G2E3_HUMAN
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 03-AUG-2022, entry version 147.
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; Q7L622; -.
DR PeptideAtlas; Q7L622; -.
DR PRIDE; Q7L622; -.
DR ProteomicsDB; 68824; -.
DR Antibodypedia; 11; 126 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 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; 199998at2759; -.
DR PhylomeDB; Q7L622; -.
DR TreeFam; TF325426; -.
DR PathwayCommons; Q7L622; -.
DR SignaLink; Q7L622; -.
DR UniPathway; UPA00143; -.
DR BioGRID-ORCS; 55632; 15 hits in 1113 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 179 other tissues.
DR ExpressionAtlas; Q7L622; baseline and differential.
DR Genevisible; Q7L622; HS.
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 CDD; cd15669; ePHD_PHF7_G2E3_like; 1.
DR CDD; cd15496; PHD_PHF7_G2E3_like; 1.
DR Gene3D; 3.30.40.10; -; 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 Pfam; PF00632; HECT; 1.
DR SMART; SM00119; HECTc; 1.
DR SMART; SM00249; PHD; 2.
DR SUPFAM; SSF56204; SSF56204; 1.
DR SUPFAM; SSF57903; SSF57903; 1.
DR PROSITE; PS51805; EPHD; 1.
DR PROSITE; PS50237; HECT; 1.
DR PROSITE; PS01359; ZF_PHD_1; 1.
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 A-
FT 147 and A-666. No activity; when associated with A-147; A-
FT 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 A-
FT 261."
FT /evidence="ECO:0000269|PubMed:18511420"
FT MUTAGEN 258
FT /note="C->A: Strong activity; when associated with A-84; A-
FT 261 and A-666. No activity; when associated with A-147; A-
FT 261 and A-666. No activity; when associated with A-84; A-
FT 147 and A-261."
FT /evidence="ECO:0000269|PubMed:18511420"
FT MUTAGEN 261
FT /note="C->A: Strong activity; when associated with A-84; A-
FT 258 and A-666. No activity; when associated with A-84; A-
FT 147 and A-258. No activity; when associated with A-147; A-
FT 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
