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UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot Q9Y3Z3: Variant p.Met385Val

Deoxynucleoside triphosphate triphosphohydrolase SAMHD1
Gene: SAMHD1
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Variant information Variant position: help 385 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 Methionine (M) to Valine (V) at position 385 (M385V, p.Met385Val). 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 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: 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; loss of oligomerization. Any additional useful information about the variant.
Other resources: help Links to websites of interest for the variant.


Sequence information Variant position: help 385 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 TRNSLHRRAYQHKVGNIIDT M ITDAFLKADDYIEITGAGGK 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                         TRNSLHRRAYQHKVGNIIDTMITDAFLKADDYIEITGAGGK

Mouse                         TRNCLHRRAYQHKISNLIDIMITDAFLKADPYVEITGTAGK

Bovine                        TRNCLHRRAYQHKVGNIIDTMITDAFLKADDHIEITGSAGR

Chicken                       TRNCLHRRAYQHKVGNIIEIMITEAFQKADCFFQIEGSKGK

Xenopus laevis                TRNCLHRRAYQHKVGNIIETMITDAFVKADPHIKIEGANGK

Zebrafish                     TRNCLHRRAYQHKVGNIIETMITEAFLKADPHIQIQGSSGR

Caenorhabditis elegans        SRQELHSKVYQHKAVRFMETLMVDALINAGDFLKYKGSNGE

Slime mold                    TRYSLHKLVYTHKVGKSIEFMIADAFTEADQFLK-------
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 366 – 366
Binding site 366 – 366
Binding site 366 – 366
Binding site 372 – 372 in chain C
Binding site 374 – 374
Binding site 375 – 375
Binding site 375 – 375
Binding site 375 – 375
Binding site 375 – 375
Binding site 376 – 376 in chain C
Binding site 376 – 376 in chain C
Binding site 376 – 376 in chain C
Binding site 376 – 376 in chain C
Binding site 377 – 377 in chain C
Binding site 377 – 377 in chain C
Binding site 377 – 377 in chain C
Binding site 377 – 377 in chain C
Mutagenesis 366 – 366 R -> A. Abolishes dNTPase activity; when associated with A-312 and A-315.
Mutagenesis 370 – 370 H -> A. Abolishes dNTPase activity; when associated with G-374.
Mutagenesis 372 – 372 R -> D. Abolished homotetramerization and dNTPase activity.
Mutagenesis 374 – 374 Y -> G. Abolishes dNTPase activity; when associated with A-370.
Mutagenesis 375 – 375 Q -> A. Abolished dNTPase activity without affecting homotetramerization.
Mutagenesis 376 – 376 H -> A. Impairs homotetramerization and abolishes dNTPase activity; when associated with A-352 and A-377.
Mutagenesis 377 – 377 K -> A. Impairs homotetramerization and abolishes dNTPase activity; when associated with A-352 and A-376.
Helix 377 – 393



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; Mutations involved in Aicardi-Goutieres syndrome implicate SAMHD1 as regulator of the innate immune response.
Rice G.I.; Bond J.; Asipu A.; Brunette R.L.; Manfield I.W.; Carr I.M.; Fuller J.C.; Jackson R.M.; Lamb T.; Briggs T.A.; Ali M.; Gornall H.; Couthard L.R.; Aeby A.; Attard-Montalto S.P.; Bertini E.; Bodemer C.; Brockmann K.; Brueton L.A.; Corry P.C.; Desguerre I.; Fazzi E.; Cazorla A.G.; Gener B.; Hamel B.C.J.; Heiberg A.; Hunter M.; van der Knaap M.S.; Kumar R.; Lagae L.; Landrieu P.G.; Lourenco C.M.; Marom D.; McDermott M.F.; van der Merwe W.; Orcesi S.; Prendiville J.S.; Rasmussen M.; Shalev S.A.; Soler D.M.; Shinawi M.; Spiegel R.; Tan T.Y.; Vanderver A.; Wakeling E.L.; Wassmer E.; Whittaker E.; Lebon P.; Stetson D.B.; Bonthron D.T.; Crow Y.J.;
Nat. Genet. 41:829-832(2009)
Cited for: VARIANTS AGS5 PRO-123; CYS-143; HIS-143; GLN-145; ASN-201; SER-209; VAL-254; SER-369 AND VAL-385; FUNCTION; SUBCELLULAR LOCATION; 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.