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Category Symbol Source: HGNC EntrezGene Ensembl GeneCards RNA genes CroW21

GIFtS
-

F2 Gene

protein-coding GIFtS: 73
GCID: GC11P046740

coagulation factor II (thrombin)

Explore 381 diseases affiliated with
F2 via

MalaCards

our new
Human Malady Compendium

(According to ¹HGNC, ²Entrez Gene,
³UniProtKB/Swiss-Prot, ⁴UniProtKB/TrEMBL, ⁵OMIM, ⁶GeneLoc, ⁷Ensembl, ⁸DME, ⁹miRBase, and/or ¹⁰fRNAdb)
About This Section

Aliases
Coagulation Factor II (Thrombin)¹ ²		Prothrombin¹
EC 3.4.21.5³ ⁸		Prothrombin B-Chain²
PT²		Serine Protease²
RPRGL2²		Coagulation Factor II³
THPH1²		EC 3.4.21⁸

External Ids:	HGNC: 3535¹	Entrez Gene: 2147²	Ensembl: ENSG00000180210⁷	OMIM: 176930⁵	UniProtKB: P00734³

Export aliases for F2 gene to outside databases

Previous GC identifers: GC11M048740 GC11P047618 GC11P046772 GC11P046705 GC11P046697 GC11P046446

(According to Entrez Gene, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
About This Section

Entrez Gene summary for F2:

Coagulation factor II is proteolytically cleaved to form thrombin in the first step of the coagulation cascade which

ultimately results in the stemming of blood loss. F2 also plays a role in maintaining vascular integrity during

development and postnatal life. Mutations in F2 leads to various forms of thrombosis and dysprothrombinemia. (provided

by RefSeq, Jul 2008)

UniProtKB/Swiss-Prot: THRB_HUMAN, P00734

Function: Thrombin, which cleaves bonds after Arg and Lys, converts fibrinogen to fibrin and activates factors V, VII,

VIII, XIII, and, in complex with thrombomodulin, protein C. Functions in blood homeostasis, inflammation and wound

healing

Gene Wiki entry for F2 (Thrombin)

(According to GeneLoc and/or HGNC, and/or
Entrez Gene (NCBI build 37),
and/or miRBase,
Genomic Views according to UCSC (hg19) and Ensembl (release 69), Regulatory elements and Epigenetics data according to QIAGEN, SABiosciences, and/or SwitchGear Genomics)
About This Section

RefSeq DNA sequence:

NC_000011.9 NC_018922.1 NT_009237.18

Regulatory elements:

SABiosciences Regulatory transcription factor binding sites in the F2 gene promoter:
CREB PPAR-gamma1 AP-1 deltaCREB ATF-2 PPAR-gamma2 c-Jun
Other transcription factors

SwitchGear Promoter luciferase reporter plasmid: F2 promoter sequence

Search SABiosciences Chromatin IP Primers for F2

Epigenetics:

QIAGEN PyroMark CpG Assay predesigned Pyrosequencing DNA Methylation assays in human, mouse, rat F2

Genomic Location:
Genomic View: UCSC Golden Path with GeneCards custom track

Entrez Gene cytogenetic band: 11p11 Ensembl cytogenetic band: 11p11.2 HGNC cytogenetic band: 11p11.2

F2 Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
F2 gene location

GeneLoc information about chromosome 11 GeneLoc Exon Structure

GeneLoc location for GC11P046740: view genomic region (about GC identifiers)

Start:	46,740,730 bp from pter	End:	46,761,056 bp from pter
Size:	20,327 bases	Orientation:	plus strand

(According to ¹UniProtKB, HORDE, neXtProt, Ensembl, and/or Reactome, Modification sites according to ²PhosphoSitePlus, Specific Peptides from DME, Protein expression images according to data from SPIRE MOPED and PaxDb, RefSeq according to NCBI, PDB rendering according to OCA and/or Proteopedia, Recombinant Proteins from EMD Millipore, R&D Systems, GenScript, Enzo Life Sciences, OriGene, Novus Biologicals, Sino Biological, ProSpec, and/or Uscn,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, and/or Uscn, Ontologies according to Gene Ontology Consortium 01 Mar 2013 and Entrez Gene, Antibodies by EMD Millipore, R&D Systems, GenScript, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, Abcam, and/or Uscn)
About This Section

UniProtKB/Swiss-Prot: THRB_HUMAN, P00734 (See protein sequence)

Recommended Name: Prothrombin precursor

Size: 622 amino acids; 70037 Da

Subunit: Heterodimer (named alpha-thrombin) of a light and a heavy chain; disulfide-linked. Forms a heterodimer with

SERPINA5

Subcellular location: Secreted, extracellular space

Miscellaneous: Prothrombin is activated on the surface of a phospholipid membrane that binds the amino end of

prothrombin and factors Va and Xa in Ca-dependent interactions; factor Xa removes the activation peptide and cleaves

the remaining part into light and heavy chains. The activation process starts slowly because factor V itself has to be

activated by the initial, small amounts of thrombin

Miscellaneous: It is not known whether 1 or 2 smaller activation peptides, with additional cleavage after Arg-314, are

released in natural blood clotting

Miscellaneous: Thrombin can itself cleave the N-terminal fragment (fragment 1) of the prothrombin, prior to its

activation by factor Xa

Miscellaneous: The cleavage after Arg-198, observed in vitro, does not occur in plasma

6/332 PDB 3D structures from and Proteopedia for F2 (see all 332):

1A2C (3D)

1A3B (3D)

1A3E (3D)

1A46 (3D)

1A4W (3D)

1A5G (3D)

Secondary accessions: B2R7F7 B4E1A7 Q4QZ40 Q53H04 Q53H06 Q7Z7P3 Q9UCA1

Explore the universe of human proteins at neXtProt for F2: NX_P00734

Post-translational modifications:

The gamma-carboxyglutamyl residues, which bind calcium ions, result from the carboxylation of glutamyl residues by a

microsomal enzyme, the vitamin K-dependent carboxylase. The modified residues are necessary for the calcium-dependent

interaction with a negatively charged phospholipid surface, which is essential for the conversion of prothrombin to

thrombin¹

N-glycosylated. N-glycan heterogeneity at Asn-121: Hex3HexNAc3 (minor), Hex4HexNAc3 (minor) and Hex5HexNAc4 (major). At

Asn-143: Hex4HexNAc3 (minor) and Hex5HexNAc4 (major)¹

View modification sites using PhosphoSitePlus²

View neXtProt modification sites for NX_P00734

4/15 DME Specific Peptides for F2 (P00734) (see all 15)

CRNPDGD

GNLEREC

VLTAAHC

WVLTAAH

F2 Protein expression data from MOPED and PaxDb: About this image

REFSEQ proteins: NP_000497.1

ENSEMBL proteins:

ENSP00000308541 ENSP00000433907 ENSP00000387413

Reactome Protein details: P00734
Human Recombinant Protein Products:

	Browse Purified and Recombinant Proteins at EMD Millipore
	R&D Systems Recombinant & Natural Proteins for F2 (Coagulation Factor II/Thrombin)
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	OriGene Purified Protein: F2 OriGene Protein Over-expression Lysate: F2 OriGene Custom Protein Services for F2
	GenScript Custom Purified and Recombinant Proteins Services for F2
	Novus Biologicals F2 Proteins Novus Biologicals F2 Lysates
	Browse Sino Biological Recombinant Proteins
	ProSpec Recombinant Protein for F2
	Uscn Proteins for F2

Gene Ontology (GO): 5/6 cellular component terms (GO ID links to tree view) (see all 6): About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0005576	extracellular region	TAS	--
GO:0005615	extracellular space	IDA	9639571
GO:0005625	soluble fraction	--	--
GO:0005788	endoplasmic reticulum lumen	TAS	--
GO:0005796	Golgi lumen	TAS	--

F2 for ontologies About GeneDecksing

F2 Antibody Products:

	EMD Millipore Mono- and Polyclonal Antibodies for the study of F2
	R&D Systems Antibodies for F2 (Coagulation Factor II/Thrombin)
	OriGene Antibodies: F2 OriGene Custom Antibody Services for F2
	GenScript Superior Antibodies for F2
	Novus Biologicals F2 Antibodies
	Abcam antibodies for F2
	Uscn Antibodies for F2
	ThermoFisher Antibodies for F2

Assay Products for F2:

	Browse Kits and Assays available from EMD Millipore
	OriGene Custom Immunoassay Development Browse OriGene Fluorogenic Cell Assay Kits
	R&D Systems Multiplex/Array Assay Kits & Reagents for F2 (Coagulation Factor II/Thrombin)
	GenScript Custom Assay Services for F2
	Browse Enzo Life Sciences for kits & assays
	Uscn ELISAs and CLIAs for F2

(According to InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
About This Section

F2 for domains About GeneDecksing

5/11 InterPro domains/families (see all 11):

IPR017857 Coagulation_fac_subgr_Gla_dom

IPR001314 Peptidase_S1A

IPR018056 Kringle_CS

IPR001254 Peptidase_S1

IPR003966 Prothrombin/thrombin

Graphical View of Domain Structure for InterPro Entry P00734

ProtoNet protein and cluster: P00734

5/6 Blocks protein families (see all 6):

IPB000001 Kringle

IPB000294 Vitamin K-dependent carboxylation/gamma-carboxyglutamic (GLA) domain

IPB001254 Serine protease

IPB001314 Chymotrypsin serine protease family (S1) signature

IPB002383 Coagulation factor GLA domain signature

UniProtKB/Swiss-Prot: THRB_HUMAN, P00734

Similarity: Belongs to the peptidase S1 family

Similarity: Contains 1 Gla (gamma-carboxy-glutamate) domain

Similarity: Contains 2 kringle domains

Similarity: Contains 1 peptidase S1 domain

(According to ¹UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or ²DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013,
bound targets from SABiosciences, miRNA Gene Targets from miRTarBase shRNA from OriGene, RNAi from EMD Millipore, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, Gene Editing from DNA2.0, Clones from EMD Millipore, OriGene, SwitchGear Genomics, GenScript, Sino Biological, DNA2.0, and Vector BioLabs, Cell Lines from GenScript, LifeMap BioReagents, In Situ Hybridization Assays from Advanced Cell Diagnostics, Ontologies according to Gene Ontology Consortium 01 Mar 2013 via Entrez Gene.)
About This Section

Function Summary:

UniProtKB/Swiss-Prot: THRB_HUMAN, P00734

Function: Thrombin, which cleaves bonds after Arg and Lys, converts fibrinogen to fibrin and activates factors V, VII,

VIII, XIII, and, in complex with thrombomodulin, protein C. Functions in blood homeostasis, inflammation and wound

healing

Catalytic activity: Selective cleavage of Arg- -Gly bonds in fibrinogen to form fibrin and release fibrinopeptides A

and B

Enzyme regulation: Inhibited by SERPINA5

Genatlas biochemistry entry for F2:

coagulation factor II,vitamin K-dependent (prothrombin)

Enzyme Numbers (IUBMB): EC 3.4.21.5¹ ² EC 3.4.21²

miRNA Products:		miRTarBase miRNAs that target F2: hsa-mir-16 (MIRT001484)

		OriGene 3'-UTR Clone: F2 Browse MicroRNA Expression Plasmids
		QIAGEN Custom miScript Target Protector blocks miRNA-binding site of human, mouse, rat F2
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		Browse SwitchGear 3'UTR luciferase reporter plasmids

Inhib. RNA Products:		Browse for Gene Knock-down Tools from EMD Millipore
		OriGene 29mer shRNA kits in GFP-retroviral vector in human, mouse, rat for F2 (see all 7) OriGene shRNA RFP: F2 OriGene siRNA: F2
		QIAGEN FlexiTube/FlexiPlate siRNA for gene silencing in human, mouse, rat F2

Gene Editing
Products:

DNA2.0 Custom Protein Engineering Service for F2

Clone Products:		Browse Clones for the Expression of Recombinant Proteins Available from EMD Millipore
		OriGene Myc/DDK tagged cDNA clones in CMV expression vector in human, mouse, rat for F2 (see all 3) OriGene untagged cDNA clones in CMV expression vector in human, mouse, rat for F2 OriGene custom cloning services � gene synthesis, subcloning, mutagenesis, variant library, vector shuttling
		GenScript: all cDNA clones in your preferred vector: F2 (NM_013265)
		Sino Biological Human cDNA Clone for F2
		DNA2.0 Custom Codon Optimized Gene Synthesis Service for F2
		Vector BioLabs ready-to-use adenovirus/AAV for human, mouse, rat F2

Cell Line Products:		GenScript Custom overexpressing Cell Line Services for F2
		Search LifeMap BioReagents cell lines for F2

In Situ Assay
Products:

Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for F2

Gene Ontology (GO): 5/7 molecular function terms (GO ID links to tree view) (see all 7): About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0004252	serine-type endopeptidase activity	IDA	1672265
GO:0005102	contributes to receptor binding	IPI	8626514
GO:0005509	calcium ion binding	IEA	--
GO:0005515	protein binding	IPI	8626514
GO:0008083	growth factor activity	TAS	8626514

F2 for ontologies About GeneDecksing

2 GenomeRNAi human phenotypes for F2:

Decreased homologous recombina

Increased G1 DNA content

Animal Models:
Mouse knock-outs for F2: F2^tm1Jes F2^tm1Sjd
15 MGI mutant phenotypes (inferred from 4 alleles) (MGI details for F2):

cardiovascular system	cellular	digestive/alimentary	embryogenesis	growth/size
hematopoietic system	homeostasis/metabolism	immune system	integument	mortality/aging
nervous system	normal	reproductive system	respiratory system	skeleton

F2 for phenotypes About GeneDecksing

(Pathways according to EMD Millipore, R&D Systems, Cell Signaling Technology, KEGG, PharmGKB, BioSystems, Reactome, Tocris Bioscience, GeneGo (Thomson Reuters), QIAGEN, and/or UniProtKB, Sets of similar genes according to GeneDecks, Interaction Networks according to SABiosciences, and/or STRING, Interactions according to ¹UniProtKB, ²MINT, ³I2D, and/or ⁴STRING, with links to IntAct and Ensembl, Ontologies according to Gene Ontology Consortium 01 Mar 2013 via Entrez Gene).
About This Section

Unified GeneCards pathways - 5/28 super-pathways (see all 28) About this table

See pathways by source

Super-pathway

contained gene-specific pathways

Gamma-carboxylation, transport, and amino-terminal cleavage of proteins

Gamma-carboxylation, transport, and amino-terminal cleavage of proteins	1.00	Transport of gamma-carboxylated protein precursors from the endoplasmic reticulum to the Golgi apparatus	0.73
Removal of aminoterminal propeptides from gamma-carboxylated proteins	0.82	Warfarin Pathway, Pharmacodynamics	0.67
Gamma-carboxylation of protein precursors	0.82

Formation of Fibrin Clot (Clotting Cascade)

	Formation of Fibrin Clot (Clotting Cascade)	1.00			Blood Coagulation Signaling Pathways	0.51
	Intrinsic Pathway	0.59			Blood Clotting Cascade	0.36

Class A/1 (Rhodopsin-like receptors)

	Class A/1 (Rhodopsin-like receptors)	1.00			Peptide ligand-binding receptors	0.61
	GPCR ligand binding	0.75			Neuroactive ligand-receptor interaction	0.38

Signaling by GPCR

	Signaling by GPCR	1.00			Signal Transduction	0.56
	GPCR downstream signaling	0.89

Cell adhesion_Integrin inside-out signaling

Cell adhesion_Integrin inside-out signaling

1.00

Cell adhesion Integrin inside-out signaling

0.99

Pathway sources
See GeneCards unified pathways
Show all pathways

1 EMD Millipore Pathway for F2

Cell adhesion Integrin inside-out signaling

1 R&D Systems Pathway for F2

Blood Coagulation Signaling Pathways

5/9 Downloadable PowerPoint Slides of QIAGEN Pathway Central Maps for F2 (see all 9)

	Endothelin-1 Signaling Pathway
	G12-G13 in Cellular Signaling
	JAK-STAT Pathway
	Thrombin Signaling
	Transendothelial Migration of Leukocytes

1 GeneGo (Thomson Reuters) Pathway for F2

Cell adhesion Integrin inside-out signaling

5/7 BioSystems Pathways for F2 (see all 7)

	Blood Clotting Cascade
	Selenium Pathway
	Complement and Coagulation Cascades
	Regulation of Actin Cytoskeleton
	Syndecan-4-mediated signaling events

5/24 Reactome Pathways for F2 (see all 24)

	Regulation of Insulin-like Growth Factor (IGF) Transport and Uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs)
	Removal of aminoterminal propeptides from gamma-carboxylated proteins
	PTM: gamma carboxylation, hypusine formation and arylsulfatase activation
	Gamma-carboxylation, transport, and amino-terminal cleavage of proteins
	Transport of gamma-carboxylated protein precursors from the endoplasmic reticulum to the Golgi apparatus

2 PharmGKB Pathways for F2

	Platelet Aggregation Inhibitor Pathway, Pharmacodynamics
	Warfarin Pathway, Pharmacodynamics

3 Kegg Pathways (Kegg details for F2):

	Neuroactive ligand-receptor interaction
	Complement and coagulation cascades
	Regulation of actin cytoskeleton

F2 for pathways About GeneDecksing

Interactions:

SABiosciences Gene Network Central^TM Interacting Genes and Proteins Network for F2

STRING Interaction Network Preview (showing 5 interactants - click image to see 25)

5/69 Interacting proteins for F2 (P00734^{1, 3} ENSP00000308541⁴) via UniProtKB, MINT, STRING, and/or I2D (see all 69)

Interactant		Interaction Details
GeneCard	External ID(s)	Interaction Details
THBD	P07204¹^,³, ENSP00000366307⁴	EBI-297094,EBI-941422 I2D: score=4 STRING: ENSP00000366307
SERPIND1	P05546³, ENSP00000215727⁴	I2D: score=3 STRING: ENSP00000215727
FGA	P02671³, ENSP00000306361⁴	I2D: score=2 STRING: ENSP00000306361
SERPINB6	P35237³, ENSP00000338358⁴	I2D: score=2 STRING: ENSP00000338358
SERPING1	P05155³, ENSP00000278407⁴	I2D: score=2 STRING: ENSP00000278407

About this table

Gene Ontology (GO): 5/30 biological process terms (GO ID links to tree view) (see all 30): About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0001934	positive regulation of protein phosphorylation	IDA	7559487
GO:0006508	proteolysis	TAS	--
GO:0006950	response to stress	--	--
GO:0006953	acute-phase response	IEA	--
GO:0007166	cell surface receptor signaling pathway	IDA	1672265

F2 for ontologies About GeneDecksing

(Chemical Compounds according to UniProtKB, Enzo Life Sciences, EMD Millipore, Tocris Bioscience HMDB, BitterDB, and/or Novoseek, and Drugs according to DrugBank, Enzo Life Sciences, and/or PharmGKB, with drugs/clinical trials/news search links to CenterWatch)
About This Section

F2 for compounds About GeneDecksing

EMD Millipore small molecules for F2:
Small Molecule - inhibitor

Enzo Life Sciences drugs & compounds for F2

Browse Tocris compounds for F2
UniProtKB/Swiss-Prot: THRB_HUMAN, P00734

Pharmaceutical: The peptide TP508 also known as Chrysalin (Orthologic) could be used to accelerate repair of both soft

and hard tissues

10/101 DrugBank Compounds for F2 (see all 101) About this table

Compound	Synonyms	CAS #	Type	Actions	PubMed Ids
Argatroban	--	74863-84-6	target	inhibitor	10608050 10353669 10608016 11752352 10226408 10362188
Bivalirudin	--	128270-60-0	target	inhibitor	11833835 11929334 11752352 11923794 11504570 11060732
Lepirudin	--	120993-53-5	target	inhibitor	10912644 10505536 11807012 11055889 11752352 11467439
Proflavine	--	92-62-6	target	other/unknown	4857231 7837275 7407200 1711542 6722124 10592235
Antihemophilic Factor	AHF (see all 3)	--	enzyme	activator	3099625 2402772 10688826 12463731 1139038
Coagulation Factor IX	Christmas factor (see all 4)	9001-28-9	target	--	10499904 10648407 10499905 10498586 11019961
Drotrecogin alfa	Anticoagulant protein C (see all 4)	60202-16-6	target	--	12208873 12070133 12062545 12296618 10463819
Menadione	2-Methyl-1,4-Naphthalenedione (see all 7)	58-27-5	target	activator	7657295 10469489 2484931 2922761 6867080
Ximelagatran	--	192939-46-1	target	inhibitor	17688383 17319469 11752352 17516699 17532684
Dabigatran etexilate	Dabigatran etexilate mesilate (salt form) (see all 2)	211915-06-9	target	inhibitor	20424539 19756950 17061960

10/128 Novoseek chemical compound relationships for F2 gene (see all 128) About this table

Compound	-log (P-Val)	Hits	PubMed IDs for Articles with Shared Sentences (# sentences)
fibrinogen	92.9	1392	2037675 (5), 9746270 (4), 11979291 (4), 16454558 (4) (see all 99)
warfarin	89.4	481	7586953 (6), 8018915 (5), 14616410 (5), 1562730 (4) (see all 99)
mnpt	81.9	16	9233567 (1), 10926265 (1), 9365404 (1), 9462248 (1) (see all 12)
hepaplastin	81.4	35	1766133 (1), 7874270 (1), 7782035 (1), 10590673 (1) (see all 32)
heparin	80.8	239	2294105 (3), 9863704 (3), 8388583 (3), 1730217 (3) (see all 99)
ecarin	78.1	28	8165613 (2), 9869177 (2), 7900080 (1), 9211628 (1) (see all 23)
gamma-carboxyglutamic acid	77.5	103	1699555 (5), 10094467 (4), 2277030 (4), 16413375 (4) (see all 36)
vitamin k1	75.9	64	9362192 (6), 1325077 (3), 15867043 (2), 17101711 (2) (see all 36)
s-warfarin	74.9	20	10702890 (2), 17192504 (2), 9839766 (2), 15632222 (1) (see all 15)
hirudin	72.7	58	11053617 (4), 8349581 (3), 9863704 (3), 7740455 (3) (see all 40)

1 PharmGKB related drug/compound annotation for F2 gene

Drug/compound	PharmGKB Annotation
tamoxifen	DL

About this table

Search CenterWatch for drugs/clinical trials and news about F2 / THRB

(Secondary structures according to fRNAdb,
GenBank/EMBL/DDBJ Accessions according to
Unigene (Build 235 Homo sapiens; Mar 10 2013) or GenBank,
RefSeq according to Entrez Gene,
DOTS (version 10), and/or AceView, transcript ids from Ensembl with links to UCSC,
exon structure from GeneLoc, alternative splicing isoforms according to ASD and/or ECgene,
RNAi Products from EMD Millipore,
siRNAs from OriGene, QIAGEN, shRNA from OriGene, microRNA from QIAGEN,
Tagged/untagged cDNA clones from OriGene, SwitchGear Genomics, GenScript, DNA2.0, Vector BioLabs, Primers from OriGene, SABiosciences, and/or QIAGEN )
About This Section

REFSEQ mRNAs for F2 gene:

NM_000506.3

Unigene Cluster for F2:

Coagulation factor II (thrombin)

Hs.655207 [show with all ESTs]

Unigene Representative Sequence: NM_000506

5 Ensembl transcripts including schematic representations, and UCSC links where relevant:

ENST00000311907(uc001ndf.4) ENST00000469189 ENST00000530231 ENST00000442468

ENST00000490274

miRNA Products:		OriGene 3'-UTR Clone: F2 Browse OriGene MicroRNA Expression Plasmids
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		Browse SwitchGear 3'UTR luciferase reporter plasmids

Inhib. RNA Products:		Browse for Gene Knock-down Tools from EMD Millipore
		OriGene 29mer shRNA kits in GFP-retroviral vector in human, mouse, rat for F2 (see all 7) OriGene shRNA RFP: F2 OriGene siRNA: F2
		QIAGEN FlexiTube/FlexiPlate siRNA for gene silencing in human, mouse, rat F2

Clone Products:		OriGene Myc/DDK tagged cDNA clones in CMV expression vector in human, mouse, rat for F2 (see all 3) OriGene untagged cDNA clones in CMV expression vector in human, mouse, rat for F2 OriGene custom cloning services � gene synthesis, subcloning, mutagenesis, variant library, vector shuttling
		GenScript: all cDNA clones in your preferred vector: F2 (NM_013265)
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		Vector BioLabs ready-to-use adenovirus/AAV for human, mouse, rat F2

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		SABiosciences RT² qPCR Primer Assay in human, mouse, rat F2
		QIAGEN QuantiTect SYBR Green Assays in human, mouse, rat F2
		QIAGEN QuantiFast Probe-based Assays in human, mouse, rat F2

Additional cDNA sequence:

AJ972449.1 AK222775.1 AK222777.1 AK293326.1 AK303747.1 AK312965.1 AY344793.1 AY344794.1

BC051332.1 M33031.1 V00595.1

4 DOTS entries:

DT.115445 DT.40132890 DT.100834099 DT.95360807

24/89 AceView cDNA sequences (see all 89):

BC051332 BQ653592 CB148992 CB111898 CR617821 CB124824 CB147238 C21032

R90940 CR594467 AV661218 CB156997 T55195 CB120344 BX463016 T28286

AL531046 R09741 T70932 R12280 T62075 BX426923 AU099063 AY344794

GeneLoc Exon Structure

4 Alternative Splicing Database (ASD) splice patterns (SP) for F2 About this scheme

ExUns:	1a	·	1b	^	2	^	3a	·	3b	^	4	^	5	^	6	^	7	^	8a	·	8b	·	8c	^	9	^	10	^	11	^	12	^	13	^	14	^	15
SP1:					-				-
SP2:									-
SP3:					-
SP4:

ECgene alternative splicing isoforms for F2

(RNA expression data according to H-InvDB, NONCODE, miRBase, and RNAdb, Expression images according to data from BioGPS, Illumina Human BodyMap, and CGAP SAGE, Sets of similar genes according to GeneDecks, in vivo and in vitro expression data from LifeMap Discovery™, plus additional links to Genevestigator, and/or SOURCE, and/or BioGPS, and/or UniProtKB,
PCR Arrays from SABiosciences, Primers from OriGene, SABiosciences, and/or QIAGEN, In Situ Hybridization Assays from Advanced Cell Diagnostics)
About This Section

F2 expression in normal human tissues (normalized intensities)
See probesets specificity/sensitivity at GeneAnnot
About this imageBioGPS
CGAP TAG: TGTTCCGCCT

About this image

F2 expression in embryonic tissues and stem cells

Expression by the Database of Embryonic development, Stem cell research, and Regenerative medicine About this table

Stem Cell Differentiation: 2 LifeMap Cells

Name

Category

Posterior foregut-like cells (A scalable, suspensi...)

Embryoid bodies (Two-step protocol fo...)

Expression:

Positive

Negative

Selective marker

Experimental details:

Curated

Microarrays

In-situ hybridization

See F2 Protein Expression from SPIRE MOPED and PaxDB
Genevestigator expression for F2

SOURCE GeneReport for Unigene cluster: Hs.655207

UniProtKB/Swiss-Prot: THRB_HUMAN, P00734

Tissue specificity: Expressed by the liver and secreted in plasma

SABiosciences Expression via Pathway-Focused PCR Arrays including F2:

Apoptosis 384HT in human mouse rat

Angiogenesis in human mouse rat

JAK / STAT Signaling Pathway in human mouse rat

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Molecular Toxicology PathwayFinder 384HT in human mouse rat

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In Situ
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(Orthologs according to ^1,2HomoloGene (²older version, for species not in ¹newer version), ³euGenes, ⁴SGD , ⁵MGI Mar 06 2013, with possible further links to Flybase and/or WormBase, and/or ⁶Ensembl pan taxonomic compara , Gene Trees according to Ensembl and TreeFam)
About This Section

This gene was present in the common ancestor of chordates.

Orthologs for F2 gene from 4/15 species (see all 15) About this table

Organism	Taxonomic classification	Gene	Description	Human Similarity	Orthology Type	Details
chicken (Gallus gallus)	Aves	F2¹	coagulation factor II (thrombin)	65.4(n) 63.04(a)		395306 NM_204605.1 NP_989936.1
lizard (Anolis carolinensis)	Reptilia	F2⁶	--	59(a)	1 ↔ 1	1(43136103-43162495)
African clawed frog (Xenopus laevis)	Amphibia	Xl.29409²	Xenopus laevis transcribed sequence with weak similarity more	76.83(n)		48021727
zebrafish (Danio rerio)	Actinopterygii	Dr.26855²	Danio rerio cDNA clone MGC66319 IMAGE5601571, complete more	76.37(n)		BC055596.1

ENSEMBL Gene Tree for F2 (if available)
TreeFam Gene Tree for F2 (if available)

(Paralogs according to ¹HomoloGene,
²Ensembl, and ³SIMAP, Pseudogenes according to ⁴Pseudogene.org Build 68)
About This Section

Paralogs for F2 gene

PROZ² PAMR1² C1S² C1R² C1RL² F9² MASP1² F10²

HPR² HP² PROC² F7² MASP2²

18/44 SIMAP similar genes for F2 using alignment to 6 protein entries: THRB_HUMAN (see all proteins) (see all similar genes):

PRRG3 PROS1 PROC1 PRRG1 PRSS21 TMPRSS11B

F7 PROZ PROC HGF HP TMPRSS11A

F9 F9 p22 factor IX F9 GAS6 TMPRSS13 C1R

F2 for paralogs About GeneDecksing

(SNPs/Variants according to the ¹NCBI SNP Database, ²Ensembl, ³PupaSUITE, UniProtKB, and DNA2.0, Linkage Disequilibrium by HapMap, Structural Variations(CNVs/InDels/Inversions) from the Database of Genomic Variants, Mutations from the Human Gene Mutation Database (HGMD) and the Locus Specific Mutation Databases (LSDB), Blood group antigen gene mutations by BGMUT, Resequencing Primers from QIAGEN, Cancer Mutation PCR Arrays and Assays and Copy Number PCR Arrays from SABiosciences)
About This Section

SNP ID	Valid	Clinical significance	Chr 11 pos	Sequence	#	AA Chg	Type	More	#	Allele freq	Pop	Total sample	More
Genomic Data					Transcription Related Data				Allele Frequencies
				--	--	--		--	--
rs62623459^1,2	C,F,	pathogenic	54778717(+)	`GCTCCG/AAAGGC`	2	/K /E	mis¹		2		NA EU	5765
rs9794941^1,2	C,	--	46444678(+)	`ttcacA/Gtccag`	1	--	us2k¹		0	--	--	--	--
rs3136430^1,2	C,F,H,	--	46445665(+)	`CACTCC/TCTGTT`	1	--	us2k¹		12		NS EA NA WA	1296
rs4752930^1,2	C,H	--	46446081(+)	`AGAAAT/GGGGCC`	1	--	us2k¹		4		NS EA	416
rs200285313^1,2	C	--	46446370(-)	`TGCTTG/TTCATC`	1	--	us2k¹		0	--	--	--	--
rs113202549^1,2		--	46446937(+)	`GGGCTG/TGAAAG`	1	--	int¹		1		CSA	2
rs3136433^1,2	C,F,H,	--	46447825(+)	`ATATTC/ATTCTC`	1	--	int¹ trp³		11		NS EA NA	770
rs112619944^1,2	C,	--	46447898(+)	`CCAGGG/ATAAAG`	1	--	int¹		1		NA	2
rs3136434^1,2	C,F,H,	--	46448166(+)	`CATCTT/CTCTGT`	1	--	int¹		19		NS NA EA	2084
rs3136436^1,2	C,F,	--	46448406(+)	`GAGGCA/GGTCCC`	1	--	int¹		5		NS NA	212

HapMap Linkage Disequilibrium report for F2 (46740730 - 46761056 bp)
Structural Variations (Copy Number Variations, Insertions/Deletions, Inversions)
Database of Genomic Variants (DGV) variations for F2: --
Human Gene Mutation Database (HGMD): F2

SABiosciences Cancer Mutation PCR Assays

QIAGEN SeqTarget long-range PCR primers in human, mouse, rat for resequencing F2

DNA2.0 Custom Variant and Variant Library Synthesis for F2

(in which this Gene is Involved, According to MalaCards, OMIM, UniProtKB, the University of Copenhagen DISEASES database, Novoseek, Genatlas, GeneTests, GAD, HuGE Navigator, and/or TGDB.)
About This Section

F2 for disorders           About GeneDecksing

OMIM gene information: 176930
OMIM disorders: 613679  188050  601367
UniProtKB/Swiss-Prot: THRB_HUMAN, P00734

Defects in F2 are the cause of factor II deficiency (FA2D) [MIM:613679]. It is a very rare blood coagulation

disorder characterized by mucocutaneous bleeding symptoms. The severity of the bleeding manifestations correlates with

blood factor II levels

Genetic variations in F2 may be a cause of susceptibility to ischemic stroke (ISCHSTR) [MIM:601367]; also

known as cerebrovascular accident or cerebral infarction. A stroke is an acute neurologic event leading to death of

neural tissue of the brain and resulting in loss of motor, sensory and/or cognitive function. Ischemic strokes,

resulting from vascular occlusion, is considered to be a highly complex disease consisting of a group of heterogeneous

disorders with multiple genetic and environmental risk factors

Defects in F2 are the cause of thrombophilia due to thrombin defect (THPH1) [MIM:188050]. It is a

multifactorial disorder of hemostasis characterized by abnormal platelet aggregation in response to various agents and

recurrent thrombi formation. Note=A common genetic variation in the 3-prime untranslated region of the prothrombin

gene is associated with elevated plasma prothrombin levels and an increased risk of venous thrombosis

Defects in F2 are associated with susceptibility to pregnancy loss, recurrent, type 2 (RPRGL2) [MIM:614390]. A

common complication of pregnancy, resulting in spontaneous abortion before the fetus has reached viability. The term

includes all miscarriages from the time of conception until 24 weeks of gestation. Recurrent pregnancy loss is defined

as 3 or more consecutive spontaneous abortions

20/381 diseases for F2 (see all 381): About MalaCards

dysprothrombinemia vitamin k-dependent clotting factors thrombosis anterior spinal artery syndrome

neonatal intrahepatic cholestasis caused by citrin deficiency bernard-soulier syndrome factor vii deficiency crimean-congo hemorrhagic fever

disseminated intravascular coagulation antithrombin iii deficiency heparin-induced thrombocytopenia deep vein thrombosis

alpha 1-antitrypsin deficiency portal vein thrombosis vitamin k deficiency hemorrhagic disease patent foramen ovale

20/36 diseases from the University of Copenhagen DISEASES database for F2 (see all 36):

Thrombophilia Liver disease Vitamin K deficiency hemorrhagic disease Antiphospholipid syndrome

Thrombocytopenia Pulmonary embolism Protein C deficiency Hepatocellular carcinoma

Heart disease Cerebrovascular accident Factor X deficiency Esophageal varix

Factor VII deficiency Varicose veins Hyperhomocysteinemia Hepatitis B

Lupus erythematosus Blood protein disease Hemophilia B Placental abruption

10/98 Novoseek disease relationships for F2 gene (see all 98) About this table

Disease	-log (P-Val)	Hits	PubMed IDs for Articles with Shared Sentences (# sentences)
pt prolonged	92.9	96	11700191 (2), 7703488 (2), 1331349 (1), 8826562 (1) (see all 83)
coagulopathy	89.9	123	8192064 (2), 17160994 (2), 19444412 (2), 1550472 (1) (see all 99)
hypoprothrombinemias	87.7	85	9863703 (4), 14629473 (4), 19598065 (4), 11241228 (3) (see all 45)
thrombophilia	87.1	93	9219324 (2), 16256098 (2), 8171409 (1), 9238178 (1) (see all 83)
bleeding	85.3	532	8402023 (3), 8259040 (3), 2383699 (3), 19444412 (3) (see all 99)
thrombosis	84.1	133	10744139 (4), 10974339 (2), 16231514 (2), 17205928 (2) (see all 99)
disseminated intravascular coagulation	82.2	29	16828603 (2), 11985056 (2), 10410587 (1), 12227006 (1) (see all 27)
dysprothrombinemia	81.1	5	1334372 (2), 11341500 (1), 15039280 (1), 9490687 (1)
vitamin k deficiency	80.8	28	2277030 (2), 11338219 (1), 11787707 (1), 10870812 (1) (see all 23)
venous thrombosis	80.7	87	8339409 (3), 17059428 (3), 9364981 (3), 12871361 (2) (see all 70)

GeneTests: F2

Prothrombin Thrombophilia

Genetic Association Database (GAD): F2
Human Genome Epidemiology (HuGE) Navigator: F2 (697 documents)

Export disorders for F2 gene to outside databases

(in PubMed. Associations of this gene to articles via ¹Entrez Gene, ²UniProtKB/Swiss-Prot, ³HGNC, ⁴GAD, ⁵PharmGKB, ⁶HMDB, ⁷DrugBank, ⁸UniProtKB/TrEMBL, ⁹ Novoseek, and/or ¹⁰fRNAdb)
About This Section

PubMed articles for F2 gene, integrated from 9 sources (see all 4314):
(articles sorted by number of sources associating them with F2)

Utopia: connect your pdf to the dynamic
world of online information

Meta-analysis of genetic studies in ischemic stroke: thirty-two genes involving approximately 18,000 cases and 58,000 controls. (PubMed id 15534175)^{1, 2, 4} Casas J.P.... Sharma P. (2004)
[Mutations of genes associated with thromboses in ischemic stroke in patients with primary antiphospholipid syndrome] (PubMed id 16320685)^{1, 4, 9} Kalashnikova L.A....Nasonov E.L. (2005)
A whole-blood homogeneous assay for the multiplex detection of the factor V G1691A and the prothrombin G20210A mutations. (PubMed id 16006096)^{1, 4, 9} Hobson-Peters J. and Toye P. (2005)
[Screening for pre-eclampsia in a low-risk population at 24 weeks: uterine artery Doppler flow velocimetry and genetic variants of factor V, prothrombin and methylenetetrahydrofolate reductase] (PubMed id 15531855)^{1, 4, 9} Driul L....Marchesoni D. (2004)
Pregnancy-associated venous thromboembolism (VTE) in combined heterozygous factor V Leiden (FVL) and prothrombin (FII) 20210 A mutation and in heterozygous FII single gene mutation alone. (PubMed id 14531916)^{1, 4, 9} Samama M.M....Conard J. (2003)
The platelet glycoprotein Ia/IIa gene polymorphism C807T/G873A: a novel risk factor for retinal vein occlusion. (PubMed id 12928694)^{1, 4, 9} Dodson P.M....Fegan C. (2003)
Prothrombin Salakta: substitution of glutamic acid-466 by alanine reduces the fibrinogen clotting activity and the esterase activity. (PubMed id 1354985)^{1, 2, 9} Miyata T....Iwanaga S. (1992)
Risk of cerebral venous thrombosis and novel gene polymorphisms of the coagulation and fibrinolytic systems. (PubMed id 16155788)^{1, 4, 9} Lichy C....Grau A. (2006)
A case control study on the contribution of factor V-Leiden, prothrombin G20210A, and MTHFR C677T mutations to the genetic susceptibility of deep venous thrombosis. (PubMed id 16082606)^{1, 4, 9} Almawi W.Y....Irani-Hakime N. (2005)
[Frequency of prothrombin gene G20210A variant in the 3'-untranslated region in Zhuang ethnic Chinese] (PubMed id 15952132)^{1, 4, 9} Chang J.H....Zhang G.S. (2005)

(in PubMed, OMIM, and NCBI Bookshelf)
About This Section

		AND	OR
Aliases
Disorders
Free Text

Query String		PubMed OMIM NCBI Bookshelf
	(Note: In FireFox, select the above section and copy using Ctrl-C)

(According to Entrez Gene, HGNC, AceView, euGenes, Ensembl, miRBase, ECgene, Kegg, and/or H-InvDB)
About This Section

Entrez Gene: 2147	HGNC: 3535	AceView: F2	Ensembl:ENSG00000180210	euGenes: HUgn2147
ECgene: F2	Kegg: 2147	H-InvDB: F2

(According to HUGE)
About This Section

(According to PharmGKB, ATLAS, HORDE, IMGT, LEIDEN, UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL,
Wikipedia and/or GeneReviews via UniProtKB/Swiss-Prot)
About This Section

Name	Description
PharmGKB entry for F2	Pharmacogenomics, SNPs, Pathways
ATLAS Chromosomes in Cancer entry for F2	Genetics and Cytogenetics in Oncology and Haematology
Wikipedia	http://en.wikipedia.org/wiki/Thrombin
GeneReviews	http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/F2
SeattleSNPs	http://pga.gs.washington.edu/data/f2/

Intellectual Property for F2 gene
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Patent Information for F2 gene:
Search GeneIP for patents involving F2

GeneCards and IP:
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F2 Gene

coagulation factor II (thrombin)

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PT PROLONGED
Pregnancy loss
Hemorrhagic diseases
ABNORMAL PLATELETS
Hepatitis Chronic
sepsis
SCOTT SYNDROME
coagulopathy
Hepatitis E Acute
GASTROINTESTINAL BLEEDING
Hypersplenism
Antithrombin III Deficiency
Factor VII Deficiency
Liver diseases
Antiphospholipid Syndrome
PULMONARY THROMBOSIS
Deep vein thrombosis
Hypofibrinogenemia
Cholestasis
BILIARY CIRRHOSIS PRIMARY
ENCEPHALOPATHY
Thrombocytopenia
CLOTTING TIME INCREASED
HEPATITIS ACUTE VIRAL
Coagulation Factor Deficiency
HEPATITIS FULMINANT
Hepatitis B Chronic
Esophageal Varices
Alcoholic Cirrhosis
PARTIAL THROMBOPLASTIN TIME PROLONGED
ARTERIAL THROMBOSIS
Protein C Deficiency
Prothrombin Thrombophilia
Liver Failure
Hepatitis
Liver Failure Acute
Hepatitis B
Hepatitis Alcoholic
LIVER DAMAGE
bacterial peritonitis
Hepatitis Autoimmune
Bernard-Soulier Syndrome
Thrombosis
Hepatic Failure Fulminant
Liver Cirrhosis
CEREBRAL VENOUS THROMBOSIS
Viral hepatitis
Disseminated Intravascular Coagulation
Preeclampsia
Hepatitis C
Thrombocytosis
Cirrhosis
APC Resistance
Hepatitis A Acute
Venous Thrombosis
Liver Fibrosis
Atrial Fibrillation
Hepatic Encephalopathy
Factor X Deficiency
hereditary factor VII deficiency
Ecchymosis
Miscarriage Recurrent
hypoalbuminemia
HEPATOCELLULAR CARCINOMA
Dysfibrinogenemia
BLEEDING TENDENCY
Intracranial Hemorrhages
Factor XI Deficiency
Inherited Coagulation Disorders
Hepatorenal Syndrome
Hypoprothrombinemias
Portal vein thrombosis
Hypertension Portal
von Willebrand Disease
Ascites
Dysprothrombinemia
Protein S Deficiency
Hemophilia A
Liver Dysfunction
Liver Diseases Alcoholic
Bleeding
Afibrinogenemia
Vitamin K Deficiency
Hepatitis C Chronic
Hepatic Coma
Blood Loss Postoperative
Hematoma
Thrombophilia
STROKE
PROLONGED BLEEDING TIME
FUNCTION LIVER ABNORMAL
acute alcoholic hepatitis
Hemophilia B
Hepatomegaly
Pulmonary Embolism
chronic liver disease
Hyperbilirubinemia
Thromboembolism
Lupus Erythematosus Systemic

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F2 Gene

coagulation factor II (thrombin)

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