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UniProtKB/Swiss-Prot P01137: Variant p.Arg45Cys

Transforming growth factor beta-1 proprotein
Gene: TGFB1
Variant information

Variant position:  45
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 Arginine (R) to Cysteine (C) at position 45 (R45C, p.Arg45Cys).
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 (C)
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 IBDIMDE; decreased TGFB1-mediated activation of SMAD signaling; reduced levels of secreated TGFB1.
Any additional useful information about the variant.



Sequence information

Variant position:  45
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:   RPAAGLSTCKTIDMELVKRK  R IEAIRGQILSKLRLASPPSQ
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                         RPAAGLSTCKTIDMELVKRKRIEAIRGQILSKLRLASPPSQ

                              RPAAGLSTCKTIDMELVKRKRIEAIRGQILSKLRLSSPPSQ

Mouse                         RPAAGLSTCKTIDMELVKRKRIEAIRGQILSKLRLASPPSQ

Rat                           RPAAGLSTCKTIDMELVKRKRIEAIRGQILSKLRLASPPSQ

Pig                           RPAAGLSTCKTIDMELVKRKRIEAIRGQILSKLRLASPPSQ

Bovine                        RPVAGLSTCKTIDMELVKRKRIEAIRGQILSKLRLASPPSQ

Sheep                         RPVAGLSTCKTIDMELVKRKGIEAIRGQILSKLRLASPPSQ

Horse                         RPAAGLSTCKTIDMELVKRKRIEAIRGQILSKLRLASPPSQ

Chicken                       --ARALSTCQRLDLEAAKKKRIEAVRGQILSKLRLTAPPPA

Xenopus laevis                --AMSLSTCKAVDMEEVRKRRIEAIRGQILSKLKLDKTPDV

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 30 – 74 Straightjacket domain
Disulfide bond 33 – 33 Interchain (with C-1359 or C-1384 in LTBP1); in inactive form
Mutagenesis 33 – 33 C -> S. Abolishes interchain disulfide bond with LTBP1 and/or LRRC32, and subsequent regulation of activation of TGF-beta-1.
Helix 33 – 57


Literature citations

Human TGF-beta1 deficiency causes severe inflammatory bowel disease and encephalopathy.
Kotlarz D.; Marquardt B.; Baroey T.; Lee W.S.; Konnikova L.; Hollizeck S.; Magg T.; Lehle A.S.; Walz C.; Borggraefe I.; Hauck F.; Bufler P.; Conca R.; Wall S.M.; Schumacher E.M.; Misceo D.; Frengen E.; Bentsen B.S.; Uhlig H.H.; Hopfner K.P.; Muise A.M.; Snapper S.B.; Stroemme P.; Klein C.;
Nat. Genet. 50:344-348(2018)
Cited for: FUNCTION; SUBCELLULAR LOCATION; INVOLVEMENT IN IBDIMDE; VARIANTS IBDIMDE CYS-45; CYS-110 AND ARG-387; CHARACTERIZATION OF VARIANTS IBDIMDE CYS-45; CYS-110 AND ARG-387;

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.