The Eukaryote Linear Motif resource for Functional Sites in Proteins
Accession:
Functional site class:
PDZ ligands
Functional site description:
The best characterised PDZ ligands are short C-terminal peptides that bind in a surface groove by beta-augmentation to a beta sheet with the PDZ domain. The peptide carboxy terminus is specifically recognised by complementary polar interactions with the PDZ domain. Although there is a considerable literature on internal sequence peptide interactions, we are not currently able to represent internal PDZ-binding peptides in ELM.
ELMs with same func. site: LIG_PDZ_Class_1  LIG_PDZ_Class_2  LIG_PDZ_Class_3 
ELM Description:
PDZ domains recognize short sequences at the carboxy terminus of target proteins. The terminal residue is apparently always hydrophobic with the -3 position being a strong determinant of specificity. The class 1 motif has a pattern such as (ST)X(VIL)*. We have made the terminal position more relaxed based on experimental binding data. However, probably not all PDZ domain instances can accept either A or F. Several less conserved positions in the motif may modulate affinity and specificity of the ligand domain interaction.
Pattern: ...[ST].[ACVILF]$
Pattern Probability: 0.0000725
Present in taxons: Eukaryota Homo sapiens Metazoa Mus musculus
Interaction Domain:
PDZ (PF00595) PDZ domain (Also known as DHR or GLGF) (Stochiometry: 1 : 1)
PDB Structure: 1D5G
<a href="http://www.rcsb.org/pdb/cgi/explore.cgi?pdbId=1D5G" title="" target="_blank"><img src="/media/pdb.ico.png"/>1D5G</a>
o See 48 Instances for LIG_PDZ_Class_1
o Abstract
PDZ domains are ~90 residue globular protein modules that can be found in eukaryotic regulatory proteins. They are found in most eukaryotes but the domain family is hugely expanded in the metazoa (~200 PDZ domain instances are found in the Human proteome). Thus nearly all of the metazoan PDZ domain functions are specific to this evolutionary lineage.

PDZ domain-containing proteins spend at least part of their time in membrane-associated complexes. Many PDZ ligands are themselves membrane proteins. Several PDZ domain containing proteins include multiple domain copies (MPDZ/MUPP1 and MAGI2 contain 13 and 6 PDZ domain instances respectively), acting as scaffolds, recruiting multiple PDZ domain binding proteins and facilitating the construction of large membrane-associated complexes. PDZ domains also co-occur regularly with other signalling/regulatory domains regulating many biological processes such as transport and signal transduction (Lee,2010). There is increasing evidence that some, ultimately perhaps most, PDZ domains also bind to phospholipid headgroups (Gallardo,2010). Thus PDZ domains have a role in assembly of signalling complexes at membrane locations determined by the appropriate lipid modification state. In large multiprotein complexes, they may do this in conjunction with other lipid-sampling domains such as C2, PH, PX and so forth to differentiate different membrane contexts. Peptide and lipid binding by PDZ domains is found to be co-operative, enabling tight integration of lipid and protein regulatory signals.

The known PDZ-binding specificities are divided into three classes. The position 0 (C-terminal residue) is always hydrophobic while the class is determined by the position -2 residue. These two positions are the most buried in the bound complexes, hence they are strong specificity determinants. The neighbouring residues can undoubtedly contribute to specificity and affinity of the interactions. In ELM we have chosen relaxed motif patterns based on the solved PDZ complexes, so it is likely that any given peptide will only bind to a subset of the PDZ domains belonging to that class.
o 14 selected references:

o 6 GO-Terms:

o 48 Instances for LIG_PDZ_Class_1
(click table headers for sorting; Notes column: =Number of Switches, =Number of Interactions)
Protein NameGene NameStartEndSubsequenceLogic#Ev.OrganismNotes
ADRB2_HUMAN ADRB2 408 413 VPSDNIDSQGRNCSTNDSLL TP 3 Homo sapiens (Human)
1 
1 
PGFRB_HUMAN PDGFRB 1101 1106 EQLPDSGCPAPRAEAEDSFL TP 3 Homo sapiens (Human)
1 
1 
BCR_HUMAN BCR 1266 1271 LEAIPAPDSKRQSILFSTEV TP 1 Homo sapiens (Human)
1 
1 
CAD23_HUMAN CDH23 3349 3354 TPLHKLRDVIMETPLEITEL TP 1 Homo sapiens (Human)
1 
CTNB1_HUMAN CTNNB1 776 781 LMDGLPPGDSNQLAWFDTDL TP 2 Homo sapiens (Human)
1 
2 
CRIPT_RAT Cript 96 101 ICAMCGKKVLDTKNYKQTSV TP 1 Rattus norvegicus (Norway rat)
1 
DCT1B_XENLA dact1-b 819 824 NLKKKILRFRSGSLKLMTTV TP 3 Xenopus laevis (African clawed frog)
1 
DHRS2_HUMAN DHRS2 253 258 PDASYVNGENIAVAGYSTRL TP 1 Homo sapiens (Human)
1 
DLGP1_RAT Dlgap1 987 992 SATESAESIEIYIPEAQTRL TP 1 Rattus norvegicus (Norway rat)
1 
FRAS1_HUMAN FRAS1 4002 4007 VKRLNLEVRVHNNLQDGTEV TP 2 Homo sapiens (Human)
1 
GRASP_RAT Grasp 389 394 RLLKFIPGLNRSLEEEESQL TP 2 Rattus norvegicus (Norway rat)
1 
2 
GUAD_RAT Gda 449 454 RNIEEVYVGGKQVVPFSSSV TP 1 Rattus norvegicus (Norway rat)
1 
GRIA1_RAT Gria1 902 907 MQSIPCMSHSSGMPLGATGL TP 6 Rattus norvegicus (Norway rat)
1 
IL5RA_HUMAN IL5RA 415 420 IEVICYIEKPGVETLEDSVF TP 6 Homo sapiens (Human)
1 
IRK4_HUMAN KCNJ4 440 445 ERMQASLPLDNISYRRESAI TP 4 Homo sapiens (Human)
1 
1 
AT2B4_HUMAN ATP2B4 1236 1241 CNQVQLPQSDSSLQSLETSV TP 1 Homo sapiens (Human)
2 
6 
ARHG7_RAT Arhgef7 641 646 KLVRKVLKNMNDPAWDETNL TP 1 Rattus norvegicus (Norway rat)
1 
RPGF6_HUMAN RAPGEF6 1596 1601 LGDVTDADSEADENEQVSAV TP 3 Homo sapiens (Human)
1 
USH1G_HUMAN USH1G 456 461 AVRRRRQAMERPPALEDTEL TP 4 Homo sapiens (Human)
1 
E4OR1_ADE09 E4 120 125 VGTLLLERVIFPSVKIATLV TP 3 Human adenovirus 9
1 
VE6_HPV16 E6 153 158 WTGRCMSCCRSSRTRRETQL TP 2 Human papillomavirus type 16
1 
VGLG_RABVE G 519 524 QSGKIISSWESHKSGGETRL TP 3 Rabies virus ERA
1 
Q7TFX0_RHCM6 141 146 IHFTVNNLILIFRVSEETQL TP 1 Rhesus cytomegalovirus strain 68-1
1 
Q9DWF6_RCMVM R35 516 521 PYSATGRRRGAVEGTRETSL TP 1 Rat cytomegalovirus Maastricht
1 
Q9Q8F7_MYXVL m147R 283 288 HKISMYRCVMQADELLETDV TP 1 Myxoma virus (strain Lausanne)
1 
Q9Q8T6_RFVKA s147R 282 287 HKISIYRCIMQADELMETDV TP 1 Rabbit fibroma virus (strain Kasza)
1 
A46_VACCW VACWR172 235 240 YFEDDDSSTCSAVTDRETDV TP 1 Vaccinia virus WR
1 
CCG2_MOUSE Cacng2 318 323 QKDSKDSLHANTANRRTTPV TP 3 Mus musculus (House mouse)
1 
GRM5_RAT Grm5 1198 1203 SSPKYDTLIIRDYTQSSSSL TP 3 Rattus norvegicus (Norway rat)
1 
APC_MOUSE Apc 2840 2845 ESSGAQSPKRHSGSYLVTSV TP 1 Mus musculus (House mouse)
1 
WWTR1_MOUSE Wwtr1 390 395 PLFNDVESALNKSEPFLTWL TP 3 Mus musculus (House mouse)
YAP1_HUMAN YAP1 483 488 DMESVLAATKLDKESFLTWL TP 5 Homo sapiens (Human)
1 
CFTR_HUMAN CFTR 1475 1480 KPQIAALKEETEEEVQDTRL TP 6 Homo sapiens (Human)
1 
1 
YAP1_HUMAN YAP1 499 504 DMESVLAATKLDKESFLTWL TP 7 Homo sapiens (Human)
1 
YAP1_HUMAN YAP1 449 454 DMESVLAATKLDKESFLTWL TP 4 Homo sapiens (Human)
VL2_HPV49 L2 516 521 SGDFYLHPSLRRRKRKRTYL TP 1 Human papillomavirus type 49
1 
VE6_HPV18 E6 153 158 HSCCNRARQERLQRRRETQV TP 3 Human papillomavirus type 18
3 
SYGP1_RAT Syngap1 1303 1308 KRLLDAQRGSFPPWVQQTRV TP 4 Rattus norvegicus (Norway rat)
2 
TAX_HTL1A tax 348 353 QISPGGLEPPSEKHFRETEV TP 4 Human T-cell lymphotrophic virus type 1 (strain ATK)
1 
5HT4R_MOUSE Htr4 382 387 HQELEKLPIHNDPESLESCF TP 4 Mus musculus (House mouse)
1 
3 
ADA22_HUMAN ADAM22 901 906 LPDEDKKVNRQSARLWETSI TP 3 Homo sapiens (Human)
1 
AT2B2_HUMAN ATP2B2 1238 1243 SKSATSSSPGSPIHSLETSL TP 4 Homo sapiens (Human)
1 
BAIP2_HUMAN BAIAP2 516 521 LDDYGARSMSSGSGTLVSTV TP 4 Homo sapiens (Human)
1 
NMDZ1_HUMAN GRIN1 917 922 HPTDITGPLNLSDPSVSTVV TP 2 Homo sapiens (Human)
6 
SYNJ2_RAT Synj2 1288 1293 FVRTVAAQRLTPVDASGSSV TP 9 Rattus norvegicus (Norway rat)
1 
1 
GRIK1_RAT Grik1 900 905 SFTSILTCHQRRTQRKETVA TP 4 Rattus norvegicus (Norway rat)
1 
1 
PKHG5_MOUSE Plekhg5 1068 1073 QLYRIRTTLLLNSTLTASEV TP 2 Mus musculus (House mouse)
1 
1 
CLCN3_HUMAN CLCN3 861 866 TDEEREETEEEVYLLNSTTL TP 3 Homo sapiens (Human)
1 
1 
Please cite: The Eukaryotic Linear Motif Resource ELM: 10 Years and Counting (PMID:24214962)

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