Q00987

※ Protein Information

Tag	Content
UniProt Accession	MDM2_HUMAN; Q00987;
Entrez ID	4193
GenBank Protein ID	NM_001145339.2; NM_001278462.1; NM_002392.5; XM_005268872.4; XM_006719399.3;
GenBank Nucleotide ID	NP_001138811.1; NP_001265391.1; NP_002383.2; XP_005268929.1; XP_006719462.1;
Protein Name	E3 ubiquitin-protein ligase Mdm2 (EC 2.3.2.27) (Double minute 2 protein) (Hdm2) (Oncoprotein Mdm2) (RING-type E3 ubiquitin transferase Mdm2) (p53-binding protein Mdm2)
Gene Name	MDM2
Organism	Homo sapiens
NCBI Taxa ID	9606
Functional Description	E3 ubiquitin-protein ligase that mediates ubiquitination of p53/TP53, leading to its degradation by the proteasome. Inhibits p53/TP53- and p73/TP73-mediated cell cycle arrest and apoptosis by binding its transcriptional activation domain. Also acts as a ubiquitin ligase E3 toward itself and ARRB1. Permits the nuclear export of p53/TP53. Promotes proteasome-dependent ubiquitin-independent degradation of retinoblastoma RB1 protein. Inhibits DAXX-mediated apoptosis by inducing its ubiquitination and degradation. Component of the TRIM28/KAP1-MDM2-p(view all) Functional Description E3 ubiquitin-protein ligase that mediates ubiquitination of p53/TP53, leading to its degradation by the proteasome. Inhibits p53/TP53- and p73/TP73-mediated cell cycle arrest and apoptosis by binding its transcriptional activation domain. Also acts as a ubiquitin ligase E3 toward itself and ARRB1. Permits the nuclear export of p53/TP53. Promotes proteasome-dependent ubiquitin-independent degradation of retinoblastoma RB1 protein. Inhibits DAXX-mediated apoptosis by inducing its ubiquitination and degradation. Component of the TRIM28/KAP1-MDM2-p53/TP53 complex involved in stabilizing p53/TP53. Also component of the TRIM28/KAP1-ERBB4-MDM2 complex which links growth factor and DNA damage response pathways. Mediates ubiquitination and subsequent proteasome degradation of DYRK2 in nucleus. Ubiquitinates IGF1R and SNAI1 and promotes them to proteasomal degradation (PubMed:12821780, PubMed:15053880, PubMed:15195100, PubMed:15632057, PubMed:16337594, PubMed:17290220, PubMed:19098711, PubMed:19219073, PubMed:19837670, PubMed:19965871, PubMed:20173098, PubMed:20385133, PubMed:20858735, PubMed:22128911). Ubiquitinates DCX, leading to DCX degradation and reduction of the dendritic spine density of olfactory bulb granule cells (By similarity). Ubiquitinates DLG4, leading to proteasomal degradation of DLG4 which is required for AMPA receptor endocytosis (By similarity).
Sequence (Fasta)	MCNTNMSVPT DGAVTTSQIP ASEQETLVRP KPLLLKLLKS VGAQKDTYTM KEVLFYLGQY 60 IMTKRLYDEK QQHIVYCSND LLGDLFGVPS FSVKEHRKIY TMIYRNLVVV NQQESSDSGT 120 SVSENRCHLE GGSDQKDLVQ ELQEEKPSSS HLVSRPSTSS RRRAISETEE NSDELSGERQ 180 RKRHKSDSIS LSFDESLALC VIREICCERS SSSESTGTPS NPDLDAGVSE HSGDWLDQDS 240 VSDQFSVEFE VESLDSEDYS LSEEGQELSD EDDEVYQVTV YQAGESDTDS FEEDPEISLA 300 DYWKCTSCNE MNPPLPSHCN RCWALRENWL PEDKGKDKGE ISEKAKLENS TQAEEGFDVP 360 DCKKTIVNDS RESCVEENDD KITQASQSQE SEDYSQPSTS SSIIYSSQED VKEFEREETQ 420 DKEESVESSL PLNAIEPCVI CQGRPKNGCI VHGKTGHLMA CFTCAKKLKK RNKPCPVCRQ 480 PIQMIVLTYF P 492 Fasta Sequence >Q00987\|MDM2\|Homo sapiens (Human) MCNTNMSVPTDGAVTTSQIPASEQETLVRPKPLLLKLLKSVGAQKDTYTMKEVLFYLGQYIMTKRLYDEKQQHIVYCSNDLLGDLFGVPSFSVKEHRKIYTMIYRNLVVVNQQESSDSGTSVSENRCHLEGGSDQKDLVQELQEEKPSSSHLVSRPSTSSRRRAISETEENSDELSGERQRKRHKSDSISLSFDESLALCVIREICCERSSSSESTGTPSNPDLDAGVSEHSGDWLDQDSVSDQFSVEFEVESLDSEDYSLSEEGQELSDEDDEVYQVTVYQAGESDTDSFEEDPEISLADYWKCTSCNEMNPPLPSHCNRCWALRENWLPEDKGKDKGEISEKAKLENSTQAEEGFDVPDCKKTIVNDSRESCVEENDDKITQASQSQESEDYSQPSTSSSIIYSSQEDVKEFEREETQDKEESVESSLPLNAIEPCVICQGRPKNGCIVHGKTGHLMACFTCAKKLKKRNKPCPVCRQPIQMIVLTYFP

※ PTM-Disease Association

Num	PTM	Disease	Type	PTM Site	PMID
1	Threonine Phosphorylation	Prostate cancer/carcinoma/adenocarcinoma	P	T158	23132866
1	[Reference]: p21-Activated kinase 6 (PAK6) inhibits prostate cancer growth via phosphorylation of androgen receptor and tumorigenic E3 ligase murine double minute-2 (Mdm2)
2	Serine Phosphorylation	B-cell lymphoma	U	S166	18467333
2	[Reference]: Additionally, the Pim kinases phosphorylate Mdm2 in vitro and in cultured cells at Ser(166) and Ser(186), two previously identified targets of other signaling pathways, including Akt. Surprisingly, at high levels of Pim expression, as would occur in tumors, active, but not inactive, Pim-1 or Pim-2 blocks the degradation of both p53 and Mdm2 in a manner that is independent of Mdm2 phosphorylation, leading to increased p53 levels and, proportionately, p53-dependent transactivation.?
3	Serine Phosphorylation	Renal cancer/carcinoma	U	S166	19920202
3	[Reference]: Primary CCRCC specimens exhibiting strong hypoxic signatures show increased levels of activated nuclear phospho-Hdm2(Ser(166)), which is concomitant with low p53 expression.
4	Serine Phosphorylation	Prostate cancer/carcinoma/adenocarcinoma	P	S186	23132866
4	[Reference]: p21-Activated kinase 6 (PAK6) inhibits prostate cancer growth via phosphorylation of androgen receptor and tumorigenic E3 ligase murine double minute-2 (Mdm2)
5	Serine Phosphorylation	B-cell lymphoma	U	S186	18467333
5	[Reference]: Elevated levels of oncogenic protein kinase Pim-1 induce the p53 pathway in cultured cells and correlate with increased Mdm2 in mantle cell lymphoma.

※ Disease Cross-ref Annotation

Database	Annotation
Cancer Gene Census	sarcoma, glioma, colorectal, other tumour types
CTD (Curated) (count: 8) (view all)	MESH:D001943 ; Breast Neoplasms MESH:D002471 ; Cell Transformation, Neoplastic MESH:D015658 ; HIV Infections MESH:D007248 ; Infertility, Male MESH:D008545 ; Melanoma MESH:D002289 ; Carcinoma, Non-Small-Cell Lung MESH:D011230 ; Precancerous Conditions MESH:D011471 ; Prostatic Neoplasms
DisGeNet (Curated) (count: 26) (view all)	C0001618; Tumors of Adrenal Cortex C0007114; Malignant neoplasm of skin C0007131; Non-Small Cell Lung Carcinoma C0007621; Neoplastic Cell Transformation C0009375; Colonic Neoplasms C0019693; HIV Infections C0021364; Male infertility C0024299; Lymphoma C0025202; melanoma C0027766; Nervous System Neoplasms C0029463; Osteosarcoma C0030297; Pancreatic Neoplasm C0032927; Precancerous Conditions C0033578; Prostatic Neoplasms C0037286; Skin Neoplasms C0085390; Li-Fraumeni Syndrome C0151811; Subcutaneous nodule C0205824; Liposarcoma, Dedifferentiated C0346647; Malignant neoplasm of pancreas C0678222; Breast Carcinoma C0746926; Multiple, subcutaneous nodules C1370889; Liposarcoma, well differentiated C1458155; Mammary Neoplasms C1838578; Encephalopathy, progressive C1842408; Increased risk of pancreatic cancer C4280575; Progressive brain disease
HGMD (count: 2)	CR082025; Bladder cancer, increased risk, association with; Regulatory CR043384; Cancer suseptibility, assoc. with; Regulatory

※ PTM Sites

PTM	Modification Sites
Phosphorylation (count: 53) (view all)	118 NQQESSDSGTSVSEN dbPAF 121 ESSDSGTSVSENRCH dbPAF 148 ELQEEKPSSSHLVSR dbPAF 157 SHLVSRPSTSSRRRA dbPAF 158 HLVSRPSTSSRRRAI dbPAF 160 VSRPSTSSRRRAISE dbPAF 166 SSRRRAISETEENSD dbPAF 168 RRRAISETEENSDEL dbPAF 17 TDGAVTTSQIPASEQ dbPAF 172 ISETEENSDELSGER dbPAF 176 EENSDELSGERQRKR dbPAF 186 RQRKRHKSDSISLSF dbPAF 188 RKRHKSDSISLSFDE dbPAF 190 RHKSDSISLSFDESL dbPAF 192 KSDSISLSFDESLAL dbPAF 196 ISLSFDESLALCVIR dbPAF 218 SSSESTGTPSNPDLD dbPAF 220 SESTGTPSNPDLDAG dbPAF 229 PDLDAGVSEHSGDWL dbPAF 240 GDWLDQDSVSDQFSV dbPAF 242 WLDQDSVSDQFSVEF dbPAF 246 DSVSDQFSVEFEVES dbPAF 253 SVEFEVESLDSEDYS dbPAF 256 FEVESLDSEDYSLSE dbPAF 260 SLDSEDYSLSEEGQE dbPAF 262 DSEDYSLSEEGQELS dbPAF 269 SEEGQELSDEDDEVY dbPAF 276 SDEDDEVYQVTVYQA dbPAF 279 DDEVYQVTVYQAGES dbPAF 281 EVYQVTVYQAGESDT dbPAF 286 TVYQAGESDTDSFEE dbPAF 288 YQAGESDTDSFEEDP dbPAF 290 AGESDTDSFEEDPEI dbPAF 302 PEISLADYWKCTSCN dbPAF 306 LADYWKCTSCNEMNP dbPAF 307 ADYWKCTSCNEMNPP dbPAF 342 GKDKGEISEKAKLEN dbPAF 350 EKAKLENSTQAEEGF dbPAF 351 KAKLENSTQAEEGFD dbPAF 365 DVPDCKKTIVNDSRE dbPAF 373 IVNDSRESCVEENDD dbPAF 386 DDKITQASQSQESED dbPAF 388 KITQASQSQESEDYS dbPAF 394 QSQESEDYSQPSTSS dbPAF 395 SQESEDYSQPSTSSS dbPAF 401 YSQPSTSSSIIYSSQ dbPAF 405 STSSSIIYSSQEDVK dbPAF 406 TSSSIIYSSQEDVKE dbPAF 407 SSSIIYSSQEDVKEF dbPAF 419 KEFEREETQDKEESV dbPAF 425 ETQDKEESVESSLPL dbPAF 429 KEESVESSLPLNAIE dbPAF 60 VLFYLGQYIMTKRLY dbPAF
Acetylation (count: 5)	39 PLLLKLLKSVGAQKD PLMD 466 MACFTCAKKLKKRNK PLMD 467 ACFTCAKKLKKRNKP PLMD 469 FTCAKKLKKRNKPCP PLMD 470 TCAKKLKKRNKPCPV PLMD
Ubiquitination (count: 11) (view all)	334 ENWLPEDKGKDKGEI PLMD 336 WLPEDKGKDKGEISE PLMD 338 PEDKGKDKGEISEKA PLMD 344 DKGEISEKAKLENST PLMD 346 GEISEKAKLENSTQA PLMD 36 RPKPLLLKLLKSVGA PLMD 363 GFDVPDCKKTIVNDS PLMD 364 FDVPDCKKTIVNDSR PLMD 45 LKSVGAQKDTYTMKE PLMD 473 KKLKKRNKPCPVCRQ PLMD 70 TKRLYDEKQQHIVYC PLMD
Sumoylation (count: 1)	446 VICQGRPKNGCIVHG PLMD

※ Protein-Protein Interaction

Network

Interaction

Source

O00463	Q00987	IntAct
O95863	Q00987	MINT
O96017	Q00987	MINT
P03372	Q00987	HPRD; IntAct
P04637	Q00987	HPRD; DIP; IntAct; MINT
P05067	Q00987	IntAct
P05412	Q00987	IntAct
P06400	Q00987	HPRD; DIP; IntAct; MINT
P08069	Q00987	HPRD; IntAct
P09211	Q00987	IntAct
P10275	Q00987	HPRD; DIP; IntAct
P15311	Q00987	IntAct
P18848	Q00987	IntAct
P20309	Q00987	IntAct
P29590	Q00987	HPRD; IntAct; MINT
P31749	Q00987	HPRD; DIP; IntAct; MINT
P42575	Q00987	IntAct
P49757	Q00987	HPRD
P53350	Q00987	MINT
Q00987	Q04206	IntAct
Q00987	Q13315	HPRD
Q00987	Q5T7V8	MINT
Q00987	Q8N726	HPRD; DIP; IntAct; MINT
Q00987	Q92736	IntAct
Q00987	Q92905	HPRD
Q00987	Q9NS23	HPRD; MINT

PTMD Annotation Information

※ Protein Information

Functional Description

Fasta Sequence

※ PTM-Disease Association

※ Disease Cross-ref Annotation

※ PTM Sites

※ Protein-Protein Interaction