 binds LPA2, P2Y1R, and NHE3, cGMP-dependent protein kinase type II (cGKII). NHERF4 PDZ1 and PDZ4 bind the epithelial Ca(2+) channels TRPV5 and TRPV6. NHERF2/NHERF3 heterodimerization is mediated by PDZ domains of NHERF2 and the C-terminal PDZ domain recognition motif of NHERF3. NHERF4 regulates several transporters mediating influx of xenobiotics and nutrients in the small intestine. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This NHERF-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.
Statistics
?
PSSM-Id: 467249
Aligned: 129 rows
Threshold Bit Score: 82.4865
Created: 18-Mar-2008
Updated: 27-Apr-2023
Structure
?
Program:
Drawing:
Aligned Rows:
 
peptide binding
Conserved site includes 13 residues -Click on image for an interactive view with Cn3D
Feature 1:peptide binding site [polypeptide binding site]
Evidence:
  • Comment:based on canonical PDZ domains with structure
  • Comment:PDZ domains specifically recognize and bind to short C-terminal peptide motifs, but can also recognize internal peptide motifs and certain lipids
  • Structure:6EZI: PDZ domain 4 of human NHERF3 binds C-terminal peptide of human PepT2; contacts at 4A
  • Structure:2KRG: PDZ domain 2 of human NHERF1 binds the C-terminus of NHERF1 in the peptide binding site; contacts at 4A
  • Comment:NHERF1 is held in an autoinhibited state through intramolecular interactions between PDZ domain 2 and the C-terminal domain that also includes a C-terminal PDZ-binding motif (-SNL)

Sequence Alignment
?
Format: Row Display: Color Bits: Type Selection:
Feature 1                   #######            #  #                            #   #  ##          
1G9O_A          5 RLCCLEKGpnGYGFHLHgek--gklGQYIRLVEpGSPAEKAGLLAGDRLVEVNGENVEketHQQVVSRIRAalnAVRLLV 82   human
6EZI_A          6 KLCRLAKGenGYGFHLNair--glpGSFIKEVQkGGPADLAGLEDEDVIIEVNGVNVLdepYEKVVDRIQSsgkNVTLLV 83   human
XP_009859854  368 RLCKLVKDegGFGFFLKdd-----dGHVLGHIEqGGSAQKAGVQESDHIIEVNGVNVQndtHDQVVDKIRKsgdHVTFLV 442  vase tunicate
XP_014350402  162 RLCYIIKDknRFGFNLSsrk--gmkGKFTLNVTsGGPAERSGVHIGDILIEINGVNVThctSSQVIRKIKEsgeKVAVLV 239  coelacanth
XP_007894319  160 RVCHVTRGprGFGFELSpsk--girGHFTLTVTeAGEAEKALVQTDDRLIEVNGENVEdctYLQVSKRIKEsgeAVTLLV 237  elephant shark
Q86UT5        222 RLCHIVKDegGFGFSVThg----nqGPFWLVLStGGAAERAGVPPGARLLEVNGVSVEkftHNQLTRKLWQsgqQVTLLV 297  human
XP_040546158  150 RLCHITRDksGFGFSVSgpe--gvkGTFQLSVRqDGPAERAGVPSGSWLLELNGHSVRscsHTQLARKLKQsgsKVTLLV 227  Gallus gallus
XP_685398     173 RLCHITKEp-GCGLGLSiipiegarGRYRLNPVtDGPAERAGIQNGDRLIWINGVSISvisYAALAKMVKKcekHLTVLV 251  zebrafish
NP_001124259  149 HLCHIRKDahGMGFNILpve--gekRKFAVSPVkGGAAERAGVRKGDHLIWIDGAMASeltHSAISKMVKKcssHMTVLV 226  zebrafish
CAG05858      121 RLCYLVNSksGFGFSLSsvn--gepGMFIKLVTpGGVAQNAGLNVNDRLVEINGENIEglsHAEVVDMINKagkSLMFLV 198  Tetraodon nig...
Feature 1           
1G9O_A         83 VD 84   human
6EZI_A         84 CG 85   human
XP_009859854  443 VN 444  vase tunicate
XP_014350402  240 ID 241  coelacanth
XP_007894319  238 AG 239  elephant shark
Q86UT5        298 AG 299  human
XP_040546158  228 AS 229  Gallus gallus
XP_685398     252 ID 253  zebrafish
NP_001124259  227 ID 228  zebrafish
CAG05858      199 VD 200  Tetraodon nigroviridis

| Disclaimer | Privacy statement | Accessibility |
NCBI Home NCBI Search NCBI SiteMap