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UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot O15151: Variant p.Thr454Met

Protein Mdm4
Gene: MDM4
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Variant information Variant position: help 454 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant: help LP/P [Disclaimer] The variants are classified into three categories: LP/P, LB/B and US.
  • LP/P: likely pathogenic or pathogenic.
  • LB/B: likely benign or benign.
  • US: uncertain significance
Residue change: help From Threonine (T) to Methionine (M) at position 454 (T454M, p.Thr454Met). Indicates the amino acid change of the variant. The one-letter and three-letter codes for amino acids used in UniProtKB/Swiss-Prot are those adopted by the commission on Biochemical Nomenclature of the IUPAC-IUB.
Physico-chemical properties: help Change from medium size and polar (T) to medium size and hydrophobic (M) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score: help -1 The score within a Blosum matrix for the corresponding wild-type to variant amino acid change. The log-odds score measures the logarithm for the ratio of the likelihood of two amino acids appearing by chance. The Blosum62 substitution matrix is used. This substitution matrix contains scores for all possible exchanges of one amino acid with another:
  • Lowest score: -4 (low probability of substitution).
  • Highest score: 11 (high probability of substitution).
More information can be found on the following page
Variant description: help In 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. Any additional useful information about the variant.
Other resources: help Links to websites of interest for the variant.


Sequence information Variant position: help 454 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length: help 490 The length of the canonical sequence.
Location on the sequence: help LKPCSLCEKRPRDGNIIHGR T GHLVTCFHCARRLKKAGASC The residue change on the sequence. Unless the variant is located at the beginning or at the end of the protein sequence, both residues upstream (20) and downstream (20) of the variant will be shown.
Residue conservation: help The multiple alignment of the region surrounding the variant against various orthologous sequences. 
Human                         LKPCSLCEKRPRDGNIIHGRTGHLVTCFHCARRLKKAGASC

Mouse                         LKPCSLCEKRPRDGNIIHGKTSHLTTCFHCARRLKKSGASC

Rat                           LKPCSLCEKRPRDGNIIHGKTSHLTTCFHCARRLKKSGASC

Bovine                        LKPCSLCEKRPRNGNIIHGRTGHLVTCFHCARRLKKAGASC

Xenopus laevis                LEPCQLCQRRQRNGSVVHGRTAHLVTCFSCACNLKKNQKGC

Zebrafish                     LEPCKLCRVRPRNGNIIHGRTAHLITCFPCARKLHKFHAPC
Sequence annotation in neighborhood: help The regions or sites of interest surrounding the variant. In general the features listed are posttranslational modifications, binding sites, enzyme active sites, local secondary structure or other characteristics reported in the cited references. The "Sequence annotation in neighborhood" lines have a fixed format:
  • Type: the type of sequence feature.
  • Positions: endpoints of the sequence feature.
  • Description: contains additional information about the feature.
TypePositionsDescription
Chain 1 – 490 Protein Mdm4
Zinc finger 437 – 478 RING-type
Region 393 – 490 Necessary for interaction with USP2
Alternative sequence 109 – 490 LATATTDAAQTLALAQDHSMDIPSQDQLKQSAEESSTSRKRTTEDDIPTLPTSEHKCIHSREDEDLIENLAQDETSRLDLGFEEWDVAGLPWWFLGNLRSNYTPRSNGSTDLQTNQDVGTAIVSDTTDDLWFLNESVSEQLGVGIKVEAADTEQTSEEVGKVSDKKVIEVGKNDDLEDSKSLSDDTDVEVTSEDEWQCTECKKFNSPSKRYCFRCWALRKDWYSDCSKLTHSLSTSDITAIPEKENEGNDVPDCRRTISAPVVRPKDAYIKKENSKLFDPCNSVEFLDLAHSSESQETISSMGEQLDNLSEQRTDTENMEDCQNLLKPCSLCEKRPRDGNIIHGRTGHLVTCFHCARRLKKAGASCPICKKEIQLVIKVFIA -> SASNNTARCNRILQSQKKN. In isoform 2.
Alternative sequence 109 – 490 LATATTDAAQTLALAQDHSMDIPSQDQLKQSAEESSTSRKRTTEDDIPTLPTSEHKCIHSREDEDLIENLAQDETSRLDLGFEEWDVAGLPWWFLGNLRSNYTPRSNGSTDLQTNQDVGTAIVSDTTDDLWFLNESVSEQLGVGIKVEAADTEQTSEEVGKVSDKKVIEVGKNDDLEDSKSLSDDTDVEVTSEDEWQCTECKKFNSPSKRYCFRCWALRKDWYSDCSKLTHSLSTSDITAIPEKENEGNDVPDCRRTISAPVVRPKDAYIKKENSKLFDPCNSVEFLDLAHSSESQETISSMGEQLDNLSEQRTDTENMEDCQNLLKPCSLCEKRPRDGNIIHGRTGHLVTCFHCARRLKKAGASCPICKKEIQLVIKVFIA -> SASNNTDAAQTLALAQDHT. In isoform 3.
Mutagenesis 437 – 437 C -> G. Fails to interact with MDM2.
Beta strand 454 – 459



Literature citations
Germline mutation of MDM4, a major p53 regulator, in a familial syndrome of defective telomere maintenance.
Toufektchan E.; Lejour V.; Durand R.; Giri N.; Draskovic I.; Bardot B.; Laplante P.; Jaber S.; Alter B.P.; Londono-Vallejo J.A.; Savage S.A.; Toledo F.;
Sci. Adv. 6:eaay3511-eaay3511(2020)
Cited for: INVOLVEMENT IN BMFS6; VARIANT BMFS6 MET-454; CHARACTERIZATION OF VARIANT BMFS6 MET-454; FUNCTION; INTERACTION WITH MDM2;
Disclaimer: Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. They are not in any way intended to be used as a substitute for professional medical advice, diagnostic, treatment or care.