MDM4_RAT
ID MDM4_RAT Reviewed; 490 AA.
AC Q5XIN1;
DT 29-APR-2008, integrated into UniProtKB/Swiss-Prot.
DT 23-NOV-2004, sequence version 1.
DT 03-AUG-2022, entry version 135.
DE RecName: Full=Protein Mdm4;
DE AltName: Full=Double minute 4 protein;
DE AltName: Full=Mdm2-like p53-binding protein;
DE AltName: Full=Protein Mdmx;
DE AltName: Full=p53-binding protein Mdm4;
GN Name=Mdm4; Synonyms=Mdmx;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=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 [2]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-180, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
CC -!- FUNCTION: Inhibits p53/TP53- and TP73/p73-mediated cell cycle arrest
CC and apoptosis by binding its transcriptional activation domain.
CC Inhibits degradation of MDM2. Can reverse MDM2-targeted degradation of
CC TP53 while maintaining suppression of TP53 transactivation and
CC apoptotic functions (By similarity). {ECO:0000250}.
CC -!- SUBUNIT: Interacts with MDM2, TP53, TP73 and USP2. Found in a trimeric
CC complex with USP2, MDM2 and MDM4. Interacts (phosphorylated) with
CC YWHAG; negatively regulates MDM4 activity toward TP53 (By similarity).
CC {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250}.
CC -!- PTM: Phosphorylated. Phosphorylation at Ser-368 promotes interaction
CC with YWHAG and subsequent ubiquitination and degradation.
CC Phosphorylation at Ser-342 also induces ubiquitination and degradation
CC but to a lower extent (By similarity). {ECO:0000250}.
CC -!- PTM: Ubiquitinated and degraded by MDM2. Deubiquitination by USP2 on
CC the other hand stabilizes the MDM4 protein (By similarity).
CC {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the MDM2/MDM4 family. {ECO:0000305}.
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DR EMBL; BC083647; AAH83647.1; -; mRNA.
DR RefSeq; NP_001012026.1; NM_001012026.1.
DR AlphaFoldDB; Q5XIN1; -.
DR SMR; Q5XIN1; -.
DR STRING; 10116.ENSRNOP00000012984; -.
DR iPTMnet; Q5XIN1; -.
DR PhosphoSitePlus; Q5XIN1; -.
DR PaxDb; Q5XIN1; -.
DR GeneID; 304798; -.
DR KEGG; rno:304798; -.
DR UCSC; RGD:1309306; rat.
DR CTD; 4194; -.
DR RGD; 1309306; Mdm4.
DR VEuPathDB; HostDB:ENSRNOG00000009696; -.
DR eggNOG; ENOG502QQNV; Eukaryota.
DR HOGENOM; CLU_043544_2_0_1; -.
DR InParanoid; Q5XIN1; -.
DR OMA; ECKKYNT; -.
DR OrthoDB; 1329283at2759; -.
DR PhylomeDB; Q5XIN1; -.
DR TreeFam; TF105306; -.
DR Reactome; R-RNO-2559580; Oxidative Stress Induced Senescence.
DR Reactome; R-RNO-2559585; Oncogene Induced Senescence.
DR Reactome; R-RNO-5689880; Ub-specific processing proteases.
DR Reactome; R-RNO-6804756; Regulation of TP53 Activity through Phosphorylation.
DR Reactome; R-RNO-6804757; Regulation of TP53 Degradation.
DR Reactome; R-RNO-6804760; Regulation of TP53 Activity through Methylation.
DR Reactome; R-RNO-69541; Stabilization of p53.
DR PRO; PR:Q5XIN1; -.
DR Proteomes; UP000002494; Chromosome 13.
DR Bgee; ENSRNOG00000009696; Expressed in testis and 19 other tissues.
DR Genevisible; Q5XIN1; RN.
DR GO; GO:0005654; C:nucleoplasm; IEA:Ensembl.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0017053; C:transcription repressor complex; ISO:RGD.
DR GO; GO:0019899; F:enzyme binding; ISO:RGD.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0002039; F:p53 binding; IBA:GO_Central.
DR GO; GO:0003283; P:atrial septum development; ISO:RGD.
DR GO; GO:0003181; P:atrioventricular valve morphogenesis; ISO:RGD.
DR GO; GO:0071456; P:cellular response to hypoxia; ISO:RGD.
DR GO; GO:0030330; P:DNA damage response, signal transduction by p53 class mediator; ISO:RGD.
DR GO; GO:0003203; P:endocardial cushion morphogenesis; ISO:RGD.
DR GO; GO:0003170; P:heart valve development; ISO:RGD.
DR GO; GO:1902254; P:negative regulation of intrinsic apoptotic signaling pathway by p53 class mediator; ISO:RGD.
DR GO; GO:0042177; P:negative regulation of protein catabolic process; ISO:RGD.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; ISO:RGD.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; ISO:RGD.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; ISO:RGD.
DR GO; GO:0050821; P:protein stabilization; ISO:RGD.
DR GO; GO:0065003; P:protein-containing complex assembly; ISO:RGD.
DR GO; GO:0051726; P:regulation of cell cycle; IEA:InterPro.
DR GO; GO:0002027; P:regulation of heart rate; ISO:RGD.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0003281; P:ventricular septum development; ISO:RGD.
DR Gene3D; 1.10.245.10; -; 1.
DR Gene3D; 3.30.40.10; -; 1.
DR InterPro; IPR015458; MDM4.
DR InterPro; IPR016495; p53_neg-reg_MDM_2/4.
DR InterPro; IPR036885; SWIB_MDM2_dom_sf.
DR InterPro; IPR003121; SWIB_MDM2_domain.
DR InterPro; IPR001876; Znf_RanBP2.
DR InterPro; IPR036443; Znf_RanBP2_sf.
DR InterPro; IPR001841; Znf_RING.
DR InterPro; IPR013083; Znf_RING/FYVE/PHD.
DR PANTHER; PTHR13844:SF20; PTHR13844:SF20; 1.
DR Pfam; PF02201; SWIB; 1.
DR Pfam; PF00641; zf-RanBP; 1.
DR PIRSF; PIRSF500699; MDM4; 1.
DR PIRSF; PIRSF006748; p53_MDM_2/4; 1.
DR SUPFAM; SSF47592; SSF47592; 1.
DR SUPFAM; SSF90209; SSF90209; 1.
DR PROSITE; PS51925; SWIB_MDM2; 1.
DR PROSITE; PS01358; ZF_RANBP2_1; 1.
DR PROSITE; PS50199; ZF_RANBP2_2; 1.
DR PROSITE; PS50089; ZF_RING_2; 1.
PE 1: Evidence at protein level;
KW Metal-binding; Nucleus; Phosphoprotein; Reference proteome;
KW Ubl conjugation; Zinc; Zinc-finger.
FT CHAIN 1..490
FT /note="Protein Mdm4"
FT /id="PRO_0000331516"
FT DOMAIN 26..109
FT /note="SWIB/MDM2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01273"
FT ZN_FING 300..329
FT /note="RanBP2-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00322"
FT ZN_FING 437..478
FT /note="RING-type; degenerate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00175"
FT REGION 136..162
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 263..294
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 393..490
FT /note="Necessary for interaction with USP2"
FT /evidence="ECO:0000250"
FT MOTIF 442..445
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000255"
FT COMPBIAS 266..294
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 180
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 342
FT /note="Phosphoserine; by CHEK2"
FT /evidence="ECO:0000250|UniProtKB:O15151"
FT MOD_RES 368
FT /note="Phosphoserine; by CHEK1 and CHEK2"
FT /evidence="ECO:0000250|UniProtKB:O15151"
SQ SEQUENCE 490 AA; 55221 MW; 7286E5E024E8AAE0 CRC64;
MTSHSTSAQC SASDSACRIS SEQINQQVRP KLQLLKILQA AGAQGEVFTM KEVMHYLGQY
IMVKQLYDQQ EQHLVYCGGD LLGDLLGCQS FSVKDPSPLY DMLRKNLVTS ASVNTDAAQT
LALAQDHTMD IPSQDRLKHG ATECSNPRKR TEEDDTHTLP TSRRKCRDSR ADEDLIEHLS
QDETSRLDLD FEEWDVAGLP WWFLGNLRNN YIPRSNGSTD LQTNQDIGTA IVSDTTDDLW
FLNETVSEQL GVGVKVEAAN CEQPSEVGRT RDKKMVEGGK DDDLEDSKSL SDDTDVEVTS
EDEWQCTECK KFNSPSKRYC FRCWALRKDW YSDCSKLTHS LSTSNITAIP EKKDNEGIDV
PDCRRTISAP VVRPKDGYLK EEKPRFDPCN SVEFLDLAHG SESQEIISST REQTDIFSEQ
KTETESMEDF QNVLKPCSLC EKRPRDGNII HGKTSHLTTC FHCARRLKKS GASCPACKKE
IQLVIKVFIA
