Reactome | Defective F8 accelerates dissociation of the A2 domain

Defective F8 accelerates dissociation of the A2 domain

Stable Identifier

R-HSA-9672387

Type

Pathway

Species

Homo sapiens

Compartment

extracellular region

ReviewStatus

5/5

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Defective F8 accelerates dissociation of the A2 domain

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Retention of A2 polypeptide is required for normal stability of activated factor VIII (FVIIIa) and dissociation of A2 correlates with FVIIIa inactivation and consequent loss of FXase activity. Hemophilia A (HA)-associated mutations (R550H, A303E, S308L, N713I, R717W and R717L) within the predicted A1-A2 and A2-A3 interface are thought to disrupt potential intersubunit hydrogen bonds and have the molecular phenotype of increased rate of inactivation of FVIIIa due to increased rate of A2 subunit dissociation (Pipe SW et al. 1999; Hakeos WH et al. 2002)

Literature References

PubMed ID	Title	Journal	Year
9864159	Mild hemophilia A caused by increased rate of factor VIII A2 subunit dissociation: evidence for nonproteolytic inactivation of factor VIIIa in vivo Pipe, SW, Eickhorst, AN, McKinley, SH, Saenko, EL, Kaufman, RJ	Blood	1999
11157485	Hemophilia A mutations associated with 1-stage/2-stage activity discrepancy disrupt protein-protein interactions within the triplicated A domains of thrombin-activated factor VIIIa Pipe, SW, Saenko, EL, Eickhorst, AN, Kemball-Cook, G, Kaufman, RJ	Blood	2001

Participants

Events

Participates

as an event of

Defective factor VIII causes hemophilia A (Homo sapiens)

Disease

Name	Identifier	Synonyms
factor VIII deficiency	DOID:12134	Congenital factor VIII disorder, Subhemophilia, Hemophilia A

Cross References

Mondo

0010602

BioModels Database

BIOMD0000000951, BIOMD0000000340, BIOMD0000000336, BIOMD0000000339, BIOMD0000000338, BIOMD0000000335

Authored

Shamovsky, V (2019-09-09)

Reviewed

D'Eustachio, P (2020-01-09)

Zhang, B (2020-04-02)

Created

Shamovsky, V (2019-12-25)

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