Tchem F12 Coagulation factor XII

Protein Classes

PANTHER Classes

Protein / Hydrolase / Protease / Serine Protease / Coagulation Factor Xii

DTO Classes

Protein / Enzyme / Protease / Serine Protease / Coagulation Factor Xii

Protein Summary

Description

Factor XII is a serum glycoprotein that participates in the initiation of blood coagulation, fibrinolysis, and the generation of bradykinin and angiotensin. Prekallikrein is cleaved by factor XII to form kallikrein, which then cleaves factor XII first to alpha-factor XIIa and then trypsin cleaves it to beta-factor XIIa. Alpha-factor XIIa activates factor XI to factor XIa. This gene encodes coagulation factor XII which circulates in blood as a zymogen. This single chain zymogen is converted to a two-chain serine protease with an heavy chain (alpha-factor XIIa) and a light chain. The heavy chain contains two fibronectin-type domains, two epidermal growth factor (EGF)-like domains, a kringle domain and a proline-rich domain, whereas the light chain contains only a catalytic domain. On activation, further cleavages takes place in the heavy chain, resulting in the production of beta-factor XIIa light chain and the alpha-factor XIIa light chain becomes beta-factor XIIa heavy chain. Prekallikrein is cleaved by factor XII to form kallikrein, which then cleaves factor XII first to alpha-factor XIIa and then to beta-factor XIIa. The active factor XIIa participates in the initiation of blood coagulation, fibrinolysis, and the generation of bradykinin and angiotensin. It activates coagulation factors VII and XI. Defects in this gene do not cause any clinical symptoms and the sole effect is that whole-blood clotting time is prolonged. [provided by RefSeq, Jul 2008]

Uniprot Accession IDs

• P00748
• P78339

Gene Name

• F12

Ensembl ID

• ENST00000253496
• ENSP00000253496
• ENSG00000131187

Symbol

• HAF
• HAE3
• HAEX

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
protein domain	1
kinase perturbation	0.97
biological term	0.8
disease	0.69
biological process	0.64

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Target Illumination GWAS Analytics (TIGA)

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GENEVA

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GlyGen

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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: 684.47   (req: < 5)

Gene RIFs: 129   (req: <= 3)

Antibodies: 656   (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: 684.47   (req: >= 5)

Gene RIFs: 129   (req: > 3)

Antibodies: 656   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 16

Tchem

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

Active Ligands: 85

Tclin

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

Active Drug: 0

Active Ligands (85)

Explore Active Ligands

1 – 10 of 85

US8598206, Table 6, 24

F12Tchem Enzyme

Ki : 6.4

CHEMBL4634303

F12Tchem Enzyme

IC50 : 6.37

CHEMBL4646710

F12Tchem Enzyme

IC50 : 6.62

CHEMBL4640835

F12Tchem Enzyme

IC50 : 6.47

CHEMBL3660184

F12Tchem Enzyme

Ki : 6.06

CHEMBL3660176

F12Tchem Enzyme

Ki : 6.2

US8598206, Table 6, 15

F12Tchem Enzyme

Ki : 6.1

US8598206, Table 6, 8

F12Tchem Enzyme

Ki : 6.19

SID24823247

F12Tchem Enzyme

IC50 : 6.31

US8598206, Table 6, 14

F12Tchem Enzyme

Ki : 6.26

GWAS Traits (57)

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GWAS Trait	EFO ID	Study Count	SNP Count	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
glomerular filtration rate	EFO_0005208	9	8	11	15.2	99.3
creatinine measurement	EFO_0004518	5	6	7		97
partial thromboplastin time	EFO_0004310	2	2	2		96.1
hematocrit	EFO_0004348	5	5	5		96.1
hemoglobin measurement	EFO_0004509	4	4	4		94.3

• Explore on Target Illumination GWAS Analytics (TIGA)

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GWAS Trait	EFO ID	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
glomerular filtration rate	EFO_0005208	11	15.2	99.3
creatinine measurement	EFO_0004518	7		97
partial thromboplastin time	EFO_0004310	2		96.1
hematocrit	EFO_0004348	5		96.1
hemoglobin measurement	EFO_0004509	4		94.3

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Orthologs (8)

1 – 5 of 8

Species	Name	Source ID	Gene ID	OMA	EggNOG	Inparanoid
Chimp	coagulation factor XII	VGNC:6868	462304
Macaque	coagulation factor XII		699875
Mouse	coagulation factor XII (Hageman factor)	MGI:1891012	58992
Rat	coagulation factor XII	RGD:1359175	306761
Horse	coagulation factor XII	VGNC:17754	100068589

Species	Name	OMA	EggNOG	Inparanoid
Chimp	coagulation factor XII
Macaque	coagulation factor XII
Mouse	coagulation factor XII (Hageman factor)
Rat	coagulation factor XII
Horse	coagulation factor XII

Protein Structure (6 Structures, 1 AlphaFold Model)

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Representation

  axes   backbone   ball+stick   cartoon   rocket   rope   spacefill

Color Scheme

  target   atomindex   bfactor   chainname   electrostatic   element   hydrophobicity   resname   sstruc

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More information can be found at RCSB PDB

AF-P00748-F1-model_v1

AlphaFold Structures Developed by DeepMind and EMBL-EBI

1 – 5 of 6

PDB Structure Id	Ligand	Method	Resolution (Å)	Residues	Fraction of Total Protein	Pub Year	Title

PDB Structure Id	Fraction of Total Protein	Resolution	Pub Year

Pathways (8)

Reactome (3)

KEGG (1)

PathwayCommons (1)

WikiPathways (3)

Formation of Fibrin Clot (Clotting Cascade) (R-HSA-140877)

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Data Source	Name	Explore in Pharos	Explore in Source
Reactome	Formation of Fibrin Clot (Clotting Cascade)	39 targets	R-HSA-140877
Reactome	Hemostasis	666 targets	R-HSA-109582
Reactome	Intrinsic Pathway of Fibrin Clot Formation	22 targets	R-HSA-140837

Name	Explore in Pharos	Explore in Source
Formation of Fibrin Clot (Clotting Cascade)	39 targets	R-HSA-140877
Hemostasis	666 targets	R-HSA-109582
Intrinsic Pathway of Fibrin Clot Formation	22 targets	R-HSA-140837

Gene Ontology Terms (21)

Functions (3)

Components (5)

Processes (13)

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Items per page:

10

1 – 3 of 3

GO Term	Evidence	Assigned by
serine-type endopeptidase activity	Inferred from Direct Assay (IDA)	BHF-UCL
misfolded protein binding	Inferred by Curator (IC)	BHF-UCL
calcium ion binding	Inferred from Electronic Annotation (IEA)	InterPro

Protein-Protein Interactions (105)

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1 – 10 of 105

• See Interactions on String-DB

ANKRD40

Tdark

Novelty:  1.06633958

p_int:  0.862601606

p_ni:  0.137398394

Score:  0.209

Data Source:  BioPlex,STRINGDB

HSPA8

Tchem

Novelty:  0.00081014

p_int:  0.797326936

p_ni:  0.202673064

Score:  0.176

Data Source:  BioPlex,STRINGDB

KNG1

Tbio

Novelty:  0.00007684

Score:  0.985

Data Source:  Reactome,STRINGDB

KLKB1

Tclin

Family:  Enzyme

Novelty:  0.00109438

Score:  0.974

Data Source:  Reactome,STRINGDB

SERPING1

Tbio

Family:  Enzyme

Novelty:  0.00068448

Score:  0.974

Data Source:  Reactome,STRINGDB

F9

Tchem

Family:  Enzyme

Novelty:  0.00032127

Score:  0.961

Data Source:  STRINGDB

F11

Tchem

Family:  Enzyme

Novelty:  0.00169618

Score:  0.959

Data Source:  Reactome,STRINGDB

SERPINC1

Tclin

Novelty:  0.00008721

Score:  0.958

Data Source:  STRINGDB

GP1BA

Tbio

Novelty:  0.00138736

Score:  0.957

Data Source:  Reactome,STRINGDB

C1QBP

Tbio

Novelty:  0.00532825

Score:  0.928

Data Source:  Reactome,STRINGDB

Publication Statistics

PubMed Score  684.47

PubMed score by year

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PubTator Score  919.39

PubTator score by year

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Amino Acid Sequence

Residue Counts

Protein Sequence

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UniProt Keyword Find Similar Targets

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3D-structure
Blood coagulation
Complete proteome
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Disulfide bond
EGF-like domain
Fibrinolysis
Glycoprotein
Hemostasis

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homeostasis/metabolism phenotype
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