GID4_HUMAN
ID GID4_HUMAN Reviewed; 300 AA.
AC Q8IVV7; Q8TEB5; Q9BW50;
DT 16-AUG-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2003, sequence version 1.
DT 03-AUG-2022, entry version 129.
DE RecName: Full=Glucose-induced degradation protein 4 homolog;
DE AltName: Full=Vacuolar import and degradation protein 24 homolog;
GN Name=GID4; Synonyms=C17orf39, VID24;
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].
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=16625196; DOI=10.1038/nature04689;
RA Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R.,
RA Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A.,
RA Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J.,
RA Chang J.L., Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J.,
RA DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., Gnerre S.,
RA Goldstein S., Grafham D.V., Grocock R., Hafez N., Hagopian D.S., Hart E.,
RA Norman C.H., Humphray S., Jaffe D.B., Jones M., Kamal M., Khodiyar V.K.,
RA LaButti K., Laird G., Lehoczky J., Liu X., Lokyitsang T., Loveland J.,
RA Lui A., Macdonald P., Major J.E., Matthews L., Mauceli E., McCarroll S.A.,
RA Mihalev A.H., Mudge J., Nguyen C., Nicol R., O'Leary S.B., Osoegawa K.,
RA Schwartz D.C., Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D.,
RA Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A.,
RA Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C.;
RT "DNA sequence of human chromosome 17 and analysis of rearrangement in the
RT human lineage.";
RL Nature 440:1045-1049(2006).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Eye, and Testis;
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 FUNCTION, IDENTIFICATION IN THE CTLH COMPLEX, AND IDENTIFICATION BY MASS
RP SPECTROMETRY.
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).
RN [5] {ECO:0007744|PDB:6CCR, ECO:0007744|PDB:6CCT, ECO:0007744|PDB:6CCU, ECO:0007744|PDB:6CD8, ECO:0007744|PDB:6CD9, ECO:0007744|PDB:6CDC, ECO:0007744|PDB:6CDG}
RP X-RAY CRYSTALLOGRAPHY (1.55 ANGSTROMS) OF 124-289 IN COMPLEXES WITH PEPTIDE
RP SUBSTRATES, FUNCTION, DOMAIN, AND MUTAGENESIS OF.
RX PubMed=29632410; DOI=10.1038/s41589-018-0036-1;
RA Dong C., Zhang H., Li L., Tempel W., Loppnau P., Min J.;
RT "Molecular basis of GID4-mediated recognition of degrons for the Pro/N-end
RT rule pathway.";
RL Nat. Chem. Biol. 14:466-473(2018).
CC -!- FUNCTION: Substrate-recognition subunit of the CTLH E3 ubiquitin-
CC protein ligase complex that selectively accepts ubiquitin from UBE2H
CC and mediates ubiquitination and subsequent proteasomal degradation of
CC the transcription factor HBP1 (Probable) (PubMed:29911972). Binds
CC proteins and peptides with a Pro/N-degron consisting of an unmodified
CC N-terminal Pro followed by a small residue, and has the highest
CC affinity for the peptide Pro-Gly-Leu-Trp (PubMed:29632410). Binds
CC peptides with an N-terminal sequence of the type Pro-[Ala,Gly]-
CC [Leu,Met,Gln,Ser,Tyr]-[Glu,Gly,His,Ser,Val,Trp,Tyr]. Does not bind
CC peptides with an acetylated N-terminal Pro residue (PubMed:29632410).
CC {ECO:0000269|PubMed:29632410, ECO:0000269|PubMed:29911972,
CC ECO:0000305}.
CC -!- SUBUNIT: Identified in the CTLH complex that contains GID4, RANBP9
CC and/or RANBP10, MKLN1, MAEA, RMND5A (or alternatively its paralog
CC RMND5B), GID8, ARMC8, WDR26 and YPEL5 (PubMed:29911972). Within this
CC 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 {ECO:0000269|PubMed:29911972}.
CC -!- DOMAIN: The first four residues of target peptides with a free N-
CC terminal Pro (a Pro/N-degron) are bound inside a deep and narrow beta-
CC barrel structure. {ECO:0000269|PubMed:29632410}.
CC -!- SIMILARITY: Belongs to the GID4/VID24 family. {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; AK074284; BAB85036.1; -; mRNA.
DR EMBL; AC087164; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC000636; AAH00636.2; -; mRNA.
DR EMBL; BC041829; AAH41829.1; -; mRNA.
DR CCDS; CCDS11190.1; -.
DR RefSeq; NP_076957.3; NM_024052.4.
DR PDB; 6CCR; X-ray; 1.60 A; A=116-300.
DR PDB; 6CCT; X-ray; 2.40 A; A=124-289.
DR PDB; 6CCU; X-ray; 1.75 A; A=116-300.
DR PDB; 6CD8; X-ray; 1.60 A; A/B=124-289.
DR PDB; 6CD9; X-ray; 1.55 A; A=124-289.
DR PDB; 6CDC; X-ray; 1.75 A; A=124-289.
DR PDB; 6CDG; X-ray; 1.60 A; A=124-289.
DR PDB; 6WZX; X-ray; 1.75 A; A/B=124-289.
DR PDB; 6WZZ; X-ray; 1.60 A; A=124-289.
DR PDB; 7NSC; EM; 3.30 A; D=1-300.
DR PDB; 7Q4Y; X-ray; 3.08 A; A/B=100-300.
DR PDB; 7Q50; X-ray; 3.16 A; A=121-290.
DR PDB; 7S12; X-ray; 2.15 A; A=124-289.
DR PDB; 7SLZ; X-ray; 1.97 A; A=124-289.
DR PDBsum; 6CCR; -.
DR PDBsum; 6CCT; -.
DR PDBsum; 6CCU; -.
DR PDBsum; 6CD8; -.
DR PDBsum; 6CD9; -.
DR PDBsum; 6CDC; -.
DR PDBsum; 6CDG; -.
DR PDBsum; 6WZX; -.
DR PDBsum; 6WZZ; -.
DR PDBsum; 7NSC; -.
DR PDBsum; 7Q4Y; -.
DR PDBsum; 7Q50; -.
DR PDBsum; 7S12; -.
DR PDBsum; 7SLZ; -.
DR AlphaFoldDB; Q8IVV7; -.
DR SMR; Q8IVV7; -.
DR BioGRID; 122487; 127.
DR IntAct; Q8IVV7; 29.
DR STRING; 9606.ENSP00000268719; -.
DR GlyGen; Q8IVV7; 3 sites, 1 O-linked glycan (3 sites).
DR iPTMnet; Q8IVV7; -.
DR PhosphoSitePlus; Q8IVV7; -.
DR BioMuta; GID4; -.
DR DMDM; 73620594; -.
DR EPD; Q8IVV7; -.
DR jPOST; Q8IVV7; -.
DR MassIVE; Q8IVV7; -.
DR MaxQB; Q8IVV7; -.
DR PaxDb; Q8IVV7; -.
DR PeptideAtlas; Q8IVV7; -.
DR PRIDE; Q8IVV7; -.
DR ProteomicsDB; 70778; -.
DR Antibodypedia; 25602; 88 antibodies from 18 providers.
DR DNASU; 79018; -.
DR Ensembl; ENST00000268719.9; ENSP00000268719.4; ENSG00000141034.10.
DR GeneID; 79018; -.
DR KEGG; hsa:79018; -.
DR MANE-Select; ENST00000268719.9; ENSP00000268719.4; NM_024052.5; NP_076957.3.
DR UCSC; uc002gsg.2; human.
DR CTD; 79018; -.
DR DisGeNET; 79018; -.
DR GeneCards; GID4; -.
DR HGNC; HGNC:28453; GID4.
DR HPA; ENSG00000141034; Tissue enhanced (testis).
DR MIM; 617699; gene.
DR neXtProt; NX_Q8IVV7; -.
DR OpenTargets; ENSG00000141034; -.
DR PharmGKB; PA134994398; -.
DR VEuPathDB; HostDB:ENSG00000141034; -.
DR eggNOG; KOG4635; Eukaryota.
DR GeneTree; ENSGT00500000044930; -.
DR HOGENOM; CLU_081159_0_0_1; -.
DR InParanoid; Q8IVV7; -.
DR OMA; KHWGQFL; -.
DR PhylomeDB; Q8IVV7; -.
DR TreeFam; TF323749; -.
DR PathwayCommons; Q8IVV7; -.
DR SignaLink; Q8IVV7; -.
DR BioGRID-ORCS; 79018; 16 hits in 1073 CRISPR screens.
DR ChiTaRS; GID4; human.
DR GenomeRNAi; 79018; -.
DR Pharos; Q8IVV7; Tbio.
DR PRO; PR:Q8IVV7; -.
DR Proteomes; UP000005640; Chromosome 17.
DR RNAct; Q8IVV7; protein.
DR Bgee; ENSG00000141034; Expressed in left testis and 190 other tissues.
DR ExpressionAtlas; Q8IVV7; baseline and differential.
DR Genevisible; Q8IVV7; HS.
DR GO; GO:0000151; C:ubiquitin ligase complex; IDA:UniProtKB.
DR GO; GO:0061630; F:ubiquitin protein ligase activity; IBA:GO_Central.
DR GO; GO:0043161; P:proteasome-mediated ubiquitin-dependent protein catabolic process; IBA:GO_Central.
DR InterPro; IPR018618; Vacuolar_import/degrad_Vid24.
DR Pfam; PF09783; Vac_ImportDeg; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Reference proteome.
FT CHAIN 1..300
FT /note="Glucose-induced degradation protein 4 homolog"
FT /id="PRO_0000079302"
FT REGION 1..55
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 91..111
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT SITE 132
FT /note="Interaction with the N-terminal Pro (Pro/N-degron)
FT of proteins that are targeted for degradation"
FT /evidence="ECO:0000269|PubMed:29632410"
FT SITE 237
FT /note="Interaction with the N-terminal Pro (Pro/N-degron)
FT of proteins that are targeted for degradation"
FT /evidence="ECO:0000269|PubMed:29632410"
FT SITE 258
FT /note="Interaction with the N-terminal Pro (Pro/N-degron)
FT of proteins that are targeted for degradation"
FT /evidence="ECO:0000269|PubMed:29632410"
FT MUTAGEN 132
FT /note="Q->A: Loss of interaction with peptides with a
FT Pro/N-degron."
FT /evidence="ECO:0000269|PubMed:29632410"
FT MUTAGEN 237
FT /note="E->A: Loss of interaction with peptides with a
FT Pro/N-degron."
FT /evidence="ECO:0000269|PubMed:29632410"
FT MUTAGEN 253
FT /note="S->D: Strongly decreased affinity for peptides with
FT a Pro/N-degron."
FT /evidence="ECO:0000269|PubMed:29632410"
FT MUTAGEN 258
FT /note="Y->A: Loss of interaction with peptides with a
FT Pro/N-degron."
FT /evidence="ECO:0000269|PubMed:29632410"
FT MUTAGEN 273
FT /note="Y->A: Loss of interaction with peptides with a
FT Pro/N-degron."
FT /evidence="ECO:0000269|PubMed:29632410"
FT MUTAGEN 282
FT /note="Q->A: Loss of interaction with peptides with a
FT Pro/N-degron."
FT /evidence="ECO:0000269|PubMed:29632410"
FT CONFLICT 146
FT /note="Q -> R (in Ref. 1; BAB85036)"
FT /evidence="ECO:0000305"
FT CONFLICT 272
FT /note="Y -> H (in Ref. 1; BAB85036)"
FT /evidence="ECO:0000305"
FT STRAND 127..133
FT /evidence="ECO:0007829|PDB:6CD9"
FT STRAND 138..149
FT /evidence="ECO:0007829|PDB:6CD9"
FT TURN 150..153
FT /evidence="ECO:0007829|PDB:6CD9"
FT STRAND 154..167
FT /evidence="ECO:0007829|PDB:6CD9"
FT STRAND 169..179
FT /evidence="ECO:0007829|PDB:6CD9"
FT STRAND 181..184
FT /evidence="ECO:0007829|PDB:6CD9"
FT HELIX 195..202
FT /evidence="ECO:0007829|PDB:6CD9"
FT HELIX 206..210
FT /evidence="ECO:0007829|PDB:6CD9"
FT TURN 211..216
FT /evidence="ECO:0007829|PDB:6CCR"
FT TURN 217..219
FT /evidence="ECO:0007829|PDB:6CDC"
FT HELIX 222..227
FT /evidence="ECO:0007829|PDB:6CD9"
FT STRAND 228..242
FT /evidence="ECO:0007829|PDB:6CD9"
FT HELIX 251..254
FT /evidence="ECO:0007829|PDB:6CCR"
FT STRAND 256..263
FT /evidence="ECO:0007829|PDB:6CD9"
FT TURN 264..267
FT /evidence="ECO:0007829|PDB:6CD9"
FT STRAND 268..274
FT /evidence="ECO:0007829|PDB:6CD9"
FT STRAND 283..289
FT /evidence="ECO:0007829|PDB:6CD9"
FT HELIX 290..292
FT /evidence="ECO:0007829|PDB:6CCR"
SQ SEQUENCE 300 AA; 33514 MW; 9FE12824E9C46CD4 CRC64;
MCARGQVGRG TQLRTGRPCS QVPGSRWRPE RLLRRQRAGG RPSRPHPARA RPGLSLPATL
LGSRAAAAVP LPLPPALAPG DPAMPVRTEC PPPAGASAAS AASLIPPPPI NTQQPGVATS
LLYSGSKFRG HQKSKGNSYD VEVVLQHVDT GNSYLCGYLK IKGLTEEYPT LTTFFEGEII
SKKHPFLTRK WDADEDVDRK HWGKFLAFYQ YAKSFNSDDF DYEELKNGDY VFMRWKEQFL
VPDHTIKDIS GASFAGFYYI CFQKSAASIE GYYYHRSSEW YQSLNLTHVP EHSAPIYEFR