Full text data of CLTC
CLTC
(CLH17, CLTCL2, KIAA0034)
[Confidence: high (present in two of the MS resources)]
Clathrin heavy chain 1 (Clathrin heavy chain on chromosome 17; CLH-17)
Clathrin heavy chain 1 (Clathrin heavy chain on chromosome 17; CLH-17)
hRBCD
IPI00024067
IPI00024067 Clathrin heavy Chain 1 Clathrin is the major protein of the polyhedral coat of coated pits and vesicles, bone marrow 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 Cytoplasmic face of coated pits and vesicles n/a found at its expected molecular weight found at molecular weight
IPI00024067 Clathrin heavy Chain 1 Clathrin is the major protein of the polyhedral coat of coated pits and vesicles, bone marrow 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 Cytoplasmic face of coated pits and vesicles n/a found at its expected molecular weight found at molecular weight
UniProt
Q00610
ID CLH1_HUMAN Reviewed; 1675 AA.
AC Q00610; D3DU00; Q6N0A0; Q86TF2;
DT 01-DEC-1992, integrated into UniProtKB/Swiss-Prot.
read moreDT 23-JAN-2007, sequence version 5.
DT 22-JAN-2014, entry version 141.
DE RecName: Full=Clathrin heavy chain 1;
DE AltName: Full=Clathrin heavy chain on chromosome 17;
DE Short=CLH-17;
GN Name=CLTC; Synonyms=CLH17, CLTCL2, KIAA0034;
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 [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Bone marrow;
RX PubMed=7584026; DOI=10.1093/dnares/1.1.27;
RA Nomura N., Miyajima N., Sazuka T., Tanaka A., Kawarabayasi Y.,
RA Sato S., Nagase T., Seki N., Ishikawa K., Tabata S.;
RT "Prediction of the coding sequences of unidentified human genes. I.
RT The coding sequences of 40 new genes (KIAA0001-KIAA0040) deduced by
RT analysis of randomly sampled cDNA clones from human immature myeloid
RT cell line KG-1.";
RL DNA Res. 1:27-35(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Fetal kidney;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H.,
RA Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K.,
RA Ottenwaelder B., Poustka A., Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [3]
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=PNS, and Testis;
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 NUCLEOTIDE SEQUENCE [MRNA] OF 560-864 (ISOFORMS 1/2).
RC TISSUE=Colon;
RX PubMed=1765375; DOI=10.1016/0888-7543(91)90115-U;
RA Dodge G.R., Kovalszky I., McBride O.W., Yi H.F., Chu M.-L., Saitta B.,
RA Stokes D.G., Iozzo R.V.;
RT "Human clathrin heavy chain (CLTC): partial molecular cloning,
RT expression, and mapping of the gene to human chromosome 17q11-qter.";
RL Genomics 11:174-178(1991).
RN [6]
RP PROTEIN SEQUENCE OF 2-8.
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 [7]
RP PROTEIN SEQUENCE OF 2-8; 64-78; 87-96; 164-205; 228-245; 270-278;
RP 298-320; 355-382; 469-481; 507-519; 572-610; 626-638; 799-806;
RP 831-852; 855-865; 882-903; 1011-1037; 1074-1101; 1123-1130; 1166-1179;
RP 1183-1204; 1216-1245; 1312-1326; 1398-1406; 1435-1453; 1482-1498;
RP 1502-1508; 1510-1516 AND 1610-1620, CLEAVAGE OF INITIATOR METHIONINE,
RP ACETYLATION AT ALA-2, AND MASS SPECTROMETRY.
RC TISSUE=Cervix carcinoma, Hepatoma, and Mammary carcinoma;
RA Bienvenut W.V., Calvo F., Matallanas D., Cooper W.N., Boldt K.,
RA von Kriegsheim A.F., Kolch W.;
RL Submitted (FEB-2008) to UniProtKB.
RN [8]
RP INTERACTION WITH HIP1.
RX PubMed=11532990; DOI=10.1093/hmg/10.17.1807;
RA Waelter S., Scherzinger E., Hasenbank R., Nordhoff E., Lurz R.,
RA Goehler H., Gauss C., Sathasivam K., Bates G.P., Lehrach H.,
RA Wanker E.E.;
RT "The huntingtin interacting protein HIP1 is a clathrin and alpha-
RT adaptin-binding protein involved in receptor-mediated endocytosis.";
RL Hum. Mol. Genet. 10:1807-1817(2001).
RN [9]
RP INTERACTION WITH ERBB2.
RX PubMed=16314522; DOI=10.1128/MCB.25.24.11005-11018.2005;
RA Giri D.K., Ali-Seyed M., Li L.Y., Lee D.F., Ling P., Bartholomeusz G.,
RA Wang S.C., Hung M.C.;
RT "Endosomal transport of ErbB-2: mechanism for nuclear entry of the
RT cell surface receptor.";
RL Mol. Cell. Biol. 25:11005-11018(2005).
RN [10]
RP SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS], AND MASS SPECTROMETRY.
RC TISSUE=Melanoma;
RX PubMed=17081065; DOI=10.1021/pr060363j;
RA Chi A., Valencia J.C., Hu Z.-Z., Watabe H., Yamaguchi H.,
RA Mangini N.J., Huang H., Canfield V.A., Cheng K.C., Yang F., Abe R.,
RA Yamagishi S., Shabanowitz J., Hearing V.J., Wu C., Appella E.,
RA Hunt D.F.;
RT "Proteomic and bioinformatic characterization of the biogenesis and
RT function of melanosomes.";
RL J. Proteome Res. 5:3135-3144(2006).
RN [11]
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 [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-394, 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 [13]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1494, AND MASS
RP SPECTROMETRY.
RX PubMed=19369195; DOI=10.1074/mcp.M800588-MCP200;
RA Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G.,
RA Mann M., Daub H.;
RT "Large-scale proteomics analysis of the human kinome.";
RL Mol. Cell. Proteomics 8:1751-1764(2009).
RN [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-634 AND TYR-1477, AND
RP MASS 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 [15]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-856; LYS-1441 AND LYS-1501,
RP AND MASS SPECTROMETRY.
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M.,
RA Walther T.C., Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [16]
RP IDENTIFICATION BY 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.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [17]
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 [18]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, 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 X-RAY CRYSTALLOGRAPHY (1.69 ANGSTROMS) OF 1-364 IN COMPLEX WITH
RP INHIBITORS, AND WD40-LIKE REPEATS.
RX PubMed=21816279; DOI=10.1016/j.cell.2011.06.025;
RA von Kleist L., Stahlschmidt W., Bulut H., Gromova K., Puchkov D.,
RA Robertson M.J., MacGregor K.A., Tomilin N., Pechstein A., Chau N.,
RA Chircop M., Sakoff J., von Kries J.P., Saenger W., Krausslich H.G.,
RA Shupliakov O., Robinson P.J., McCluskey A., Haucke V.;
RT "Role of the clathrin terminal domain in regulating coated pit
RT dynamics revealed by small molecule inhibition.";
RL Cell 146:471-484(2011).
CC -!- FUNCTION: Clathrin is the major protein of the polyhedral coat of
CC coated pits and vesicles. Two different adapter protein complexes
CC link the clathrin lattice either to the plasma membrane or to the
CC trans-Golgi network.
CC -!- SUBUNIT: Clathrin triskelions, composed of 3 heavy chains and 3
CC light chains, are the basic subunits of the clathrin coat. In the
CC presence of light chains, hub assembly is influenced by both the
CC pH and the concentration of calcium. Interacts with HIP1.
CC Interacts with DENND1A, DENND1B and DENND1C (By similarity). May
CC interact with OCRL. Interacts with ERBB2 (By similarity).
CC -!- INTERACTION:
CC P10242:MYB; NbExp=4; IntAct=EBI-354967, EBI-298355;
CC Q01968:OCRL; NbExp=4; IntAct=EBI-354967, EBI-6148898;
CC O75674:TOM1L1; NbExp=4; IntAct=EBI-354967, EBI-712991;
CC -!- SUBCELLULAR LOCATION: Cytoplasmic vesicle membrane; Peripheral
CC membrane protein; Cytoplasmic side. Membrane, coated pit;
CC Peripheral membrane protein; Cytoplasmic side. Melanosome.
CC Note=Cytoplasmic face of coated pits and vesicles. Identified by
CC mass spectrometry in melanosome fractions from stage I to stage
CC IV.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q00610-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q00610-2; Sequence=VSP_011570, VSP_011571;
CC Note=No experimental confirmation available;
CC -!- DOMAIN: The N-terminal seven-bladed beta-propeller is formed by
CC WD40-like repeats, and projects inward from the polyhedral outer
CC clathrin coat. It consitutes a major protein-protein interaction
CC node.
CC -!- SIMILARITY: Belongs to the clathrin heavy chain family.
CC -!- SIMILARITY: Contains 7 CHCR (clathrin heavy-chain) repeats.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAA04801.2; Type=Erroneous initiation;
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology
CC and Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/CLTCID360.html";
CC -!- WEB RESOURCE: Name=Wikipedia; Note=Clathrin entry;
CC URL="http://en.wikipedia.org/wiki/Clathrin";
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; D21260; BAA04801.2; ALT_INIT; mRNA.
DR EMBL; BX640615; CAE45761.1; -; mRNA.
DR EMBL; CH471109; EAW94396.1; -; Genomic_DNA.
DR EMBL; CH471109; EAW94399.1; -; Genomic_DNA.
DR EMBL; BC051800; AAH51800.1; -; mRNA.
DR EMBL; BC054489; AAH54489.1; -; mRNA.
DR EMBL; X55878; CAA39363.1; -; mRNA.
DR PIR; A40573; A40573.
DR RefSeq; NP_004850.1; NM_004859.3.
DR UniGene; Hs.491351; -.
DR PDB; 2XZG; X-ray; 1.70 A; A=1-364.
DR PDB; 4G55; X-ray; 1.69 A; A=1-364.
DR PDBsum; 2XZG; -.
DR PDBsum; 4G55; -.
DR ProteinModelPortal; Q00610; -.
DR SMR; Q00610; 1-493, 1077-1630.
DR IntAct; Q00610; 45.
DR MINT; MINT-4998595; -.
DR STRING; 9606.ENSP00000269122; -.
DR PhosphoSite; Q00610; -.
DR DMDM; 1705916; -.
DR PaxDb; Q00610; -.
DR PRIDE; Q00610; -.
DR DNASU; 1213; -.
DR Ensembl; ENST00000269122; ENSP00000269122; ENSG00000141367.
DR Ensembl; ENST00000393043; ENSP00000376763; ENSG00000141367.
DR GeneID; 1213; -.
DR KEGG; hsa:1213; -.
DR UCSC; uc002ixq.1; human.
DR CTD; 1213; -.
DR GeneCards; GC17P057697; -.
DR H-InvDB; HIX0039315; -.
DR HGNC; HGNC:2092; CLTC.
DR HPA; CAB010389; -.
DR HPA; CAB011571; -.
DR HPA; CAB017155; -.
DR MIM; 118955; gene.
DR neXtProt; NX_Q00610; -.
DR Orphanet; 178342; Inflammatory myofibroblastic tumor.
DR Orphanet; 319308; Translocation renal cell carcinoma.
DR PharmGKB; PA26618; -.
DR eggNOG; NOG314149; -.
DR HOGENOM; HOG000188877; -.
DR HOVERGEN; HBG005344; -.
DR InParanoid; Q00610; -.
DR KO; K04646; -.
DR OMA; SNLEIYY; -.
DR OrthoDB; EOG7Z0JVM; -.
DR PhylomeDB; Q00610; -.
DR Reactome; REACT_11123; Membrane Trafficking.
DR Reactome; REACT_6900; Immune System.
DR SignaLink; Q00610; -.
DR ChiTaRS; CLTC; human.
DR EvolutionaryTrace; Q00610; -.
DR GeneWiki; CLTC; -.
DR GenomeRNAi; 1213; -.
DR NextBio; 4999; -.
DR PRO; PR:Q00610; -.
DR ArrayExpress; Q00610; -.
DR Bgee; Q00610; -.
DR CleanEx; HS_CLTC; -.
DR Genevestigator; Q00610; -.
DR GO; GO:0030118; C:clathrin coat; NAS:UniProtKB.
DR GO; GO:0030132; C:clathrin coat of coated pit; IEA:InterPro.
DR GO; GO:0030130; C:clathrin coat of trans-Golgi network vesicle; IEA:InterPro.
DR GO; GO:0030669; C:clathrin-coated endocytic vesicle membrane; TAS:Reactome.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0070062; C:extracellular vesicular exosome; IDA:UniProtKB.
DR GO; GO:0042470; C:melanosome; IEA:UniProtKB-SubCell.
DR GO; GO:0005739; C:mitochondrion; IEA:Ensembl.
DR GO; GO:0005819; C:spindle; IDA:UniProtKB.
DR GO; GO:0032588; C:trans-Golgi network membrane; TAS:Reactome.
DR GO; GO:0003725; F:double-stranded RNA binding; IDA:MGI.
DR GO; GO:0005198; F:structural molecule activity; NAS:UniProtKB.
DR GO; GO:0019886; P:antigen processing and presentation of exogenous peptide antigen via MHC class II; TAS:Reactome.
DR GO; GO:0006886; P:intracellular protein transport; NAS:UniProtKB.
DR GO; GO:0007067; P:mitosis; IMP:UniProtKB.
DR GO; GO:0006892; P:post-Golgi vesicle-mediated transport; TAS:Reactome.
DR GO; GO:0031623; P:receptor internalization; IMP:BHF-UCL.
DR GO; GO:0033572; P:transferrin transport; IMP:BHF-UCL.
DR Gene3D; 1.25.40.10; -; 4.
DR Gene3D; 2.130.10.110; -; 1.
DR InterPro; IPR016024; ARM-type_fold.
DR InterPro; IPR000547; Clathrin_H-chain/VPS_repeat.
DR InterPro; IPR016025; Clathrin_H-chain_link/propller.
DR InterPro; IPR015348; Clathrin_H-chain_linker_core.
DR InterPro; IPR001473; Clathrin_H-chain_propeller_N.
DR InterPro; IPR022365; Clathrin_H-chain_propeller_rpt.
DR InterPro; IPR016341; Clathrin_heavy_chain.
DR InterPro; IPR011990; TPR-like_helical.
DR Pfam; PF00637; Clathrin; 7.
DR Pfam; PF09268; Clathrin-link; 1.
DR Pfam; PF01394; Clathrin_propel; 3.
DR PIRSF; PIRSF002290; Clathrin_H_chain; 1.
DR SMART; SM00299; CLH; 7.
DR SUPFAM; SSF48371; SSF48371; 6.
DR SUPFAM; SSF50989; SSF50989; 1.
DR PROSITE; PS50236; CHCR; 7.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; Coated pit;
KW Complete proteome; Cytoplasmic vesicle; Direct protein sequencing;
KW Membrane; Phosphoprotein; Reference proteome; Repeat.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 1675 Clathrin heavy chain 1.
FT /FTId=PRO_0000205778.
FT REPEAT 537 683 CHCR 1.
FT REPEAT 686 828 CHCR 2.
FT REPEAT 833 972 CHCR 3.
FT REPEAT 979 1124 CHCR 4.
FT REPEAT 1128 1269 CHCR 5.
FT REPEAT 1274 1420 CHCR 6.
FT REPEAT 1423 1566 CHCR 7.
FT REGION 2 479 Globular terminal domain.
FT REGION 24 67 WD40-like repeat 1.
FT REGION 68 107 WD40-like repeat 2.
FT REGION 108 149 WD40-like repeat 3.
FT REGION 150 195 WD40-like repeat 4.
FT REGION 196 257 WD40-like repeat 5.
FT REGION 258 301 WD40-like repeat 6.
FT REGION 302 330 WD40-like repeat 7.
FT REGION 449 465 Binding site for the uncoating ATPase,
FT involved in lattice disassembly
FT (Potential).
FT REGION 480 523 Flexible linker.
FT REGION 524 1675 Heavy chain arm.
FT REGION 524 634 Distal segment.
FT REGION 639 1675 Proximal segment.
FT REGION 1213 1522 Involved in binding clathrin light chain
FT (By similarity).
FT REGION 1550 1675 Trimerization (By similarity).
FT MOD_RES 2 2 N-acetylalanine.
FT MOD_RES 184 184 Phosphotyrosine (By similarity).
FT MOD_RES 394 394 Phosphothreonine.
FT MOD_RES 634 634 Phosphotyrosine.
FT MOD_RES 856 856 N6-acetyllysine.
FT MOD_RES 899 899 Phosphotyrosine (By similarity).
FT MOD_RES 1206 1206 Phosphotyrosine (By similarity).
FT MOD_RES 1441 1441 N6-acetyllysine.
FT MOD_RES 1477 1477 Phosphotyrosine.
FT MOD_RES 1487 1487 Phosphotyrosine (By similarity).
FT MOD_RES 1494 1494 Phosphoserine.
FT MOD_RES 1501 1501 N6-acetyllysine.
FT VAR_SEQ 1636 1639 QPQL -> NLSL (in isoform 2).
FT /FTId=VSP_011570.
FT VAR_SEQ 1640 1675 Missing (in isoform 2).
FT /FTId=VSP_011571.
FT CONFLICT 560 560 Q -> R (in Ref. 5; CAA39363).
FT CONFLICT 817 817 G -> V (in Ref. 5; CAA39363).
FT CONFLICT 923 923 R -> H (in Ref. 2; CAE45761).
FT CONFLICT 1563 1563 R -> G (in Ref. 2; CAE45761).
FT CONFLICT 1652 1652 Q -> R (in Ref. 2; CAE45761).
FT STRAND 6 14
FT HELIX 15 18
FT HELIX 22 24
FT TURN 27 29
FT STRAND 30 34
FT STRAND 37 44
FT STRAND 47 54
FT STRAND 62 65
FT STRAND 69 73
FT STRAND 75 84
FT STRAND 87 92
FT TURN 93 96
FT STRAND 97 103
FT STRAND 108 113
FT STRAND 115 133
FT STRAND 139 143
FT HELIX 146 148
FT STRAND 152 158
FT STRAND 164 173
FT STRAND 176 185
FT TURN 186 189
FT STRAND 190 194
FT STRAND 197 204
FT STRAND 213 222
FT STRAND 225 232
FT STRAND 246 250
FT STRAND 261 267
FT TURN 268 271
FT STRAND 272 277
FT STRAND 280 286
FT TURN 287 289
FT STRAND 292 297
FT STRAND 303 309
FT HELIX 310 312
FT STRAND 314 319
FT STRAND 323 329
FT TURN 331 333
FT HELIX 334 340
FT HELIX 345 354
SQ SEQUENCE 1675 AA; 191615 MW; 6C4F2D54950079E2 CRC64;
MAQILPIRFQ EHLQLQNLGI NPANIGFSTL TMESDKFICI REKVGEQAQV VIIDMNDPSN
PIRRPISADS AIMNPASKVI ALKAGKTLQI FNIEMKSKMK AHTMTDDVTF WKWISLNTVA
LVTDNAVYHW SMEGESQPVK MFDRHSSLAG CQIINYRTDA KQKWLLLTGI SAQQNRVVGA
MQLYSVDRKV SQPIEGHAAS FAQFKMEGNA EESTLFCFAV RGQAGGKLHI IEVGTPPTGN
QPFPKKAVDV FFPPEAQNDF PVAMQISEKH DVVFLITKYG YIHLYDLETG TCIYMNRISG
ETIFVTAPHE ATAGIIGVNR KGQVLSVCVE EENIIPYITN VLQNPDLALR MAVRNNLAGA
EELFARKFNA LFAQGNYSEA AKVAANAPKG ILRTPDTIRR FQSVPAQPGQ TSPLLQYFGI
LLDQGQLNKY ESLELCRPVL QQGRKQLLEK WLKEDKLECS EELGDLVKSV DPTLALSVYL
RANVPNKVIQ CFAETGQVQK IVLYAKKVGY TPDWIFLLRN VMRISPDQGQ QFAQMLVQDE
EPLADITQIV DVFMEYNLIQ QCTAFLLDAL KNNRPSEGPL QTRLLEMNLM HAPQVADAIL
GNQMFTHYDR AHIAQLCEKA GLLQRALEHF TDLYDIKRAV VHTHLLNPEW LVNYFGSLSV
EDSLECLRAM LSANIRQNLQ ICVQVASKYH EQLSTQSLIE LFESFKSFEG LFYFLGSIVN
FSQDPDVHFK YIQAACKTGQ IKEVERICRE SNCYDPERVK NFLKEAKLTD QLPLIIVCDR
FDFVHDLVLY LYRNNLQKYI EIYVQKVNPS RLPVVIGGLL DVDCSEDVIK NLILVVRGQF
STDELVAEVE KRNRLKLLLP WLEARIHEGC EEPATHNALA KIYIDSNNNP ERFLRENPYY
DSRVVGKYCE KRDPHLACVA YERGQCDLEL INVCNENSLF KSLSRYLVRR KDPELWGSVL
LESNPYRRPL IDQVVQTALS ETQDPEEVSV TVKAFMTADL PNELIELLEK IVLDNSVFSE
HRNLQNLLIL TAIKADRTRV MEYINRLDNY DAPDIANIAI SNELFEEAFA IFRKFDVNTS
AVQVLIEHIG NLDRAYEFAE RCNEPAVWSQ LAKAQLQKGM VKEAIDSYIK ADDPSSYMEV
VQAANTSGNW EELVKYLQMA RKKARESYVE TELIFALAKT NRLAELEEFI NGPNNAHIQQ
VGDRCYDEKM YDAAKLLYNN VSNFGRLAST LVHLGEYQAA VDGARKANST RTWKEVCFAC
VDGKEFRLAQ MCGLHIVVHA DELEELINYY QDRGYFEELI TMLEAALGLE RAHMGMFTEL
AILYSKFKPQ KMREHLELFW SRVNIPKVLR AAEQAHLWAE LVFLYDKYEE YDNAIITMMN
HPTDAWKEGQ FKDIITKVAN VELYYRAIQF YLEFKPLLLN DLLMVLSPRL DHTRAVNYFS
KVKQLPLVKP YLRSVQNHNN KSVNESLNNL FITEEDYQAL RTSIDAYDNF DNISLAQRLE
KHELIEFRRI AAYLFKGNNR WKQSVELCKK DSLYKDAMQY ASESKDTELA EELLQWFLQE
EKRECFGACL FTCYDLLRPD VVLETAWRHN IMDFAMPYFI QVMKEYLTKV DKLDASESLR
KEEEQATETQ PIVYGQPQLM LTAGPSVAVP PQAPFGYGYT APPYGQPQPG FGYSM
//
ID CLH1_HUMAN Reviewed; 1675 AA.
AC Q00610; D3DU00; Q6N0A0; Q86TF2;
DT 01-DEC-1992, integrated into UniProtKB/Swiss-Prot.
read moreDT 23-JAN-2007, sequence version 5.
DT 22-JAN-2014, entry version 141.
DE RecName: Full=Clathrin heavy chain 1;
DE AltName: Full=Clathrin heavy chain on chromosome 17;
DE Short=CLH-17;
GN Name=CLTC; Synonyms=CLH17, CLTCL2, KIAA0034;
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 [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Bone marrow;
RX PubMed=7584026; DOI=10.1093/dnares/1.1.27;
RA Nomura N., Miyajima N., Sazuka T., Tanaka A., Kawarabayasi Y.,
RA Sato S., Nagase T., Seki N., Ishikawa K., Tabata S.;
RT "Prediction of the coding sequences of unidentified human genes. I.
RT The coding sequences of 40 new genes (KIAA0001-KIAA0040) deduced by
RT analysis of randomly sampled cDNA clones from human immature myeloid
RT cell line KG-1.";
RL DNA Res. 1:27-35(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Fetal kidney;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H.,
RA Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K.,
RA Ottenwaelder B., Poustka A., Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [3]
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=PNS, and Testis;
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 NUCLEOTIDE SEQUENCE [MRNA] OF 560-864 (ISOFORMS 1/2).
RC TISSUE=Colon;
RX PubMed=1765375; DOI=10.1016/0888-7543(91)90115-U;
RA Dodge G.R., Kovalszky I., McBride O.W., Yi H.F., Chu M.-L., Saitta B.,
RA Stokes D.G., Iozzo R.V.;
RT "Human clathrin heavy chain (CLTC): partial molecular cloning,
RT expression, and mapping of the gene to human chromosome 17q11-qter.";
RL Genomics 11:174-178(1991).
RN [6]
RP PROTEIN SEQUENCE OF 2-8.
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 [7]
RP PROTEIN SEQUENCE OF 2-8; 64-78; 87-96; 164-205; 228-245; 270-278;
RP 298-320; 355-382; 469-481; 507-519; 572-610; 626-638; 799-806;
RP 831-852; 855-865; 882-903; 1011-1037; 1074-1101; 1123-1130; 1166-1179;
RP 1183-1204; 1216-1245; 1312-1326; 1398-1406; 1435-1453; 1482-1498;
RP 1502-1508; 1510-1516 AND 1610-1620, CLEAVAGE OF INITIATOR METHIONINE,
RP ACETYLATION AT ALA-2, AND MASS SPECTROMETRY.
RC TISSUE=Cervix carcinoma, Hepatoma, and Mammary carcinoma;
RA Bienvenut W.V., Calvo F., Matallanas D., Cooper W.N., Boldt K.,
RA von Kriegsheim A.F., Kolch W.;
RL Submitted (FEB-2008) to UniProtKB.
RN [8]
RP INTERACTION WITH HIP1.
RX PubMed=11532990; DOI=10.1093/hmg/10.17.1807;
RA Waelter S., Scherzinger E., Hasenbank R., Nordhoff E., Lurz R.,
RA Goehler H., Gauss C., Sathasivam K., Bates G.P., Lehrach H.,
RA Wanker E.E.;
RT "The huntingtin interacting protein HIP1 is a clathrin and alpha-
RT adaptin-binding protein involved in receptor-mediated endocytosis.";
RL Hum. Mol. Genet. 10:1807-1817(2001).
RN [9]
RP INTERACTION WITH ERBB2.
RX PubMed=16314522; DOI=10.1128/MCB.25.24.11005-11018.2005;
RA Giri D.K., Ali-Seyed M., Li L.Y., Lee D.F., Ling P., Bartholomeusz G.,
RA Wang S.C., Hung M.C.;
RT "Endosomal transport of ErbB-2: mechanism for nuclear entry of the
RT cell surface receptor.";
RL Mol. Cell. Biol. 25:11005-11018(2005).
RN [10]
RP SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS], AND MASS SPECTROMETRY.
RC TISSUE=Melanoma;
RX PubMed=17081065; DOI=10.1021/pr060363j;
RA Chi A., Valencia J.C., Hu Z.-Z., Watabe H., Yamaguchi H.,
RA Mangini N.J., Huang H., Canfield V.A., Cheng K.C., Yang F., Abe R.,
RA Yamagishi S., Shabanowitz J., Hearing V.J., Wu C., Appella E.,
RA Hunt D.F.;
RT "Proteomic and bioinformatic characterization of the biogenesis and
RT function of melanosomes.";
RL J. Proteome Res. 5:3135-3144(2006).
RN [11]
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 [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-394, 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 [13]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1494, AND MASS
RP SPECTROMETRY.
RX PubMed=19369195; DOI=10.1074/mcp.M800588-MCP200;
RA Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G.,
RA Mann M., Daub H.;
RT "Large-scale proteomics analysis of the human kinome.";
RL Mol. Cell. Proteomics 8:1751-1764(2009).
RN [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-634 AND TYR-1477, AND
RP MASS 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 [15]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-856; LYS-1441 AND LYS-1501,
RP AND MASS SPECTROMETRY.
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M.,
RA Walther T.C., Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [16]
RP IDENTIFICATION BY 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.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [17]
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 [18]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, 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 X-RAY CRYSTALLOGRAPHY (1.69 ANGSTROMS) OF 1-364 IN COMPLEX WITH
RP INHIBITORS, AND WD40-LIKE REPEATS.
RX PubMed=21816279; DOI=10.1016/j.cell.2011.06.025;
RA von Kleist L., Stahlschmidt W., Bulut H., Gromova K., Puchkov D.,
RA Robertson M.J., MacGregor K.A., Tomilin N., Pechstein A., Chau N.,
RA Chircop M., Sakoff J., von Kries J.P., Saenger W., Krausslich H.G.,
RA Shupliakov O., Robinson P.J., McCluskey A., Haucke V.;
RT "Role of the clathrin terminal domain in regulating coated pit
RT dynamics revealed by small molecule inhibition.";
RL Cell 146:471-484(2011).
CC -!- FUNCTION: Clathrin is the major protein of the polyhedral coat of
CC coated pits and vesicles. Two different adapter protein complexes
CC link the clathrin lattice either to the plasma membrane or to the
CC trans-Golgi network.
CC -!- SUBUNIT: Clathrin triskelions, composed of 3 heavy chains and 3
CC light chains, are the basic subunits of the clathrin coat. In the
CC presence of light chains, hub assembly is influenced by both the
CC pH and the concentration of calcium. Interacts with HIP1.
CC Interacts with DENND1A, DENND1B and DENND1C (By similarity). May
CC interact with OCRL. Interacts with ERBB2 (By similarity).
CC -!- INTERACTION:
CC P10242:MYB; NbExp=4; IntAct=EBI-354967, EBI-298355;
CC Q01968:OCRL; NbExp=4; IntAct=EBI-354967, EBI-6148898;
CC O75674:TOM1L1; NbExp=4; IntAct=EBI-354967, EBI-712991;
CC -!- SUBCELLULAR LOCATION: Cytoplasmic vesicle membrane; Peripheral
CC membrane protein; Cytoplasmic side. Membrane, coated pit;
CC Peripheral membrane protein; Cytoplasmic side. Melanosome.
CC Note=Cytoplasmic face of coated pits and vesicles. Identified by
CC mass spectrometry in melanosome fractions from stage I to stage
CC IV.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q00610-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q00610-2; Sequence=VSP_011570, VSP_011571;
CC Note=No experimental confirmation available;
CC -!- DOMAIN: The N-terminal seven-bladed beta-propeller is formed by
CC WD40-like repeats, and projects inward from the polyhedral outer
CC clathrin coat. It consitutes a major protein-protein interaction
CC node.
CC -!- SIMILARITY: Belongs to the clathrin heavy chain family.
CC -!- SIMILARITY: Contains 7 CHCR (clathrin heavy-chain) repeats.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAA04801.2; Type=Erroneous initiation;
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology
CC and Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/CLTCID360.html";
CC -!- WEB RESOURCE: Name=Wikipedia; Note=Clathrin entry;
CC URL="http://en.wikipedia.org/wiki/Clathrin";
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; D21260; BAA04801.2; ALT_INIT; mRNA.
DR EMBL; BX640615; CAE45761.1; -; mRNA.
DR EMBL; CH471109; EAW94396.1; -; Genomic_DNA.
DR EMBL; CH471109; EAW94399.1; -; Genomic_DNA.
DR EMBL; BC051800; AAH51800.1; -; mRNA.
DR EMBL; BC054489; AAH54489.1; -; mRNA.
DR EMBL; X55878; CAA39363.1; -; mRNA.
DR PIR; A40573; A40573.
DR RefSeq; NP_004850.1; NM_004859.3.
DR UniGene; Hs.491351; -.
DR PDB; 2XZG; X-ray; 1.70 A; A=1-364.
DR PDB; 4G55; X-ray; 1.69 A; A=1-364.
DR PDBsum; 2XZG; -.
DR PDBsum; 4G55; -.
DR ProteinModelPortal; Q00610; -.
DR SMR; Q00610; 1-493, 1077-1630.
DR IntAct; Q00610; 45.
DR MINT; MINT-4998595; -.
DR STRING; 9606.ENSP00000269122; -.
DR PhosphoSite; Q00610; -.
DR DMDM; 1705916; -.
DR PaxDb; Q00610; -.
DR PRIDE; Q00610; -.
DR DNASU; 1213; -.
DR Ensembl; ENST00000269122; ENSP00000269122; ENSG00000141367.
DR Ensembl; ENST00000393043; ENSP00000376763; ENSG00000141367.
DR GeneID; 1213; -.
DR KEGG; hsa:1213; -.
DR UCSC; uc002ixq.1; human.
DR CTD; 1213; -.
DR GeneCards; GC17P057697; -.
DR H-InvDB; HIX0039315; -.
DR HGNC; HGNC:2092; CLTC.
DR HPA; CAB010389; -.
DR HPA; CAB011571; -.
DR HPA; CAB017155; -.
DR MIM; 118955; gene.
DR neXtProt; NX_Q00610; -.
DR Orphanet; 178342; Inflammatory myofibroblastic tumor.
DR Orphanet; 319308; Translocation renal cell carcinoma.
DR PharmGKB; PA26618; -.
DR eggNOG; NOG314149; -.
DR HOGENOM; HOG000188877; -.
DR HOVERGEN; HBG005344; -.
DR InParanoid; Q00610; -.
DR KO; K04646; -.
DR OMA; SNLEIYY; -.
DR OrthoDB; EOG7Z0JVM; -.
DR PhylomeDB; Q00610; -.
DR Reactome; REACT_11123; Membrane Trafficking.
DR Reactome; REACT_6900; Immune System.
DR SignaLink; Q00610; -.
DR ChiTaRS; CLTC; human.
DR EvolutionaryTrace; Q00610; -.
DR GeneWiki; CLTC; -.
DR GenomeRNAi; 1213; -.
DR NextBio; 4999; -.
DR PRO; PR:Q00610; -.
DR ArrayExpress; Q00610; -.
DR Bgee; Q00610; -.
DR CleanEx; HS_CLTC; -.
DR Genevestigator; Q00610; -.
DR GO; GO:0030118; C:clathrin coat; NAS:UniProtKB.
DR GO; GO:0030132; C:clathrin coat of coated pit; IEA:InterPro.
DR GO; GO:0030130; C:clathrin coat of trans-Golgi network vesicle; IEA:InterPro.
DR GO; GO:0030669; C:clathrin-coated endocytic vesicle membrane; TAS:Reactome.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0070062; C:extracellular vesicular exosome; IDA:UniProtKB.
DR GO; GO:0042470; C:melanosome; IEA:UniProtKB-SubCell.
DR GO; GO:0005739; C:mitochondrion; IEA:Ensembl.
DR GO; GO:0005819; C:spindle; IDA:UniProtKB.
DR GO; GO:0032588; C:trans-Golgi network membrane; TAS:Reactome.
DR GO; GO:0003725; F:double-stranded RNA binding; IDA:MGI.
DR GO; GO:0005198; F:structural molecule activity; NAS:UniProtKB.
DR GO; GO:0019886; P:antigen processing and presentation of exogenous peptide antigen via MHC class II; TAS:Reactome.
DR GO; GO:0006886; P:intracellular protein transport; NAS:UniProtKB.
DR GO; GO:0007067; P:mitosis; IMP:UniProtKB.
DR GO; GO:0006892; P:post-Golgi vesicle-mediated transport; TAS:Reactome.
DR GO; GO:0031623; P:receptor internalization; IMP:BHF-UCL.
DR GO; GO:0033572; P:transferrin transport; IMP:BHF-UCL.
DR Gene3D; 1.25.40.10; -; 4.
DR Gene3D; 2.130.10.110; -; 1.
DR InterPro; IPR016024; ARM-type_fold.
DR InterPro; IPR000547; Clathrin_H-chain/VPS_repeat.
DR InterPro; IPR016025; Clathrin_H-chain_link/propller.
DR InterPro; IPR015348; Clathrin_H-chain_linker_core.
DR InterPro; IPR001473; Clathrin_H-chain_propeller_N.
DR InterPro; IPR022365; Clathrin_H-chain_propeller_rpt.
DR InterPro; IPR016341; Clathrin_heavy_chain.
DR InterPro; IPR011990; TPR-like_helical.
DR Pfam; PF00637; Clathrin; 7.
DR Pfam; PF09268; Clathrin-link; 1.
DR Pfam; PF01394; Clathrin_propel; 3.
DR PIRSF; PIRSF002290; Clathrin_H_chain; 1.
DR SMART; SM00299; CLH; 7.
DR SUPFAM; SSF48371; SSF48371; 6.
DR SUPFAM; SSF50989; SSF50989; 1.
DR PROSITE; PS50236; CHCR; 7.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; Coated pit;
KW Complete proteome; Cytoplasmic vesicle; Direct protein sequencing;
KW Membrane; Phosphoprotein; Reference proteome; Repeat.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 1675 Clathrin heavy chain 1.
FT /FTId=PRO_0000205778.
FT REPEAT 537 683 CHCR 1.
FT REPEAT 686 828 CHCR 2.
FT REPEAT 833 972 CHCR 3.
FT REPEAT 979 1124 CHCR 4.
FT REPEAT 1128 1269 CHCR 5.
FT REPEAT 1274 1420 CHCR 6.
FT REPEAT 1423 1566 CHCR 7.
FT REGION 2 479 Globular terminal domain.
FT REGION 24 67 WD40-like repeat 1.
FT REGION 68 107 WD40-like repeat 2.
FT REGION 108 149 WD40-like repeat 3.
FT REGION 150 195 WD40-like repeat 4.
FT REGION 196 257 WD40-like repeat 5.
FT REGION 258 301 WD40-like repeat 6.
FT REGION 302 330 WD40-like repeat 7.
FT REGION 449 465 Binding site for the uncoating ATPase,
FT involved in lattice disassembly
FT (Potential).
FT REGION 480 523 Flexible linker.
FT REGION 524 1675 Heavy chain arm.
FT REGION 524 634 Distal segment.
FT REGION 639 1675 Proximal segment.
FT REGION 1213 1522 Involved in binding clathrin light chain
FT (By similarity).
FT REGION 1550 1675 Trimerization (By similarity).
FT MOD_RES 2 2 N-acetylalanine.
FT MOD_RES 184 184 Phosphotyrosine (By similarity).
FT MOD_RES 394 394 Phosphothreonine.
FT MOD_RES 634 634 Phosphotyrosine.
FT MOD_RES 856 856 N6-acetyllysine.
FT MOD_RES 899 899 Phosphotyrosine (By similarity).
FT MOD_RES 1206 1206 Phosphotyrosine (By similarity).
FT MOD_RES 1441 1441 N6-acetyllysine.
FT MOD_RES 1477 1477 Phosphotyrosine.
FT MOD_RES 1487 1487 Phosphotyrosine (By similarity).
FT MOD_RES 1494 1494 Phosphoserine.
FT MOD_RES 1501 1501 N6-acetyllysine.
FT VAR_SEQ 1636 1639 QPQL -> NLSL (in isoform 2).
FT /FTId=VSP_011570.
FT VAR_SEQ 1640 1675 Missing (in isoform 2).
FT /FTId=VSP_011571.
FT CONFLICT 560 560 Q -> R (in Ref. 5; CAA39363).
FT CONFLICT 817 817 G -> V (in Ref. 5; CAA39363).
FT CONFLICT 923 923 R -> H (in Ref. 2; CAE45761).
FT CONFLICT 1563 1563 R -> G (in Ref. 2; CAE45761).
FT CONFLICT 1652 1652 Q -> R (in Ref. 2; CAE45761).
FT STRAND 6 14
FT HELIX 15 18
FT HELIX 22 24
FT TURN 27 29
FT STRAND 30 34
FT STRAND 37 44
FT STRAND 47 54
FT STRAND 62 65
FT STRAND 69 73
FT STRAND 75 84
FT STRAND 87 92
FT TURN 93 96
FT STRAND 97 103
FT STRAND 108 113
FT STRAND 115 133
FT STRAND 139 143
FT HELIX 146 148
FT STRAND 152 158
FT STRAND 164 173
FT STRAND 176 185
FT TURN 186 189
FT STRAND 190 194
FT STRAND 197 204
FT STRAND 213 222
FT STRAND 225 232
FT STRAND 246 250
FT STRAND 261 267
FT TURN 268 271
FT STRAND 272 277
FT STRAND 280 286
FT TURN 287 289
FT STRAND 292 297
FT STRAND 303 309
FT HELIX 310 312
FT STRAND 314 319
FT STRAND 323 329
FT TURN 331 333
FT HELIX 334 340
FT HELIX 345 354
SQ SEQUENCE 1675 AA; 191615 MW; 6C4F2D54950079E2 CRC64;
MAQILPIRFQ EHLQLQNLGI NPANIGFSTL TMESDKFICI REKVGEQAQV VIIDMNDPSN
PIRRPISADS AIMNPASKVI ALKAGKTLQI FNIEMKSKMK AHTMTDDVTF WKWISLNTVA
LVTDNAVYHW SMEGESQPVK MFDRHSSLAG CQIINYRTDA KQKWLLLTGI SAQQNRVVGA
MQLYSVDRKV SQPIEGHAAS FAQFKMEGNA EESTLFCFAV RGQAGGKLHI IEVGTPPTGN
QPFPKKAVDV FFPPEAQNDF PVAMQISEKH DVVFLITKYG YIHLYDLETG TCIYMNRISG
ETIFVTAPHE ATAGIIGVNR KGQVLSVCVE EENIIPYITN VLQNPDLALR MAVRNNLAGA
EELFARKFNA LFAQGNYSEA AKVAANAPKG ILRTPDTIRR FQSVPAQPGQ TSPLLQYFGI
LLDQGQLNKY ESLELCRPVL QQGRKQLLEK WLKEDKLECS EELGDLVKSV DPTLALSVYL
RANVPNKVIQ CFAETGQVQK IVLYAKKVGY TPDWIFLLRN VMRISPDQGQ QFAQMLVQDE
EPLADITQIV DVFMEYNLIQ QCTAFLLDAL KNNRPSEGPL QTRLLEMNLM HAPQVADAIL
GNQMFTHYDR AHIAQLCEKA GLLQRALEHF TDLYDIKRAV VHTHLLNPEW LVNYFGSLSV
EDSLECLRAM LSANIRQNLQ ICVQVASKYH EQLSTQSLIE LFESFKSFEG LFYFLGSIVN
FSQDPDVHFK YIQAACKTGQ IKEVERICRE SNCYDPERVK NFLKEAKLTD QLPLIIVCDR
FDFVHDLVLY LYRNNLQKYI EIYVQKVNPS RLPVVIGGLL DVDCSEDVIK NLILVVRGQF
STDELVAEVE KRNRLKLLLP WLEARIHEGC EEPATHNALA KIYIDSNNNP ERFLRENPYY
DSRVVGKYCE KRDPHLACVA YERGQCDLEL INVCNENSLF KSLSRYLVRR KDPELWGSVL
LESNPYRRPL IDQVVQTALS ETQDPEEVSV TVKAFMTADL PNELIELLEK IVLDNSVFSE
HRNLQNLLIL TAIKADRTRV MEYINRLDNY DAPDIANIAI SNELFEEAFA IFRKFDVNTS
AVQVLIEHIG NLDRAYEFAE RCNEPAVWSQ LAKAQLQKGM VKEAIDSYIK ADDPSSYMEV
VQAANTSGNW EELVKYLQMA RKKARESYVE TELIFALAKT NRLAELEEFI NGPNNAHIQQ
VGDRCYDEKM YDAAKLLYNN VSNFGRLAST LVHLGEYQAA VDGARKANST RTWKEVCFAC
VDGKEFRLAQ MCGLHIVVHA DELEELINYY QDRGYFEELI TMLEAALGLE RAHMGMFTEL
AILYSKFKPQ KMREHLELFW SRVNIPKVLR AAEQAHLWAE LVFLYDKYEE YDNAIITMMN
HPTDAWKEGQ FKDIITKVAN VELYYRAIQF YLEFKPLLLN DLLMVLSPRL DHTRAVNYFS
KVKQLPLVKP YLRSVQNHNN KSVNESLNNL FITEEDYQAL RTSIDAYDNF DNISLAQRLE
KHELIEFRRI AAYLFKGNNR WKQSVELCKK DSLYKDAMQY ASESKDTELA EELLQWFLQE
EKRECFGACL FTCYDLLRPD VVLETAWRHN IMDFAMPYFI QVMKEYLTKV DKLDASESLR
KEEEQATETQ PIVYGQPQLM LTAGPSVAVP PQAPFGYGYT APPYGQPQPG FGYSM
//
MIM
118955
*RECORD*
*FIELD* NO
118955
*FIELD* TI
*118955 CLATHRIN, HEAVY POLYPEPTIDE; CLTC
;;CLATHRIN HEAVY CHAIN; CHC
CLTC/TFE3 FUSION GENE, INCLUDED;;
read moreCLTC/ALK FUSION GENE, INCLUDED
*FIELD* TX
DESCRIPTION
Clathrin is a major protein component of the cytoplasmic face of
intracellular organelles, called coated vesicles and coated pits. These
specialized organelles are involved in the intracellular trafficking of
receptors and endocytosis of a variety of macromolecules. Clathrin
molecules have a triskelion structure composed of 3 noncovalently bound
heavy chains (CLTC) and 3 light chains (e.g., CLTA; 118960) (Dodge et
al., 1991).
CLONING
Dodge et al. (1991) isolated a 916-bp cDNA for the heavy chain of
clathrin.
GENE FUNCTION
Huntingtin-interacting protein 1 (HIP1; 601767) is enriched in
membrane-containing cell fractions and has been implicated in vesicle
trafficking. It is a multidomain protein containing an epsin (607262)
N-terminal homology (ENTH) domain, a central coiled-coil-forming region,
and a C-terminal actin-binding domain. Waelter et al. (2001) identified
3 HIP1-associated proteins, clathrin heavy chain and alpha-adaptin A and
C (AP2A1; 601026). In vitro binding studies revealed that the central
coiled-coil domain of HIP1 is required for the interaction with
clathrin, whereas DPF-like motifs located upstream to this domain are
important for HIP1 binding to the C-terminal 'appendage' domain of
alpha-adaptin A and C. Expression of full-length HIP1 in mammalian cells
resulted in a punctate cytoplasmic immunostaining characteristic of
clathrin-coated vesicles. In contrast, when a truncated HIP1 protein
containing both the DPF-like motifs and the coiled-coil domain was
overexpressed, large perinuclear vesicle-like structures containing
HIP1, huntingtin (613004), clathrin, and endocytosed transferrin were
observed, suggesting that HIP1 is an endocytic protein, the structural
integrity of which may be crucial for maintenance of normal vesicle size
in vivo.
Royle et al. (2005) showed that clathrin stabilizes fibers of the
mitotic spindle to aid congression of chromosomes. Clathrin bound to the
spindle directly by the N-terminal domain of clathrin heavy chain.
Depletion of clathrin heavy chain using RNA interference prolonged
mitosis; kinetochore fibers were destabilized, leading to defective
congression of chromosomes to the metaphase plate and persistent
activation of the spindle checkpoint. Normal mitosis was rescued by
clathrin triskelia but not the N-terminal domain of clathrin heavy
chain, indicating that stabilization of kinetochore fibers was dependent
on the unique structure of clathrin.
Enari et al. (2006) found that CHC localized to both cytosol and nuclei
in several human cell lines. Immunoprecipitation analysis showed that
CHC interacted directly with p53 (TP53; 191170). CHC overexpression
enhanced p53-dependent transactivation, whereas reduction of CHC
expression by RNA interference attenuated p53 transcriptional activity.
CHC bound to a p53-responsive promoter in vivo and stabilized the
interaction between p53 and p300 (EP300; 602700) to promote p53-mediated
transcription. Binding of p300 and p53 increased in a CHC dose-dependent
manner, and CHC formed a complex with p53 and p300 in response to DNA
damage. Clathrin light chains were absent from nuclear CHC-p53
complexes, and CLTA or CLTB (118970) blocked p53-CHC associations in
vitro by sequestering CHC. Enari et al. (2006) hypothesized that CHC
recruits p300 and p53 to p53-responsive promoters and may function as a
scaffold protein bridging p53 and p300.
Deborde et al. (2008) showed that clathrin is required for polarity of
the basolateral plasma membrane proteins in the epithelial cell line
MDCK. Clathrin knockdown depolarized most basolateral proteins, by
interfering with their biosynthetic delivery and recycling, but did not
affect the polarity of apical proteins. Quantitative live imaging showed
that chronic and acute clathrin knockdown selectively slowed down the
exit of basolateral proteins from the Golgi complex, and promoted their
missorting into apical carrier vesicles. Deborde et al. (2008) concluded
that their results demonstrated a broad requirement for clathrin in
basolateral protein trafficking in epithelial cells.
BIOCHEMICAL FEATURES
- Crystal Structure
Fotin et al. (2004) reported the structure of a clathrin lattice at
subnanometer resolution, obtained from electron cryomicroscopy of
clathrin coats assembled in vitro. They traced most of the 1,675-residue
clathrin heavy chain by fitting known crystal structures of 2 segments,
and homology models of the rest, into the electron microscopy density
map. They also defined the position of the central helical segment of
the light chain. A helical tripod, the carboxy-terminal parts of 3 heavy
chains, projects inward from the vertex of each 3-legged clathrin
triskelion, linking that vertex to 'ankles' of triskelions centered 2
vertices away. Analysis of coats with distinct diameters showed an
invariant pattern of contacts in the neighborhood of each vertex, with
more variable interactions along the extended parts of the triskelion
'legs.' These invariant local interactions appear to stabilize the
lattice, allowing assembly and uncoating to be controlled by events at a
few specific sites.
Fotin et al. (2004) used electron cryomicroscopy to determine the
12-angstrom resolution structures of in vitro-assembled clathrin coats
in association with a C-terminal fragment of auxilin (608375) that
contains both the clathrin-binding region and the J domain. They located
the auxilin fragment by computing differences between these structures
and those lacking auxilin. Auxilin binds within the clathrin lattice
near contacts between inward-projecting C-terminal helical tripod and
the crossing of 2 'ankle' segments; it also contacts the terminal domain
of yet another clathrin 'leg.' Auxilin therefore recruits HSC70 (600816)
to the neighborhood of a set of critical interactions. Auxilin binding
produces a local change in heavy-chain contacts, creating a detectable
global distortion of the clathrin coat. Fotin et al. (2004) proposed a
mechanism by which local destabilization of the lattice promotes general
uncoating.
MAPPING
By Southern analysis of human/rodent somatic cell hybrids, Dodge et al.
(1991) localized the CLTC gene to chromosome 17. Additional analyses
using panels of human/rodent somatic cell hybrids with specific
chromosomal translocations and deletions mapped the human clathrin heavy
chain gene to 17q11-qter.
In the course of comparative mapping of the human 22q11 region in mice,
Puech et al. (1997) found that the mouse clathrin D gene (CLTD; 601273),
which lies in the center of a cluster of genes whose homologs reside on
mouse chromosome 16, is not located there. A gene they referred to as
Cltd-rs-4 was located in the central region of mouse chromosome 11 that
shares a large region of homology with human chromosome 17. Human CLTC,
which is 84.7% identical to CLTD, maps to 17q11-qter. Puech et al.
(1997) interpreted their findings as suggesting that in mouse either
Cltc and Cltd are tandemly duplicated loci that map to the central
region of mouse chromosome 11 or that the mouse genome does not contain
a gene corresponding to human CLTD. They favored the latter hypothesis.
CYTOGENETICS
Argani et al. (2003) reported a case of renal cell carcinoma (RCCX1;
300854) in which the 5-prime exons of the CLTC gene were fused with the
3-prime exons of the TFE3 gene (314310) as a result of a translocation,
t(X;17)(p11.2;q23). The patient was a 14-year-old boy who presented with
gross hematuria and was found by CT to have a finely calcified left
renal mass.
In a patient with ALK (105590)-negative inflammatory myofibroblastic
tumors and an unknown karyotype, Cools et al. (2002) identified fusion
of exons of the CLTC gene to exons of the ALK gene from chromosome 2p23.
The predicted fusion protein contains 1,634 N-terminal amino acids of
CLTC fused to 562 amino acids of ALK, including the ALK kinase domain.
*FIELD* RF
1. Argani, P.; Lui, M. Y.; Couturier, J.; Bouvier, R.; Fournet, J.-C.;
Ladanyi, M.: A novel CLTC-TFE3 gene fusion in pediatric renal adenocarcinoma
with t(X;17)(p11.2;q23). Oncogene 22: 5374-5378, 2003.
2. Cools, J.; Wlodarska, I.; Somers, R.; Mentens, N.; Pedeutour, F.;
Maes, B.; De Wolf-Peeters, C.; Pauwels, P.; Hagemeijer, A.; Marynen,
P.: Identification of novel fusion partners of ALK, the anaplastic
lymphoma kinase, in anaplastic large-cell lymphoma and inflammatory
myofibroblastic tumor. Genes Chromosomes Cancer 34: 354-362, 2002.
3. Deborde, S.; Perret, E.; Gravotta, D.; Deora, A.; Salvarezza, S.;
Schreiner, R.; Rodriguez-Boulan, E.: Clathrin is a key regulator
of basolateral polarity. Nature 452: 719-723, 2008.
4. Dodge, G. R.; Kovalszky, I.; McBride, O. W.; Yi, H. F.; Chu, M.;
Saitta, B.; Stokes, D. G.; Iozzo, R. V.: Human clathrin heavy chain
(CLTC): partial molecular cloning, expression, and mapping of the
gene to human chromosome 17q11-qter. Genomics 11: 174-178, 1991.
5. Enari, M.; Ohmori, K.; Kitabayashi, I.; Taya, Y.: Requirement
of clathrin heavy chain for p53-mediated transcription. Genes Dev. 20:
1087-1099, 2006.
6. Fotin, A.; Cheng, Y.; Grigorieff, N.; Walz, T.; Harrison, S. C.;
Kirchhausen, T.: Structure of an auxilin-bound clathrin coat and
its implications for the mechanism of uncoating. Nature 432: 649-653,
2004.
7. Fotin, A.; Cheng, Y.; Sliz, P.; Grigorieff, N.; Harrison, S. C.;
Kirchhausen, T.; Walz, T.: Molecular model for a complete clathrin
lattice from electron cryomicroscopy. Nature 432: 573-579, 2004.
8. Puech, A.; Saint-Jore, B.; Funke, B.; Gilbert, D. J.; Sirotkin,
H.; Copeland, N. G.; Jenkins, N. A.; Kucherlapati, R.; Morrow, B.;
Skoultchi, A. I.: Comparative mapping of the human 22q11 chromosomal
region and the orthologous region in mice reveals complex changes
in gene organization. Proc. Nat. Acad. Sci. 94: 14608-14613, 1997.
9. Royle, S. J.; Bright, N. A.; Lagnado, L.: Clathrin is required
for the function of the mitotic spindle. Nature 434: 1152-1157,
2005.
10. Waelter, S.; Scherzinger, E.; Hasenbank, R.; Nordhoff, E.; Lurz,
R.; Goehler, H.; Gauss, C.; Sathasivam, K.; Bates, G. P.; Lehrach,
H.; Wanker, E. E.: The huntingtin interacting protein HIP1 is a clathrin
and alpha-adaptin-binding protein involved in receptor-mediated endocytosis. Hum.
Molec. Genet. 10: 1807-1817, 2001.
*FIELD* CN
Patricia A. Hartz - updated: 2/23/2011
Ada Hamosh - updated: 5/21/2008
Patricia A. Hartz - updated: 6/23/2006
Ada Hamosh - updated: 5/25/2005
Ada Hamosh - updated: 1/19/2005
Victor A. McKusick - updated: 10/31/2003
George E. Tiller - updated: 2/14/2002
Victor A. McKusick - updated: 2/15/1998
*FIELD* CD
Victor A. McKusick: 9/12/1991
*FIELD* ED
carol: 09/15/2011
ckniffin: 9/13/2011
mgross: 2/23/2011
carol: 9/15/2009
alopez: 5/28/2008
terry: 5/21/2008
mgross: 6/23/2006
terry: 6/23/2006
tkritzer: 5/25/2005
terry: 5/25/2005
wwang: 1/31/2005
wwang: 1/27/2005
terry: 1/19/2005
carol: 10/31/2003
terry: 10/31/2003
mgross: 9/27/2002
cwells: 2/14/2002
terry: 4/23/1999
mark: 2/16/1998
mark: 2/15/1998
supermim: 3/16/1992
carol: 9/12/1991
*RECORD*
*FIELD* NO
118955
*FIELD* TI
*118955 CLATHRIN, HEAVY POLYPEPTIDE; CLTC
;;CLATHRIN HEAVY CHAIN; CHC
CLTC/TFE3 FUSION GENE, INCLUDED;;
read moreCLTC/ALK FUSION GENE, INCLUDED
*FIELD* TX
DESCRIPTION
Clathrin is a major protein component of the cytoplasmic face of
intracellular organelles, called coated vesicles and coated pits. These
specialized organelles are involved in the intracellular trafficking of
receptors and endocytosis of a variety of macromolecules. Clathrin
molecules have a triskelion structure composed of 3 noncovalently bound
heavy chains (CLTC) and 3 light chains (e.g., CLTA; 118960) (Dodge et
al., 1991).
CLONING
Dodge et al. (1991) isolated a 916-bp cDNA for the heavy chain of
clathrin.
GENE FUNCTION
Huntingtin-interacting protein 1 (HIP1; 601767) is enriched in
membrane-containing cell fractions and has been implicated in vesicle
trafficking. It is a multidomain protein containing an epsin (607262)
N-terminal homology (ENTH) domain, a central coiled-coil-forming region,
and a C-terminal actin-binding domain. Waelter et al. (2001) identified
3 HIP1-associated proteins, clathrin heavy chain and alpha-adaptin A and
C (AP2A1; 601026). In vitro binding studies revealed that the central
coiled-coil domain of HIP1 is required for the interaction with
clathrin, whereas DPF-like motifs located upstream to this domain are
important for HIP1 binding to the C-terminal 'appendage' domain of
alpha-adaptin A and C. Expression of full-length HIP1 in mammalian cells
resulted in a punctate cytoplasmic immunostaining characteristic of
clathrin-coated vesicles. In contrast, when a truncated HIP1 protein
containing both the DPF-like motifs and the coiled-coil domain was
overexpressed, large perinuclear vesicle-like structures containing
HIP1, huntingtin (613004), clathrin, and endocytosed transferrin were
observed, suggesting that HIP1 is an endocytic protein, the structural
integrity of which may be crucial for maintenance of normal vesicle size
in vivo.
Royle et al. (2005) showed that clathrin stabilizes fibers of the
mitotic spindle to aid congression of chromosomes. Clathrin bound to the
spindle directly by the N-terminal domain of clathrin heavy chain.
Depletion of clathrin heavy chain using RNA interference prolonged
mitosis; kinetochore fibers were destabilized, leading to defective
congression of chromosomes to the metaphase plate and persistent
activation of the spindle checkpoint. Normal mitosis was rescued by
clathrin triskelia but not the N-terminal domain of clathrin heavy
chain, indicating that stabilization of kinetochore fibers was dependent
on the unique structure of clathrin.
Enari et al. (2006) found that CHC localized to both cytosol and nuclei
in several human cell lines. Immunoprecipitation analysis showed that
CHC interacted directly with p53 (TP53; 191170). CHC overexpression
enhanced p53-dependent transactivation, whereas reduction of CHC
expression by RNA interference attenuated p53 transcriptional activity.
CHC bound to a p53-responsive promoter in vivo and stabilized the
interaction between p53 and p300 (EP300; 602700) to promote p53-mediated
transcription. Binding of p300 and p53 increased in a CHC dose-dependent
manner, and CHC formed a complex with p53 and p300 in response to DNA
damage. Clathrin light chains were absent from nuclear CHC-p53
complexes, and CLTA or CLTB (118970) blocked p53-CHC associations in
vitro by sequestering CHC. Enari et al. (2006) hypothesized that CHC
recruits p300 and p53 to p53-responsive promoters and may function as a
scaffold protein bridging p53 and p300.
Deborde et al. (2008) showed that clathrin is required for polarity of
the basolateral plasma membrane proteins in the epithelial cell line
MDCK. Clathrin knockdown depolarized most basolateral proteins, by
interfering with their biosynthetic delivery and recycling, but did not
affect the polarity of apical proteins. Quantitative live imaging showed
that chronic and acute clathrin knockdown selectively slowed down the
exit of basolateral proteins from the Golgi complex, and promoted their
missorting into apical carrier vesicles. Deborde et al. (2008) concluded
that their results demonstrated a broad requirement for clathrin in
basolateral protein trafficking in epithelial cells.
BIOCHEMICAL FEATURES
- Crystal Structure
Fotin et al. (2004) reported the structure of a clathrin lattice at
subnanometer resolution, obtained from electron cryomicroscopy of
clathrin coats assembled in vitro. They traced most of the 1,675-residue
clathrin heavy chain by fitting known crystal structures of 2 segments,
and homology models of the rest, into the electron microscopy density
map. They also defined the position of the central helical segment of
the light chain. A helical tripod, the carboxy-terminal parts of 3 heavy
chains, projects inward from the vertex of each 3-legged clathrin
triskelion, linking that vertex to 'ankles' of triskelions centered 2
vertices away. Analysis of coats with distinct diameters showed an
invariant pattern of contacts in the neighborhood of each vertex, with
more variable interactions along the extended parts of the triskelion
'legs.' These invariant local interactions appear to stabilize the
lattice, allowing assembly and uncoating to be controlled by events at a
few specific sites.
Fotin et al. (2004) used electron cryomicroscopy to determine the
12-angstrom resolution structures of in vitro-assembled clathrin coats
in association with a C-terminal fragment of auxilin (608375) that
contains both the clathrin-binding region and the J domain. They located
the auxilin fragment by computing differences between these structures
and those lacking auxilin. Auxilin binds within the clathrin lattice
near contacts between inward-projecting C-terminal helical tripod and
the crossing of 2 'ankle' segments; it also contacts the terminal domain
of yet another clathrin 'leg.' Auxilin therefore recruits HSC70 (600816)
to the neighborhood of a set of critical interactions. Auxilin binding
produces a local change in heavy-chain contacts, creating a detectable
global distortion of the clathrin coat. Fotin et al. (2004) proposed a
mechanism by which local destabilization of the lattice promotes general
uncoating.
MAPPING
By Southern analysis of human/rodent somatic cell hybrids, Dodge et al.
(1991) localized the CLTC gene to chromosome 17. Additional analyses
using panels of human/rodent somatic cell hybrids with specific
chromosomal translocations and deletions mapped the human clathrin heavy
chain gene to 17q11-qter.
In the course of comparative mapping of the human 22q11 region in mice,
Puech et al. (1997) found that the mouse clathrin D gene (CLTD; 601273),
which lies in the center of a cluster of genes whose homologs reside on
mouse chromosome 16, is not located there. A gene they referred to as
Cltd-rs-4 was located in the central region of mouse chromosome 11 that
shares a large region of homology with human chromosome 17. Human CLTC,
which is 84.7% identical to CLTD, maps to 17q11-qter. Puech et al.
(1997) interpreted their findings as suggesting that in mouse either
Cltc and Cltd are tandemly duplicated loci that map to the central
region of mouse chromosome 11 or that the mouse genome does not contain
a gene corresponding to human CLTD. They favored the latter hypothesis.
CYTOGENETICS
Argani et al. (2003) reported a case of renal cell carcinoma (RCCX1;
300854) in which the 5-prime exons of the CLTC gene were fused with the
3-prime exons of the TFE3 gene (314310) as a result of a translocation,
t(X;17)(p11.2;q23). The patient was a 14-year-old boy who presented with
gross hematuria and was found by CT to have a finely calcified left
renal mass.
In a patient with ALK (105590)-negative inflammatory myofibroblastic
tumors and an unknown karyotype, Cools et al. (2002) identified fusion
of exons of the CLTC gene to exons of the ALK gene from chromosome 2p23.
The predicted fusion protein contains 1,634 N-terminal amino acids of
CLTC fused to 562 amino acids of ALK, including the ALK kinase domain.
*FIELD* RF
1. Argani, P.; Lui, M. Y.; Couturier, J.; Bouvier, R.; Fournet, J.-C.;
Ladanyi, M.: A novel CLTC-TFE3 gene fusion in pediatric renal adenocarcinoma
with t(X;17)(p11.2;q23). Oncogene 22: 5374-5378, 2003.
2. Cools, J.; Wlodarska, I.; Somers, R.; Mentens, N.; Pedeutour, F.;
Maes, B.; De Wolf-Peeters, C.; Pauwels, P.; Hagemeijer, A.; Marynen,
P.: Identification of novel fusion partners of ALK, the anaplastic
lymphoma kinase, in anaplastic large-cell lymphoma and inflammatory
myofibroblastic tumor. Genes Chromosomes Cancer 34: 354-362, 2002.
3. Deborde, S.; Perret, E.; Gravotta, D.; Deora, A.; Salvarezza, S.;
Schreiner, R.; Rodriguez-Boulan, E.: Clathrin is a key regulator
of basolateral polarity. Nature 452: 719-723, 2008.
4. Dodge, G. R.; Kovalszky, I.; McBride, O. W.; Yi, H. F.; Chu, M.;
Saitta, B.; Stokes, D. G.; Iozzo, R. V.: Human clathrin heavy chain
(CLTC): partial molecular cloning, expression, and mapping of the
gene to human chromosome 17q11-qter. Genomics 11: 174-178, 1991.
5. Enari, M.; Ohmori, K.; Kitabayashi, I.; Taya, Y.: Requirement
of clathrin heavy chain for p53-mediated transcription. Genes Dev. 20:
1087-1099, 2006.
6. Fotin, A.; Cheng, Y.; Grigorieff, N.; Walz, T.; Harrison, S. C.;
Kirchhausen, T.: Structure of an auxilin-bound clathrin coat and
its implications for the mechanism of uncoating. Nature 432: 649-653,
2004.
7. Fotin, A.; Cheng, Y.; Sliz, P.; Grigorieff, N.; Harrison, S. C.;
Kirchhausen, T.; Walz, T.: Molecular model for a complete clathrin
lattice from electron cryomicroscopy. Nature 432: 573-579, 2004.
8. Puech, A.; Saint-Jore, B.; Funke, B.; Gilbert, D. J.; Sirotkin,
H.; Copeland, N. G.; Jenkins, N. A.; Kucherlapati, R.; Morrow, B.;
Skoultchi, A. I.: Comparative mapping of the human 22q11 chromosomal
region and the orthologous region in mice reveals complex changes
in gene organization. Proc. Nat. Acad. Sci. 94: 14608-14613, 1997.
9. Royle, S. J.; Bright, N. A.; Lagnado, L.: Clathrin is required
for the function of the mitotic spindle. Nature 434: 1152-1157,
2005.
10. Waelter, S.; Scherzinger, E.; Hasenbank, R.; Nordhoff, E.; Lurz,
R.; Goehler, H.; Gauss, C.; Sathasivam, K.; Bates, G. P.; Lehrach,
H.; Wanker, E. E.: The huntingtin interacting protein HIP1 is a clathrin
and alpha-adaptin-binding protein involved in receptor-mediated endocytosis. Hum.
Molec. Genet. 10: 1807-1817, 2001.
*FIELD* CN
Patricia A. Hartz - updated: 2/23/2011
Ada Hamosh - updated: 5/21/2008
Patricia A. Hartz - updated: 6/23/2006
Ada Hamosh - updated: 5/25/2005
Ada Hamosh - updated: 1/19/2005
Victor A. McKusick - updated: 10/31/2003
George E. Tiller - updated: 2/14/2002
Victor A. McKusick - updated: 2/15/1998
*FIELD* CD
Victor A. McKusick: 9/12/1991
*FIELD* ED
carol: 09/15/2011
ckniffin: 9/13/2011
mgross: 2/23/2011
carol: 9/15/2009
alopez: 5/28/2008
terry: 5/21/2008
mgross: 6/23/2006
terry: 6/23/2006
tkritzer: 5/25/2005
terry: 5/25/2005
wwang: 1/31/2005
wwang: 1/27/2005
terry: 1/19/2005
carol: 10/31/2003
terry: 10/31/2003
mgross: 9/27/2002
cwells: 2/14/2002
terry: 4/23/1999
mark: 2/16/1998
mark: 2/15/1998
supermim: 3/16/1992
carol: 9/12/1991