GA45G_HUMAN
ID GA45G_HUMAN Reviewed; 159 AA.
AC O95257; Q5VZ87; Q9C076;
DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-1999, sequence version 1.
DT 03-AUG-2022, entry version 166.
DE RecName: Full=Growth arrest and DNA damage-inducible protein GADD45 gamma;
DE AltName: Full=Cytokine-responsive protein CR6;
DE AltName: Full=DNA damage-inducible transcript 2 protein;
DE Short=DDIT-2;
GN Name=GADD45G; Synonyms=CR6, DDIT2;
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].
RX PubMed=9827804; DOI=10.1016/s0092-8674(00)81619-0;
RA Takekawa M., Saito H.;
RT "A family of stress-inducible GADD45-like proteins mediate activation of
RT the stress-responsive MTK1/MEKK4 MAPKKK.";
RL Cell 95:521-530(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=10597261; DOI=10.1038/sj.onc.1203054;
RA Fan W., Richter G., Cereseto A., Beadling C., Smith K.A.;
RT "Cytokine response gene 6 induces p21 and regulates both cell growth and
RT arrest.";
RL Oncogene 18:6573-6582(1999).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RA Jung N., Yi Y., Kim D., Shong M., Hong S., Lee H., Bae I.;
RT "Cloning and characterization of Gadd45 gamma gene and its regulation by
RT C/EBP.";
RL Submitted (MAY-2000) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT SER-112.
RX PubMed=10773677; DOI=10.1159/000015496;
RA Gong R., Yu L., Zhang H., Tu Q., Zhao Y., Yang J., Xu Y., Zhao S.;
RT "Assignment of human GADD45G to chromosome 9q22.1-->q22.3 by radiation
RT hybrid mapping.";
RL Cytogenet. Cell Genet. 88:95-96(2000).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
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 [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor vector.";
RL Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT SER-112.
RG NIEHS SNPs program;
RL Submitted (MAR-2002) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton 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 (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Lung;
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 [10]
RP INTERACTION WITH GADD45GIP1.
RC TISSUE=Colon carcinoma;
RX PubMed=12716909; DOI=10.1074/jbc.m212835200;
RA Chung H.K., Yi Y.-W., Jung N.-C., Kim D., Suh J.M., Kim H., Park K.C.,
RA Song J.H., Kim D.W., Hwang E.S., Yoon S.-H., Bae Y.-S., Kim J.M., Bae I.,
RA Shong M.;
RT "CR6-interacting factor 1 interacts with Gadd45 family proteins and
RT modulates the cell cycle.";
RL J. Biol. Chem. 278:28079-28088(2003).
RN [11]
RP X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS), SUBUNIT, MUTAGENESIS OF ALA-47;
RP ILE-76; LEU-80; ALA-83; GLU-87 AND ASP-89, AND INTERACTION WITH PCNA.
RX PubMed=22058036; DOI=10.1007/s13238-011-1090-6;
RA Zhang W., Fu S., Liu X., Zhao X., Zhang W., Peng W., Wu C., Li Y., Li X.,
RA Bartlam M., Zeng Z.H., Zhan Q., Rao Z.;
RT "Crystal structure of human Gadd45gamma reveals an active dimer.";
RL Protein Cell 2:814-826(2011).
CC -!- FUNCTION: Involved in the regulation of growth and apoptosis. Mediates
CC activation of stress-responsive MTK1/MEKK4 MAPKKK.
CC -!- SUBUNIT: Undergoes concentration-dependent homodimerization, which is
CC required for growth inhibititory activity and enhances interaction with
CC PCNA. Interacts with GADD45GIP1. Interacts with PCNA.
CC {ECO:0000269|PubMed:12716909, ECO:0000269|PubMed:22058036}.
CC -!- INTERACTION:
CC O95257; P12814: ACTN1; NbExp=3; IntAct=EBI-448202, EBI-351710;
CC O95257; Q8TED9: AFAP1L1; NbExp=8; IntAct=EBI-448202, EBI-1053644;
CC O95257; Q9BPX5: ARPC5L; NbExp=4; IntAct=EBI-448202, EBI-711189;
CC O95257; Q8N7W2-2: BEND7; NbExp=3; IntAct=EBI-448202, EBI-10181188;
CC O95257; Q6QNY1: BLOC1S2; NbExp=3; IntAct=EBI-448202, EBI-465872;
CC O95257; Q9P2H0: CEP126; NbExp=2; IntAct=EBI-448202, EBI-473176;
CC O95257; Q8IYX8-2: CEP57L1; NbExp=3; IntAct=EBI-448202, EBI-10181988;
CC O95257; Q96MT7: CFAP44; NbExp=3; IntAct=EBI-448202, EBI-12551219;
CC O95257; Q92600-3: CNOT9; NbExp=3; IntAct=EBI-448202, EBI-12907584;
CC O95257; Q13561: DCTN2; NbExp=5; IntAct=EBI-448202, EBI-715074;
CC O95257; Q96D03: DDIT4L; NbExp=3; IntAct=EBI-448202, EBI-742054;
CC O95257; Q9H0I2: ENKD1; NbExp=5; IntAct=EBI-448202, EBI-744099;
CC O95257; Q8NDB6: FAM156A; NbExp=3; IntAct=EBI-448202, EBI-749727;
CC O95257; Q8TAE8: GADD45GIP1; NbExp=4; IntAct=EBI-448202, EBI-372506;
CC O95257; Q6IC98: GRAMD4; NbExp=3; IntAct=EBI-448202, EBI-10962409;
CC O95257; Q92993: KAT5; NbExp=2; IntAct=EBI-448202, EBI-399080;
CC O95257; Q5T3J3: LRIF1; NbExp=4; IntAct=EBI-448202, EBI-473196;
CC O95257; Q9Y3C7: MED31; NbExp=2; IntAct=EBI-448202, EBI-394707;
CC O95257; P08949-2: NMB; NbExp=3; IntAct=EBI-448202, EBI-12302085;
CC O95257; A6NK89: RASSF10; NbExp=3; IntAct=EBI-448202, EBI-6912267;
CC O95257; Q15293: RCN1; NbExp=3; IntAct=EBI-448202, EBI-948278;
CC O95257; Q04864: REL; NbExp=4; IntAct=EBI-448202, EBI-307352;
CC O95257; Q9Y3A4: RRP7A; NbExp=3; IntAct=EBI-448202, EBI-7223720;
CC O95257; P57060: RWDD2B; NbExp=15; IntAct=EBI-448202, EBI-724442;
CC O95257; Q99598: TSNAX; NbExp=4; IntAct=EBI-448202, EBI-742638;
CC O95257; Q9BVJ6: UTP14A; NbExp=3; IntAct=EBI-448202, EBI-473284;
CC O95257; Q8N3J9: ZNF664; NbExp=3; IntAct=EBI-448202, EBI-2799450;
CC O95257; Q0D2J5: ZNF763; NbExp=3; IntAct=EBI-448202, EBI-10226414;
CC -!- DOMAIN: Two central helices mediate homodimerization through parallel
CC packing.
CC -!- SIMILARITY: Belongs to the GADD45 family. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/gadd45g/";
CC -!- WEB RESOURCE: Name=Wikipedia; Note=GADD45G entry;
CC URL="https://en.wikipedia.org/wiki/GADD45G";
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DR EMBL; AF078078; AAC83329.1; -; mRNA.
DR EMBL; AF079806; AAD28544.1; -; mRNA.
DR EMBL; AF265659; AAF73468.1; -; Genomic_DNA.
DR EMBL; AF087883; AAK00414.1; -; mRNA.
DR EMBL; AK313689; BAG36438.1; -; mRNA.
DR EMBL; BT007234; AAP35898.1; -; mRNA.
DR EMBL; AF494037; AAM00007.1; -; Genomic_DNA.
DR EMBL; CH471089; EAW62774.1; -; Genomic_DNA.
DR EMBL; BC000465; AAH00465.1; -; mRNA.
DR EMBL; BC019325; AAH19325.1; -; mRNA.
DR CCDS; CCDS6686.1; -.
DR RefSeq; NP_006696.1; NM_006705.3.
DR PDB; 2WAL; X-ray; 2.40 A; A/B=1-159.
DR PDB; 3FFM; X-ray; 2.30 A; A=1-159.
DR PDBsum; 2WAL; -.
DR PDBsum; 3FFM; -.
DR AlphaFoldDB; O95257; -.
DR SMR; O95257; -.
DR BioGRID; 116117; 76.
DR CORUM; O95257; -.
DR DIP; DIP-24218N; -.
DR IntAct; O95257; 59.
DR MINT; O95257; -.
DR STRING; 9606.ENSP00000252506; -.
DR BioMuta; GADD45G; -.
DR PaxDb; O95257; -.
DR PRIDE; O95257; -.
DR ProteomicsDB; 50751; -.
DR Antibodypedia; 13541; 878 antibodies from 35 providers.
DR DNASU; 10912; -.
DR Ensembl; ENST00000252506.11; ENSP00000252506.6; ENSG00000130222.11.
DR GeneID; 10912; -.
DR KEGG; hsa:10912; -.
DR MANE-Select; ENST00000252506.11; ENSP00000252506.6; NM_006705.4; NP_006696.1.
DR UCSC; uc004aqq.4; human.
DR CTD; 10912; -.
DR DisGeNET; 10912; -.
DR GeneCards; GADD45G; -.
DR HGNC; HGNC:4097; GADD45G.
DR HPA; ENSG00000130222; Tissue enhanced (liver).
DR MIM; 604949; gene.
DR neXtProt; NX_O95257; -.
DR OpenTargets; ENSG00000130222; -.
DR PharmGKB; PA28512; -.
DR VEuPathDB; HostDB:ENSG00000130222; -.
DR eggNOG; ENOG502RXKU; Eukaryota.
DR GeneTree; ENSGT00950000182964; -.
DR HOGENOM; CLU_118164_0_0_1; -.
DR InParanoid; O95257; -.
DR OMA; SRSAYDW; -.
DR OrthoDB; 1517160at2759; -.
DR PhylomeDB; O95257; -.
DR TreeFam; TF300196; -.
DR PathwayCommons; O95257; -.
DR SignaLink; O95257; -.
DR SIGNOR; O95257; -.
DR BioGRID-ORCS; 10912; 16 hits in 1075 CRISPR screens.
DR ChiTaRS; GADD45G; human.
DR EvolutionaryTrace; O95257; -.
DR GeneWiki; GADD45G; -.
DR GenomeRNAi; 10912; -.
DR Pharos; O95257; Tbio.
DR PRO; PR:O95257; -.
DR Proteomes; UP000005640; Chromosome 9.
DR RNAct; O95257; protein.
DR Bgee; ENSG00000130222; Expressed in mucosa of stomach and 121 other tissues.
DR ExpressionAtlas; O95257; baseline and differential.
DR Genevisible; O95257; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
DR GO; GO:0030154; P:cell differentiation; IEA:UniProtKB-KW.
DR GO; GO:0043065; P:positive regulation of apoptotic process; IDA:UniProtKB.
DR GO; GO:0120162; P:positive regulation of cold-induced thermogenesis; ISS:YuBioLab.
DR GO; GO:0046330; P:positive regulation of JNK cascade; IDA:UniProtKB.
DR GO; GO:1900745; P:positive regulation of p38MAPK cascade; IDA:UniProtKB.
DR GO; GO:0051726; P:regulation of cell cycle; IBA:GO_Central.
DR Gene3D; 3.30.1330.30; -; 1.
DR InterPro; IPR024824; GADD45.
DR InterPro; IPR029064; L30e-like.
DR InterPro; IPR004038; Ribosomal_L7Ae/L30e/S12e/Gad45.
DR PANTHER; PTHR10411; PTHR10411; 1.
DR Pfam; PF01248; Ribosomal_L7Ae; 1.
DR SUPFAM; SSF55315; SSF55315; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Apoptosis; Developmental protein; Differentiation;
KW Reference proteome.
FT CHAIN 1..159
FT /note="Growth arrest and DNA damage-inducible protein
FT GADD45 gamma"
FT /id="PRO_0000148336"
FT REGION 43..86
FT /note="Homodimerization"
FT VARIANT 112
FT /note="G -> S (in dbSNP:rs3138505)"
FT /evidence="ECO:0000269|PubMed:10773677, ECO:0000269|Ref.7"
FT /id="VAR_018888"
FT MUTAGEN 47
FT /note="A->R: 30-fold reduction in homodimerization affinity
FT and 90% decrease in growth inhibition activity and ability
FT to stop cell cycle; when associated with E-77, E-80 and R-
FT 83."
FT /evidence="ECO:0000269|PubMed:22058036"
FT MUTAGEN 76
FT /note="I->E: 30-fold reduction in homodimerization affinity
FT and 90% decrease in growth inhibition activity and ability
FT to stop cell cycle; when associated with R-47, E-80 and R-
FT 83."
FT /evidence="ECO:0000269|PubMed:22058036"
FT MUTAGEN 80
FT /note="L->E: 30-fold reduction in homodimerization affinity
FT and 90% decrease in growth inhibition activity and ability
FT to stop cell cycle; when associated with R-47, E-77 and R-
FT 83."
FT /evidence="ECO:0000269|PubMed:22058036"
FT MUTAGEN 83
FT /note="A->R: 30-fold reduction in homodimerization affinity
FT and 90% decrease in growth inhibition activity and ability
FT to stop cell cycle; when associated with R-47, E-77 and E-
FT 80."
FT /evidence="ECO:0000269|PubMed:22058036"
FT MUTAGEN 87
FT /note="E->K: Reduced growth inhibition activity; when
FT associated with K-89."
FT /evidence="ECO:0000269|PubMed:22058036"
FT MUTAGEN 89
FT /note="D->K: Reduced growth inhibition activity; when
FT associated with K-87."
FT /evidence="ECO:0000269|PubMed:22058036"
FT CONFLICT 34..35
FT /note="QR -> HG (in Ref. 4; AAK00414)"
FT /evidence="ECO:0000305"
FT CONFLICT 113..115
FT /note="APG -> CAC (in Ref. 4; AAK00414)"
FT /evidence="ECO:0000305"
FT HELIX 17..35
FT /evidence="ECO:0007829|PDB:3FFM"
FT STRAND 39..42
FT /evidence="ECO:0007829|PDB:3FFM"
FT HELIX 43..52
FT /evidence="ECO:0007829|PDB:3FFM"
FT HELIX 54..56
FT /evidence="ECO:0007829|PDB:3FFM"
FT STRAND 57..63
FT /evidence="ECO:0007829|PDB:3FFM"
FT HELIX 66..68
FT /evidence="ECO:0007829|PDB:3FFM"
FT HELIX 72..87
FT /evidence="ECO:0007829|PDB:3FFM"
FT STRAND 91..96
FT /evidence="ECO:0007829|PDB:3FFM"
FT HELIX 98..105
FT /evidence="ECO:0007829|PDB:3FFM"
FT STRAND 111..113
FT /evidence="ECO:0007829|PDB:3FFM"
FT STRAND 118..123
FT /evidence="ECO:0007829|PDB:3FFM"
FT STRAND 125..128
FT /evidence="ECO:0007829|PDB:3FFM"
FT HELIX 133..147
FT /evidence="ECO:0007829|PDB:3FFM"
SQ SEQUENCE 159 AA; 17121 MW; 26427E5881941E64 CRC64;
MTLEEVRGQD TVPESTARMQ GAGKALHELL LSAQRQGCLT AGVYESAKVL NVDPDNVTFC
VLAAGEEDEG DIALQIHFTL IQAFCCENDI DIVRVGDVQR LAAIVGAGEE AGAPGDLHCI
LISNPNEDAW KDPALEKLSL FCEESRSVND WVPSITLPE
