Tbio KNG1 Kininogen-1

Protein Summary

Description

(1) Kininogens are inhibitors of thiol proteases; (2) HMW-kininogen plays an important role in blood coagulation by helping to position optimally prekallikrein and factor XI next to factor XII; (3) HMW-kininogen inhibits the thrombin- and plasmin-induced aggregation of thrombocytes; (4) the active peptide bradykinin that is released from HMW-kininogen shows a variety of physiological effects: (4A) influence in smooth muscle contraction, (4B) induction of hypotension, (4C) natriuresis and diuresis, (4D) decrease in blood glucose level, (4E) it is a mediator of inflammation and causes (4E1) increase in vascular permeability, (4E2) stimulation of nociceptors (4E3) release of other mediators of inflammation (e.g. prostaglandins), (4F) it has a cardioprotective effect (directly via bradykinin action, indirectly via endothelium-derived relaxing factor action); (5) LMW-kininogen inhibits the aggregation of thrombocytes; (6) LMW-kininogen is in contrast to HMW-kininogen not involved in blood clotting. This gene uses alternative splicing to generate two different proteins- high molecular weight kininogen (HMWK) and low molecular weight kininogen (LMWK). HMWK is essential for blood coagulation and assembly of the kallikrein-kinin system. Also, bradykinin, a peptide causing numerous physiological effects, is released from HMWK. Bradykinin also functions as an antimicrobial peptide with antibacterial and antifungal activity. In contrast to HMWK, LMWK is not involved in blood coagulation. Three transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Nov 2014]

Uniprot Accession IDs

• P01042
• A8K474
• B2RCR2
• C9JEX1
• P01043
• Q53EQ0
• Q6PAU9
• Q7M4P1

Gene Name

• KNG1

Ensembl ID

• ENST00000265023
• ENSP00000265023
• ENSG00000113889
• ENST00000287611
• ENSP00000287611
• ENST00000447445
• ENSP00000396025
• ENST00000644859
• ENSP00000493985
• ENST00000645909
• ENSP00000496167

Symbol

• BDK
• KNG
• BK
• BDK
• KNG
• HMWK

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
biological process	0.88
chemical	0.83
virus perturbation	0.83
co-expressed gene	0.76
molecular function	0.76

Protein Classes

PANTHER Classes

Protein / ... / Protease Inhibitor / Kininogen-1

DTO Classes

Protein / Enzyme Modulator / Protease Inhibitor / Kininogen-1

IDG Development Level Summary

Tdark

These are targets about which virtually nothing is known. They do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 13097.01   (req: < 5)

Gene RIFs: 75   (req: <= 3)

Antibodies: 673   (req: <= 50)

Tbio

These targets do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 13097.01   (req: >= 5)

Gene RIFs: 75   (req: > 3)

Antibodies: 673   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 19

Tchem

Target has at least one ChEMBL compound with an activity cutoff of < 30 nM - AND - satisfies the preceding conditions

Active Ligand: 0

Tclin

Target has at least one approved drug - AND - satisfies the preceding conditions

Active Drug: 0

Expression Data (0 Tissues)

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No expression data found

Protein Sequence and Structure

Residue Counts

Protein Sequence

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Related Tools (4)

Target Illumination GWAS Analytics (TIGA)

TIGA scores and ranks GWAS discovered associations according to the quantity and quality of the evidence supporting the association.

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GENEVA

GENEVA (GENe Expression Variance Analysis) allows you to identify RNA-sequencing datasets from the Gene Expression Omnibus (GEO) that contain conditions modulating a gene or a gene signature.

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GlyGen

GlyGen is a data integration and dissemination project for carbohydrate and glycoconjugate related data.

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ARCHS4

ARCHS4 provides access to gene-function predictions based on RNA-seq co-expression, and gene expression levels across cell and tissues.

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Approved Drugs (0)

No approved drugs found

Active Ligands (0)

No active ligands found

Protein-Protein Interactions (698)

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1 – 10 of 698

• See Interactions on String-DB

CTSO

Tbio

Family:  Enzyme

Novelty:  0.09963965

p_int:  0.999990261

p_ni:  0.000009734

p_wrong:  5e-9

Score:  0.206

Data Source:  BioPlex,STRINGDB

GDPD1

Tbio

Family:  Enzyme

Novelty:  0.28722153

p_int:  0.999435407

p_ni:  0.000564271

p_wrong:  3.22e-7

Data Source:  BioPlex

CAPN1

Tchem

Novelty:  0.00252811

p_int:  0.999234184

p_ni:  0.000765816

Score:  0.509

Data Source:  BioPlex,STRINGDB

ANAPC1

Tbio

Family:  Enzyme

Novelty:  0.0521845

p_int:  0.998921108

p_ni:  0.001078892

Score:  0.183

Data Source:  BioPlex,STRINGDB

P3H3

Tbio

Family:  Enzyme

Novelty:  0.0010004

p_int:  0.994106249

p_ni:  0.005893751

Score:  0.17

Data Source:  BioPlex,STRINGDB

CTSV

Tchem

Family:  Enzyme

Novelty:  0.00916301

p_int:  0.989946728

p_ni:  0.010053272

Score:  0.564

Data Source:  BioPlex,STRINGDB

VHL

Tchem

Family:  Enzyme

Novelty:  0.00285782

p_int:  0.985073491

p_ni:  0.014926243

p_wrong:  2.66e-7

Data Source:  BioPlex

PPP2R2C

Tbio

Family:  Enzyme

Novelty:  0.05453128

p_int:  0.985011144

p_ni:  0.002364233

p_wrong:  0.012624623

Data Source:  BioPlex

ZNF562

Tdark

Family:  TF

Novelty:  12.38372093

p_int:  0.977562749

p_ni:  0.022434957

p_wrong:  0.000002293

Score:  0.161

Data Source:  BioPlex,STRINGDB

ANAPC5

Tbio

Family:  Enzyme

Novelty:  0.02102572

p_int:  0.962820952

p_ni:  0.037179048

Data Source:  BioPlex

Nearest Tclin Targets (2)

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Upstream (1)

Downstream (1)

1 – 1 of 1

KLKB1

Tclin

Family:  Enzyme

KEGG Distance:  1

Common Pathways:  1

1: Complement and coagulation cascades

Pathways (82)

Reactome (18)

KEGG (9)

PathwayCommons (9)

WikiPathways (46)

Class A/1 (Rhodopsin-like receptors) (R-HSA-373076)

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Data Source	Name	Explore in Pharos	Explore in Source
Reactome	Class A/1 (Rhodopsin-like receptors)	323 targets	R-HSA-373076
Reactome	Formation of Fibrin Clot (Clotting Cascade)	39 targets	R-HSA-140877
Reactome	G alpha (i) signalling events	408 targets	R-HSA-418594
Reactome	G alpha (q) signalling events	219 targets	R-HSA-416476
Reactome	GPCR downstream signalling	1152 targets	R-HSA-388396

Name	Explore in Pharos	Explore in Source
Class A/1 (Rhodopsin-like receptors)	323 targets	R-HSA-373076
Formation of Fibrin Clot (Clotting Cascade)	39 targets	R-HSA-140877
G alpha (i) signalling events	408 targets	R-HSA-418594
G alpha (q) signalling events	219 targets	R-HSA-416476
GPCR downstream signalling	1152 targets	R-HSA-388396

Viral Interactions (0)

No viral interactions found

Gene Ontology Terms (27)

Functions (4)

Components (8)

Processes (15)

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1 – 4 of 4

GO Term	Evidence	Assigned by
cysteine-type endopeptidase inhibitor activity	Inferred from Direct Assay (IDA)	UniProtKB
signaling receptor binding	Inferred from Physical Interaction (IPI)	UniProtKB
heparin binding	Non-traceable Author Statement (NAS)	UniProtKB
zinc ion binding	Non-traceable Author Statement (NAS)	UniProtKB

Disease Associations (null)

No disease associations found

GWAS Traits (34)

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5

1 – 5 of 34

GWAS Trait	EFO ID	Study Count	SNP Count	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
adiponectin measurement	EFO_0004502	4	5	5		99.1
factor XI measurement	EFO_0004694	2	2	2		98.8
partial thromboplastin time	EFO_0004310	2	3	3		98.7
blood protein measurement	EFO_0007937	44	32	65		97.8
glomerular filtration rate	EFO_0005208	10	6	9	8.1	96.7

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5

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GWAS Trait	EFO ID	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
adiponectin measurement	EFO_0004502	5		99.1
factor XI measurement	EFO_0004694	2		98.8
partial thromboplastin time	EFO_0004310	3		98.7
blood protein measurement	EFO_0007937	65		97.8
glomerular filtration rate	EFO_0005208	9	8.1	96.7

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UniProt Keyword Find Similar Targets

No Header	No Header
3D-structure
Alternative splicing
Blood coagulation
Complete proteome
Direct protein sequencing
Disulfide bond
Glycoprotein
Hemostasis
Hydroxylation
Inflammatory response

GWAS Trait Find Similar Targets

No Header	No Header
adiponectin measurement
alpha-2-HS-glycoprotein measurement
blood metabolite measurement
blood protein measurement
blood urea nitrogen measurement
BMI-adjusted adiponectin measurement
calcium measurement
CD27 antigen measurement
creatinine measurement
dual specificity mitogen-activated protein kinase kinase 4 measurement

MGI Phenotype Find Similar Targets

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growth/size/body region phenotype
homeostasis/metabolism phenotype

IDG Resources

No IDG generated resources found

Orthologs (9)

1 – 5 of 9

Species	Name	Source ID	Gene ID	OMA	EggNOG	Inparanoid
Chimp	kininogen 1	VGNC:1858	460916
Macaque	kininogen 1		707466
Mouse	kininogen 2	MGI:3027157	385643
Dog	kininogen 1	VGNC:53466	478666
Horse	kininogen 1	VGNC:19498	100068133

Species	Name	OMA	EggNOG	Inparanoid
Chimp	kininogen 1
Macaque	kininogen 1
Mouse	kininogen 2
Dog	kininogen 1
Horse	kininogen 1

Publication Statistics

PubMed Score 13097.01

PubMed score by year

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PubTator Score 4971.59

PubTator score by year

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Related Publications

Text Mined References (162)

GeneRif Annotations (75)

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PMID	Year	Title