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FLASH GENE

Symbol

CUBN

contributors: mct - updated : 12-12-2018

HGNC name	cubilin (intrinsic factor-cobalamin receptor)
HGNC id	2548

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

Corresponding disease	MGA2 juvenile megaloblastic anemia
Location	10p13      Physical location : 16.865.965 - 17.171.816
Synonym name	cubilin
	intrinsic factor-vitamin B12 receptor
Synonym symbol(s)	GIFR, IFCR, GP280, FLJ90055, FLJ90747, MGA1

DNA

TYPE	functioning gene
STRUCTURE	306.53 kb     68 Exon(s)

10 Kb 5' upstream gene genomic sequence study

MAPPING

cloned

Y

linked

N

status

provisional

Map	pter - D10S1653 - D10S1763 - D10S1661 - D10S674 - D10S1477 - D10S1476 - [D10S504 - CUBN - D10S1714 ] - D10S548 - cen
Authors	Aminoff (99)
Text	[MGA1 ]

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_001081 68 - 11933 NP_001072 - 3623 - -

EXPRESSION

Type

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Reproductive male system testis       Mus musculus Adult   male system testis       Mus musculus Fetal Urinary kidney nephron renal capsule glomerulus   Homo sapiens   kidney tubule convoluted tubule proximal tubule highly Homo sapiens

cells

System Cell Pubmed Species Stage Rna symbol Reproductive spermatid Mus musculus Adult Reproductive spermatid Mus musculus Fetal Reproductive spermatocyte Mus musculus Fetal Reproductive spermatogonia Mus musculus Fetal Urinary podocyte Homo sapiens

cell lineage

cell lines

fluid/secretion

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	eight EGF repeats followed by 27 CUB domains
	two distinct ligand binding domains(for IF-CBL and albumin)
	lacking a transmembrane domain but anchoring to apical membranes by forming complexes with AMN or Megalin

HOMOLOGY

interspecies

homolog to rattus Cubilin

Homologene

FAMILY

papain cysteine protease family

CATEGORY

receptor membrane , transport

SUBCELLULAR LOCALIZATION	plasma membrane
	intracellular
	intracellular,cytoplasm,organelle,endoplasmic reticulum
	intracellular,cytoplasm,organelle,Golgi
	intracellular,cytoplasm,cytosolic,vesicle
text	colocalizing with megalin (LRP2) in the kidney proximal tubule

basic FUNCTION	multiligand receptor for cobalamin, iron and protein
	facilitating the endocytic process by sequestering steroid-multiligand complexes on the cell surface before megalin-mediated internalization of te cubilin-bound ligand
	also high affinity apoprotein APO A-1 receptor facilitating endocytosis of high-density lipoprotein (HDL)
	with LRP2, are multifunctional endocytotic receptors expressed in many absorptive epithelia
	role for cubilin as a drug receptor for aminoglycosides and possibly other ototoxic substances
	multiligand endocytic receptor critical for the intestinal absorption of vitamin B12 and renal protein reabsorption
	is a receptor for vitamins and various protein ligands
	potential role of CUBN in endocytosis during early spermiogenesis
	may likely participate in the endocytotic uptake of nutrients in germ cells and somatic cells

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

endocytosis transport

PATHWAY

metabolism

signaling

a component

forming a complex (cubam) with AMN (amnionless) directing subcellular localization and endocytosis of cubilin with its ligand

INTERACTION

DNA

RNA

small molecule

protein	interacting with LRP2
	FGF8, a key mediator of cell survival, migration, proliferation, and patterning in the developing head, is a high affinity ligand for CUBN
	plasma membrane binding of FGF8, and most likely of the FGF8 family members FGF17 and FGF18, to CUBN improves Fgf ligand endocytosis and availability to FgfRs, thus modulating Fgf signaling activity
	LRP2 and CUBN may be important in human maternal-fetal transfer, and they increase across gestation to facilitate this function
	CUBN functions as a multi-ligand receptor by binding to the transmembrane protein, AMN and AMN -mediated glycosylation is crucial for cell surface targeting of CUBN in renal and intestinal cells
	CUBN-FGF8 interaction may be relevant in human pathology, including in cancer progression, heart or neural tube defects

cell & other

REGULATION

ASSOCIATED DISORDERS

corresponding disease(s)

MGA2

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function constitutional       loss of function leads to urinary loss of albumin and APOA1

Susceptibility

to diabetes-associated end stage renal disease to albuminuria

Variant & Polymorphism SNP	cubilin rare variant associated with diabetes-associated end stage renal disease
	missense CUBN variant associating with levels of albuminuria in both the general population and in individuals with diabetes

Candidate gene
Marker
Therapy target
	System Type Disorder Pubmed miscelleaneous urinary chronic kidney disease therapeutic increase of renal cubilin expression might reduce proteinuria and increase blood levels of albumin and HDL

ANIMAL & CELL MODELS

cubilin HT mice displayed significantly decreased blood levels of albumin, ApoA1, and HDL