UniProtKB/Swiss-Prot P01137: Variant p.His222Asp

Transforming growth factor beta-1
Gene: TGFB1
Chromosomal location: 19q13.1
Variant information

Variant position:  222
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 have been found in patients and disease-association is reported in literature. However, this classification is not a definitive assessment of variant pathogenicity.
  • Polymorphism: No disease-association has been reported.
  • Unclassified: Variants have been found in patients but disease-association remains unclear.

Residue change:  From Histidine (H) to Aspartate (D) at position 222 (H222D, p.His222Asp).
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 (H) to medium size and acidic (D)
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 CE; sporadic case; higher levels of active TGF-beta-1 in the culture medium.
Any additional useful information about the variant.



Sequence information

Variant position:  222
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  390
The length of the canonical sequence.

Location on the sequence:   GVVRQWLSRGGEIEGFRLSA  H CSCDSRDNTLQVDINGFTTG
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                         GVVRQWLSRGGEIEGFRLSAHCSCDSRDNTLQVDINGFTTG

Mouse                         GVVRQWLNQGDGIQGFRFSAHCSCDSKDNKLHVEINGISPK

Rat                           GVVRQWLNQGDGIQGFRFSAHCSCDSKDNVLHVEINGISPK

Pig                           GVVRQWLTRREAIEGFRLSAHCSCDSKDNTLHVEINGFNSG

Bovine                        GVVRQWLTRREEIEGFRLSAHCSCDSKDNTLQVDINGFSSG

Sheep                         GVVRQWLTHREEIEGFRLSAHCSCDSKDNTLQVDINGFSSG

Dog                           GVVRQWLSHGGEVEGFRLSAHCSCDSKDNTLQVDINGFSSS

Horse                         GVVRQWLSQGGAMEGFRLSAHCSCDSKDNTLRVGINGFSSS

Xenopus laevis                KTVNEWLKRAEENEQFGLQPACKCPTPQAK-DIDIEGF-PA

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 30 – 278 Latency-associated peptide
Region 75 – 271 Arm domain
Disulfide bond 223 – 223 Interchain (with C-225)
Disulfide bond 225 – 225 Interchain (with C-223)


Literature citations

Transforming growth factor-beta-1 mutations in Camurati-Engelmann disease lead to increased signaling by altering either activation or secretion of the mutant protein.
Janssens K.; ten Dijke P.; Ralston S.H.; Bergmann C.; Van Hul W.;
J. Biol. Chem. 278:7718-7724(2003)
Cited for: CHARACTERIZATION OF VARIANTS CE HIS-81; CYS-218; ASP-222 AND ARG-225;

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.