EHD4_HUMAN
ID EHD4_HUMAN Reviewed; 541 AA.
AC Q9H223; Q9HAR1; Q9NZN2;
DT 26-SEP-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2001, sequence version 1.
DT 03-AUG-2022, entry version 187.
DE RecName: Full=EH domain-containing protein 4 {ECO:0000305};
DE AltName: Full=Hepatocellular carcinoma-associated protein 10/11 {ECO:0000303|PubMed:12097419};
DE AltName: Full=PAST homolog 4 {ECO:0000305};
GN Name=EHD4 {ECO:0000312|HGNC:HGNC:3245};
GN Synonyms=HCA10 {ECO:0000303|PubMed:12097419},
GN HCA11 {ECO:0000303|PubMed:12097419}, PAST4 {ECO:0000312|HGNC:HGNC:3245};
GN ORFNames=FKSG7 {ECO:0000312|EMBL:AAG28784.1};
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Hepatoma;
RX PubMed=12097419; DOI=10.4049/jimmunol.169.2.1102;
RA Wang Y., Han K.-J., Pang X.-W., Vaughan H.A., Qu W., Dong X.-Y.,
RA Peng J.-R., Zhao H.-T., Rui J.-A., Leng X.-S., Cebon J., Burgess A.W.,
RA Chen W.-F.;
RT "Large scale identification of human hepatocellular carcinoma-associated
RT antigens by autoantibodies.";
RL J. Immunol. 169:1102-1109(2002).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Brain;
RA Wang Y.-G.;
RT "Cloning of FKSG7, a novel gene which encodes an EH domain-containing
RT protein.";
RL Submitted (SEP-2000) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Benjamin S., Horowitz M.;
RT "hEHD4, an EH domain containing protein-4.";
RL Submitted (DEC-2001) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain, and Placenta;
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 project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 60-541, AND TISSUE SPECIFICITY.
RC TISSUE=Brain;
RX PubMed=10673336; DOI=10.1006/geno.1999.6087;
RA Pohl U., Smith J.S., Tachibana I., Ueki K., Lee H.K., Ramaswamy S., Wu Q.,
RA Mohrenweiser H.W., Jenkins R.B., Louis D.N.;
RT "EHD2, EHD3, and EHD4 encode novel members of a highly conserved family of
RT EH domain-containing proteins.";
RL Genomics 63:255-262(2000).
RN [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-451, AND IDENTIFICATION BY
RP 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 cells.";
RL Nat. Biotechnol. 23:94-101(2005).
RN [7]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in signaling
RT networks.";
RL Cell 127:635-648(2006).
RN [8]
RP FUNCTION, 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., Band V.,
RA Band H.;
RT "Shared as well as distinct roles of EHD proteins revealed by biochemical
RT and functional comparisons in mammalian cells and C. elegans.";
RL BMC Cell Biol. 8:3-3(2007).
RN [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-459, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
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 [10]
RP FUNCTION, INTERACTION WITH EHD1 AND EHD3, AND SUBCELLULAR LOCATION.
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 [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-459, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
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., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [12]
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., Buerckstuemmer T.,
RA 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 [13]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-162 AND SER-459, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [14]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [15]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25944712; DOI=10.1002/pmic.201400617;
RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT "N-terminome analysis of the human mitochondrial proteome.";
RL Proteomics 15:2519-2524(2015).
CC -!- FUNCTION: ATP- and membrane-binding protein that probably controls
CC membrane reorganization/tubulation upon ATP hydrolysis. Plays a role in
CC early endosomal transport. {ECO:0000269|PubMed:17233914,
CC ECO:0000269|PubMed:18331452}.
CC -!- SUBUNIT: Homooligomer, and heterooligomer with EHD1, EHD2 and EHD3.
CC {ECO:0000269|PubMed:17233914}.
CC -!- SUBCELLULAR LOCATION: Early endosome membrane
CC {ECO:0000269|PubMed:18331452}; Peripheral membrane protein
CC {ECO:0000305}; Cytoplasmic side {ECO:0000305}. Recycling endosome
CC membrane {ECO:0000269|PubMed:18331452}; Peripheral membrane protein
CC {ECO:0000305}; Cytoplasmic side {ECO:0000305}. Cell membrane
CC {ECO:0000250|UniProtKB:Q9EQP2}; Peripheral membrane protein
CC {ECO:0000305}; Cytoplasmic side {ECO:0000305}.
CC -!- TISSUE SPECIFICITY: Highly expressed in pancreas and heart.
CC {ECO:0000269|PubMed:10673336}.
CC -!- DOMAIN: The EH domain interacts with Asn-Pro-Phe (NPF) motifs of target
CC proteins. {ECO:0000250|UniProtKB:Q9WVK4}.
CC -!- SIMILARITY: Belongs to the TRAFAC class dynamin-like GTPase
CC superfamily. Dynamin/Fzo/YdjA family. EHD subfamily.
CC {ECO:0000255|PROSITE-ProRule:PRU01055}.
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DR EMBL; AF323924; AAK11599.1; -; mRNA.
DR EMBL; AF307137; AAG28784.1; -; mRNA.
DR EMBL; AF454953; AAL51079.1; -; mRNA.
DR EMBL; BC006287; AAH06287.1; -; mRNA.
DR EMBL; BC051823; AAH51823.1; -; mRNA.
DR EMBL; AF181265; AAF40472.1; -; mRNA.
DR CCDS; CCDS10081.1; -.
DR RefSeq; NP_644670.1; NM_139265.3.
DR AlphaFoldDB; Q9H223; -.
DR SMR; Q9H223; -.
DR BioGRID; 119054; 101.
DR IntAct; Q9H223; 63.
DR MINT; Q9H223; -.
DR STRING; 9606.ENSP00000220325; -.
DR GlyGen; Q9H223; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q9H223; -.
DR MetOSite; Q9H223; -.
DR PhosphoSitePlus; Q9H223; -.
DR BioMuta; EHD4; -.
DR DMDM; 18202935; -.
DR EPD; Q9H223; -.
DR jPOST; Q9H223; -.
DR MassIVE; Q9H223; -.
DR MaxQB; Q9H223; -.
DR PaxDb; Q9H223; -.
DR PeptideAtlas; Q9H223; -.
DR PRIDE; Q9H223; -.
DR ProteomicsDB; 80476; -.
DR Antibodypedia; 23470; 151 antibodies from 28 providers.
DR DNASU; 30844; -.
DR Ensembl; ENST00000220325.9; ENSP00000220325.4; ENSG00000103966.11.
DR GeneID; 30844; -.
DR KEGG; hsa:30844; -.
DR MANE-Select; ENST00000220325.9; ENSP00000220325.4; NM_139265.4; NP_644670.1.
DR UCSC; uc001zot.4; human.
DR CTD; 30844; -.
DR DisGeNET; 30844; -.
DR GeneCards; EHD4; -.
DR HGNC; HGNC:3245; EHD4.
DR HPA; ENSG00000103966; Low tissue specificity.
DR MIM; 605892; gene.
DR neXtProt; NX_Q9H223; -.
DR OpenTargets; ENSG00000103966; -.
DR PharmGKB; PA27680; -.
DR VEuPathDB; HostDB:ENSG00000103966; -.
DR eggNOG; KOG1954; Eukaryota.
DR GeneTree; ENSGT00940000158601; -.
DR HOGENOM; CLU_017595_1_1_1; -.
DR InParanoid; Q9H223; -.
DR OMA; CDNDGML; -.
DR OrthoDB; 377342at2759; -.
DR PhylomeDB; Q9H223; -.
DR TreeFam; TF314429; -.
DR PathwayCommons; Q9H223; -.
DR SignaLink; Q9H223; -.
DR BioGRID-ORCS; 30844; 11 hits in 1079 CRISPR screens.
DR ChiTaRS; EHD4; human.
DR GeneWiki; EHD4; -.
DR GenomeRNAi; 30844; -.
DR Pharos; Q9H223; Tbio.
DR PRO; PR:Q9H223; -.
DR Proteomes; UP000005640; Chromosome 15.
DR RNAct; Q9H223; protein.
DR Bgee; ENSG00000103966; Expressed in heart right ventricle and 201 other tissues.
DR ExpressionAtlas; Q9H223; baseline and differential.
DR Genevisible; Q9H223; HS.
DR GO; GO:0005769; C:early endosome; IBA:GO_Central.
DR GO; GO:0031901; C:early endosome membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0030139; C:endocytic vesicle; IBA:GO_Central.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:LIFEdb.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IBA:GO_Central.
DR GO; GO:0016020; C:membrane; HDA:UniProtKB.
DR GO; GO:0005634; C:nucleus; TAS:ProtInc.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IBA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0055038; C:recycling endosome membrane; IDA:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0045296; F:cadherin binding; HDA:BHF-UCL.
DR GO; GO:0005509; F:calcium ion binding; IEA:InterPro.
DR GO; GO:0005525; F:GTP binding; IEA:InterPro.
DR GO; GO:0003676; F:nucleic acid binding; TAS:ProtInc.
DR GO; GO:0071363; P:cellular response to growth factor stimulus; IEA:Ensembl.
DR GO; GO:0060271; P:cilium assembly; IBA:GO_Central.
DR GO; GO:0032456; P:endocytic recycling; IGI:UniProtKB.
DR GO; GO:0006897; P:endocytosis; IBA:GO_Central.
DR GO; GO:0016197; P:endosomal transport; IBA:GO_Central.
DR GO; GO:0006907; P:pinocytosis; IEA:Ensembl.
DR GO; GO:0050731; P:positive regulation of peptidyl-tyrosine phosphorylation; IEA:Ensembl.
DR GO; GO:0051260; P:protein homooligomerization; IPI:UniProtKB.
DR GO; GO:0072659; P:protein localization to plasma membrane; IBA:GO_Central.
DR GO; GO:0030100; P:regulation of endocytosis; IEA:Ensembl.
DR CDD; cd00052; EH; 1.
DR Gene3D; 3.40.50.300; -; 1.
DR InterPro; IPR040990; DUF5600.
DR InterPro; IPR045063; Dynamin_N.
DR InterPro; IPR011992; EF-hand-dom_pair.
DR InterPro; IPR018247; EF_Hand_1_Ca_BS.
DR InterPro; IPR002048; EF_hand_dom.
DR InterPro; IPR000261; EH_dom.
DR InterPro; IPR029952; EHD4.
DR InterPro; IPR031692; EHD_N.
DR InterPro; IPR030381; G_DYNAMIN_dom.
DR InterPro; IPR027417; P-loop_NTPase.
DR PANTHER; PTHR11216:SF57; PTHR11216:SF57; 1.
DR Pfam; PF18150; DUF5600; 1.
DR Pfam; PF00350; Dynamin_N; 1.
DR Pfam; PF12763; EF-hand_4; 1.
DR Pfam; PF16880; EHD_N; 1.
DR SMART; SM00027; EH; 1.
DR SUPFAM; SSF47473; SSF47473; 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.
DR PROSITE; PS51718; G_DYNAMIN_2; 1.
PE 1: Evidence at protein level;
KW Acetylation; ATP-binding; Calcium; Cell membrane; Endosome; Membrane;
KW Metal-binding; Nucleotide-binding; Phosphoprotein; Reference proteome.
FT CHAIN 1..541
FT /note="EH domain-containing protein 4"
FT /id="PRO_0000146114"
FT DOMAIN 58..289
FT /note="Dynamin-type G"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01055"
FT DOMAIN 447..535
FT /note="EH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00077"
FT DOMAIN 479..514
FT /note="EF-hand"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT REGION 68..75
FT /note="G1 motif"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01055"
FT REGION 94..95
FT /note="G2 motif"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01055"
FT REGION 156..159
FT /note="G3 motif"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01055"
FT REGION 222..225
FT /note="G4 motif"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01055"
FT REGION 246
FT /note="G5 motif"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01055"
FT BINDING 68..75
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q8BH64"
FT BINDING 223
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q8BH64"
FT BINDING 261
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q8BH64"
FT BINDING 492
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 494
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 496
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 498
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 503
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT MOD_RES 1
FT /note="N-acetylmethionine"
FT /evidence="ECO:0000250|UniProtKB:Q9H4M9"
FT MOD_RES 162
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 451
FT /note="Phosphotyrosine"
FT /evidence="ECO:0007744|PubMed:15592455"
FT MOD_RES 459
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:23186163"
FT VARIANT 154
FT /note="V -> I (in dbSNP:rs11549015)"
FT /id="VAR_053070"
FT CONFLICT 297
FT /note="L -> I (in Ref. 2; AAG28784)"
FT /evidence="ECO:0000305"
FT CONFLICT 421..433
FT /note="TEGPFNQGYGEGA -> PRAPSTRATGRVP (in Ref. 2;
FT AAG28784)"
FT /evidence="ECO:0000305"
FT CONFLICT 439
FT /note="E -> Q (in Ref. 2; AAG28784)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 541 AA; 61175 MW; 72DDE551829B7BF5 CRC64;
MFSWMGRQAG GRERAGGADA VQTVTGGLRS LYLRKVLPLE EAYRFHEFHS PALEDADFEN
KPMILLVGQY STGKTTFIRY LLEQDFPGMR IGPEPTTDSF IAVMYGETEG STPGNALVVD
PKKPFRKLSR FGNAFLNRFM CSQLPNQVLK SISVIDSPGI LSGEKQRISR GYDFCQVLQW
FAERVDRIIL LFDAHKLDIS DEFSEAIKAF RGQDDKIRVV LNKADQVDTQ QLMRVYGALM
WSLGKVINTP EVLRVYIGSF WAQPLQNTDN RRLFEAEAQD LFRDIQSLPQ KAAVRKLNDL
IKRARLAKVH AYIISYLKKE MPSVFGKENK KRELISRLPE IYIQLQREYQ ISAGDFPEVK
AMQEQLENYD FTKFHSLKPK LIEAVDNMLS NKISPLMNLI SQEETSTPTQ LVQGGAFDGT
TEGPFNQGYG EGAKEGADEE EWVVAKDKPV YDELFYTLSP INGKISGVNA KKEMVTSKLP
NSVLGKIWKL ADCDCDGMLD EEEFALAKHL IKIKLDGYEL PSSLPPHLVP PSHRKSLPKA
D
