DDI2_MOUSE
ID DDI2_MOUSE Reviewed; 399 AA.
AC A2ADY9;
DT 15-MAY-2007, integrated into UniProtKB/Swiss-Prot.
DT 20-FEB-2007, sequence version 1.
DT 03-AUG-2022, entry version 113.
DE RecName: Full=Protein DDI1 homolog 2 {ECO:0000305};
DE EC=3.4.23.- {ECO:0000250|UniProtKB:Q5TDH0};
GN Name=Ddi2 {ECO:0000312|MGI:MGI:1917244};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [2]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-121 AND SER-128, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=17242355; DOI=10.1073/pnas.0609836104;
RA Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.;
RT "Large-scale phosphorylation analysis of mouse liver.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007).
RN [3]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-121; SER-128 AND SER-194, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Spleen, and
RC Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
CC -!- FUNCTION: Aspartic protease that mediates the cleavage of NFE2L1/NRF1
CC at 'Leu-104', thereby promoting release of NFE2L1/NRF1 from the
CC endoplasmic reticulum membrane. Ubiquitination of NFE2L1/NRF1 is a
CC prerequisite for cleavage, suggesting that DDI2 specifically recognizes
CC and binds ubiquitinated NFE2L1/NRF1. Seems to act as a proteasomal
CC shuttle which links the proteasome and replication fork proteins like
CC RTF2. Required, with DDI1, for cellular survival following replication
CC stress. Together or redudantly with DDI1, removes RTF2 from stalled
CC forks to allow cell cycle progression after replication stress and
CC maintains genome integrity. {ECO:0000250|UniProtKB:Q5TDH0}.
CC -!- SUBUNIT: Homodimer. {ECO:0000250|UniProtKB:Q5TDH0}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol
CC {ECO:0000250|UniProtKB:Q5TDH0}. Chromosome
CC {ECO:0000250|UniProtKB:Q5TDH0}.
CC -!- SIMILARITY: Belongs to the DDI1 family. {ECO:0000305}.
CC -!- CAUTION: Although this protein contains the conserved Asp-252 that
CC functions as an active site, this protein does not have proteolytic
CC activity, and may therefore be catalytically inactive.
CC {ECO:0000250|UniProtKB:Q5TDH0}.
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DR EMBL; AL671733; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR CCDS; CCDS18880.1; -.
DR RefSeq; NP_001017966.1; NM_001017966.2.
DR AlphaFoldDB; A2ADY9; -.
DR SMR; A2ADY9; -.
DR BioGRID; 213067; 6.
DR STRING; 10090.ENSMUSP00000099542; -.
DR MEROPS; A28.003; -.
DR iPTMnet; A2ADY9; -.
DR PhosphoSitePlus; A2ADY9; -.
DR EPD; A2ADY9; -.
DR jPOST; A2ADY9; -.
DR MaxQB; A2ADY9; -.
DR PaxDb; A2ADY9; -.
DR PeptideAtlas; A2ADY9; -.
DR PRIDE; A2ADY9; -.
DR ProteomicsDB; 279320; -.
DR DNASU; 68817; -.
DR Ensembl; ENSMUST00000102484; ENSMUSP00000099542; ENSMUSG00000078515.
DR GeneID; 68817; -.
DR KEGG; mmu:68817; -.
DR UCSC; uc008vpd.1; mouse.
DR CTD; 84301; -.
DR MGI; MGI:1917244; Ddi2.
DR VEuPathDB; HostDB:ENSMUSG00000078515; -.
DR eggNOG; KOG0012; Eukaryota.
DR GeneTree; ENSGT00390000005744; -.
DR HOGENOM; CLU_020435_1_0_1; -.
DR InParanoid; A2ADY9; -.
DR OMA; IHMVQIQ; -.
DR PhylomeDB; A2ADY9; -.
DR TreeFam; TF333421; -.
DR BioGRID-ORCS; 68817; 17 hits in 75 CRISPR screens.
DR ChiTaRS; Ddi2; mouse.
DR PRO; PR:A2ADY9; -.
DR Proteomes; UP000000589; Chromosome 4.
DR RNAct; A2ADY9; protein.
DR Bgee; ENSMUSG00000078515; Expressed in otolith organ and 224 other tissues.
DR ExpressionAtlas; A2ADY9; baseline and differential.
DR Genevisible; A2ADY9; MM.
DR GO; GO:0005694; C:chromosome; IEA:UniProtKB-SubCell.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0004190; F:aspartic-type endopeptidase activity; ISS:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; ISS:UniProtKB.
DR GO; GO:0043130; F:ubiquitin binding; ISO:MGI.
DR GO; GO:0072711; P:cellular response to hydroxyurea; ISS:UniProtKB.
DR GO; GO:0010498; P:proteasomal protein catabolic process; ISS:UniProtKB.
DR GO; GO:0016485; P:protein processing; ISS:UniProtKB.
DR GO; GO:0097752; P:regulation of DNA stability; ISS:UniProtKB.
DR GO; GO:0031647; P:regulation of protein stability; ISS:UniProtKB.
DR CDD; cd05479; RP_DDI; 1.
DR CDD; cd01796; Ubl_Ddi1_like; 1.
DR Gene3D; 2.40.70.10; -; 1.
DR InterPro; IPR033882; DDI1_N.
DR InterPro; IPR019103; Peptidase_aspartic_DDI1-type.
DR InterPro; IPR021109; Peptidase_aspartic_dom_sf.
DR InterPro; IPR000626; Ubiquitin-like_dom.
DR InterPro; IPR029071; Ubiquitin-like_domsf.
DR Pfam; PF09668; Asp_protease; 1.
DR Pfam; PF00240; ubiquitin; 1.
DR SUPFAM; SSF50630; SSF50630; 1.
DR SUPFAM; SSF54236; SSF54236; 1.
DR PROSITE; PS50053; UBIQUITIN_2; 1.
PE 1: Evidence at protein level;
KW Aspartyl protease; Chromosome; Cytoplasm; Hydrolase; Phosphoprotein;
KW Protease; Reference proteome.
FT CHAIN 1..399
FT /note="Protein DDI1 homolog 2"
FT /id="PRO_0000287091"
FT DOMAIN 1..81
FT /note="Ubiquitin-like"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00214"
FT REGION 99..134
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 376..395
FT /note="Ubiquitin-binding"
FT /evidence="ECO:0000305"
FT COMPBIAS 99..128
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 252
FT /evidence="ECO:0000305"
FT MOD_RES 104
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q5TDH0"
FT MOD_RES 121
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17242355,
FT ECO:0007744|PubMed:21183079"
FT MOD_RES 128
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17242355,
FT ECO:0007744|PubMed:21183079"
FT MOD_RES 150
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q5TDH0"
FT MOD_RES 194
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
SQ SEQUENCE 399 AA; 44591 MW; 25FBCEB27CC886DA CRC64;
MLLTVYCVRR DLSEVTFSLQ VDADFELHNF RALCELESGI PAAESQIVYA ERPLTDNHRS
LASYGLKDGD VVILRQKENA DPRPAVQFSN LPRIDFSSIA VPGTSNPQQR QLPRTQAQHS
SPGEMASSPQ GLDNPALLRD MLLANPHELS LLKERNPPLA EALLSGDLEK FSRVLVEQQQ
DRARREQERI RLFSADPFDL EAQAKIEEDI RQQNIEENMT IAMEEAPESF GQVAMLYINC
RVNGHPVKAF VDSGAQMTIM SQACAERCNI MRLVDRRWAG IAKGVGTQKI IGRVHLAQVQ
IEGDFLACSF SILEEQPMDM LLGLDMLKRH QCSIDLKKNV LVIGTTGSQT TFLPEGELPE
CARLAYGTGR EDIRPEEIAD QELAEAIQKS AEDAERQKP
