HECD1_HUMAN
ID HECD1_HUMAN Reviewed; 2610 AA.
AC Q9ULT8; D3DS86; Q6P445; Q86VJ1; Q96F34; Q9UFZ7;
DT 12-FEB-2003, integrated into UniProtKB/Swiss-Prot.
DT 23-FEB-2022, sequence version 4.
DT 03-AUG-2022, entry version 192.
DE RecName: Full=E3 ubiquitin-protein ligase HECTD1 {ECO:0000305};
DE EC=2.3.2.26 {ECO:0000269|PubMed:33711283};
DE AltName: Full=E3 ligase for inhibin receptor;
DE Short=EULIR {ECO:0000303|Ref.1};
DE AltName: Full=HECT domain-containing protein 1;
GN Name=HECTD1 {ECO:0000303|PubMed:33711283, ECO:0000312|HGNC:HGNC:20157};
GN Synonyms=KIAA1131;
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 [MRNA], AND VARIANT LEU-2027.
RA Zhang H.;
RT "EULIR is an E3 ubiquitin ligase for inhibin receptor.";
RL Submitted (MAR-2003) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=12508121; DOI=10.1038/nature01348;
RA Heilig R., Eckenberg R., Petit J.-L., Fonknechten N., Da Silva C.,
RA Cattolico L., Levy M., Barbe V., De Berardinis V., Ureta-Vidal A.,
RA Pelletier E., Vico V., Anthouard V., Rowen L., Madan A., Qin S., Sun H.,
RA Du H., Pepin K., Artiguenave F., Robert C., Cruaud C., Bruels T.,
RA Jaillon O., Friedlander L., Samson G., Brottier P., Cure S., Segurens B.,
RA Aniere F., Samain S., Crespeau H., Abbasi N., Aiach N., Boscus D.,
RA Dickhoff R., Dors M., Dubois I., Friedman C., Gouyvenoux M., James R.,
RA Madan A., Mairey-Estrada B., Mangenot S., Martins N., Menard M., Oztas S.,
RA Ratcliffe A., Shaffer T., Trask B., Vacherie B., Bellemere C., Belser C.,
RA Besnard-Gonnet M., Bartol-Mavel D., Boutard M., Briez-Silla S.,
RA Combette S., Dufosse-Laurent V., Ferron C., Lechaplais C., Louesse C.,
RA Muselet D., Magdelenat G., Pateau E., Petit E., Sirvain-Trukniewicz P.,
RA Trybou A., Vega-Czarny N., Bataille E., Bluet E., Bordelais I., Dubois M.,
RA Dumont C., Guerin T., Haffray S., Hammadi R., Muanga J., Pellouin V.,
RA Robert D., Wunderle E., Gauguet G., Roy A., Sainte-Marthe L., Verdier J.,
RA Verdier-Discala C., Hillier L.W., Fulton L., McPherson J., Matsuda F.,
RA Wilson R., Scarpelli C., Gyapay G., Wincker P., Saurin W., Quetier F.,
RA Waterston R., Hood L., Weissenbach J.;
RT "The DNA sequence and analysis of human chromosome 14.";
RL Nature 421:601-607(2003).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton 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 443-2610.
RC TISSUE=Brain;
RX PubMed=10574461; DOI=10.1093/dnares/6.5.329;
RA Hirosawa M., Nagase T., Ishikawa K., Kikuno R., Nomura N., Ohara O.;
RT "Characterization of cDNA clones selected by the GeneMark analysis from
RT size-fractionated cDNA libraries from human brain.";
RL DNA Res. 6:329-336(1999).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1652-2610.
RC TISSUE=Testis;
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., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 2091-2610.
RC TISSUE=Muscle, and Urinary bladder;
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 [7]
RP INTERACTION WITH IGSF1.
RX PubMed=12421765; DOI=10.1101/gr.406902;
RA Nakayama M., Kikuno R., Ohara O.;
RT "Protein-protein interactions between large proteins: two-hybrid screening
RT using a functionally classified library composed of long cDNAs.";
RL Genome Res. 12:1773-1784(2002).
RN [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1488, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
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 [9]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a
RT refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [10]
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., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [11]
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 [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-631, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [13]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-1760 AND SER-1772, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and 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).
RN [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-2318, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [15]
RP FUNCTION, CATALYTIC ACTIVITY, PATHWAY, AND MUTAGENESIS OF CYS-2579.
RX PubMed=33711283; DOI=10.1016/j.stem.2021.02.008;
RA Lv K., Gong C., Antony C., Han X., Ren J.G., Donaghy R., Cheng Y.,
RA Pellegrino S., Warren A.J., Paralkar V.R., Tong W.;
RT "HectD1 controls hematopoietic stem cell regeneration by coordinating
RT ribosome assembly and protein synthesis.";
RL Cell Stem Cell 28:1275-1290(2021).
RN [16]
RP STRUCTURE BY NMR OF 1266-1338.
RG RIKEN structural genomics initiative (RSGI);
RT "Solution structure of MIB-HERC2 domain in HECT domain containing protein
RT 1.";
RL Submitted (OCT-2006) to the PDB data bank.
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
CC (PubMed:33711283). Mediates 'Lys-63'-linked polyubiquitination of
CC HSP90AA1 which leads to its intracellular localization and reduced
CC secretion (By similarity). Negatively regulating HSP90AA1 secretion in
CC cranial mesenchyme cells may impair their emigration and may be
CC essential for the correct development of the cranial neural folds and
CC neural tube closure (By similarity). Catalyzes ubiquitination and
CC degradation of ZNF622, an assembly factor for the ribosomal 60S
CC subunit, in hematopoietic cells, thereby promoting hematopoietic stem
CC cell renewal (PubMed:33711283). {ECO:0000250|UniProtKB:Q69ZR2,
CC ECO:0000269|PubMed:33711283}.
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:0000269|PubMed:33711283};
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC {ECO:0000269|PubMed:33711283}.
CC -!- SUBUNIT: Interacts with IGSF1 (PubMed:12421765).
CC {ECO:0000269|PubMed:12421765}.
CC -!- SIMILARITY: Belongs to the UPL family. K-HECT subfamily. {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AY254380; AAP13073.1; -; mRNA.
DR EMBL; AL121808; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL136418; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471078; EAW65950.1; -; Genomic_DNA.
DR EMBL; CH471078; EAW65952.1; -; Genomic_DNA.
DR EMBL; AB032957; BAA86445.2; -; mRNA.
DR EMBL; AL110222; CAB53681.1; -; mRNA.
DR EMBL; BC011658; AAH11658.2; -; mRNA.
DR EMBL; BC063686; AAH63686.1; -; mRNA.
DR CCDS; CCDS41939.1; -.
DR PIR; T14761; T14761.
DR RefSeq; NP_056197.3; NM_015382.3.
DR RefSeq; XP_005267559.2; XM_005267502.2.
DR PDB; 2DK3; NMR; -; A=1266-1338.
DR PDB; 2LC3; NMR; -; A=1879-1966.
DR PDB; 3DKM; X-ray; 1.60 A; A=1271-1341.
DR PDBsum; 2DK3; -.
DR PDBsum; 2LC3; -.
DR PDBsum; 3DKM; -.
DR AlphaFoldDB; Q9ULT8; -.
DR BMRB; Q9ULT8; -.
DR SMR; Q9ULT8; -.
DR BioGRID; 117359; 381.
DR DIP; DIP-31669N; -.
DR IntAct; Q9ULT8; 47.
DR MINT; Q9ULT8; -.
DR STRING; 9606.ENSP00000382269; -.
DR GlyGen; Q9ULT8; 12 sites, 2 O-linked glycans (12 sites).
DR iPTMnet; Q9ULT8; -.
DR PhosphoSitePlus; Q9ULT8; -.
DR SwissPalm; Q9ULT8; -.
DR BioMuta; HECTD1; -.
DR DMDM; 313104227; -.
DR EPD; Q9ULT8; -.
DR jPOST; Q9ULT8; -.
DR MassIVE; Q9ULT8; -.
DR MaxQB; Q9ULT8; -.
DR PaxDb; Q9ULT8; -.
DR PeptideAtlas; Q9ULT8; -.
DR PRIDE; Q9ULT8; -.
DR ProteomicsDB; 85108; -.
DR Antibodypedia; 5457; 121 antibodies from 25 providers.
DR DNASU; 25831; -.
DR Ensembl; ENST00000399332.6; ENSP00000382269.1; ENSG00000092148.14.
DR Ensembl; ENST00000553700.5; ENSP00000450697.1; ENSG00000092148.14.
DR GeneID; 25831; -.
DR KEGG; hsa:25831; -.
DR MANE-Select; ENST00000399332.6; ENSP00000382269.1; NM_015382.4; NP_056197.3.
DR UCSC; uc001wrc.1; human.
DR CTD; 25831; -.
DR DisGeNET; 25831; -.
DR GeneCards; HECTD1; -.
DR HGNC; HGNC:20157; HECTD1.
DR HPA; ENSG00000092148; Tissue enhanced (skeletal).
DR MIM; 618649; gene.
DR neXtProt; NX_Q9ULT8; -.
DR OpenTargets; ENSG00000092148; -.
DR PharmGKB; PA134989284; -.
DR VEuPathDB; HostDB:ENSG00000092148; -.
DR eggNOG; KOG4276; Eukaryota.
DR GeneTree; ENSGT00940000156572; -.
DR HOGENOM; CLU_000869_0_0_1; -.
DR InParanoid; Q9ULT8; -.
DR OrthoDB; 34110at2759; -.
DR PhylomeDB; Q9ULT8; -.
DR TreeFam; TF323674; -.
DR PathwayCommons; Q9ULT8; -.
DR Reactome; R-HSA-983168; Antigen processing: Ubiquitination & Proteasome degradation.
DR SignaLink; Q9ULT8; -.
DR SIGNOR; Q9ULT8; -.
DR UniPathway; UPA00143; -.
DR BioGRID-ORCS; 25831; 289 hits in 1133 CRISPR screens.
DR ChiTaRS; HECTD1; human.
DR EvolutionaryTrace; Q9ULT8; -.
DR GenomeRNAi; 25831; -.
DR Pharos; Q9ULT8; Tbio.
DR PRO; PR:Q9ULT8; -.
DR Proteomes; UP000005640; Chromosome 14.
DR RNAct; Q9ULT8; protein.
DR Bgee; ENSG00000092148; Expressed in tibialis anterior and 174 other tissues.
DR ExpressionAtlas; Q9ULT8; baseline and differential.
DR Genevisible; Q9ULT8; HS.
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; ISS:FlyBase.
DR GO; GO:0048856; P:anatomical structure development; IBA:GO_Central.
DR GO; GO:0035904; P:aorta development; ISS:BHF-UCL.
DR GO; GO:0003170; P:heart valve development; ISS:BHF-UCL.
DR GO; GO:0001779; P:natural killer cell differentiation; IEA:Ensembl.
DR GO; GO:1903077; P:negative regulation of protein localization to plasma membrane; IEA:Ensembl.
DR GO; GO:0001843; P:neural tube closure; IEA:Ensembl.
DR GO; GO:0032436; P:positive regulation of proteasomal ubiquitin-dependent protein catabolic process; ISS:FlyBase.
DR GO; GO:0043161; P:proteasome-mediated ubiquitin-dependent protein catabolic process; IBA:GO_Central.
DR GO; GO:0051865; P:protein autoubiquitination; IEA:Ensembl.
DR GO; GO:0070534; P:protein K63-linked ubiquitination; IBA:GO_Central.
DR GO; GO:0072659; P:protein localization to plasma membrane; IEA:Ensembl.
DR GO; GO:0000209; P:protein polyubiquitination; IBA:GO_Central.
DR GO; GO:0060708; P:spongiotrophoblast differentiation; IEA:Ensembl.
DR GO; GO:0060707; P:trophoblast giant cell differentiation; IEA:Ensembl.
DR GO; GO:0003281; P:ventricular septum development; ISS:BHF-UCL.
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; IPR041200; FKBP3_BTHB.
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; PF18410; BTHB; 1.
DR Pfam; PF00632; HECT; 1.
DR Pfam; PF06701; MIB_HERC2; 1.
DR Pfam; PF07738; Sad1_UNC; 1.
DR SMART; SM00248; ANK; 3.
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; 2.
DR PROSITE; PS50237; HECT; 1.
DR PROSITE; PS51416; MIB_HERC2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; ANK repeat; Phosphoprotein; Reference proteome; Repeat;
KW Transferase; Ubl conjugation pathway.
FT CHAIN 1..2610
FT /note="E3 ubiquitin-protein ligase HECTD1"
FT /id="PRO_0000083945"
FT REPEAT 395..424
FT /note="ANK 1"
FT REPEAT 426..455
FT /note="ANK 2"
FT REPEAT 459..491
FT /note="ANK 3"
FT REPEAT 579..612
FT /note="ANK 4"
FT DOMAIN 1266..1338
FT /note="MIB/HERC2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00749"
FT DOMAIN 2151..2610
FT /note="HECT"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00104"
FT REGION 246..269
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 489..513
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 627..657
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 707..748
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1343..1406
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1433..1483
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1496..1515
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1592..1611
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1674..1757
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1777..1797
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2029..2103
FT /note="K-box"
FT REGION 2297..2318
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 252..269
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 489..512
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 733..748
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1345..1401
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1433..1457
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1675..1700
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1701..1721
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1743..1757
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 2579
FT /note="Glycyl thioester intermediate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00104"
FT MOD_RES 631
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21406692"
FT MOD_RES 640
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q69ZR2"
FT MOD_RES 1384
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q69ZR2"
FT MOD_RES 1488
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 1567
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q69ZR2"
FT MOD_RES 1760
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 1772
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 2318
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT VARIANT 656
FT /note="Q -> H (in dbSNP:rs11620816)"
FT /id="VAR_059666"
FT VARIANT 2027
FT /note="P -> L (in dbSNP:rs1315794)"
FT /evidence="ECO:0000269|Ref.1"
FT /id="VAR_067707"
FT MUTAGEN 2579
FT /note="C->G: Abolished E3 ubiquitin-protein ligase
FT activity."
FT /evidence="ECO:0000269|PubMed:33711283"
FT CONFLICT 561
FT /note="K -> Q (in Ref. 1; AAP13073)"
FT /evidence="ECO:0000305"
FT CONFLICT 603
FT /note="L -> I (in Ref. 1; AAP13073)"
FT /evidence="ECO:0000305"
FT CONFLICT 611..613
FT /note="FLD -> YKH (in Ref. 1; AAP13073)"
FT /evidence="ECO:0000305"
FT CONFLICT 653
FT /note="K -> Q (in Ref. 1; AAP13073)"
FT /evidence="ECO:0000305"
FT CONFLICT 894
FT /note="E -> K (in Ref. 1; AAP13073)"
FT /evidence="ECO:0000305"
FT CONFLICT 927..944
FT /note="SMDLDMKQDCSQLVERIN -> VSIFRATKQKQNEVPKVILS (in Ref.
FT 1; AAP13073)"
FT /evidence="ECO:0000305"
FT CONFLICT 951
FT /note="S -> T (in Ref. 1; AAP13073)"
FT /evidence="ECO:0000305"
FT CONFLICT 1281
FT /note="I -> T (in Ref. 2; BAA86445)"
FT /evidence="ECO:0000305"
FT HELIX 1270..1272
FT /evidence="ECO:0007829|PDB:2DK3"
FT STRAND 1279..1282
FT /evidence="ECO:0007829|PDB:3DKM"
FT TURN 1289..1292
FT /evidence="ECO:0007829|PDB:3DKM"
FT STRAND 1299..1301
FT /evidence="ECO:0007829|PDB:3DKM"
FT STRAND 1309..1314
FT /evidence="ECO:0007829|PDB:3DKM"
FT TURN 1315..1317
FT /evidence="ECO:0007829|PDB:2DK3"
FT STRAND 1319..1325
FT /evidence="ECO:0007829|PDB:3DKM"
FT HELIX 1326..1328
FT /evidence="ECO:0007829|PDB:3DKM"
FT STRAND 1332..1334
FT /evidence="ECO:0007829|PDB:3DKM"
FT HELIX 1883..1886
FT /evidence="ECO:0007829|PDB:2LC3"
FT HELIX 1896..1902
FT /evidence="ECO:0007829|PDB:2LC3"
FT STRAND 1905..1908
FT /evidence="ECO:0007829|PDB:2LC3"
FT HELIX 1910..1920
FT /evidence="ECO:0007829|PDB:2LC3"
FT HELIX 1923..1928
FT /evidence="ECO:0007829|PDB:2LC3"
FT HELIX 1935..1941
FT /evidence="ECO:0007829|PDB:2LC3"
FT HELIX 1944..1957
FT /evidence="ECO:0007829|PDB:2LC3"
FT TURN 1960..1962
FT /evidence="ECO:0007829|PDB:2LC3"
SQ SEQUENCE 2610 AA; 289368 MW; C02FB51A2AABF98B CRC64;
MADVDPDTLL EWLQMGQGDE RDMQLIALEQ LCMLLLMSDN VDRCFETCPP RTFLPALCKI
FLDESAPDNV LEVTARAITY YLDVSAECTR RIVGVDGAIK ALCNRLVVVE LNNRTSRDLA
EQCVKVLELI CTRESGAVFE AGGLNCVLTF IRDSGHLVHK DTLHSAMAVV SRLCGKMEPQ
DSSLEICVES LSSLLKHEDH QVSDGALRCF ASLADRFTRR GVDPAPLAKH GLTEELLSRM
AAAGGTVSGP SSACKPGRST TGAPSTTADS KLSNQVSTIV SLLSTLCRGS PVVTHDLLRS
ELPDSIESAL QGDERCVLDT MRLVDLLLVL LFEGRKALPK SSAGSTGRIP GLRRLDSSGE
RSHRQLIDCI RSKDTDALID AIDTGAFEVN FMDDVGQTLL NWASAFGTQE MVEFLCERGA
DVNRGQRSSS LHYAACFGRP QVAKTLLRHG ANPDLRDEDG KTPLDKARER GHSEVVAILQ
SPGDWMCPVN KGDDKKKKDT NKDEEECNEP KGDPEMAPIY LKRLLPVFAQ TFQQTMLPSI
RKASLALIRK MIHFCSEALL KEVCDSDVGH NLPTILVEIT ATVLDQEDDD DGHLLALQII
RDLVDKGGDI FLDQLARLGV ISKVSTLAGP SSDDENEEES KPEKEDEPQE DAKELQQGKP
YHWRDWSIIR GRDCLYIWSD AAALELSNGS NGWFRFILDG KLATMYSSGS PEGGSDSSES
RSEFLEKLQR ARGQVKPSTS SQPILSAPGP TKLTVGNWSL TCLKEGEIAI HNSDGQQATI
LKEDLPGFVF ESNRGTKHSF TAETSLGSEF VTGWTGKRGR KLKSKLEKTK QKVRTMARDL
YDDHFKAVES MPRGVVVTLR NIATQLESSW ELHTNRQCIE SENTWRDLMK TALENLIVLL
KDENTISPYE MCSSGLVQAL LTVLNNSMDL DMKQDCSQLV ERINVFKTAF SENEDDESRP
AVALIRKLIA VLESIERLPL HLYDTPGSTY NLQILTRRLR FRLERAPGET ALIDRTGRML
KMEPLATVES LEQYLLKMVA KQWYDFDRSS FVFVRKLREG QNFIFRHQHD FDENGIIYWI
GTNAKTAYEW VNPAAYGLVV VTSSEGRNLP YGRLEDILSR DNSALNCHSN DDKNAWFAID
LGLWVIPSAY TLRHARGYGR SALRNWVFQV SKDGQNWTSL YTHVDDCSLN EPGSTATWPL
DPPKDEKQGW RHVRIKQMGK NASGQTHYLS LSGFELYGTV NGVCEDQLGK AAKEAEANLR
RQRRLVRSQV LKYMVPGARV IRGLDWKWRD QDGSPQGEGT VTGELHNGWI DVTWDAGGSN
SYRMGAEGKF DLKLAPGYDP DTVASPKPVS STVSGTTQSW SSLVKNNCPD KTSAAAGSSS
RKGSSSSVCS VASSSDISLG STKTERRSEI VMEHSIVSGA DVHEPIVVLS SAENVPQTEV
GSSSSASTST LTAETGSENA ERKLGPDSSV RTPGESSAIS MGIVSVSSPD VSSVSELTNK
EAASQRPLSS SASNRLSVSS LLAAGAPMSS SASVPNLSSR ETSSLESFVR RVANIARTNA
TNNMNLSRSS SDNNTNTLGR NVMSTATSPL MGAQSFPNLT TPGTTSTVTM STSSVTSSSN
VATATTVLSV GQSLSNTLTT SLTSTSSESD TGQEAEYSLY DFLDSCRAST LLAELDDDED
LPEPDEEDDE NEDDNQEDQE YEEVMILRRP SLQRRAGSRS DVTHHAVTSQ LPQVPAGAGS
RPIGEQEEEE YETKGGRRRT WDDDYVLKRQ FSALVPAFDP RPGRTNVQQT TDLEIPPPGT
PHSELLEEVE CTPSPRLALT LKVTGLGTTR EVELPLTNFR STIFYYVQKL LQLSCNGNVK
SDKLRRIWEP TYTIMYREMK DSDKEKENGK MGCWSIEHVE QYLGTDELPK NDLITYLQKN
ADAAFLRHWK LTGTNKSIRK NRNCSQLIAA YKDFCEHGTK SGLNQGAIST LQSSDILNLT
KEQPQAKAGN GQNSCGVEDV LQLLRILYIV ASDPYSRISQ EDGDEQPQFT FPPDEFTSKK
ITTKILQQIE EPLALASGAL PDWCEQLTSK CPFLIPFETR QLYFTCTAFG ASRAIVWLQN
RREATVERTR TTSSVRRDDP GEFRVGRLKH ERVKVPRGES LMEWAENVMQ IHADRKSVLE
VEFLGEEGTG LGPTLEFYAL VAAEFQRTDL GAWLCDDNFP DDESRHVDLG GGLKPPGYYV
QRSCGLFTAP FPQDSDELER ITKLFHFLGI FLAKCIQDNR LVDLPISKPF FKLMCMGDIK
SNMSKLIYES RGDRDLHCTE SQSEASTEEG HDSLSVGSFE EDSKSEFILD PPKPKPPAWF
NGILTWEDFE LVNPHRARFL KEIKDLAIKR RQILSNKGLS EDEKNTKLQE LVLKNPSGSG
PPLSIEDLGL NFQFCPSSRI YGFTAVDLKP SGEDEMITMD NAEEYVDLMF DFCMHTGIQK
QMEAFRDGFN KVFPMEKLSS FSHEEVQMIL CGNQSPSWAA EDIINYTEPK LGYTRDSPGF
LRFVRVLCGM SSDERKAFLQ FTTGCSTLPP GGLANLHPRL TVVRKVDATD ASYPSVNTCV
HYLKLPEYSS EEIMRERLLA ATMEKGFHLN
