ID HECD3_HUMAN Reviewed; 861 AA.
AC Q5T447; B3KPV7; B3KRH4; Q5T448; Q9H783;
DT 27-JUN-2006, integrated into UniProtKB/Swiss-Prot.
DT 21-DEC-2004, sequence version 1.
DT 24-JAN-2024, entry version 162.
DE RecName: Full=E3 ubiquitin-protein ligase HECTD3;
DE EC=2.3.2.26;
DE AltName: Full=HECT domain-containing protein 3;
DE AltName: Full=HECT-type E3 ubiquitin transferase HECTD3;
GN Name=HECTD3;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), AND NUCLEOTIDE SEQUENCE
RP [LARGE SCALE MRNA] OF 644-861 (ISOFORM 1).
RC TISSUE=Brain, and Prostate;
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., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., 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., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA 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 [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 649-861 (ISOFORM 1).
RC TISSUE=Muscle;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP FUNCTION, INTERACTION WITH TRIOBP, AND MUTAGENESIS OF CYS-823.
RX PubMed=18194665; DOI=10.1016/j.bbrc.2008.01.022;
RA Yu J., Lan J., Zhu Y., Li X., Lai X., Xue Y., Jin C., Huang H.;
RT "The E3 ubiquitin ligase HECTD3 regulates ubiquitination and degradation of
RT Tara.";
RL Biochem. Biophys. Res. Commun. 367:805-812(2008).
RN [6]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [7]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RX PubMed=22223895; DOI=10.1074/mcp.m111.015131;
RA Bienvenut W.V., Sumpton D., Martinez A., Lilla S., Espagne C., Meinnel T.,
RA Giglione C.;
RT "Comparative large-scale characterisation of plant vs. mammal proteins
RT reveals similar and idiosyncratic N-alpha acetylation features.";
RL Mol. Cell. Proteomics 11:M111.015131-M111.015131(2012).
RN [8]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
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., Timmerman E.,
RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-terminal
RT acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-12, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
CC -!- FUNCTION: E3 ubiquitin ligases accepts ubiquitin from an E2 ubiquitin-
CC conjugating enzyme in the form of a thioester and then directly
CC transfers the ubiquitin to targeted substrates. Mediates ubiquitination
CC of TRIOBP and its subsequent proteasomal degradation, thus facilitating
CC cell cycle progression by regulating the turn-over of TRIOBP. Mediates
CC also ubiquitination of STX8 (By similarity).
CC {ECO:0000250|UniProtKB:Q3U487, ECO:0000269|PubMed:18194665}.
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;
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC -!- SUBUNIT: Interacts with TRIOBP. Interacts with STX8 (By similarity).
CC {ECO:0000250|UniProtKB:Q3U487, ECO:0000269|PubMed:18194665}.
CC -!- INTERACTION:
CC Q5T447; O60437: PPL; NbExp=3; IntAct=EBI-2691157, EBI-368321;
CC Q5T447-2; P22607: FGFR3; NbExp=3; IntAct=EBI-25854793, EBI-348399;
CC Q5T447-2; Q14957: GRIN2C; NbExp=3; IntAct=EBI-25854793, EBI-8285963;
CC Q5T447-2; P06396: GSN; NbExp=3; IntAct=EBI-25854793, EBI-351506;
CC Q5T447-2; Q9UMX0: UBQLN1; NbExp=3; IntAct=EBI-25854793, EBI-741480;
CC Q5T447-2; Q9Y649; NbExp=3; IntAct=EBI-25854793, EBI-25900580;
CC -!- SUBCELLULAR LOCATION: Cytoplasm, perinuclear region {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q5T447-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q5T447-2; Sequence=VSP_019439, VSP_019440;
CC -!- SEQUENCE CAUTION:
CC Sequence=BAB15015.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Sequence of unknown origin in the N-terminal part.; Evidence={ECO:0000305};
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DR EMBL; AK024809; BAB15015.1; ALT_SEQ; mRNA.
DR EMBL; AK056873; BAG51819.1; -; mRNA.
DR EMBL; AK091583; BAG52386.1; -; mRNA.
DR EMBL; AL359473; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471059; EAX07010.1; -; Genomic_DNA.
DR EMBL; BC019105; AAH19105.2; -; mRNA.
DR CCDS; CCDS41318.1; -. [Q5T447-1]
DR RefSeq; NP_078878.3; NM_024602.5. [Q5T447-1]
DR AlphaFoldDB; Q5T447; -.
DR SMR; Q5T447; -.
DR BioGRID; 122781; 136.
DR IntAct; Q5T447; 47.
DR MINT; Q5T447; -.
DR STRING; 9606.ENSP00000361245; -.
DR GlyGen; Q5T447; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q5T447; -.
DR PhosphoSitePlus; Q5T447; -.
DR BioMuta; HECTD3; -.
DR DMDM; 74744877; -.
DR EPD; Q5T447; -.
DR jPOST; Q5T447; -.
DR MassIVE; Q5T447; -.
DR MaxQB; Q5T447; -.
DR PaxDb; 9606-ENSP00000361245; -.
DR PeptideAtlas; Q5T447; -.
DR ProteomicsDB; 64431; -. [Q5T447-1]
DR ProteomicsDB; 64432; -. [Q5T447-2]
DR Pumba; Q5T447; -.
DR Antibodypedia; 32577; 143 antibodies from 25 providers.
DR DNASU; 79654; -.
DR Ensembl; ENST00000372168.7; ENSP00000361241.3; ENSG00000126107.15. [Q5T447-2]
DR Ensembl; ENST00000372172.5; ENSP00000361245.4; ENSG00000126107.15. [Q5T447-1]
DR GeneID; 79654; -.
DR KEGG; hsa:79654; -.
DR MANE-Select; ENST00000372172.5; ENSP00000361245.4; NM_024602.6; NP_078878.3.
DR UCSC; uc001cmy.5; human. [Q5T447-1]
DR AGR; HGNC:26117; -.
DR CTD; 79654; -.
DR DisGeNET; 79654; -.
DR GeneCards; HECTD3; -.
DR HGNC; HGNC:26117; HECTD3.
DR HPA; ENSG00000126107; Low tissue specificity.
DR MIM; 618638; gene.
DR neXtProt; NX_Q5T447; -.
DR OpenTargets; ENSG00000126107; -.
DR PharmGKB; PA142671698; -.
DR VEuPathDB; HostDB:ENSG00000126107; -.
DR eggNOG; KOG0939; Eukaryota.
DR GeneTree; ENSGT00940000159923; -.
DR HOGENOM; CLU_002173_11_0_1; -.
DR InParanoid; Q5T447; -.
DR OMA; PAWDYTL; -.
DR OrthoDB; 2899647at2759; -.
DR PhylomeDB; Q5T447; -.
DR BRENDA; 2.3.2.26; 2681.
DR PathwayCommons; Q5T447; -.
DR Reactome; R-HSA-983168; Antigen processing: Ubiquitination & Proteasome degradation.
DR SignaLink; Q5T447; -.
DR SIGNOR; Q5T447; -.
DR UniPathway; UPA00143; -.
DR BioGRID-ORCS; 79654; 47 hits in 1196 CRISPR screens.
DR ChiTaRS; HECTD3; human.
DR GenomeRNAi; 79654; -.
DR Pharos; Q5T447; Tdark.
DR PRO; PR:Q5T447; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; Q5T447; Protein.
DR Bgee; ENSG00000126107; Expressed in ileal mucosa and 185 other cell types or tissues.
DR Genevisible; Q5T447; HS.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; ISS:UniProtKB.
DR GO; GO:0019905; F:syntaxin binding; IEA:Ensembl.
DR GO; GO:0004842; F:ubiquitin-protein transferase activity; IDA:UniProtKB.
DR GO; GO:0043161; P:proteasome-mediated ubiquitin-dependent protein catabolic process; IDA:UniProtKB.
DR GO; GO:0016567; P:protein ubiquitination; IEA:UniProtKB-UniPathway.
DR CDD; cd08666; APC10-HECTD3; 1.
DR Gene3D; 2.60.120.260; Galactose-binding domain-like; 1.
DR Gene3D; 3.30.2160.10; Hect, E3 ligase catalytic domain; 1.
DR Gene3D; 3.30.2410.10; Hect, E3 ligase catalytic domain; 1.
DR Gene3D; 3.90.1750.10; Hect, E3 ligase catalytic domains; 1.
DR InterPro; IPR004939; APC_su10/DOC_dom.
DR InterPro; IPR008979; Galactose-bd-like_sf.
DR InterPro; IPR000569; HECT_dom.
DR InterPro; IPR035983; Hect_E3_ubiquitin_ligase.
DR InterPro; IPR042469; HECTD3.
DR PANTHER; PTHR46654; E3 UBIQUITIN-PROTEIN LIGASE HECTD3; 1.
DR PANTHER; PTHR46654:SF1; E3 UBIQUITIN-PROTEIN LIGASE HECTD3; 1.
DR Pfam; PF03256; ANAPC10; 1.
DR Pfam; PF00632; HECT; 1.
DR SMART; SM01337; APC10; 1.
DR SMART; SM00119; HECTc; 1.
DR SUPFAM; SSF49785; Galactose-binding domain-like; 1.
DR SUPFAM; SSF56204; Hect, E3 ligase catalytic domain; 1.
DR PROSITE; PS51284; DOC; 1.
DR PROSITE; PS50237; HECT; 1.
PE 1: Evidence at protein level;
KW Acetylation; Alternative splicing; Cytoplasm; Phosphoprotein;
KW Reference proteome; Transferase; Ubl conjugation pathway.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0007744|PubMed:22223895,
FT ECO:0007744|PubMed:22814378"
FT CHAIN 2..861
FT /note="E3 ubiquitin-protein ligase HECTD3"
FT /id="PRO_0000241445"
FT DOMAIN 219..397
FT /note="DOC"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00614"
FT DOMAIN 512..857
FT /note="HECT"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00104"
FT ACT_SITE 823
FT /note="Glycyl thioester intermediate"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0007744|PubMed:22223895,
FT ECO:0007744|PubMed:22814378"
FT MOD_RES 12
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT VAR_SEQ 1..390
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_019439"
FT VAR_SEQ 391..412
FT /note="VRYPRLEGTDPEVLYRRAVLLQ -> MLGSWGCYRYAKLFSCSLSTHA (in
FT isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_019440"
FT MUTAGEN 823
FT /note="C->A: Loss of ubiquitin-ligase activity."
FT /evidence="ECO:0000269|PubMed:18194665"
SQ SEQUENCE 861 AA; 97113 MW; 91009CE9FB84F4E7 CRC64;
MAGPGPGAVL ESPRQLLGRV RFLAEAARSL RAGRPLPAAL AFVPREVLYK LYKDPAGPSR
VLLPVWEAEG LGLRVGAAGP APGTGSGPLR AARDSIELRR GACVRTTGEE LCNGHGLWVK
LTKEQLAEHL GDCGLQEGWL LVCRPAEGGA RLVPIDTPNH LQRQQQLFGV DYRPVLRWEQ
VVDLTYSHRL GSRPQPAEAY AEAVQRLLYV PPTWTYECDE DLIHFLYDHL GKEDENLGSV
KQYVESIDVS SYTEEFNVSC LTDSNADTYW ESDGSQCQHW VRLTMKKGTI VKKLLLTVDT
TDDNFMPKRV VVYGGEGDNL KKLSDVSIDE TLIGDVCVLE DMTVHLPIIE IRIVECRDDG
IDVRLRGVKI KSSRQRELGL NADLFQPTSL VRYPRLEGTD PEVLYRRAVL LQRFIKILDS
VLHHLVPAWD HTLGTFSEIK QVKQFLLLSR QRPGLVAQCL RDSESSKPSF MPRLYINRRL
AMEHRACPSR DPACKNAVFT QVYEGLKPSD KYEKPLDYRW PMRYDQWWEC KFIAEGIIDQ
GGGFRDSLAD MSEELCPSSA DTPVPLPFFV RTANQGNGTG EARDMYVPNP SCRDFAKYEW
IGQLMGAALR GKEFLVLALP GFVWKQLSGE EVSWSKDFPA VDSVLVKLLE VMEGMDKETF
EFKFGKELTF TTVLSDQQVV ELIPGGAGIV VGYGDRSRFI QLVQKARLEE SKEQVAAMQA
GLLKVVPQAV LDLLTWQELE KKVCGDPEVT VDALRKLTRF EDFEPSDSRV QYFWEALNNF
TNEDRSRFLR FVTGRSRLPA RIYIYPDKLG YETTDALPES STCSSTLFLP HYASAKVCEE
KLRYAAYNCV AIDTDMSPWE E
//
