Human Gene F12 (uc003mgo.4) Description and Page Index
  Description: Homo sapiens coagulation factor XII (Hageman factor) (F12), mRNA.
RefSeq Summary (NM_000505): 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]. Publication Note: This RefSeq record includes a subset of the publications that are available for this gene. Please see the Gene record to access additional publications. ##Evidence-Data-START## Transcript exon combination :: AB095845.1, M31315.1 [ECO:0000332] RNAseq introns :: mixed/partial sample support SAMEA1965299, SAMEA1968540 [ECO:0000350] ##Evidence-Data-END## ##RefSeq-Attributes-START## RefSeq Select criteria :: based on conservation, expression, longest protein regulatory uORF :: PMID: 19372376 ##RefSeq-Attributes-END##
Transcript (Including UTRs)
   Position: hg19 chr5:176,829,139-176,836,577 Size: 7,439 Total Exon Count: 14 Strand: -
Coding Region
   Position: hg19 chr5:176,829,293-176,836,528 Size: 7,236 Coding Exon Count: 14 

Page IndexSequence and LinksUniProtKB CommentsGenetic AssociationsMalaCardsCTD
Gene AllelesRNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein StructureOther Species
GO AnnotationsmRNA DescriptionsPathwaysOther NamesModel InformationMethods
Data last updated: 2013-06-14

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr5:176,829,139-176,836,577)mRNA (may differ from genome)Protein (615 aa)
Gene SorterGenome BrowserOther Species FASTAGene interactionsTable SchemaBioGPS
CGAPEnsemblEntrez GeneExonPrimerGeneCardsGeneNetwork
H-INVHGNCHPRDLynxMGIneXtProt
OMIMPubMedReactomeStanford SOURCETreefamUniProtKB
Wikipedia

-  Comments and Description Text from UniProtKB
  ID: FA12_HUMAN
DESCRIPTION: RecName: Full=Coagulation factor XII; EC=3.4.21.38; AltName: Full=Hageman factor; Short=HAF; Contains: RecName: Full=Coagulation factor XIIa heavy chain; Contains: RecName: Full=Beta-factor XIIa part 1; Contains: RecName: Full=Beta-factor XIIa part 2; Contains: RecName: Full=Coagulation factor XIIa light chain; Flags: Precursor;
FUNCTION: 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.
CATALYTIC ACTIVITY: Selective cleavage of Arg-|-Ile bonds in factor VII to form factor VIIa and factor XI to form factor XIa.
SUBUNIT: Interacts with HRG; the interaction, which is enhanced in the presence of zinc ions and inhibited by heparin-binding, inhibits factor XII autoactivation and contact-initiated coagulation.
SUBCELLULAR LOCATION: Secreted.
PTM: Factor XII is activated by kallikrein in alpha-factor XIIa, which is then further converted by trypsin into beta-factor XIIa. Alpha-factor XIIa is composed of the NH2-terminal heavy chain (Coagulation factor XIIa heavy chain) and the COOH-terminal light chain (Coagulation factor XIIa light chain), connected by a disulfide bond. Beta-factor XIIa is composed of 2 chains linked by a disulfide bond, a light chain (Beta-factor XIIa part 2), corresponding to the COOH-terminal light chain (Coagulation factor XIIa light chain) and a nonapeptide (Beta-factor XIIa part 1).
PTM: O- and N-glycosylated. The O-linked polysaccharides were not identified, but are probably the mucin type linked to GalNAc.
DISEASE: Defects in F12 are the cause of factor XII deficiency (FA12D) [MIM:234000]; also known as Hageman factor deficiency. This trait is an asymptomatic anomaly of in vitro blood coagulation. Its diagnosis is based on finding a low plasma activity of the factor in coagulating assays. It is usually only accidentally discovered through pre-operative blood tests. F12 deficiency is divided into two categories, a cross-reacting material (CRM)-negative group (negative F12 antigen detection) and a CRM-positive group (positive F12 antigen detection).
DISEASE: Defects in F12 are the cause of hereditary angioedema type 3 (HAE3) [MIM:610618]; also known as estrogen-related HAE or hereditary angioneurotic edema with normal C1 inhibitor concentration and function. HAE is characterized by episodic local subcutaneous edema, and submucosal edema involving the upper respiratory and gastrointestinal tracts. HAE3 occurs exclusively in women and is precipitated or worsened by high estrogen levels (e.g. during pregnancy or treatment with oral contraceptives). It differs from HAE types 1 and 2 in that both concentration and function of C1 inhibitor are normal.
SIMILARITY: Belongs to the peptidase S1 family.
SIMILARITY: Contains 2 EGF-like domains.
SIMILARITY: Contains 1 fibronectin type-I domain.
SIMILARITY: Contains 1 fibronectin type-II domain.
SIMILARITY: Contains 1 kringle domain.
SIMILARITY: Contains 1 peptidase S1 domain.
WEB RESOURCE: Name=Wikipedia; Note=Factor XII entry; URL="http://en.wikipedia.org/wiki/Factor_XII";
WEB RESOURCE: Name=F12base; Note=F12 mutation db; URL="http://bioinf.uta.fi/F12base/";
WEB RESOURCE: Name=SeattleSNPs; URL="http://pga.gs.washington.edu/data/f12/";

-  Genetic Association Studies of Complex Diseases and Disorders
  Genetic Association Database (archive): F12
CDC HuGE Published Literature: F12
Positive Disease Associations: Activated factor XII levels , atherosclerosis, coronary , Blood Platelets , C-reactive protein myocardial infarct , cardiovascular , coronary heart disease , f12 plasma deficiency, moderate , factor XII-deficient patients , high or low factor XIII specific activity. , Metabolism , myocardial infarct , Partial Thromboplastin Time , pregnancy loss, recurrent , Protein S Deficiency|Venous Thrombosis , thromboembolism, venous
Related Studies:
  1. Activated factor XII levels
    Ishii K et al. 2000, Activated factor XII levels are dependent on factor XII 46C/T genotypes and factor XII zymogen levels and are associated with vascular risk factors in patients and healthy subjects., Blood coagulation & fibrinolysis. 2000 Apr;11(3):277-84. [PubMed 10870808]
  2. atherosclerosis, coronary
    Santamaria, A. et al. 2004, Homozygosity of the T allele of the 46 C-->T polymorphism in the F12 gene is a risk factor for acute coronary artery disease in the Spanish population., Haematologica. 2004 Jul;89(7):878-9. [PubMed 15257949]
    We found a 6-fold higher risk of acute CAD associated with the homozygosity of the T allele of the F12, 46C-->T polymorphism in the Spanish population.
  3. Blood Platelets
    JA Guerrero et al. Haematologica 2011, Novel loci involved in platelet function and platelet count identified by a genome-wide study performed in children., Haematologica. [PubMed 21546496]
    Our genome-wide association study performed in children, followed by a validation analysis, led us to the identification of new genes potentially relevant in platelet function and biogenesis.
           more ... click here to view the complete list

-  MalaCards Disease Associations
  MalaCards Gene Search: F12
Diseases sorted by gene-association score: factor xii deficiency* (1711), angioedema, hereditary, type iii* (1650), angioedema* (454), urticaria* (404), hereditary angioedema* (324), angioedema, hereditary, types i and ii* (283), bilirubin metabolic disorder* (283), hypertension, early-onset, autosomal dominant, with exacerbation in pregnancy* (200), hypertension, essential* (126), periodontosis (15), cloacogenic carcinoma (9), chronic tic disorder (8), patent foramen ovale (7), intracranial embolism (7), cerebrovascular disease (3)
* = Manually curated disease association

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene
  • D013749 Tetrachlorodibenzodioxin
  • D002994 Clofibrate
  • C016403 2,4-dinitrotoluene
  • C023514 2,6-dinitrotoluene
  • C532162 2-(1H-indazol-4-yl)-6-(4-methanesulfonylpiperazin-1-ylmethyl)-4-morpholin-4-ylthieno(3,2-d)pyrimidine
  • D016604 Aflatoxin B1
  • D000806 Angiotensin-Converting Enzyme Inhibitors
  • D001564 Benzo(a)pyrene
  • D002809 Chondroitin Sulfates
  • D003300 Copper
          more ... click here to view the complete list

+  Common Gene Haplotype Alleles
  Press "+" in the title bar above to open this section.

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 227.82 RPKM in Liver
Total median expression: 281.57 RPKM



View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -13.3049-0.271 Picture PostScript Text
3' UTR -52.20154-0.339 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR014394 - Coagulation_fac_XIIa/HGFA
IPR000742 - EG-like_dom
IPR013032 - EGF-like_CS
IPR000083 - Fibronectin_type1
IPR000562 - FN_type2_col-bd
IPR000001 - Kringle
IPR013806 - Kringle-like
IPR018056 - Kringle_CS
IPR009003 - Pept_cys/ser_Trypsin-like
IPR018114 - Peptidase_S1/S6_AS
IPR001254 - Peptidase_S1_S6
IPR001314 - Peptidase_S1A

Pfam Domains:
PF00008 - EGF-like domain
PF00039 - Fibronectin type I domain
PF00040 - Fibronectin type II domain
PF00051 - Kringle domain
PF00089 - Trypsin
PF12661 - Human growth factor-like EGF
PF13365 - Trypsin-like peptidase domain

SCOP Domains:
50494 - Trypsin-like serine proteases
57440 - Kringle-like
57196 - EGF/Laminin

ModBase Predicted Comparative 3D Structure on P00748
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The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.

-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
No orthologNo orthologNo orthologNo orthologNo orthologNo ortholog
Gene Details     
Gene Sorter     
      
      
      

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0004252 serine-type endopeptidase activity
GO:0005509 calcium ion binding
GO:0005515 protein binding
GO:0008233 peptidase activity
GO:0008236 serine-type peptidase activity
GO:0016787 hydrolase activity
GO:0051787 misfolded protein binding

Biological Process:
GO:0002353 plasma kallikrein-kinin cascade
GO:0002542 Factor XII activation
GO:0006508 proteolysis
GO:0007596 blood coagulation
GO:0007597 blood coagulation, intrinsic pathway
GO:0007599 hemostasis
GO:0010756 positive regulation of plasminogen activation
GO:0016485 protein processing
GO:0016540 protein autoprocessing
GO:0030193 regulation of blood coagulation
GO:0030194 positive regulation of blood coagulation
GO:0031638 zymogen activation
GO:0042730 fibrinolysis
GO:0045087 innate immune response
GO:0051788 response to misfolded protein
GO:0051919 positive regulation of fibrinolysis

Cellular Component:
GO:0005576 extracellular region
GO:0005615 extracellular space
GO:0005886 plasma membrane
GO:0070062 extracellular exosome


-  Descriptions from all associated GenBank mRNAs
  M31315 - Human coagulation factor XII (Hageman) mRNA, 3' end.
AB095845 - Homo sapiens mRNA for coagulation factor XII-Mie, complete cds.
CS203621 - Sequence 1 from Patent EP1598428.
CS210562 - Sequence 1 from Patent WO2005111233.
JA312083 - Sequence 1 from Patent EP2287339.
LQ432546 - Sequence 1 from Patent EP3056571.
BC012390 - Homo sapiens coagulation factor XII (Hageman factor), mRNA (cDNA clone IMAGE:3881207), complete cds.
JD073622 - Sequence 54646 from Patent EP1572962.
M11723 - Human blood coagulation factor XII (Hageman factor) mRNA.
JD444995 - Sequence 426019 from Patent EP1572962.
M13147 - Human factor XII (Hageman factor) mRNA, 3' end.
JD347076 - Sequence 328100 from Patent EP1572962.
JD480305 - Sequence 461329 from Patent EP1572962.
JD067488 - Sequence 48512 from Patent EP1572962.
JD215775 - Sequence 196799 from Patent EP1572962.
KJ901422 - Synthetic construct Homo sapiens clone ccsbBroadEn_10816 F12 gene, encodes complete protein.
KR710723 - Synthetic construct Homo sapiens clone CCSBHm_00016119 F12 (F12) mRNA, encodes complete protein.
KR710724 - Synthetic construct Homo sapiens clone CCSBHm_00016123 F12 (F12) mRNA, encodes complete protein.
BT007350 - Homo sapiens coagulation factor XII (Hageman factor) mRNA, complete cds.
BC168381 - Synthetic construct Homo sapiens clone IMAGE:100068277, MGC:195894 coagulation factor XII (Hageman factor) (F12) mRNA, encodes complete protein.
JD386424 - Sequence 367448 from Patent EP1572962.
JD405438 - Sequence 386462 from Patent EP1572962.
JD353620 - Sequence 334644 from Patent EP1572962.

-  Biochemical and Signaling Pathways
  KEGG - Kyoto Encyclopedia of Genes and Genomes
hsa04610 - Complement and coagulation cascades

BioCarta from NCI Cancer Genome Anatomy Project
h_intrinsicPathway - Intrinsic Prothrombin Activation Pathway

Reactome (by CSHL, EBI, and GO)

Protein P00748 (Reactome details) participates in the following event(s):

R-HSA-158313 factor XII -> factor XIIa
R-HSA-158357 factor XIIa + C1Inh -> factor XIIa:C1Inh
R-HSA-158300 factor XI:platelet glycoprotein (GP) Ib:IX:V complex -> factor XIa:platelet glycoprotein (GP) Ib:IX:V complex (XIIa catalyst)
R-HSA-140837 Intrinsic Pathway of Fibrin Clot Formation
R-HSA-140877 Formation of Fibrin Clot (Clotting Cascade)
R-HSA-109582 Hemostasis

-  Other Names for This Gene
  Alternate Gene Symbols: FA12_HUMAN, NM_000505, NP_000496, P00748, P78339
UCSC ID: uc003mgo.4
RefSeq Accession: NM_000505
Protein: P00748 (aka FA12_HUMAN)
CCDS: CCDS34302.1

-  Gene Model Information
 
category: coding nonsense-mediated-decay: no RNA accession: NM_000505.3
exon count: 14CDS single in 3' UTR: no RNA size: 2060
ORF size: 1848CDS single in intron: no Alignment % ID: 100.00
txCdsPredict score: 3893.50frame shift in genome: no % Coverage: 99.56
has start codon: yes stop codon in genome: no # of Alignments: 1
has end codon: yes retained intron: no # AT/AC introns 0
selenocysteine: no end bleed into intron: 0# strange splices: 0
Click here for a detailed description of the fields of the table above.

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.