The Eukaryote Linear Motif resource for Functional Sites in Proteins
Accession:
Functional site class:
EH ligand
Functional site description:
Asn-Pro-Phe motif responsible for the interaction with Eps15 homology (EH) domain.
ELM 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.
Pattern Probability: 0.0000586
Present in taxons: Eukaryota Homo sapiens Mus musculus
Interaction Domains:
PDB Structure: 2JXC
<a href="http://www.rcsb.org/pdb/cgi/explore.cgi?pdbId=2JXC" title="" target="_blank"><img src="/media/pdb.ico.png"/>2JXC</a>
o See 88 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 88 Instances for LIG_EH_1
(click table headers for sorting; Notes column: =Number of Switches, =Number of Interactions)
Acc., Gene-, NameStartEndSubsequenceLogic#Ev.OrganismNotes
P52594 AGFG1
AGFG1_HUMAN
448 452 GPSVASSTNPFQTNARGATA TP 1 Homo sapiens (Human)
P52594 AGFG1
AGFG1_HUMAN
558 562 MTGAPTGQFPTGSSSTNPFL TP 6 Homo sapiens (Human)
O95081 AGFG2
AGFG2_HUMAN
380 384 AQSPLPSTNPFQPNGLAPGP TP 1 Homo sapiens (Human)
Q3MUI1 Numb
Q3MUI1_RAT
577 581 QRTNPSPTNPFSSDAQKAFE TP 2 Rattus norvegicus (Norway rat)
Q62910 Synj1
SYNJ1_RAT
1400 1404 QESVGSSANPFPSLPTRNPF TP 3 Rattus norvegicus (Norway rat)
O88339 Epn1
EPN1_RAT
500 504 TPPGAKASNPFLPSGAPATG TP 4 Rattus norvegicus (Norway rat)
Q62910 Synj1
SYNJ1_RAT
1420 1424 TDRTAAPGNPFRVQSQESEA TP 4 Rattus norvegicus (Norway rat)
P52594 AGFG1
AGFG1_HUMAN
539 543 VAAAGVSSNPFMTGAPTGQF TP 2 Homo sapiens (Human)
Q8K2K6 Agfg1
AGFG1_MOUSE
557 561 MTGAPTGQLPTGSSSTNPFL TP 1 Mus musculus (House mouse)
P16554 numb
NUMB_DROME
538 542 SPLARHSTNPFISPPKAPAQ TP 1 Drosophila melanogaster (Fruit fly)
O95081 AGFG2
AGFG2_HUMAN
458 462 SQPAGISTNPFMTGPSSSPF TP 1 Homo sapiens (Human)
P52594 AGFG1
AGFG1_HUMAN
433 437 PFGATPSTNPFVAAAGPSVA TP 2 Homo sapiens (Human)
O95081 AGFG2
AGFG2_HUMAN
365 369 GLAFGAFTNPFTAPAAQSPL TP 1 Homo sapiens (Human)
Q9Y6R0 NUMBL
NUMBL_HUMAN
594 598 KATVEKPSNPFSGDLQKTFE TP 1 Homo sapiens (Human)
O95081 AGFG2
AGFG2_HUMAN
477 481 MTGPSSSPFASKPPTTNPFL TP 1 Homo sapiens (Human)
Q62910 Synj1
SYNJ1_RAT
1409 1413 PFPSLPTRNPFTDRTAAPGN TP 3 Rattus norvegicus (Norway rat)
O88339 Epn1
EPN1_RAT
516 520 PATGPSVTNPFQPAPPATLT TP 3 Rattus norvegicus (Norway rat)
P49757 NUMB
NUMB_HUMAN
636 640 QRTNPSPTNPFSSDLQKTFE TP 4 Homo sapiens (Human)
O88339 Epn1
EPN1_RAT
570 574 GLPPMMPPGPPAPNTNPFLL TP 3 Rattus norvegicus (Norway rat)
Q9H1K0 ZFYVE20
RBNS5_HUMAN
625 629 QQHEGPSLNPFDEEDLSSPM TP 3 Homo sapiens (Human)
Q80VP1 Epn1
EPN1_MOUSE
500 504 TPPGSKASNPFLPSGAPPTG TP 1 Mus musculus (House mouse)
Q80VP1 Epn1
EPN1_MOUSE
516 520 PPTGPSVTNPFQPAPPATLT TP 1 Mus musculus (House mouse)
Q8BH64 Ehd2
EHD2_MOUSE
125 129 PEKPFRKLNPFGNTFLNRFM TP 1 Mus musculus (House mouse)
Q80VP1 Epn1
EPN1_MOUSE
570 574 GLPPMMPPGPPAPNTNPFLL TP 1 Mus musculus (House mouse)
P38856 YAP1801
AP18A_YEAST
362 366 NQTQQIANNPFVSQTQPQVM TP 2 Saccharomyces cerevisiae (Baker"s yeast)
Q9H1K0 ZFYVE20
RBNS5_HUMAN
661 665 SARILKEYNPFEEEDEEEEA TP 3 Homo sapiens (Human)
Q8CHU3 Epn2
EPN2_MOUSE
493 497 PAPPAQSLNPFLAPGAAAPA TP 2 Mus musculus (House mouse)
P56603 Scamp1
SCAM1_RAT
6 10 MSDFDSNPFADPDLNNPFKD TP 2 Rattus norvegicus (Norway rat)
Q8CHU3 Epn2
EPN2_MOUSE
507 511 GAAAPAPVNPFQVNQPQPLT TP 2 Mus musculus (House mouse)
O95208 EPN2
EPN2_HUMAN
551 555 APATSAPVNPFQVNQPQPLT TP 1 Homo sapiens (Human)
Q8CHU3 Epn2
EPN2_MOUSE
590 594 SVGIPPSAAQSTGTTNPFLL TP 2 Mus musculus (House mouse)
P56603 Scamp1
SCAM1_RAT
15 19 PFADPDLNNPFKDPSVTQVT TP 2 Rattus norvegicus (Norway rat)
Q9H1K0 ZFYVE20
RBNS5_HUMAN
676 680 EEEEAVAGNPFIQPDSPAPN TP 1 Homo sapiens (Human)
P56603 Scamp1
SCAM1_RAT
37 41 VPPGLDEYNPFSDSRTPPPG TP 2 Rattus norvegicus (Norway rat)
P38856 YAP1801
AP18A_YEAST
479 483 PAHENVLNNPFSRPNFDEQN TP 3 Saccharomyces cerevisiae (Baker"s yeast)
Q9H1K0 ZFYVE20
RBNS5_HUMAN
687 691 IQPDSPAPNPFSEEDEHPQQ TP 1 Homo sapiens (Human)
Q8WXE9 STON2
STON2_HUMAN
312 316 EASPWRATNPFLNETLQDVQ TP 7 Homo sapiens (Human)
Q8WXE9 STON2
STON2_HUMAN
328 332 QDVQPSPINPFSAFFEEQER TP 6 Homo sapiens (Human)
Q9H1K0 ZFYVE20
RBNS5_HUMAN
708 712 LSSPLVPGNPFEEPTCINPF TP 1 Homo sapiens (Human)
P53309 YAP1802
AP18B_YEAST
339 343 PTVPQDAYNPFGSQQQDLNN TP 1 Saccharomyces cerevisiae (Baker"s yeast)
Q9Z0W5 Pacsin1
PACN1_RAT
363 367 EWSDDESGNPFGGNEANGGA TP 5 Rattus norvegicus (Norway rat)
Q9H1K0 ZFYVE20
RBNS5_HUMAN
717 721 PFEEPTCINPFEMDSDSGPE TP 1 Homo sapiens (Human)
Q9Z0W5 Pacsin1
PACN1_RAT
375 379 GNEANGGANPFEDDAKGVRV TP 6 Rattus norvegicus (Norway rat)
Q9QY17 Pacsin2
PACN2_RAT
363 367 STQLQSSYNPFEDEDDTGSS TP 4 Rattus norvegicus (Norway rat)
Q3I768 RAB11FIP2
Q3I768_HUMAN
322 326 FATLPRKKNPFEESSETWDS TP 4 Homo sapiens (Human)
Q9QY17 Pacsin2
PACN2_RAT
406 410 DWSDDESNNPFSSTDANGDS TP 4 Rattus norvegicus (Norway rat)
Q9QY17 Pacsin2
PACN2_RAT
418 422 STDANGDSNPFDEDTTSGTE TP 4 Rattus norvegicus (Norway rat)
P53309 YAP1802
AP18B_YEAST
452 456 DPTKTGSNNPFSLENIAREQ TP 1 Saccharomyces cerevisiae (Baker"s yeast)
Q3I768 RAB11FIP2
Q3I768_HUMAN
405 409 DYFDYESTNPFTAKFRASNI TP 5 Homo sapiens (Human)
Q3I768 RAB11FIP2
Q3I768_HUMAN
459 463 DLRKIPDSNPFDATAGYRSL TP 1 Homo sapiens (Human)
P53309 YAP1802
AP18B_YEAST
493 497 ILAHSQTGNPFQAQNVVTSP TP 1 Saccharomyces cerevisiae (Baker"s yeast)
O55012 Picalm
PICA_RAT
429 433 VDDAIPSLNPFLTKSSGDVH TP 2 Rattus norvegicus (Norway rat)
O55012 Picalm
PICA_RAT
626 630 SQPVMRPPNPFGPVPGAQIQ TP 2 Rattus norvegicus (Norway rat)
P34552 alx-1
ALX1_CAEEL
878 882 PQFGQQNQQQGGGGGANPFQ TP 3 Caenorhabditis elegans
Q04206 RELA
TF65_HUMAN
138 142 SQRIQTNNNPFQVPIEEQRG TP 1 Homo sapiens (Human)
P38856 YAP1801
AP18A_YEAST
336 340 TVTAAQSYNPFGTDSSMHTN TP 1 Saccharomyces cerevisiae (Baker"s yeast)
Q9Z2P6 Snap29
SNP29_RAT
8 12 MSGYPKSYNPFDDDVEDEDT TP 3 Rattus norvegicus (Norway rat)
P38856 YAP1801
AP18A_YEAST
456 460 SHSQTGSNNPFALHNAATIA TP 3 Saccharomyces cerevisiae (Baker"s yeast)
P38856 YAP1801
AP18A_YEAST
502 506 PLQQQIISNPFQNQTYNQQQ TP 3 Saccharomyces cerevisiae (Baker"s yeast)
P53309 YAP1802
AP18B_YEAST
372 376 AQVPQPTANPFLIPQQQQQA TP 1 Saccharomyces cerevisiae (Baker"s yeast)
P53309 YAP1802
AP18B_YEAST
473 477 QQNFQNSPNPFTLQQAQTTP TP 1 Saccharomyces cerevisiae (Baker"s yeast)
Q12518 ENT1
ENT1_YEAST
305 309 QQQQAMSNNPFAKSEQSSSS TP 2 Saccharomyces cerevisiae (Baker"s yeast)
Q12518 ENT1
ENT1_YEAST
406 410 QVSDDPNHNPFLNSQYTGLP TP 3 Saccharomyces cerevisiae (Baker"s yeast)
Q05785 ENT2
ENT2_YEAST
346 350 QPLPTGSNNPFSMDNLERQK TP 1 Saccharomyces cerevisiae (Baker"s yeast)
Q05785 ENT2
ENT2_YEAST
490 494 QVTNEPKNNPFLSNQYTGLP TP 1 Saccharomyces cerevisiae (Baker"s yeast)
P40559 INP51
INP51_YEAST
931 935 MINPKRDPNPFVENEDEPLF TP 1 Saccharomyces cerevisiae (Baker"s yeast)
O95208 EPN2
EPN2_HUMAN
536 540 PAPPAQSLNPFLAPGAPATS TP 1 Homo sapiens (Human)
O95208 EPN2
EPN2_HUMAN
636 640 SVGIPPSAAQATGTTNPFLL TP 1 Homo sapiens (Human)
Q13492 PICALM
PICAL_HUMAN
436 440 VDDAIPSLNPFLTKSSGDVH TP 1 Homo sapiens (Human)
Q13492 PICALM
PICAL_HUMAN
638 642 SQPVMRPPNPFGPVSGAQIQ TP 1 Homo sapiens (Human)
Q8NDI1 EHBP1
EHBP1_HUMAN
267 271 KDLATVNSNPFDDPDAAELN TP 1 Homo sapiens (Human)
Q8NDI1 EHBP1
EHBP1_HUMAN
278 282 DDPDAAELNPFGDPDSEEPI TP 1 Homo sapiens (Human)
Q8NDI1 EHBP1
EHBP1_HUMAN
308 312 DSFYNNSYNPFKEVQTPQYL TP 1 Homo sapiens (Human)
Q8NDI1 EHBP1
EHBP1_HUMAN
320 324 EVQTPQYLNPFDEPEAFVTI TP 1 Homo sapiens (Human)
Q8NDI1 EHBP1
EHBP1_HUMAN
369 373 EEEELDESNPFYEPKSTPPP TP 1 Homo sapiens (Human)
Q9Y6I3 EPN1
EPN1_HUMAN
501 505 TPPGAKASNPFLPGGGPATG TP 3 Homo sapiens (Human)
Q9Y6I3 EPN1
EPN1_HUMAN
517 521 PATGPSVTNPFQPAPPATLT TP 3 Homo sapiens (Human)
Q9Y6I3 EPN1
EPN1_HUMAN
571 575 GLPPMMPPGPPAPNTNPFLL TP 3 Homo sapiens (Human)
Q24212 stnB
STNB_DROME
2 6 MANPFLMDEDLDGCDAAANP TP 2 Drosophila melanogaster (Fruit fly)
Q24212 stnB
STNB_DROME
18 22 LDGCDAAANPFLMQSEPEPS TP 2 Drosophila melanogaster (Fruit fly)
Q24212 stnB
STNB_DROME
32 36 SEPEPSSDNPFMAATVASNP TP 2 Drosophila melanogaster (Fruit fly)
Q24212 stnB
STNB_DROME
42 46 FMAATVASNPFAFGADDLEL TP 2 Drosophila melanogaster (Fruit fly)
Q24212 stnB
STNB_DROME
209 213 VAGGVRLDNPFAVPTAVPNI TP 2 Drosophila melanogaster (Fruit fly)
Q24212 stnB
STNB_DROME
492 496 ASSGQLSANPFASPDEEEPN TP 2 Drosophila melanogaster (Fruit fly)
Q24212 stnB
STNB_DROME
672 676 TSLPGLTVNPFEDVSGFPAP TP 2 Drosophila melanogaster (Fruit fly)
O43426 SYNJ1
SYNJ1_HUMAN
1393 1397 QENMRSSPNPFITGLTRTNP TP 2 Homo sapiens (Human)
3 
O43426 SYNJ1
SYNJ1_HUMAN
1403 1407 FITGLTRTNPFSDRTAAPGN TP 2 Homo sapiens (Human)
3 
O43426 SYNJ1
SYNJ1_HUMAN
1414 1418 SDRTAAPGNPFRAKSEESEA TP 2 Homo sapiens (Human)
3 
Please cite: The Eukaryotic Linear Motif Resource ELM: 10 Years and Counting (PMID:24214962)

ELM data can be downloaded & distributed for non-commercial use according to the ELM Software License Agreement
feedback@elm.eu.org