AiPD: Autoinhibited Protein Database

O15151

Gene name	MDM4 (MDMX)
Protein name	Protein Mdm4
Names	Double minute 4 protein, Mdm2-like p53-binding protein, Protein Mdmx, p53-binding protein Mdm4
Species	Homo sapiens (Human)
KEGG Pathway	hsa:4194
EC number
Protein Class	MITOCHONDRIAL UBIQUITIN LIGASE ACTIVATOR OF NFKB 1 (PTHR12183)

Descriptions

MDM4 is a homologous protein that binds to p53 and regulates its activity. Residues 190-210 in that intrinsically disordered region constitute an inhibitory module. It competes with the p53TAD for binding to the N-terminal SWIB-like domain (NTD) of MDMX, thus lowering the affinity of MDMX for p53. Efficient binding of MDMX to p53 requires a mechanism to relieve the allosteric self-inhibition.

Autoinhibitory domains (AIDs)

Target domain	25-108 (N-terminal SWIB-like domain)
Relief mechanism	Partner binding
Assay	Deletion assay, Mutagenesis experiment, Structural analysis

AID

190-210 (Tryptophan-rich segment)

Target domain

25-108 (N-terminal SWIB-like domain)

Relief mechanism

Partner binding (Regulatory protein binding)

Assay

Deletion assay, Mutagenesis experiment, Structural analysis

Accessory elements

No accessory elements

References

Bista M et al. (2013) "MDMX contains an autoinhibitory sequence element", Proceedings of the National Academy of Sciences of the United States of America, 110, 17814-9

Autoinhibited structure

Activated structure

40 structures for O15151

Entry ID	Method	Resolution	Chain	Position	Source
2CR8	NMR	-	A	300-339	PDB
2MWY	NMR	-	A	23-111	PDB
2N06	NMR	-	A	23-111	PDB
2N0U	NMR	-	A	23-111	PDB
2N0W	NMR	-	A	23-111	PDB
2N14	NMR	-	A	23-111	PDB
2VJE	X-ray	220 A	B/D	428-490	PDB
2VJF	X-ray	230 A	B/D	428-490	PDB
2VYR	X-ray	200 A	A/B/C/D	16-116	PDB
3DAB	X-ray	190 A	A/C/E/G	23-111	PDB
3EQY	X-ray	163 A	A/B	24-108	PDB
3FDO	X-ray	140 A	A	23-111	PDB
3FE7	X-ray	135 A	A	14-111	PDB
3FEA	X-ray	133 A	A	14-111	PDB
3JZO	X-ray	180 A	A	23-111	PDB
3JZP	X-ray	174 A	A	23-111	PDB
3JZQ	X-ray	180 A	A/B	23-111	PDB
3LBJ	X-ray	150 A	E	23-111	PDB
3MQR	X-ray	180 A	B	395-404	PDB
3U15	X-ray	180 A	A/B/C/D	14-111	PDB
4RXZ	X-ray	155 A	A/B	24-108	PDB
5MNJ	X-ray	216 A	D/H	427-490	PDB
5UML	X-ray	300 A	A/B/E/G	24-108	PDB
5VK1	X-ray	269 A	A/C/E/G/I/K/M/O	24-108	PDB
6Q9Q	X-ray	210 A	A/B/C/D	14-111	PDB
6Q9S	X-ray	240 A	A/B/C	14-111	PDB
6Q9U	X-ray	240 A	A	14-111	PDB
6Q9W	X-ray	155 A	A/B	14-111	PDB
6Q9Y	X-ray	120 A	A/B	14-111	PDB
6YR5	X-ray	225 A	O/P/Q/R	361-374	PDB
6YR7	X-ray	210 A	C/Q	335-374	PDB
7C3Q	X-ray	180 A	A	23-108	PDB
7C3Y	X-ray	163 A	A	23-108	PDB
7C44	X-ray	165 A	A	23-108	PDB
7EL4	X-ray	211 A	A	23-111	PDB
7KJN	X-ray	280 A	A	24-108	PDB
7MLA	NMR	-	A	428-490	PDB
8HDG	X-ray	173 A	A/B/C/D	23-111	PDB
8IA5	X-ray	193 A	A	23-111	PDB
AF-O15151-F1	Predicted				AlphaFoldDB

289 variants for O15151

Variant ID(s)	Position	Change	Description	Diseaes Association	Provenance
VAR_084553 CA344369028 RCV001531036 RCV001089508 rs1270135772	454	T>M	Bone marrow failure syndrome 6 BMFS6; altered capacity to interact with MDM2 RING domain in a yeast two-hybrid assay; no effect on ATP binding; expressed at lower levels than wild-type; when expressed in a mouse model, leads to increased TP53 activity, decreased telomerase length and ultimately to bone marrow failure [ClinVar, UniProt]	Yes	ClinGen ClinVar UniProt TOPMed dbSNP
CA344359728 rs1382884218	2	T>A		No	ClinGen TOPMed gnomAD
rs1382884218 CA344359726	2	T>S		No	ClinGen TOPMed gnomAD
CA35809540 rs558828094	6	T>A		No	ClinGen TOPMed gnomAD
rs558828094 CA344359784	6	T>S		No	ClinGen TOPMed gnomAD
rs115828402 RCV000881022 CA1348462	8	A>T		No	ClinGen ClinVar 1000Genomes ESP ExAC TOPMed dbSNP gnomAD
CA344359810 rs1202317431	9	Q>E		No	ClinGen gnomAD
rs905303517 CA35809547	12	T>A		No	ClinGen TOPMed gnomAD
rs905303517 CA344359851	12	T>P		No	ClinGen TOPMed gnomAD
CA1348463 rs780902661	16	A>T		No	ClinGen ExAC
rs1249145025 CA344359920	17	C>R		No	ClinGen TOPMed
rs754269993 CA35809585	18	R>G		No	ClinGen Ensembl
CA1348465 rs148900701	19	I>M		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
CA344360289 rs1185480236	19	I>S		No	ClinGen gnomAD
rs779696576 CA1348466	20	S>F		No	ClinGen ExAC
rs1481232207 CA344360306	21	P>S		No	ClinGen TOPMed gnomAD
rs1481232207 CA344360303	21	P>T		No	ClinGen TOPMed gnomAD
rs748876366 CA1348467	22	G>R		No	ClinGen ExAC gnomAD
CA1348469 rs773983041	23	Q>H		No	ClinGen ExAC gnomAD
rs773983041 CA344360339	23	Q>H		No	ClinGen ExAC gnomAD
CA344360331 rs1428358052	23	Q>K		No	ClinGen gnomAD
CA1348468 rs369657471	23	Q>L		No	ClinGen ESP ExAC TOPMed gnomAD
CA344360333 rs369657471	23	Q>P		No	ClinGen ESP ExAC TOPMed gnomAD
CA344360345 rs1345762411	24	I>V		No	ClinGen gnomAD
rs1011975434 CA35809621	25	N>I		No	ClinGen gnomAD
rs1056671167 CA344360370	25	N>K		No	ClinGen TOPMed gnomAD
rs771203637 CA35810119	28	R>L		No	ClinGen TOPMed
rs1572460727 CA344360460	30	K>N		No	ClinGen Ensembl
rs181171068 CA1348493	32	P>L		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
rs983496580 CA35810142	36	I>V		No	ClinGen TOPMed
rs1420607588 CA344360555	45	E>A		No	ClinGen gnomAD
CA344360567 rs910719305	46	M>I		No	ClinGen TOPMed
CA35810154 rs910719305	46	M>I		No	ClinGen TOPMed
rs1365149083 CA344360564	46	M>T		No	ClinGen gnomAD
rs746990526 CA344361725	54	H>N		No	ClinGen ExAC TOPMed gnomAD
CA1348533 rs746990526	54	H>Y		No	ClinGen ExAC TOPMed gnomAD
rs113224250 CA35814121	60	I>V		No	ClinGen Ensembl
CA344361851 rs764056854	62	V>A		No	ClinGen TOPMed gnomAD
CA35814139 rs764056854	62	V>G		No	ClinGen TOPMed gnomAD
rs1330250688 CA344361848	62	V>L		No	ClinGen TOPMed
CA1348535 rs141432826	63	K>N		No	ClinGen ESP ExAC gnomAD
CA1348536 rs749291331	73	M>L		No	ClinGen ExAC gnomAD
CA344361981 rs1202947445	80	L>F		No	ClinGen gnomAD
rs1440744656 CA344362019	86	G>A		No	ClinGen gnomAD
rs200898280 CA1348540	87	R>C		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
CA344362025 rs1242872664	87	R>H		No	ClinGen TOPMed gnomAD
rs1475208909 CA344362039	89	S>N		No	ClinGen gnomAD
rs1470544871 CA344362057	92	V>L		No	ClinGen gnomAD
rs918199683 CA35814210	94	D>H		No	ClinGen TOPMed
rs755218701 CA35815147	103	R>S		No	ClinGen Ensembl
CA344362148 rs1196101375	103	R>T		No	ClinGen gnomAD
CA344362152 rs1237403664	104	K>E		No	ClinGen gnomAD
CA1348559 rs747269339	104	K>R		No	ClinGen ExAC gnomAD
CA35815186 rs113738032	107	V>A		No	ClinGen Ensembl
rs771482652 CA1348560	107	V>L		No	ClinGen ExAC gnomAD
rs766097677 CA35815191	109	L>S		No	ClinGen Ensembl
rs760083970 CA1348562	111	T>I		No	ClinGen ExAC gnomAD
CA1348563 rs376084672	112	A>G		No	ClinGen ESP ExAC TOPMed gnomAD
CA344362199 rs1490583709	112	A>T		No	ClinGen gnomAD
rs774960191 CA1348564	113	T>A		No	ClinGen ExAC TOPMed gnomAD
rs774960191 CA344362205	113	T>S		No	ClinGen ExAC TOPMed gnomAD
CA35815240 rs1050390379	114	T>A		No	ClinGen Ensembl
rs771633808 CA1348624	115	D>G		No	ClinGen ExAC gnomAD
CA344363187 rs1274138921	119	T>A		No	ClinGen TOPMed
CA344363198 rs1487408075	121	A>T		No	ClinGen gnomAD
rs1408706805 CA344363208	122	L>P		No	ClinGen gnomAD
CA1348627 rs145156544 COSM902609	123	A>T	endometrium [Cosmic]	No	ClinGen cosmic curated ESP ExAC gnomAD
CA1348629 rs759570763	127	S>G		No	ClinGen ExAC gnomAD
CA344363257 rs1304033183	128	M>I		No	ClinGen gnomAD
CA344363254 rs1426814470	128	M>T		No	ClinGen gnomAD
rs1572496018 CA344363251	128	M>V		No	ClinGen Ensembl
CA344363292 rs1434843775	132	S>R		No	ClinGen gnomAD
CA344363309 rs1300401186	134	D>E		No	ClinGen gnomAD
CA35819719 rs978267601	136	L>P		No	ClinGen Ensembl
rs755704621 CA1348686	138	Q>R		No	ClinGen ExAC gnomAD
rs779925757 CA1348687	139	S>G		No	ClinGen ExAC gnomAD
rs1386068406 CA344363628	143	S>G		No	ClinGen TOPMed gnomAD
CA1348688 rs748966155	145	T>P		No	ClinGen ExAC gnomAD
CA344363683 rs1308647052	146	S>C		No	ClinGen gnomAD
rs1317149366 CA344363696	147	R>G		No	ClinGen gnomAD
CA1348690 rs778877475	148	K>E		No	ClinGen ExAC gnomAD
rs748072156 CA1348691	148	K>R		No	ClinGen ExAC TOPMed gnomAD
CA1348692 rs771038153	149	R>G		No	ClinGen ExAC gnomAD
rs1267526562 CA344363737	149	R>T		No	ClinGen gnomAD
rs1357482189 CA344363747	150	T>A		No	ClinGen gnomAD
rs776550793 CA1348693	151	T>A		No	ClinGen ExAC gnomAD
rs1257063291 CA344363780	152	E>K		No	ClinGen TOPMed
rs116197192 CA1348695	153	D>G		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
rs763354177 CA1348698	154	D>A		No	ClinGen ExAC gnomAD
rs763354177 CA1348697	154	D>G		No	ClinGen ExAC gnomAD
rs555716350 CA35773093	157	T>A		No	ClinGen Ensembl
CA344363891 rs1161279887	159	P>S		No	ClinGen gnomAD
rs562881470 CA344363908	160	T>A		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
rs562881470 CA1348699	160	T>P		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
CA1348700 rs762382380	161	S>L		No	ClinGen ExAC TOPMed gnomAD
rs763865861 CA1348702	163	H>L		No	ClinGen ExAC gnomAD
CA35773100 rs61754766	163	H>N		No	ClinGen gnomAD
rs755791990 CA1348703	164	K>R		No	ClinGen ExAC
CA344364013 rs1341299919	166	I>M		No	ClinGen gnomAD
CA344364026 rs1244465537	167	H>L		No	ClinGen gnomAD
CA344364023 rs1244465537	167	H>R		No	ClinGen gnomAD
CA344364019 rs1327800677	167	H>Y		No	ClinGen TOPMed
rs909253047 CA35773112	169	R>G		No	ClinGen Ensembl
rs765886049 CA1348704	169	R>T		No	ClinGen ExAC gnomAD
rs991142439 CA35775447	173	D>Y		No	ClinGen Ensembl
CA1348724 VAR_017106 rs4252716	175	I>T		No	ClinGen UniProt 1000Genomes ESP ExAC TOPMed dbSNP gnomAD
rs1481389127 CA344365139	178	L>S		No	ClinGen gnomAD
rs146492402 CA1348725	179	A>G		No	ClinGen ESP ExAC TOPMed gnomAD
CA344365189 rs1378241666	181	D>G		No	ClinGen gnomAD
CA1348728 rs746941519	183	T>I		No	ClinGen ExAC gnomAD
rs148953645 CA1348727	183	T>P		No	ClinGen ESP ExAC TOPMed gnomAD
rs1280230499 CA344365226	184	S>P		No	ClinGen TOPMed
CA344365225 rs1280230499	184	S>T		No	ClinGen TOPMed
CA1348729 rs756186071	191	E>A		No	ClinGen ExAC TOPMed gnomAD
CA1348730 rs756186071	191	E>V		No	ClinGen ExAC TOPMed gnomAD
rs1338978165 CA344365359	192	E>D		No	ClinGen TOPMed gnomAD
CA35775527 rs746877904	193	W>C		No	ClinGen Ensembl
rs1017001295 CA35775529	195	V>I		No	ClinGen TOPMed gnomAD
rs964207769 CA35775530	196	A>P		No	ClinGen TOPMed
CA1348732 rs143656556	204	G>R		No	ClinGen ESP ExAC gnomAD
rs1311090584 CA344365526	206	L>W		No	ClinGen gnomAD
rs774892133 CA1348733	208	S>G		No	ClinGen ExAC gnomAD
CA1348735 rs772463918	209	N>S		No	ClinGen ExAC TOPMed gnomAD
CA1348737 rs755494629	210	Y>C		No	ClinGen ExAC TOPMed gnomAD
CA1348736 rs755494629	210	Y>S		No	ClinGen ExAC TOPMed gnomAD
rs1476793528 CA344365558	211	T>A		No	ClinGen TOPMed
rs1251818031 CA344365560	211	T>I		No	ClinGen TOPMed
CA35775565 rs879018393	212	P>L		No	ClinGen Ensembl
rs1558330791 CA344365565	212	P>S		No	ClinGen Ensembl
CA1348738 rs765865190	213	R>K		No	ClinGen ExAC gnomAD
CA344365576 rs1193892713	214	S>G		No	ClinGen TOPMed
rs776062479 CA344365578	214	S>I		No	ClinGen ExAC gnomAD
rs776062479 CA1348739	214	S>T		No	ClinGen ExAC gnomAD
rs1349484367 CA344365581	215	N>H		No	ClinGen gnomAD
CA1348740 rs759193175	215	N>S		No	ClinGen ExAC gnomAD
rs1266653539 CA344365591	216	G>D		No	ClinGen gnomAD
rs1245991403 CA344365607	219	D>H		No	ClinGen TOPMed
rs376011037 CA1348741	220	L>V		No	ClinGen ESP ExAC TOPMed gnomAD
CA35775580 rs922891256	223	N>H		No	ClinGen Ensembl
rs889445007 CA35776580	227	G>C		No	ClinGen Ensembl
CA344365683 rs1333999832	228	T>I		No	ClinGen gnomAD
CA344365692 rs114818444	230	I>L		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
CA1348758 rs114818444	230	I>V		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
rs776150230 CA1348759	231	V>F		No	ClinGen ExAC gnomAD
CA1348762 rs376089705	236	D>A		No	ClinGen ESP ExAC TOPMed gnomAD
CA344365731 rs1172014856	236	D>N		No	ClinGen TOPMed
rs762660837 CA1348763	238	L>F		No	ClinGen ExAC gnomAD
rs1043496589 CA35776628	239	W>S		No	ClinGen Ensembl
rs369124799 CA1348765	244	S>P		No	ClinGen ESP ExAC TOPMed gnomAD
rs372940927 CA1348766	245	V>A		No	ClinGen ESP ExAC TOPMed gnomAD
rs1458223067 CA344365807	245	V>I		No	ClinGen gnomAD
rs1473911496 CA344365821	246	S>P		No	ClinGen gnomAD
rs1473911496 CA344365826	246	S>T		No	ClinGen gnomAD
rs750366954 CA344365860	248	Q>P		No	ClinGen ExAC TOPMed gnomAD
rs750366954 CA1348768	248	Q>R		No	ClinGen ExAC TOPMed gnomAD
CA344365898 rs1474468928	250	G>D		No	ClinGen gnomAD
CA344365906 rs1173438933	251	V>D		No	ClinGen gnomAD
rs1401673629 CA344366004	257	A>V		No	ClinGen gnomAD
CA344366033 rs1277485959	259	D>E		No	ClinGen TOPMed
CA1348770 rs779132860	260	T>A		No	ClinGen ExAC TOPMed gnomAD
rs1257369938 CA344366070	262	Q>E		No	ClinGen TOPMed
CA1348773 rs758590171	265	E>D		No	ClinGen ExAC
CA1348775 rs747359088	267	V>E		No	ClinGen ExAC gnomAD
rs1376687901 CA344366162	267	V>I		No	ClinGen gnomAD
CA1348776 rs771363738	268	G>E		No	ClinGen ExAC gnomAD
rs781700116 CA1348777	270	V>I		No	ClinGen ExAC gnomAD
rs896754557 CA35776678	271	S>N		No	ClinGen Ensembl
CA35776686 rs777113316	273	K>Q		No	ClinGen Ensembl
CA1348790 rs201166880	275	V>L		No	ClinGen ESP ExAC TOPMed gnomAD
rs935980957 CA35778044	276	I>M		No	ClinGen gnomAD
rs764328425 CA1348791	276	I>T		No	ClinGen ExAC TOPMed gnomAD
rs1478031328 CA344366468	278	V>E		No	ClinGen gnomAD
rs61748997 CA1348792	280	K>N		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
rs757657818 CA1348793	281	N>D		No	ClinGen ExAC gnomAD
CA344366485 rs1198437208	281	N>S		No	ClinGen TOPMed gnomAD
CA344366491 rs1158913937	282	D>Y		No	ClinGen gnomAD
CA344366499 rs1201039598	283	D>Y		No	ClinGen TOPMed
rs756552616 CA1348796	285	E>Q		No	ClinGen ExAC gnomAD
CA1348799 rs559351941	286	D>E		No	ClinGen 1000Genomes ExAC gnomAD
CA1348797 rs779541672	286	D>H		No	ClinGen ExAC gnomAD
CA1348798 rs779541672	286	D>N		No	ClinGen ExAC gnomAD
CA344366524 rs1205280431	287	S>A		No	ClinGen TOPMed
rs774096960 CA1348800	288	K>E		No	ClinGen ExAC TOPMed gnomAD
rs528182432 CA344366533	288	K>N		No	ClinGen 1000Genomes gnomAD
rs774096960 CA35778099	288	K>Q		No	ClinGen ExAC TOPMed gnomAD
rs28495289 CA35778127	291	S>G		No	ClinGen Ensembl
rs560966150 CA35778129	291	S>N		No	ClinGen Ensembl
CA344366569 rs1287086267	293	D>N		No	ClinGen gnomAD
rs772053413 CA1348802	294	T>N		No	ClinGen ExAC TOPMed gnomAD
CA1348804 rs760694069	295	D>N		No	ClinGen ExAC gnomAD
CA1348805 rs760694069	295	D>Y		No	ClinGen ExAC gnomAD
CA1348806 rs775454432	297	E>Q		No	ClinGen ExAC gnomAD
CA1348807 rs763141402	299	T>I		No	ClinGen ExAC gnomAD
rs764048372 CA1348808	300	S>F		No	ClinGen ExAC gnomAD
rs1341431862 CA344367381	302	D>N		No	ClinGen gnomAD
rs767684417 CA1348833	307	T>I		No	ClinGen ExAC gnomAD
CA35779596 rs1048855060	307	T>S		No	ClinGen Ensembl
rs1320657714 CA344367440	309	C>*		No	ClinGen gnomAD
CA1348834 rs750804706	311	K>N		No	ClinGen ExAC gnomAD
rs1218659753 CA344367450	311	K>Q		No	ClinGen gnomAD
CA344367474 rs1479394318	314	S>P		No	ClinGen gnomAD
CA344367484 rs1256440438	315	P>L		No	ClinGen gnomAD
CA344367534 rs1405649744	322	R>C		No	ClinGen gnomAD
CA1348837 rs754429631	329	D>Y		No	ClinGen ExAC
rs1169931742 CA344367612	332	S>L		No	ClinGen gnomAD
rs55958721 CA35779643	336	K>E		No	ClinGen 1000Genomes
rs778492078 CA1348839	338	T>S		No	ClinGen ExAC TOPMed gnomAD
CA1348840 rs752216927	339	H>Y		No	ClinGen ExAC gnomAD
rs758146762 CA1348841	340	S>F		No	ClinGen ExAC gnomAD
rs557473906 CA1348842	341	L>F		No	ClinGen 1000Genomes ExAC gnomAD
rs746628364 CA35779694	342	S>F		No	ClinGen ExAC TOPMed gnomAD
CA1348843 rs746628364	342	S>Y		No	ClinGen ExAC TOPMed gnomAD
rs1342830157 CA344367680	343	T>M		No	ClinGen TOPMed gnomAD
CA1348845 rs780833829	345	D>G		No	ClinGen ExAC TOPMed gnomAD
rs997328622 CA16040400	346	I>V		No	ClinGen TOPMed gnomAD
CA35779704 rs79824231	347	T>P		No	ClinGen Ensembl
CA344367705 rs1256184414	348	A>T		No	ClinGen TOPMed gnomAD
rs1346731264 CA344367712	349	I>V		No	ClinGen TOPMed gnomAD
CA1348846 rs745829749	352	K>N		No	ClinGen ExAC gnomAD
rs953405377 CA35779721	356	G>R		No	ClinGen gnomAD
CA35779739 rs913129198	360	P>S		No	ClinGen TOPMed
CA1348848 rs774519008	363	R>G		No	ClinGen ExAC TOPMed gnomAD
rs761828808 CA1348849	363	R>Q		No	ClinGen ExAC TOPMed gnomAD
CA35779757 rs1042877914	365	T>N		No	ClinGen TOPMed
rs1172050470 CA344367831	366	I>T		No	ClinGen gnomAD
rs201947927 COSM23543 CA1348852	367	S>L	upper_aerodigestive_tract liver large_intestine [Cosmic]	No	ClinGen cosmic curated 1000Genomes ExAC TOPMed gnomAD
rs1288732549 CA344367839	368	A>P		No	ClinGen gnomAD
rs140091735 CA1348855	369	P>A		No	ClinGen 1000Genomes ExAC gnomAD
rs765614202 CA1348856	369	P>L		No	ClinGen ExAC gnomAD
CA1348854 rs140091735	369	P>S		No	ClinGen 1000Genomes ExAC gnomAD
COSM282735 rs966981669 CA35779793	371	V>I	large_intestine [Cosmic]	No	ClinGen cosmic curated TOPMed gnomAD
RCV000488014 rs41299595 CA1348858	374	K>Q		No	ClinGen ClinVar 1000Genomes ESP ExAC TOPMed dbSNP gnomAD
rs777416962 CA1348859	376	A>G		No	ClinGen ExAC TOPMed gnomAD
CA344367910 rs1287792236	376	A>T		No	ClinGen gnomAD
rs777416962 CA1348860	376	A>V		No	ClinGen ExAC TOPMed gnomAD
CA344367942 rs201482788	378	I>L		No	ClinGen 1000Genomes gnomAD
rs774729619 CA35779817	378	I>M		No	ClinGen gnomAD
CA35779813 rs201482788	378	I>V		No	ClinGen 1000Genomes gnomAD
rs370220372 CA1348862	379	K>Q		No	ClinGen ESP ExAC TOPMed gnomAD
CA1348863 rs374162474	384	K>R		No	ClinGen ESP ExAC gnomAD
CA1348864 rs769790390	385	L>F		No	ClinGen ExAC gnomAD
rs762197216 CA35779865	385	L>R		No	ClinGen TOPMed gnomAD
rs1420651047 CA344368085	387	D>Y		No	ClinGen gnomAD
CA1348865 rs61754765	388	P>A		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
CA1348866 rs61754765	388	P>S		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
rs200412021 CA1348868	389	C>R		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
CA344368136 rs1294700976	390	N>H		No	ClinGen gnomAD
CA344368141 rs1393081884	390	N>S		No	ClinGen gnomAD
CA344368167 rs1310908548	392	V>M		No	ClinGen gnomAD
CA344368196 rs1377218815	394	F>I		No	ClinGen gnomAD
rs1222941863 CA344368203	394	F>S		No	ClinGen TOPMed gnomAD
rs773221224 CA1348869	395	L>F		No	ClinGen ExAC gnomAD
CA344368232 rs1419841121	396	D>N		No	ClinGen gnomAD
rs150420477 CA1348870	398	A>V		No	ClinGen ESP ExAC TOPMed gnomAD
rs901230245 CA35779893	400	S>R		No	ClinGen TOPMed
rs771020373 CA1348871	401	S>A		No	ClinGen ExAC
rs1272531793 CA344368311	401	S>C		No	ClinGen gnomAD
CA1348872 rs777077869	404	Q>H		No	ClinGen ExAC gnomAD
rs1209610511 CA344368333	404	Q>R		No	ClinGen TOPMed
CA1348873 rs759868051	405	E>K		No	ClinGen ExAC gnomAD
CA1348874 rs4252741 VAR_017107	406	T>I		No	ClinGen UniProt ExAC TOPMed dbSNP gnomAD
rs1558337735 CA344368363	407	I>V		No	ClinGen Ensembl
CA35779933 rs561122159	409	S>G		No	ClinGen TOPMed gnomAD
rs1425989939 CA344368402	409	S>N		No	ClinGen gnomAD
CA35779936 rs866034137	410	M>V		No	ClinGen TOPMed gnomAD
rs763540719 CA1348876	411	G>E		No	ClinGen ExAC TOPMed gnomAD
rs763708092 CA1348877	412	E>K		No	ClinGen ExAC gnomAD
rs1298278427 CA344368468	413	Q>K		No	ClinGen gnomAD
CA1348878 rs751045697	413	Q>R		No	ClinGen ExAC gnomAD
CA35779947 rs145207570	416	N>K		No	ClinGen ESP ExAC TOPMed gnomAD
CA344368543 rs1400001545	418	S>P		No	ClinGen TOPMed gnomAD
CA1348880 rs767025919	420	Q>R		No	ClinGen ExAC gnomAD
CA1348881 rs372145936	421	R>T		No	ClinGen ESP ExAC TOPMed gnomAD
rs755898653 CA1348882	422	T>A		No	ClinGen ExAC gnomAD
rs1392816145 CA344368631	423	D>G		No	ClinGen TOPMed
CA1348883 rs779814322	424	T>R		No	ClinGen ExAC TOPMed gnomAD
rs749242315 CA1348884	425	E>G		No	ClinGen ExAC gnomAD
rs1455728624 CA344368687	427	M>V		No	ClinGen TOPMed
CA1348885 rs754846508	428	E>K		No	ClinGen ExAC
CA35779975 rs773722705	430	C>G		No	ClinGen Ensembl
CA1348887 rs777864820	431	Q>P		No	ClinGen ExAC TOPMed gnomAD
CA1348886 rs777864820	431	Q>R		No	ClinGen ExAC TOPMed gnomAD
rs1159959429 CA344368783	432	N>S		No	ClinGen TOPMed
CA344369082 rs1474497547	462	H>R		No	ClinGen gnomAD
rs1052644 CA35780044	470	A>G		No	ClinGen TOPMed gnomAD
CA344369139 rs1052644	470	A>V		No	ClinGen TOPMed gnomAD
rs1419605022 CA344369143	471	G>E		No	ClinGen gnomAD
rs1321047401 CA344369146	472	A>S		No	ClinGen TOPMed
CA1348895 rs773932299	490	A>T		No	ClinGen ExAC TOPMed gnomAD

1 associated diseases with O15151

[MIM: 618849]: Bone marrow failure syndrome 6 (BMFS6)

A form of bone marrow failure syndrome, a heterogeneous group of life-threatening disorders characterized by hematopoietic defects in association with a range of variable extra-hematopoietic manifestations. BMFS6 is an autosomal dominant form characterized by intermittent neutropenia, lymphopenia, or anemia associated with hypocellular bone marrow, and increased susceptibility to cancer. {ECO:0000269|PubMed:32300648}. Note=The disease is caused by variants affecting the gene represented in this entry.

Without disease ID

A form of bone marrow failure syndrome, a heterogeneous group of life-threatening disorders characterized by hematopoietic defects in association with a range of variable extra-hematopoietic manifestations. BMFS6 is an autosomal dominant form characterized by intermittent neutropenia, lymphopenia, or anemia associated with hypocellular bone marrow, and increased susceptibility to cancer. {ECO:0000269|PubMed:32300648}. Note=The disease is caused by variants affecting the gene represented in this entry.

3 regional properties for O15151

Type	Name	Position	InterPro Accession
domain	Zinc finger, RING-type	437 - 478	IPR001841
domain	Zinc finger, RanBP2-type	300 - 329	IPR001876
domain	SWIB/MDM2 domain	25 - 108	IPR003121

Functions

		Description
EC Number
Subcellular Localization	Nucleus
PANTHER Family	PTHR12183	MITOCHONDRIAL UBIQUITIN LIGASE ACTIVATOR OF NFKB 1
PANTHER Subfamily	PTHR12183:SF37	PROTEIN MDM4
PANTHER Protein Class
PANTHER Pathway Category	p53 pathway Mdm2 P53 pathway feedback loops 1 MDM-2 p53 pathway feedback loops 2 Mdm2 Insulin/IGF pathway-protein kinase B signaling cascade Mdm2 P53 pathway feedback loops 1 Mdm2 p53 pathway feedback loops 2 MDM-2 p53 pathway MDM-2 Insulin/IGF pathway-protein kinase B signaling cascade Mdm2

3 GO annotations of cellular component

Name	Definition
nucleoplasm	That part of the nuclear content other than the chromosomes or the nucleolus.
nucleus	A membrane-bounded organelle of eukaryotic cells in which chromosomes are housed and replicated. In most cells, the nucleus contains all of the cell's chromosomes except the organellar chromosomes, and is the site of RNA synthesis and processing. In some species, or in specialized cell types, RNA metabolism or DNA replication may be absent.
transcription repressor complex	A protein complex that possesses activity that prevents or downregulates transcription.

3 GO annotations of molecular function

Name	Definition
enzyme binding	Binding to an enzyme, a protein with catalytic activity.
p53 binding	Binding to one of the p53 family of proteins.
zinc ion binding	Binding to a zinc ion (Zn).

16 GO annotations of biological process

Name	Definition
atrial septum development	The progression of the atrial septum over time, from its initial formation to the mature structure.
atrioventricular valve morphogenesis	The process in which the structure of the atrioventricular valve is generated and organized.
cellular response to hypoxia	Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a stimulus indicating lowered oxygen tension. Hypoxia, defined as a decline in O2 levels below normoxic levels of 20.8 - 20.95%, results in metabolic adaptation at both the cellular and organismal level.
DNA damage response, signal transduction by p53 class mediator	A cascade of processes induced by the cell cycle regulator phosphoprotein p53, or an equivalent protein, in response to the detection of DNA damage.
endocardial cushion morphogenesis	The process in which the anatomical structure of the endocardial cushion is generated and organized. The endocardial cushion is a specialized region of mesenchymal cells that will give rise to the heart septa and valves.
heart valve development	The progression of a heart valve over time, from its formation to the mature structure. A heart valve is a structure that restricts the flow of blood to different regions of the heart and forms from an endocardial cushion.
negative regulation of apoptotic process	Any process that stops, prevents, or reduces the frequency, rate or extent of cell death by apoptotic process.
negative regulation of cell population proliferation	Any process that stops, prevents or reduces the rate or extent of cell proliferation.
negative regulation of protein catabolic process	Any process that stops, prevents or reduces the frequency, rate or extent of protein catabolic process.
negative regulation of transcription by RNA polymerase II	Any process that stops, prevents, or reduces the frequency, rate or extent of transcription mediated by RNA polymerase II.
negative regulation of transcription, DNA-templated	Any process that stops, prevents, or reduces the frequency, rate or extent of cellular DNA-templated transcription.
protein stabilization	Any process involved in maintaining the structure and integrity of a protein and preventing it from degradation or aggregation.
protein-containing complex assembly	The aggregation, arrangement and bonding together of a set of macromolecules to form a protein-containing complex.
regulation of cell cycle	Any process that modulates the rate or extent of progression through the cell cycle.
regulation of transcription by RNA polymerase II	Any process that modulates the frequency, rate or extent of transcription mediated by RNA polymerase II.
ventricular septum development	The progression of the ventricular septum over time from its formation to the mature structure.

5 homologous proteins in AiPD

UniProt AC	Gene Name	Protein Name	Species	Evidence Code
Q2HJ21	MDM4	Protein Mdm4	Bos taurus (Bovine)	SS
E1C4B0	MDM4	Double minute 4 protein	Gallus gallus (Chicken)	SS
O35618	Mdm4	Protein Mdm4	Mus musculus (Mouse)	SS
Q5XIN1	Mdm4	Protein Mdm4	Rattus norvegicus (Rat)	SS
Q7ZUW7	mdm4	Protein Mdm4	Danio rerio (Zebrafish) (Brachydanio rerio)	SS

10	20	30	40	50	60
MTSFSTSAQC	STSDSACRIS	PGQINQVRPK	LPLLKILHAA	GAQGEMFTVK	EVMHYLGQYI
70	80	90	100	110	120
MVKQLYDQQE	QHMVYCGGDL	LGELLGRQSF	SVKDPSPLYD	MLRKNLVTLA	TATTDAAQTL
130	140	150	160	170	180
ALAQDHSMDI	PSQDQLKQSA	EESSTSRKRT	TEDDIPTLPT	SEHKCIHSRE	DEDLIENLAQ
190	200	210	220	230	240
DETSRLDLGF	EEWDVAGLPW	WFLGNLRSNY	TPRSNGSTDL	QTNQDVGTAI	VSDTTDDLWF
250	260	270	280	290	300
LNESVSEQLG	VGIKVEAADT	EQTSEEVGKV	SDKKVIEVGK	NDDLEDSKSL	SDDTDVEVTS
310	320	330	340	350	360
EDEWQCTECK	KFNSPSKRYC	FRCWALRKDW	YSDCSKLTHS	LSTSDITAIP	EKENEGNDVP
370	380	390	400	410	420
DCRRTISAPV	VRPKDAYIKK	ENSKLFDPCN	SVEFLDLAHS	SESQETISSM	GEQLDNLSEQ
430	440	450	460	470	480
RTDTENMEDC	QNLLKPCSLC	EKRPRDGNII	HGRTGHLVTC	FHCARRLKKA	GASCPICKKE

IQLVIKVFIA