UniProtKB/SwissProt variant VAR

Variant information

Variant position:

487

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 Asparagine (N) to Serine (S) at position 487 (N487S, p.Asn487Ser).

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 medium size and polar (N) to small size and polar (S)

The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:

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

Involvement in disease:

Erythrocytosis, familial, 1 (ECYT1) [MIM:133100]: An autosomal dominant disorder characterized by increased serum red blood cell mass, elevated hemoglobin and hematocrit, hypersensitivity of erythroid progenitors to erythropoietin, erythropoietin low serum levels, and no increase in platelets nor leukocytes. It has a relatively benign course and does not progress to leukemia. {ECO:0000269|PubMed:8506290, ECO:0000269|PubMed:8608241}. Note=The disease is caused by mutations affecting the gene represented in this entry.

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 ECYT1 and erythroleukemia.

Any additional useful information about the variant.

Other resources:

Links to websites of interest for the variant.

Variant rs62638745 [ dbSNP | Ensembl ]

Sequence information

Variant position:

487

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

Protein sequence length:

508

The length of the canonical sequence.

Location on the sequence:

DYSSGDSQGAQGGLSDGPYS N PYENSLIPAAEPLPPSYVAC

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                         DYSSGDSQGAQGGLSDGPYSNPYENSLIPAAEPLPPSYVAC

                              DYSSGGSQGAQGDSLNSPFLNPYENSLIPAPEPSPPGYVAC

Mouse                         DYSSGGSQGVHGDSSDGPYSHPYENSLVPDSEPLHPGYVAC

Rat                           DYSSGGSQGVHGDSSDGPYSHPYENSLVPDTEPLRPSYVAC

Pig                           DYSSGGSQETQGGSSSGPYSNPYENSLVPAPEPSPPNYVTC

Xenopus laevis                -----------GEHSPPPSPNFYQNS--PITNFLAPIYSQS

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.

Type	Positions	Description
Chain	25 – 508	Erythropoietin receptor
Topological domain	274 – 508	Cytoplasmic
Site	485 – 485	Required for CrkL binding
Modified residue	468 – 468	Phosphotyrosine; by JAK2
Modified residue	485 – 485	Phosphotyrosine; by JAK2
Modified residue	489 – 489	Phosphotyrosine; by JAK2
Modified residue	504 – 504	Phosphotyrosine; by JAK2
Alternative sequence	242 – 508	Missing. In isoform EPOR-S.
Alternative sequence	329 – 508	Missing. In isoform EPOR-T.
Mutagenesis	468 – 468	Y -> F. No effect on STAT1/STAT3 nor STAT5 activity.

Literature citations

Missense mutation of the erythropoietin receptor is a rare event in human erythroid malignancies.
Le Couedic J.-P.; Mitjavila M.-T.; Villeval J.-L.; Feger F.; Gobert S.; Mayeux P.; Casadevall N.; Vainchenker W.;
Blood 87:1502-1511(1996)
Cited for: VARIANT ECYT1 SER-487; VARIANT ERYTHROLEUKEMIA SER-487;

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot P19235: Variant p.Asn487Ser