Target Information
Target General Information | Top | |||||
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Target ID |
T37510
(Former ID: TTDS00204)
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Target Name |
Coagulation factor Va (F5)
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Synonyms |
Factor Va; F5
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Gene Name |
F5
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Target Type |
Successful target
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[1] | ||||
Disease | [+] 2 Target-related Diseases | + | ||||
1 | Cerebral ischaemia [ICD-11: 8B1Z] | |||||
2 | Sepsis [ICD-11: 1G40-1G41] | |||||
Function |
Central regulator of hemostasis. It serves as a critical cofactor for the prothrombinase activity of factor Xa that results in the activation of prothrombin to thrombin.
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UniProt ID | ||||||
Sequence |
MFPGCPRLWVLVVLGTSWVGWGSQGTEAAQLRQFYVAAQGISWSYRPEPTNSSLNLSVTS
FKKIVYREYEPYFKKEKPQSTISGLLGPTLYAEVGDIIKVHFKNKADKPLSIHPQGIRYS KLSEGASYLDHTFPAEKMDDAVAPGREYTYEWSISEDSGPTHDDPPCLTHIYYSHENLIE DFNSGLIGPLLICKKGTLTEGGTQKTFDKQIVLLFAVFDESKSWSQSSSLMYTVNGYVNG TMPDITVCAHDHISWHLLGMSSGPELFSIHFNGQVLEQNHHKVSAITLVSATSTTANMTV GPEGKWIISSLTPKHLQAGMQAYIDIKNCPKKTRNLKKITREQRRHMKRWEYFIAAEEVI WDYAPVIPANMDKKYRSQHLDNFSNQIGKHYKKVMYTQYEDESFTKHTVNPNMKEDGILG PIIRAQVRDTLKIVFKNMASRPYSIYPHGVTFSPYEDEVNSSFTSGRNNTMIRAVQPGET YTYKWNILEFDEPTENDAQCLTRPYYSDVDIMRDIASGLIGLLLICKSRSLDRRGIQRAA DIEQQAVFAVFDENKSWYLEDNINKFCENPDEVKRDDPKFYESNIMSTINGYVPESITTL GFCFDDTVQWHFCSVGTQNEILTIHFTGHSFIYGKRHEDTLTLFPMRGESVTVTMDNVGT WMLTSMNSSPRSKKLRLKFRDVKCIPDDDEDSYEIFEPPESTVMATRKMHDRLEPEDEES DADYDYQNRLAAALGIRSFRNSSLNQEEEEFNLTALALENGTEFVSSNTDIIVGSNYSSP SNISKFTVNNLAEPQKAPSHQQATTAGSPLRHLIGKNSVLNSSTAEHSSPYSEDPIEDPL QPDVTGIRLLSLGAGEFKSQEHAKHKGPKVERDQAAKHRFSWMKLLAHKVGRHLSQDTGS PSGMRPWEDLPSQDTGSPSRMRPWKDPPSDLLLLKQSNSSKILVGRWHLASEKGSYEIIQ DTDEDTAVNNWLISPQNASRAWGESTPLANKPGKQSGHPKFPRVRHKSLQVRQDGGKSRL KKSQFLIKTRKKKKEKHTHHAPLSPRTFHPLRSEAYNTFSERRLKHSLVLHKSNETSLPT DLNQTLPSMDFGWIASLPDHNQNSSNDTGQASCPPGLYQTVPPEEHYQTFPIQDPDQMHS TSDPSHRSSSPELSEMLEYDRSHKSFPTDISQMSPSSEHEVWQTVISPDLSQVTLSPELS QTNLSPDLSHTTLSPELIQRNLSPALGQMPISPDLSHTTLSPDLSHTTLSLDLSQTNLSP ELSQTNLSPALGQMPLSPDLSHTTLSLDFSQTNLSPELSHMTLSPELSQTNLSPALGQMP ISPDLSHTTLSLDFSQTNLSPELSQTNLSPALGQMPLSPDPSHTTLSLDLSQTNLSPELS QTNLSPDLSEMPLFADLSQIPLTPDLDQMTLSPDLGETDLSPNFGQMSLSPDLSQVTLSP DISDTTLLPDLSQISPPPDLDQIFYPSESSQSLLLQEFNESFPYPDLGQMPSPSSPTLND TFLSKEFNPLVIVGLSKDGTDYIEIIPKEEVQSSEDDYAEIDYVPYDDPYKTDVRTNINS SRDPDNIAAWYLRSNNGNRRNYYIAAEEISWDYSEFVQRETDIEDSDDIPEDTTYKKVVF RKYLDSTFTKRDPRGEYEEHLGILGPIIRAEVDDVIQVRFKNLASRPYSLHAHGLSYEKS SEGKTYEDDSPEWFKEDNAVQPNSSYTYVWHATERSGPESPGSACRAWAYYSAVNPEKDI HSGLIGPLLICQKGILHKDSNMPMDMREFVLLFMTFDEKKSWYYEKKSRSSWRLTSSEMK KSHEFHAINGMIYSLPGLKMYEQEWVRLHLLNIGGSQDIHVVHFHGQTLLENGNKQHQLG VWPLLPGSFKTLEMKASKPGWWLLNTEVGENQRAGMQTPFLIMDRDCRMPMGLSTGIISD SQIKASEFLGYWEPRLARLNNGGSYNAWSVEKLAAEFASKPWIQVDMQKEVIITGIQTQG AKHYLKSCYTTEFYVAYSSNQINWQIFKGNSTRNVMYFNGNSDASTIKENQFDPPIVARY IRISPTRAYNRPTLRLELQGCEVNGCSTPLGMENGKIENKQITASSFKKSWWGDYWEPFR ARLNAQGRVNAWQAKANNNKQWLEIDLLKIKKITAIITQGCKSLSSEMYVKSYTIHYSEQ GVEWKPYRLKSSMVDKIFEGNTNTKGHVKNFFNPPIISRFIRVIPKTWNQSIALRLELFG CDIY Click to Show/Hide
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3D Structure | Click to Show 3D Structure of This Target | AlphaFold |
Drugs and Modes of Action | Top | |||||
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Approved Drug(s) | [+] 1 Approved Drugs | + | ||||
1 | Drotrecogin alfa | Drug Info | Approved | Cerebrovascular ischaemia | [2], [3], [4] | |
Mode of Action | [+] 1 Modes of Action | + | ||||
Inhibitor | [+] 3 Inhibitor drugs | + | ||||
1 | Drotrecogin alfa | Drug Info | [1] | |||
2 | Phenylmercury | Drug Info | [5] | |||
3 | RAZAXABAN | Drug Info | [6] |
Cell-based Target Expression Variations | Top | |||||
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Cell-based Target Expression Variations |
Drug Binding Sites of Target | Top | |||||
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Ligand Name: Phenylmercury | Ligand Info | |||||
Structure Description | CRYSTAL STRUCTURE OF THE C2 DOMAIN OF HUMAN COAGULATION FACTOR V: COMPLEX WITH PHENYLMERCURY | PDB:1CZS | ||||
Method | X-ray diffraction | Resolution | 1.90 Å | Mutation | No | [7] |
PDB Sequence |
GCSTPLGMEN
9 GKIENKQITA19 SSFKKSWWGD29 YWEPFRARLN39 AQGRVNAWQA49 KANNNKQWLE 59 IDLLKIKKIT69 AIITQGCKSL79 SSEMYVKSYT89 IHYSEQGVEW99 KPYRLKSSMV 109 DKIFEGNTNT119 KGHVKNFFNP129 PIISRFIRVI139 PKTWNQSITL149 RLELFGCDIY 159
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Click to View More Binding Site Information of This Target with Different Ligands |
Different Human System Profiles of Target | Top |
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Human Similarity Proteins
of target is determined by comparing the sequence similarity of all human proteins with the target based on BLAST. The similarity proteins for a target are defined as the proteins with E-value < 0.005 and outside the protein families of the target.
A target that has fewer human similarity proteins outside its family is commonly regarded to possess a greater capacity to avoid undesired interactions and thus increase the possibility of finding successful drugs
(Brief Bioinform, 21: 649-662, 2020).
Human Tissue Distribution
of target is determined from a proteomics study that quantified more than 12,000 genes across 32 normal human tissues. Tissue Specificity (TS) score was used to define the enrichment of target across tissues.
The distribution of targets among different tissues or organs need to be taken into consideration when assessing the target druggability, as it is generally accepted that the wider the target distribution, the greater the concern over potential adverse effects
(Nat Rev Drug Discov, 20: 64-81, 2021).
Human Pathway Affiliation
of target is determined by the life-essential pathways provided on KEGG database. The target-affiliated pathways were defined based on the following two criteria (a) the pathways of the studied target should be life-essential for both healthy individuals and patients, and (b) the studied target should occupy an upstream position in the pathways and therefore had the ability to regulate biological function.
Targets involved in a fewer pathways have greater likelihood to be successfully developed, while those associated with more human pathways increase the chance of undesirable interferences with other human processes
(Pharmacol Rev, 58: 259-279, 2006).
Biological Network Descriptors
of target is determined based on a human protein-protein interactions (PPI) network consisting of 9,309 proteins and 52,713 PPIs, which were with a high confidence score of ≥ 0.95 collected from STRING database.
The network properties of targets based on protein-protein interactions (PPIs) have been widely adopted for the assessment of target’s druggability. Proteins with high node degree tend to have a high impact on network function through multiple interactions, while proteins with high betweenness centrality are regarded to be central for communication in interaction networks and regulate the flow of signaling information
(Front Pharmacol, 9, 1245, 2018;
Curr Opin Struct Biol. 44:134-142, 2017).
Human Similarity Proteins
Human Tissue Distribution
Human Pathway Affiliation
Biological Network Descriptors
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Note:
If a protein has TS (tissue specficity) scores at least in one tissue >= 2.5, this protein is called tissue-enriched (including tissue-enriched-but-not-specific and tissue-specific). In the plots, the vertical lines are at thresholds 2.5 and 4.
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KEGG Pathway | Pathway ID | Affiliated Target | Pathway Map |
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Complement and coagulation cascades | hsa04610 | Affiliated Target |
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Class: Organismal Systems => Immune system | Pathway Hierarchy |
Degree | 4 | Degree centrality | 4.30E-04 | Betweenness centrality | 1.57E-05 |
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Closeness centrality | 1.78E-01 | Radiality | 1.29E+01 | Clustering coefficient | 5.00E-01 |
Neighborhood connectivity | 1.53E+01 | Topological coefficient | 3.57E-01 | Eccentricity | 13 |
Download | Click to Download the Full PPI Network of This Target | ||||
Chemical Structure based Activity Landscape of Target | Top |
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Target Poor or Non Binders | Top | |||||
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Target Poor or Non Binders |
Target Profiles in Patients | Top | |||||
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Target Expression Profile (TEP) |
Target Affiliated Biological Pathways | Top | |||||
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KEGG Pathway | [+] 1 KEGG Pathways | + | ||||
1 | Complement and coagulation cascades | |||||
Pathwhiz Pathway | [+] 1 Pathwhiz Pathways | + | ||||
1 | Coagulation | |||||
Reactome | [+] 4 Reactome Pathways | + | ||||
1 | Platelet degranulation | |||||
2 | Common Pathway of Fibrin Clot Formation | |||||
3 | COPII (Coat Protein 2) Mediated Vesicle Transport | |||||
4 | Cargo concentration in the ER | |||||
WikiPathways | [+] 3 WikiPathways | + | ||||
1 | Complement and Coagulation Cascades | |||||
2 | Blood Clotting Cascade | |||||
3 | Formation of Fibrin Clot (Clotting Cascade) |
Target-Related Models and Studies | Top | |||||
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Target Validation |
References | Top | |||||
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REF 1 | Protein C in critical illness. Am J Health Syst Pharm. 2009 Jun 15;66(12):1089-96. | |||||
REF 2 | URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 6788). | |||||
REF 3 | Natural products as sources of new drugs over the last 25 years. J Nat Prod. 2007 Mar;70(3):461-77. | |||||
REF 4 | Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015 | |||||
REF 5 | How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6. | |||||
REF 6 | Aminobenzisoxazoles with biaryl P4 moieties as potent, selective, and orally bioavailable factor Xa inhibitors. Bioorg Med Chem Lett. 2006 Apr 1;16(7):1795-8. | |||||
REF 7 | Crystal structures of the membrane-binding C2 domain of human coagulation factor V. Nature. 1999 Nov 25;402(6760):434-9. |
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