UniProtKB - Q7YRZ8 (MDM2_FELCA)
E3 ubiquitin-protein ligase Mdm2
MDM2
Functioni
Catalytic activityi
- S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine + [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-cysteine + N(6)-ubiquitinyl-[acceptor protein]-L-lysine.By similarity EC:2.3.2.27
Regions
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Zinc fingeri | 299 – 328 | RanBP2-typePROSITE-ProRule annotationAdd BLAST | 30 | |
Zinc fingeri | 438 – 479 | RING-typePROSITE-ProRule annotationAdd BLAST | 42 |
GO - Molecular functioni
- 5S rRNA binding Source: UniProtKB
- identical protein binding Source: InterPro
- metal ion binding Source: UniProtKB-KW
- ribonucleoprotein complex binding Source: UniProtKB
- ubiquitin binding Source: UniProtKB
- ubiquitin protein ligase activity Source: GO_Central
GO - Biological processi
- negative regulation of apoptotic process Source: InterPro
- negative regulation of cell cycle arrest Source: InterPro
- negative regulation of transcription, DNA-templated Source: UniProtKB
- negative regulation of transcription by RNA polymerase II Source: UniProtKB
- positive regulation of transcription by RNA polymerase II Source: GOC
- protein ubiquitination Source: UniProtKB
- regulation of transcription by RNA polymerase II Source: GO_Central
Keywordsi
Molecular function | Transferase |
Biological process | Ubl conjugation pathway |
Ligand | Metal-binding, Zinc |
Names & Taxonomyi
Protein namesi | Recommended name: E3 ubiquitin-protein ligase Mdm2 (EC:2.3.2.27By similarity)Alternative name(s): Double minute 2 protein RING-type E3 ubiquitin transferase Mdm2Curated p53-binding protein Mdm2 |
Gene namesi | Name:MDM2 |
Organismi | Felis catus (Cat) (Felis silvestris catus) |
Taxonomic identifieri | 9685 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Laurasiatheria › Carnivora › Feliformia › Felidae › Felinae › Felis |
Proteomesi |
|
Subcellular locationi
Nucleus
- nucleoplasm By similarity
- nucleolus By similarity
Other locations
- Cytoplasm By similarity
Note: Expressed predominantly in the nucleoplasm. Interaction with ARF(P14) results in the localization of both proteins to the nucleolus. The nucleolar localization signals in both ARF(P14) and MDM2 may be necessary to allow efficient nucleolar localization of both proteins. Colocalizes with RASSF1 isoform A in the nucleus (By similarity). Interacts with IGF1R (By similarity).By similarity
Nucleus
- nucleolus Source: UniProtKB
- nucleoplasm Source: UniProtKB
- nucleus Source: UniProtKB
Other locations
- cytoplasm Source: UniProtKB-SubCell
Keywords - Cellular componenti
Cytoplasm, NucleusPTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000157330 | 1 – 491 | E3 ubiquitin-protein ligase Mdm2Add BLAST | 491 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 166 | Phosphoserine; by SGK1By similarity | 1 | |
Modified residuei | 190 | PhosphoserineBy similarity | 1 | |
Modified residuei | 240 | PhosphoserineBy similarity | 1 | |
Modified residuei | 242 | PhosphoserineBy similarity | 1 | |
Modified residuei | 246 | PhosphoserineBy similarity | 1 | |
Modified residuei | 260 | PhosphoserineBy similarity | 1 | |
Modified residuei | 262 | PhosphoserineBy similarity | 1 | |
Modified residuei | 386 | Phosphoserine; by ATMBy similarity | 1 | |
Modified residuei | 395 | Phosphoserine; by ATMBy similarity | 1 | |
Modified residuei | 407 | Phosphoserine; by ATMBy similarity | 1 | |
Modified residuei | 419 | Phosphothreonine; by ATMBy similarity | 1 | |
Modified residuei | 429 | Phosphoserine; by ATMBy similarity | 1 |
Post-translational modificationi
Keywords - PTMi
Phosphoprotein, Ubl conjugationProteomic databases
PRIDEi | Q7YRZ8 |
Interactioni
Subunit structurei
Interacts with p53/TP53, TP73/p73, RBL5 and RP11. Binds specifically to RNA. Can interact with RB1, E1A-associated protein EP300 and the E2F1 transcription factor.
Forms a ternary complex with p53/TP53 and WWOX.
Interacts with CDKN2AIP, RFWD3, USP7, PYHIN1 and RBBP6.
Interacts with ARRB1 and ARRB2.
Interacts with PSMA3.
Found in a trimeric complex with MDM2, MDM4 and USP2.
Interacts with USP2 (via N-terminus and C-terminus).
Interacts with MDM4.
Part of a complex with MDM2, DAXX, RASSF1 and USP7.
Part of a complex with DAXX, MDM2 and USP7.
Interacts directly with DAXX and USP7.
Interacts (via C-terminus) with RASSF1 isoform A (via N-terminus); the interaction is independent of TP53.
Interacts with APEX1; leading to its ubiquitination and degradation.
Interacts with RYBP; this inhibits ubiquitination of TP53.
Identified in a complex with RYBP and p53/TP53. Also component of the TRIM28/KAP1-MDM2-p53/TP53 complex involved in regulating p53/TP53 stabilization and activity. Binds directly both p53/TP53 and TRIM28.
Component of the TRIM28/KAP1-ERBB4-MDM2 complex involved in connecting growth factor responses with DNA damage.
Interacts directly with both TRIM28 and ERBB4 in the complex.
Interacts with DYRK2.
Interacts with IGF1R.
Interacts with TRIM13; the interaction ubiquitinates MDM2 leading to its proteasomal degradation.
Interacts with SNAI1; this interaction promotes SNAI1 ubiquitination.
Interacts with NOTCH1 (via intracellular domain).
Interacts with FHIT.
Interacts with RFFL and RNF34; the interaction stabilizes MDM2.
Interacts with CDK5RAP3 and CDKN2A/ARF; form a ternary complex involved in regulation of p53/TP53.
Interacts with MTA1.
Interacts with AARB2.
Interacts with MTBP.
Interacts with PML.
Interacts with RPL11.
Interacts with TBRG1.
Interacts with the 5S RNP which is composed of the 5S RNA, RPL5 and RPL11; the interaction is direct occurs in the nucleoplasm and negatively regulates MDM2-mediated TP53 ubiquitination and degradation.
Interacts with ADGRB1; the interaction results in inhibition of MDM2-mediated ubiquitination and degradation of DLG4/PSD95, promoting DLG4 stability and regulating synaptic plasticity.
Interacts with RPL23A; this interaction may promote p53/TP53 polyubiquitination (By similarity).
By similarityGO - Molecular functioni
- identical protein binding Source: InterPro
- ubiquitin binding Source: UniProtKB
Protein-protein interaction databases
STRINGi | 9685.ENSFCAP00000025067 |
Structurei
Secondary structure
3D structure databases
BMRBi | Q7YRZ8 |
SMRi | Q7YRZ8 |
ModBasei | Search... |
PDBe-KBi | Search... |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 26 – 109 | SWIB/MDM2PROSITE-ProRule annotationAdd BLAST | 84 |
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 1 – 110 | Necessary for interaction with USP2By similarityAdd BLAST | 110 | |
Regioni | 150 – 230 | Interaction with PYHIN1 and necessary for interaction with RFFL and RNF34By similarityAdd BLAST | 81 | |
Regioni | 170 – 306 | Interaction with MTBPBy similarityAdd BLAST | 137 | |
Regioni | 210 – 304 | ARF-bindingAdd BLAST | 95 | |
Regioni | 223 – 232 | Interaction with USP7By similarity | 10 | |
Regioni | 242 – 331 | Region IIAdd BLAST | 90 | |
Regioni | 276 – 491 | Necessary for interaction with USP2By similarityAdd BLAST | 216 |
Motif
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Motifi | 179 – 185 | Nuclear localization signalSequence analysis | 7 | |
Motifi | 190 – 202 | Nuclear export signalAdd BLAST | 13 | |
Motifi | 466 – 473 | Nucleolar localization signalSequence analysis | 8 |
Compositional bias
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Compositional biasi | 210 – 215 | Poly-Ser | 6 | |
Compositional biasi | 243 – 301 | Asp/Glu-rich (acidic)Add BLAST | 59 |
Domaini
Sequence similaritiesi
Zinc finger
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Zinc fingeri | 299 – 328 | RanBP2-typePROSITE-ProRule annotationAdd BLAST | 30 | |
Zinc fingeri | 438 – 479 | RING-typePROSITE-ProRule annotationAdd BLAST | 42 |
Keywords - Domaini
Zinc-fingerPhylogenomic databases
eggNOGi | ENOG502QQNV, Eukaryota |
InParanoidi | Q7YRZ8 |
OrthoDBi | 1329283at2759 |
Family and domain databases
CDDi | cd16783, mRING-HC-C2H2C4_MDM2, 1 hit |
Gene3Di | 1.10.245.10, 1 hit 3.30.40.10, 1 hit |
InterProi | View protein in InterPro IPR028340, Mdm2 IPR015459, MDM2_E3_ligase IPR044080, MDM2_mRING-HC-C2H2C4 IPR016495, p53_neg-reg_MDM_2/4 IPR036885, SWIB_MDM2_dom_sf IPR003121, SWIB_MDM2_domain IPR001876, Znf_RanBP2 IPR036443, Znf_RanBP2_sf IPR001841, Znf_RING IPR013083, Znf_RING/FYVE/PHD |
PANTHERi | PTHR13844:SF15, PTHR13844:SF15, 1 hit |
Pfami | View protein in Pfam PF02201, SWIB, 1 hit PF00641, zf-RanBP, 1 hit |
PIRSFi | PIRSF500700, MDM2, 1 hit PIRSF006748, p53_MDM_2/4, 1 hit |
SUPFAMi | SSF47592, SSF47592, 2 hits SSF90209, SSF90209, 1 hit |
PROSITEi | View protein in PROSITE PS51925, SWIB_MDM2, 1 hit PS01358, ZF_RANBP2_1, 1 hit PS50199, ZF_RANBP2_2, 1 hit PS50089, ZF_RING_2, 1 hit |
i Sequence
Sequence statusi: Complete.
10 20 30 40 50
MCNTNMSVST DGAVSTSQMP ASEQETLVRP KPLLLKLLKS VGAQKDTYTM
60 70 80 90 100
KEVIFYLGQY IMTKRLYDEK QQHIVYCSND LLGDLFGVPS FSVKEHRKIY
110 120 130 140 150
TMIYRNLVVV NQHEPSDSGT SVSENRCHLE GGSDQKDPVQ ELQEEKPSSS
160 170 180 190 200
DLVSRPSTSS RRRTISETEE HSDELPGERQ RKRHKSDSIS LSFDESLALC
210 220 230 240 250
VIREICCERS SSSESTGTPS NPDLDAGVSE HSGDWLDQDS VSDQFSVEFE
260 270 280 290 300
VESLDSEDYS LSEEGQELSD EDDEVYRVTV YQAGESDTDS FEEDPEISLA
310 320 330 340 350
DYWKCTSCNE MNPPLPPHCN RCWALRENWL PEDKGKDKGK MPEKAKVENS
360 370 380 390 400
TQVEEGFDVP DCKRTTVNDS RESCAEENDD KITQASQSQE SEDYSQPSTS
410 420 430 440 450
NSIIHSSQED VKEFEREETQ DKEEIVEPSF PHNAIEPCVI CQGRPKNGCI
460 470 480 490
VHGKTGHLMA CFTCAKKLKK RNKPCPVCRQ PIQMIVLTYF P
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AB099709 mRNA Translation: BAC78209.1 |
RefSeqi | NP_001009346.1, NM_001009346.1 |
Genome annotation databases
GeneIDi | 493939 |
KEGGi | fca:493939 |
Similar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AB099709 mRNA Translation: BAC78209.1 |
RefSeqi | NP_001009346.1, NM_001009346.1 |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
6SQS | X-ray | 1.83 | A/D | 428-491 | [»] | |
BMRBi | Q7YRZ8 | |||||
SMRi | Q7YRZ8 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
STRINGi | 9685.ENSFCAP00000025067 |
Proteomic databases
PRIDEi | Q7YRZ8 |
Genome annotation databases
GeneIDi | 493939 |
KEGGi | fca:493939 |
Organism-specific databases
CTDi | 4193 |
Phylogenomic databases
eggNOGi | ENOG502QQNV, Eukaryota |
InParanoidi | Q7YRZ8 |
OrthoDBi | 1329283at2759 |
Family and domain databases
CDDi | cd16783, mRING-HC-C2H2C4_MDM2, 1 hit |
Gene3Di | 1.10.245.10, 1 hit 3.30.40.10, 1 hit |
InterProi | View protein in InterPro IPR028340, Mdm2 IPR015459, MDM2_E3_ligase IPR044080, MDM2_mRING-HC-C2H2C4 IPR016495, p53_neg-reg_MDM_2/4 IPR036885, SWIB_MDM2_dom_sf IPR003121, SWIB_MDM2_domain IPR001876, Znf_RanBP2 IPR036443, Znf_RanBP2_sf IPR001841, Znf_RING IPR013083, Znf_RING/FYVE/PHD |
PANTHERi | PTHR13844:SF15, PTHR13844:SF15, 1 hit |
Pfami | View protein in Pfam PF02201, SWIB, 1 hit PF00641, zf-RanBP, 1 hit |
PIRSFi | PIRSF500700, MDM2, 1 hit PIRSF006748, p53_MDM_2/4, 1 hit |
SUPFAMi | SSF47592, SSF47592, 2 hits SSF90209, SSF90209, 1 hit |
PROSITEi | View protein in PROSITE PS51925, SWIB_MDM2, 1 hit PS01358, ZF_RANBP2_1, 1 hit PS50199, ZF_RANBP2_2, 1 hit PS50089, ZF_RING_2, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | MDM2_FELCA | |
Accessioni | Q7YRZ8Primary (citable) accession number: Q7YRZ8 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | November 23, 2004 |
Last sequence update: | October 1, 2003 | |
Last modified: | February 10, 2021 | |
This is version 114 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program |
Miscellaneousi
Keywords - Technical termi
3D-structure, Reference proteomeDocuments
- PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families