The Eukaryote Linear Motif resource for Functional Sites in Proteins
LIG_EH_1 56
 
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Functional site class: EH ligand
Functional site description: Asn-Pro-Phe motif responsible for the interaction with Eps15 homology (EH) domain
ELMs: LIG_EH_1
Description: The canonical EH binding peptide is a strongly conserved NPF motif. The adjacent residues can affect affinity but are too poorly conserved to be modeled in the regular expression.
Pattern: .NPF. (Probability: 0.0000586)
Present in taxons: Eukaryota Homo sapiens Mus musculus
PDB Structure: 2JXC
PDB:2JXC
Interaction Domain:

efhand (PF00036)
EF hand
(Stochiometry: 1 : 1)

efhand_3 (PF12763)
Cytoskeletal-regulatory complex EF hand
(Stochiometry: 1 : 1)

o See 85 Instances for LIG_EH_1


o Abstract

The EH (for Eps15 homology) domain is present in three copies in the amino terminus of the tyrosine kinase substrates Eps15 and Eps15R and shared with other proteins of mammals, flies, nematode, plants, yeast and possibly all other eukaryotes. EH domains are exclusively found in proteins that function in endocytosis and vesicular trafficking and are believed to regulate these processes. They recognize proteins containing single or multiple NPF (Asn-Pro-Phe) motifs, such as RAB, NUMB, SCAMP, Syndapin, Stonin2, CALM, synaptojanin and epsin. Some of the interactions between EH-domain containing proteins and NPF-containing proteins are known to regulate receptor-mediated endocytosis.

EH domains consist of four helices: Helices 1 and 2 as well as 3 and 4 constitute helix-loop-helix motifs of the EF hand type. The pattern of amino acids defining EH domains consists of a central tryptophan residue situated on the third helix that is flanked by an array of highly conserved, mostly hydrophobic residues. These residues form a hydrophobic groove between helices 2 and 3 which accommodates the NPF motif of the binding partner. Measurements of EH interactions are often in the mid-micromolar range, somewhat lower affinity than most linear motifs. This suggests that co-operativity will be important to generate stable binding interactions.

For the EH domains of Eps15 (more precisely the N-terminal and central EH domain) binding is enhanced when Thr or Ser occupy the two positions preceding NPF and when a hydrophobic or basic residue follows. Acidic residues in the flanking regions are mostly found in ligands of the family of EHD (EH domain containing) proteins, whereas they decrease the affinity of NPF ligands towards the EH domains of Eps15 or Intersectin.

Some variations of the canonical binding mode have been reported. The EH domains of Reps, for example, have been reported to bind to DPF (Asp-Pro-Phe) motifs in addition to NPF motifs. Furthermore the EH domain of EHD2 has been shown to bind to an internal GPF (Gly-Pro-Phe) motif, which might constitute an autoinhibitory mechanism. An interaction between two adjacent NPF motifs, found within Stonin2, and a single EH domain of Eps15 was found to increase specificity and affinity dramatically. Given that NPF motifs as well as EH domains often occur in multiple copies within a single protein, co-operative, multivalent binding modes might be a general mechanism by which EH domains modulate their binding properties.

o 19 selected references:

o 11 GO-Terms:

o 85 Instances for LIG_EH_1
(click table headers for sorting)
SequenceStartEndSubsequence
Instance LogicPDB Organism
AGFG1_HUMAN 448 452 GPSVASSTNPFQTNARGATA true positive --- Homo sapiens (Human)
AGFG1_HUMAN 558 562 MTGAPTGQFPTGSSSTNPFL true positive 1FF1
 Homo sapiens (Human)
AGFG2_HUMAN 380 384 AQSPLPSTNPFQPNGLAPGP true positive --- Homo sapiens (Human)
Q3MUI1_RAT 577 581 QRTNPSPTNPFSSDAQKAFE true positive --- Rattus norvegicus (Norway rat)
SYNJ1_RAT 1400 1404 QESVGSSANPFPSLPTRNPF true positive --- Rattus norvegicus (Norway rat)
EPN1_RAT 500 504 TPPGAKASNPFLPSGAPATG true positive --- Rattus norvegicus (Norway rat)
SYNJ1_RAT 1420 1424 TDRTAAPGNPFRVQSQESEA true positive --- Rattus norvegicus (Norway rat)
AGFG1_HUMAN 539 543 VAAAGVSSNPFMTGAPTGQF true positive --- Homo sapiens (Human)
AGFG1_MOUSE 557 561 MTGAPTGQLPTGSSSTNPFL true positive --- Mus musculus (House mouse)
NUMB_DROME 538 542 SPLARHSTNPFISPPKAPAQ true positive --- Drosophila melanogaster (Fruit fly)
AGFG2_HUMAN 458 462 SQPAGISTNPFMTGPSSSPF true positive --- Homo sapiens (Human)
AGFG1_HUMAN 433 437 PFGATPSTNPFVAAAGPSVA true positive --- Homo sapiens (Human)
AGFG2_HUMAN 365 369 GLAFGAFTNPFTAPAAQSPL true positive --- Homo sapiens (Human)
NUMBL_HUMAN 594 598 KATVEKPSNPFSGDLQKTFE true positive --- Homo sapiens (Human)
AGFG2_HUMAN 477 481 MTGPSSSPFASKPPTTNPFL true positive --- Homo sapiens (Human)
SYNJ1_RAT 1409 1413 PFPSLPTRNPFTDRTAAPGN true positive --- Rattus norvegicus (Norway rat)
EPN1_RAT 516 520 PATGPSVTNPFQPAPPATLT true positive --- Rattus norvegicus (Norway rat)
NUMB_HUMAN 636 640 QRTNPSPTNPFSSDLQKTFE true positive --- Homo sapiens (Human)
EPN1_RAT 570 574 GLPPMMPPGPPAPNTNPFLL true positive --- Rattus norvegicus (Norway rat)
RBNS5_HUMAN 625 629 QQHEGPSLNPFDEEDLSSPM true positive --- Homo sapiens (Human)
EPN1_MOUSE 500 504 TPPGSKASNPFLPSGAPPTG true positive --- Mus musculus (House mouse)
EPN1_MOUSE 516 520 PPTGPSVTNPFQPAPPATLT true positive --- Mus musculus (House mouse)
EHD2_MOUSE 125 129 PEKPFRKLNPFGNTFLNRFM true positive --- Mus musculus (House mouse)
EPN1_MOUSE 570 574 GLPPMMPPGPPAPNTNPFLL true positive --- Mus musculus (House mouse)
AP18A_YEAST 362 366 NQTQQIANNPFVSQTQPQVM true positive --- Saccharomyces cerevisiae (Baker's yeast)
RBNS5_HUMAN 661 665 SARILKEYNPFEEEDEEEEA true positive --- Homo sapiens (Human)
EPN2_MOUSE 493 497 PAPPAQSLNPFLAPGAAAPA true positive --- Mus musculus (House mouse)
SCAM1_RAT 6 10 MSDFDSNPFADPDLNNPFKD true positive --- Rattus norvegicus (Norway rat)
EPN2_MOUSE 507 511 GAAAPAPVNPFQVNQPQPLT true positive --- Mus musculus (House mouse)
EPN2_HUMAN 551 555 APATSAPVNPFQVNQPQPLT true positive --- Homo sapiens (Human)
EPN2_MOUSE 590 594 SVGIPPSAAQSTGTTNPFLL true positive --- Mus musculus (House mouse)
SCAM1_RAT 15 19 PFADPDLNNPFKDPSVTQVT true positive --- Rattus norvegicus (Norway rat)
RBNS5_HUMAN 676 680 EEEEAVAGNPFIQPDSPAPN true positive --- Homo sapiens (Human)
SCAM1_RAT 37 41 VPPGLDEYNPFSDSRTPPPG true positive --- Rattus norvegicus (Norway rat)
AP18A_YEAST 479 483 PAHENVLNNPFSRPNFDEQN true positive --- Saccharomyces cerevisiae (Baker's yeast)
RBNS5_HUMAN 687 691 IQPDSPAPNPFSEEDEHPQQ true positive --- Homo sapiens (Human)
STON2_HUMAN 312 316 EASPWRATNPFLNETLQDVQ true positive 2JXC
 Homo sapiens (Human)
STON2_HUMAN 328 332 QDVQPSPINPFSAFFEEQER true positive 2JXC
 Homo sapiens (Human)
RBNS5_HUMAN 708 712 LSSPLVPGNPFEEPTCINPF true positive --- Homo sapiens (Human)
AP18B_YEAST 339 343 PTVPQDAYNPFGSQQQDLNN true positive --- Saccharomyces cerevisiae (Baker's yeast)
PACN1_RAT 363 367 EWSDDESGNPFGGNEANGGA true positive --- Rattus norvegicus (Norway rat)
RBNS5_HUMAN 717 721 PFEEPTCINPFEMDSDSGPE true positive --- Homo sapiens (Human)
PACN1_RAT 375 379 GNEANGGANPFEDDAKGVRV true positive --- Rattus norvegicus (Norway rat)
PACN2_RAT 363 367 STQLQSSYNPFEDEDDTGSS true positive --- Rattus norvegicus (Norway rat)
Q3I768_HUMAN 322 326 FATLPRKKNPFEESSETWDS true positive --- Homo sapiens (Human)
PACN2_RAT 406 410 DWSDDESNNPFSSTDANGDS true positive --- Rattus norvegicus (Norway rat)
PACN2_RAT 418 422 STDANGDSNPFDEDTTSGTE true positive --- Rattus norvegicus (Norway rat)
AP18B_YEAST 452 456 DPTKTGSNNPFSLENIAREQ true positive --- Saccharomyces cerevisiae (Baker's yeast)
Q3I768_HUMAN 405 409 DYFDYESTNPFTAKFRASNI true positive --- Homo sapiens (Human)
Q3I768_HUMAN 459 463 DLRKIPDSNPFDATAGYRSL true positive --- Homo sapiens (Human)
AP18B_YEAST 493 497 ILAHSQTGNPFQAQNVVTSP true positive --- Saccharomyces cerevisiae (Baker's yeast)
PICA_RAT 429 433 VDDAIPSLNPFLTKSSGDVH true positive --- Rattus norvegicus (Norway rat)
PICA_RAT 626 630 SQPVMRPPNPFGPVPGAQIQ true positive --- Rattus norvegicus (Norway rat)
ALX1_CAEEL 878 882 PQFGQQNQQQGGGGGANPFQ true positive --- Caenorhabditis elegans
TF65_HUMAN 138 142 SQRIQTNNNPFQVPIEEQRG true positive --- Homo sapiens (Human)
AP18A_YEAST 336 340 TVTAAQSYNPFGTDSSMHTN true positive --- Saccharomyces cerevisiae (Baker's yeast)
SNP29_RAT 8 12 MSGYPKSYNPFDDDVEDEDT true positive --- Rattus norvegicus (Norway rat)
AP18A_YEAST 456 460 SHSQTGSNNPFALHNAATIA true positive --- Saccharomyces cerevisiae (Baker's yeast)
AP18A_YEAST 502 506 PLQQQIISNPFQNQTYNQQQ true positive --- Saccharomyces cerevisiae (Baker's yeast)
AP18B_YEAST 372 376 AQVPQPTANPFLIPQQQQQA true positive --- Saccharomyces cerevisiae (Baker's yeast)
AP18B_YEAST 473 477 QQNFQNSPNPFTLQQAQTTP true positive --- Saccharomyces cerevisiae (Baker's yeast)
ENT1_YEAST 305 309 QQQQAMSNNPFAKSEQSSSS true positive --- Saccharomyces cerevisiae (Baker's yeast)
ENT1_YEAST 406 410 QVSDDPNHNPFLNSQYTGLP true positive --- Saccharomyces cerevisiae (Baker's yeast)
ENT2_YEAST 346 350 QPLPTGSNNPFSMDNLERQK true positive --- Saccharomyces cerevisiae (Baker's yeast)
ENT2_YEAST 490 494 QVTNEPKNNPFLSNQYTGLP true positive --- Saccharomyces cerevisiae (Baker's yeast)
INP51_YEAST 931 935 MINPKRDPNPFVENEDEPLF true positive --- Saccharomyces cerevisiae (Baker's yeast)
EPN2_HUMAN 536 540 PAPPAQSLNPFLAPGAPATS true positive --- Homo sapiens (Human)
EPN2_HUMAN 636 640 SVGIPPSAAQATGTTNPFLL true positive --- Homo sapiens (Human)
PICAL_HUMAN 436 440 VDDAIPSLNPFLTKSSGDVH true positive --- Homo sapiens (Human)
PICAL_HUMAN 638 642 SQPVMRPPNPFGPVSGAQIQ true positive --- Homo sapiens (Human)
EHBP1_HUMAN 267 271 KDLATVNSNPFDDPDAAELN true positive --- Homo sapiens (Human)
EHBP1_HUMAN 278 282 DDPDAAELNPFGDPDSEEPI true positive --- Homo sapiens (Human)
EHBP1_HUMAN 308 312 DSFYNNSYNPFKEVQTPQYL true positive --- Homo sapiens (Human)
EHBP1_HUMAN 320 324 EVQTPQYLNPFDEPEAFVTI true positive --- Homo sapiens (Human)
EHBP1_HUMAN 369 373 EEEELDESNPFYEPKSTPPP true positive --- Homo sapiens (Human)
EPN1_HUMAN 501 505 TPPGAKASNPFLPGGGPATG true positive --- Homo sapiens (Human)
EPN1_HUMAN 517 521 PATGPSVTNPFQPAPPATLT true positive --- Homo sapiens (Human)
EPN1_HUMAN 571 575 GLPPMMPPGPPAPNTNPFLL true positive --- Homo sapiens (Human)
STNB_DROME 2 6 MANPFLMDEDLDGCDAAANP true positive --- Drosophila melanogaster (Fruit fly)
STNB_DROME 18 22 LDGCDAAANPFLMQSEPEPS true positive --- Drosophila melanogaster (Fruit fly)
STNB_DROME 32 36 SEPEPSSDNPFMAATVASNP true positive --- Drosophila melanogaster (Fruit fly)
STNB_DROME 42 46 FMAATVASNPFAFGADDLEL true positive --- Drosophila melanogaster (Fruit fly)
STNB_DROME 209 213 VAGGVRLDNPFAVPTAVPNI true positive --- Drosophila melanogaster (Fruit fly)
STNB_DROME 492 496 ASSGQLSANPFASPDEEEPN true positive --- Drosophila melanogaster (Fruit fly)
STNB_DROME 672 676 TSLPGLTVNPFEDVSGFPAP true positive --- Drosophila melanogaster (Fruit fly)
Please cite: ELM - the database of eukaryotic linear motifs (PMID:22110040)
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