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Reviewed, UniProtKB/Swiss-Prot O15151 (MDM4_HUMAN)

Last modified February 9, 2010. Version 104. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data | Customize display text xml rdf/xml gff fasta
Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Binary interactions · Alternative products · Sequence annotation (Features) · Sequences · References · Web resources · Cross-references · Entry information · Relevant documents

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Names and origin

Protein namesRecommended name:
    Protein Mdm4
Alternative name(s):
    p53-binding protein Mdm4
    Mdm2-like p53-binding protein
    Protein Mdmx
    Double minute 4 protein
Gene names
Name: MDM4
Synonyms: MDMX
OrganismHomo sapiens (Human) [Complete proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

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Protein attributes

Sequence length490 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level.

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General annotation (Comments)

Function

Inhibits p53- and p73-mediated cell cycle arrest and apoptosis by binding its transcriptional activation domain. Inhibits degradation of MDM2. Can reverse MDM2-targeted degradation of p53 while maintaining suppression of p53 transactivation and apoptotic functions.

Subunit structure

Binds to p53, p73 and MDM2.

Subcellular location

Nucleus.

Tissue specificity

In all tissues tested, with high levels in thymus.

Domain

Region I is sufficient for binding p53 and inhibiting its G1 arrest and apoptosis functions. It also binds p73. Region II contains most of a central acidic region and a putative C4-type zinc finger. The RING finger domain which coordinates two molecules of zinc mediates the heterooligomerization with MDM2.

Sequence similarities

Belongs to the MDM2/MDM4 family.

Contains 1 RanBP2-type zinc finger.

Contains 1 RING-type zinc finger.

Contains 1 SWIB domain.

Mass spectrometry

Molecular mass is 54863.3 Da from positions 1 - 490. Determined by MALDI. Ref.8

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Binary interactions

With

Entry

#Exp.

IntAct

Notes

MDM2Q009872EBI-398437,EBI-389668
TP53P046372EBI-398437,EBI-366083

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Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Note: Additional isoforms seem to exist.
Isoform 1 (identifier: O15151-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform 2 (identifier: O15151-2)

Also known as: MDMX-S;

The sequence of this isoform differs from the canonical sequence as follows:
     109-490: LATATTDAAQ...IQLVIKVFIA → SASNNTARCNRILQSQKKN
Note: No experimental confirmation available.
Isoform 3 (identifier: O15151-3)

Also known as: MDMX;

The sequence of this isoform differs from the canonical sequence as follows:
     109-490: LATATTDAAQ...IQLVIKVFIA → SASNNTDAAQTLALAQDHT
Note: No experimental confirmation available.

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Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 490490Protein Mdm4
PRO_0000157336

Regions

Domain26 – 10681SWIB
Zinc finger300 – 32930RanBP2-type
Zinc finger437 – 47842RING-type
Region246 – 33287Region II
Motif442 – 4454Nuclear localization signal Potential
Compositional bias243 – 30866Asp/Glu-rich (acidic)

Natural variations

Alternative sequence109 – 490382LATAT…KVFIA → SASNNTARCNRILQSQKKN in isoform 2.
VSP_035669
Alternative sequence109 – 490382LATAT…KVFIA → SASNNTDAAQTLALAQDHT in isoform 3.
VSP_035670
Natural variant1751I → T: dbSNP rs4252716. Ref.3
VAR_017106
Natural variant4061T → I: dbSNP rs4252741. Ref.3
VAR_017107

Experimental info

Mutagenesis4371C → G: Fails to interact with MDM2. Ref.7
Sequence conflict941D → N in AAB62928. Ref.1

Secondary structure

1 ............................. 490
Helix Strand Turn

Details...

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Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified September 27, 2005. Version 2.
Checksum: 415E6FA5A0C69857

FASTA49054,864
        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 

       490 
IQLVIKVFIA

« Hide

Isoform 2 (MDMX-S).

Checksum: 59649D26B113EFB4
Show »

FASTA12714,185
Isoform 3 (MDMX).

Checksum: 0A00E52B32331543
Show »

FASTA12713,981

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References

« Hide 'large scale' references
[1]"Isolation and identification of the human homolog of a new p53-binding protein, Mdmx."
Shvarts A., Bazuine M., Dekker P., Ramos Y.F.M., Steegenga W.T., Merckx G., van Ham R.C.A., van der Houven van Oordt W., van der Eb A.J., Jochemsen A.G.
Genomics 43:34-42(1997) [PubMed: 9226370] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Colon tumor.
[2]Suzuki Y., Sugano S., Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S.
Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Gastric mucosa.
[3]NIEHS SNPs program
Submitted (DEC-2002) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS THR-175 AND ILE-406.
[4]"The DNA sequence and biological annotation of human chromosome 1."
Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K. expand/collapse author list , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.
Nature 441:315-321(2006) [PubMed: 16710414] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Testis.
[6]"Identification of a domain within MDMX-S that is responsible for its high affinity interaction with p53 and high-level expression in mammalian cells."
Rallapalli R., Strachan G., Tuan R.S., Hall D.J.
J. Cell. Biochem. 89:563-575(2003) [PubMed: 12761890] [Abstract]
Cited for: ALTERNATIVE SPLICING (ISOFORMS 2 AND 3).
[7]"Stabilization of the MDM2 oncoprotein by interaction with the structurally related MDMX protein."
Sharp D.A., Kratowicz S.A., Sank M.J., George D.L.
J. Biol. Chem. 274:38189-38196(1999) [PubMed: 10608892] [Abstract]
Cited for: MUTAGENESIS OF CYS-437.
[8]"Cluster analysis of an extensive human breast cancer cell line protein expression map database."
Harris R.A., Yang A., Stein R.C., Lucy K., Brusten L., Herath A., Parekh R., Waterfield M.D., O'Hare M.J., Neville M.A., Page M.J., Zvelebil M.J.
Proteomics 2:212-223(2002) [PubMed: 11840567] [Abstract]
Cited for: MASS SPECTROMETRY.
Tissue: Mammary cancer.
[9]"Solution structure of the ZF-RANBP domain of p53-binding protein MDM4."
RIKEN structural genomics initiative (RSGI)
Submitted (NOV-2005) to the PDB data bank
Cited for: STRUCTURE BY NMR OF 300-340.
+Additional computationally mapped references.

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Web resources

NIEHS-SNPs

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Cross-references

Sequence databases

EMBL
GenBank
DDBJ		AF007111 mRNA. Translation: AAB62928.1.
AK223228 mRNA. Translation: BAD96948.1.
AY207458 Genomic DNA. Translation: AAO13494.1.
AL512306 Genomic DNA. Translation: CAI14100.1.
BC067299 mRNA. Translation: AAH67299.1.
IPIIPI00005170.
IPI00914644.
IPI00914667.
RefSeqNP_002384.2.
UniGeneHs.497492

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2CR8NMR-A300-339[»]
2VJEX-ray2.20B/D428-490[»]
2VJFX-ray2.30B/D428-490[»]
2VYRX-ray2.00A/B/C/D16-116[»]
3DABX-ray1.90A/C/E/G23-111[»]
3EQYX-ray1.63A/B24-108[»]
3FDOX-ray1.40A23-111[»]
3FE7X-ray1.35A14-111[»]
3FEAX-ray1.33A14-111[»]
3JZOX-ray1.80A23-111[»]
3JZPX-ray1.74A23-111[»]
3JZQX-ray1.80A/B23-111[»]
ModBaseSearch...

Protein-protein interaction databases

DIPDIP-24199N.
IntActO15151. 7 interactions.
STRINGO15151.

PTM databases

PhosphoSiteO15151.

Proteomic databases

PRIDEO15151.

Genome annotation databases

EnsemblENST00000367182; ENSP00000356150; ENSG00000198625; Homo sapiens. [Genome view]
GeneID4194.
KEGGhsa:4194.
UCSCuc001hba.1. human.

Organism-specific databases

CTD4194.
GeneCardsGC01P202752.
HGNCHGNC:6974. MDM4.
HPAHPA018919.
MIM602704. gene.
PharmGKBPA30719.
GenAtlasSearch...

Phylogenomic databases

eggNOGprNOG13131.
HOGENOMHBG717854.
HOVERGENO15151.
InParanoidO15151.
OMAQETISSM.
OrthoDBEOG9W9MPH.
PhylomeDBO15151.

Gene expression databases

ArrayExpressO15151.
BgeeO15151.
CleanExHS_MDM4.
GenevestigatorO15151.
GermOnlineENSG00000198625. Homo sapiens.

Family and domain databases

InterProIPR015458. MDM4.
IPR016495. p53_neg-reg_MDM_2/4.
IPR003121. SWIB_MDM2_domain.
IPR001876. Znf_RanBP2.
IPR001841. Znf_RING.
[Graphical view]
Gene3DG3DSA:1.10.245.10. SWIB_MDM2. 1 hit.
PANTHERPTHR10360:SF10. MDM4. 1 hit.
PfamPF02201. SWIB. 1 hit.
[Graphical view]
PIRSFPIRSF006748. p53_MDM_2/4. 1 hit.
SMARTSM00184. RING. 1 hit.
SM00547. ZnF_RBZ. 1 hit.
[Graphical view]
PROSITEPS01358. ZF_RANBP2_1. 1 hit.
PS50199. ZF_RANBP2_2. 1 hit.
PS00518. ZF_RING_1. False negative.
PS50089. ZF_RING_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other Resources

NextBio16538.
PMAP-CutDBO15151.
SOURCESearch...

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Entry information

Entry nameMDM4_HUMAN
AccessionPrimary (citable) accession number: O15151
Secondary accession number(s): Q6GS18, Q8IV83
Entry history
Integrated into UniProtKB/Swiss-Prot: May 30, 2000
Last sequence update: September 27, 2005
Last modified: February 9, 2010
This is version 104 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation projectHPI (Human Proteome Initiative)
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

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Relevant documents

Human chromosome 1

Human chromosome 1: entries, gene names and cross-references to MIM

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List of human entries with polymorphisms or disease mutations

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

SIMILARITY comments

Index of protein domains and families

Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Binary interactions · Alternative products · Sequence annotation (Features) · Sequences · References · Web resources · Cross-references · Entry information · Relevant documents