HECD2_HUMAN
ID HECD2_HUMAN Reviewed; 776 AA.
AC Q5U5R9; Q5VZ97; Q5VZ98; Q5VZ99; Q8N1X7; Q8TCP5;
DT 27-JUN-2006, integrated into UniProtKB/Swiss-Prot.
DT 27-JUN-2006, sequence version 2.
DT 03-AUG-2022, entry version 147.
DE RecName: Full=Probable E3 ubiquitin-protein ligase HECTD2;
DE EC=2.3.2.26 {ECO:0000305|PubMed:28584101};
DE AltName: Full=HECT domain-containing protein 2;
DE AltName: Full=HECT-type E3 ubiquitin transferase HECTD2;
GN Name=HECTD2 {ECO:0000303|PubMed:28584101, ECO:0000312|HGNC:HGNC:26736};
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 VARIANT ALA-19.
RC TISSUE=Amygdala;
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=15164054; DOI=10.1038/nature02462;
RA Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L.,
RA Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K.,
RA Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L.,
RA Taylor A., Battles J., Bird C.P., Ainscough R., Almeida J.P.,
RA Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y.,
RA Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N.,
RA Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A.,
RA Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C.,
RA Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D.,
RA Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C.,
RA Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K.,
RA Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A.,
RA Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S.,
RA McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S.,
RA Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V.,
RA Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A.,
RA Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M.,
RA Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A.,
RA Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P.,
RA Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y.,
RA Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D.,
RA Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 10.";
RL Nature 429:375-381(2004).
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] (ISOFORM 1), AND VARIANT ALA-19.
RC TISSUE=Brain;
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 NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 541-776 (ISOFORM 1).
RC TISSUE=Amygdala;
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 FUNCTION, FUNCTION (MICROBIAL INFECTION), AND CATALYTIC ACTIVITY.
RX PubMed=28584101; DOI=10.1073/pnas.1621076114;
RA Tsai Y.C., Kotiya A., Kiris E., Yang M., Bavari S., Tessarollo L.,
RA Oyler G.A., Weissman A.M.;
RT "Deubiquitinating enzyme VCIP135 dictates the duration of botulinum
RT neurotoxin type A intoxication.";
RL Proc. Natl. Acad. Sci. U.S.A. 114:E5158-E5166(2017).
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 {ECO:0000269|PubMed:28584101}.
CC -!- FUNCTION: (Microbial infection) Catalyzes ubiquitination of Botulinum
CC neurotoxin A light chain (LC) of C.botulinum neurotoxin type A
CC (BoNT/A). {ECO:0000269|PubMed:28584101}.
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:0000305|PubMed:28584101};
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC {ECO:0000269|PubMed:28584101}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q5U5R9-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q5U5R9-2; Sequence=VSP_044965, VSP_044966;
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DR EMBL; AK094625; BAC04388.1; -; mRNA.
DR EMBL; AC023902; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL161798; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471066; EAW50111.1; -; Genomic_DNA.
DR EMBL; BC040187; AAH40187.1; -; mRNA.
DR EMBL; AL713675; CAD28480.1; -; mRNA.
DR CCDS; CCDS7414.1; -. [Q5U5R9-1]
DR CCDS; CCDS7415.1; -. [Q5U5R9-2]
DR RefSeq; NP_001271203.1; NM_001284274.2.
DR RefSeq; NP_775768.3; NM_173497.3. [Q5U5R9-2]
DR RefSeq; NP_877497.3; NM_182765.5. [Q5U5R9-1]
DR AlphaFoldDB; Q5U5R9; -.
DR SMR; Q5U5R9; -.
DR BioGRID; 126794; 12.
DR IntAct; Q5U5R9; 3.
DR STRING; 9606.ENSP00000401023; -.
DR iPTMnet; Q5U5R9; -.
DR PhosphoSitePlus; Q5U5R9; -.
DR BioMuta; HECTD2; -.
DR DMDM; 109892196; -.
DR EPD; Q5U5R9; -.
DR MassIVE; Q5U5R9; -.
DR MaxQB; Q5U5R9; -.
DR PaxDb; Q5U5R9; -.
DR PeptideAtlas; Q5U5R9; -.
DR PRIDE; Q5U5R9; -.
DR ProteomicsDB; 65231; -. [Q5U5R9-1]
DR ProteomicsDB; 65686; -.
DR Antibodypedia; 30347; 193 antibodies from 26 providers.
DR DNASU; 143279; -.
DR Ensembl; ENST00000298068.10; ENSP00000298068.5; ENSG00000165338.17. [Q5U5R9-1]
DR Ensembl; ENST00000371681.8; ENSP00000360746.4; ENSG00000165338.17. [Q5U5R9-2]
DR GeneID; 143279; -.
DR KEGG; hsa:143279; -.
DR MANE-Select; ENST00000298068.10; ENSP00000298068.5; NM_182765.6; NP_877497.4.
DR UCSC; uc001khk.4; human. [Q5U5R9-1]
DR CTD; 143279; -.
DR DisGeNET; 143279; -.
DR GeneCards; HECTD2; -.
DR HGNC; HGNC:26736; HECTD2.
DR HPA; ENSG00000165338; Low tissue specificity.
DR neXtProt; NX_Q5U5R9; -.
DR OpenTargets; ENSG00000165338; -.
DR PharmGKB; PA134933711; -.
DR VEuPathDB; HostDB:ENSG00000165338; -.
DR eggNOG; KOG0941; Eukaryota.
DR GeneTree; ENSGT00940000157750; -.
DR HOGENOM; CLU_1325997_0_0_1; -.
DR InParanoid; Q5U5R9; -.
DR OMA; WFSSWKS; -.
DR OrthoDB; 339404at2759; -.
DR PhylomeDB; Q5U5R9; -.
DR TreeFam; TF315189; -.
DR PathwayCommons; Q5U5R9; -.
DR Reactome; R-HSA-983168; Antigen processing: Ubiquitination & Proteasome degradation.
DR SignaLink; Q5U5R9; -.
DR UniPathway; UPA00143; -.
DR BioGRID-ORCS; 143279; 38 hits in 1123 CRISPR screens.
DR ChiTaRS; HECTD2; human.
DR GenomeRNAi; 143279; -.
DR Pharos; Q5U5R9; Tbio.
DR PRO; PR:Q5U5R9; -.
DR Proteomes; UP000005640; Chromosome 10.
DR RNAct; Q5U5R9; protein.
DR Bgee; ENSG00000165338; Expressed in calcaneal tendon and 181 other tissues.
DR ExpressionAtlas; Q5U5R9; baseline and differential.
DR Genevisible; Q5U5R9; HS.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0061630; F:ubiquitin protein ligase activity; IBA:GO_Central.
DR CDD; cd00078; HECTc; 1.
DR InterPro; IPR000569; HECT_dom.
DR InterPro; IPR035983; Hect_E3_ubiquitin_ligase.
DR Pfam; PF00632; HECT; 1.
DR SMART; SM00119; HECTc; 1.
DR SUPFAM; SSF56204; SSF56204; 1.
DR PROSITE; PS50237; HECT; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Phosphoprotein; Reference proteome; Transferase;
KW Ubl conjugation pathway.
FT CHAIN 1..776
FT /note="Probable E3 ubiquitin-protein ligase HECTD2"
FT /id="PRO_0000240851"
FT DOMAIN 437..776
FT /note="HECT"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00104"
FT REGION 1..46
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 744
FT /note="Glycyl thioester intermediate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00104"
FT MOD_RES 9
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8CDU6"
FT VAR_SEQ 201..207
FT /note="PQDVQKT -> VSIMTCK (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_044965"
FT VAR_SEQ 208..776
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_044966"
FT VARIANT 19
FT /note="P -> A (in dbSNP:rs7081569)"
FT /evidence="ECO:0000269|PubMed:14702039,
FT ECO:0000269|PubMed:15489334"
FT /id="VAR_026836"
FT CONFLICT 85
FT /note="P -> L (in Ref. 4; AAH40187)"
FT /evidence="ECO:0000305"
FT CONFLICT 519
FT /note="L -> F (in Ref. 4; AAH40187)"
FT /evidence="ECO:0000305"
FT CONFLICT 540
FT /note="D -> G (in Ref. 4; AAH40187)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 776 AA; 88122 MW; 45B98DD76B33AB1A CRC64;
MSEAVRVPSP ATPLVVAAPA PEERKGKESE REKLPPIVSA GAGATAGLDR GAKGQISTFS
SFISAVSPKK EAAENRSSPA HLVFPNIKNV REPPPICLDV RQKQRTSMDA SSSEMKAPVL
PEPILPIQPK TVKDFQEDVE KVKSSGDWKA VHDFYLTTFD SFPELNAAFK KDATASFNTI
EDSGINAKFV NAVYDTLLNT PQDVQKTVLK GIINSLLREW KGPRTKDDLR AYFILLQNPQ
FNNTSTYVIY AHLLRQIATL VEADHHFLVH WFKKLSQKRF KQLVERLLQF ISLRLFPAKP
EEFPPITKCS WWIPSAAKVL ALLNTANNLV HPPLIPYTDF YNSTLDHIDL MEEYHTWQNF
GNSHRFSFCQ YPFVISVAAK KIIIQRDSEQ QMINIARQSL VDKVSRRQRP DMNILFLNMK
VRRTHLVSDS LDELTRKRAD LKKKLKVTFV GEAGLDMGGL TKEWFLLLIR QIFHPDYGMF
TYHKDSHCHW FSSFKCDNYS EFRLVGILMG LAVYNSITLD IRFPPCCYKK LLSPPIIPSD
QNIPVGICNV TVDDLCQIMP ELAHGLSELL SHEGNVEEDF YSTFQVFQEE FGIIKSYNLK
PGGDKISVTN QNRKEYVQLY TDFLLNKSIY KQFAAFYYGF HSVCASNALM LLRPEEVEIL
VCGSPDLDMH ALQRSTQYDG YAKTDLTIKY FWDVVLGFPL DLQKKLLHFT TGSDRVPVGG
MADLNFKISK NETSTNCLPV AHTCFNQLCL PPYKSKKDLK QKLIIGISNS EGFGLE
