GID8_HUMAN
ID GID8_HUMAN Reviewed; 228 AA.
AC Q9NWU2; E1P5I3; Q8N5M5;
DT 01-FEB-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2000, sequence version 1.
DT 03-AUG-2022, entry version 160.
DE RecName: Full=Glucose-induced degradation protein 8 homolog;
DE AltName: Full=Two hybrid-associated protein 1 with RanBPM {ECO:0000303|PubMed:28829046};
DE Short=Twa1 {ECO:0000303|PubMed:28829046};
GN Name=GID8;
GN Synonyms=C20orf11, TWA1 {ECO:0000303|PubMed:12559565,
GN ECO:0000303|PubMed:24143168, ECO:0000303|PubMed:28829046};
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, INTERACTION WITH RANBP9,
RP AND IDENTIFICATION IN A COMPLEX WITH MKLN1 AND RANBP9.
RX PubMed=12559565; DOI=10.1016/s0378-1119(02)01153-8;
RA Umeda M., Nishitani H., Nishimoto T.;
RT "A novel nuclear protein, Twa1, and Muskelin comprise a complex with
RT RanBPM.";
RL Gene 303:47-54(2003).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Gastric carcinoma;
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=11780052; DOI=10.1038/414865a;
RA Deloukas P., Matthews L.H., Ashurst J.L., Burton J., Gilbert J.G.R.,
RA Jones M., Stavrides G., Almeida J.P., Babbage A.K., Bagguley C.L.,
RA Bailey J., Barlow K.F., Bates K.N., Beard L.M., Beare D.M., Beasley O.P.,
RA Bird C.P., Blakey S.E., Bridgeman A.M., Brown A.J., Buck D., Burrill W.D.,
RA Butler A.P., Carder C., Carter N.P., Chapman J.C., Clamp M., Clark G.,
RA Clark L.N., Clark S.Y., Clee C.M., Clegg S., Cobley V.E., Collier R.E.,
RA Connor R.E., Corby N.R., Coulson A., Coville G.J., Deadman R., Dhami P.D.,
RA Dunn M., Ellington A.G., Frankland J.A., Fraser A., French L., Garner P.,
RA Grafham D.V., Griffiths C., Griffiths M.N.D., Gwilliam R., Hall R.E.,
RA Hammond S., Harley J.L., Heath P.D., Ho S., Holden J.L., Howden P.J.,
RA Huckle E., Hunt A.R., Hunt S.E., Jekosch K., Johnson C.M., Johnson D.,
RA Kay M.P., Kimberley A.M., King A., Knights A., Laird G.K., Lawlor S.,
RA Lehvaeslaiho M.H., Leversha M.A., Lloyd C., Lloyd D.M., Lovell J.D.,
RA Marsh V.L., Martin S.L., McConnachie L.J., McLay K., McMurray A.A.,
RA Milne S.A., Mistry D., Moore M.J.F., Mullikin J.C., Nickerson T.,
RA Oliver K., Parker A., Patel R., Pearce T.A.V., Peck A.I.,
RA Phillimore B.J.C.T., Prathalingam S.R., Plumb R.W., Ramsay H., Rice C.M.,
RA Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S., Skuce C.D.,
RA Smith M.L., Soderlund C., Steward C.A., Sulston J.E., Swann R.M.,
RA Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A., Tracey A.,
RA Tromans A.C., Vaudin M., Wall M., Wallis J.M., Whitehead S.L.,
RA Whittaker P., Willey D.L., Williams L., Williams S.A., Wilming L.,
RA Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S., Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 20.";
RL Nature 414:865-871(2001).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Muscle;
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 [6]
RP IDENTIFICATION IN THE CTLH COMPLEX, AND SUBCELLULAR LOCATION.
RX PubMed=17467196; DOI=10.1016/j.gene.2007.02.032;
RA Kobayashi N., Yang J., Ueda A., Suzuki T., Tomaru K., Takeno M., Okuda K.,
RA Ishigatsubo Y.;
RT "RanBPM, Muskelin, p48EMLP, p44CTLH, and the armadillo-repeat proteins
RT ARMC8alpha and ARMC8beta are components of the CTLH complex.";
RL Gene 396:236-247(2007).
RN [7]
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 [8]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=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 [9]
RP SUBCELLULAR LOCATION.
RX PubMed=24143168; DOI=10.1371/journal.pone.0075217;
RA Francis O., Han F., Adams J.C.;
RT "Molecular phylogeny of a RING E3 ubiquitin ligase, conserved in eukaryotic
RT cells and dominated by homologous components, the muskelin/RanBPM/CTLH
RT complex.";
RL PLoS ONE 8:E75217-E75217(2013).
RN [10]
RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND INTERACTION WITH
RP AXIN1; GSK3B AND CTNNB1.
RX PubMed=28829046; DOI=10.1038/cr.2017.107;
RA Lu Y., Xie S., Zhang W., Zhang C., Gao C., Sun Q., Cai Y., Xu Z., Xiao M.,
RA Xu Y., Huang X., Wu X., Liu W., Wang F., Kang Y., Zhou T.;
RT "Twa1/Gid8 is a beta-catenin nuclear retention factor in Wnt signaling and
RT colorectal tumorigenesis.";
RL Cell Res. 27:1422-1440(2017).
RN [11]
RP FUNCTION, IDENTIFICATION IN THE CTLH COMPLEX, IDENTIFICATION BY MASS
RP SPECTROMETRY, AND SUBCELLULAR LOCATION.
RX PubMed=29911972; DOI=10.7554/elife.35528;
RA Lampert F., Stafa D., Goga A., Soste M.V., Gilberto S., Olieric N.,
RA Picotti P., Stoffel M., Peter M.;
RT "The multi-subunit GID/CTLH E3 ligase promotes proliferation and targets
RT the transcription factor Hbp1 for degradation.";
RL Elife 7:0-0(2018).
CC -!- FUNCTION: Core component of the CTLH E3 ubiquitin-protein ligase
CC complex that selectively accepts ubiquitin from UBE2H and mediates
CC ubiquitination and subsequent proteasomal degradation of the
CC transcription factor HBP1 (PubMed:29911972). Acts as a positive
CC regulator of Wnt signaling pathway by promoting beta-catenin (CTNNB1)
CC nuclear accumulation (PubMed:28829046). {ECO:0000269|PubMed:28829046,
CC ECO:0000269|PubMed:29911972}.
CC -!- SUBUNIT: Homodimer; may also form higher oligomers (By similarity).
CC Identified in the CTLH complex that contains GID4, RANBP9 and/or
CC RANBP10, MKLN1, MAEA, RMND5A (or alternatively its paralog RMND5B),
CC GID8, ARMC8, WDR26 and YPEL5 (PubMed:17467196, PubMed:29911972). Within
CC this complex, MAEA, RMND5A (or alternatively its paralog RMND5B), GID8,
CC WDR26, and RANBP9 and/or RANBP10 form the catalytic core, while GID4,
CC MKLN1, ARMC8 and YPEL5 have ancillary roles (PubMed:29911972).
CC Interacts with RANBP9. Part of a complex consisting of RANBP9, MKLN1
CC and GID8 (PubMed:12559565). Interacts with CTNNB1, AXIN1 and GSK3B
CC (PubMed:28829046). {ECO:0000250|UniProtKB:Q9D7M1,
CC ECO:0000269|PubMed:12559565, ECO:0000269|PubMed:17467196,
CC ECO:0000269|PubMed:28829046, ECO:0000269|PubMed:29911972}.
CC -!- INTERACTION:
CC Q9NWU2; Q8IUR7-6: ARMC8; NbExp=4; IntAct=EBI-1051077, EBI-11942961;
CC Q9NWU2; Q9H871: RMND5A; NbExp=8; IntAct=EBI-1051077, EBI-2797992;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:17467196,
CC ECO:0000269|PubMed:24143168, ECO:0000269|PubMed:28829046}. Nucleus
CC {ECO:0000269|PubMed:12559565, ECO:0000269|PubMed:17467196,
CC ECO:0000269|PubMed:24143168, ECO:0000269|PubMed:28829046,
CC ECO:0000269|PubMed:29911972}. Note=Localizes in the cytoplasm in the
CC absence of Wnt stimulation and in the nucleus in the presence of Wnt
CC stimulation. {ECO:0000269|PubMed:28829046}.
CC -!- TISSUE SPECIFICITY: Up-regulated in colorectal cancer tissues (at
CC protein level). {ECO:0000269|PubMed:28829046}.
CC -!- PTM: Polyubiquitinated through 'Lys-48'-polyubiquitin chains, leading
CC to proteasomal degradation in the absence of Wnt stimulation.
CC {ECO:0000269|PubMed:28829046}.
CC -!- SIMILARITY: Belongs to the GID8 family. {ECO:0000305}.
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DR EMBL; AK000609; BAA91285.1; -; mRNA.
DR EMBL; AL121673; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471077; EAW75318.1; -; Genomic_DNA.
DR EMBL; CH471077; EAW75319.1; -; Genomic_DNA.
DR EMBL; BC032120; AAH32120.1; -; mRNA.
DR CCDS; CCDS13510.1; -.
DR RefSeq; NP_060366.1; NM_017896.2.
DR PDB; 7NSC; EM; 3.30 A; H=1-228.
DR PDBsum; 7NSC; -.
DR AlphaFoldDB; Q9NWU2; -.
DR SMR; Q9NWU2; -.
DR BioGRID; 120327; 146.
DR CORUM; Q9NWU2; -.
DR IntAct; Q9NWU2; 52.
DR MINT; Q9NWU2; -.
DR STRING; 9606.ENSP00000266069; -.
DR iPTMnet; Q9NWU2; -.
DR PhosphoSitePlus; Q9NWU2; -.
DR BioMuta; GID8; -.
DR DMDM; 28201788; -.
DR EPD; Q9NWU2; -.
DR jPOST; Q9NWU2; -.
DR MassIVE; Q9NWU2; -.
DR MaxQB; Q9NWU2; -.
DR PaxDb; Q9NWU2; -.
DR PeptideAtlas; Q9NWU2; -.
DR PRIDE; Q9NWU2; -.
DR ProteomicsDB; 82982; -.
DR Antibodypedia; 29626; 157 antibodies from 28 providers.
DR DNASU; 54994; -.
DR Ensembl; ENST00000266069.5; ENSP00000266069.3; ENSG00000101193.8.
DR GeneID; 54994; -.
DR KEGG; hsa:54994; -.
DR MANE-Select; ENST00000266069.5; ENSP00000266069.3; NM_017896.3; NP_060366.1.
DR UCSC; uc002ydy.4; human.
DR CTD; 54994; -.
DR DisGeNET; 54994; -.
DR GeneCards; GID8; -.
DR HGNC; HGNC:15857; GID8.
DR HPA; ENSG00000101193; Low tissue specificity.
DR MIM; 611625; gene.
DR neXtProt; NX_Q9NWU2; -.
DR OpenTargets; ENSG00000101193; -.
DR PharmGKB; PA25649; -.
DR VEuPathDB; HostDB:ENSG00000101193; -.
DR eggNOG; KOG2659; Eukaryota.
DR GeneTree; ENSGT00390000015162; -.
DR HOGENOM; CLU_073203_1_0_1; -.
DR InParanoid; Q9NWU2; -.
DR OMA; QNGRIQE; -.
DR OrthoDB; 1365635at2759; -.
DR PhylomeDB; Q9NWU2; -.
DR TreeFam; TF300176; -.
DR PathwayCommons; Q9NWU2; -.
DR SignaLink; Q9NWU2; -.
DR BioGRID-ORCS; 54994; 57 hits in 1090 CRISPR screens.
DR ChiTaRS; GID8; human.
DR GenomeRNAi; 54994; -.
DR Pharos; Q9NWU2; Tbio.
DR PRO; PR:Q9NWU2; -.
DR Proteomes; UP000005640; Chromosome 20.
DR RNAct; Q9NWU2; protein.
DR Bgee; ENSG00000101193; Expressed in esophagus squamous epithelium and 195 other tissues.
DR Genevisible; Q9NWU2; HS.
DR GO; GO:0030054; C:cell junction; IDA:HPA.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0000151; C:ubiquitin ligase complex; IDA:UniProtKB.
DR GO; GO:0042803; F:protein homodimerization activity; IEA:Ensembl.
DR GO; GO:0090263; P:positive regulation of canonical Wnt signaling pathway; IMP:UniProtKB.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; IMP:UniProtKB.
DR GO; GO:0043161; P:proteasome-mediated ubiquitin-dependent protein catabolic process; IBA:GO_Central.
DR GO; GO:0016055; P:Wnt signaling pathway; IEA:UniProtKB-KW.
DR InterPro; IPR013144; CRA_dom.
DR InterPro; IPR024964; CTLH/CRA.
DR InterPro; IPR006595; CTLH_C.
DR InterPro; IPR006594; LisH.
DR Pfam; PF10607; CLTH; 1.
DR Pfam; PF08513; LisH; 1.
DR SMART; SM00757; CRA; 1.
DR SMART; SM00668; CTLH; 1.
DR SMART; SM00667; LisH; 1.
DR PROSITE; PS50897; CTLH; 1.
DR PROSITE; PS50896; LISH; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cytoplasm; Nucleus; Reference proteome; Ubl conjugation;
KW Wnt signaling pathway.
FT CHAIN 1..228
FT /note="Glucose-induced degradation protein 8 homolog"
FT /id="PRO_0000079411"
FT DOMAIN 25..57
FT /note="LisH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00126"
FT DOMAIN 63..120
FT /note="CTLH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00058"
FT REGION 116..212
FT /note="Interaction with CTNNB1"
FT /evidence="ECO:0000269|PubMed:28829046"
FT CONFLICT 59
FT /note="V -> L (in Ref. 5; AAH32120)"
FT /evidence="ECO:0000305"
FT HELIX 28..39
FT /evidence="ECO:0007829|PDB:7NSC"
FT HELIX 45..50
FT /evidence="ECO:0007829|PDB:7NSC"
FT TURN 60..63
FT /evidence="ECO:0007829|PDB:7NSC"
FT HELIX 65..74
FT /evidence="ECO:0007829|PDB:7NSC"
FT TURN 75..77
FT /evidence="ECO:0007829|PDB:7NSC"
FT HELIX 79..86
FT /evidence="ECO:0007829|PDB:7NSC"
FT TURN 94..96
FT /evidence="ECO:0007829|PDB:7NSC"
FT HELIX 98..113
FT /evidence="ECO:0007829|PDB:7NSC"
FT HELIX 166..183
FT /evidence="ECO:0007829|PDB:7NSC"
FT HELIX 191..207
FT /evidence="ECO:0007829|PDB:7NSC"
FT TURN 208..210
FT /evidence="ECO:0007829|PDB:7NSC"
FT HELIX 217..219
FT /evidence="ECO:0007829|PDB:7NSC"
SQ SEQUENCE 228 AA; 26749 MW; 21466BDCB335DE98 CRC64;
MSYAEKPDEI TKDEWMEKLN NLHVQRADMN RLIMNYLVTE GFKEAAEKFR MESGIEPSVD
LETLDERIKI REMILKGQIQ EAIALINSLH PELLDTNRYL YFHLQQQHLI ELIRQRETEA
ALEFAQTQLA EQGEESRECL TEMERTLALL AFDSPEESPF GDLLHTMQRQ KVWSEVNQAV
LDYENRESTP KLAKLLKLLL WAQNELDQKK VKYPKMTDLS KGVIEEPK
