The reference OMIM entry for this protein is 607788

Multiple coagulation factor deficiency protein 2; mcfd2

CLONING

Deka et al. (1988) cloned a gene they designated T+ due to the presence of a transposon-like human repeat element (THE1) in the unusually long 3-prime untranslated region. The deduced protein contains 79 amino acids and shares significant similarity with troponin-c (see 191040) and calmodulin (see 114180) within a conserved 12-amino acid motif. Deka et al. (1988) also identified a transcribed pseudogene, which they called T-, that contains an interspersed Alu repeat instead of the THE1 element. Northern blot analysis of tissues and cell lines detected major transcripts of 4.0, 3.0, 1.9, and 0.85 kb. A 2.5-kb transcript was also detected in a neuroblastoma sample. The 4.0- and 1.9-kb transcripts were present in HeLa cell polysome fractions, leading the authors to conclude that they are likely translated. Using a positional cloning strategy, Zhang et al. (2003) searched for the gene responsible for the form of combined deficiency of factor V and factor VIII that mapped to the region 2p21-p16.3 (F5F8D2; 613625). The candidate genetic interval of approximately 2.4 Mb in the draft human genome sequence contained about 20 known and predicted genes and a number of partial ESTs, none of which had sequence homology to known components of the endoplasmic reticulum (ER) or Golgi. Direct DNA sequencing of individual candidate genes identified mutations in the predicted exons and intron-exon junctions of a partial cDNA, HUMTRANSC, previously reported based on its unusually long 3-prime untranslated region containing a THE1. This gene, renamed MCFD2 (multiple coagulation factor deficiency protein-2) by Zhang et al. (2003), contains a 145-amino acid open reading frame and is identical to the T+ gene reported by Deka et al. (1988). Notable features include a predicted signal peptide at the N terminus and 2 calmodulin-like EF-hands for putative calcium binding at the C terminus. Northern blot analysis showed that MCFD2 is expressed in multiple tissues.

GENE FUNCTION

Zhang et al. (2003) showed that MCFD2 and the LMAN1 gene, which is mutant in the most common form of F5F8D (F5F8D1; 227300), colocalize in the endoplasmic reticulum-Golgi intermediate compartment (ERGIC) and that MCFD2 is localized to the ERGIC through a direct, calcium-dependent interaction with LMAN1.

GENE STRUCTURE

Zhang et al. (2003) determined that the MCFD2 gene contains 4 exons encompassing approximately 19 kb of genomic DNA. Deka et al. (1988) determined that the promoter region of the MCFD2 gene contains a CAAT element and a TATA element. The THE1 element is oriented in the reverse direction of the gene.

MAPPING

Zhang et al. (2003) identified the MCFD2 gene within a critical region on chromosome 2p21-p16.3 associated with F5F8D.

MOLECULAR GENETICS

Zhang et al. (2003) identified 7 distinct mutations in the MCFD2 gene accounting for F5F8D in 9 of 12 families. The affected individual in 1 of these families was 1 of the original F5F8D probands reported by Oeri et al. (1954). Most of the mutations resulted in a null allele with complete lack of protein expression (607788.0001-607788.0005). The other 2 mutations were missense (607788.0006-607788.0007). In vitro functional expression studies in HeLa cells showed that LMAN1 did not coimmunoprecipitate with missense mutant MCFD2. The results suggested an essential role for the second EF-hand of MCFD2 in the calcium-dependent interaction with LMAN1 and the subsequent function of t ... More on the omim web site

Subscribe to this protein entry history

Nov. 17, 2018: Protein entry updated
Automatic update: OMIM entry 607788 was added.

Oct. 19, 2018: Additional information
Initial protein addition to the database. This entry was referenced in Bryk and co-workers. (2017).