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FLASH GENE

Symbol

COL4A3BP

contributors: mct/npt/pgu - updated : 08-03-2017

HGNC name	collagen, type IV, alpha 3 (Goodpasture antigen) binding protein
HGNC id	2205

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	a N terminal pleckstrin homology domain, a phosphoinositide-binding pleckstrin homology (PH) domain for Golgi-targeting , and basic groove in the PH domain plays a critical role in the Golgi recognition
	a short peptide motif named FFAT, which associates with the ER-resident membrane protein VAPA, VAPB
	a serine rich motif (variant 1)
	a C-terminal steroidogenic acute regulatory protein-related lipid transfer (START) domain, and for intermembrane transfer of ceramide , and PH and START domains are both indispensable for the COL4A3BP ceramide transport activity

HOMOLOGY

Homologene

FAMILY

CATEGORY

immunity/defense

SUBCELLULAR LOCALIZATION	extracellular
	intracellular
	intracellular,cytoplasm,organelle,mitochondria
	intracellular,cytoplasm,organelle,endoplasmic reticulum
	intracellular,cytoplasm,organelle,Golgi
	intracellular,cytoplasm,cytosolic
	intracellular,nucleus,nucleoplasm
text	is found in plasma and in the extracellular matrix

basic FUNCTION	protein serine/threonine kinase II
	phosphorylating the Goodpasture antigen (COL4A3)
	mediating nonvesicular transfer of ceramide from the endoplasmic reticulum to the Golgi complex
	critical role for protein kinase D activation and protein kinase D-dependent protein cargo transport to the plasma membrane
	cooperative control of its functionally distinct domains is a novel molecular event to regulate the intracellular trafficking of ceramide
	may serves as transporter of ceramide between the endoplasmic reticulum and the Golgi apparatus
	implicated in a multicompartmental program for protein secretion including phosphorylation and regulation of protein molecular/supramolecular organization and interorganelle ceramide trafficking and regulation of protein cargo transport to the plasma membrane
	plays an important role in central nervous system neuron function
	orchestrate a biological program that regulates protein folding and secretion
	is responsible for the non-vesicular trafficking of ceramide between the endoplasmic reticulum and Golgi
	exportable non-conventional Ser/Thr kinase that regulating glomerular basement membrane collagen organization
	directs myofibril formation, an observation that expands its reported role in supramolecular organization of structural proteins to the intracellular compartment
	it is likely that during cellular stress, disassembly of Golgi structure together with inactivation of COL4A3BP by caspases causes a reduction in ceramide trafficking and SM (sphingomyelin) synthesis, and could contribute to the cellular response to pro-apoptotic stress
	contribute to deterioration of mitochondrial structure and function in aging oocytes
	role of COL4A3BP in innate immunity, especially in the clearance of apoptotic cells
	mediates the inter-organelle transport of ceramide for the synthesis of sphingomyelin, presumably through endoplasmic reticulum (ER)-Golgi membrane contact sites
	transfers ceramide from the endoplasmic reticulum (ER) to the Golgi complex

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

immunity/defense

text	autoimmune response

PATHWAY

metabolism

signaling

a component

INTERACTION

DNA

RNA

small molecule

protein	binding the C terminal, non collagenous region of COL4A3
	cholesterol, 25-hydroxycholesterol, phosphatidylcholine, phosphatidylethanolamine and ceramides are ligands for STAR/STARD3/STARD5, STARD5, PCTP/STARD10, STARD10 and COL4A3BP, respectively
	targets FILIP1L, which binds to myosin and promotes its myofibrillar assembly
	is a nonconventional Ser/Thr kinase for basement membrane type IV collagen
	COL4A3BP specifically binds APCS in its physiological conformations, pentamers and decamers, and START domain in COL4A3BP is important for this interaction
	VAPA, VAPB are endoplasmic reticulum (ER)-resident integral membrane protein that controls a nonvesicular mode of ceramide and cholesterol transfer from the ER to the Golgi complex by interacting with COL4A3BP and oxysterol-binding protein (OSBP), respectively

cell & other

REGULATION

Other

phosphorylation of COL4A3BP at the FFAT motif-adjacent serine affected its affinity for VAPA, VAPB, which may regulate the inter-organelle trafficking of ceramide in response to the perturbation of cellular sphingomyelin and/or other sphingolipids

ASSOCIATED DISORDERS

corresponding disease(s)

MRD34

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function constitutional       loss of function can attenuate a key metabolic protective mechanism against ceramide-induced apoptosis in keratinocytes constitutional       loss of function compromises organelle function and leads to senescence in primary cells

Susceptibility

Variant & Polymorphism

Candidate gene

Marker

Therapy target

ANIMAL & CELL MODELS

Cert deficient embryos die from cardiac failure due to defective organogenesis, but not due to ceramide induced apoptotic or necrotic cell death