MCFD2

Protein identityUniProt · HPA

UniProt accession

Q8NI22

Gene

MCFD2

Ensembl

ENSG00000180398

Chromosome

2

Canonical length

146 aa

Protein class

Disease related genes, Human disease related genes, Plasma proteins, Potential drug targets, Predicted intracellular proteins, Transporters

Secretome location

Intracellular and membrane

OverviewNCBI Gene

This gene encodes a soluble luminal protein with two calmodulin-like EF-hand motifs at its C-terminus. This protein forms a complex with LMAN1 (lectin mannose binding protein 1; also known as ERGIC-53) that facilitates the transport of coagulation factors V (FV) and VIII (FVIII) from the endoplasmic reticulum to the Golgi apparatus via an endoplasmic reticulum Golgi intermediate compartment (ERGIC). Mutations in this gene cause combined deficiency of FV and FVIII (F5F8D); a rare autosomal recessive bleeding disorder characterized by mild to moderate bleeding and coordinate reduction in plasma FV and FVIII levels. This protein has also been shown to maintain stem cell potential in adult central nervous system and is a marker for testicular germ cell tumors. The 3' UTR of this gene contains a transposon-like human repeat element named 'THE 1'. A processed RNA pseudogene of this gene is on chromosome 6p22.1. Alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Apr 2016]

Canonical amino-acid sequenceUniProt

146 residues, UniProt reviewed canonical sequence.

>Q8NI22|MCFD2
     1  MTMRSLLRTP FLCGLLWAFC APGARAEEPA ASFSQPGSMG LDKNTVHDQE HIMEHLEGVI
    61  NKPEAEMSPQ ELQLHYFKMH DYDGNNLLDG LELSTAITHV HKEEGSEQAP LMSEDELINI
   121  IDGVLRDDDK NNDGYIDYAE FAKSLQ

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against MCFD2 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Intracellular

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.43

Highest tissue expression

146 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about MCFD2.

Disease | AllUniProt

Conditions MCFD2 is implicated in, by any mechanism.

• Factor V and factor VIII combined deficiency 2 (F5F8D2) MIM:613625

Disease | GeneticClinVar

12 pathogenic / likely-pathogenic of 174 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Factor 5 and Factor VIII, combined deficiency of, 2
• Factor V and factor VIII, combined deficiency of, type 1
• MCFD2-related disorder
• Reduced quantity of Von Willebrand factor
• Reduced von Willebrand factor activity

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

1.27

gnomAD pLI

0.1

gnomAD missense Z

-0.58

DepMap mean gene effect

-0.01

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 6% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• gene expression
• protein transport
• vesicle-mediated transport

Molecular functions

• calcium ion binding

Cellular components

• endoplasmic reticulum membrane
• endoplasmic reticulum-Golgi intermediate compartment membrane
• ER to Golgi transport vesicle membrane
• Golgi apparatus

Protein domainsUniProt · Pfam · InterPro

• EF-hand domain
• EF-hand domain pair
• EF-Hand 1, calcium-binding site
• Multiple coagulation factor deficiency protein 2-like
• EF-hand domain pair

KeywordsUniProt

• Calcium
• Endoplasmic reticulum
• ER-Golgi transport
• Golgi apparatus
• Metal-binding
• Phosphoprotein
• Protein transport
• Repeat
• Signal
• Transport

InteractionsUniProt · HPA

Protein binding partners of MCFD2 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• LMAN1
• COPE