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: 2EGK
<a href="http://www.rcsb.org/pdb/cgi/explore.cgi?pdbId=2EGK" title="" target="_blank"><img src="/media/pdb.ico.png"/>2EGK</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)
Acc., Gene-, NameStartEndSubsequenceLogic#Ev.OrganismNotes
P07550 ADRB2
ADRB2_HUMAN
408 413 VPSDNIDSQGRNCSTNDSLL TP 3 Homo sapiens (Human)
1 
1 
P09619 PDGFRB
PGFRB_HUMAN
1101 1106 EQLPDSGCPAPRAEAEDSFL TP 3 Homo sapiens (Human)
1 
1 
P11274 BCR
BCR_HUMAN
1266 1271 LEAIPAPDSKRQSILFSTEV TP 1 Homo sapiens (Human)
1 
1 
Q9H251 CDH23
CAD23_HUMAN
3349 3354 TPLHKLRDVIMETPLEITEL TP 1 Homo sapiens (Human)
1 
P35222 CTNNB1
CTNB1_HUMAN
776 781 LMDGLPPGDSNQLAWFDTDL TP 2 Homo sapiens (Human)
1 
2 
Q792Q4 Cript
CRIPT_RAT
96 101 ICAMCGKKVLDTKNYKQTSV TP 1 Rattus norvegicus (Norway rat)
1 
Q8QG92 dact1-b
DCT1B_XENLA
819 824 NLKKKILRFRSGSLKLMTTV TP 3 Xenopus laevis (African clawed frog)
1 
Q13268 DHRS2
DHRS2_HUMAN
253 258 PDASYVNGENIAVAGYSTRL TP 1 Homo sapiens (Human)
1 
P97836 Dlgap1
DLGP1_RAT
987 992 SATESAESIEIYIPEAQTRL TP 1 Rattus norvegicus (Norway rat)
1 
Q86XX4 FRAS1
FRAS1_HUMAN
4002 4007 VKRLNLEVRVHNNLQDGTEV TP 2 Homo sapiens (Human)
1 
Q8R4T5 Grasp
GRASP_RAT
389 394 RLLKFIPGLNRSLEEEESQL TP 2 Rattus norvegicus (Norway rat)
1 
2 
Q9WTT6 Gda
GUAD_RAT
449 454 RNIEEVYVGGKQVVPFSSSV TP 1 Rattus norvegicus (Norway rat)
1 
P19490 Gria1
GRIA1_RAT
902 907 MQSIPCMSHSSGMPLGATGL TP 6 Rattus norvegicus (Norway rat)
1 
Q01344 IL5RA
IL5RA_HUMAN
415 420 IEVICYIEKPGVETLEDSVF TP 6 Homo sapiens (Human)
1 
P48050 KCNJ4
IRK4_HUMAN
440 445 ERMQASLPLDNISYRRESAI TP 4 Homo sapiens (Human)
1 
1 
P23634 ATP2B4
AT2B4_HUMAN
1236 1241 CNQVQLPQSDSSLQSLETSV TP 1 Homo sapiens (Human)
2 
6 
O55043 Arhgef7
ARHG7_RAT
641 646 KLVRKVLKNMNDPAWDETNL TP 1 Rattus norvegicus (Norway rat)
1 
Q8TEU7 RAPGEF6
RPGF6_HUMAN
1596 1601 LGDVTDADSEADENEQVSAV TP 3 Homo sapiens (Human)
1 
Q495M9 USH1G
USH1G_HUMAN
456 461 AVRRRRQAMERPPALEDTEL TP 4 Homo sapiens (Human)
1 
P89079 E4
E4OR1_ADE09
120 125 VGTLLLERVIFPSVKIATLV TP 3 Human adenovirus 9
1 
P03126 E6
VE6_HPV16
153 158 WTGRCMSCCRSSRTRRETQL TP 2 Human papillomavirus type 16
1 
P03524 G
VGLG_RABVE
519 524 QSGKIISSWESHKSGGETRL TP 3 Rabies virus ERA
1 
Q7TFX0 
Q7TFX0_RHCM6
141 146 IHFTVNNLILIFRVSEETQL TP 1 Rhesus cytomegalovirus strain 68-1
1 
Q9DWF6 R35
Q9DWF6_RCMVM
516 521 PYSATGRRRGAVEGTRETSL TP 1 Rat cytomegalovirus Maastricht
1 
Q9Q8F7 m147R
Q9Q8F7_MYXVL
283 288 HKISMYRCVMQADELLETDV TP 1 Myxoma virus (strain Lausanne)
1 
Q9Q8T6 s147R
Q9Q8T6_RFVKA
282 287 HKISIYRCIMQADELMETDV TP 1 Rabbit fibroma virus (strain Kasza)
1 
P26672 VACWR172
A46_VACCW
235 240 YFEDDDSSTCSAVTDRETDV TP 1 Vaccinia virus WR
1 
O88602 Cacng2
CCG2_MOUSE
318 323 QKDSKDSLHANTANRRTTPV TP 3 Mus musculus (House mouse)
1 
P31424 Grm5
GRM5_RAT
1198 1203 SSPKYDTLIIRDYTQSSSSL TP 3 Rattus norvegicus (Norway rat)
1 
Q61315 Apc
APC_MOUSE
2840 2845 ESSGAQSPKRHSGSYLVTSV TP 1 Mus musculus (House mouse)
1 
Q9EPK5 Wwtr1
WWTR1_MOUSE
390 395 PLFNDVESALNKSEPFLTWL TP 3 Mus musculus (House mouse)
P46937-2 YAP1
YAP1_HUMAN
483 488 DMESVLAATKLDKESFLTWL TP 5 Homo sapiens (Human)
1 
P13569 CFTR
CFTR_HUMAN
1475 1480 KPQIAALKEETEEEVQDTRL TP 6 Homo sapiens (Human)
1 
1 
P46937 YAP1
YAP1_HUMAN
499 504 DMESVLAATKLDKESFLTWL TP 7 Homo sapiens (Human)
1 
P46937-3 YAP1
YAP1_HUMAN
449 454 DMESVLAATKLDKESFLTWL TP 4 Homo sapiens (Human)
P36762 L2
VL2_HPV49
516 521 SGDFYLHPSLRRRKRKRTYL TP 1 Human papillomavirus type 49
1 
P06463 E6
VE6_HPV18
153 158 HSCCNRARQERLQRRRETQV TP 3 Human papillomavirus type 18
3 
Q9QUH6 Syngap1
SYGP1_RAT
1303 1308 KRLLDAQRGSFPPWVQQTRV TP 4 Rattus norvegicus (Norway rat)
2 
P03409 tax
TAX_HTL1A
348 353 QISPGGLEPPSEKHFRETEV TP 4 Human T-cell lymphotrophic virus type 1 (strain ATK)
1 
P97288-2 Htr4
5HT4R_MOUSE
382 387 HQELEKLPIHNDPESLESCF TP 4 Mus musculus (House mouse)
1 
3 
Q9P0K1 ADAM22
ADA22_HUMAN
901 906 LPDEDKKVNRQSARLWETSI TP 3 Homo sapiens (Human)
1 
Q01814 ATP2B2
AT2B2_HUMAN
1238 1243 SKSATSSSPGSPIHSLETSL TP 4 Homo sapiens (Human)
1 
Q9UQB8-4 BAIAP2
BAIP2_HUMAN
516 521 LDDYGARSMSSGSGTLVSTV TP 4 Homo sapiens (Human)
1 
Q05586-4 GRIN1
NMDZ1_HUMAN
917 922 HPTDITGPLNLSDPSVSTVV TP 2 Homo sapiens (Human)
6 
O55207-3 Synj2
SYNJ2_RAT
1288 1293 FVRTVAAQRLTPVDASGSSV TP 9 Rattus norvegicus (Norway rat)
1 
1 
P22756-2 Grik1
GRIK1_RAT
900 905 SFTSILTCHQRRTQRKETVA TP 4 Rattus norvegicus (Norway rat)
1 
1 
Q66T02 Plekhg5
PKHG5_MOUSE
1068 1073 QLYRIRTTLLLNSTLTASEV TP 2 Mus musculus (House mouse)
1 
1 
P51790-2 CLCN3
CLCN3_HUMAN
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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