ID G2E3_HUMAN Reviewed; 706 AA. AC Q7L622; Q9BVR2; Q9H9E9; Q9NXC0; Q9P2L3; DT 05-SEP-2006, integrated into UniProtKB/Swiss-Prot. DT 05-JUL-2004, sequence version 1. DT 27-MAR-2024, entry version 156. DE RecName: Full=G2/M phase-specific E3 ubiquitin-protein ligase; DE EC=2.3.2.26; DE AltName: Full=G2/M phase-specific HECT-type E3 ubiquitin transferase; GN Name=G2E3; Synonyms=KIAA1333; 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], SUBCELLULAR LOCATION, AND MUTAGENESIS OF RP 30-LYS-LYS-31 AND CYS-666. RX PubMed=17239372; DOI=10.1016/j.yexcr.2006.11.020; RA Brooks W.S., Banerjee S., Crawford D.F.; RT "G2E3 is a nucleo-cytoplasmic shuttling protein with DNA damage responsive RT localization."; RL Exp. Cell Res. 313:665-676(2007). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND TISSUE SPECIFICITY. RC TISSUE=Brain; RX PubMed=10718198; DOI=10.1093/dnares/7.1.65; RA Nagase T., Kikuno R., Ishikawa K., Hirosawa M., Ohara O.; RT "Prediction of the coding sequences of unidentified human genes. XVI. The RT complete sequences of 150 new cDNA clones from brain which code for large RT proteins in vitro."; RL DNA Res. 7:65-73(2000). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Hepatoma, and Teratocarcinoma; 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 [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Placenta; 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 INDUCTION. RX PubMed=11483598; DOI=10.1074/jbc.m103414200; RA Crawford D.F., Piwnica-Worms H.; RT "The G(2) DNA damage checkpoint delays expression of genes encoding mitotic RT regulators."; RL J. Biol. Chem. 276:37166-37177(2001). RN [6] RP FUNCTION, DOMAIN, AND MUTAGENESIS OF CYS-84; CYS-147; CYS-258; CYS-261 AND RP CYS-666. RX PubMed=18511420; DOI=10.1074/jbc.m803238200; RA Brooks W.S., Helton E.S., Banerjee S., Venable M., Johnson L., Schoeb T.R., RA Kesterson R.A., Crawford D.F.; RT "G2E3 is a dual function ubiquitin ligase required for early embryonic RT development."; RL J. Biol. Chem. 283:22304-22315(2008). 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. Essential in CC early embryonic development to prevent apoptotic death. CC {ECO:0000269|PubMed:18511420}. 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 -!- INTERACTION: CC Q7L622; Q86V38: ATN1; NbExp=3; IntAct=EBI-751757, EBI-11954292; CC Q7L622; P42858: HTT; NbExp=6; IntAct=EBI-751757, EBI-466029; CC Q7L622; Q92876: KLK6; NbExp=3; IntAct=EBI-751757, EBI-2432309; CC Q7L622; P07196: NEFL; NbExp=3; IntAct=EBI-751757, EBI-475646; CC Q7L622; P62841: RPS15; NbExp=3; IntAct=EBI-751757, EBI-372635; CC Q7L622; Q7Z699: SPRED1; NbExp=3; IntAct=EBI-751757, EBI-5235340; CC Q7L622; O76024: WFS1; NbExp=3; IntAct=EBI-751757, EBI-720609; CC -!- SUBCELLULAR LOCATION: Nucleus, nucleolus {ECO:0000269|PubMed:17239372}. CC Cytoplasm {ECO:0000269|PubMed:17239372}. Note=Shuttles between the CC nucleus and the cytoplasm. In the nucleus, delocalizes from the CC nucleolus to the nucleoplasm in response to DNA damage. CC {ECO:0000269|PubMed:17239372}. CC -!- TISSUE SPECIFICITY: Predominantly expressed in brain, liver, kidney, CC testes and ovary. {ECO:0000269|PubMed:10718198}. CC -!- INDUCTION: Up-regulated approximately 4-fold in G2 when compared to S CC phase. Down-regulated approximately 3-fold by gamma-irradiation. CC {ECO:0000269|PubMed:11483598}. CC -!- DOMAIN: Ubiquitin ligase activity is mediated by two distinct domains, CC PHD-type zinc fingers 2 and 3. The use of these distinct domains may CC allow ubiquitination of different targets by each domain. The HECT CC domain is catalytically inactive and does not contribute to this CC activity. {ECO:0000269|PubMed:18511420}. CC -!- SEQUENCE CAUTION: CC Sequence=BAA92571.1; Type=Erroneous initiation; Evidence={ECO:0000305}; CC Sequence=BAB14280.1; Type=Erroneous initiation; Evidence={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; AB037754; BAA92571.1; ALT_INIT; mRNA. DR EMBL; AK000340; BAA91095.1; -; mRNA. DR EMBL; AK022867; BAB14280.1; ALT_INIT; mRNA. DR EMBL; BC000973; AAH00973.2; -; mRNA. DR CCDS; CCDS9638.1; -. DR RefSeq; NP_001295026.1; NM_001308097.1. DR RefSeq; NP_060239.2; NM_017769.4. DR RefSeq; XP_011535227.1; XM_011536925.2. DR AlphaFoldDB; Q7L622; -. DR SMR; Q7L622; -. DR BioGRID; 120771; 19. DR IntAct; Q7L622; 15. DR MINT; Q7L622; -. DR STRING; 9606.ENSP00000206595; -. DR iPTMnet; Q7L622; -. DR PhosphoSitePlus; Q7L622; -. DR BioMuta; G2E3; -. DR DMDM; 74738611; -. DR EPD; Q7L622; -. DR jPOST; Q7L622; -. DR MassIVE; Q7L622; -. DR MaxQB; Q7L622; -. DR PaxDb; 9606-ENSP00000206595; -. DR PeptideAtlas; Q7L622; -. DR ProteomicsDB; 68824; -. DR Pumba; Q7L622; -. DR Antibodypedia; 11; 143 antibodies from 19 providers. DR DNASU; 55632; -. DR Ensembl; ENST00000206595.11; ENSP00000206595.6; ENSG00000092140.16. DR GeneID; 55632; -. DR KEGG; hsa:55632; -. DR MANE-Select; ENST00000206595.11; ENSP00000206595.6; NM_017769.5; NP_060239.2. DR UCSC; uc001wqk.3; human. DR AGR; HGNC:20338; -. DR CTD; 55632; -. DR DisGeNET; 55632; -. DR GeneCards; G2E3; -. DR HGNC; HGNC:20338; G2E3. DR HPA; ENSG00000092140; Tissue enhanced (testis). DR MIM; 611299; gene. DR neXtProt; NX_Q7L622; -. DR OpenTargets; ENSG00000092140; -. DR PharmGKB; PA164720127; -. DR VEuPathDB; HostDB:ENSG00000092140; -. DR eggNOG; KOG1084; Eukaryota. DR GeneTree; ENSGT00950000182865; -. DR InParanoid; Q7L622; -. DR OrthoDB; 2899995at2759; -. DR PhylomeDB; Q7L622; -. DR TreeFam; TF325426; -. DR PathwayCommons; Q7L622; -. DR SignaLink; Q7L622; -. DR SIGNOR; Q7L622; -. DR UniPathway; UPA00143; -. DR BioGRID-ORCS; 55632; 15 hits in 1191 CRISPR screens. DR ChiTaRS; G2E3; human. DR GeneWiki; KIAA1333; -. DR GenomeRNAi; 55632; -. DR Pharos; Q7L622; Tbio. DR PRO; PR:Q7L622; -. DR Proteomes; UP000005640; Chromosome 14. DR RNAct; Q7L622; Protein. DR Bgee; ENSG00000092140; Expressed in sperm and 181 other cell types or tissues. DR ExpressionAtlas; Q7L622; baseline and differential. DR GO; GO:0005829; C:cytosol; IDA:HPA. DR GO; GO:0005794; C:Golgi apparatus; IDA:HPA. DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:HPA. DR GO; GO:0005730; C:nucleolus; IEA:UniProtKB-SubCell. DR GO; GO:0005634; C:nucleus; IBA:GO_Central. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0004842; F:ubiquitin-protein transferase activity; IEA:InterPro. DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW. DR GO; GO:0016567; P:protein ubiquitination; IEA:UniProtKB-UniPathway. DR CDD; cd15669; ePHD_PHF7_G2E3_like; 1. DR CDD; cd15496; PHD_PHF7_G2E3_like; 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 Gene3D; 3.30.40.10; Zinc/RING finger domain, C3HC4 (zinc finger); 2. DR InterPro; IPR034732; EPHD. DR InterPro; IPR000569; HECT_dom. DR InterPro; IPR035983; Hect_E3_ubiquitin_ligase. DR InterPro; IPR042013; PHF7/G2E3_ePHD. DR InterPro; IPR042012; PHF7/G2E3_PHD. DR InterPro; IPR019786; Zinc_finger_PHD-type_CS. DR InterPro; IPR011011; Znf_FYVE_PHD. DR InterPro; IPR001965; Znf_PHD. DR InterPro; IPR013083; Znf_RING/FYVE/PHD. DR PANTHER; PTHR12420:SF37; G2_M PHASE-SPECIFIC E3 UBIQUITIN-PROTEIN LIGASE; 1. DR PANTHER; PTHR12420; PHD FINGER PROTEIN; 1. DR Pfam; PF00632; HECT; 1. DR Pfam; PF13771; zf-HC5HC2H; 1. DR SMART; SM00119; HECTc; 1. DR SMART; SM00249; PHD; 2. DR SUPFAM; SSF57903; FYVE/PHD zinc finger; 1. DR SUPFAM; SSF56204; Hect, E3 ligase catalytic domain; 1. DR PROSITE; PS51805; EPHD; 1. DR PROSITE; PS50237; HECT; 1. DR PROSITE; PS01359; ZF_PHD_1; 1. DR Genevisible; Q7L622; HS. PE 1: Evidence at protein level; KW Apoptosis; Cytoplasm; Developmental protein; Metal-binding; Nucleus; KW Reference proteome; Repeat; Transferase; Ubl conjugation pathway; Zinc; KW Zinc-finger. FT CHAIN 1..706 FT /note="G2/M phase-specific E3 ubiquitin-protein ligase" FT /id="PRO_0000248343" FT DOMAIN 371..698 FT /note="HECT" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00104" FT ZN_FING 11..51 FT /note="C2HC pre-PHD-type" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01146" FT ZN_FING 79..128 FT /note="PHD-type 1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01146" FT ZN_FING 143..193 FT /note="PHD-type 2; degenerate" FT ZN_FING 237..286 FT /note="PHD-type 3" FT VARIANT 232 FT /note="R -> H (in dbSNP:rs17096934)" FT /id="VAR_027273" FT MUTAGEN 30..31 FT /note="KK->AA: Loss of nucleolar localization. No effect on FT nuclear localization." FT /evidence="ECO:0000269|PubMed:17239372" FT MUTAGEN 84 FT /note="C->A: Strong activity; when associated with A-258; FT A-261 and A-666. Strong activity; when associated with FT A-147 and A-666. No activity; when associated with A-147; FT A-258 and A-261." FT /evidence="ECO:0000269|PubMed:18511420" FT MUTAGEN 147 FT /note="C->A: Strong activity; when associated with A-84 and FT A-666. No activity; when associated with A-258; A-261 and FT A-666. No activity; when associated with A-84; A-258 and FT A-261." FT /evidence="ECO:0000269|PubMed:18511420" FT MUTAGEN 258 FT /note="C->A: Strong activity; when associated with A-84; FT A-261 and A-666. No activity; when associated with A-147; FT A-261 and A-666. No activity; when associated with A-84; FT A-147 and A-261." FT /evidence="ECO:0000269|PubMed:18511420" FT MUTAGEN 261 FT /note="C->A: Strong activity; when associated with A-84; FT A-258 and A-666. No activity; when associated with A-84; FT A-147 and A-258. No activity; when associated with A-147; FT A-258 and A-666." FT /evidence="ECO:0000269|PubMed:18511420" FT MUTAGEN 666 FT /note="C->A: No effect on subcellular location. Strong FT activity; when associated with A-84; A-258 and A261. Strong FT activity; when associated with A-84 and A-147. No activity; FT when associated with A-147; A-258 and A-261." FT /evidence="ECO:0000269|PubMed:17239372, FT ECO:0000269|PubMed:18511420" FT CONFLICT 184 FT /note="V -> A (in Ref. 3; BAA91095)" FT /evidence="ECO:0000305" FT CONFLICT 627 FT /note="T -> A (in Ref. 3; BAB14280)" FT /evidence="ECO:0000305" FT CONFLICT 665 FT /note="K -> E (in Ref. 3; BAA91095)" FT /evidence="ECO:0000305" SQ SEQUENCE 706 AA; 80504 MW; 4B46ACF8782F941A CRC64; MNESKPGDSQ NLACVFCRKH DDCPNKYGEK KTKEKWNLTV HYYCLLMSSG IWQRGKEEEG VYGFLIEDIR KEVNRASKLK CCVCKKNGAS IGCVAPRCKR SYHFPCGLQR ECIFQFTGNF ASFCWDHRPV QIITSNNYRE SLPCTICLEF IEPIPSYNIL RSPCCKNAWF HRDCLQVQAI NAGVFFFRCT ICNNSDIFQK EMLRMGIHIP EKDASWELEE NAYQELLQHY ERCDVRRCRC KEGRDYNAPD SKWEIKRCQC CGSSGTHLAC SSLRSWEQNW ECLECRGIIY NSGEFQKAKK HVLPNSNNVG ITDCLLEESS PKLPRQSPGS QSKDLLRQGS KFRRNVSTLL IELGFQIKKK TKRLYINKAN IWNSALDAFR NRNFNPSYAI EVAYVIENDN FGSEHPGSKQ EFLSLLMQHL ENSSLFEGSL SKNLSLNSQA LKENLYYEAG KMLAISLVHG GPSPGFFSKT LFNCLVYGPE NTQPILDDVS DFDVAQIIIR INTATTVADL KSIINECYNY LELIGCLRLI TTLSDKYMLV KDILGYHVIQ RVHTPFESFK QGLKTLGVLE KIQAYPEAFC SILCHKPESL SAKILSELFT VHTLPDVKAL GFWNSYLQAV EDGKSTTTME DILIFATGCS SIPPAGFKPT PSIECLHVDF PVGNKCNNCL AIPITNTYKE FQENMDFTIR NTLRLEKEES SHYIGH //