UniProtKB/Swiss-Prot P46937: Variant p.Pro139Leu

• Variant information
• Sequence information
• Literature citations
• All

Variant information

Variant position: 139 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant: LB/B 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 139 (P139L, p.Pro139Leu). 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
Other resources: Links to websites of interest for the variant.

• Variant rs1162286204 [ dbSNP | Ensembl ]

Sequence information

Variant position: 139 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length: 504 The length of the canonical sequence.
Location on the sequence: TPQHVRAHSSPASLQLGAVS P GTLTPTGVVSGPAATPTAQH 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.
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	1 – 504	Transcriptional coactivator YAP1
Region	133 – 158	Disordered
Modified residue	119 – 119	Phosphothreonine; by MAPK8 and MAPK9
Modified residue	127 – 127	Phosphoserine; by LATS1 and LATS2
Modified residue	128 – 128	Phosphoserine
Modified residue	131 – 131	Phosphoserine
Modified residue	138 – 138	Phosphoserine; by MAPK8 and MAPK9
Modified residue	154 – 154	Phosphothreonine; by MAPK8 and MAPK9
Alternative sequence	1 – 178	Missing. In isoform 4.
Mutagenesis	122 – 122	H -> ARNK. Loss of phosphorylation by LATS1.
Mutagenesis	122 – 122	H -> LY. Significantly decreased phosphorylation at S-127 and decreased interaction with YWHAB.
Mutagenesis	124 – 124	R -> A. Loss of phosphorylation by LATS1.
Mutagenesis	127 – 127	S -> A. Reduced phosphorylation by LATS2, loss of phosphorylation by LATS1, loss of interaction with YWHAB, decreased interaction with ERBB4 and increased nuclear localization and transcriptional coactivation activity toward ERBB4. In YAP-4SA; prevents phosphorylation by LATS1 and LATS2, promoting retention in the nucleus; when associated with A-61; A-109; A-127 and A-164.
Mutagenesis	129 – 129	P -> D. No effect on phosphorylation but loss of interaction with YWHAB.

Literature citations

Heterozygous loss-of-function mutations in YAP1 cause both isolated and syndromic optic fissure closure defects.
Williamson K.A.; Rainger J.; Floyd J.A.; Ansari M.; Meynert A.; Aldridge K.V.; Rainger J.K.; Anderson C.A.; Moore A.T.; Hurles M.E.; Clarke A.; van Heyningen V.; Verloes A.; Taylor M.S.; Wilkie A.O.; Fitzpatrick D.R.; Hurles M.; FitzPatrick D.R.; Al-Turki S.; Anderson C.; Barroso I.; Beales P.; Bentham J.; Bhattacharya S.; Carss K.; Chatterjee K.; Cirak S.; Cosgrove C.; Daly A.; Floyd J.; Franklin C.; Futema M.; Humphries S.; McCarthy S.; Mitchison H.; Muntoni F.; Onoufriadis A.; Parker V.; Payne F.; Plagnol V.; Raymond L.; Savage D.; Scambler P.; Schmidts M.; Semple R.; Serra E.; Stalker J.; van Kogelenberg M.; Vijayarangakannan P.; Walter K.; Wood G.;
Am. J. Hum. Genet. 94:295-302(2014)
Cited for: INVOLVEMENT IN COB1; VARIANTS LEU-139; LEU-227; VAL-330 AND GLU-462;