Full text data of EHD1
EHD1
(PAST, PAST1)
[Confidence: high (present in two of the MS resources)]
EH domain-containing protein 1 (PAST homolog 1; hPAST1; Testilin)
EH domain-containing protein 1 (PAST homolog 1; hPAST1; Testilin)
hRBCD
IPI00017184
IPI00017184 EH-domain containing protein 1 platalet soluble n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a not mentioned n/a found at its expected molecular weight found at molecular weight
IPI00017184 EH-domain containing protein 1 platalet soluble n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a not mentioned n/a found at its expected molecular weight found at molecular weight
UniProt
Q9H4M9
ID EHD1_HUMAN Reviewed; 534 AA.
AC Q9H4M9; O14611; Q2M3Q4; Q9UNR3;
DT 26-SEP-2001, integrated into UniProtKB/Swiss-Prot.
read moreDT 26-SEP-2001, sequence version 2.
DT 22-JAN-2014, entry version 117.
DE RecName: Full=EH domain-containing protein 1;
DE AltName: Full=PAST homolog 1;
DE Short=hPAST1;
DE AltName: Full=Testilin;
GN Name=EHD1; Synonyms=PAST, PAST1; ORFNames=CDABP0131;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=9253601;
RA Guru S.C., Agarwal S.K., Manickam P., Olufemi S.-E., Crabtree J.S.,
RA Weisemann J.M., Kester M.B., Kim Y.S., Wang Y., Emmert-Buck M.R.,
RA Liotta L.A., Spiegel A.M., Boguski M.S., Roe B.A., Collins F.S.,
RA Burns A.L., Marx S.J., Chandrasekharappa S.C.;
RT "A transcript map for the 2.8-Mb region containing the multiple
RT endocrine neoplasia type 1 locus.";
RL Genome Res. 7:725-735(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=10395801; DOI=10.1006/geno.1999.5800;
RA Mintz L., Galperin E., Pasmanik-Chor M., Tulzinsky S., Bromberg Y.,
RA Kozak C.A., Joyner A., Fein A., Horowitz M.;
RT "EHD1 -- an EH-domain-containing protein with a specific expression
RT pattern.";
RL Genomics 59:66-76(1999).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Leukemia;
RA Zhou J., Yu W., Tang H., Mei G., Tsang Y.T.M., Bouck J., Gibbs R.A.,
RA Margolin J.F.;
RT "Pediatric leukemia cDNA sequencing project.";
RL Submitted (JUL-2000) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP PROTEIN SEQUENCE OF 1-10.
RC TISSUE=Platelet;
RX PubMed=12665801; DOI=10.1038/nbt810;
RA Gevaert K., Goethals M., Martens L., Van Damme J., Staes A.,
RA Thomas G.R., Vandekerckhove J.;
RT "Exploring proteomes and analyzing protein processing by mass
RT spectrometric identification of sorted N-terminal peptides.";
RL Nat. Biotechnol. 21:566-569(2003).
RN [6]
RP FUNCTION IN ENDOSOMAL RECYCLING, INTERACTION WITH ZFYVE20, AND
RP SUBCELLULAR LOCATION.
RX PubMed=15020713; DOI=10.1091/mbc.E03-10-0733;
RA Naslavsky N., Boehm M., Backlund P.S. Jr., Caplan S.;
RT "Rabenosyn-5 and EHD1 interact and sequentially regulate protein
RT recycling to the plasma membrane.";
RL Mol. Biol. Cell 15:2410-2422(2004).
RN [7]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=15592455; DOI=10.1038/nbt1046;
RA Rush J., Moritz A., Lee K.A., Guo A., Goss V.L., Spek E.J., Zhang H.,
RA Zha X.-M., Polakiewicz R.D., Comb M.J.;
RT "Immunoaffinity profiling of tyrosine phosphorylation in cancer
RT cells.";
RL Nat. Biotechnol. 23:94-101(2005).
RN [8]
RP FUNCTION, SUBCELLULAR LOCATION, AND SUBUNIT.
RX PubMed=17233914; DOI=10.1186/1471-2121-8-3;
RA George M., Ying G., Rainey M.A., Solomon A., Parikh P.T., Gao Q.,
RA Band V., Band H.;
RT "Shared as well as distinct roles of EHD proteins revealed by
RT biochemical and functional comparisons in mammalian cells and C.
RT elegans.";
RL BMC Cell Biol. 8:3-3(2007).
RN [9]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007;
RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,
RA Greff Z., Keri G., Stemmann O., Mann M.;
RT "Kinase-selective enrichment enables quantitative phosphoproteomics of
RT the kinome across the cell cycle.";
RL Mol. Cell 31:438-448(2008).
RN [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-456, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [11]
RP INTERACTION WITH EHD4.
RX PubMed=18331452; DOI=10.1111/j.1600-0854.2008.00732.x;
RA Sharma M., Naslavsky N., Caplan S.;
RT "A role for EHD4 in the regulation of early endosomal transport.";
RL Traffic 9:995-1018(2008).
RN [12]
RP INTERACTION WITH MICALL1 AND RAB8A, SUBCELLULAR LOCATION, AND
RP MUTAGENESIS OF LYS-483 AND TRP-485.
RX PubMed=19864458; DOI=10.1091/mbc.E09-06-0535;
RA Sharma M., Giridharan S.S., Rahajeng J., Naslavsky N., Caplan S.;
RT "MICAL-L1 links EHD1 to tubular recycling endosomes and regulates
RT receptor recycling.";
RL Mol. Biol. Cell 20:5181-5194(2009).
RN [13]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-456, AND MASS
RP SPECTROMETRY.
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [14]
RP FUNCTION IN ENDOCYTOSIS.
RX PubMed=20801876; DOI=10.1074/jbc.C110.166066;
RA Rahajeng J., Giridharan S.S., Naslavsky N., Caplan S.;
RT "Collapsin response mediator protein-2 (Crmp2) regulates trafficking
RT by linking endocytic regulatory proteins to dynein motors.";
RL J. Biol. Chem. 285:31918-31922(2010).
RN [15]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-456, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [16]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [17]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-456, AND MASS
RP SPECTROMETRY.
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J.,
RA Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V.,
RA Blagoev B.;
RT "System-wide temporal characterization of the proteome and
RT phosphoproteome of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [18]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND MASS SPECTROMETRY.
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E.,
RA Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K.,
RA Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-
RT terminal acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [19]
RP INTERACTION WITH PACSIN2, AND SUBCELLULAR LOCATION.
RX PubMed=23596323; DOI=10.1091/mbc.E13-01-0026;
RA Giridharan S.S., Cai B., Vitale N., Naslavsky N., Caplan S.;
RT "Cooperation of MICAL-L1, syndapin2, and phosphatidic acid in tubular
RT recycling endosome biogenesis.";
RL Mol. Biol. Cell 24:1776-1790(2013).
RN [20]
RP STRUCTURE BY NMR OF 435-534 IN COMPLEX WITH MICALL1 PEPTIDE, AND
RP MUTAGENESIS OF LYS-468.
RX PubMed=20106972; DOI=10.1074/jbc.M109.045666;
RA Kieken F., Sharma M., Jovic M., Giridharan S.S., Naslavsky N.,
RA Caplan S., Sorgen P.L.;
RT "Mechanism for the selective interaction of C-terminal Eps15 homology
RT domain proteins with specific Asn-Pro-Phe-containing partners.";
RL J. Biol. Chem. 285:8687-8694(2010).
RN [21]
RP STRUCTURE BY NMR OF 401-534 IN COMPLEX WITH CALCIUM IONS.
RX PubMed=17899392; DOI=10.1007/s10858-007-9196-0;
RA Kieken F., Jovic M., Naslavsky N., Caplan S., Sorgen P.L.;
RT "EH domain of EHD1.";
RL J. Biomol. NMR 39:323-329(2007).
CC -!- FUNCTION: Acts in early endocytic membrane fusion and membrane
CC trafficking of recycling endosomes. Plays a role in myoblast
CC fusion. Recruited to endosomal membranes upon nerve growth factor
CC stimulation, indirectly regulates neurite outgrowth.
CC -!- SUBUNIT: Homooligomer, and heterooligomer with EHD2, EHD3 and
CC EHD4. Interacts (via EH domain) with MICALL1 (via NPF1 motif); the
CC interaction is direct and recruits EHD1 to membranes. Interacts
CC with RAB35; the interaction is indirect through MICALL1 and
CC recruits EHD1 to membranes. Interacts (via EH domain) with PACSIN2
CC (via NPF motifs); regulates localization to tubular recycling
CC endosome membranes. Interacts with PACSIN1. Interacts with RAB8A.
CC Interacts with FER1L5 (via second C2 domain). Interacts with MYOF.
CC Interacts with ZFYVE20.
CC -!- SUBCELLULAR LOCATION: Recycling endosome membrane; Peripheral
CC membrane protein. Early endosome membrane; Peripheral membrane
CC protein. Cell membrane; Peripheral membrane protein; Cytoplasmic
CC side. Note=Preferentially associates with tubular recycling
CC endosomes. Colocalizes with FER1L5 at plasma membrane in myoblasts
CC and myotubes.
CC -!- TISSUE SPECIFICITY: Highly expressed in testis.
CC -!- DOMAIN: The EH domain interacts with Asn-Pro-Phe (NPF) motifs of
CC target proteins (By similarity).
CC -!- SIMILARITY: Contains 1 EF-hand domain.
CC -!- SIMILARITY: Contains 1 EH domain.
CC -----------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution-NoDerivs License
CC -----------------------------------------------------------------------
DR EMBL; AF001434; AAB81204.1; -; mRNA.
DR EMBL; AF099011; AAD45866.1; -; mRNA.
DR EMBL; AY007161; AAG02009.1; -; mRNA.
DR EMBL; BC104799; AAI04800.1; -; mRNA.
DR EMBL; BC104825; AAI04826.1; -; mRNA.
DR RefSeq; NP_001269373.1; NM_001282444.1.
DR RefSeq; NP_001269374.1; NM_001282445.1.
DR RefSeq; NP_006786.2; NM_006795.3.
DR UniGene; Hs.523774; -.
DR PDB; 2JQ6; NMR; -; A=401-534.
DR PDB; 2KFF; NMR; -; A=435-534.
DR PDB; 2KFG; NMR; -; A=435-534.
DR PDB; 2KFH; NMR; -; A=435-534.
DR PDB; 2KSP; NMR; -; A=435-534.
DR PDBsum; 2JQ6; -.
DR PDBsum; 2KFF; -.
DR PDBsum; 2KFG; -.
DR PDBsum; 2KFH; -.
DR PDBsum; 2KSP; -.
DR ProteinModelPortal; Q9H4M9; -.
DR SMR; Q9H4M9; 19-534.
DR IntAct; Q9H4M9; 4.
DR MINT; MINT-4999249; -.
DR STRING; 9606.ENSP00000320516; -.
DR PhosphoSite; Q9H4M9; -.
DR DMDM; 18202945; -.
DR PaxDb; Q9H4M9; -.
DR PeptideAtlas; Q9H4M9; -.
DR PRIDE; Q9H4M9; -.
DR Ensembl; ENST00000320631; ENSP00000320516; ENSG00000110047.
DR Ensembl; ENST00000359393; ENSP00000352354; ENSG00000110047.
DR GeneID; 10938; -.
DR KEGG; hsa:10938; -.
DR UCSC; uc001obu.1; human.
DR CTD; 10938; -.
DR GeneCards; GC11M064619; -.
DR H-InvDB; HIX0171322; -.
DR HGNC; HGNC:3242; EHD1.
DR MIM; 605888; gene.
DR neXtProt; NX_Q9H4M9; -.
DR PharmGKB; PA27677; -.
DR eggNOG; NOG136252; -.
DR HOGENOM; HOG000242040; -.
DR HOVERGEN; HBG018183; -.
DR InParanoid; Q9H4M9; -.
DR KO; K12483; -.
DR OMA; QAYIISS; -.
DR OrthoDB; EOG757CX9; -.
DR PhylomeDB; Q9H4M9; -.
DR Reactome; REACT_604; Hemostasis.
DR EvolutionaryTrace; Q9H4M9; -.
DR GeneWiki; EHD1; -.
DR GenomeRNAi; 10938; -.
DR NextBio; 41547; -.
DR PRO; PR:Q9H4M9; -.
DR ArrayExpress; Q9H4M9; -.
DR Bgee; Q9H4M9; -.
DR CleanEx; HS_EHD1; -.
DR Genevestigator; Q9H4M9; -.
DR GO; GO:0031901; C:early endosome membrane; IDA:UniProtKB.
DR GO; GO:0030139; C:endocytic vesicle; IEA:Ensembl.
DR GO; GO:0005811; C:lipid particle; ISS:BHF-UCL.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IEA:Ensembl.
DR GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
DR GO; GO:0031095; C:platelet dense tubular network membrane; ISS:BHF-UCL.
DR GO; GO:0055038; C:recycling endosome membrane; IDA:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0005509; F:calcium ion binding; IEA:InterPro.
DR GO; GO:0005525; F:GTP binding; IEA:InterPro.
DR GO; GO:0003924; F:GTPase activity; IEA:InterPro.
DR GO; GO:0007596; P:blood coagulation; TAS:Reactome.
DR GO; GO:1990090; P:cellular response to nerve growth factor stimulus; ISS:UniProtKB.
DR GO; GO:0042632; P:cholesterol homeostasis; ISS:BHF-UCL.
DR GO; GO:0032456; P:endocytic recycling; IMP:UniProtKB.
DR GO; GO:0006897; P:endocytosis; IMP:UniProtKB.
DR GO; GO:0006184; P:GTP catabolic process; IEA:GOC.
DR GO; GO:0006886; P:intracellular protein transport; IMP:UniProtKB.
DR GO; GO:0034383; P:low-density lipoprotein particle clearance; ISS:BHF-UCL.
DR GO; GO:0031175; P:neuron projection development; ISS:UniProtKB.
DR GO; GO:0010886; P:positive regulation of cholesterol storage; ISS:BHF-UCL.
DR GO; GO:2001137; P:positive regulation of endocytic recycling; ISS:UniProtKB.
DR GO; GO:1901741; P:positive regulation of myoblast fusion; ISS:UniProtKB.
DR GO; GO:0051260; P:protein homooligomerization; IPI:UniProtKB.
DR Gene3D; 1.10.238.10; -; 1.
DR InterPro; IPR001401; Dynamin_GTPase.
DR InterPro; IPR011992; EF-hand-dom_pair.
DR InterPro; IPR018247; EF_Hand_1_Ca_BS.
DR InterPro; IPR002048; EF_hand_dom.
DR InterPro; IPR000261; EPS15_homology.
DR InterPro; IPR027417; P-loop_NTPase.
DR Pfam; PF00350; Dynamin_N; 1.
DR SMART; SM00027; EH; 1.
DR SUPFAM; SSF52540; SSF52540; 1.
DR PROSITE; PS00018; EF_HAND_1; 1.
DR PROSITE; PS50222; EF_HAND_2; 1.
DR PROSITE; PS50031; EH; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; ATP-binding; Calcium; Cell membrane;
KW Coiled coil; Complete proteome; Direct protein sequencing; Endosome;
KW Membrane; Metal-binding; Nucleotide-binding; Phosphoprotein;
KW Reference proteome.
FT CHAIN 1 534 EH domain-containing protein 1.
FT /FTId=PRO_0000146109.
FT DOMAIN 444 532 EH.
FT DOMAIN 476 511 EF-hand.
FT NP_BIND 65 72 ATP (By similarity).
FT CA_BIND 489 500
FT COILED 198 227 Potential.
FT BINDING 220 220 ATP (By similarity).
FT BINDING 258 258 ATP (By similarity).
FT MOD_RES 1 1 N-acetylmethionine.
FT MOD_RES 456 456 Phosphoserine.
FT MUTAGEN 468 468 K->A: Loss of interaction with MICALL1.
FT MUTAGEN 483 483 K->E: Loss of association with
FT tubulovesicular structures and altered
FT MICALL1 localization. No effect on
FT MICALL1 localization; when associated
FT with A-485.
FT MUTAGEN 485 485 W->A: No effect on MICALL1 localization;
FT when associated with E-483.
FT CONFLICT 127 127 A -> R (in Ref. 2; AAD45866).
FT CONFLICT 180 182 ERV -> DCW (in Ref. 2; AAD45866).
FT CONFLICT 194 194 L -> Q (in Ref. 2; AAD45866).
FT CONFLICT 198 198 D -> H (in Ref. 2; AAD45866).
FT CONFLICT 216 216 V -> M (in Ref. 2; AAD45866).
FT CONFLICT 435 435 D -> H (in Ref. 1; AAB81204).
FT CONFLICT 447 447 T -> S (in Ref. 2; AAD45866).
FT CONFLICT 467 467 A -> V (in Ref. 2; AAD45866).
FT CONFLICT 480 480 V -> E (in Ref. 2; AAD45866).
FT CONFLICT 530 534 KRRHE -> SAWGH (in Ref. 3; AAG02009).
FT HELIX 440 443
FT HELIX 445 454
FT STRAND 458 463
FT HELIX 464 473
FT HELIX 478 488
FT STRAND 494 497
FT HELIX 498 512
FT TURN 523 525
FT HELIX 528 530
SQ SEQUENCE 534 AA; 60627 MW; 3330218772A26CE4 CRC64;
MFSWVSKDAR RKKEPELFQT VAEGLRQLYA QKLLPLEEHY RFHEFHSPAL EDADFDNKPM
VLLVGQYSTG KTTFIRHLIE QDFPGMRIGP EPTTDSFIAV MHGPTEGVVP GNALVVDPRR
PFRKLNAFGN AFLNRFMCAQ LPNPVLDSIS IIDTPGILSG EKQRISRGYD FAAVLEWFAE
RVDRIILLFD AHKLDISDEF SEVIKALKNH EDKIRVVLNK ADQIETQQLM RVYGALMWSL
GKIINTPEVV RVYIGSFWSH PLLIPDNRKL FEAEEQDLFK DIQSLPRNAA LRKLNDLIKR
ARLAKVHAYI ISSLKKEMPN VFGKESKKKE LVNNLGEIYQ KIEREHQISP GDFPSLRKMQ
ELLQTQDFSK FQALKPKLLD TVDDMLANDI ARLMVMVRQE ESLMPSQVVK GGAFDGTMNG
PFGHGYGEGA GEGIDDVEWV VGKDKPTYDE IFYTLSPVNG KITGANAKKE MVKSKLPNTV
LGKIWKLADV DKDGLLDDEE FALANHLIKV KLEGHELPAD LPPHLVPPSK RRHE
//
ID EHD1_HUMAN Reviewed; 534 AA.
AC Q9H4M9; O14611; Q2M3Q4; Q9UNR3;
DT 26-SEP-2001, integrated into UniProtKB/Swiss-Prot.
read moreDT 26-SEP-2001, sequence version 2.
DT 22-JAN-2014, entry version 117.
DE RecName: Full=EH domain-containing protein 1;
DE AltName: Full=PAST homolog 1;
DE Short=hPAST1;
DE AltName: Full=Testilin;
GN Name=EHD1; Synonyms=PAST, PAST1; ORFNames=CDABP0131;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=9253601;
RA Guru S.C., Agarwal S.K., Manickam P., Olufemi S.-E., Crabtree J.S.,
RA Weisemann J.M., Kester M.B., Kim Y.S., Wang Y., Emmert-Buck M.R.,
RA Liotta L.A., Spiegel A.M., Boguski M.S., Roe B.A., Collins F.S.,
RA Burns A.L., Marx S.J., Chandrasekharappa S.C.;
RT "A transcript map for the 2.8-Mb region containing the multiple
RT endocrine neoplasia type 1 locus.";
RL Genome Res. 7:725-735(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=10395801; DOI=10.1006/geno.1999.5800;
RA Mintz L., Galperin E., Pasmanik-Chor M., Tulzinsky S., Bromberg Y.,
RA Kozak C.A., Joyner A., Fein A., Horowitz M.;
RT "EHD1 -- an EH-domain-containing protein with a specific expression
RT pattern.";
RL Genomics 59:66-76(1999).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Leukemia;
RA Zhou J., Yu W., Tang H., Mei G., Tsang Y.T.M., Bouck J., Gibbs R.A.,
RA Margolin J.F.;
RT "Pediatric leukemia cDNA sequencing project.";
RL Submitted (JUL-2000) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP PROTEIN SEQUENCE OF 1-10.
RC TISSUE=Platelet;
RX PubMed=12665801; DOI=10.1038/nbt810;
RA Gevaert K., Goethals M., Martens L., Van Damme J., Staes A.,
RA Thomas G.R., Vandekerckhove J.;
RT "Exploring proteomes and analyzing protein processing by mass
RT spectrometric identification of sorted N-terminal peptides.";
RL Nat. Biotechnol. 21:566-569(2003).
RN [6]
RP FUNCTION IN ENDOSOMAL RECYCLING, INTERACTION WITH ZFYVE20, AND
RP SUBCELLULAR LOCATION.
RX PubMed=15020713; DOI=10.1091/mbc.E03-10-0733;
RA Naslavsky N., Boehm M., Backlund P.S. Jr., Caplan S.;
RT "Rabenosyn-5 and EHD1 interact and sequentially regulate protein
RT recycling to the plasma membrane.";
RL Mol. Biol. Cell 15:2410-2422(2004).
RN [7]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=15592455; DOI=10.1038/nbt1046;
RA Rush J., Moritz A., Lee K.A., Guo A., Goss V.L., Spek E.J., Zhang H.,
RA Zha X.-M., Polakiewicz R.D., Comb M.J.;
RT "Immunoaffinity profiling of tyrosine phosphorylation in cancer
RT cells.";
RL Nat. Biotechnol. 23:94-101(2005).
RN [8]
RP FUNCTION, SUBCELLULAR LOCATION, AND SUBUNIT.
RX PubMed=17233914; DOI=10.1186/1471-2121-8-3;
RA George M., Ying G., Rainey M.A., Solomon A., Parikh P.T., Gao Q.,
RA Band V., Band H.;
RT "Shared as well as distinct roles of EHD proteins revealed by
RT biochemical and functional comparisons in mammalian cells and C.
RT elegans.";
RL BMC Cell Biol. 8:3-3(2007).
RN [9]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007;
RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,
RA Greff Z., Keri G., Stemmann O., Mann M.;
RT "Kinase-selective enrichment enables quantitative phosphoproteomics of
RT the kinome across the cell cycle.";
RL Mol. Cell 31:438-448(2008).
RN [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-456, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [11]
RP INTERACTION WITH EHD4.
RX PubMed=18331452; DOI=10.1111/j.1600-0854.2008.00732.x;
RA Sharma M., Naslavsky N., Caplan S.;
RT "A role for EHD4 in the regulation of early endosomal transport.";
RL Traffic 9:995-1018(2008).
RN [12]
RP INTERACTION WITH MICALL1 AND RAB8A, SUBCELLULAR LOCATION, AND
RP MUTAGENESIS OF LYS-483 AND TRP-485.
RX PubMed=19864458; DOI=10.1091/mbc.E09-06-0535;
RA Sharma M., Giridharan S.S., Rahajeng J., Naslavsky N., Caplan S.;
RT "MICAL-L1 links EHD1 to tubular recycling endosomes and regulates
RT receptor recycling.";
RL Mol. Biol. Cell 20:5181-5194(2009).
RN [13]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-456, AND MASS
RP SPECTROMETRY.
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [14]
RP FUNCTION IN ENDOCYTOSIS.
RX PubMed=20801876; DOI=10.1074/jbc.C110.166066;
RA Rahajeng J., Giridharan S.S., Naslavsky N., Caplan S.;
RT "Collapsin response mediator protein-2 (Crmp2) regulates trafficking
RT by linking endocytic regulatory proteins to dynein motors.";
RL J. Biol. Chem. 285:31918-31922(2010).
RN [15]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-456, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [16]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [17]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-456, AND MASS
RP SPECTROMETRY.
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J.,
RA Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V.,
RA Blagoev B.;
RT "System-wide temporal characterization of the proteome and
RT phosphoproteome of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [18]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND MASS SPECTROMETRY.
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E.,
RA Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K.,
RA Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-
RT terminal acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [19]
RP INTERACTION WITH PACSIN2, AND SUBCELLULAR LOCATION.
RX PubMed=23596323; DOI=10.1091/mbc.E13-01-0026;
RA Giridharan S.S., Cai B., Vitale N., Naslavsky N., Caplan S.;
RT "Cooperation of MICAL-L1, syndapin2, and phosphatidic acid in tubular
RT recycling endosome biogenesis.";
RL Mol. Biol. Cell 24:1776-1790(2013).
RN [20]
RP STRUCTURE BY NMR OF 435-534 IN COMPLEX WITH MICALL1 PEPTIDE, AND
RP MUTAGENESIS OF LYS-468.
RX PubMed=20106972; DOI=10.1074/jbc.M109.045666;
RA Kieken F., Sharma M., Jovic M., Giridharan S.S., Naslavsky N.,
RA Caplan S., Sorgen P.L.;
RT "Mechanism for the selective interaction of C-terminal Eps15 homology
RT domain proteins with specific Asn-Pro-Phe-containing partners.";
RL J. Biol. Chem. 285:8687-8694(2010).
RN [21]
RP STRUCTURE BY NMR OF 401-534 IN COMPLEX WITH CALCIUM IONS.
RX PubMed=17899392; DOI=10.1007/s10858-007-9196-0;
RA Kieken F., Jovic M., Naslavsky N., Caplan S., Sorgen P.L.;
RT "EH domain of EHD1.";
RL J. Biomol. NMR 39:323-329(2007).
CC -!- FUNCTION: Acts in early endocytic membrane fusion and membrane
CC trafficking of recycling endosomes. Plays a role in myoblast
CC fusion. Recruited to endosomal membranes upon nerve growth factor
CC stimulation, indirectly regulates neurite outgrowth.
CC -!- SUBUNIT: Homooligomer, and heterooligomer with EHD2, EHD3 and
CC EHD4. Interacts (via EH domain) with MICALL1 (via NPF1 motif); the
CC interaction is direct and recruits EHD1 to membranes. Interacts
CC with RAB35; the interaction is indirect through MICALL1 and
CC recruits EHD1 to membranes. Interacts (via EH domain) with PACSIN2
CC (via NPF motifs); regulates localization to tubular recycling
CC endosome membranes. Interacts with PACSIN1. Interacts with RAB8A.
CC Interacts with FER1L5 (via second C2 domain). Interacts with MYOF.
CC Interacts with ZFYVE20.
CC -!- SUBCELLULAR LOCATION: Recycling endosome membrane; Peripheral
CC membrane protein. Early endosome membrane; Peripheral membrane
CC protein. Cell membrane; Peripheral membrane protein; Cytoplasmic
CC side. Note=Preferentially associates with tubular recycling
CC endosomes. Colocalizes with FER1L5 at plasma membrane in myoblasts
CC and myotubes.
CC -!- TISSUE SPECIFICITY: Highly expressed in testis.
CC -!- DOMAIN: The EH domain interacts with Asn-Pro-Phe (NPF) motifs of
CC target proteins (By similarity).
CC -!- SIMILARITY: Contains 1 EF-hand domain.
CC -!- SIMILARITY: Contains 1 EH domain.
CC -----------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution-NoDerivs License
CC -----------------------------------------------------------------------
DR EMBL; AF001434; AAB81204.1; -; mRNA.
DR EMBL; AF099011; AAD45866.1; -; mRNA.
DR EMBL; AY007161; AAG02009.1; -; mRNA.
DR EMBL; BC104799; AAI04800.1; -; mRNA.
DR EMBL; BC104825; AAI04826.1; -; mRNA.
DR RefSeq; NP_001269373.1; NM_001282444.1.
DR RefSeq; NP_001269374.1; NM_001282445.1.
DR RefSeq; NP_006786.2; NM_006795.3.
DR UniGene; Hs.523774; -.
DR PDB; 2JQ6; NMR; -; A=401-534.
DR PDB; 2KFF; NMR; -; A=435-534.
DR PDB; 2KFG; NMR; -; A=435-534.
DR PDB; 2KFH; NMR; -; A=435-534.
DR PDB; 2KSP; NMR; -; A=435-534.
DR PDBsum; 2JQ6; -.
DR PDBsum; 2KFF; -.
DR PDBsum; 2KFG; -.
DR PDBsum; 2KFH; -.
DR PDBsum; 2KSP; -.
DR ProteinModelPortal; Q9H4M9; -.
DR SMR; Q9H4M9; 19-534.
DR IntAct; Q9H4M9; 4.
DR MINT; MINT-4999249; -.
DR STRING; 9606.ENSP00000320516; -.
DR PhosphoSite; Q9H4M9; -.
DR DMDM; 18202945; -.
DR PaxDb; Q9H4M9; -.
DR PeptideAtlas; Q9H4M9; -.
DR PRIDE; Q9H4M9; -.
DR Ensembl; ENST00000320631; ENSP00000320516; ENSG00000110047.
DR Ensembl; ENST00000359393; ENSP00000352354; ENSG00000110047.
DR GeneID; 10938; -.
DR KEGG; hsa:10938; -.
DR UCSC; uc001obu.1; human.
DR CTD; 10938; -.
DR GeneCards; GC11M064619; -.
DR H-InvDB; HIX0171322; -.
DR HGNC; HGNC:3242; EHD1.
DR MIM; 605888; gene.
DR neXtProt; NX_Q9H4M9; -.
DR PharmGKB; PA27677; -.
DR eggNOG; NOG136252; -.
DR HOGENOM; HOG000242040; -.
DR HOVERGEN; HBG018183; -.
DR InParanoid; Q9H4M9; -.
DR KO; K12483; -.
DR OMA; QAYIISS; -.
DR OrthoDB; EOG757CX9; -.
DR PhylomeDB; Q9H4M9; -.
DR Reactome; REACT_604; Hemostasis.
DR EvolutionaryTrace; Q9H4M9; -.
DR GeneWiki; EHD1; -.
DR GenomeRNAi; 10938; -.
DR NextBio; 41547; -.
DR PRO; PR:Q9H4M9; -.
DR ArrayExpress; Q9H4M9; -.
DR Bgee; Q9H4M9; -.
DR CleanEx; HS_EHD1; -.
DR Genevestigator; Q9H4M9; -.
DR GO; GO:0031901; C:early endosome membrane; IDA:UniProtKB.
DR GO; GO:0030139; C:endocytic vesicle; IEA:Ensembl.
DR GO; GO:0005811; C:lipid particle; ISS:BHF-UCL.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IEA:Ensembl.
DR GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
DR GO; GO:0031095; C:platelet dense tubular network membrane; ISS:BHF-UCL.
DR GO; GO:0055038; C:recycling endosome membrane; IDA:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0005509; F:calcium ion binding; IEA:InterPro.
DR GO; GO:0005525; F:GTP binding; IEA:InterPro.
DR GO; GO:0003924; F:GTPase activity; IEA:InterPro.
DR GO; GO:0007596; P:blood coagulation; TAS:Reactome.
DR GO; GO:1990090; P:cellular response to nerve growth factor stimulus; ISS:UniProtKB.
DR GO; GO:0042632; P:cholesterol homeostasis; ISS:BHF-UCL.
DR GO; GO:0032456; P:endocytic recycling; IMP:UniProtKB.
DR GO; GO:0006897; P:endocytosis; IMP:UniProtKB.
DR GO; GO:0006184; P:GTP catabolic process; IEA:GOC.
DR GO; GO:0006886; P:intracellular protein transport; IMP:UniProtKB.
DR GO; GO:0034383; P:low-density lipoprotein particle clearance; ISS:BHF-UCL.
DR GO; GO:0031175; P:neuron projection development; ISS:UniProtKB.
DR GO; GO:0010886; P:positive regulation of cholesterol storage; ISS:BHF-UCL.
DR GO; GO:2001137; P:positive regulation of endocytic recycling; ISS:UniProtKB.
DR GO; GO:1901741; P:positive regulation of myoblast fusion; ISS:UniProtKB.
DR GO; GO:0051260; P:protein homooligomerization; IPI:UniProtKB.
DR Gene3D; 1.10.238.10; -; 1.
DR InterPro; IPR001401; Dynamin_GTPase.
DR InterPro; IPR011992; EF-hand-dom_pair.
DR InterPro; IPR018247; EF_Hand_1_Ca_BS.
DR InterPro; IPR002048; EF_hand_dom.
DR InterPro; IPR000261; EPS15_homology.
DR InterPro; IPR027417; P-loop_NTPase.
DR Pfam; PF00350; Dynamin_N; 1.
DR SMART; SM00027; EH; 1.
DR SUPFAM; SSF52540; SSF52540; 1.
DR PROSITE; PS00018; EF_HAND_1; 1.
DR PROSITE; PS50222; EF_HAND_2; 1.
DR PROSITE; PS50031; EH; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; ATP-binding; Calcium; Cell membrane;
KW Coiled coil; Complete proteome; Direct protein sequencing; Endosome;
KW Membrane; Metal-binding; Nucleotide-binding; Phosphoprotein;
KW Reference proteome.
FT CHAIN 1 534 EH domain-containing protein 1.
FT /FTId=PRO_0000146109.
FT DOMAIN 444 532 EH.
FT DOMAIN 476 511 EF-hand.
FT NP_BIND 65 72 ATP (By similarity).
FT CA_BIND 489 500
FT COILED 198 227 Potential.
FT BINDING 220 220 ATP (By similarity).
FT BINDING 258 258 ATP (By similarity).
FT MOD_RES 1 1 N-acetylmethionine.
FT MOD_RES 456 456 Phosphoserine.
FT MUTAGEN 468 468 K->A: Loss of interaction with MICALL1.
FT MUTAGEN 483 483 K->E: Loss of association with
FT tubulovesicular structures and altered
FT MICALL1 localization. No effect on
FT MICALL1 localization; when associated
FT with A-485.
FT MUTAGEN 485 485 W->A: No effect on MICALL1 localization;
FT when associated with E-483.
FT CONFLICT 127 127 A -> R (in Ref. 2; AAD45866).
FT CONFLICT 180 182 ERV -> DCW (in Ref. 2; AAD45866).
FT CONFLICT 194 194 L -> Q (in Ref. 2; AAD45866).
FT CONFLICT 198 198 D -> H (in Ref. 2; AAD45866).
FT CONFLICT 216 216 V -> M (in Ref. 2; AAD45866).
FT CONFLICT 435 435 D -> H (in Ref. 1; AAB81204).
FT CONFLICT 447 447 T -> S (in Ref. 2; AAD45866).
FT CONFLICT 467 467 A -> V (in Ref. 2; AAD45866).
FT CONFLICT 480 480 V -> E (in Ref. 2; AAD45866).
FT CONFLICT 530 534 KRRHE -> SAWGH (in Ref. 3; AAG02009).
FT HELIX 440 443
FT HELIX 445 454
FT STRAND 458 463
FT HELIX 464 473
FT HELIX 478 488
FT STRAND 494 497
FT HELIX 498 512
FT TURN 523 525
FT HELIX 528 530
SQ SEQUENCE 534 AA; 60627 MW; 3330218772A26CE4 CRC64;
MFSWVSKDAR RKKEPELFQT VAEGLRQLYA QKLLPLEEHY RFHEFHSPAL EDADFDNKPM
VLLVGQYSTG KTTFIRHLIE QDFPGMRIGP EPTTDSFIAV MHGPTEGVVP GNALVVDPRR
PFRKLNAFGN AFLNRFMCAQ LPNPVLDSIS IIDTPGILSG EKQRISRGYD FAAVLEWFAE
RVDRIILLFD AHKLDISDEF SEVIKALKNH EDKIRVVLNK ADQIETQQLM RVYGALMWSL
GKIINTPEVV RVYIGSFWSH PLLIPDNRKL FEAEEQDLFK DIQSLPRNAA LRKLNDLIKR
ARLAKVHAYI ISSLKKEMPN VFGKESKKKE LVNNLGEIYQ KIEREHQISP GDFPSLRKMQ
ELLQTQDFSK FQALKPKLLD TVDDMLANDI ARLMVMVRQE ESLMPSQVVK GGAFDGTMNG
PFGHGYGEGA GEGIDDVEWV VGKDKPTYDE IFYTLSPVNG KITGANAKKE MVKSKLPNTV
LGKIWKLADV DKDGLLDDEE FALANHLIKV KLEGHELPAD LPPHLVPPSK RRHE
//
MIM
605888
*RECORD*
*FIELD* NO
605888
*FIELD* TI
*605888 EH DOMAIN-CONTAINING 1; EHD1
*FIELD* TX
DESCRIPTION
The EH domain-containing-1 gene belongs to a highly conserved gene
read morefamily encoding eps15 homology (EH) domain-containing proteins. The
protein-binding EH domain has approximately 100 residues and was first
noted in Eps15 (600051), a substrate for the epidermal growth factor
receptor. The EH domain has been shown to be an important motif in
proteins involved in protein-protein interactions and in intracellular
sorting (Di Fiore et al., 1997).
CLONING
By screening a human cerebellar cDNA library with a mouse genomic
fragment, Mintz et al. (1999) isolated a cDNA which was then used as a
probe to screen a mouse brain cDNA library. The sequences of the deduced
human and mouse proteins, designated EHD1, contain 534 amino acids and
share approximately 94% homology. Both proteins have an EH domain,
including an EF-Ca(2+)-binding motif, at their C terminus, a highly
conserved ATP/GTP-binding domain, and a central coiled-coil structure.
Cotransfection experiments indicated that the human EHD1 protein has a
molecular mass of 62 kD. Northern blot analysis indicated the existence
of 2 EHD1 RNA species in mouse and 3 in human (2.0, 3.2, 3.6 kb). In
mouse, both transcripts are highly expressed in testis and are present
in kidney, heart, intestine, and brain. In human, the smallest
transcript is predominant in testis, while the largest transcript is
present in other tissues as well. RT-PCR analysis indicated that the
3.2-kb mRNA results from skipping of exon 3. Subcellular localization
experiments indicated that EHD1 colocalizes with transferrin
(190000)-containing endocytic vesicles. EHD1 was also present in other
cellular structures, including the Golgi apparatus. Immunohistochemical
analyses in mice demonstrated EHD1 expression in male germ cells, in
adipocytes, in several retinal layers, and, to a lesser extent, in
uterus, skeletal muscle, and kidney. In situ hybridization and
immunohistochemical analyses indicated that Ehd1 was expressed by day
9.5 in the limb buds and pharyngeal arches and at day 10.5 in
sclerotomes, at various elements of the branchial apparatus, and in the
occipital region. At day 15.5 Ehd1 expression peaked in cartilage,
preceding hypertrophy and ossification, and at day 17.5 there was no
expression in the bones.
GENE FUNCTION
Rotem-Yehudar et al. (2001) found evidence for a role for EHD1 in the
endocytosis of IGF1 receptors (IGF1R; 147370). Through
immunoprecipitation of rat tissues, they found that EHD1 interacts
directly with the synaptosomal-associated protein SNAP29 (604202) and
that both are present in complexes with IGF1R. They also found that IGF1
induction of EHD1-transfected CHO cells results in intracellular
colocalization of EHD1 and IGF1R.
By immunofluorescence microscopy of HeLa cells, Naslavsky et al. (2004)
detected EHD1 partly colocalized with rabenosyn-5 (ZFYVE20; 609511) in
vesicular and tubular structures. Depletion of either EHD1 or
rabenosyn-5 in HeLa cells by RNA interference (RNAi) delayed recycling
of transferrin and major histocompatibility complex class I (see HLA-A;
142800) to the plasma membrane. Depletion of EHD1 caused accumulation of
internalized cargo in a compact juxtanuclear compartment, but depletion
of rabenosyn-5 caused retention of cargo within a dispersed peripheral
compartment. Simultaneous depletion of both rabenosyn-5 and EHD1
resulted in a phenotype similar to that observed with rabenosyn-5 RNAi
alone, suggesting that rabenosyn-5 acts before EHD1 in the regulation of
endocytic recycling. Naslavsky et al. (2004) concluded that rabenosyn-5
and EHD1 act sequentially in the transport of proteins from early
endosomes to the endosomal recycling compartment and back to the plasma
membrane.
GENE STRUCTURE
By direct BAC sequencing, Haider et al. (1999) determined that the EHD1
gene contains 5 exons.
MAPPING
By interspecific backcross mapping, Mintz et al. (1999) mapped the mouse
Ehd1 gene to proximal chromosome 19. By sequence homology with a mapped
STS, they localized the human EHD1 gene to a region of conserved synteny
on chromosome 11q13. Haider et al. (1999) determined that the EHD1 gene
is identical to HPAST, a gene isolated and mapped to 11q13 by Guru et
al. (1997). By radiation hybrid analysis, they mapped the EHD1 gene to
11q13 within the Bardet-Biedl syndrome-1 (BBS1; see 209900) locus
region.
MOLECULAR GENETICS
By mutation analysis of the EHD1 gene in a large cohort of BBS patients
showing linkage to 11q13, Haider et al. (1999) found no disease-causing
mutations.
*FIELD* RF
1. Di Fiore, P. P.; Pelicci, P. G.; Sorkin, A.: EH: a novel protein-protein
interaction domain potentially involved in intracellular sorting. Trends
Biochem. Sci. 22: 411-413, 1997.
2. Guru, S. C.; Agarwal, S. K.; Manickam, P.; Olufemi, S.-E.; Crabtree,
J. S.; Weisemann, J. M.; Kester, M. B.; Kim, Y. S.; Wang, Y.; Emmert-Buck,
M. R.; Liotta, L. A.; Spiegel, A. M.; Boguski, M. S.; Roe, B. A.;
Collins, F. S.; Marx, S. J.; Burns, L.; Chandrasekharappa, S. C.:
A transcript map for the 2.8-Mb region containing the multiple endocrine
neoplasia type 1 locus. Genome Res. 7: 725-735, 1997.
3. Haider, N. B.; Searby, C.; Galperin, E.; Mintz, L.; Horowitz, M.;
Stone, E. M.; Sheffield, V. C.: Evaluation and molecular characterization
of EHD1, a candidate gene for Bardet-Biedl syndrome 1 (BBS1). Gene 240:
227-232, 1999.
4. Mintz, L.; Galperin, E.; Pasmanik-Chor, M.; Tulzinsky, S.; Bromberg,
Y.; Kozak, C. A.; Joyner, A.; Fein, A.; Horowitz, M.: EHD1--an EH-domain-containing
protein with a specific expression pattern. Genomics 59: 66-76,
1999.
5. Naslavsky, N.; Boehm, M.; Backlund, P. S., Jr.; Caplan, S.: Rabenosyn-5
and EHD1 interact and sequentially regulate protein recycling to the
plasma membrane. Molec. Biol. Cell 15: 2410-2422, 2004.
6. Rotem-Yehudar, R.; Galperin, E.; Horowitz, M.: Association of
insulin-like growth factor 1 receptor with EHD1 and SNAP29. J. Biol.
Chem. 276: 33054-33060, 2001.
*FIELD* CN
Patricia A. Hartz - updated: 08/02/2005
Patricia A. Hartz - updated: 4/29/2002
*FIELD* CD
Carol A. Bocchini: 4/30/2001
*FIELD* ED
mgross: 08/02/2005
carol: 8/19/2004
carol: 4/30/2002
terry: 4/29/2002
cwells: 5/4/2001
mcapotos: 5/2/2001
carol: 5/1/2001
*RECORD*
*FIELD* NO
605888
*FIELD* TI
*605888 EH DOMAIN-CONTAINING 1; EHD1
*FIELD* TX
DESCRIPTION
The EH domain-containing-1 gene belongs to a highly conserved gene
read morefamily encoding eps15 homology (EH) domain-containing proteins. The
protein-binding EH domain has approximately 100 residues and was first
noted in Eps15 (600051), a substrate for the epidermal growth factor
receptor. The EH domain has been shown to be an important motif in
proteins involved in protein-protein interactions and in intracellular
sorting (Di Fiore et al., 1997).
CLONING
By screening a human cerebellar cDNA library with a mouse genomic
fragment, Mintz et al. (1999) isolated a cDNA which was then used as a
probe to screen a mouse brain cDNA library. The sequences of the deduced
human and mouse proteins, designated EHD1, contain 534 amino acids and
share approximately 94% homology. Both proteins have an EH domain,
including an EF-Ca(2+)-binding motif, at their C terminus, a highly
conserved ATP/GTP-binding domain, and a central coiled-coil structure.
Cotransfection experiments indicated that the human EHD1 protein has a
molecular mass of 62 kD. Northern blot analysis indicated the existence
of 2 EHD1 RNA species in mouse and 3 in human (2.0, 3.2, 3.6 kb). In
mouse, both transcripts are highly expressed in testis and are present
in kidney, heart, intestine, and brain. In human, the smallest
transcript is predominant in testis, while the largest transcript is
present in other tissues as well. RT-PCR analysis indicated that the
3.2-kb mRNA results from skipping of exon 3. Subcellular localization
experiments indicated that EHD1 colocalizes with transferrin
(190000)-containing endocytic vesicles. EHD1 was also present in other
cellular structures, including the Golgi apparatus. Immunohistochemical
analyses in mice demonstrated EHD1 expression in male germ cells, in
adipocytes, in several retinal layers, and, to a lesser extent, in
uterus, skeletal muscle, and kidney. In situ hybridization and
immunohistochemical analyses indicated that Ehd1 was expressed by day
9.5 in the limb buds and pharyngeal arches and at day 10.5 in
sclerotomes, at various elements of the branchial apparatus, and in the
occipital region. At day 15.5 Ehd1 expression peaked in cartilage,
preceding hypertrophy and ossification, and at day 17.5 there was no
expression in the bones.
GENE FUNCTION
Rotem-Yehudar et al. (2001) found evidence for a role for EHD1 in the
endocytosis of IGF1 receptors (IGF1R; 147370). Through
immunoprecipitation of rat tissues, they found that EHD1 interacts
directly with the synaptosomal-associated protein SNAP29 (604202) and
that both are present in complexes with IGF1R. They also found that IGF1
induction of EHD1-transfected CHO cells results in intracellular
colocalization of EHD1 and IGF1R.
By immunofluorescence microscopy of HeLa cells, Naslavsky et al. (2004)
detected EHD1 partly colocalized with rabenosyn-5 (ZFYVE20; 609511) in
vesicular and tubular structures. Depletion of either EHD1 or
rabenosyn-5 in HeLa cells by RNA interference (RNAi) delayed recycling
of transferrin and major histocompatibility complex class I (see HLA-A;
142800) to the plasma membrane. Depletion of EHD1 caused accumulation of
internalized cargo in a compact juxtanuclear compartment, but depletion
of rabenosyn-5 caused retention of cargo within a dispersed peripheral
compartment. Simultaneous depletion of both rabenosyn-5 and EHD1
resulted in a phenotype similar to that observed with rabenosyn-5 RNAi
alone, suggesting that rabenosyn-5 acts before EHD1 in the regulation of
endocytic recycling. Naslavsky et al. (2004) concluded that rabenosyn-5
and EHD1 act sequentially in the transport of proteins from early
endosomes to the endosomal recycling compartment and back to the plasma
membrane.
GENE STRUCTURE
By direct BAC sequencing, Haider et al. (1999) determined that the EHD1
gene contains 5 exons.
MAPPING
By interspecific backcross mapping, Mintz et al. (1999) mapped the mouse
Ehd1 gene to proximal chromosome 19. By sequence homology with a mapped
STS, they localized the human EHD1 gene to a region of conserved synteny
on chromosome 11q13. Haider et al. (1999) determined that the EHD1 gene
is identical to HPAST, a gene isolated and mapped to 11q13 by Guru et
al. (1997). By radiation hybrid analysis, they mapped the EHD1 gene to
11q13 within the Bardet-Biedl syndrome-1 (BBS1; see 209900) locus
region.
MOLECULAR GENETICS
By mutation analysis of the EHD1 gene in a large cohort of BBS patients
showing linkage to 11q13, Haider et al. (1999) found no disease-causing
mutations.
*FIELD* RF
1. Di Fiore, P. P.; Pelicci, P. G.; Sorkin, A.: EH: a novel protein-protein
interaction domain potentially involved in intracellular sorting. Trends
Biochem. Sci. 22: 411-413, 1997.
2. Guru, S. C.; Agarwal, S. K.; Manickam, P.; Olufemi, S.-E.; Crabtree,
J. S.; Weisemann, J. M.; Kester, M. B.; Kim, Y. S.; Wang, Y.; Emmert-Buck,
M. R.; Liotta, L. A.; Spiegel, A. M.; Boguski, M. S.; Roe, B. A.;
Collins, F. S.; Marx, S. J.; Burns, L.; Chandrasekharappa, S. C.:
A transcript map for the 2.8-Mb region containing the multiple endocrine
neoplasia type 1 locus. Genome Res. 7: 725-735, 1997.
3. Haider, N. B.; Searby, C.; Galperin, E.; Mintz, L.; Horowitz, M.;
Stone, E. M.; Sheffield, V. C.: Evaluation and molecular characterization
of EHD1, a candidate gene for Bardet-Biedl syndrome 1 (BBS1). Gene 240:
227-232, 1999.
4. Mintz, L.; Galperin, E.; Pasmanik-Chor, M.; Tulzinsky, S.; Bromberg,
Y.; Kozak, C. A.; Joyner, A.; Fein, A.; Horowitz, M.: EHD1--an EH-domain-containing
protein with a specific expression pattern. Genomics 59: 66-76,
1999.
5. Naslavsky, N.; Boehm, M.; Backlund, P. S., Jr.; Caplan, S.: Rabenosyn-5
and EHD1 interact and sequentially regulate protein recycling to the
plasma membrane. Molec. Biol. Cell 15: 2410-2422, 2004.
6. Rotem-Yehudar, R.; Galperin, E.; Horowitz, M.: Association of
insulin-like growth factor 1 receptor with EHD1 and SNAP29. J. Biol.
Chem. 276: 33054-33060, 2001.
*FIELD* CN
Patricia A. Hartz - updated: 08/02/2005
Patricia A. Hartz - updated: 4/29/2002
*FIELD* CD
Carol A. Bocchini: 4/30/2001
*FIELD* ED
mgross: 08/02/2005
carol: 8/19/2004
carol: 4/30/2002
terry: 4/29/2002
cwells: 5/4/2001
mcapotos: 5/2/2001
carol: 5/1/2001