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UniProtKB/Swiss-Prot Q05066: Variant p.Pro125Leu

Sex-determining region Y protein
Gene: SRY
Variant information

Variant position:  125
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Type of variant:  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:  From Proline (P) to Leucine (L) at position 125 (P125L, p.Pro125Leu).
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:  Similar physico-chemical property. Both residues are medium size and hydrophobic.
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  -3
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 SRXY1.
Any additional useful information about the variant.



Sequence information

Variant position:  125
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  204
The length of the canonical sequence.

Location on the sequence:   EKWPFFQEAQKLQAMHREKY  P NYKYRPRRKAKMLPKNCSLL
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                         EKWPFFQEAQKLQAMHREKYPNYKYRPRRKAKMLPKNCSLL

Gorilla                       EKWPFFQEAQKLQAMHREKYPNYKYRPRRKAKMLPKNCSLL

                              EKWPFFEEAQRLQAMHREKYPDYKYRPRRKAT-AQKSHKLL

Rhesus macaque                DKWPFFQEAQKLQAMHREKYPNYKYRPRRKAKMLQNSCSLL

Chimpanzee                    EKWPFFQEAQKLQAMHREKYPNYKYRPRRKANMLPKNCSLL

Mouse                         EKRPFFQEAQRLKILHREKYPNYKYQPHRRAKVSQRSGILQ

Rat                           EKRPFFQEAQRLKTLHREKYPNYKYQPHRRVKVPQRSYTLQ

Pig                           EKRPFFEEAQRLQAVHRDKYPGYKYRPRRKG---ERAQNLL

Bovine                        EKRPFFEEAQRLLAIHRDKYPGYKYRPRRRAKRPQKS---L

Goat                          EKRPFFEEAQRLLAIHRDKYPGYKYRPRRKAKRPQKS---L

Sheep                         EKRPFFEEAQRLLAIHRDKYPGYKYRPRRKAKRPQKS---L

Cat                           EKWPFFEEAQRLQALHREKYPGYRYRPRRKAR-PEKSDKLP

Horse                         EKLPFFEEAQRLRAMHQEKYPDYKYRPRRKAKMPQKSDKPL

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 1 – 204 Sex-determining region Y protein
DNA binding 60 – 128 HMG box
Region 59 – 136 Sufficient for interaction with KPNB1
Region 107 – 139 Sufficient for interaction with EP300
Modified residue 136 – 136 N6-acetyllysine
Mutagenesis 115 – 115 K -> R. Does not abolish acetylation activity.
Mutagenesis 123 – 123 K -> R. Does not abolish acetylation.
Mutagenesis 128 – 128 K -> R. Does not abolish acetylation.
Mutagenesis 133 – 133 R -> W. Reduces nuclear localization. Strongly reduces nuclear localization; when associated with G-62. Reduces interaction with KPNB1. Does not reduce interaction with CAML. Does not abolish DNA-binding.
Mutagenesis 134 – 134 K -> R. Does not abolish acetylation.
Mutagenesis 136 – 136 K -> R. Abolishes acetylation. Does not abolish interaction with EP300. Does not abolish DNA-binding. Enhances cytoplasmic localization. Abolishes interaction with KPNB1.
Beta strand 124 – 126


Literature citations

Two novel SRY missense mutations reducing DNA binding identified in XY females and their mosaic fathers.
Schmitt-Ney M.; Thiele H.; Kaltwasser P.; Bardoni B.; Cisternino M.; Scherer G.;
Am. J. Hum. Genet. 56:862-869(1995)
Cited for: VARIANTS SRXY1 GLY-91 AND LEU-125;

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.