Q7Z7L1 · SLN11_HUMAN
- ProteinSchlafen family member 11
- GeneSLFN11
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids901 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Inhibitor of DNA replication that promotes cell death in response to DNA damage (PubMed:22927417, PubMed:26658330, PubMed:29395061).
Acts as a guardian of the genome by killing cells with defective replication (PubMed:29395061).
Persistently blocks stressed replication forks by opening chromatin across replication initiation sites at stressed replication forks, possibly leading to unwind DNA ahead of the MCM helicase and block fork progression, ultimately leading to cell death (PubMed:29395061).
Upon DNA damage, inhibits translation of ATR or ATM based on distinct codon usage without disrupting early DNA damage response signaling (PubMed:30374083).
Antiviral restriction factor with manganese-dependent type II tRNA endoribonuclease (PubMed:36115853).
A single tRNA molecule is bound and cleaved by the SLFN11 dimer (PubMed:36115853).
Specifically abrogates the production of retroviruses such as human immunodeficiency virus 1 (HIV-1) by acting as a specific inhibitor of the synthesis of retroviruses encoded proteins in a codon-usage-dependent manner (PubMed:23000900).
Impairs the replication of human cytomegalovirus (HCMV) and some Flaviviruses (PubMed:35105802, PubMed:36115853).
Exploits the unique viral codon bias towards A/T nucleotides (PubMed:23000900).
Also acts as an interferon (IFN)-induced antiviral protein which acts as an inhibitor of retrovirus protein synthesis (PubMed:23000900).
Acts as a guardian of the genome by killing cells with defective replication (PubMed:29395061).
Persistently blocks stressed replication forks by opening chromatin across replication initiation sites at stressed replication forks, possibly leading to unwind DNA ahead of the MCM helicase and block fork progression, ultimately leading to cell death (PubMed:29395061).
Upon DNA damage, inhibits translation of ATR or ATM based on distinct codon usage without disrupting early DNA damage response signaling (PubMed:30374083).
Antiviral restriction factor with manganese-dependent type II tRNA endoribonuclease (PubMed:36115853).
A single tRNA molecule is bound and cleaved by the SLFN11 dimer (PubMed:36115853).
Specifically abrogates the production of retroviruses such as human immunodeficiency virus 1 (HIV-1) by acting as a specific inhibitor of the synthesis of retroviruses encoded proteins in a codon-usage-dependent manner (PubMed:23000900).
Impairs the replication of human cytomegalovirus (HCMV) and some Flaviviruses (PubMed:35105802, PubMed:36115853).
Exploits the unique viral codon bias towards A/T nucleotides (PubMed:23000900).
Also acts as an interferon (IFN)-induced antiviral protein which acts as an inhibitor of retrovirus protein synthesis (PubMed:23000900).
Miscellaneous
Dominant determinant of sensitivity to DNA-damaging anticancer drugs: acts by mediating cell death in response to DNA damage induced by anticancer drugs (PubMed:29395061).
Down-regulated in a number of chemoresistant tumors (PubMed:26625211, PubMed:27440269, PubMed:28196596, PubMed:28212573).
Down-regulated in a number of chemoresistant tumors (PubMed:26625211, PubMed:27440269, PubMed:28196596, PubMed:28212573).
Cofactor
Features
Showing features for binding site, active site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Binding site | 209 | Mg2+ (UniProtKB | ChEBI); catalytic | ||||
Sequence: E | ||||||
Binding site | 214 | Mg2+ (UniProtKB | ChEBI); catalytic | ||||
Sequence: E | ||||||
Active site | 216 | |||||
Sequence: K | ||||||
Binding site | 285 | Zn2+ (UniProtKB | ChEBI) | ||||
Sequence: H | ||||||
Binding site | 287 | Zn2+ (UniProtKB | ChEBI) | ||||
Sequence: C | ||||||
Binding site | 321 | Zn2+ (UniProtKB | ChEBI) | ||||
Sequence: C | ||||||
Binding site | 322 | Zn2+ (UniProtKB | ChEBI) | ||||
Sequence: C | ||||||
Binding site | 599-606 | ATP (UniProtKB | ChEBI) | ||||
Sequence: GLPGSGKT |
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | cytosol | |
Cellular Component | nucleoplasm | |
Cellular Component | nucleus | |
Cellular Component | site of DNA damage | |
Molecular Function | ATP binding | |
Molecular Function | ATP hydrolysis activity | |
Molecular Function | DNA binding | |
Molecular Function | endonuclease activity | |
Molecular Function | helicase activity | |
Molecular Function | tRNA binding | |
Biological Process | chromatin remodeling | |
Biological Process | defense response to virus | |
Biological Process | DNA damage response | |
Biological Process | immune system process | |
Biological Process | negative regulation of DNA replication | |
Biological Process | negative regulation of G1/S transition of mitotic cell cycle | |
Biological Process | replication fork arrest |
Keywords
- Molecular function
- Biological process
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameSchlafen family member 11
- EC number
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionQ7Z7L1
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Keywords
- Cellular component
Disease & Variants
Features
Showing features for natural variant, mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Natural variant | VAR_031492 | 121 | in dbSNP:rs12453150 | |||
Sequence: V → F | ||||||
Mutagenesis | 209 | Complete loss of endonuclease activity. | ||||
Sequence: E → A | ||||||
Mutagenesis | 214 | Complete loss of endonuclease activity. | ||||
Sequence: E → A | ||||||
Mutagenesis | 216 | Complete loss of endonuclease activity. | ||||
Sequence: K → A | ||||||
Mutagenesis | 234 | No effect on endonuclease activity. | ||||
Sequence: Y → A | ||||||
Mutagenesis | 252 | Slight increase in endonuclease activity. | ||||
Sequence: D → A | ||||||
Natural variant | VAR_031493 | 301 | in dbSNP:rs4796077 | |||
Sequence: N → D | ||||||
Natural variant | VAR_062186 | 489 | in dbSNP:rs9898983 | |||
Sequence: R → L | ||||||
Mutagenesis | 605 | Abolishes ATPase activity without affecting its role in DNA damage response; when associated with A-668. | ||||
Sequence: K → M | ||||||
Mutagenesis | 668 | Abolishes ATPase activity without affecting its role in DNA damage response; when associated with M-605. | ||||
Sequence: D → A | ||||||
Mutagenesis | 669 | Abolishes ATPase activity, leading to abolish ability to inhibit DNA replication without affecting subcellular location. | ||||
Sequence: E → Q | ||||||
Mutagenesis | 753 | Complete loss of tRNA cleavage and ssDNA binding. | ||||
Sequence: S → D | ||||||
Natural variant | VAR_031494 | 822 | in dbSNP:rs3803860 | |||
Sequence: Y → C |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 1,272 variants from UniProt as well as other sources including ClinVar and dbSNP.
Organism-specific databases
Miscellaneous
Genetic variation databases
PTM/Processing
Features
Showing features for chain, modified residue (large scale data).
Type | ID | Position(s) | Source | Description | |||
---|---|---|---|---|---|---|---|
Chain | PRO_0000283091 | 1-901 | UniProt | Schlafen family member 11 | |||
Sequence: MEANQCPLVVEPSYPDLVINVGEVTLGEENRKKLQKIQRDQEKERVMRAACALLNSGGGVIRMAKKVEHPVEMGLDLEQSLRELIQSSDLQAFFETKQQGRCFYIFVKSWSSGPFPEDRSVKPRLCSLSSSLYRRSETSVRSMDSREAFCFLKTKRKPKILEEGPFHKIHKGVYQELPNSDPADPNSDPADLIFQKDYLEYGEILPFPESQLVEFKQFSTKHFQEYVKRTIPEYVPAFANTGGGYLFIGVDDKSREVLGCAKENVDPDSLRRKIEQAIYKLPCVHFCQPQRPITFTLKIVNVLKRGELYGYACMIRVNPFCCAVFSEAPNSWIVEDKYVCSLTTEKWVGMMTDTDPDLLQLSEDFECQLSLSSGPPLSRPVYSKKGLEHKKELQQLLFSVPPGYLRYTPESLWRDLISEHRGLEELINKQMQPFFRGILIFSRSWAVDLNLQEKPGVICDALLIAQNSTPILYTILREQDAEGQDYCTRTAFTLKQKLVNMGGYTGKVCVRAKVLCLSPESSAEALEAAVSPMDYPASYSLAGTQHMEALLQSLVIVLLGFRSLLSDQLGCEVLNLLTAQQYEIFSRSLRKNRELFVHGLPGSGKTIMAMKIMEKIRNVFHCEAHRILYVCENQPLRNFISDRNICRAETRKTFLRENFEHIQHIVIDEAQNFRTEDGDWYGKAKSITRRAKGGPGILWIFLDYFQTSHLDCSGLPPLSDQYPREELTRIVRNADPIAKYLQKEMQVIRSNPSFNIPTGCLEVFPEAEWSQGVQGTLRIKKYLTVEQIMTCVADTCRRFFDRGYSPKDVAVLVSTAKEVEHYKYELLKAMRKKRVVQLSDACDMLGDHIVLDSVRRFSGLERSIVFGIHPRTADPAILPNVLICLASRAKQHLYIFPWGGH | |||||||
Modified residue (large scale data) | 130 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 131 | PRIDE | Phosphoserine | ||||
Sequence: S |
Proteomic databases
PTM databases
Expression
Tissue specificity
Exhibits a wider expression range in ovarian and colon adenocarcinoma than in their corresponding healthy tissues.
Induction
Down-regulated in small cell lung cancer (SCLC) cells resistant to PARP inhibitor drugs (PubMed:26625211, PubMed:27440269, PubMed:28196596, PubMed:28212573).
Up-regulated by type I interferons, poly-IC and poly-dAdT (PubMed:20956525, PubMed:23000900).
Up-regulated by type I interferons, poly-IC and poly-dAdT (PubMed:20956525, PubMed:23000900).
Gene expression databases
Organism-specific databases
Structure
Family & Domains
Domain
The N-terminus contains an endonuclease domain. The C-terminus displays homology to superfamily I DNA/RNA helicases, although it is in an autoinhibited conformation.
Sequence similarities
Belongs to the Schlafen family. Subgroup III subfamily.
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Length901
- Mass (Da)102,836
- Last updated2010-11-30 v2
- Checksum514FD89CB7C12E8D
Computationally mapped potential isoform sequences
There are 8 potential isoforms mapped to this entry
Sequence caution
Features
Showing features for sequence conflict.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Sequence conflict | 20 | in Ref. 1; BAC03835 | ||||
Sequence: N → S | ||||||
Sequence conflict | 143 | in Ref. 1; BAC03835 | ||||
Sequence: M → T | ||||||
Sequence conflict | 324 | in Ref. 2; CAD38606 | ||||
Sequence: V → M | ||||||
Sequence conflict | 665 | in Ref. 1; BAC03835 and 2; CAD38606 | ||||
Sequence: I → V |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AK074184 EMBL· GenBank· DDBJ | BAB85010.1 EMBL· GenBank· DDBJ | mRNA | Frameshift | |
AK092241 EMBL· GenBank· DDBJ | BAC03835.1 EMBL· GenBank· DDBJ | mRNA | ||
AL831964 EMBL· GenBank· DDBJ | CAD38606.2 EMBL· GenBank· DDBJ | mRNA | ||
AC060766 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
CH471147 EMBL· GenBank· DDBJ | EAW80156.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
CH471147 EMBL· GenBank· DDBJ | EAW80157.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
CH471147 EMBL· GenBank· DDBJ | EAW80158.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
BC052586 EMBL· GenBank· DDBJ | AAH52586.1 EMBL· GenBank· DDBJ | mRNA |