HECD1_CAEEL
ID HECD1_CAEEL Reviewed; 2648 AA.
AC V6CLA2;
DT 20-JUN-2018, integrated into UniProtKB/Swiss-Prot.
DT 19-FEB-2014, sequence version 1.
DT 03-AUG-2022, entry version 64.
DE RecName: Full=E3 ubiquitin-protein ligase hecd-1 {ECO:0000305};
DE EC=2.3.2.26 {ECO:0000250|UniProtKB:Q69ZR2};
GN Name=hecd-1 {ECO:0000303|PubMed:21673654, ECO:0000312|WormBase:C34D4.14a};
GN ORFNames=C34D4.14 {ECO:0000312|WormBase:C34D4.14a};
OS Caenorhabditis elegans.
OC Eukaryota; Metazoa; Ecdysozoa; Nematoda; Chromadorea; Rhabditida;
OC Rhabditina; Rhabditomorpha; Rhabditoidea; Rhabditidae; Peloderinae;
OC Caenorhabditis.
OX NCBI_TaxID=6239 {ECO:0000312|Proteomes:UP000001940};
RN [1] {ECO:0000312|Proteomes:UP000001940}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Bristol N2 {ECO:0000312|Proteomes:UP000001940};
RX PubMed=9851916; DOI=10.1126/science.282.5396.2012;
RG The C. elegans sequencing consortium;
RT "Genome sequence of the nematode C. elegans: a platform for investigating
RT biology.";
RL Science 282:2012-2018(1998).
RN [2] {ECO:0000305}
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=20153198; DOI=10.1016/j.cub.2009.12.061;
RA Zahreddine H., Zhang H., Diogon M., Nagamatsu Y., Labouesse M.;
RT "CRT-1/calreticulin and the E3 ligase EEL-1/HUWE1 control hemidesmosome
RT maturation in C. elegans development.";
RL Curr. Biol. 20:322-327(2010).
RN [3] {ECO:0000305}
RP FUNCTION, PATHWAY, AND TISSUE SPECIFICITY.
RX PubMed=21673654; DOI=10.1038/emboj.2011.195;
RA Liu G., Rogers J., Murphy C.T., Rongo C.;
RT "EGF signalling activates the ubiquitin proteasome system to modulate C.
RT elegans lifespan.";
RL EMBO J. 30:2990-3003(2011).
RN [4] {ECO:0000305}
RP FUNCTION, PATHWAY, AND MUTAGENESIS OF ALA-977; 1304-TRP--ASN-2648;
RP 1460-TRP--ASN-2648 AND 2282-TRP--ASN-2648.
RX PubMed=24703696; DOI=10.1016/j.cmet.2014.01.016;
RA Segref A., Kevei E., Pokrzywa W., Schmeisser K., Mansfeld J.,
RA Livnat-Levanon N., Ensenauer R., Glickman M.H., Ristow M., Hoppe T.;
RT "Pathogenesis of human mitochondrial diseases is modulated by reduced
RT activity of the ubiquitin/proteasome system.";
RL Cell Metab. 19:642-652(2014).
RN [5] {ECO:0000305}
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=25552605; DOI=10.1534/g3.114.015321;
RA Chen Y., Greenwald I.;
RT "hecd-1 modulates notch activity in Caenorhabditis elegans.";
RL G3 (Bethesda) 5:353-359(2014).
RN [6] {ECO:0000305}
RP FUNCTION.
RX PubMed=27669035; DOI=10.1038/nsmb.3296;
RA Ackermann L., Schell M., Pokrzywa W., Kevei E., Gartner A., Schumacher B.,
RA Hoppe T.;
RT "E4 ligase-specific ubiquitination hubs coordinate DNA double-strand-break
RT repair and apoptosis.";
RL Nat. Struct. Mol. Biol. 23:995-1002(2016).
CC -!- FUNCTION: E3 ubiquitin-protein ligase which accepts ubiquitin from an
CC E2 ubiquitin-conjugating enzyme in the form of a thioester and then
CC directly transfers the ubiquitin to targeted substrates (By
CC similarity). Involved in the ubiquitination and proteasomal-mediated
CC degradation of cytoplasmic and mitochondrial proteins (PubMed:24703696,
CC PubMed:21673654). Positively regulates lin-12 activity in the anchor
CC cell (AC)/vulval precursor (VU) cell fate decision (PubMed:25552605).
CC Negatively regulates glp-1 activity in germline proliferation
CC (PubMed:25552605). May play a role in the formation of fibrous
CC organelles, a hemidesmosome-like structure attaching muscles to the
CC epidermis (PubMed:20153198). Regulates germline DNA double-strand-break
CC repair and apoptosis in response to DNA damage by recruiting E4
CC ubiquitin-protein ligase ufd-2 to DNA repair foci (PubMed:27669035).
CC {ECO:0000250|UniProtKB:Q69ZR2, ECO:0000269|PubMed:20153198,
CC ECO:0000269|PubMed:21673654, ECO:0000269|PubMed:24703696,
CC ECO:0000269|PubMed:25552605, ECO:0000269|PubMed:27669035}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine +
CC [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-
CC cysteine + N(6)-ubiquitinyl-[acceptor protein]-L-lysine.;
CC EC=2.3.2.26; Evidence={ECO:0000250|UniProtKB:Q69ZR2};
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC {ECO:0000305|PubMed:21673654, ECO:0000305|PubMed:24703696}.
CC -!- TISSUE SPECIFICITY: Expressed in most tissues, including hypodermis,
CC muscle, intestine, vulva, and neurons. {ECO:0000269|PubMed:21673654}.
CC -!- DISRUPTION PHENOTYPE: RNAi-mediated knockdown causes no visible
CC phenotype (PubMed:20153198). RNAi-mediated knockdown in a glp-1(ar202)
CC mutant background causes an increase in the number of sterile animals
CC (PubMed:25552605). RNAi-mediated knockdown in a vab-10(e698) mutant
CC background causes 50 percent larval lethality associated with the
CC detachment of muscles from the epidermis (PubMed:20153198).
CC {ECO:0000269|PubMed:20153198, ECO:0000269|PubMed:25552605}.
CC -!- SIMILARITY: Belongs to the UPL family. K-HECT subfamily. {ECO:0000305}.
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DR EMBL; BX284604; CDK13339.1; -; Genomic_DNA.
DR RefSeq; NP_001293688.1; NM_001306759.1.
DR AlphaFoldDB; V6CLA2; -.
DR SMR; V6CLA2; -.
DR STRING; 6239.C34D4.14; -.
DR EPD; V6CLA2; -.
DR PaxDb; V6CLA2; -.
DR PeptideAtlas; V6CLA2; -.
DR EnsemblMetazoa; C34D4.14a.1; C34D4.14a.1; WBGene00016405.
DR EnsemblMetazoa; C34D4.14a.2; C34D4.14a.2; WBGene00016405.
DR GeneID; 177486; -.
DR CTD; 177486; -.
DR WormBase; C34D4.14a; CE49267; WBGene00016405; hecd-1.
DR HOGENOM; CLU_000869_0_0_1; -.
DR Reactome; R-CEL-983168; Antigen processing: Ubiquitination & Proteasome degradation.
DR UniPathway; UPA00143; -.
DR PRO; PR:V6CLA2; -.
DR Proteomes; UP000001940; Chromosome IV.
DR Bgee; WBGene00016405; Expressed in pharyngeal muscle cell (C elegans) and 4 other tissues.
DR ExpressionAtlas; V6CLA2; baseline and differential.
DR GO; GO:0016607; C:nuclear speck; IBA:GO_Central.
DR GO; GO:0046872; F:metal ion binding; IEA:InterPro.
DR GO; GO:0061630; F:ubiquitin protein ligase activity; IBA:GO_Central.
DR GO; GO:0048856; P:anatomical structure development; IBA:GO_Central.
DR GO; GO:0008340; P:determination of adult lifespan; IMP:UniProtKB.
DR GO; GO:0045746; P:negative regulation of Notch signaling pathway; IMP:UniProtKB.
DR GO; GO:0045747; P:positive regulation of Notch signaling pathway; IMP:UniProtKB.
DR GO; GO:0032436; P:positive regulation of proteasomal ubiquitin-dependent protein catabolic process; IMP:UniProtKB.
DR GO; GO:0043161; P:proteasome-mediated ubiquitin-dependent protein catabolic process; IMP:UniProtKB.
DR GO; GO:0070534; P:protein K63-linked ubiquitination; IBA:GO_Central.
DR GO; GO:0000209; P:protein polyubiquitination; IBA:GO_Central.
DR GO; GO:0042659; P:regulation of cell fate specification; IGI:UniProtKB.
DR GO; GO:1905936; P:regulation of germ cell proliferation; IGI:UniProtKB.
DR GO; GO:1902882; P:regulation of response to oxidative stress; IMP:UniProtKB.
DR GO; GO:0040028; P:regulation of vulval development; IGI:UniProtKB.
DR CDD; cd00078; HECTc; 1.
DR Gene3D; 1.25.10.10; -; 1.
DR Gene3D; 1.25.40.20; -; 1.
DR InterPro; IPR002110; Ankyrin_rpt.
DR InterPro; IPR036770; Ankyrin_rpt-contain_sf.
DR InterPro; IPR011989; ARM-like.
DR InterPro; IPR016024; ARM-type_fold.
DR InterPro; IPR008979; Galactose-bd-like_sf.
DR InterPro; IPR000569; HECT_dom.
DR InterPro; IPR035983; Hect_E3_ubiquitin_ligase.
DR InterPro; IPR045322; HECTD1/TRIP12-like.
DR InterPro; IPR010606; Mib_Herc2.
DR InterPro; IPR037252; Mib_Herc2_sf.
DR InterPro; IPR012919; SUN_dom.
DR PANTHER; PTHR45670; PTHR45670; 1.
DR Pfam; PF12796; Ank_2; 1.
DR Pfam; PF00632; HECT; 1.
DR Pfam; PF06701; MIB_HERC2; 1.
DR Pfam; PF07738; Sad1_UNC; 1.
DR SMART; SM00248; ANK; 2.
DR SMART; SM00119; HECTc; 1.
DR SUPFAM; SSF159034; SSF159034; 1.
DR SUPFAM; SSF48371; SSF48371; 1.
DR SUPFAM; SSF48403; SSF48403; 1.
DR SUPFAM; SSF49785; SSF49785; 1.
DR SUPFAM; SSF56204; SSF56204; 1.
DR PROSITE; PS50297; ANK_REP_REGION; 1.
DR PROSITE; PS50088; ANK_REPEAT; 1.
DR PROSITE; PS50237; HECT; 1.
DR PROSITE; PS51416; MIB_HERC2; 1.
PE 1: Evidence at protein level;
KW ANK repeat; Reference proteome; Repeat; Transferase;
KW Ubl conjugation pathway.
FT CHAIN 1..2648
FT /note="E3 ubiquitin-protein ligase hecd-1"
FT /id="PRO_0000444432"
FT REPEAT 374..403
FT /note="ANK 1"
FT /evidence="ECO:0000255"
FT REPEAT 405..434
FT /note="ANK 2"
FT /evidence="ECO:0000255"
FT DOMAIN 1438..1510
FT /note="MIB/HERC2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00749"
FT DOMAIN 2240..2648
FT /note="HECT"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00104"
FT REGION 433..494
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 645..714
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1376..1400
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1538..1562
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1575..1629
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1652..1796
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1811..1836
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 433..456
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 479..493
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 648..714
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1382..1400
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1541..1562
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1669..1722
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1754..1785
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1811..1826
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 2617
FT /note="Glycyl thioester intermediate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00104"
FT MUTAGEN 977
FT /note="A->T: In hh2; loss of degradation of ubiquitinated
FT proteins; when associated with 1304-W--N-2648 DEL."
FT /evidence="ECO:0000269|PubMed:24703696"
FT MUTAGEN 1304..2648
FT /note="Missing: In hh2; loss of degradation of
FT ubiquitinated proteins; when associated with T-977."
FT /evidence="ECO:0000269|PubMed:24703696"
FT MUTAGEN 1460..2648
FT /note="Missing: In hh3; loss of degradation of
FT ubiquitinated proteins."
FT /evidence="ECO:0000269|PubMed:24703696"
FT MUTAGEN 2282..2648
FT /note="Missing: In hh4; loss of degradation of
FT ubiquitinated proteins."
FT /evidence="ECO:0000269|PubMed:24703696"
SQ SEQUENCE 2648 AA; 292210 MW; DD84EE54AB8E9922 CRC64;
MDGIDPETLL EWLQTGIGDE RDLQLMALEQ LCMLLLMADN IDRCFESCPP RTFIPALCKI
FIDETAPDNV LEVTARAITY YLDVSNECTR RITQVDGAVK AICTRLAAAD ISDRSSKDLA
EQCVKLLEHV CQRETMAVYD AGGINAMLTL VRVHGTQVHK DTMHSAMSVV TRLCGKMEPT
DPELGKCAES LGALLEHEDP KVSESALRCF AALTDRFVRK MMDPAELAMH SNLVEHLISI
MVASNDENSP TTASANILSI VLSLIGNLCR GSSLITEKVL TSPNMITGLK ATLTNKEERV
VTDGLRFCDL LLVLLCEGRS ALPLTSVVSG DYAAGSGAER VHRQLIDAIR QKDLTALVDA
IESGQVDVNF ADDVGQSLTN WASAFGSIEM VQYLCDKGSD VNKGHKSSSL HYAACFGRPD
VVKLLLQRGA NPDLRDEDGK TALDKARERS DDDHNQVANI LESPSAFMRN KEDPKVKAST
SKQPGTSTKP ELPNPNLVRK VLHQLLPIFC EIFQKSLNGS VRRTSLSLMR KIVENIGDLR
QSAVGDGNAP AAQSARKMST DVSAGAESLV AVVVSVMDQE DDHEGHEQVL LILESLLEKD
AELWVIELVR LGVFERVEAM AKEPPKGLEE VLNAIHLEGR SRVTPMEIDF ENQPSSSTAV
PTANDIMDTT VPSSSGGADA ESNSNPSTIE MADPESSTPS SSTQQSISKP KATASSTASS
AILQVVSKLS SVASLDKSAA AVDKKPTKTV LSQGTPYRWK EWRIVRGTTS LFIWSDVLLI
ELPFQSNGWF RYLADNDSHV QFVTGTASVD QQMTEEEKDN FQKTERREMV SRWNAVKGVF
DDDWSSVPIA VLGIPSNAKK VSQKLEVPAW ELWSSKSSEL QIKSISSSAP TGQANTMLTT
IKDDAGGFLF ETGTGRKTNV MPEHALPSDF HTGWSSHGVS TRKMKFRQDI QKRKVQELAW
KLWNDHLKEA HAKPREALVR LENAARTIES TIRHVKAQSN FKHRNVKQPR IERVQEYCAA
ISTLHESIVD DRRLSTFEFS VSGIVPALFG LLSMMEKFPD SFPSRIFKEQ FSKGEALSYL
ALKIVAVLEA NEKFPQHLYD SPGGSSFGLQ LLSRRVRTKL EMLPRADGKE NNDENLVNKT
GKIVKCEPLA SVGAIRAYLH RMVTRQWHDR ERANYRYVKE IQELKTKGKS IELRHVSDFD
ENGVIYWIGT NGRAAPLWTN PATVKAVKIT CSDTRQPFGK PEDLLSRDQN PINCHTSDDK
NAHFTIDLGL FVVPTSYSLR HSRGYGRSAL RNWMLQGSVD AKRWENVIVH TDDKGLGEPG
STATWHVGEK GTTAFRFFRI AQNGKNSSGQ THYLSCSGFE IYGDIVDVVT EAICEDPPKK
DSPAGTSSTP GSSSSAALPP LTKEQVLEML PARENNNRLK SGLSLETVTS MLQRSRHRSR
GSYKISESKS KVVRGKDWRW EDQDGGEGKF GRITSPPESG WVDVTWDNGN ANSYRFGANG
NFDIERVTST GHRYSTPSLA SHVPTSVMEA VRRNRAFYTP KTTGGPPSSS VFGTSSSAGS
SRGAASALSR FASVKNTTPA GTPSSGGSSG GAIGKKSMST TNLVDERQKT SGPSVASTGQ
AASAESLQHQ TPSLENLLAR AMPHAFGRIA ENQEPEDEPM GGEESDSAAS MRSAASSNSQ
MSMGSSSQQQ QQQDSDMTPR DSAGTPSTPR DDKNQTLSVS APDLAAARQR QASAETDGDA
DADETNSEDK TVGADDAMEE DDEEEETMED EEDDDDDDDD ESSNENQEKL VELLGGERGL
FDKLKEVITG ESLSDASSSA KDATTNEAQK KGGKKPKKWF KKMSSYTDVL KGLMQNRYPV
ALLDPAAAGI EMDEMMDDDD YYDFSEDGPD DGDSVEDEVA AHLGMPVDSF ASMVAARTPI
TWRQFSELMS GSNRERAAMA RAVASSRGSP WEDDATVKCT FEALIPAFDP RPGRSNVNQT
LEVELPTVVK DFGSTKASSS KIDKDDQMRF FLRGPNMSGV DNVTIEMNDD SASLFRYMQI
INNSVNWATK SDRSRRIWEP TYSICYCSAD QTNVEVSKIP DEESSTPCQV NQCLETIGLL
SRIQQAMPEA EITPNVFISD KLTLKVTQVL SDALVVAARS LPEWCSRLVY KYPCLFTVET
RNMYMQATAF GVSRTIVWLQ QRRDAAVERA RGSAQAGNSS AARQHDRYHE YRVGRLRHER
VKVTRAEETL LDQAIRLMKF HADRKAVLEI EYTNEEGTGL GPTLEFYALV AAELQRKSLA
LWVCDDDDTH ASKSGEEREV DLGEGKKPIG YYVRRVGGLF PAPLPPGTDE TKRAADMFRV
LGVFLAKVLL DGRLVDLPLS RPFLKLLVHP QIGDDARGPN LHKILSLDDF EEVNPVKGSF
LKELRALAQR KRLIENDTSI DSNSKRRKIA ELKLHIKGST CRVEDLALNF TVNPPSKVFQ
YAEMELVDGG SDIDVTIDNV EQYVEKCEEF YLNTGIAYQM RAFRDGFDRV FPLRTLRAYS
PEEVQRLLSG EQCPEWSRDD ILNYTEPKLG YTRESPGFLR FVDVMEALTA QERKNFLQFA
TGCSSLPPGG LANLHPRLTI VRKVESGDGS YPSVNTCVHY LKLPEYSSSA ILRERLLTAI
NEKGFHLN
