HECW2_MOUSE
ID HECW2_MOUSE Reviewed; 1578 AA.
AC Q6I6G8; Q3KNL8; Q6ZPU4; Q8C956;
DT 20-FEB-2007, integrated into UniProtKB/Swiss-Prot.
DT 19-JUL-2004, sequence version 1.
DT 03-AUG-2022, entry version 139.
DE RecName: Full=E3 ubiquitin-protein ligase HECW2;
DE EC=2.3.2.26;
DE AltName: Full=HECT, C2 and WW domain-containing protein 2;
DE AltName: Full=HECT-type E3 ubiquitin transferase HECW2;
DE AltName: Full=NEDD4-like E3 ubiquitin-protein ligase 2;
GN Name=Hecw2; Synonyms=Kiaa1301, Nedl2;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RA Miyazaki K., Takeda M., Aiyama Y., Nakagawara A.;
RT "Mus musculus NEDL2 mRNA for NEDD4-like ubiquitin ligase 2.";
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC STRAIN=C57BL/6J; TISSUE=Cerebellum;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 124-1578 (ISOFORM 1).
RC TISSUE=Brain;
RX PubMed=14621295; DOI=10.1093/dnares/10.4.167;
RA Okazaki N., Kikuno R., Ohara R., Inamoto S., Koseki H., Hiraoka S.,
RA Saga Y., Nagase T., Ohara O., Koga H.;
RT "Prediction of the coding sequences of mouse homologues of KIAA gene: III.
RT The complete nucleotide sequences of 500 mouse KIAA-homologous cDNAs
RT identified by screening of terminal sequences of cDNA clones randomly
RT sampled from size-fractionated libraries.";
RL DNA Res. 10:167-180(2003).
RN [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-48, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
CC -!- FUNCTION: E3 ubiquitin-protein ligase that mediates ubiquitination of
CC TP73. Acts to stabilize TP73 and enhance activation of transcription by
CC TP73. Involved in the regulation of mitotic metaphase/anaphase
CC transition. {ECO:0000250|UniProtKB:Q9P2P5}.
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 TP73 (By similarity). Interacts with FZR1 (By
CC similarity). {ECO:0000250|UniProtKB:Q9P2P5}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}. Cytoplasm, cytoskeleton,
CC spindle {ECO:0000250|UniProtKB:Q9P2P5}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q6I6G8-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q6I6G8-2; Sequence=VSP_023078;
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DR EMBL; AB182244; BAD23960.1; -; mRNA.
DR EMBL; AK042922; BAC31406.1; -; mRNA.
DR EMBL; BC107219; AAI07220.1; -; mRNA.
DR EMBL; AK129325; BAC98135.1; -; mRNA.
DR CCDS; CCDS14956.1; -. [Q6I6G8-1]
DR CCDS; CCDS14957.1; -. [Q6I6G8-2]
DR RefSeq; NP_001001883.1; NM_001001883.3. [Q6I6G8-1]
DR RefSeq; NP_766243.2; NM_172655.3. [Q6I6G8-2]
DR RefSeq; XP_006496129.1; XM_006496066.3. [Q6I6G8-1]
DR RefSeq; XP_006496130.1; XM_006496067.1. [Q6I6G8-1]
DR RefSeq; XP_006496131.1; XM_006496068.3. [Q6I6G8-1]
DR AlphaFoldDB; Q6I6G8; -.
DR BMRB; Q6I6G8; -.
DR SMR; Q6I6G8; -.
DR STRING; 10090.ENSMUSP00000113283; -.
DR iPTMnet; Q6I6G8; -.
DR PhosphoSitePlus; Q6I6G8; -.
DR MaxQB; Q6I6G8; -.
DR PaxDb; Q6I6G8; -.
DR PeptideAtlas; Q6I6G8; -.
DR PRIDE; Q6I6G8; -.
DR ProteomicsDB; 269691; -. [Q6I6G8-1]
DR ProteomicsDB; 269692; -. [Q6I6G8-2]
DR Antibodypedia; 34059; 189 antibodies from 26 providers.
DR DNASU; 329152; -.
DR Ensembl; ENSMUST00000087659; ENSMUSP00000084942; ENSMUSG00000042807. [Q6I6G8-1]
DR Ensembl; ENSMUST00000097741; ENSMUSP00000095348; ENSMUSG00000042807. [Q6I6G8-2]
DR Ensembl; ENSMUST00000120904; ENSMUSP00000113283; ENSMUSG00000042807. [Q6I6G8-1]
DR GeneID; 329152; -.
DR KEGG; mmu:329152; -.
DR UCSC; uc007azk.2; mouse. [Q6I6G8-1]
DR CTD; 57520; -.
DR MGI; MGI:2685817; Hecw2.
DR VEuPathDB; HostDB:ENSMUSG00000042807; -.
DR eggNOG; KOG0940; Eukaryota.
DR GeneTree; ENSGT00940000155466; -.
DR HOGENOM; CLU_002173_14_0_1; -.
DR InParanoid; Q6I6G8; -.
DR OMA; TAGQHRE; -.
DR OrthoDB; 117748at2759; -.
DR PhylomeDB; Q6I6G8; -.
DR TreeFam; TF313938; -.
DR Reactome; R-MMU-983168; Antigen processing: Ubiquitination & Proteasome degradation.
DR UniPathway; UPA00143; -.
DR BioGRID-ORCS; 329152; 0 hits in 73 CRISPR screens.
DR ChiTaRS; Hecw2; mouse.
DR PRO; PR:Q6I6G8; -.
DR Proteomes; UP000000589; Chromosome 1.
DR RNAct; Q6I6G8; protein.
DR Bgee; ENSMUSG00000042807; Expressed in epithelium of stomach and 183 other tissues.
DR ExpressionAtlas; Q6I6G8; baseline and differential.
DR Genevisible; Q6I6G8; MM.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0072686; C:mitotic spindle; ISO:MGI.
DR GO; GO:0061630; F:ubiquitin protein ligase activity; IBA:GO_Central.
DR GO; GO:2000650; P:negative regulation of sodium ion transmembrane transporter activity; IBA:GO_Central.
DR GO; GO:0043161; P:proteasome-mediated ubiquitin-dependent protein catabolic process; IBA:GO_Central.
DR GO; GO:0000209; P:protein polyubiquitination; IBA:GO_Central.
DR GO; GO:0016567; P:protein ubiquitination; IBA:GO_Central.
DR GO; GO:0048814; P:regulation of dendrite morphogenesis; IBA:GO_Central.
DR GO; GO:0030071; P:regulation of mitotic metaphase/anaphase transition; ISO:MGI.
DR CDD; cd08691; C2_NEDL1-like; 1.
DR CDD; cd00078; HECTc; 1.
DR CDD; cd00201; WW; 2.
DR Gene3D; 2.60.40.150; -; 1.
DR InterPro; IPR000008; C2_dom.
DR InterPro; IPR035892; C2_domain_sf.
DR InterPro; IPR037795; C2_HECW.
DR InterPro; IPR000569; HECT_dom.
DR InterPro; IPR035983; Hect_E3_ubiquitin_ligase.
DR InterPro; IPR040524; HECW1_helix.
DR InterPro; IPR032348; HECW_N.
DR InterPro; IPR001202; WW_dom.
DR InterPro; IPR036020; WW_dom_sf.
DR Pfam; PF00168; C2; 1.
DR Pfam; PF00632; HECT; 1.
DR Pfam; PF18436; HECW1_helix; 1.
DR Pfam; PF16562; HECW_N; 1.
DR Pfam; PF00397; WW; 1.
DR SMART; SM00239; C2; 1.
DR SMART; SM00119; HECTc; 1.
DR SMART; SM00456; WW; 2.
DR SUPFAM; SSF49562; SSF49562; 1.
DR SUPFAM; SSF51045; SSF51045; 2.
DR SUPFAM; SSF56204; SSF56204; 1.
DR PROSITE; PS50004; C2; 1.
DR PROSITE; PS50237; HECT; 1.
DR PROSITE; PS01159; WW_DOMAIN_1; 2.
DR PROSITE; PS50020; WW_DOMAIN_2; 2.
PE 1: Evidence at protein level;
KW Alternative splicing; Coiled coil; Cytoplasm; Cytoskeleton; Phosphoprotein;
KW Reference proteome; Repeat; Transferase; Ubl conjugation pathway.
FT CHAIN 1..1578
FT /note="E3 ubiquitin-protein ligase HECW2"
FT /id="PRO_0000277668"
FT DOMAIN 171..298
FT /note="C2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT DOMAIN 813..846
FT /note="WW 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00224"
FT DOMAIN 991..1024
FT /note="WW 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00224"
FT DOMAIN 1243..1578
FT /note="HECT"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00104"
FT REGION 341..453
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 496..802
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 737..1074
FT /note="Interaction with TP73"
FT /evidence="ECO:0000250"
FT REGION 1030..1075
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1167..1193
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 853..880
FT /evidence="ECO:0000255"
FT COMPBIAS 381..412
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 436..453
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 509..534
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 543..627
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 641..672
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 691..710
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 781..802
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1169..1187
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 1546
FT /note="Glycyl thioester intermediate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00104"
FT MOD_RES 48
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 858
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9P2P5"
FT MOD_RES 915
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9P2P5"
FT MOD_RES 1181
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9P2P5"
FT VAR_SEQ 295..1578
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:16141072"
FT /id="VSP_023078"
FT CONFLICT 226
FT /note="H -> R (in Ref. 2; BAC31406)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1578 AA; 176235 MW; 6711C52EA0AF9CBF CRC64;
MASSAREHLL FVRRRNPQMR YTLSPENLQS LAAQNSMPEN MALQRANSDT DLVTSESRSS
LTASMYEYTL GQAQNLIIFW DIKEEVDPSD WIGLYHIDEN SPANFWDSKN RGVTGTQKGQ
IVWRIEPGPY FMEPEIKICF KYYHGISGAL RATTPCITVK NPAVMMGAEG MEGGASGSLH
SRKLVSFTLS DLRAVGLKKG MFFNPDPYLK MSIQPGKKSS FPTCAHHGQE RRSTIISNTT
NPIWHREKYS FFALLTDVLE IEIKDKFAKS RPIIKRFLGK LTIPVQRLLE RQAGDQMLSY
NLGRRLPADH VSGYLQFKVE VTSSAHEDAS PEAVGTILGV HTVNGDLGSP SDEEDMPGSH
HDSTICANGP VSEDSVADGT PKHSFRTSST LEIDTEDLIS TSSRNSPPRG RQDSLNDYLD
AIEHNGPARP GAASSSERSM GASPKLRSSF PTDTRLNAML HIDSDEEDHE FQQDLGYPSS
LEEEGGLIMC SRASRIDDGS LTSQTKPEDD NPVENEDASI HETASLEERL ENLPEVADGS
LPSSTAPDEN EANLEPQPSA DQGSTELCSS QEVDQPTSGA DAGASDTSGG SRRAASETES
LDQGSEPSQV SSETEPSDPA RTESVSEAST RPEGESDPEG ADSSCNESVT TQLSSVETRC
SSLESARFPE TPAFSSQEEE DGACAAEPTS SGPAEGSQES VCTPSSLPAV QVPSREEEGS
AAEAAALSEQ GELGEVWQRR GSLEGAAAAA PAAAATDSQP QEDGDAGDAQ GACEGATAQE
EGATGGSQTN GHQPLRSLPS VRQDVSRYQR VDEALPPNWE ARIDSHGRIF YVDHVNRTTT
WQRPTAPPAP QVLQRSNSIQ QMEQLNRRYQ SIRRTMTNER PEENTSAIDG AGEEADFHQA
SADFRRENVL PHSTSRSRLT LLLQSPPVKF LISPEFFTVL HSNPSAYRMF TNNTCLKHMI
TKVRRDTHHF ERYQHNRDLV GFLNMFANKQ LELPRGWEMK HDHQGKAFFV DHNSRTTTFI
DPRLPLQSSR PTSALVHRQH LTRQRSHSAG EVGEDSRHAG PPVLPRPSST FNTVSRPQYQ
DMVPVAYNDK IVAFLRQPNI LEILQERQPD LARNHSLREK IQFIRTEGTP GLVRLSSDAD
LVMLLSLFEE EIMSYVPPHA LLHPSYCQSP RGSPVSSPQN SPGTQRANAR APAPYKRDFE
AKLRNFYRKL ETKGYGQGPG KLKLIIRRDH LLEDAFNQIM GYSRKDLQRN KLYVTFVGEE
GLDYSGPSRE FFFLVSRELF NPYYGLFEYS ANDTYTVQIS PMSAFVDNHH EWFRFSGRIL
GLALIHQYLL DAFFTRPFYK ALLRILCDLS DLEYLDEEFH QSLQWMKDND IHDILDLTFT
VNEEVFGQIT ERELKPGGAN IPVTEKNKKE YIERMVKWRI ERGVVQQTES LVRGFYEVVD
ARLVSVFDAR ELELVIAGTA EIDLNDWRNN TEYRGGYHDN HIVIRWFWAA VERFNNEQRL
RLLQFVTGTS SIPYEGFASL RGSNGPRRFC VEKWGKITAL PRAHTCFNRL DLPPYPSFSM
LYEKLLTAVE ETSTFGLE
