CLH_DICDI
ID CLH_DICDI Reviewed; 1694 AA.
AC P25870; Q54ZZ9;
DT 01-MAY-1992, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-1992, sequence version 1.
DT 25-MAY-2022, entry version 146.
DE RecName: Full=Clathrin heavy chain;
GN Name=chcA; ORFNames=DDB_G0277221;
OS Dictyostelium discoideum (Slime mold).
OC Eukaryota; Amoebozoa; Evosea; Eumycetozoa; Dictyostelia; Dictyosteliales;
OC Dictyosteliaceae; Dictyostelium.
OX NCBI_TaxID=44689;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND DEVELOPMENTAL STAGE.
RC STRAIN=AX3;
RX PubMed=1605855; DOI=10.1089/dna.1992.11.321;
RA O'Halloran T.J., Anderson R.G.;
RT "Characterization of the clathrin heavy chain from Dictyostelium
RT discoideum.";
RL DNA Cell Biol. 11:321-330(1992).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=AX4;
RX PubMed=12097910; DOI=10.1038/nature00847;
RA Gloeckner G., Eichinger L., Szafranski K., Pachebat J.A., Bankier A.T.,
RA Dear P.H., Lehmann R., Baumgart C., Parra G., Abril J.F., Guigo R.,
RA Kumpf K., Tunggal B., Cox E.C., Quail M.A., Platzer M., Rosenthal A.,
RA Noegel A.A.;
RT "Sequence and analysis of chromosome 2 of Dictyostelium discoideum.";
RL Nature 418:79-85(2002).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=AX4;
RX PubMed=15875012; DOI=10.1038/nature03481;
RA Eichinger L., Pachebat J.A., Gloeckner G., Rajandream M.A., Sucgang R.,
RA Berriman M., Song J., Olsen R., Szafranski K., Xu Q., Tunggal B.,
RA Kummerfeld S., Madera M., Konfortov B.A., Rivero F., Bankier A.T.,
RA Lehmann R., Hamlin N., Davies R., Gaudet P., Fey P., Pilcher K., Chen G.,
RA Saunders D., Sodergren E.J., Davis P., Kerhornou A., Nie X., Hall N.,
RA Anjard C., Hemphill L., Bason N., Farbrother P., Desany B., Just E.,
RA Morio T., Rost R., Churcher C.M., Cooper J., Haydock S., van Driessche N.,
RA Cronin A., Goodhead I., Muzny D.M., Mourier T., Pain A., Lu M., Harper D.,
RA Lindsay R., Hauser H., James K.D., Quiles M., Madan Babu M., Saito T.,
RA Buchrieser C., Wardroper A., Felder M., Thangavelu M., Johnson D.,
RA Knights A., Loulseged H., Mungall K.L., Oliver K., Price C., Quail M.A.,
RA Urushihara H., Hernandez J., Rabbinowitsch E., Steffen D., Sanders M.,
RA Ma J., Kohara Y., Sharp S., Simmonds M.N., Spiegler S., Tivey A.,
RA Sugano S., White B., Walker D., Woodward J.R., Winckler T., Tanaka Y.,
RA Shaulsky G., Schleicher M., Weinstock G.M., Rosenthal A., Cox E.C.,
RA Chisholm R.L., Gibbs R.A., Loomis W.F., Platzer M., Kay R.R.,
RA Williams J.G., Dear P.H., Noegel A.A., Barrell B.G., Kuspa A.;
RT "The genome of the social amoeba Dictyostelium discoideum.";
RL Nature 435:43-57(2005).
RN [4]
RP FUNCTION.
RX PubMed=1522112; DOI=10.1083/jcb.118.6.1371;
RA O'Halloran T.J., Anderson R.G.;
RT "Clathrin heavy chain is required for pinocytosis, the presence of large
RT vacuoles, and development in Dictyostelium.";
RL J. Cell Biol. 118:1371-1377(1992).
RN [5]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=8034739; DOI=10.1083/jcb.126.2.343;
RA Ruscetti T., Cardelli J.A., Niswonger M.L., O'Halloran T.J.;
RT "Clathrin heavy chain functions in sorting and secretion of lysosomal
RT enzymes in Dictyostelium discoideum.";
RL J. Cell Biol. 126:343-352(1994).
RN [6]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=9053320; DOI=10.1242/dev.124.2.443;
RA Niswonger M.L., O'Halloran T.J.;
RT "Clathrin heavy chain is required for spore cell but not stalk cell
RT differentiation in Dictyostelium discoideum.";
RL Development 124:443-451(1997).
RN [7]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=9238018; DOI=10.1073/pnas.94.16.8575;
RA Niswonger M.L., O'Halloran T.J.;
RT "A novel role for clathrin in cytokinesis.";
RL Proc. Natl. Acad. Sci. U.S.A. 94:8575-8578(1997).
RN [8]
RP INTERACTION WITH CLC.
RX PubMed=9425628; DOI=10.1006/prep.1997.0793;
RA Riddelle-Spencer K.S., O'Halloran T.J.;
RT "Purification of clathrin heavy and light chain from Dictyostelium
RT discoideum.";
RL Protein Expr. Purif. 11:250-256(1997).
RN [9]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=10588667; DOI=10.1091/mbc.10.12.4419;
RA Aguado-Velasco C., Bretscher M.S.;
RT "Circulation of the plasma membrane in Dictyostelium.";
RL Mol. Biol. Cell 10:4419-4427(1999).
RN [10]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=10591622; DOI=10.1242/jcs.113.1.21;
RA Wessels D., Reynolds J., Johnson O., Voss E., Burns R., Daniels K.,
RA Garrard E., O'Halloran T.J., Soll D.R.;
RT "Clathrin plays a novel role in the regulation of cell polarity, pseudopod
RT formation, uropod stability and motility in Dictyostelium.";
RL J. Cell Sci. 113:21-36(2000).
RN [11]
RP SUBCELLULAR LOCATION.
RX PubMed=10848635; DOI=10.1091/mbc.11.6.2151;
RA Damer C.K., O'Halloran T.J.;
RT "Spatially regulated recruitment of clathrin to the plasma membrane during
RT capping and cell translocation.";
RL Mol. Biol. Cell 11:2151-2159(2000).
RN [12]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=11223952;
RX DOI=10.1002/1097-0169(200103)48:3<213::aid-cm1010>3.0.co;2-v;
RA Gerald N.J., Damer C.K., O'Halloran T.J., De Lozanne A.;
RT "Cytokinesis failure in clathrin-minus cells is caused by cleavage furrow
RT instability.";
RL Cell Motil. Cytoskeleton 48:213-223(2001).
RN [13]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=16512674; DOI=10.1021/pr050350q;
RA Reinders Y., Schulz I., Graef R., Sickmann A.;
RT "Identification of novel centrosomal proteins in Dictyostelium discoideum
RT by comparative proteomic approaches.";
RL J. Proteome Res. 5:589-598(2006).
RN [14]
RP INTERACTION WITH CLC.
RX PubMed=16734666; DOI=10.1111/j.1600-0854.2006.00438.x;
RA Wang J., Wang Y., O'Halloran T.J.;
RT "Clathrin light chain: importance of the conserved carboxy terminal domain
RT to function in living cells.";
RL Traffic 7:824-832(2006).
CC -!- FUNCTION: Clathrin is the major protein of the polyhedral coat of
CC coated pits and vesicles. {ECO:0000269|PubMed:10588667,
CC ECO:0000269|PubMed:10591622, ECO:0000269|PubMed:11223952,
CC ECO:0000269|PubMed:1522112, ECO:0000269|PubMed:8034739,
CC ECO:0000269|PubMed:9053320, ECO:0000269|PubMed:9238018}.
CC -!- SUBUNIT: Clathrin coats are formed from molecules containing 3 heavy
CC chains and 3 light chains.
CC -!- SUBCELLULAR LOCATION: Cytoplasmic vesicle membrane
CC {ECO:0000269|PubMed:10848635}; Peripheral membrane protein
CC {ECO:0000269|PubMed:10848635}; Cytoplasmic side
CC {ECO:0000269|PubMed:10848635}. Membrane, coated pit
CC {ECO:0000269|PubMed:10848635}; Peripheral membrane protein
CC {ECO:0000269|PubMed:10848635}; Cytoplasmic side
CC {ECO:0000269|PubMed:10848635}. Note=Cytoplasmic face of coated pits and
CC vesicles. Localized to punctae scattered within the cytoplasm, along
CC the plasma membrane and concentrated in the perinuclear region.
CC Localizes to the posterior plasma membrane in cells which retract their
CC tails when moving forward or changing direction. Recruited to the
CC plasma membrane under the tight cap of cross-linked receptors prior to
CC internalization of the capped ligand. Does not localize to the plasma
CC membrane during phagocytosis.
CC -!- DEVELOPMENTAL STAGE: Expressed at highest levels in vegetatively
CC growing cells. Expression declines during development.
CC {ECO:0000269|PubMed:1605855}.
CC -!- DOMAIN: The C-terminal third of the heavy chains forms the hub of the
CC triskelion. This region contains the trimerization domain and the
CC light-chain binding domain involved in the assembly of the clathrin
CC lattice.
CC -!- DOMAIN: The N-terminal seven-bladed beta-propeller is formed by WD40-
CC like repeats, and projects inward from the polyhedral outer clathrin
CC coat. It constitutes a major protein-protein interaction node (By
CC similarity). {ECO:0000250}.
CC -!- DISRUPTION PHENOTYPE: Cells display lacks of coated pits, lacks of
CC coated vesicles and large translucent vesicles that serve as endosomes
CC and contractile vacuoles, and displays impaired macropinocytosis and
CC osmoregulation defects. Phagocytosis is normal in loss-of-function
CC mutant. Mutants lacking chcA show defects in the regulation of
CC pseudopod formation, uropod stability, cell polarity and chemotaxis,
CC and stream and aggregate more slowly than wild-type cells in response
CC to starvation. Late development is impaired in mutants lacking chcA
CC which show defects in prestalk and prespore cell patterning, and spore
CC cells fail to differentiate. Mutants lacking chcA display defects in
CC the sorting of precursor hydrolases from the constitutive secretory
CC pathway to the lysosomal pathway, and reduced secretion of mature
CC alpha-mannosidase from the lysosome to the extracellular space. Mutants
CC lacking chcA fail to undergo cytokinesis in suspension culture due to
CC the failure to assemble a functional contractile ring.
CC {ECO:0000269|PubMed:10588667, ECO:0000269|PubMed:10591622,
CC ECO:0000269|PubMed:11223952, ECO:0000269|PubMed:8034739,
CC ECO:0000269|PubMed:9053320, ECO:0000269|PubMed:9238018}.
CC -!- SIMILARITY: Belongs to the clathrin heavy chain family. {ECO:0000305}.
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DR EMBL; M83660; AAA33179.1; -; mRNA.
DR EMBL; AAFI02000019; EAL68796.1; -; Genomic_DNA.
DR RefSeq; XP_642717.1; XM_637625.1.
DR AlphaFoldDB; P25870; -.
DR SMR; P25870; -.
DR IntAct; P25870; 1.
DR STRING; 44689.DDB0185029; -.
DR PaxDb; P25870; -.
DR EnsemblProtists; EAL68796; EAL68796; DDB_G0277221.
DR GeneID; 8620910; -.
DR KEGG; ddi:DDB_G0277221; -.
DR dictyBase; DDB_G0277221; chcA.
DR eggNOG; KOG0985; Eukaryota.
DR HOGENOM; CLU_002136_0_0_1; -.
DR InParanoid; P25870; -.
DR OMA; QVNEACV; -.
DR PhylomeDB; P25870; -.
DR Reactome; R-DDI-196025; Formation of annular gap junctions.
DR Reactome; R-DDI-432720; Lysosome Vesicle Biogenesis.
DR Reactome; R-DDI-437239; Recycling pathway of L1.
DR Reactome; R-DDI-8856828; Clathrin-mediated endocytosis.
DR Reactome; R-DDI-8866427; VLDLR internalisation and degradation.
DR Reactome; R-DDI-8964038; LDL clearance.
DR Reactome; R-DDI-9013420; RHOU GTPase cycle.
DR Reactome; R-DDI-9013424; RHOV GTPase cycle.
DR PRO; PR:P25870; -.
DR Proteomes; UP000002195; Chromosome 2.
DR GO; GO:0030118; C:clathrin coat; IDA:dictyBase.
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:0071439; C:clathrin complex; IDA:dictyBase.
DR GO; GO:0032051; F:clathrin light chain binding; IBA:GO_Central.
DR GO; GO:0005198; F:structural molecule activity; IEA:InterPro.
DR GO; GO:0000915; P:actomyosin contractile ring assembly; IMP:dictyBase.
DR GO; GO:0031152; P:aggregation involved in sorocarp development; IMP:dictyBase.
DR GO; GO:0048268; P:clathrin coat assembly; IMP:dictyBase.
DR GO; GO:0072583; P:clathrin-dependent endocytosis; IMP:dictyBase.
DR GO; GO:0006886; P:intracellular protein transport; IEA:InterPro.
DR GO; GO:0007041; P:lysosomal transport; IMP:dictyBase.
DR GO; GO:0000281; P:mitotic cytokinesis; IMP:dictyBase.
DR GO; GO:0006907; P:pinocytosis; IMP:dictyBase.
DR GO; GO:0006898; P:receptor-mediated endocytosis; IMP:dictyBase.
DR GO; GO:0006970; P:response to osmotic stress; IMP:dictyBase.
DR GO; GO:0030435; P:sporulation resulting in formation of a cellular spore; IMP:dictyBase.
DR GO; GO:0007033; P:vacuole organization; IMP:dictyBase.
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; IPR015348; Clathrin_H-chain_linker_core.
DR InterPro; IPR016025; Clathrin_H-chain_N.
DR InterPro; IPR022365; Clathrin_H-chain_propeller_rpt.
DR InterPro; IPR016341; Clathrin_heavy_chain.
DR InterPro; IPR011990; TPR-like_helical_dom_sf.
DR Pfam; PF00637; Clathrin; 7.
DR Pfam; PF09268; Clathrin-link; 1.
DR Pfam; PF01394; Clathrin_propel; 4.
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 Coated pit; Coiled coil; Cytoplasmic vesicle; Membrane; Reference proteome;
KW Repeat.
FT CHAIN 1..1694
FT /note="Clathrin heavy chain"
FT /id="PRO_0000205782"
FT REPEAT 537..681
FT /note="CHCR 1"
FT REPEAT 687..829
FT /note="CHCR 2"
FT REPEAT 834..973
FT /note="CHCR 3"
FT REPEAT 980..1125
FT /note="CHCR 4"
FT REPEAT 1129..1270
FT /note="CHCR 5"
FT REPEAT 1275..1421
FT /note="CHCR 6"
FT REPEAT 1424..1567
FT /note="CHCR 7"
FT REGION 1..478
FT /note="Globular terminal domain"
FT REGION 23..67
FT /note="WD40-like repeat 1"
FT REGION 68..107
FT /note="WD40-like repeat 2"
FT REGION 108..149
FT /note="WD40-like repeat 3"
FT REGION 150..195
FT /note="WD40-like repeat 4"
FT REGION 196..256
FT /note="WD40-like repeat 5"
FT REGION 257..300
FT /note="WD40-like repeat 6"
FT REGION 301..329
FT /note="WD40-like repeat 7"
FT REGION 448..464
FT /note="Binding site for the uncoating ATPase, involved in
FT lattice disassembly"
FT /evidence="ECO:0000255"
FT REGION 479..522
FT /note="Flexible linker"
FT REGION 523..1694
FT /note="Heavy chain arm"
FT REGION 523..?
FT /note="Distal segment"
FT REGION 1214..1523
FT /note="Involved in binding clathrin light chain"
FT /evidence="ECO:0000250"
FT REGION 1551..1694
FT /note="Trimerization"
FT /evidence="ECO:0000250"
FT REGION ?..1694
FT /note="Proximal segment"
FT COILED 1610..1640
FT /evidence="ECO:0000255"
SQ SEQUENCE 1694 AA; 193599 MW; 27BEE52D93DFB493 CRC64;
MTNLPIRFQE VLQLTNLGIG SNSIGFSTLT MESEKYICIR ETTPDDKNNV VIIDTDNPSQ
ILRKQMKTDA AIMNPKEPIL ALKIGQVLQL ISIEQKMQLK SCQMQEPLEF WKWISPNTLA
LVTATSVFHW TKEGNSDPVK VFDRHPDLQN TEIINYRSDS TQNWLVLVAI HQRDGRVVGR
IQLYSVEKQI SQSIEGHAAC FANYIVPGAT RPSTLFAISS RTQNASKILV LEVSKGDGPN
FQKRASDVFY PPEIGASDFP VAMQVSEKYE VIYMVTKLGY IHLFDLGTAN LIYRNRISNE
NIFVTAFEES TNGIIAVNRK GQVLSVSIDD KNIIPYICNT LNNLELAISM ACKNNLPGAE
GLLTTQFERY FQQGQYKEAA KVAADSPGSI LRNLQTIQKF QSIPPIPDQP SALLQYFGML
LEKGKLNKVE SLELVRPVLA QGKKPILEKW LTEDKLECSE QLGDEVRPHD RKLALSIYYR
ANASDKVITL FAETGEFDKI IAYCKKFNYK PDFMFLLQRM ANANPMGAAD FAVKLVKEEG
GPYIDANQVV ELFSARNMIQ ETSNFLFAIL DGDRPQDANL QTKLLEINLL HAPQNADAIM
GGQKFTHYNR LRIGGLCEKA GLYQRALEHY TDLADIKRVL SHAGHMVNQE FLVSYFGSLN
PEDRMECMRD FLRTNPRQNL QLVVAIAVSY SDQITPEAII AMFESFRLYE GLYLYLTQVV
VTSTSPEVHF KYIEAAAKIN QFKEVERMCR DSNYYDPEKT RDFLKEAKLP DQLPLIIVCD
RYEFISDLTN YLYKNNLSKY IEAYVQKINP VNTPLVVGAL LDLDCQEDYL RNLIMSVRNM
CPADSLVEQV EKRNRLKLLL PWLEARVAEG NIEPAIHNAL AKIYIDSNKN PEAFLLHNQF
YDSKVVGKYC EKRDPYLSFV AYKRGLCDYE LIEVTNKNTL FKNQARYLVE RQDPDLWAYV
LSDQNEYKRS LIDQVVQTAL PESTNATEVS ATVKAFMDAN LPNELIELLE KIVLEGKEFK
TAKELQNLLI LTAIRADKSR VTDYINRLDN FDGSKLAPIA IESQLYEEAF FMYKKFQFNV
EAIDVLITHI GSIERAHDFA ERCNQTEVYS KLGVAQLKAE MVKECIESFI KANDTEHYQE
VVAAAERKDE YEDLVKFLQM CRKKIKEPAI ESELIFAYAK VNKLAEMEDF INSPNSAHIQ
VVGDRCFENG LYEAAKVLYT NISNFSRLTS CLVKLGQYQA AVDAARKANS TKTWKEVSAA
CIDAKEFRLA QVCGINIIVH GDELEELIRQ YEDRGYFNEL ISLLESGLAS ERAHVGMFTE
LAILYSKYKE EKLMEHLKLF YSRLNVPKVI KACQANQQWP QLTYLYIHYD EHDNAIQTMI
NHSIEAWDHV LFKETIPKVA KLDLYYSAIS FYLEEQPLLI NDLLSVLSPR IDHTRAVTLI
RSLGHLPLVK PYLVSAQDQN VAALNEALNE LYVEEEDYES LRSSIDANSN FGTIALAQKL
EKHELLEFRR IAAYLYKKNN RWAQSVELSK KDKLYKDAIQ SASDSKNPAI GEELLQYFVD
QQNNSAFAAC LYTCYDFLKP DAVIELAWRN NILNYSFPYL IQYVKEYTTK VDQLVDDFKA
RQKKTEEEKE QQNIESSQYQ PDLTNLSYGY AATGGMLALP PAVGYQQQQQ PQQMYNPNQM
MGGFQQNYNQ YGGF
