Full text data of CLINT1
CLINT1
(ENTH, EPN4, EPNR, KIAA0171)
[Confidence: low (only semi-automatic identification from reviews)]
Clathrin interactor 1 (Clathrin-interacting protein localized in the trans-Golgi region; Clint; Enthoprotin; Epsin-4; Epsin-related protein; EpsinR)
Clathrin interactor 1 (Clathrin-interacting protein localized in the trans-Golgi region; Clint; Enthoprotin; Epsin-4; Epsin-related protein; EpsinR)
UniProt
Q14677
ID EPN4_HUMAN Reviewed; 625 AA.
AC Q14677; B7Z6F8; D3DQJ6; Q8NAF1; Q96E05;
DT 16-JAN-2004, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-NOV-1996, sequence version 1.
DT 22-JAN-2014, entry version 134.
DE RecName: Full=Clathrin interactor 1;
DE AltName: Full=Clathrin-interacting protein localized in the trans-Golgi region;
DE Short=Clint;
DE AltName: Full=Enthoprotin;
DE AltName: Full=Epsin-4;
DE AltName: Full=Epsin-related protein;
DE Short=EpsinR;
GN Name=CLINT1; Synonyms=ENTH, EPN4, EPNR, KIAA0171;
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 [GENOMIC DNA], PROTEIN SEQUENCE OF 14-27; 30-49;
RP 110-129; 134-146; 157-171; 201-218; 248-274 AND 284-297 (ISOFORM 1),
RP MASS SPECTROMETRY, INTERACTION WITH CLATHRIN; AP1G1 AND GGA2, AND
RP SUBCELLULAR LOCATION.
RX PubMed=12213833; DOI=10.1083/jcb.200205078;
RA Wasiak S., Legendre-Guillemin V., Puertollano R., Blondeau F.,
RA Girard M., de Heuvel E., Boismenu D., Bell A.W., Bonifacino J.S.,
RA McPherson P.S.;
RT "Enthoprotin: a novel clathrin-associated protein identified through
RT subcellular proteomics.";
RL J. Cell Biol. 158:855-862(2002).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RA Hong W.;
RT "KIAA0171 as a new member (epsin 4) of the epsin family.";
RL Submitted (OCT-2001) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Bone marrow;
RX PubMed=8724849; DOI=10.1093/dnares/3.1.17;
RA Nagase T., Seki N., Ishikawa K., Tanaka A., Nomura N.;
RT "Prediction of the coding sequences of unidentified human genes. V.
RT The coding sequences of 40 new genes (KIAA0161-KIAA0200) deduced by
RT analysis of cDNA clones from human cell line KG-1.";
RL DNA Res. 3:17-24(1996).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2 AND 3).
RC TISSUE=Placenta, and Small intestine;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15372022; DOI=10.1038/nature02919;
RA Schmutz J., Martin J., Terry A., Couronne O., Grimwood J., Lowry S.,
RA Gordon L.A., Scott D., Xie G., Huang W., Hellsten U., Tran-Gyamfi M.,
RA She X., Prabhakar S., Aerts A., Altherr M., Bajorek E., Black S.,
RA Branscomb E., Caoile C., Challacombe J.F., Chan Y.M., Denys M.,
RA Detter J.C., Escobar J., Flowers D., Fotopulos D., Glavina T.,
RA Gomez M., Gonzales E., Goodstein D., Grigoriev I., Groza M.,
RA Hammon N., Hawkins T., Haydu L., Israni S., Jett J., Kadner K.,
RA Kimball H., Kobayashi A., Lopez F., Lou Y., Martinez D., Medina C.,
RA Morgan J., Nandkeshwar R., Noonan J.P., Pitluck S., Pollard M.,
RA Predki P., Priest J., Ramirez L., Retterer J., Rodriguez A.,
RA Rogers S., Salamov A., Salazar A., Thayer N., Tice H., Tsai M.,
RA Ustaszewska A., Vo N., Wheeler J., Wu K., Yang J., Dickson M.,
RA Cheng J.-F., Eichler E.E., Olsen A., Pennacchio L.A., Rokhsar D.S.,
RA Richardson P., Lucas S.M., Myers R.M., Rubin E.M.;
RT "The DNA sequence and comparative analysis of human chromosome 5.";
RL Nature 431:268-274(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Lung, and Skin;
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 [8]
RP FUNCTION, MUTAGENESIS OF 423-LEU--LEU-426, INTERACTION WITH CLATHRIN;
RP AP1G1 AND AP-2, TISSUE SPECIFICITY, AND SUBCELLULAR LOCATION.
RX PubMed=12429846; DOI=10.1091/mbc.E02-03-0171;
RA Kalthoff C., Groos S., Kohl R., Mahrhold S., Ungewickell E.J.;
RT "Clint: a novel clathrin-binding ENTH-domain protein at the Golgi.";
RL Mol. Biol. Cell 13:4060-4073(2002).
RN [9]
RP FUNCTION, TISSUE SPECIFICITY, SUBCELLULAR LOCATION, MUTAGENESIS OF
RP ASP-34; ASP-349; ASP-371 AND ASP-422, AND INTERACTION WITH AP1G1; AP-2
RP AND CLATHRIN.
RX PubMed=12538641; DOI=10.1083/jcb.200208023;
RA Mills I.G., Praefcke G.J.K., Vallis Y., Peter B.J., Olesen L.E.,
RA Gallop J.L., Butler P.J.G., Evans P.R., McMahon H.T.;
RT "EpsinR: an AP1/clathrin interacting protein involved in vesicle
RT trafficking.";
RL J. Cell Biol. 160:213-222(2003).
RN [10]
RP POSSIBLE INVOLVEMENT IN SCZD1.
RX PubMed=15793701; DOI=10.1086/430095;
RA Pimm J., McQuillin A., Thirumalai S., Lawrence J., Quested D.,
RA Bass N., Lamb G., Moorey H., Datta S.R., Kalsi G., Badacsonyi A.,
RA Kelly K., Morgan J., Punukollu B., Curtis D., Gurling H.;
RT "The Epsin 4 gene on chromosome 5q, which encodes the clathrin-
RT associated protein enthoprotin, is involved in the genetic
RT susceptibility to schizophrenia.";
RL Am. J. Hum. Genet. 76:902-907(2005).
RN [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-227, AND MASS
RP SPECTROMETRY.
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.,
RA Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in
RT signaling networks.";
RL Cell 127:635-648(2006).
RN [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-245 AND SER-299, AND
RP MASS SPECTROMETRY.
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 [13]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-245 AND SER-299, AND
RP MASS 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 [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-227, AND MASS
RP SPECTROMETRY.
RC TISSUE=Liver;
RX PubMed=18318008; DOI=10.1002/pmic.200700884;
RA Han G., Ye M., Zhou H., Jiang X., Feng S., Jiang X., Tian R., Wan D.,
RA Zou H., Gu J.;
RT "Large-scale phosphoproteome analysis of human liver tissue by
RT enrichment and fractionation of phosphopeptides with strong anion
RT exchange chromatography.";
RL Proteomics 8:1346-1361(2008).
RN [15]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J.,
RA Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in
RT a refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [16]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-299, 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 [17]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-245 AND SER-299, AND
RP MASS 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 [18]
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 [19]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-299, 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).
CC -!- FUNCTION: Binds to membranes enriched in phosphatidylinositol 4,5-
CC bisphosphate (PtdIns(4,5)P2). May have a role in transport via
CC clathrin-coated vesicles from the trans-Golgi network to
CC endosomes. Stimulates clathrin assembly.
CC -!- SUBUNIT: Binds clathrin heavy chain, GGA2, AP-2 and AP1G1.
CC -!- INTERACTION:
CC P22892:Ap1g1 (xeno); NbExp=10; IntAct=EBI-1171113, EBI-1040262;
CC Q9H0R8:GABARAPL1; NbExp=2; IntAct=EBI-1171113, EBI-746969;
CC Q9GZQ8:MAP1LC3B; NbExp=2; IntAct=EBI-1171113, EBI-373144;
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Cytoplasm, perinuclear region.
CC Membrane; Peripheral membrane protein. Cytoplasmic vesicle,
CC clathrin-coated vesicle. Note=Found throughout the cell, with the
CC exception of the cell surface. Concentrated in the perinuclear
CC region and associated with clathrin-coated vesicles close to the
CC trans-Golgi network.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q14677-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q14677-2; Sequence=VSP_009160, VSP_009161;
CC Name=3;
CC IsoId=Q14677-3; Sequence=VSP_043302;
CC Note=No experimental confirmation available;
CC -!- TISSUE SPECIFICITY: Ubiquitously expressed at low to intermediate
CC levels.
CC -!- POLYMORPHISM: Genetic variations in CLINT1 may contribute to
CC susceptibility to schizophrenia and psychotic disorders in some
CC populations.
CC -!- SIMILARITY: Belongs to the epsin family.
CC -!- SIMILARITY: Contains 1 ENTH (epsin N-terminal homology) domain.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAA11488.2; Type=Erroneous initiation;
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DR EMBL; BK000414; DAA00062.1; -; Genomic_DNA.
DR EMBL; AF434813; AAL30768.1; -; mRNA.
DR EMBL; D79993; BAA11488.2; ALT_INIT; mRNA.
DR EMBL; AK092765; BAC03971.1; -; mRNA.
DR EMBL; AK300257; BAH13244.1; -; mRNA.
DR EMBL; AC011394; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC026407; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471062; EAW61585.1; -; Genomic_DNA.
DR EMBL; CH471062; EAW61588.1; -; Genomic_DNA.
DR EMBL; BC004467; AAH04467.1; -; mRNA.
DR EMBL; BC013091; AAH13091.1; -; mRNA.
DR RefSeq; NP_001182484.1; NM_001195555.1.
DR RefSeq; NP_001182485.1; NM_001195556.1.
DR RefSeq; NP_055481.1; NM_014666.3.
DR UniGene; Hs.644000; -.
DR PDB; 1XGW; X-ray; 1.90 A; A=1-165.
DR PDB; 2QY7; X-ray; 2.00 A; A/B/C=20-166.
DR PDB; 2V8S; X-ray; 2.22 A; E=20-166.
DR PDBsum; 1XGW; -.
DR PDBsum; 2QY7; -.
DR PDBsum; 2V8S; -.
DR ProteinModelPortal; Q14677; -.
DR SMR; Q14677; 17-152.
DR IntAct; Q14677; 20.
DR MINT; MINT-4999242; -.
DR STRING; 9606.ENSP00000388340; -.
DR PhosphoSite; Q14677; -.
DR DMDM; 41016993; -.
DR PaxDb; Q14677; -.
DR PRIDE; Q14677; -.
DR Ensembl; ENST00000296951; ENSP00000296951; ENSG00000113282.
DR Ensembl; ENST00000411809; ENSP00000388340; ENSG00000113282.
DR Ensembl; ENST00000523094; ENSP00000429345; ENSG00000113282.
DR Ensembl; ENST00000523908; ENSP00000429824; ENSG00000113282.
DR Ensembl; ENST00000530742; ENSP00000433419; ENSG00000113282.
DR GeneID; 9685; -.
DR KEGG; hsa:9685; -.
DR UCSC; uc003lxj.2; human.
DR CTD; 9685; -.
DR GeneCards; GC05M157212; -.
DR HGNC; HGNC:23186; CLINT1.
DR HPA; HPA043280; -.
DR MIM; 607265; gene.
DR neXtProt; NX_Q14677; -.
DR Orphanet; 3140; Schizophrenia.
DR PharmGKB; PA145149115; -.
DR eggNOG; NOG290795; -.
DR HOGENOM; HOG000082415; -.
DR HOVERGEN; HBG048921; -.
DR InParanoid; Q14677; -.
DR OMA; PMSRSQP; -.
DR OrthoDB; EOG73V6K0; -.
DR PhylomeDB; Q14677; -.
DR Reactome; REACT_11123; Membrane Trafficking.
DR ChiTaRS; CLINT1; human.
DR EvolutionaryTrace; Q14677; -.
DR GeneWiki; CLINT1; -.
DR GenomeRNAi; 9685; -.
DR NextBio; 36372; -.
DR PRO; PR:Q14677; -.
DR Bgee; Q14677; -.
DR CleanEx; HS_CLINT1; -.
DR Genevestigator; Q14677; -.
DR GO; GO:0030136; C:clathrin-coated vesicle; IEA:UniProtKB-SubCell.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005794; C:Golgi apparatus; IDA:UniProtKB.
DR GO; GO:0016020; C:membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0008289; F:lipid binding; IEA:UniProtKB-KW.
DR GO; GO:0006897; P:endocytosis; IEA:UniProtKB-KW.
DR GO; GO:0006892; P:post-Golgi vesicle-mediated transport; TAS:Reactome.
DR Gene3D; 1.25.40.90; -; 1.
DR InterPro; IPR008942; ENTH_VHS.
DR InterPro; IPR013809; Epsin-like_N.
DR InterPro; IPR001026; Epsin_dom_N.
DR Pfam; PF01417; ENTH; 1.
DR SMART; SM00273; ENTH; 1.
DR SUPFAM; SSF48464; SSF48464; 1.
DR PROSITE; PS50942; ENTH; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Complete proteome; Cytoplasm;
KW Cytoplasmic vesicle; Direct protein sequencing; Endocytosis;
KW Lipid-binding; Membrane; Phosphoprotein; Reference proteome.
FT CHAIN 1 625 Clathrin interactor 1.
FT /FTId=PRO_0000074521.
FT DOMAIN 16 149 ENTH.
FT COMPBIAS 549 605 Met-rich.
FT BINDING 29 29 Phosphatidylinositol lipid headgroup (By
FT similarity).
FT BINDING 67 67 Phosphatidylinositol lipid headgroup (By
FT similarity).
FT MOD_RES 163 163 Phosphoserine (By similarity).
FT MOD_RES 227 227 Phosphoserine.
FT MOD_RES 245 245 Phosphoserine.
FT MOD_RES 299 299 Phosphoserine.
FT VAR_SEQ 1 18 Missing (in isoform 2).
FT /FTId=VSP_009160.
FT VAR_SEQ 459 459 S -> SQPLQNVSTVLQKPNPLYN (in isoform 3).
FT /FTId=VSP_043302.
FT VAR_SEQ 460 460 Q -> QPLQNVSTVLQKPNPLYNQ (in isoform 2).
FT /FTId=VSP_009161.
FT MUTAGEN 29 29 R->L: Reduces lipid binding. Abolishes
FT lipid binding; when associated with G-34.
FT MUTAGEN 34 34 D->G: Abolishes lipid binding; when
FT associated with L-29.
FT MUTAGEN 349 349 D->R: Decreases AP-1 and AP-2 binding.
FT MUTAGEN 371 371 D->R: Slightly decreases AP-1 binding.
FT MUTAGEN 422 422 D->R: Strongly decreases clathrin
FT binding.
FT MUTAGEN 423 426 LFDL->AFAA: Strongly reduces clathrin
FT binding.
FT CONFLICT 476 476 T -> A (in Ref. 4; BAC03971).
FT HELIX 23 31
FT STRAND 33 37
FT HELIX 41 50
FT TURN 54 56
FT HELIX 57 69
FT HELIX 76 92
FT HELIX 95 103
FT HELIX 105 109
FT HELIX 110 113
FT HELIX 125 139
FT HELIX 142 151
SQ SEQUENCE 625 AA; 68259 MW; 6C8C6689861E9F0D CRC64;
MLNMWKVREL VDKATNVVMN YSEIESKVRE ATNDDPWGPS GQLMGEIAKA TFMYEQFPEL
MNMLWSRMLK DNKKNWRRVY KSLLLLAYLI RNGSERVVTS AREHIYDLRS LENYHFVDEH
GKDQGINIRQ KVKELVEFAQ DDDRLREERK KAKKNKDKYV GVSSDSVGGF RYSERYDPEP
KSKWDEEWDK NKSAFPFSDK LGELSDKIGS TIDDTISKFR RKDREDSPER CSDSDEEKKA
RRGRSPKGEF KDEEETVTTK HIHITQATET TTTRHKRTAN PSKTIDLGAA AHYTGDKASP
DQNASTHTPQ SSVKTSVPSS KSSGDLVDLF DGTSQSTGGS ADLFGGFADF GSAAASGSFP
SQVTATSGNG DFGDWSAFNQ APSGPVASSG EFFGSASQPA VELVSGSQSA LGPPPAASNS
SDLFDLMGSS QATMTSSQSM NFSMMSTNTV GLGLPMSRSQ NTDMVQKSVS KTLPSTWSDP
SVNISLDNLL PGMQPSKPQQ PSLNTMIQQQ NMQQPMNVMT QSFGAVNLSS PSNMLPVRPQ
TNALIGGPMP MSMPNVMTGT MGMAPLGNTP MMNQSMMGMN MNIGMSAAGM GLTGTMGMGM
PNIAMTSGTV QPKQDAFANF ANFSK
//
ID EPN4_HUMAN Reviewed; 625 AA.
AC Q14677; B7Z6F8; D3DQJ6; Q8NAF1; Q96E05;
DT 16-JAN-2004, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-NOV-1996, sequence version 1.
DT 22-JAN-2014, entry version 134.
DE RecName: Full=Clathrin interactor 1;
DE AltName: Full=Clathrin-interacting protein localized in the trans-Golgi region;
DE Short=Clint;
DE AltName: Full=Enthoprotin;
DE AltName: Full=Epsin-4;
DE AltName: Full=Epsin-related protein;
DE Short=EpsinR;
GN Name=CLINT1; Synonyms=ENTH, EPN4, EPNR, KIAA0171;
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 [GENOMIC DNA], PROTEIN SEQUENCE OF 14-27; 30-49;
RP 110-129; 134-146; 157-171; 201-218; 248-274 AND 284-297 (ISOFORM 1),
RP MASS SPECTROMETRY, INTERACTION WITH CLATHRIN; AP1G1 AND GGA2, AND
RP SUBCELLULAR LOCATION.
RX PubMed=12213833; DOI=10.1083/jcb.200205078;
RA Wasiak S., Legendre-Guillemin V., Puertollano R., Blondeau F.,
RA Girard M., de Heuvel E., Boismenu D., Bell A.W., Bonifacino J.S.,
RA McPherson P.S.;
RT "Enthoprotin: a novel clathrin-associated protein identified through
RT subcellular proteomics.";
RL J. Cell Biol. 158:855-862(2002).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RA Hong W.;
RT "KIAA0171 as a new member (epsin 4) of the epsin family.";
RL Submitted (OCT-2001) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Bone marrow;
RX PubMed=8724849; DOI=10.1093/dnares/3.1.17;
RA Nagase T., Seki N., Ishikawa K., Tanaka A., Nomura N.;
RT "Prediction of the coding sequences of unidentified human genes. V.
RT The coding sequences of 40 new genes (KIAA0161-KIAA0200) deduced by
RT analysis of cDNA clones from human cell line KG-1.";
RL DNA Res. 3:17-24(1996).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2 AND 3).
RC TISSUE=Placenta, and Small intestine;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15372022; DOI=10.1038/nature02919;
RA Schmutz J., Martin J., Terry A., Couronne O., Grimwood J., Lowry S.,
RA Gordon L.A., Scott D., Xie G., Huang W., Hellsten U., Tran-Gyamfi M.,
RA She X., Prabhakar S., Aerts A., Altherr M., Bajorek E., Black S.,
RA Branscomb E., Caoile C., Challacombe J.F., Chan Y.M., Denys M.,
RA Detter J.C., Escobar J., Flowers D., Fotopulos D., Glavina T.,
RA Gomez M., Gonzales E., Goodstein D., Grigoriev I., Groza M.,
RA Hammon N., Hawkins T., Haydu L., Israni S., Jett J., Kadner K.,
RA Kimball H., Kobayashi A., Lopez F., Lou Y., Martinez D., Medina C.,
RA Morgan J., Nandkeshwar R., Noonan J.P., Pitluck S., Pollard M.,
RA Predki P., Priest J., Ramirez L., Retterer J., Rodriguez A.,
RA Rogers S., Salamov A., Salazar A., Thayer N., Tice H., Tsai M.,
RA Ustaszewska A., Vo N., Wheeler J., Wu K., Yang J., Dickson M.,
RA Cheng J.-F., Eichler E.E., Olsen A., Pennacchio L.A., Rokhsar D.S.,
RA Richardson P., Lucas S.M., Myers R.M., Rubin E.M.;
RT "The DNA sequence and comparative analysis of human chromosome 5.";
RL Nature 431:268-274(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Lung, and Skin;
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 [8]
RP FUNCTION, MUTAGENESIS OF 423-LEU--LEU-426, INTERACTION WITH CLATHRIN;
RP AP1G1 AND AP-2, TISSUE SPECIFICITY, AND SUBCELLULAR LOCATION.
RX PubMed=12429846; DOI=10.1091/mbc.E02-03-0171;
RA Kalthoff C., Groos S., Kohl R., Mahrhold S., Ungewickell E.J.;
RT "Clint: a novel clathrin-binding ENTH-domain protein at the Golgi.";
RL Mol. Biol. Cell 13:4060-4073(2002).
RN [9]
RP FUNCTION, TISSUE SPECIFICITY, SUBCELLULAR LOCATION, MUTAGENESIS OF
RP ASP-34; ASP-349; ASP-371 AND ASP-422, AND INTERACTION WITH AP1G1; AP-2
RP AND CLATHRIN.
RX PubMed=12538641; DOI=10.1083/jcb.200208023;
RA Mills I.G., Praefcke G.J.K., Vallis Y., Peter B.J., Olesen L.E.,
RA Gallop J.L., Butler P.J.G., Evans P.R., McMahon H.T.;
RT "EpsinR: an AP1/clathrin interacting protein involved in vesicle
RT trafficking.";
RL J. Cell Biol. 160:213-222(2003).
RN [10]
RP POSSIBLE INVOLVEMENT IN SCZD1.
RX PubMed=15793701; DOI=10.1086/430095;
RA Pimm J., McQuillin A., Thirumalai S., Lawrence J., Quested D.,
RA Bass N., Lamb G., Moorey H., Datta S.R., Kalsi G., Badacsonyi A.,
RA Kelly K., Morgan J., Punukollu B., Curtis D., Gurling H.;
RT "The Epsin 4 gene on chromosome 5q, which encodes the clathrin-
RT associated protein enthoprotin, is involved in the genetic
RT susceptibility to schizophrenia.";
RL Am. J. Hum. Genet. 76:902-907(2005).
RN [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-227, AND MASS
RP SPECTROMETRY.
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.,
RA Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in
RT signaling networks.";
RL Cell 127:635-648(2006).
RN [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-245 AND SER-299, AND
RP MASS SPECTROMETRY.
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 [13]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-245 AND SER-299, AND
RP MASS 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 [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-227, AND MASS
RP SPECTROMETRY.
RC TISSUE=Liver;
RX PubMed=18318008; DOI=10.1002/pmic.200700884;
RA Han G., Ye M., Zhou H., Jiang X., Feng S., Jiang X., Tian R., Wan D.,
RA Zou H., Gu J.;
RT "Large-scale phosphoproteome analysis of human liver tissue by
RT enrichment and fractionation of phosphopeptides with strong anion
RT exchange chromatography.";
RL Proteomics 8:1346-1361(2008).
RN [15]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J.,
RA Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in
RT a refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [16]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-299, 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 [17]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-245 AND SER-299, AND
RP MASS 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 [18]
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 [19]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-299, 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).
CC -!- FUNCTION: Binds to membranes enriched in phosphatidylinositol 4,5-
CC bisphosphate (PtdIns(4,5)P2). May have a role in transport via
CC clathrin-coated vesicles from the trans-Golgi network to
CC endosomes. Stimulates clathrin assembly.
CC -!- SUBUNIT: Binds clathrin heavy chain, GGA2, AP-2 and AP1G1.
CC -!- INTERACTION:
CC P22892:Ap1g1 (xeno); NbExp=10; IntAct=EBI-1171113, EBI-1040262;
CC Q9H0R8:GABARAPL1; NbExp=2; IntAct=EBI-1171113, EBI-746969;
CC Q9GZQ8:MAP1LC3B; NbExp=2; IntAct=EBI-1171113, EBI-373144;
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Cytoplasm, perinuclear region.
CC Membrane; Peripheral membrane protein. Cytoplasmic vesicle,
CC clathrin-coated vesicle. Note=Found throughout the cell, with the
CC exception of the cell surface. Concentrated in the perinuclear
CC region and associated with clathrin-coated vesicles close to the
CC trans-Golgi network.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q14677-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q14677-2; Sequence=VSP_009160, VSP_009161;
CC Name=3;
CC IsoId=Q14677-3; Sequence=VSP_043302;
CC Note=No experimental confirmation available;
CC -!- TISSUE SPECIFICITY: Ubiquitously expressed at low to intermediate
CC levels.
CC -!- POLYMORPHISM: Genetic variations in CLINT1 may contribute to
CC susceptibility to schizophrenia and psychotic disorders in some
CC populations.
CC -!- SIMILARITY: Belongs to the epsin family.
CC -!- SIMILARITY: Contains 1 ENTH (epsin N-terminal homology) domain.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAA11488.2; Type=Erroneous initiation;
CC -----------------------------------------------------------------------
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DR EMBL; BK000414; DAA00062.1; -; Genomic_DNA.
DR EMBL; AF434813; AAL30768.1; -; mRNA.
DR EMBL; D79993; BAA11488.2; ALT_INIT; mRNA.
DR EMBL; AK092765; BAC03971.1; -; mRNA.
DR EMBL; AK300257; BAH13244.1; -; mRNA.
DR EMBL; AC011394; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC026407; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471062; EAW61585.1; -; Genomic_DNA.
DR EMBL; CH471062; EAW61588.1; -; Genomic_DNA.
DR EMBL; BC004467; AAH04467.1; -; mRNA.
DR EMBL; BC013091; AAH13091.1; -; mRNA.
DR RefSeq; NP_001182484.1; NM_001195555.1.
DR RefSeq; NP_001182485.1; NM_001195556.1.
DR RefSeq; NP_055481.1; NM_014666.3.
DR UniGene; Hs.644000; -.
DR PDB; 1XGW; X-ray; 1.90 A; A=1-165.
DR PDB; 2QY7; X-ray; 2.00 A; A/B/C=20-166.
DR PDB; 2V8S; X-ray; 2.22 A; E=20-166.
DR PDBsum; 1XGW; -.
DR PDBsum; 2QY7; -.
DR PDBsum; 2V8S; -.
DR ProteinModelPortal; Q14677; -.
DR SMR; Q14677; 17-152.
DR IntAct; Q14677; 20.
DR MINT; MINT-4999242; -.
DR STRING; 9606.ENSP00000388340; -.
DR PhosphoSite; Q14677; -.
DR DMDM; 41016993; -.
DR PaxDb; Q14677; -.
DR PRIDE; Q14677; -.
DR Ensembl; ENST00000296951; ENSP00000296951; ENSG00000113282.
DR Ensembl; ENST00000411809; ENSP00000388340; ENSG00000113282.
DR Ensembl; ENST00000523094; ENSP00000429345; ENSG00000113282.
DR Ensembl; ENST00000523908; ENSP00000429824; ENSG00000113282.
DR Ensembl; ENST00000530742; ENSP00000433419; ENSG00000113282.
DR GeneID; 9685; -.
DR KEGG; hsa:9685; -.
DR UCSC; uc003lxj.2; human.
DR CTD; 9685; -.
DR GeneCards; GC05M157212; -.
DR HGNC; HGNC:23186; CLINT1.
DR HPA; HPA043280; -.
DR MIM; 607265; gene.
DR neXtProt; NX_Q14677; -.
DR Orphanet; 3140; Schizophrenia.
DR PharmGKB; PA145149115; -.
DR eggNOG; NOG290795; -.
DR HOGENOM; HOG000082415; -.
DR HOVERGEN; HBG048921; -.
DR InParanoid; Q14677; -.
DR OMA; PMSRSQP; -.
DR OrthoDB; EOG73V6K0; -.
DR PhylomeDB; Q14677; -.
DR Reactome; REACT_11123; Membrane Trafficking.
DR ChiTaRS; CLINT1; human.
DR EvolutionaryTrace; Q14677; -.
DR GeneWiki; CLINT1; -.
DR GenomeRNAi; 9685; -.
DR NextBio; 36372; -.
DR PRO; PR:Q14677; -.
DR Bgee; Q14677; -.
DR CleanEx; HS_CLINT1; -.
DR Genevestigator; Q14677; -.
DR GO; GO:0030136; C:clathrin-coated vesicle; IEA:UniProtKB-SubCell.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005794; C:Golgi apparatus; IDA:UniProtKB.
DR GO; GO:0016020; C:membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0008289; F:lipid binding; IEA:UniProtKB-KW.
DR GO; GO:0006897; P:endocytosis; IEA:UniProtKB-KW.
DR GO; GO:0006892; P:post-Golgi vesicle-mediated transport; TAS:Reactome.
DR Gene3D; 1.25.40.90; -; 1.
DR InterPro; IPR008942; ENTH_VHS.
DR InterPro; IPR013809; Epsin-like_N.
DR InterPro; IPR001026; Epsin_dom_N.
DR Pfam; PF01417; ENTH; 1.
DR SMART; SM00273; ENTH; 1.
DR SUPFAM; SSF48464; SSF48464; 1.
DR PROSITE; PS50942; ENTH; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Complete proteome; Cytoplasm;
KW Cytoplasmic vesicle; Direct protein sequencing; Endocytosis;
KW Lipid-binding; Membrane; Phosphoprotein; Reference proteome.
FT CHAIN 1 625 Clathrin interactor 1.
FT /FTId=PRO_0000074521.
FT DOMAIN 16 149 ENTH.
FT COMPBIAS 549 605 Met-rich.
FT BINDING 29 29 Phosphatidylinositol lipid headgroup (By
FT similarity).
FT BINDING 67 67 Phosphatidylinositol lipid headgroup (By
FT similarity).
FT MOD_RES 163 163 Phosphoserine (By similarity).
FT MOD_RES 227 227 Phosphoserine.
FT MOD_RES 245 245 Phosphoserine.
FT MOD_RES 299 299 Phosphoserine.
FT VAR_SEQ 1 18 Missing (in isoform 2).
FT /FTId=VSP_009160.
FT VAR_SEQ 459 459 S -> SQPLQNVSTVLQKPNPLYN (in isoform 3).
FT /FTId=VSP_043302.
FT VAR_SEQ 460 460 Q -> QPLQNVSTVLQKPNPLYNQ (in isoform 2).
FT /FTId=VSP_009161.
FT MUTAGEN 29 29 R->L: Reduces lipid binding. Abolishes
FT lipid binding; when associated with G-34.
FT MUTAGEN 34 34 D->G: Abolishes lipid binding; when
FT associated with L-29.
FT MUTAGEN 349 349 D->R: Decreases AP-1 and AP-2 binding.
FT MUTAGEN 371 371 D->R: Slightly decreases AP-1 binding.
FT MUTAGEN 422 422 D->R: Strongly decreases clathrin
FT binding.
FT MUTAGEN 423 426 LFDL->AFAA: Strongly reduces clathrin
FT binding.
FT CONFLICT 476 476 T -> A (in Ref. 4; BAC03971).
FT HELIX 23 31
FT STRAND 33 37
FT HELIX 41 50
FT TURN 54 56
FT HELIX 57 69
FT HELIX 76 92
FT HELIX 95 103
FT HELIX 105 109
FT HELIX 110 113
FT HELIX 125 139
FT HELIX 142 151
SQ SEQUENCE 625 AA; 68259 MW; 6C8C6689861E9F0D CRC64;
MLNMWKVREL VDKATNVVMN YSEIESKVRE ATNDDPWGPS GQLMGEIAKA TFMYEQFPEL
MNMLWSRMLK DNKKNWRRVY KSLLLLAYLI RNGSERVVTS AREHIYDLRS LENYHFVDEH
GKDQGINIRQ KVKELVEFAQ DDDRLREERK KAKKNKDKYV GVSSDSVGGF RYSERYDPEP
KSKWDEEWDK NKSAFPFSDK LGELSDKIGS TIDDTISKFR RKDREDSPER CSDSDEEKKA
RRGRSPKGEF KDEEETVTTK HIHITQATET TTTRHKRTAN PSKTIDLGAA AHYTGDKASP
DQNASTHTPQ SSVKTSVPSS KSSGDLVDLF DGTSQSTGGS ADLFGGFADF GSAAASGSFP
SQVTATSGNG DFGDWSAFNQ APSGPVASSG EFFGSASQPA VELVSGSQSA LGPPPAASNS
SDLFDLMGSS QATMTSSQSM NFSMMSTNTV GLGLPMSRSQ NTDMVQKSVS KTLPSTWSDP
SVNISLDNLL PGMQPSKPQQ PSLNTMIQQQ NMQQPMNVMT QSFGAVNLSS PSNMLPVRPQ
TNALIGGPMP MSMPNVMTGT MGMAPLGNTP MMNQSMMGMN MNIGMSAAGM GLTGTMGMGM
PNIAMTSGTV QPKQDAFANF ANFSK
//
MIM
607265
*RECORD*
*FIELD* NO
607265
*FIELD* TI
*607265 CLATHRIN INTERACTOR 1; CLINT1
;;EPSIN 4; EPN4;;
EPSIN-RELATED PROTEIN; EPNR;;
read moreENTHOPROTIN;;
KIAA0171
*FIELD* TX
For background information on epsins, see EPN1 (607262).
CLONING
Nagase et al. (1996) isolated a cDNA encoding EPN4, which they
designated KIAA0171, from the immature myeloid cell line KG-1. The
deduced protein contains 625 amino acids. Northern blot analysis
revealed moderate expression in all tissues tested, with highest
expression in skeletal muscle.
Wasiak et al. (2002) identified rat Epn4, which they called enthoprotin,
by subcellular proteomics of clathrin-coated vesicles (CCVs). Epn4 was
highly enriched on CCVs isolated from rat brain and liver extracts. By
sequence analysis of tryptic peptides, they identified an epsin
N-terminal homology (ENTH) domain and a consensus type-2 clathrin box in
the C-terminal domain. The predicted molecular mass is about 68 kD, and
Epn4 expressed by transfected COS-7 cells showed an apparent molecular
mass of about 80 kD. Endogenous Epn4 localized in COS-7 cells in a
punctate pattern that was enriched in a perinuclear pool that
colocalized with clathrin (118955) and with the clathrin adaptor protein
complex AP1 (see 607291).
GENE FUNCTION
Using pull-down assays, Wasiak et al. (2002) found that rat Epn4
interacts with AP1, AP2, clathrin, and GGA2 (606005). They determined
that, through its C-terminal domain, Epn4 binds to the terminal domain
of the clathrin heavy chain and stimulates clathrin assembly.
Saint-Pol et al. (2004) found that HeLa cell EPN4 was involved in
retrograde transport of endogenous cargo proteins and bacterial Shiga
toxin from early and recycling endosomes to the trans-Golgi network.
MAPPING
By radiation hybrid analysis, Nagase et al. (1996) mapped the EPN4 gene
to chromosome 5.
MOLECULAR GENETICS
Pimm et al. (2005) investigated 450 unrelated white English, Irish,
Welsh, and Scottish research subjects with schizophrenia and 450
ancestrally matched supernormal controls. Four adjacent markers at the
5-prime end of the EPN4 gene showed significant evidence of linkage
disequilibrium with schizophrenia. These included included 2
microsatellite markers and 2 SNPs within the EPN4 gene. A series of
different 2- and 3-marker haplotypes were also significantly associated
with schizophrenia. Since the EPN4 gene encodes enthoprotin, which has a
role in transport and stability of neurotransmitter vesicles at the
synapses and within neurons, they considered it likely that a
genetically determined abnormality in the structure, function, or
expression of this protein is responsible for genetic susceptibility to
a subtype of schizophrenia on 5q33.3 (SCZD1; 181510).
BIOCHEMICAL FEATURES
- Crystal Structure
Miller et al. (2007) characterized the molecular details governing the
sorting of a SNARE into clathrin-coated vesicles, namely, the direct
recognition of the 3-helical bundle H(abc) domain of the mouse SNARE
Vti1b (603207) by the human clathrin adaptor epsinR (EPNR, also known as
CLINT1). Structures of each domain and of their complex showed that this
interaction (dissociation constant 22 microM) is mediated by surface
patches composed of approximately 15 residues each, the topographies of
which are dependent on each domain's overall fold. Disruption of the
interface with point mutations abolished the interaction in vitro and
caused Vti1b to become relocalized to late endosomes and lysosomes.
Miller et al. (2007) stated that this new class of highly specific,
surface-surface interaction between the clathrin coat component and the
cargo is distinct from the widely observed binding of short, linear
cargo motifs by the assembly polypeptide (AP) complex and GGA adaptors
and is therefore not vulnerable to competition from standard
motif-containing cargoes for incorporation into clathrin-coated
vesicles. Miller et al. (2007) proposed that conceptually similar but
mechanistically different interactions direct the post-Golgi trafficking
of many SNAREs.
*FIELD* RF
1. Miller, S. E.; Collins, B. M.; McCoy, A. J.; Robinson, M. S.; Owen,
D. J.: A SNARE-adaptor interaction is a new mode of cargo recognition
in clathrin-coated vesicles. Nature 450: 570-574, 2007.
2. Nagase, T.; Seki, N.; Ishikawa, K.; Tanaka, A.; Nomura, N.: Prediction
of the coding sequences of unidentified human genes. V. The coding
sequences of 40 new genes (KIAA0161-KIAA0200) deduced by analysis
of cDNA clones from human cell line KG-1. DNA Res. 3: 17-24, 1996.
3. Pimm, J.; McQuillin, A.; Thirumalai, S.; Lawrence, J.; Quested,
D.; Bass, N.; Lamb, G.; Moorey, H.; Datta, S. R.; Kalsi, G.; Badacsonyi,
A.; Kelly, K.; Morgan, J.; Punukollu, B.; Curtis, D.; Gurling, H.
: The epsin 4 gene on chromosome 5q, which encodes the clathrin-associated
protein enthoprotin, is involved in the genetic susceptibility to
schizophrenia. Am. J. Hum. Genet. 76: 902-907, 2005.
4. Saint-Pol, A.; Yelamos, B.; Amessou, M.; Mills, I. G.; Dugast,
M.; Tenza, D.; Schu, P.; Antony, C.; McMahon, H. T.; Lamaze, C.; Johannes,
L.: Clathrin adaptor epsinR is required for retrograde sorting on
early endosomal membranes. Dev. Cell 6: 525-538, 2004.
5. Wasiak, S.; Legendre-Guillemin, V.; Puertollano, R.; Blondeau,
F.; Girard, M.; de Heuvel, E.; Boismenu, D.; Bell, A. W.; Bonifacino,
J. S.; McPherson, P. S.: Enthoprotin: a novel clathrin-associated
protein identified through subcellular proteomics. J. Cell Biol. 158:
855-862, 2002.
*FIELD* CN
Ada Hamosh - updated: 4/22/2008
Victor A. McKusick - updated: 4/13/2005
Patricia A. Hartz - updated: 5/13/2004
Patricia A. Hartz - updated: 10/29/2002
*FIELD* CD
Patricia A. Hartz: 9/27/2002
*FIELD* ED
alopez: 05/14/2008
terry: 4/22/2008
alopez: 3/26/2007
terry: 2/3/2006
alopez: 4/15/2005
terry: 4/13/2005
terry: 7/19/2004
mgross: 5/13/2004
terry: 5/13/2004
mgross: 10/29/2002
mgross: 9/27/2002
*RECORD*
*FIELD* NO
607265
*FIELD* TI
*607265 CLATHRIN INTERACTOR 1; CLINT1
;;EPSIN 4; EPN4;;
EPSIN-RELATED PROTEIN; EPNR;;
read moreENTHOPROTIN;;
KIAA0171
*FIELD* TX
For background information on epsins, see EPN1 (607262).
CLONING
Nagase et al. (1996) isolated a cDNA encoding EPN4, which they
designated KIAA0171, from the immature myeloid cell line KG-1. The
deduced protein contains 625 amino acids. Northern blot analysis
revealed moderate expression in all tissues tested, with highest
expression in skeletal muscle.
Wasiak et al. (2002) identified rat Epn4, which they called enthoprotin,
by subcellular proteomics of clathrin-coated vesicles (CCVs). Epn4 was
highly enriched on CCVs isolated from rat brain and liver extracts. By
sequence analysis of tryptic peptides, they identified an epsin
N-terminal homology (ENTH) domain and a consensus type-2 clathrin box in
the C-terminal domain. The predicted molecular mass is about 68 kD, and
Epn4 expressed by transfected COS-7 cells showed an apparent molecular
mass of about 80 kD. Endogenous Epn4 localized in COS-7 cells in a
punctate pattern that was enriched in a perinuclear pool that
colocalized with clathrin (118955) and with the clathrin adaptor protein
complex AP1 (see 607291).
GENE FUNCTION
Using pull-down assays, Wasiak et al. (2002) found that rat Epn4
interacts with AP1, AP2, clathrin, and GGA2 (606005). They determined
that, through its C-terminal domain, Epn4 binds to the terminal domain
of the clathrin heavy chain and stimulates clathrin assembly.
Saint-Pol et al. (2004) found that HeLa cell EPN4 was involved in
retrograde transport of endogenous cargo proteins and bacterial Shiga
toxin from early and recycling endosomes to the trans-Golgi network.
MAPPING
By radiation hybrid analysis, Nagase et al. (1996) mapped the EPN4 gene
to chromosome 5.
MOLECULAR GENETICS
Pimm et al. (2005) investigated 450 unrelated white English, Irish,
Welsh, and Scottish research subjects with schizophrenia and 450
ancestrally matched supernormal controls. Four adjacent markers at the
5-prime end of the EPN4 gene showed significant evidence of linkage
disequilibrium with schizophrenia. These included included 2
microsatellite markers and 2 SNPs within the EPN4 gene. A series of
different 2- and 3-marker haplotypes were also significantly associated
with schizophrenia. Since the EPN4 gene encodes enthoprotin, which has a
role in transport and stability of neurotransmitter vesicles at the
synapses and within neurons, they considered it likely that a
genetically determined abnormality in the structure, function, or
expression of this protein is responsible for genetic susceptibility to
a subtype of schizophrenia on 5q33.3 (SCZD1; 181510).
BIOCHEMICAL FEATURES
- Crystal Structure
Miller et al. (2007) characterized the molecular details governing the
sorting of a SNARE into clathrin-coated vesicles, namely, the direct
recognition of the 3-helical bundle H(abc) domain of the mouse SNARE
Vti1b (603207) by the human clathrin adaptor epsinR (EPNR, also known as
CLINT1). Structures of each domain and of their complex showed that this
interaction (dissociation constant 22 microM) is mediated by surface
patches composed of approximately 15 residues each, the topographies of
which are dependent on each domain's overall fold. Disruption of the
interface with point mutations abolished the interaction in vitro and
caused Vti1b to become relocalized to late endosomes and lysosomes.
Miller et al. (2007) stated that this new class of highly specific,
surface-surface interaction between the clathrin coat component and the
cargo is distinct from the widely observed binding of short, linear
cargo motifs by the assembly polypeptide (AP) complex and GGA adaptors
and is therefore not vulnerable to competition from standard
motif-containing cargoes for incorporation into clathrin-coated
vesicles. Miller et al. (2007) proposed that conceptually similar but
mechanistically different interactions direct the post-Golgi trafficking
of many SNAREs.
*FIELD* RF
1. Miller, S. E.; Collins, B. M.; McCoy, A. J.; Robinson, M. S.; Owen,
D. J.: A SNARE-adaptor interaction is a new mode of cargo recognition
in clathrin-coated vesicles. Nature 450: 570-574, 2007.
2. Nagase, T.; Seki, N.; Ishikawa, K.; Tanaka, A.; Nomura, N.: Prediction
of the coding sequences of unidentified human genes. V. The coding
sequences of 40 new genes (KIAA0161-KIAA0200) deduced by analysis
of cDNA clones from human cell line KG-1. DNA Res. 3: 17-24, 1996.
3. Pimm, J.; McQuillin, A.; Thirumalai, S.; Lawrence, J.; Quested,
D.; Bass, N.; Lamb, G.; Moorey, H.; Datta, S. R.; Kalsi, G.; Badacsonyi,
A.; Kelly, K.; Morgan, J.; Punukollu, B.; Curtis, D.; Gurling, H.
: The epsin 4 gene on chromosome 5q, which encodes the clathrin-associated
protein enthoprotin, is involved in the genetic susceptibility to
schizophrenia. Am. J. Hum. Genet. 76: 902-907, 2005.
4. Saint-Pol, A.; Yelamos, B.; Amessou, M.; Mills, I. G.; Dugast,
M.; Tenza, D.; Schu, P.; Antony, C.; McMahon, H. T.; Lamaze, C.; Johannes,
L.: Clathrin adaptor epsinR is required for retrograde sorting on
early endosomal membranes. Dev. Cell 6: 525-538, 2004.
5. Wasiak, S.; Legendre-Guillemin, V.; Puertollano, R.; Blondeau,
F.; Girard, M.; de Heuvel, E.; Boismenu, D.; Bell, A. W.; Bonifacino,
J. S.; McPherson, P. S.: Enthoprotin: a novel clathrin-associated
protein identified through subcellular proteomics. J. Cell Biol. 158:
855-862, 2002.
*FIELD* CN
Ada Hamosh - updated: 4/22/2008
Victor A. McKusick - updated: 4/13/2005
Patricia A. Hartz - updated: 5/13/2004
Patricia A. Hartz - updated: 10/29/2002
*FIELD* CD
Patricia A. Hartz: 9/27/2002
*FIELD* ED
alopez: 05/14/2008
terry: 4/22/2008
alopez: 3/26/2007
terry: 2/3/2006
alopez: 4/15/2005
terry: 4/13/2005
terry: 7/19/2004
mgross: 5/13/2004
terry: 5/13/2004
mgross: 10/29/2002
mgross: 9/27/2002