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   27-MAR-2024, entry version 196.
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}, HCA11
GN   {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; 116.
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   SwissPalm; Q9H223; -.
DR   BioMuta; EHD4; -.
DR   DMDM; 18202935; -.
DR   EPD; Q9H223; -.
DR   jPOST; Q9H223; -.
DR   MassIVE; Q9H223; -.
DR   MaxQB; Q9H223; -.
DR   PaxDb; 9606-ENSP00000220325; -.
DR   PeptideAtlas; Q9H223; -.
DR   ProteomicsDB; 80476; -.
DR   Pumba; Q9H223; -.
DR   Antibodypedia; 23470; 178 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   AGR; HGNC:3245; -.
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; ISAKKEM; -.
DR   OrthoDB; 12127at2759; -.
DR   PhylomeDB; Q9H223; -.
DR   TreeFam; TF314429; -.
DR   PathwayCommons; Q9H223; -.
DR   SignaLink; Q9H223; -.
DR   BioGRID-ORCS; 30844; 11 hits in 1157 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 203 other cell types or tissues.
DR   ExpressionAtlas; Q9H223; baseline and differential.
DR   GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
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: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; IBA:GO_Central.
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: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   CDD; cd09913; EHD; 1.
DR   Gene3D; 1.10.268.20; -; 1.
DR   Gene3D; 1.10.238.10; EF-hand; 1.
DR   Gene3D; 3.40.50.300; P-loop containing nucleotide triphosphate hydrolases; 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; IPR031692; EHD_N.
DR   InterPro; IPR030381; G_DYNAMIN_dom.
DR   InterPro; IPR027417; P-loop_NTPase.
DR   PANTHER; PTHR11216; EH DOMAIN; 1.
DR   PANTHER; PTHR11216:SF161; EPIDERMAL GROWTH FACTOR RECEPTOR PATHWAY SUBSTRATE CLONE 15, ISOFORM A; 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; EF-hand; 1.
DR   SUPFAM; SSF52540; P-loop containing nucleoside triphosphate hydrolases; 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.
DR   Genevisible; Q9H223; HS.
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
//