ABCB4
entrez
5244
canonical
uniprot
P21439
canonical
ensembl
ENSG00000005471
resolver
ensp
ENSP00000265723
resolver
ensp
ENSP00000392983
resolver
ensp
ENSP00000496956
resolver
ensp
ENSP00000609485
resolver
ensp
ENSP00000780159
resolver
genesymbol
ABCB4
resolver
genesymbol_syn
MDR3
resolver
genesymbol_syn
PGY3
resolver
hgnc
HGNC:45
resolver
uniprot
A0A2V7
resolver
uniprot
A4D1D3
resolver
uniprot
A4D1D4
resolver
uniprot
A4D1D5
resolver
uniprot
D6W5P3
resolver
uniprot
D6W5P4
resolver
uniprot
Q14813
resolver
uniprot_entry
MDR3_HUMAN
resolver
uniprot_sec
A0A2V7
resolver
uniprot_sec
A4D1D3
resolver
uniprot_sec
A4D1D4
resolver
uniprot_sec
A4D1D5
resolver
uniprot_sec
D6W5P3
resolver
uniprot_sec
D6W5P4
resolver
uniprot_sec
Q14813
resolver
activity_regulation
ACTIVITY REGULATION: Translocation activity is inhibited by the ATPase inhibitor vanadate and the calcium channel blocker verapamil (PubMed:17523162, PubMed:23468132). Translocation activity is enhanced by the addition of the bile salt taurocholate (PubMed:17523162, PubMed:23468132). {ECO:0000269|PubMed:17523162, ECO:0000269|PubMed:23468132}.
uniprot
proteins
amino_acid_sequence
MDLEAAKNGTAWRPTSAEGDFELGISSKQKRKKTKTVKMIGVLTLFRYSDWQDKLFMSLGTIMAIAHGSGLPLMMIVFGEMTDKFVDTAGNFSFPVNFSLSLLNPGKILEEEMTRYAYYYSGLGAGVLVAAYIQVSFWTLAAGRQIRKIRQKFFHAILRQEIGWFDINDTTELNTRLTDDISKISEGIGDKVGMFFQAVATFFAGFIVGFIRGWKLTLVIMAISPILGLSAAVWAKILSAFSDKELAAYAKAGAVAEEALGAIRTVIAFGGQNKELERYQKHLENAKEIGIKKAISANISMGIAFLLIYASYALAFWYGSTLVISKEYTIGNAMTVFFSILIGAFSVGQAAPCIDAFANARGAAYVIFDIIDNNPKIDSFSERGHKPDSIKGNLEFNDVHFSYPSRANVKILKGLNLKVQSGQTVALVGSSGCGKSTTVQLIQRLYDPDEGTINIDGQDIRNFNVNYLREIIGVVSQEPVLFSTTIAENICYGRGNVTMDEIKKAVKEANAYEFIMKLPQKFDTLVGERGAQLSGGQKQRIAIARALVRNPKILLLDEATSALDTESEAEVQAALDKAREGRTTIVIAHRLSTVRNADVIAGFEDGVIVEQGSHSELMKKEGVYFKLVNMQTSGSQIQSEEFELNDEKAATRMAPNGWKSRLFRHSTQKNLKNSQMCQKSLDVETDGLEANVPPVSFLKVLKLNKTEWPYFVVGTVCAIANGGLQPAFSVIFSEIIAIFGPGDDAVKQQKCNIFSLIFLFLGIISFFTFFLQGFTFGKAGEILTRRLRSMAFKAMLRQDMSWFDDHKNSTGALSTRLATDAAQVQGATGTRLALIAQNIANLGTGIIISFIYGWQLTLLLLAVVPIIAVSGIVEMKLLAGNAKRDKKELEAAGKIATEAIENIRTVVSLTQERKFESMYVEKLYGPYRNSVQKAHIYGITFSISQAFMYFSYAGCFRFGAYLIVNGHMRFRDVILVFSAIVFGAVALGHASSFAPDYAKAKLSAAHLFMLFERQPLIDSYSEEGLKPDKFEGNITFNEVVFNYPTRANVPVLQGLSLEVKKGQTLALVGSSGCGKSTVVQLLERFYDPLAGTVFVDFGFQLLDGQEAKKLNVQWLRAQLGIVSQEPILFDCSIAENIAYGDNSRVVSQDEIVSAAKAANIHPFIETLPHKYETRVGDKGTQLSGGQKQRIAIARALIRQPQILLLDEATSALDTESEKVVQEALDKAREGRTCIVIAHRLSTIQNADLIVVFQNGRVKEHGTHQQLLAQKGIYFSMVSVQAGTQNL
uniprot
proteins
disease_involvement
DISEASE: Cholestasis, progressive familial intrahepatic, 3 (PFIC3) [MIM:602347]: A disorder characterized by early onset of cholestasis that progresses to hepatic fibrosis, cirrhosis, and end-stage liver disease before adulthood. PFIC3 inheritance is autosomal recessive. {ECO:0000269|PubMed:11313315, ECO:0000269|PubMed:12671900, ECO:0000269|PubMed:17726488, ECO:0000269|PubMed:21119540, ECO:0000269|PubMed:24045840, ECO:0000269|PubMed:24594635, ECO:0000269|PubMed:24806754, ECO:0000269|PubMed:28012258, ECO:0000269|PubMed:9419367}. Note=The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Cholestasis of pregnancy, intrahepatic 3 (ICP3) [MIM:614972]: A liver disorder of pregnancy. It presents during the second or, more commonly, the third trimester of pregnancy with intense pruritus which becomes more severe with advancing gestation and cholestasis. It causes fetal distress, spontaneous premature delivery and intrauterine death. Patients have spontaneous and progressive disappearance of cholestasis after delivery. Cholestasis results from abnormal biliary transport from the liver into the small intestine. {ECO:0000269|PubMed:10767346, ECO:0000269|PubMed:12746424, ECO:0000269|PubMed:15077010}. Note=The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Gallbladder disease 1 (GBD1) [MIM:600803]: One of the major digestive diseases. Gallstones composed of cholesterol (cholelithiasis) are the common manifestations in western countries. Most people with gallstones, however, remain asymptomatic through their lifetimes. {ECO:0000269|PubMed:11313316, ECO:0000269|PubMed:12891548, ECO:0000269|PubMed:22331132, ECO:0000269|PubMed:23533021, ECO:0000269|PubMed:24723470, ECO:0000269|PubMed:28012258, ECO:0000269|PubMed:28587926, ECO:0000269|Ref.2}. Note=The disease is caused by variants affecting the gene represented in this entry.
uniprot
proteins
ec_number
7.6.2.1
uniprot
proteins
function
FUNCTION: [Isoform 1]: Energy-dependent phospholipid efflux translocator that acts as a positive regulator of biliary lipid secretion. Functions as a floppase that translocates specifically phosphatidylcholine (PC) from the inner to the outer leaflet of the canalicular membrane bilayer into the canaliculi of hepatocytes. Translocation of PC makes the biliary phospholipids available for extraction into the canaliculi lumen by bile salt mixed micelles and therefore protects the biliary tree from the detergent activity of bile salts (PubMed:17523162, PubMed:21820390, PubMed:23468132, PubMed:24594635, PubMed:24723470, PubMed:24806754, PubMed:31873305, PubMed:7957936, PubMed:8898203, PubMed:9366571). Plays a role in the recruitment of phosphatidylcholine (PC), phosphatidylethanolamine (PE) and sphingomyelin (SM) molecules to nonraft membranes and to further enrichment of SM and cholesterol in raft membranes in hepatocytes (PubMed:23468132). Required for proper phospholipid bile formation (By similarity). Indirectly involved in cholesterol efflux activity from hepatocytes into the canalicular lumen in the presence of bile salts in an ATP-dependent manner (PubMed:24045840). Promotes biliary phospholipid secretion as canaliculi-containing vesicles from the canalicular plasma membrane (PubMed:28012258, PubMed:9366571). In cooperation with ATP8B1, functions to protect hepatocytes from the deleterious detergent activity of bile salts (PubMed:21820390). Does not confer multidrug resistance (By similarity). {ECO:0000250|UniProtKB:P21440, ECO:0000269|PubMed:17523162, ECO:0000269|PubMed:21820390, ECO:0000269|PubMed:23468132, ECO:0000269|PubMed:24045840, ECO:0000269|PubMed:24594635, ECO:0000269|PubMed:24723470, ECO:0000269|PubMed:24806754, ECO:0000269|PubMed:28012258, ECO:0000269|PubMed:31873305, ECO:0000269|PubMed:7957936, ECO:0000269|PubMed:8898203, ECO:0000269|PubMed:9366571}.
uniprot
proteins
mass_dalton
141523
uniprot
proteins
mutagenesis
MUTAGEN 34; /note="T->D: Does not inhibit efflux activity for PC."; /evidence="ECO:0000269|PubMed:24723470"; MUTAGEN 44; /note="T->A: Reduces efflux activity for PC. Does not alter apical membrane location."; /evidence="ECO:0000269|PubMed:24723470"; MUTAGEN 49; /note="S->A: Reduces efflux activity for PC. Does not alter apical membrane location."; /evidence="ECO:0000269|PubMed:24723470"; MUTAGEN 435; /note="K->M: Inhibits efflux activity for PC and cholesterol, but does not alter glycosylation and surface expression in the presence of taurocholate."; /evidence="ECO:0000269|PubMed:17523162"; MUTAGEN 558; /note="E->Q: Loss of floppase activity. Strongly reduces the ATPase activity."; /evidence="ECO:0000269|PubMed:31873305"; MUTAGEN 953; /note="A->D: Accumulates predominantly in intracellular compartments with only a small fraction at the plasma membrane and inhibits partially the efflux activity for PC."; /evidence="ECO:0000269|PubMed:24806754"; MUTAGEN 985; /note="V->M: Significantly reduces phosphatidylcholine floppase activity; when associated with Q-989 and V-990."; /evidence="ECO:0000269|PubMed:31873305"; MUTAGEN 989; /note="H->Q: Significantly reduces phosphatidylcholine floppase activity; when associated with M-985 and V-990."; /evidence="ECO:0000269|PubMed:31873305"; MUTAGEN 990; /note="A->V: Significantly reduces phosphatidylcholine floppase activity; when associated with M-985 and Q-989."; /evidence="ECO:0000269|PubMed:31873305"; MUTAGEN 1075; /note="K->M: Inhibits efflux activity for PC and cholesterol, but does not alter glycosylation and surface expression in the presence of taurocholate."; /evidence="ECO:0000269|PubMed:17523162
uniprot
proteins
post_translational_modification
PTM: Phosphorylated (PubMed:24723470). Phosphorylation on Thr-34 is required for PC efflux activity. Phosphorylation occurs on serine and threonine residues in a protein kinase A- or C-dependent manner (PubMed:24723470). May be phosphorylated on Thr-44 and Ser-49 (PubMed:24723470). {ECO:0000269|PubMed:24723470}.; PTM: Glycosylated (PubMed:17523162, PubMed:21820390, PubMed:24723470). {ECO:0000269|PubMed:17523162, ECO:0000269|PubMed:21820390, ECO:0000269|PubMed:24723470}.
uniprot
proteins
protein_family
ABC transporter superfamily
uniprot
proteins
protein_family
ABCB family
uniprot
proteins
protein_family
Multidrug resistance exporter (TC 3.A.1.201) subfamily
uniprot
proteins
pubmed
10767346
uniprot
proteins
pubmed
11313315
uniprot
proteins
pubmed
11313316
uniprot
proteins
pubmed
12671900
uniprot
proteins
pubmed
12690205
uniprot
proteins
pubmed
12746424
uniprot
proteins
pubmed
12853948
uniprot
proteins
pubmed
12891548
uniprot
proteins
pubmed
15077010
uniprot
proteins
pubmed
15258199
uniprot
proteins
pubmed
16763017
uniprot
proteins
pubmed
17264802
uniprot
proteins
pubmed
17523162
uniprot
proteins
pubmed
17726488
uniprot
proteins
pubmed
19261551
uniprot
proteins
pubmed
19674157
uniprot
proteins
pubmed
2002063
uniprot
proteins
pubmed
21119540
uniprot
proteins
pubmed
21820390
uniprot
proteins
pubmed
22331132
uniprot
proteins
pubmed
23468132
uniprot
proteins
pubmed
23533021
uniprot
proteins
pubmed
24045840
uniprot
proteins
pubmed
24122873
uniprot
proteins
pubmed
24594635
uniprot
proteins
pubmed
24723470
uniprot
proteins
pubmed
24806754
uniprot
proteins
pubmed
28012258
uniprot
proteins
pubmed
28587926
uniprot
proteins
pubmed
2892668
uniprot
proteins
pubmed
2906314
uniprot
proteins
pubmed
31873305
uniprot
proteins
pubmed
7893760
uniprot
proteins
pubmed
7957936
uniprot
proteins
pubmed
8898203
uniprot
proteins
pubmed
9366571
uniprot
proteins
pubmed
9419367
uniprot
proteins
sequence_length
1286
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:23468132, ECO:0000269|PubMed:24045840, ECO:0000269|PubMed:24806754, ECO:0000269|PubMed:28012258}; Multi-pass membrane protein {ECO:0000255|PROSITE-ProRule:PRU00441}. Apical cell membrane {ECO:0000269|PubMed:15258199, ECO:0000269|PubMed:19674157, ECO:0000269|PubMed:21820390, ECO:0000269|PubMed:24122873, ECO:0000269|PubMed:24594635, ECO:0000269|PubMed:24723470, ECO:0000269|PubMed:8898203}; Multi-pass membrane protein {ECO:0000255|PROSITE-ProRule:PRU00441}. Membrane raft {ECO:0000269|PubMed:23468132}. Cytoplasm {ECO:0000269|PubMed:24045840}. Cytoplasmic vesicle, clathrin-coated vesicle {ECO:0000250|UniProtKB:Q08201}. Note=Localized at the apical canalicular membrane of the epithelial cells lining the lumen of the bile canaliculi and biliary ductules (By similarity). Transported from the Golgi to the apical bile canalicular membrane in a RACK1-dependent manner (PubMed:19674157). Redistributed into pseudocanaliculi formed between cells in a bezafibrate- or PPARA-dependent manner (PubMed:15258199). Localized preferentially in lipid nonraft domains of canalicular plasma membranes (PubMed:23468132). {ECO:0000250|UniProtKB:P21440, ECO:0000269|PubMed:15258199, ECO:0000269|PubMed:19674157, ECO:0000269|PubMed:23468132}.
uniprot
proteins
transmembrane_region
TRANSMEM 51..73; /note="Helical"; /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"; TRANSMEM 119..139; /note="Helical"; /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"; TRANSMEM 189..210; /note="Helical"; /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"; TRANSMEM 218..238; /note="Helical"; /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"; TRANSMEM 297..318; /note="Helical"; /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"; TRANSMEM 333..354; /note="Helical"; /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"; TRANSMEM 712..732; /note="Helical"; /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"; TRANSMEM 756..776; /note="Helical"; /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"; TRANSMEM 832..852; /note="Helical"; /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"; TRANSMEM 854..873; /note="Helical"; /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"; TRANSMEM 934..956; /note="Helical"; /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"; TRANSMEM 973..994; /note="Helical"; /evidence="ECO:0000255|PROSITE-ProRule:PRU00441
uniprot
proteins