SAMHD1

Protein identityUniProt · HPA

UniProt accession

Q9Y3Z3

Gene

SAMHD1

Ensembl

ENSG00000101347

Chromosome

20

Canonical length

626 aa

Protein class

Disease related genes, Human disease related genes, Plasma proteins, Predicted intracellular proteins

Subcellular location

Nucleoplasm,Plasma membrane

Quaternary structure

Homotetramer

OverviewNCBI Gene

This gene may play a role in regulation of the innate immune response. The encoded protein is upregulated in response to viral infection and may be involved in mediation of tumor necrosis factor-alpha proinflammatory responses. Mutations in this gene have been associated with Aicardi-Goutieres syndrome. [provided by RefSeq, Mar 2010]

Canonical amino-acid sequenceUniProt

626 residues, UniProt reviewed canonical sequence.

>Q9Y3Z3|SAMHD1
     1  MQRADSEQPS KRPRCDDSPR TPSNTPSAEA DWSPGLELHP DYKTWGPEQV CSFLRRGGFE
    61  EPVLLKNIRE NEITGALLPC LDESRFENLG VSSLGERKKL LSYIQRLVQI HVDTMKVIND
   121  PIHGHIELHP LLVRIIDTPQ FQRLRYIKQL GGGYYVFPGA SHNRFEHSLG VGYLAGCLVH
   181  ALGEKQPELQ ISERDVLCVQ IAGLCHDLGH GPFSHMFDGR FIPLARPEVK WTHEQGSVMM
   241  FEHLINSNGI KPVMEQYGLI PEEDICFIKE QIVGPLESPV EDSLWPYKGR PENKSFLYEI
   301  VSNKRNGIDV DKWDYFARDC HHLGIQNNFD YKRFIKFARV CEVDNELRIC ARDKEVGNLY
   361  DMFHTRNSLH RRAYQHKVGN IIDTMITDAF LKADDYIEIT GAGGKKYRIS TAIDDMEAYT
   421  KLTDNIFLEI LYSTDPKLKD AREILKQIEY RNLFKYVGET QPTGQIKIKR EDYESLPKEV
   481  ASAKPKVLLD VKLKAEDFIV DVINMDYGMQ EKNPIDHVSF YCKTAPNRAI RITKNQVSQL
   541  LPEKFAEQLI RVYCKKVDRK SLYAARQYFV QWCADRNFTK PQDGDVIAPL ITPQKKEWND
   601  STSVQNPTRL REASKSRVQL FKDDPM

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against SAMHD1 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Intracellular

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.28

Highest tissue expression

87 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about SAMHD1.

Disease | AllUniProt

Conditions SAMHD1 is implicated in, by any mechanism.

• Aicardi-Goutieres syndrome 5 (AGS5) MIM:612952
• Chilblain lupus 2 (CHBL2) MIM:614415

Disease | GeneticClinVar

138 pathogenic / likely-pathogenic of 1,002 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Aicardi-Goutieres syndrome 5
• Aicardi Goutieres syndrome
• Chilblain lupus 2
• SAMHD1-related disorder
• Inborn genetic diseases

ReferencesPubMed · IEDB

Publications for SAMHD1 from three distinct lines of evidence, kept separate because they answer different questions: whether antibodies are directed at the protein, whether a B-cell epitope has been mapped on it, and whether a T-cell epitope has. Each is labelled with its source.

Sources: PubMed — antigen-level antibody evidence from a custom retrieval. Records matching a controlled set of autoantibody terms (the MeSH descriptors Autoantibodies and Autoantigens, with title and abstract term variants) were obtained through NCBI E-utilities, and their titles and abstracts parsed for constructions that direct an antibody at a named protein rather than for co-occurrence. Captured names were resolved against UniProt nomenclature and each antigen adjudicated individually against the source text. Bibliographic records from PubMed and MeSH, U.S. National Library of Medicine; citation metrics from NIH iCite (Hutchins et al., PLoS Biology 2016). Titles link to PubMed; abstracts are not reproduced here. The NLM does not endorse this analysis.

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.94

gnomAD pLI

0

gnomAD missense Z

1.55

DepMap mean gene effect

-0.14

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 5% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• dATP catabolic process
• defense response to virus
• deoxyribonucleotide catabolic process
• dGTP catabolic process
• DNA damage response
• DNA strand resection involved in replication fork processing
• double-strand break repair via homologous recombination
• immune response
• innate immune response
• negative regulation of type I interferon-mediated signaling pathway
• protein homotetramerization
• regulation of innate immune response
• somatic hypermutation of immunoglobulin genes

Molecular functions

• GTP binding
• identical protein binding
• nucleic acid binding
• RNA binding
• RNA nuclease activity
• single-stranded DNA binding
• zinc ion binding
• deoxynucleoside triphosphate hydrolase activity
• dGTP binding
• dGTPase activity

Cellular components

• nucleoplasm
• nucleus
• plasma membrane
• site of double-strand break
• tetraspanin-enriched microdomain

Protein domainsUniProt · Pfam · InterPro

• Sterile alpha motif domain
• HD/PDEase domain
• HD domain
• Sterile alpha motif/pointed domain superfamily
• SAM domain (Sterile alpha motif)
• Deoxyguanosinetriphosphate triphosphohydrolase-like
• HD domain

KeywordsUniProt

• Acetylation
• Aicardi-Goutieres syndrome
• Allosteric enzyme
• Antiviral defense
• Chromosome
• DNA damage
• DNA repair
• DNA replication
• GTP-binding
• Host-virus interaction
• Hydrolase
• Immunity
• Innate immunity
• Isopeptide bond
• Metal-binding
• Nucleotide-binding
• Nucleus
• Phosphoprotein
• Ubl conjugation
• Zinc

InteractionsUniProt · HPA

Protein binding partners of SAMHD1 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• MRE11
• CD81
• RBBP8
• DCAF1
• DYSF
• LGALS3BP
• TIRAP