MultifacetedProtDB - Bologna Biocomputing Group

EC number	EC number description
3.1.-.-	Hydrolases; Acting on ester bonds; ;
3.6.4.12	Hydrolases; Acting on acid anhydrides; Acting on acid anhydrides to facilitate cellular and subcellular movement; DNA helicase.

Structure

PDB	Resolution (Å)	PDB name
2AXL		Solution structure of a multifunctional DNA- and protein-binding domain of human Werner syndrome protein
2DGZ		Solution structure of the Helicase and RNase D C-terminal domain in Werner syndrome ATP-dependent helicase
2E1E	2.3	Crystal structure of the HRDC Domain of Human Werner Syndrome Protein, WRN
2E1F	2.0	Crystal structure of the HRDC Domain of Human Werner Syndrome Protein, WRN
2FBT	2.05	WRN exonuclease
2FBV	2.4	WRN exonuclease, Mn complex
2FBX	2.2	WRN exonuclease, Mg complex
2FBY	2.0	WRN exonuclease, Eu complex
2FC0	2.0	WRN exonuclease, Mn dGMP complex
3AAF	1.9	Structure of WRN RQC domain bound to double-stranded DNA
6TYV	1.92611	Structure of Ku80 von Willebrand domain complexed with WRN Ku Binding Motif
6YHR	2.2	Crystal structure of Werner syndrome helicase

GO term

GO ontology	GO term	GO description
Biological Process	GO:0006974	DNA damage response
Biological Process	GO:0032508	DNA duplex unwinding
Biological Process	GO:0006259	DNA metabolic process
Biological Process	GO:0006260	DNA replication
Biological Process	GO:0000731	DNA synthesis involved in DNA repair
Biological Process	GO:0006268	DNA unwinding involved in DNA replication
Biological Process	GO:0044806	G-quadruplex DNA unwinding
Biological Process	GO:0007568	aging
Biological Process	GO:0006284	base-excision repair
Biological Process	GO:0007420	brain development
Biological Process	GO:0071480	cellular response to gamma radiation
Biological Process	GO:0009267	cellular response to starvation
Biological Process	GO:0090398	cellular senescence
Biological Process	GO:0008340	determination of adult lifespan
Biological Process	GO:0006302	double-strand break repair
Biological Process	GO:0000724	double-strand break repair via homologous recombination
Biological Process	GO:0010259	multicellular organism aging
Biological Process	GO:0051345	positive regulation of hydrolase activity
Biological Process	GO:0098530	positive regulation of strand invasion
Biological Process	GO:1902570	protein localization to nucleolus
Biological Process	GO:0040009	regulation of growth rate
Biological Process	GO:0031297	replication fork processing
Biological Process	GO:0090399	replicative senescence
Biological Process	GO:0010225	response to UV-C
Biological Process	GO:0006979	response to oxidative stress
Biological Process	GO:0090656	t-circle formation
Biological Process	GO:0000723	telomere maintenance
Biological Process	GO:0032201	telomere maintenance via semi-conservative replication
Biological Process	GO:0061820	telomeric D-loop disassembly
Molecular Function	GO:0043138	3'-5' DNA helicase activity
Molecular Function	GO:0008408	3'-5' exonuclease activity
Molecular Function	GO:0070337	3'-flap-structured DNA binding
Molecular Function	GO:1905773	8-hydroxy-2'-deoxyguanosine DNA binding
Molecular Function	GO:0005524	ATP binding
Molecular Function	GO:0016887	ATP hydrolysis activity
Molecular Function	GO:0003677	DNA binding
Molecular Function	GO:0003678	DNA helicase activity
Molecular Function	GO:0051880	G-quadruplex DNA binding
Molecular Function	GO:0032405	MutLalpha complex binding
Molecular Function	GO:0000403	Y-form DNA binding
Molecular Function	GO:0000405	bubble DNA binding
Molecular Function	GO:0003682	chromatin binding
Molecular Function	GO:0004527	exonuclease activity
Molecular Function	GO:0061749	forked DNA-dependent helicase activity
Molecular Function	GO:0000400	four-way junction DNA binding
Molecular Function	GO:0009378	four-way junction helicase activity
Molecular Function	GO:0000287	magnesium ion binding
Molecular Function	GO:0030145	manganese ion binding
Molecular Function	GO:0042803	protein homodimerization activity
Molecular Function	GO:0044877	protein-containing complex binding
Molecular Function	GO:0061821	telomeric D-loop binding
Molecular Function	GO:0061849	telomeric G-quadruplex DNA binding
Cellular Component	GO:0005813	centrosome
Cellular Component	GO:0005694	chromosome
Cellular Component	GO:0000781	chromosome, telomeric region
Cellular Component	GO:0005737	cytoplasm
Cellular Component	GO:0043005	neuron projection
Cellular Component	GO:0016607	nuclear speck
Cellular Component	GO:0005730	nucleolus
Cellular Component	GO:0005654	nucleoplasm
Cellular Component	GO:0005634	nucleus
Cellular Component	GO:0005657	replication fork

InterPro / Pfam

InterPro	InterPro name
IPR001650	Helicase, C-terminal
IPR002121	HRDC domain
IPR002562	3'-5' exonuclease domain
IPR004589	DNA helicase, ATP-dependent, RecQ type
IPR010997	HRDC-like superfamily
IPR011545	DEAD/DEAH box helicase domain
IPR012337	Ribonuclease H-like superfamily
IPR014001	Helicase superfamily 1/2, ATP-binding domain
IPR018982	RQC domain
IPR027417	P-loop containing nucleoside triphosphate hydrolase
IPR029491	Helicase Helix-turn-helix domain
IPR032284	ATP-dependent DNA helicase RecQ, zinc-binding domain
IPR036388	Winged helix-like DNA-binding domain superfamily
IPR036390	Winged helix DNA-binding domain superfamily
IPR036397	Ribonuclease H superfamily
IPR044876	HRDC domain superfamily

Pfam	Pfam name
PF00270	DEAD/DEAH box helicase
PF00271	Helicase conserved C-terminal domain
PF00570	HRDC domain
PF01612	3'-5' exonuclease
PF09382	RQC domain
PF14493	Helix-turn-helix domain
PF16124	RecQ zinc-binding

Reactome

Reactome	Reactome Name	Node type	Reactome Root	Reactome Root Name
R-HSA-174414	Processive synthesis on the C-strand of the telomere	Internal node	R-HSA-1640170	Cell Cycle
R-HSA-174437	Removal of the Flap Intermediate from the C-strand	Leaf	R-HSA-1640170	Cell Cycle
R-HSA-3108214	SUMOylation of DNA damage response and repair proteins	Leaf	R-HSA-392499	Metabolism of proteins
R-HSA-5685938	HDR through Single Strand Annealing (SSA)	Leaf	R-HSA-73894	DNA Repair
R-HSA-5685942	HDR through Homologous Recombination (HRR)	Internal node	R-HSA-73894	DNA Repair
R-HSA-5693554	Resolution of D-loop Structures through Synthesis-Dependent Strand Annealing (SDSA)	Leaf	R-HSA-73894	DNA Repair
R-HSA-5693568	Resolution of D-loop Structures through Holliday Junction Intermediates	Leaf	R-HSA-73894	DNA Repair
R-HSA-5693579	Homologous DNA Pairing and Strand Exchange	Internal node	R-HSA-73894	DNA Repair
R-HSA-5693607	Processing of DNA double-strand break ends	Leaf	R-HSA-73894	DNA Repair
R-HSA-5693616	Presynaptic phase of homologous DNA pairing and strand exchange	Leaf	R-HSA-73894	DNA Repair
R-HSA-6804756	Regulation of TP53 Activity through Phosphorylation	Leaf	R-HSA-74160	Gene expression (Transcription)
R-HSA-69473	G2/M DNA damage checkpoint	Internal node	R-HSA-1640170	Cell Cycle
R-HSA-9701192	Defective homologous recombination repair (HRR) due to BRCA1 loss of function	Leaf	R-HSA-1643685	Disease
R-HSA-9704331	Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of BRCA1 binding function	Leaf	R-HSA-1643685	Disease
R-HSA-9704646	Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of BRCA2/RAD51/RAD51C binding function	Leaf	R-HSA-1643685	Disease
R-HSA-9709570	Impaired BRCA2 binding to RAD51	Leaf	R-HSA-1643685	Disease
R-HSA-9709603	Impaired BRCA2 binding to PALB2	Leaf	R-HSA-1643685	Disease

Subcellular location

Location	ECO term	Pubmed
Chromosome	ECO:0000269	PubMed:27063109
Nucleus	ECO:0000269	PubMed:17563354
Nucleus	ECO:0000269	PubMed:19652551
Nucleus	ECO:0000269	PubMed:23180761
Nucleus, nucleolus	ECO:0000269	PubMed:23180761
Nucleus, nucleolus	ECO:0000269	PubMed:9618508
Nucleus, nucleoplasm	ECO:0000269	PubMed:21639834

Interactor | Variant | Drug

Phenotype

HPO ID	HPO name
HP:0000007	Autosomal recessive inheritance
HP:0000035	Abnormal testis morphology
HP:0000135	Hypogonadism
HP:0000144	Decreased fertility
HP:0000275	Narrow face
HP:0000320	Bird-like facies
HP:0000444	Convex nasal ridge
HP:0000518	Cataract
HP:0000546	Retinal degeneration
HP:0000765	Abnormal thorax morphology
HP:0000819	Diabetes mellitus
HP:0000822	Hypertension
HP:0000855	Insulin resistance
HP:0000869	Secondary amenorrhea
HP:0000934	Chondrocalcinosis
HP:0000939	Osteoporosis
HP:0000962	Hyperkeratosis
HP:0001387	Joint stiffness
HP:0001533	Slender build
HP:0001601	Laryngomalacia
HP:0001608	Abnormality of the voice
HP:0001620	High pitched voice
HP:0001635	Congestive heart failure
HP:0001658	Myocardial infarction
HP:0001838	Rocker bottom foot
HP:0002155	Hypertriglyceridemia
HP:0002209	Sparse scalp hair
HP:0002211	White forelock
HP:0002216	Premature graying of hair
HP:0002293	Alopecia of scalp
HP:0002621	Atherosclerosis
HP:0002664	Neoplasm
HP:0002669	Osteosarcoma
HP:0002672	Gastrointestinal carcinoma
HP:0002858	Meningioma
HP:0002860	Squamous cell carcinoma
HP:0002861	Melanoma
HP:0002890	Thyroid carcinoma
HP:0003002	Breast carcinoma
HP:0003202	Skeletal muscle atrophy
HP:0003419	Low back pain
HP:0003621	Juvenile onset
HP:0003777	Pili torti
HP:0004322	Short stature
HP:0004349	Reduced bone mineral density
HP:0004415	Pulmonary artery stenosis
HP:0005177	Premature arteriosclerosis
HP:0005268	Miscarriage
HP:0005328	Progeroid facial appearance
HP:0005978	Type II diabetes mellitus
HP:0007495	Prematurely aged appearance
HP:0007618	Subcutaneous calcification
HP:0007703	Abnormality of retinal pigmentation
HP:0008065	Aplasia/Hypoplasia of the skin
HP:0009125	Lipodystrophy
HP:0009726	Renal neoplasm
HP:0010468	Aplasia/Hypoplasia of the testes
HP:0010721	Abnormal hair whorl
HP:0011001	Increased bone mineral density
HP:0012056	Cutaneous melanoma
HP:0012060	Acral lentiginous melanoma
HP:0031956	Elevated circulating aspartate aminotransferase concentration
HP:0031964	Elevated circulating alanine aminotransferase concentration
HP:0040217	Elevated hemoglobin A1c
HP:0100242	Sarcoma
HP:0100324	Scleroderma
HP:0100526	Neoplasm of the lung
HP:0100578	Lipoatrophy
HP:0100585	Telangiectasia of the skin
HP:0100615	Ovarian neoplasm
HP:0100649	Neoplasm of the oral cavity
HP:0100659	Abnormal cerebral vascular morphology
HP:0100679	Lack of skin elasticity
HP:0100833	Neoplasm of the small intestine
HP:0200042	Skin ulcer
HP:0200055	Small hand

Tissue and cell type

Tissue	Cell type	Expression level	Reliability
adrenal gland	glandular cells	Medium	Approved
bone marrow	hematopoietic cells	Low	Approved
bronchus	respiratory epithelial cells	Medium	Approved
caudate	glial cells	Low	Approved
cerebellum	Purkinje cells	Medium	Approved
cerebellum	cells in molecular layer	Medium	Approved
cerebral cortex	neuronal cells	Medium	Approved
cervix	glandular cells	Low	Approved
colon	glandular cells	Medium	Approved
endometrium 1	cells in endometrial stroma	Low	Approved
endometrium 2	cells in endometrial stroma	Low	Approved
endometrium 2	glandular cells	Low	Approved
epididymis	glandular cells	Low	Approved
esophagus	squamous epithelial cells	Medium	Approved
gallbladder	glandular cells	Medium	Approved
kidney	cells in glomeruli	Medium	Approved
kidney	cells in tubules	Medium	Approved
lymph node	non-germinal center cells	Low	Approved
nasopharynx	respiratory epithelial cells	Medium	Approved
oral mucosa	squamous epithelial cells	Medium	Approved
pancreas	exocrine glandular cells	Low	Approved
placenta	decidual cells	Medium	Approved
placenta	trophoblastic cells	Medium	Approved
rectum	glandular cells	Medium	Approved
skin 1	fibroblasts	Low	Approved
skin 1	keratinocytes	Medium	Approved
skin 1	melanocytes	Low	Approved
skin 2	epidermal cells	Medium	Approved
testis	Leydig cells	Low	Approved
testis	spermatogonia cells	Low	Approved
thyroid gland	glandular cells	Low	Approved
urinary bladder	urothelial cells	Low	Approved
vagina	squamous epithelial cells	Medium	Approved

Disease name	MONDO ID	ICD10	ICD10 chapter	OMIM	Orphanet
colorectal cancer	MONDO:0005575	C18	chapter2, Neoplasms	OMIM:114500	Orphanet:466667
werner syndrome	MONDO:0010196	E34	chapter4, Endocrine, nutritional and metabolic diseases	OMIM:277700	Orphanet:902

Summary of Q14191

Gene: WRN, RECQ3, RECQL2
Protein: Bifunctional 3'-5' exonuclease/ATP-dependent helicase WRN

Structure

GO term

InterPro / Pfam

Reactome

Subcellular location

Interactor | Variant | Drug

Phenotype

Tissue and cell type

Disease

Summary of Q14191

Gene: WRN, RECQ3, RECQL2 Protein: Bifunctional 3'-5' exonuclease/ATP-dependent helicase WRN

Structure

GO term

InterPro / Pfam

Reactome

Subcellular location

Interactor | Variant | Drug

Phenotype

Tissue and cell type

Disease

Gene: WRN, RECQ3, RECQL2
Protein: Bifunctional 3'-5' exonuclease/ATP-dependent helicase WRN