Homo sapiens complex locus F5, encoding coagulation factor V (proaccelerin, labile factor).
SUMMARY back to top
RefSeq summary
[F5F5] This gene encodes an essential cofactor of the blood coagulation cascade. This factor circulates in plasma, and is converted to the active form by the release of the activation peptide by thrombin during coagulation. This generates a heavy chain and a light chain which are held together by calcium ions. The activated protein is a cofactor that participates with activated coagulation factor X to activate prothrombin to thrombin. Defects in this gene result in either an autosomal recessive hemorrhagic diathesis or an autosomal dominant form of thrombophilia, which is known as activated protein C resistance. [provided by RefSeq].

RefSeq annotates one representative transcript (NM included in AceView variant.a), but Homo sapiens cDNA sequences in GenBank, dbEST, Trace and SRA, filtered against clone rearrangements, coaligned on the genome and clustered in a minimal non-redundant way by the manually supervised AceView program, support at least 5 spliced variants.

AceView synopsis, each blue text links to tables and details
Note that this locus is complex: it appears to produce several proteins with no sequence overlap.
Expression: According to AceView, this gene is expressed at high level, 3.5 times the average gene in this release. The sequence of this gene is defined by 399 GenBank accessions from 385 cDNA clones, some from placenta (seen 33 times), liver and spleen (25), lung (22), carcinoid (21), placenta normal (12), eye (9), liver (9) and 30 other tissues. We annotate structural defects or features in 10 cDNA clones.
Alternative mRNA variants and regulation: The gene contains 27 distinct introns (25 gt-ag, 2 gc-ag). Transcription produces 5 alternatively spliced mRNAs. There are 3 probable alternative promotors, 3 non overlapping alternative last exons and 4 validated alternative polyadenylation sites (see the diagram). The mRNAs appear to differ by truncation of the 5' end, truncation of the 3' end, presence or absence of a cassette exon, overlapping exons with different boundaries, splicing versus retention of one intron.
Note that mRNA .bAug10 was found in vivo, although it is a predicted target of nonsense mediated mRNA decay (NMD).
Efficacy of translation may be reduced by the presence of a shorter translated product (uORF) initiating at an AUG upstream of the main open reading frame (in variant bAug10).
Function: There are 978 articles specifically referring to this gene in PubMed. Functionally, the gene has been tested for association to diseases (OMIM: Budd-Chiari syndrome; Factor V deficiency; stroke, ischemic; thrombophilia due to activated protein c resistance; Other sources: Abortion, Spontaneous; Abruptio Placentae; Acute Disease; Amaurosis Fugax; Atherosclerosis and 60 others), proposed to participate in pathways (Complement and coagulation cascades, Extrinsic Prothrombin Activation Pathway, Intrinsic Prothrombin Activation Pathway) and processes (blood coagulation, cell adhesion, oxidation reduction). Proteins are expected to have molecular functions (copper ion binding, metal ion binding, oxidoreductase activity) and to localize in various compartments (extracellular space, nucleus). Putative protein interactors have been described (CALR, CSNK2A1, CTSG, ELANE, F2, F5, F10, MMRN1, PROC, PROS1, SERPINA4ANDSERPINA5ANDSERPINA3).
Protein coding potential: 4 spliced mRNAs putatively encode good proteins, altogether 4 different isoforms (3 complete, 1 partial), some containing domains Multicopper oxidase, F5/8 type C domain, Coagulation Factor V LSPD Repeat [Pfam], a second peroximal domain [Psort2]; 1 of the 3 complete proteins appears to be secreted. The remaining mRNA variant (spliced) appears not to encode a good protein. Finally proteins from this gene may be modulated by acetylation; phosphorylation, as detailed at PhosphoSite.

Please quote: AceView: a comprehensive cDNA-supported gene and transcripts annotation, Genome Biology 2006, 7(Suppl 1):S12.
Map on chromosome 1, links to other databases and other names
Map: This gene F5 maps on chromosome 1, at 1q23 according to Entrez Gene. In AceView, it covers 74.68 kb, from 169555862 to 169481184 (NCBI 37, August 2010), on the reverse strand.
Links to: manual annotations from OMIM_600880, OMIM_601367, OMIM_188055, OMIM_227400, GAD, KEGG_04610, PhosphoSite, the SNP view, gene overviews from Entrez Gene 2153, GeneCards, expression data from ECgene, UniGene, molecular and other annotations from UCSC. The previous AceView annotation is here.
Other names: The gene is also known as F5, FVL or PCCF, LOC2153. It has been described as coagulation factor V, factor V Leiden, OTTHUMP00000032548, proaccelerin, labile factor, activated protein c cofactor, coagulation factor V jinjiang A2 domain.
Closest AceView homologs in other species ?
The closest mouse gene, according to BlastP, is the AceView gene F5 (e=0.0).
The closest C.elegans gene, according to BlastP, is the AceView/WormGene ddr-1 (e=3 10-08), which may contain interesting functional annotation.
The closest A.thaliana genes, according to BlastP, are the AceView genes LAC12 (e=0.028), IRX12\/LAC4 (e=0.052), LAC11 (e=0.094), LAC3 (e=0.22), SKS16 (e=0.43), LAC17 (e=0.65), which may contain interesting functional annotation
RNA_seq discoveries back to top
Expression/conservation in primates tissues evaluated by cross-mapping to human. back to top
RNA-seq gene expression profile across 16 selected tissues from the Non-Human Primates Reference Transcriptome Resource (link to NHPRTR project).
- Primates: Apes (HUM: Human (Illumina BodyMap 2), CHP: Chimpanzee), Old World monkeys (PTM: Pig-Tailed Macaque, JMI Japanese Macaque, RMI Rhesus Macaque Indian, RMC Rhesus Macaque Chinese, CMM Cynomolgus Macaque Mauritian, CMC Cynomolgus Macaque Chinese, BAB Olive Baboon, SMY Sooty Mangabey); New World monkeys (MST common Marmoset, SQM Squirrel Monkey, OWL Owl Monkey); and Lemurs (MLM Mouse Lemur, RTL Ring-Tailed Lemur).
- The level for significantly expressed genes is color coded in 8 equal sized bins (light to dark green). Light gray is for weak not-accurately measured expression (2 to 8 reads above intergenic background); dark gray for no expression or no sequence conservation (0 read in gene). The plot to the right shows the distribution of measured expression values in all tissues for all genes (blue) and for this gene (green), in Magic index = log2(1000 sFPKM).
You may also examine the strand-specific genome coverage plots on the experimental AceView/Magic hub at UCSC, by tissue or by species. Tracks may be slow to load; please reload if some tracks come up yellow-greenish, and thanks to UCSC for the great work!.
          Complete gene on genome diagram: back to top
Please choose between the zoomable GIF version., and the Flash version.
This diagram shows in true scale the gene on the genome, the mRNAs and the cDNA clones.
Compact gene diagram back to top
Alternative mRNAs are shown aligned from 5' to 3' on a virtual genome where introns have been shrunk to a minimal length. Exon size is proportional to length, intron height reflects the number of cDNAs supporting each intron, the small numbers show the support of the introns in deep sequencing (with details in mouse-over) . Introns of the same color are identical, of different colors are different. 'Good proteins' are pink, partial or not-good proteins are yellow, uORFs are green. 5' cap or3' poly A flags show completeness of the transcript.
Sequences: click on the numbers to get the DNA back to top
mRNA variant mRNA matching the genome Best predicted protein 5' UTR 3' UTR uORF Upstream sequence Transcription
Downstream sequence
aAug10 9276 bp 2224 aa 238 bp 2363 bp 2kb possibly including promoter 74675 bp 1kb
bAug10 1714 bp 332 aa 414 bp 301 bp 183 bp 2kb probably including promoter 39993 bp 1kb
cAug10 713 bp 237 aa 2kb 764 bp 1kb
dAug10 596 bp 77 aa 215 bp 147 bp 45 bp 2kb possibly including promoter 1580 bp 1kb
eAug10 819 bp 34 aa 170 bp 544 bp 2kb 2775 bp 1kb

Gene neighbors and Navigator on chromosome 1q23 back to top
ZOOM IN                D:disease,C:conserved,I:interactions,R:regulation,P:publications        
Annotated mRNA diagrams back to top
Bibliography:               978 articles in PubMed back to top
? Gene Summary Gene on genome mRNA:.a, .b, .c, .d, .e Alternative mRNAs features, proteins, introns, exons, sequences Expression Tissue Function, regulation, related genes DCI

To mine knowledge about the gene, please click the 'Gene Summary' or the 'Function, regulation, related genes ' tab at the top of the page. The 'Gene Summary' page includes all we learnt about the gene, functional annotations of neighboring genes, maps, links to other sites and the bibliography. The 'Function, regulation, related genes ' page includes Diseases (D), Pathways, GO annotations, conserved domains (C), interactions (I) reference into function, and pointers to all genes with the same functional annotation.
To compare alternative variants, their summarized annotations, predicted proteins, introns and exons, or to access any sequence, click the 'Alternative mRNAs features' tab. To see a specific mRNA variant diagram, sequence and annotation, click the variant name in the 'mRNA' tab. To examine expression data from all cDNAs clustered in this gene by AceView, click the 'Expression tissue'.

If you know more about this gene, or found errors, please share your knowledge. Thank you !