Expasy logo

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot Q9Y3Z3: Variant p.Ile448Thr

Deoxynucleoside triphosphate triphosphohydrolase SAMHD1
Gene: SAMHD1
Feedback?
Variant information Variant position: help 448 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant: help 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: help From Isoleucine (I) to Threonine (T) at position 448 (I448T, p.Ile448Thr). 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: help Change from medium size and hydrophobic (I) to medium size and polar (T) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score: help -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: help In AGS5; loss of function in defense response to virus; decreased oligomerization; does not affect localization to nucleus; novel localization to the cytoplasm. Any additional useful information about the variant.
Other resources: help Links to websites of interest for the variant.


Sequence information Variant position: help 448 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length: help 626 The length of the canonical sequence.
Location on the sequence: help LEILYSTDPKLKDAREILKQ I EYRNLFKYVGETQPTGQIKI 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: help The multiple alignment of the region surrounding the variant against various orthologous sequences. 
Human                         LEILYS--TDPKLKDAREILKQIEYRNLFKYVG--ETQPTGQIKI

Mouse                         LEVLHS--TDPQLSEAQSILRNIECRNLYKYLG--ETQPKR

Bovine                        LEILYS--TDPNLNDARMILKKIESRNLYKFVG--ETQPMI

Chicken                       LEILHS--SRPELSEAREILHKIERRELYKFLG--ETQPEK

Xenopus laevis                HQILYS--NDPNLKEAREILQKVERRHLYKYIG--QTHPHS

Zebrafish                     EQILYS--SGPELSEARAILQNIICRRLYKCVG--QTTSET

Caenorhabditis elegans        QEILNSQITDPKMIEAQTALLKIQRREIGCKLGYFEMNPEN

Slime mold                    RRIETS--KEPELEKSRKIIKNIRNRNLYKFVD--EIIVST
Sequence annotation in neighborhood: help 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 – 626 Deoxynucleoside triphosphate triphosphohydrolase SAMHD1
Binding site 451 – 451 in chain C
Binding site 455 – 455 in chain C
Cross 467 – 467 Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)
Mutagenesis 451 – 451 R -> E. Impairs homotetramerization and abolishes dNTPase activity.
Helix 439 – 450



Literature citations
A SAMHD1 mutation associated with Aicardi-Goutieres Syndrome uncouples the ability of SAMHD1 to restrict HIV-1 from its ability to downmodulate type I interferon in humans.
White T.E.; Brandariz-Nunez A.; Martinez-Lopez A.; Knowlton C.; Lenzi G.; Kim B.; Ivanov D.; Diaz-Griffero F.;
Hum. Mutat. 38:658-668(2017)
Cited for: FUNCTION; SUBUNIT; SUBCELLULAR LOCATION; CHARACTERIZATION OF VARIANTS AGS5 PRO-123; CYS-143; HIS-143; GLN-145; TYR-167; ASN-201; SER-209; VAL-254; HIS-290; SER-369; VAL-385 AND THR-448; MUTAGENESIS OF ARG-226; ASP-311 AND GLN-548; Assessment of interferon-related biomarkers in Aicardi-Goutieres syndrome associated with mutations in TREX1, RNASEH2A, RNASEH2B, RNASEH2C, SAMHD1, and ADAR: a case-control study.
Rice G.I.; Forte G.M.; Szynkiewicz M.; Chase D.S.; Aeby A.; Abdel-Hamid M.S.; Ackroyd S.; Allcock R.; Bailey K.M.; Balottin U.; Barnerias C.; Bernard G.; Bodemer C.; Botella M.P.; Cereda C.; Chandler K.E.; Dabydeen L.; Dale R.C.; De Laet C.; De Goede C.G.; Del Toro M.; Effat L.; Enamorado N.N.; Fazzi E.; Gener B.; Haldre M.; Lin J.P.; Livingston J.H.; Lourenco C.M.; Marques W. Jr.; Oades P.; Peterson P.; Rasmussen M.; Roubertie A.; Schmidt J.L.; Shalev S.A.; Simon R.; Spiegel R.; Swoboda K.J.; Temtamy S.A.; Vassallo G.; Vilain C.N.; Vogt J.; Wermenbol V.; Whitehouse W.P.; Soler D.; Olivieri I.; Orcesi S.; Aglan M.S.; Zaki M.S.; Abdel-Salam G.M.; Vanderver A.; Kisand K.; Rozenberg F.; Lebon P.; Crow Y.J.;
Lancet Neurol. 12:1159-1169(2013)
Cited for: VARIANTS AGS5 120-ASP--HIS-123 DEL; PRO-123; HIS-143; ASN-201; VAL-254; VAL-385 AND THR-448;
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.