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UniProtKB/Swiss-Prot P01588: Variant p.Arg177Gln

Erythropoietin
Gene: EPO
Variant information

Variant position:  177
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 Arginine (R) to Glutamine (Q) at position 177 (R177Q, p.Arg177Gln).
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 large size and basic (R) to medium size and polar (Q)
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

Variant description:  In DBAL; loss of support of normal erythroid expansion or differentiation; reduced ability to promote EPOR dimer formation upon binding, resulting in reduced JAK2 activation and decreased STAT1 and STAT3 phosphorylation; mild decrease in affinity for EPOR; no effect on STAT5A phosphorylation.
Any additional useful information about the variant.

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



Sequence information

Variant position:  177
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  193
The length of the canonical sequence.

Location on the sequence:   LRTITADTFRKLFRVYSNFL  R GKLKLYTGEACRTGDR
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                         LRTITADTFRKLFRVYSNFLRGKLKLYTGEA--CRTGDR

                              LRTFTVDTLCKLFRIYSNFLRGKLTLYTGEA--CRRG

Rhesus macaque                LRTITADTFCKLFRVYSNFLRGKLKLYTGEA--CRRG

Mouse                         LRTLTVDTFCKLFRVYANFLRGKLKLYTGEV--CRRG

Rat                           LRTLTADTFCKLFRVYSNFLRGKLKLYTGEA--CRRG

Pig                           LRTFAVDTLCKLFRNYSNFLRGKLTLYTGEA--CRRR

Bovine                        LRAFTVDALSKLFRIYSNFLRGKLTLYTGEA--CRRG

Rabbit                        LRTVAADTLCKLFRIYSNFLRGKLKLYTGEA--CRRG

Sheep                         LRIFTVDALSKLFRIYSNFLRGKLTLYTGEA--CRRG

Cat                           LRTFTVDTLCKLFRIYSNFLRGKLTLYTGEA--CRRG

Horse                         LRTFAVDTLCKLFRIYSNFLRGKLKLYTGEA--CRRG

Zebrafish                     -ETQKISSISELFQVHVNFLRGKARLLLANAPVCRQG

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 28 – 193 Erythropoietin
Disulfide bond 34 – 188
Helix 165 – 177


Literature citations

Functional selectivity in cytokine signaling revealed through a pathogenic EPO mutation.
Kim A.R.; Ulirsch J.C.; Wilmes S.; Unal E.; Moraga I.; Karakukcu M.; Yuan D.; Kazerounian S.; Abdulhay N.J.; King D.S.; Gupta N.; Gabriel S.B.; Lander E.S.; Patiroglu T.; Ozcan A.; Ozdemir M.A.; Garcia K.C.; Piehler J.; Gazda H.T.; Klein D.E.; Sankaran V.G.;
Cell 168:1053-1064(2017)
Cited for: INVOLVEMENT IN DBAL; VARIANT DBAL GLN-177; CHARACTERIZATION OF VARIANT DBAL GLN-177; FUNCTION; MUTAGENESIS OF SER-127;

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.