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UniProtKB/Swiss-Prot Q9C0C7: Variant p.Ser1043Phe

Activating molecule in BECN1-regulated autophagy protein 1
Gene: AMBRA1
Variant information

Variant position:  1043
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Type of variant:  US
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 Serine (S) to Phenylalanine (F) at position 1043 (S1043F, p.Ser1043Phe).
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

Variant description:  Found in a fetus with anencephaly and spina bifida; unknown pathological significance; does not impair induction of autophagy.
Any additional useful information about the variant.



Sequence information

Variant position:  1043
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  1298
The length of the canonical sequence.

Location on the sequence:   GLAYGTNKGDLVICRPEALN  S GVEYYWDQLNETVFTVHSNS
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                         GLAYGTNKGDLVICRPEALNSGVEYYWDQLNETVFTVHSNS

Mouse                         GLAYGTNKGDLVICRPEALNSGIEYYWDQLSETVFTVHSSS

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 – 1298 Activating molecule in BECN1-regulated autophagy protein 1
Motif 1043 – 1052 LIR
Modified residue 1043 – 1043 Phosphoserine; by IKKA
Alternative sequence 881 – 1298 Missing. In isoform 6.
Mutagenesis 1043 – 1043 S -> A. Abolished phosphorylation by CHUK/IKKA, leading to impaired interaction with ATG8 family proteins and reduced mitophagic activity.
Mutagenesis 1043 – 1043 S -> D. Phospho-mimetic mutant; increased interaction with ATG8 family proteins and increased mitophagic activity.


Literature citations

Rare mutations in the autophagy-regulating gene AMBRA1 contribute to human neural tube defects.
Ye J.; Tong Y.; Lv J.; Peng R.; Chen S.; Kuang L.; Su K.; Zheng Y.; Zhang T.; Zhang F.; Jin L.; Yang X.; Wang H.;
Hum. Mutat. 41:1383-1393(2020)
Cited for: VARIANTS MET-80; PHE-364; PHE-833; VAL-974 AND PHE-1043; CHARACTERIZATION OF VARIANTS MET-80; PHE-364; PHE-833; VAL-974 AND PHE-1043; FUNCTION;

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.