P46063 · RECQ1_HUMAN
- ProteinATP-dependent DNA helicase Q1
- GeneRECQL
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids649 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
DNA helicase that plays a role in DNA damage repair and genome stability (PubMed:15886194, PubMed:35025765, PubMed:7527136, PubMed:7961977, PubMed:8056767).
Exhibits a Mg2+- and ATP-dependent DNA-helicase activity that unwinds single- and double-stranded DNA in a 3'-5' direction (PubMed:19151156, PubMed:35025765, PubMed:7527136, PubMed:8056767).
Full-length protein unwinds forked DNA substrates, resolves Holliday junctions, and has DNA strand annealing activity (PubMed:19151156, PubMed:25831490).
Plays a role in restoring regressed replication forks (PubMed:35025765).
Required to restart stalled replication forks induced by abortive topoisomerase 1 and 2 lesions (PubMed:35025765).
Does not unwind G-quadruplex DNA (PubMed:18426915).
May play a role in the repair of DNA that is damaged by ultraviolet light or other mutagens (PubMed:15886194, PubMed:7961977).
Exhibits a Mg2+- and ATP-dependent DNA-helicase activity that unwinds single- and double-stranded DNA in a 3'-5' direction (PubMed:19151156, PubMed:35025765, PubMed:7527136, PubMed:8056767).
Full-length protein unwinds forked DNA substrates, resolves Holliday junctions, and has DNA strand annealing activity (PubMed:19151156, PubMed:25831490).
Plays a role in restoring regressed replication forks (PubMed:35025765).
Required to restart stalled replication forks induced by abortive topoisomerase 1 and 2 lesions (PubMed:35025765).
Does not unwind G-quadruplex DNA (PubMed:18426915).
May play a role in the repair of DNA that is damaged by ultraviolet light or other mutagens (PubMed:15886194, PubMed:7961977).
Catalytic activity
- ATP + H2O = ADP + H+ + phosphateThis reaction proceeds in the forward direction.
- dATP + H2O = dADP + H+ + phosphateThis reaction proceeds in the forward direction.
Cofactor
Protein has several cofactor binding sites:
Mn2+ (UniProtKB | Rhea| CHEBI:29035 )
Note: Binds 1 Zn2+ per monomer (PubMed:19151156).
Kinetics
KM | SUBSTRATE | pH | TEMPERATURE[C] | NOTES | EVIDENCE | |
---|---|---|---|---|---|---|
95.3 μM | ATP | |||||
115 μM | ATP |
Vmax | pH | TEMPERATURE[C] | NOTES | EVIDENCE | |
---|---|---|---|---|---|
84 nmol/min/ng | with ATP as substrate |
Features
Showing features for binding site, active site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Binding site | 91 | ATP (UniProtKB | ChEBI) | ||||
Sequence: K | ||||||
Binding site | 93 | ATP (UniProtKB | ChEBI) | ||||
Sequence: R | ||||||
Binding site | 96 | ATP (UniProtKB | ChEBI) | ||||
Sequence: Q | ||||||
Binding site | 116 | ATP (UniProtKB | ChEBI) | ||||
Sequence: G | ||||||
Binding site | 118 | ATP (UniProtKB | ChEBI) | ||||
Sequence: G | ||||||
Active site | 119 | |||||
Sequence: K | ||||||
Binding site | 119 | ATP (UniProtKB | ChEBI) | ||||
Sequence: K | ||||||
Binding site | 120 | ATP (UniProtKB | ChEBI) | ||||
Sequence: S | ||||||
Binding site | 453 | Zn2+ (UniProtKB | ChEBI) | ||||
Sequence: C | ||||||
Binding site | 471 | Zn2+ (UniProtKB | ChEBI) | ||||
Sequence: C | ||||||
Binding site | 475 | Zn2+ (UniProtKB | ChEBI) | ||||
Sequence: C | ||||||
Binding site | 478 | Zn2+ (UniProtKB | ChEBI) | ||||
Sequence: C |
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | chromosome | |
Cellular Component | cytoplasm | |
Cellular Component | membrane | |
Cellular Component | nucleoplasm | |
Cellular Component | nucleus | |
Molecular Function | 3'-5' DNA helicase activity | |
Molecular Function | ATP binding | |
Molecular Function | ATP hydrolysis activity | |
Molecular Function | DNA helicase activity | |
Molecular Function | DNA/DNA annealing activity | |
Molecular Function | double-stranded DNA helicase activity | |
Molecular Function | four-way junction helicase activity | |
Molecular Function | isomerase activity | |
Molecular Function | metal ion binding | |
Biological Process | DNA repair | |
Biological Process | DNA unwinding involved in DNA replication | |
Biological Process | double-strand break repair via homologous recombination | |
Biological Process | replication fork processing |
Keywords
- Molecular function
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameATP-dependent DNA helicase Q1
- EC number
- Alternative names
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionP46063
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
Disease & Variants
Involvement in disease
RECON progeroid syndrome (RECON)
- Note
- DescriptionAn autosomal recessive syndrome characterized by short stature, progeroid facial features, a hypoplastic nose, xeroderma, skin photosensitivity, muscle wasting with reduced subcutaneous fat, and slender elongated thumbs.
- See alsoMIM:620370
Natural variants in RECON
Variant ID | Position(s) | Change | Description | |
---|---|---|---|---|
VAR_088584 | 459 | A>S | in RECON; likely pathogenic; reduces DNA helicase activity on a forked duplex DNA substrate; decreases ATPase activity; reduces DNA-binding; defect in repairing abortive TOP1/topoisomerase 1 and TOP2/topoisomerase 2 cleavage complexes; failure to efficiently restart replication following exposure to genotoxins, such as hydroxyurea (HU) and methyl methane sulfonate (MMS); no impact on nuclear localization and interaction with PARP1; no effect on capacity to promote single-strand DNA annealing; dbSNP:rs1055710310 |
Features
Showing features for natural variant, mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Natural variant | VAR_034679 | 102 | in dbSNP:rs1065751 | |||
Sequence: V → I | ||||||
Mutagenesis | 119 | Abrogates helicase activity. | ||||
Sequence: K → A | ||||||
Natural variant | VAR_051732 | 372 | in dbSNP:rs2230003 | |||
Sequence: V → I | ||||||
Natural variant | VAR_088584 | 459 | in RECON; likely pathogenic; reduces DNA helicase activity on a forked duplex DNA substrate; decreases ATPase activity; reduces DNA-binding; defect in repairing abortive TOP1/topoisomerase 1 and TOP2/topoisomerase 2 cleavage complexes; failure to efficiently restart replication following exposure to genotoxins, such as hydroxyurea (HU) and methyl methane sulfonate (MMS); no impact on nuclear localization and interaction with PARP1; no effect on capacity to promote single-strand DNA annealing; dbSNP:rs1055710310 | |||
Sequence: A → S | ||||||
Natural variant | VAR_016140 | 487 | in dbSNP:rs6501 | |||
Sequence: K → T | ||||||
Natural variant | VAR_016141 | 495 | in dbSNP:rs6499 | |||
Sequence: D → H | ||||||
Mutagenesis | 511-514 | Considerably reduced DNA unwinding and branch migration on Holliday junctions, small change in DNA annealing. | ||||
Sequence: TPLK → APLA | ||||||
Mutagenesis | 528 | Reduced DNA unwinding and branch migration on Holliday junctions, small change in DNA annealing. | ||||
Sequence: R → A | ||||||
Mutagenesis | 555-572 | Complete loss of DNA fork unwinding, retains ATPase activity (in a 49-616 residue fragment). | ||||
Sequence: LKEDYSFTAYATISYLKI → AA | ||||||
Mutagenesis | 560-567 | Complete loss of DNA fork unwinding, retains ATPase activity (in a 49-616 residue fragment). | ||||
Sequence: SFTAYATI → AA | ||||||
Mutagenesis | 564 | Nearly complete loss of DNA fork unwinding, retains ATPase activity (in a 49-616 residue fragment). | ||||
Sequence: Y → A |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 1,039 variants from UniProt as well as other sources including ClinVar and dbSNP.
Keywords
- Disease
Organism-specific databases
Miscellaneous
Chemistry
Genetic variation databases
PTM/Processing
Features
Showing features for chain, modified residue (large scale data), modified residue.
Type | ID | Position(s) | Source | Description | |||
---|---|---|---|---|---|---|---|
Chain | PRO_0000205049 | 1-649 | UniProt | ATP-dependent DNA helicase Q1 | |||
Sequence: MASVSALTEELDSITSELHAVEIQIQELTERQQELIQKKKVLTKKIKQCLEDSDAGASNEYDSSPAAWNKEDFPWSGKVKDILQNVFKLEKFRPLQLETINVTMAGKEVFLVMPTGGGKSLCYQLPALCSDGFTLVICPLISLMEDQLMVLKQLGISATMLNASSSKEHVKWVHAEMVNKNSELKLIYVTPEKIAKSKMFMSRLEKAYEARRFTRIAVDEVHCCSQWGHDFRPDYKALGILKRQFPNASLIGLTATATNHVLTDAQKILCIEKCFTFTASFNRPNLYYEVRQKPSNTEDFIEDIVKLINGRYKGQSGIIYCFSQKDSEQVTVSLQNLGIHAGAYHANLEPEDKTTVHRKWSANEIQVVVATVAFGMGIDKPDVRFVIHHSMSKSMENYYQESGRAGRDDMKADCILYYGFGDIFRISSMVVMENVGQQKLYEMVSYCQNISKCRRVLMAQHFDEVWNSEACNKMCDNCCKDSAFERKNITEYCRDLIKILKQAEELNEKLTPLKLIDSWMGKGAAKLRVAGVVAPTLPREDLEKIIAHFLIQQYLKEDYSFTAYATISYLKIGPKANLLNNEAHAITMQVTKSTQNSFRAESSQTCHSEQGDKKMEEKNSGNFQKKAANMLQQSGSKNTGAKKRKIDDA | |||||||
Modified residue (large scale data) | 5 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 53 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 58 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 63 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 64 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 511 | PRIDE | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue | 514 | UniProt | N6-acetyllysine | ||||
Sequence: K | |||||||
Modified residue | 522 | UniProt | N6-acetyllysine | ||||
Sequence: K | |||||||
Modified residue | 597 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 597 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 602 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 603 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 634 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 634 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 636 | PRIDE | Phosphoserine | ||||
Sequence: S |
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Tissue specificity
High expression in heart, lung, skeletal muscle and kidney, low expression in brain.
Gene expression databases
Organism-specific databases
Interaction
Subunit
May form homodimers or higher order oligomers (PubMed:19151156, PubMed:35025765).
Forms a dimer in complex with tailed duplex DNA; the DNA only mkaes contact with one of the monomers (PubMed:25831490).
Probably forms flat tetramers on Holliday junction DNA (Probable) (PubMed:25831490).
Interacts with EXO1 (PubMed:15886194).
Interacts with MLH1 (PubMed:15886194).
Interacts with PARP1 (PubMed:19151156, PubMed:25831490, PubMed:35025765).
Forms a dimer in complex with tailed duplex DNA; the DNA only mkaes contact with one of the monomers (PubMed:25831490).
Probably forms flat tetramers on Holliday junction DNA (Probable) (PubMed:25831490).
Interacts with EXO1 (PubMed:15886194).
Interacts with MLH1 (PubMed:15886194).
Interacts with PARP1 (PubMed:19151156, PubMed:25831490, PubMed:35025765).
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
BINARY | P46063 | KPNA2 P52292 | 2 | EBI-2823728, EBI-349938 | |
BINARY | P46063 | KPNA4 O00629 | 2 | EBI-2823728, EBI-396343 | |
BINARY | P46063 | PARP1 P09874 | 9 | EBI-2823728, EBI-355676 |
Protein-protein interaction databases
Chemistry
Miscellaneous
Structure
Family & Domains
Features
Showing features for domain, motif, region, compositional bias.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Domain | 100-275 | Helicase ATP-binding | ||||
Sequence: INVTMAGKEVFLVMPTGGGKSLCYQLPALCSDGFTLVICPLISLMEDQLMVLKQLGISATMLNASSSKEHVKWVHAEMVNKNSELKLIYVTPEKIAKSKMFMSRLEKAYEARRFTRIAVDEVHCCSQWGHDFRPDYKALGILKRQFPNASLIGLTATATNHVLTDAQKILCIEKCF | ||||||
Motif | 219-222 | DEVH box | ||||
Sequence: DEVH | ||||||
Domain | 300-451 | Helicase C-terminal | ||||
Sequence: FIEDIVKLINGRYKGQSGIIYCFSQKDSEQVTVSLQNLGIHAGAYHANLEPEDKTTVHRKWSANEIQVVVATVAFGMGIDKPDVRFVIHHSMSKSMENYYQESGRAGRDDMKADCILYYGFGDIFRISSMVVMENVGQQKLYEMVSYCQNIS | ||||||
Region | 481-592 | Winged-helix domain | ||||
Sequence: DSAFERKNITEYCRDLIKILKQAEELNEKLTPLKLIDSWMGKGAAKLRVAGVVAPTLPREDLEKIIAHFLIQQYLKEDYSFTAYATISYLKIGPKANLLNNEAHAITMQVTK | ||||||
Region | 595-649 | Disordered | ||||
Sequence: QNSFRAESSQTCHSEQGDKKMEEKNSGNFQKKAANMLQQSGSKNTGAKKRKIDDA | ||||||
Compositional bias | 606-621 | Basic and acidic residues | ||||
Sequence: CHSEQGDKKMEEKNSG | ||||||
Compositional bias | 622-639 | Polar residues | ||||
Sequence: NFQKKAANMLQQSGSKNT |
Domain
A helical hairpin (residues 554-573) in the winged-helix proble DNA-binding domain couples the ATPase (and probably ssDNA translocation) to DNA unwinding (PubMed:19151156).
The isolated WH domain (residues 481-624) anneals DNA as well as full-length protein (PubMed:25831490).
The isolated WH domain (residues 481-624) anneals DNA as well as full-length protein (PubMed:25831490).
Sequence similarities
Belongs to the helicase family. RecQ subfamily.
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Length649
- Mass (Da)73,457
- Last updated2008-12-16 v3
- ChecksumF616DC3191F79391
Computationally mapped potential isoform sequences
There are 6 potential isoforms mapped to this entry
Sequence caution
Features
Showing features for sequence conflict, compositional bias.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Sequence conflict | 1 | in Ref. 2; BAA07200 | ||||
Sequence: M → S | ||||||
Sequence conflict | 175 | in Ref. 1; AAA60261 | ||||
Sequence: A → D | ||||||
Sequence conflict | 453 | in Ref. 1; AAA60261 | ||||
Sequence: C → S | ||||||
Sequence conflict | 566 | in Ref. 1; AAA60261 | ||||
Sequence: T → A | ||||||
Compositional bias | 606-621 | Basic and acidic residues | ||||
Sequence: CHSEQGDKKMEEKNSG | ||||||
Sequence conflict | 617 | in Ref. 3; AAP35783 and 7; AAH01052 | ||||
Sequence: E → K | ||||||
Compositional bias | 622-639 | Polar residues | ||||
Sequence: NFQKKAANMLQQSGSKNT |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
L36140 EMBL· GenBank· DDBJ | AAA60261.1 EMBL· GenBank· DDBJ | mRNA | Frameshift | |
D37984 EMBL· GenBank· DDBJ | BAA07200.1 EMBL· GenBank· DDBJ | mRNA | ||
BT007119 EMBL· GenBank· DDBJ | AAP35783.1 EMBL· GenBank· DDBJ | mRNA | ||
AK291627 EMBL· GenBank· DDBJ | BAF84316.1 EMBL· GenBank· DDBJ | mRNA | ||
AC006559 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
CH471094 EMBL· GenBank· DDBJ | EAW96434.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
BC001052 EMBL· GenBank· DDBJ | AAH01052.1 EMBL· GenBank· DDBJ | mRNA |