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UniProtKB/Swiss-Prot Q01081: Variant p.Ser34Phe

Splicing factor U2AF 35 kDa subunit
Gene: U2AF1
Variant information

Variant position:  34
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Type of variant:  Disease [Disclaimer]
The variants are classified into three categories: Disease, Polymorphism and Unclassified.
  • Disease: Variants implicated in disease according to literature reports.
  • Polymorphism: Variants not reported to be implicated in disease.
  • Unclassified: Variants with uncertain implication in disease according to literature reports. Evidence against or in favor of a pathogenic role is limited and/or conflicting.

Residue change:  From Serine (S) to Phenylalanine (F) at position 34 (S34F, p.Ser34Phe).
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:  Change from small size and polar (S) to large size and aromatic (F)
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  -2
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

Involvement in disease:  Myelodysplastic syndrome (MDS) [MIM:614286]: A heterogeneous group of closely related clonal hematopoietic disorders. All are characterized by a hypercellular or hypocellular bone marrow with impaired morphology and maturation, dysplasia of the myeloid, megakaryocytic and/or erythroid lineages, and peripheral blood cytopenias resulting from ineffective blood cell production. Included diseases are: refractory anemia (RA), refractory anemia with ringed sideroblasts (RARS), refractory anemia with excess blasts (RAEB), refractory cytopenia with multilineage dysplasia and ringed sideroblasts (RCMD-RS); chronic myelomonocytic leukemia (CMML) is a myelodysplastic/myeloproliferative disease. MDS is considered a premalignant condition in a subgroup of patients that often progresses to acute myeloid leukemia (AML). {ECO:0000269|PubMed:22158538, ECO:0000269|PubMed:25311244}. Note=The gene represented in this entry may be involved in disease pathogenesis. Mutation altering U2AF1 function in the context of specific RNA sequences can lead to aberrant alternative splicing of target genes, some of which may be relevant for MDS pathogenesis. {ECO:0000269|PubMed:25311244}.
The name and a short description of the disease associated with the variant. For more information about the disease, the user can refer to OMIM, following the link provided after the disease acronym.

Variant description:  In MDS; somatic mutation; affects alternative splicing of target sequences resulting in increased splicing efficiency, exon skipping and alternative splice site utilization; no effect on localization to nuclear speckles.
Any additional useful information about the variant.

Other resources:  
Links to websites of interest for the variant.



Sequence information

Variant position:  34
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  240
The length of the canonical sequence.

Location on the sequence:   DKVNCSFYFKIGACRHGDRC  S RLHNKPTFSQTIALLNIYRN
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: 
The multiple alignment of the region surrounding the variant against various orthologous sequences.

Human                         DKVNCSFYFKIGACRHGDRCSRLHNKPTFSQTIALLNIYRN

Mouse                         DKVNCSFYFKIGACRHGDRCSRLHNKPTFSQTIALLNIYRN

Bovine                        DKVNCSFYFKIGACRHGDRCSRLHNKPTFSQTIALLNIYRN

Drosophila                    DKVNCSFYFKIGACRHGDRCSRIHNKPTFSQTVLLQNLYVN

Fission yeast                 DKVNCSFYYKIGACRHGERCSRKHVKPNFSQTILCPNMYKN

Sequence annotation in neighborhood:  
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 2 – 240 Splicing factor U2AF 35 kDa subunit
Zinc finger 12 – 40 C3H1-type 1
Modified residue 39 – 39 N6-methyllysine
Alternative sequence 1 – 73 Missing. In isoform 4.


Literature citations

Recurrent mutations in the U2AF1 splicing factor in myelodysplastic syndromes.
Graubert T.A.; Shen D.; Ding L.; Okeyo-Owuor T.; Lunn C.L.; Shao J.; Krysiak K.; Harris C.C.; Koboldt D.C.; Larson D.E.; McLellan M.D.; Dooling D.J.; Abbott R.M.; Fulton R.S.; Schmidt H.; Kalicki-Veizer J.; O'Laughlin M.; Grillot M.; Baty J.; Heath S.; Frater J.L.; Nasim T.; Link D.C.; Tomasson M.H.; Westervelt P.; DiPersio J.F.; Mardis E.R.; Ley T.J.; Wilson R.K.; Walter M.J.;
Nat. Genet. 44:53-57(2011)
Cited for: FUNCTION; INVOLVEMENT IN MDS; VARIANTS MDS PHE-34; TYR-34 AND ARG-157; CHARACTERIZATION OF VARIANT MDS PHE-34;

U2AF1 mutations alter sequence specificity of pre-mRNA binding and splicing.
Okeyo-Owuor T.; White B.S.; Chatrikhi R.; Mohan D.R.; Kim S.; Griffith M.; Ding L.; Ketkar-Kulkarni S.; Hundal J.; Laird K.M.; Kielkopf C.L.; Ley T.J.; Walter M.J.; Graubert T.A.;
Leukemia 29:909-917(2015)
Cited for: FUNCTION; INVOLVEMENT IN MDS; SUBCELLULAR LOCATION; CHARACTERIZATION OF VARIANTS MDS PHE-34; TYR-34 AND ARG-157;

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.