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FLASH GENE

Symbol

ABCB4

contributors: mct - updated : 28-06-2015

HGNC name	ATP-binding cassette, sub-family B (MDR/TAP), member 4
HGNC id	45

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

Corresponding disease	LPAC low phospholipid-associated cholelithiasis PFIC3 cholestasis progressive familial intrahepatic 3
Location	7q21.12      Physical location : 87.031.360 - 87.105.019
Synonym name	P glycoprotein 3
	mulidrug resistance 3
Synonym symbol(s)	PGY3, ABC21, MDR3, MDR2, PFIC-3, GBD1, MDR2/3
EC.number	3.6.3.44

DNA

TYPE	functioning gene
STRUCTURE	73.66 kb     28 Exon(s)

10 Kb 5' upstream gene genomic sequence study

regulatory sequence	Promoter (CAAT box)
	cytosine-phosphate-guanine/HTF
	Binding site   transcription factor
text structure	composed of GC-rich sequences and contains multiple putative SP1 binding sites
	a highly conserved farnesoid X receptor (FXR) response element in the distal region of the MDR3 promoter, and transcription of MDR3 can be trans-activated by FXR
	contains a CCAAT box with the sequence AGATCCAATGAC, which would be recognized by NFY.A, NFYB, NFYC

MAPPING

cloned

Y

linked

N

status

confirmed

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_000443 28 - 3967 NP_000434 140.6 1279 - 2004 15258199 NM_018849 28 splicing 3988 NP_061337 - 1286 - 2004 15258199 an alternate in-frame splice site in the 3' coding region NM_018850 27 splicing 3826 NP_061338 - 1232 - 2004 15258199 lacking an alternate in-frame exon

EXPRESSION

Type	restricted

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 Cardiovascular heart         Digestive liver         Homo sapiens Endocrine adrenal gland           pancreas         Reproductive male system testis

cells

System Cell Pubmed Species Stage Rna symbol Digestive hepatocyte Homo sapiens

cell lineage

cell lines

fluid/secretion

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	ABC transporter, traffic ATPase with two ATP binding
	two transmembrane (2TM) domains (2x6 segments), localized to the hepatocyte canalicular membrane

conjugated

GlycoP

HOMOLOGY

intraspecies

homolog to ABCB1

Homologene

FAMILY	ATP binding cassette superfamily
	subfamily B (MDR/TAP)

CATEGORY

transport carrier

SUBCELLULAR LOCALIZATION

plasma membrane

basic FUNCTION	involved in phosphatidylcholine translocation into the bile
	critical trans-locator for phospholipids across canalicular membranes of hepatocytes
	liver-specific membrane transporter of phosphatidylcholine, a major and exclusive component of bile
	translocates phosphatidylcholine from the inner to the outer leaflet of the canalicular membrane
	ABCB4 and ATP8B1 cooperate to protect hepatocytes from bile salts
	might play a critical role in glucose homeostasis
	plays an important role in protecting the liver from bile acids
	may be involved in the transport of a broad array of drugs, because ABCB4 shows high amino acid homology to ABCB1 that plays an important role in transporting of various clinical drugs such as digoxin and paclitaxel
	located in nonrafts, but not in rafts, is predominantly involved in the efflux of phospholipids and other substrates

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

a component

INTERACTION

DNA

RNA

small molecule

protein	NFYA, NFYB, NFYC can act as a transcriptional activator of ABCB4
	interaction of ABCB4 with SLC9A3R1 through its PDZ-like motif plays a critical role in the regulation of ABCB4 expression and stability at the canalicular plasma membrane

cell & other

REGULATION

Other

ABCB4 activity is regulated by phosphorylation, in particular, of N-terminal residues

ASSOCIATED DISORDERS

corresponding disease(s)

PFIC3 , LPAC

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function constitutional germinal mutation       cause intrahepatic cholestasis of pregnancy, with normal gamma-GT and may be associated with stillbirths and gallstone disease constitutional germinal mutation       splicing mutations cause intrahepatic cholestasis of pregnancy in women with high gamma-glutamyl transpeptidase (Tavian 2009)

Susceptibility

to drug-induced cholestasis to higher BMI and triglyceride and cholesterol levels to to drug-induced cholestatic liver injury

Variant & Polymorphism SNP , other	polylmorphisms increasing drug-induced cholestasis (Lang 2007)
	SNP C.504C > T associated with higher BMI and triglyceride and cholesterol levels (Acalovschi 2009)
	g.-1584C>T and g.-1014A>G, may be associated with a susceptibility. to drug-induced cholestatic liver injury

Candidate gene

Marker

Therapy target

ANIMAL & CELL MODELS