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Protein

Growth arrest and DNA damage-inducible protein GADD45 gamma

Gene

GADD45G

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Involved in the regulation of growth and apoptosis. Mediates activation of stress-responsive MTK1/MEKK4 MAPKKK.

GO - Biological processi

  1. activation of MAPKK activity Source: Ensembl
  2. activation of MAPKKK activity Source: UniProtKB
  3. apoptotic process Source: UniProtKB-KW
  4. cell differentiation Source: UniProtKB-KW
  5. multicellular organismal development Source: UniProtKB-KW
  6. negative regulation of protein kinase activity Source: Ensembl
  7. positive regulation of apoptotic process Source: UniProtKB
  8. positive regulation of JNK cascade Source: UniProtKB
  9. positive regulation of p38MAPK cascade Source: UniProtKB
  10. regulation of cell cycle Source: Ensembl
  11. response to stress Source: InterPro
Complete GO annotation...

Keywords - Molecular functioni

Developmental protein

Keywords - Biological processi

Apoptosis, Differentiation

Enzyme and pathway databases

SignaLinkiO95257.

Names & Taxonomyi

Protein namesi
Recommended name:
Growth arrest and DNA damage-inducible protein GADD45 gamma
Alternative name(s):
Cytokine-responsive protein CR6
DNA damage-inducible transcript 2 protein
Short name:
DDIT-2
Gene namesi
Name:GADD45G
Synonyms:CR6, DDIT2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 9

Organism-specific databases

HGNCiHGNC:4097. GADD45G.

Subcellular locationi

GO - Cellular componenti

  1. cytoplasm Source: UniProtKB
  2. nucleus Source: UniProtKB
Complete GO annotation...

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi47 – 471A → R: 30-fold reduction in homodimerization affinity and 90% decrease in growth inhibition activity and ability to stop cell cycle; when associated with E-77, E-80 and R-83. 1 Publication
Mutagenesisi76 – 761I → E: 30-fold reduction in homodimerization affinity and 90% decrease in growth inhibition activity and ability to stop cell cycle; when associated with R-47, E-80 and R-83. 1 Publication
Mutagenesisi80 – 801L → E: 30-fold reduction in homodimerization affinity and 90% decrease in growth inhibition activity and ability to stop cell cycle; when associated with R-47, E-77 and R-83. 1 Publication
Mutagenesisi83 – 831A → R: 30-fold reduction in homodimerization affinity and 90% decrease in growth inhibition activity and ability to stop cell cycle; when associated with R-47, E-77 and E-80. 1 Publication
Mutagenesisi87 – 871E → K: Reduced growth inhibition activity; when associated with K-89. 1 Publication
Mutagenesisi89 – 891D → K: Reduced growth inhibition activity; when associated with K-87. 1 Publication

Organism-specific databases

PharmGKBiPA28512.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 159159Growth arrest and DNA damage-inducible protein GADD45 gammaPRO_0000148336Add
BLAST

Proteomic databases

PaxDbiO95257.
PRIDEiO95257.

Expressioni

Gene expression databases

BgeeiO95257.
CleanExiHS_GADD45G.
ExpressionAtlasiO95257. baseline and differential.
GenevestigatoriO95257.

Organism-specific databases

HPAiHPA023606.

Interactioni

Subunit structurei

Undergoes concentration-dependent homodimerization, which is required for growth inhibititory activity and enhances interaction with PCNA. Interacts with GADD45GIP1. Interacts with PCNA.2 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
GADD45GIP1Q8TAE84EBI-448202,EBI-372506
KAT5Q929932EBI-448202,EBI-399080
KIAA1377Q9P2H02EBI-448202,EBI-473176
MED31Q9Y3C72EBI-448202,EBI-394707
UTP14AQ9BVJ63EBI-448202,EBI-473284

Protein-protein interaction databases

BioGridi116117. 55 interactions.
DIPiDIP-24218N.
IntActiO95257. 40 interactions.
MINTiMINT-265043.
STRINGi9606.ENSP00000252506.

Structurei

Secondary structure

1
159
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi17 – 3519Combined sources
Beta strandi39 – 424Combined sources
Helixi43 – 5210Combined sources
Helixi54 – 563Combined sources
Beta strandi57 – 637Combined sources
Helixi66 – 683Combined sources
Helixi72 – 8716Combined sources
Beta strandi91 – 966Combined sources
Helixi98 – 1058Combined sources
Beta strandi111 – 1133Combined sources
Beta strandi118 – 1236Combined sources
Beta strandi125 – 1284Combined sources
Helixi133 – 14715Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
2WALX-ray2.40A/B1-159[»]
3FFMX-ray2.30A1-159[»]
ProteinModelPortaliO95257.
SMRiO95257. Positions 15-159.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiO95257.

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni43 – 8644HomodimerizationAdd
BLAST

Domaini

Two central helices mediate homodimerization through parallel packing.

Sequence similaritiesi

Belongs to the GADD45 family.Curated

Phylogenomic databases

eggNOGiNOG79725.
GeneTreeiENSGT00390000016506.
HOGENOMiHOG000013221.
HOVERGENiHBG051684.
InParanoidiO95257.
KOiK04402.
OMAiDWVPTIT.
OrthoDBiEOG7J1819.
PhylomeDBiO95257.
TreeFamiTF300196.

Family and domain databases

InterProiIPR024824. GADD45.
IPR029064. L30e-like.
IPR004038. Ribosomal_L7Ae/L30e/S12e/Gad45.
[Graphical view]
PANTHERiPTHR10411. PTHR10411. 1 hit.
PfamiPF01248. Ribosomal_L7Ae. 1 hit.
[Graphical view]
SUPFAMiSSF55315. SSF55315. 1 hit.

Sequencei

Sequence statusi: Complete.

O95257-1 [UniParc]FASTAAdd to Basket

« Hide

        10         20         30         40         50
MTLEEVRGQD TVPESTARMQ GAGKALHELL LSAQRQGCLT AGVYESAKVL
60 70 80 90 100
NVDPDNVTFC VLAAGEEDEG DIALQIHFTL IQAFCCENDI DIVRVGDVQR
110 120 130 140 150
LAAIVGAGEE AGAPGDLHCI LISNPNEDAW KDPALEKLSL FCEESRSVND

WVPSITLPE
Length:159
Mass (Da):17,121
Last modified:May 1, 1999 - v1
Checksum:i26427E5881941E64
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti34 – 352QR → HG in AAK00414. (PubMed:10773677)Curated
Sequence conflicti113 – 1153APG → CAC in AAK00414. (PubMed:10773677)Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti112 – 1121G → S.2 Publications
Corresponds to variant rs3138505 [ dbSNP | Ensembl ].
VAR_018888

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF078078 mRNA. Translation: AAC83329.1.
AF079806 mRNA. Translation: AAD28544.1.
AF265659 Genomic DNA. Translation: AAF73468.1.
AF087883 mRNA. Translation: AAK00414.1.
AK313689 mRNA. Translation: BAG36438.1.
BT007234 mRNA. Translation: AAP35898.1.
AF494037 Genomic DNA. Translation: AAM00007.1.
CH471089 Genomic DNA. Translation: EAW62774.1.
BC000465 mRNA. Translation: AAH00465.1.
BC019325 mRNA. Translation: AAH19325.1.
CCDSiCCDS6686.1.
RefSeqiNP_006696.1. NM_006705.3.
UniGeneiHs.9701.

Genome annotation databases

EnsembliENST00000252506; ENSP00000252506; ENSG00000130222.
GeneIDi10912.
KEGGihsa:10912.
UCSCiuc004aqq.3. human.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Web resourcesi

NIEHS-SNPs
Wikipedia

GADD45G entry

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF078078 mRNA. Translation: AAC83329.1.
AF079806 mRNA. Translation: AAD28544.1.
AF265659 Genomic DNA. Translation: AAF73468.1.
AF087883 mRNA. Translation: AAK00414.1.
AK313689 mRNA. Translation: BAG36438.1.
BT007234 mRNA. Translation: AAP35898.1.
AF494037 Genomic DNA. Translation: AAM00007.1.
CH471089 Genomic DNA. Translation: EAW62774.1.
BC000465 mRNA. Translation: AAH00465.1.
BC019325 mRNA. Translation: AAH19325.1.
CCDSiCCDS6686.1.
RefSeqiNP_006696.1. NM_006705.3.
UniGeneiHs.9701.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
2WALX-ray2.40A/B1-159[»]
3FFMX-ray2.30A1-159[»]
ProteinModelPortaliO95257.
SMRiO95257. Positions 15-159.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi116117. 55 interactions.
DIPiDIP-24218N.
IntActiO95257. 40 interactions.
MINTiMINT-265043.
STRINGi9606.ENSP00000252506.

Proteomic databases

PaxDbiO95257.
PRIDEiO95257.

Protocols and materials databases

DNASUi10912.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000252506; ENSP00000252506; ENSG00000130222.
GeneIDi10912.
KEGGihsa:10912.
UCSCiuc004aqq.3. human.

Organism-specific databases

CTDi10912.
GeneCardsiGC09P092219.
H-InvDBHIX0169359.
HGNCiHGNC:4097. GADD45G.
HPAiHPA023606.
MIMi604949. gene.
neXtProtiNX_O95257.
PharmGKBiPA28512.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiNOG79725.
GeneTreeiENSGT00390000016506.
HOGENOMiHOG000013221.
HOVERGENiHBG051684.
InParanoidiO95257.
KOiK04402.
OMAiDWVPTIT.
OrthoDBiEOG7J1819.
PhylomeDBiO95257.
TreeFamiTF300196.

Enzyme and pathway databases

SignaLinkiO95257.

Miscellaneous databases

ChiTaRSiGADD45G. human.
EvolutionaryTraceiO95257.
GeneWikiiGADD45G.
GenomeRNAii10912.
NextBioi41445.
PROiO95257.
SOURCEiSearch...

Gene expression databases

BgeeiO95257.
CleanExiHS_GADD45G.
ExpressionAtlasiO95257. baseline and differential.
GenevestigatoriO95257.

Family and domain databases

InterProiIPR024824. GADD45.
IPR029064. L30e-like.
IPR004038. Ribosomal_L7Ae/L30e/S12e/Gad45.
[Graphical view]
PANTHERiPTHR10411. PTHR10411. 1 hit.
PfamiPF01248. Ribosomal_L7Ae. 1 hit.
[Graphical view]
SUPFAMiSSF55315. SSF55315. 1 hit.
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "A family of stress-inducible GADD45-like proteins mediate activation of the stress-responsive MTK1/MEKK4 MAPKKK."
    Takekawa M., Saito H.
    Cell 95:521-530(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
  2. "Cytokine response gene 6 induces p21 and regulates both cell growth and arrest."
    Fan W., Richter G., Cereseto A., Beadling C., Smith K.A.
    Oncogene 18:6573-6582(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
  3. "Cloning and characterization of Gadd45 gamma gene and its regulation by C/EBP."
    Jung N., Yi Y., Kim D., Shong M., Hong S., Lee H., Bae I.
    Submitted (MAY-2000) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
  4. "Assignment of human GADD45G to chromosome 9q22.1-->q22.3 by radiation hybrid mapping."
    Gong R., Yu L., Zhang H., Tu Q., Zhao Y., Yang J., Xu Y., Zhao S.
    Cytogenet. Cell Genet. 88:95-96(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT SER-112.
  5. "Complete sequencing and characterization of 21,243 full-length human cDNAs."
    Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.
    , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
    Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Tissue: Brain.
  6. "Cloning of human full-length CDSs in BD Creator(TM) system donor vector."
    Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A.
    Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
  7. NIEHS SNPs program
    Submitted (MAR-2002) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT SER-112.
  8. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  9. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Tissue: Lung.
  10. "CR6-interacting factor 1 interacts with Gadd45 family proteins and modulates the cell cycle."
    Chung H.K., Yi Y.-W., Jung N.-C., Kim D., Suh J.M., Kim H., Park K.C., Song J.H., Kim D.W., Hwang E.S., Yoon S.-H., Bae Y.-S., Kim J.M., Bae I., Shong M.
    J. Biol. Chem. 278:28079-28088(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH GADD45GIP1.
    Tissue: Colon carcinoma.
  11. "Crystal structure of human Gadd45gamma reveals an active dimer."
    Zhang W., Fu S., Liu X., Zhao X., Zhang W., Peng W., Wu C., Li Y., Li X., Bartlam M., Zeng Z.H., Zhan Q., Rao Z.
    Protein Cell 2:814-826(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS), SUBUNIT, MUTAGENESIS OF ALA-47; ILE-76; LEU-80; ALA-83; GLU-87 AND ASP-89, INTERACTION WITH PCNA.

Entry informationi

Entry nameiGA45G_HUMAN
AccessioniPrimary (citable) accession number: O95257
Secondary accession number(s): Q5VZ87, Q9C076
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 30, 2000
Last sequence update: May 1, 1999
Last modified: February 4, 2015
This is version 120 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 9
    Human chromosome 9: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.