F12

Protein identityUniProt · HPA

UniProt accession

P00748

Gene

F12

Ensembl

ENSG00000131187

Chromosome

5

Canonical length

615 aa

Protein class

Candidate cardiovascular disease genes, Disease related genes, Enzymes, FDA approved drug targets, Human disease related genes, Plasma proteins, Predicted secreted proteins

Secretome location

Secreted to blood

OverviewNCBI Gene

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]

Canonical amino-acid sequenceUniProt

615 residues, UniProt reviewed canonical sequence.

>P00748|F12
     1  MRALLLLGFL LVSLESTLSI PPWEAPKEHK YKAEEHTVVL TVTGEPCHFP FQYHRQLYHK
    61  CTHKGRPGPQ PWCATTPNFD QDQRWGYCLE PKKVKDHCSK HSPCQKGGTC VNMPSGPHCL
   121  CPQHLTGNHC QKEKCFEPQL LRFFHKNEIW YRTEQAAVAR CQCKGPDAHC QRLASQACRT
   181  NPCLHGGRCL EVEGHRLCHC PVGYTGAFCD VDTKASCYDG RGLSYRGLAR TTLSGAPCQP
   241  WASEATYRNV TAEQARNWGL GGHAFCRNPD NDIRPWCFVL NRDRLSWEYC DLAQCQTPTQ
   301  AAPPTPVSPR LHVPLMPAQP APPKPQPTTR TPPQSQTPGA LPAKREQPPS LTRNGPLSCG
   361  QRLRKSLSSM TRVVGGLVAL RGAHPYIAAL YWGHSFCAGS LIAPCWVLTA AHCLQDRPAP
   421  EDLTVVLGQE RRNHSCEPCQ TLAVRSYRLH EAFSPVSYQH DLALLRLQED ADGSCALLSP
   481  YVQPVCLPSG AARPSETTLC QVAGWGHQFE GAEEYASFLQ EAQVPFLSLE RCSAPDVHGS
   541  SILPGMLCAG FLEGGTDACQ GDSGGPLVCE DQAAERRLTL QGIISWGSGC GDRNKPGVYT
   601  DVAYYLAWIR EHTVS

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against F12 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Secreted

Secreted

Yes

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.35

Highest tissue expression

593 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about F12.

Disease | AllUniProt

Conditions F12 is implicated in, by any mechanism.

• Factor XII deficiency (FA12D) MIM:234000
• Angioedema, hereditary, 3 (HAE3) MIM:610618

Disease | GeneticClinVar

20 pathogenic / likely-pathogenic of 248 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Factor XII deficiency disease
• Hereditary angioedema type 3
• FACTOR XII (LOCARNO)
• FACTOR XII (WASHINGTON D.C.)
• Hereditary angioneurotic edema

Disease | ImmuneIEDB

Conditions an epitope on F12 was assayed in.

• rheumatoid arthritis B cell

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.78

gnomAD pLI

0

gnomAD missense Z

0.92

DepMap mean gene effect

0.02

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• blood coagulation
• blood coagulation, intrinsic pathway
• Factor XII activation
• fibrinolysis
• innate immune response
• plasma kallikrein-kinin cascade
• positive regulation of blood coagulation
• positive regulation of fibrinolysis
• positive regulation of plasminogen activation
• protein autoprocessing
• protein processing
• response to misfolded protein
• zymogen activation

Molecular functions

• calcium ion binding
• misfolded protein binding
• serine-type endopeptidase activity

Cellular components

• extracellular exosome
• extracellular matrix
• extracellular region
• extracellular space
• plasma membrane
• rough endoplasmic reticulum

Protein domainsUniProt · Pfam · InterPro

• Kringle
• Fibronectin, type I
• Fibronectin type II domain
• EGF-like domain
• Serine proteases, trypsin domain
• Peptidase S1A, chymotrypsin family
• EGF-like calcium-binding domain
• Peptidase S1, PA clan
• Kringle-like fold
• Coagulation factor XII/hepatocyte growth factor activator
• Kringle, conserved site
• Serine proteases, trypsin family, histidine active site
• Serine proteases, trypsin family, serine active site
• Fibronectin type II domain superfamily
• Kringle superfamily
• Serine Proteases (Peptidase S1 Family)
• EGF-like domain
• Fibronectin type I domain
• Fibronectin type II domain
• Kringle domain
• Trypsin

KeywordsUniProt

• Blood coagulation
• Disulfide bond
• EGF-like domain
• Fibrinolysis
• Glycoprotein
• Hemostasis
• Hydrolase
• Kringle
• Protease
• Repeat
• Secreted
• Serine protease
• Signal
• Zymogen

InteractionsUniProt · HPA

Protein binding partners of F12 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• HRG