P21439 (MDR3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Multidrug resistance protein 3
EC=3.6.3.44

Alternative name(s):
ATP-binding cassette sub-family B member 4
P-glycoprotein 3

Gene names

Name:	ABCB4
Synonyms:	MDR3, PGY3

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	1286 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Mediates ATP-dependent export of organic anions and drugs from the cytoplasm. Hydrolyzes ATP with low efficiency. Not capable of conferring drug resistance. Mediates the translocation of phosphatidylcholine across the canalicular membrane of the hepatocyte.
Catalytic activity	ATP + H2O + xenobiotic(In) = ADP + phosphate + xenobiotic(Out).
Subunit structure	Interacts with HAX1 By similarity.
Subcellular location	Cell membrane; Multi-pass membrane protein.
Involvement in 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. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.9 Ref.11 Ref.13 Cholestasis of pregnancy, intrahepatic 3 (ICP3) [MIM:614972]: A liver disorder of pregnancy. It presents during the second or, more commonly, the third trimestre 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. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.10 Ref.15 Ref.16 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. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.12 Ref.14
Sequence similarities	Belongs to the ABC transporter superfamily. ABCB family. Multidrug resistance exporter (TC 3.A.1.201) subfamily. [View classification] Contains 2 ABC transmembrane type-1 domains. Contains 2 ABC transporter domains.
Sequence caution	The sequence CAA84542.1 differs from that shown. Reason: Probable cloning artifact.

Ontologies

Keywords
Biological process	Transport
Cellular component	Cell membrane Membrane
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Disease mutation Intrahepatic cholestasis
Domain	Repeat Transmembrane Transmembrane helix
Ligand	ATP-binding Nucleotide-binding
Molecular function	Hydrolase
PTM	Glycoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	cellular lipid metabolic process Traceable author statement. Source: Reactome response to drug Traceable author statement PubMed 7912658. Source: ProtInc
Cellular_component	Golgi membrane Inferred from Biological aspect of Ancestor. Source: RefGenome apical plasma membrane Inferred from Biological aspect of Ancestor. Source: RefGenome integral to plasma membrane Traceable author statement PubMed 7912658. Source: ProtInc intercellular canaliculus Inferred from Biological aspect of Ancestor. Source: RefGenome
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW ATPase activity, coupled to transmembrane movement of substances Inferred from Biological aspect of Ancestor. Source: RefGenome xenobiotic-transporting ATPase activity Inferred from electronic annotation. Source: EC
Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: P21439-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: P21439-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1094-1100: Missing.

Isoform 3 (identifier: P21439-3)

The sequence of this isoform differs from the canonical sequence as follows:
     929-975: Missing.
     1094-1100: Missing.

Note: No experimental confirmation available. Gene prediction based on EST data.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 1286	1286	Multidrug resistance protein 3		PRO_0000093333
Regions
	Topological domain	1 – 50	50	Cytoplasmic By similarity
	Transmembrane	51 – 73	23	Helical; By similarity
	Topological domain	74 – 118	45	Extracellular By similarity
	Transmembrane	119 – 139	21	Helical; By similarity
	Topological domain	140 – 188	49	Cytoplasmic By similarity
	Transmembrane	189 – 210	22	Helical; By similarity
	Topological domain	211 – 217	7	Extracellular By similarity
	Transmembrane	218 – 238	21	Helical; By similarity
	Topological domain	239 – 296	58	Cytoplasmic By similarity
	Transmembrane	297 – 318	22	Helical; By similarity
	Topological domain	319 – 332	14	Extracellular By similarity
	Transmembrane	333 – 354	22	Helical; By similarity
	Topological domain	355 – 711	357	Cytoplasmic By similarity
	Transmembrane	712 – 732	21	Helical; By similarity
	Topological domain	733 – 755	23	Extracellular By similarity
	Transmembrane	756 – 776	21	Helical; By similarity
	Topological domain	777 – 831	55	Cytoplasmic By similarity
	Transmembrane	832 – 852	21	Helical; By similarity
	Topological domain	853	1	Extracellular By similarity
	Transmembrane	854 – 873	20	Helical; By similarity
	Topological domain	874 – 933	60	Cytoplasmic By similarity
	Transmembrane	934 – 956	23	Helical; By similarity
	Topological domain	957 – 972	16	Extracellular By similarity
	Transmembrane	973 – 994	22	Helical; By similarity
	Topological domain	995 – 1286	292	Cytoplasmic By similarity
	Domain	57 – 359	303	ABC transmembrane type-1 1
	Domain	394 – 630	237	ABC transporter 1
	Domain	711 – 999	289	ABC transmembrane type-1 2
	Domain	1034 – 1279	246	ABC transporter 2
	Nucleotide binding	429 – 436	8	ATP 1 By similarity
	Nucleotide binding	1069 – 1076	8	ATP 2 By similarity
	Region	625 – 647	23	Interaction with HAX1 By similarity
Amino acid modifications
	Glycosylation	91	1	N-linked (GlcNAc...) Potential
	Glycosylation	97	1	N-linked (GlcNAc...) Potential
Natural variations
	Alternative sequence	929 – 975	47	Missing in isoform 3.		VSP_046258
	Alternative sequence	1094 – 1100	7	Missing in isoform 2 and isoform 3.		VSP_023263
	Natural variant	87	1	D → E. Ref.17		VAR_043078
	Natural variant	95	1	P → S. Ref.17		VAR_043079
	Natural variant	138	1	W → R in PFIC3. Ref.11		VAR_043080
	Natural variant	150	1	R → K in ICP3. Ref.15		VAR_043081
	Natural variant	165	1	F → I in GBD1. Ref.14		VAR_043082
	Natural variant	175	1	T → A. Ref.12 Ref.14 Ref.16 Ref.17 Ref.18 Corresponds to variant rs58238559 [ dbSNP | Ensembl ].		VAR_023501
	Natural variant	238	1	L → V. Ref.2 Corresponds to variant rs45596335 [ dbSNP | Ensembl ].		VAR_020223
	Natural variant	263	1	I → V. Ref.2 Corresponds to variant rs45547936 [ dbSNP | Ensembl ].		VAR_030763
	Natural variant	301	1	M → T in GBD1. Ref.14		VAR_043083
	Natural variant	320	1	S → F in ICP3 and GBD1. Ref.12 Ref.14 Ref.16		VAR_023502
	Natural variant	346	1	S → I in PFIC3. Ref.11		VAR_043084
	Natural variant	367	1	I → V. Ref.17		VAR_043085
	Natural variant	395	1	E → G in PFIC3. Ref.11		VAR_043086
	Natural variant	424	1	T → A in PFIC3. Ref.11		VAR_043087
	Natural variant	425	1	V → M in PFIC3. Ref.11		VAR_043088
	Natural variant	450	1	E → G. Ref.17		VAR_043089
	Natural variant	528	1	E → D. Ref.2 Ref.14 Ref.16 Corresponds to variant rs8187797 [ dbSNP | Ensembl ].		VAR_043090
	Natural variant	535	1	G → D in PFIC3. Ref.13		VAR_043091
	Natural variant	541	1	I → F in PFIC3. Ref.11		VAR_043092
	Natural variant	546	1	A → D in ICP3; disruption of protein trafficking with subsequent lack of functional protein at the cell surface. Ref.10		VAR_023503
	Natural variant	556	1	L → R in PFIC3. Ref.11		VAR_043093
	Natural variant	564	1	D → G in PFIC3. Ref.11		VAR_043094
	Natural variant	590	1	R → Q. Ref.2 Ref.14 Ref.17 Ref.18 Corresponds to variant rs45575636 [ dbSNP | Ensembl ].		VAR_043095
	Natural variant	591	1	L → Q in GBD1. Ref.14		VAR_043096
	Natural variant	651	1	T → N. Ref.2 Corresponds to variant rs45476795 [ dbSNP | Ensembl ].		VAR_030765
	Natural variant	652	1	R → G. Ref.2 Ref.11 Ref.14 Ref.15 Ref.16 Ref.17 Ref.18 Corresponds to variant rs2230028 [ dbSNP | Ensembl ].		VAR_020225
	Natural variant	711	1	F → S in PFIC3. Ref.11		VAR_043097
	Natural variant	742	1	G → S. Ref.14		VAR_043098
	Natural variant	762	1	G → E in ICP3. Ref.16		VAR_043099
	Natural variant	764	1	I → L in a heterozygous patient with risperidone-induced cholestasis. Ref.18		VAR_043100
	Natural variant	775	1	T → M. Ref.16		VAR_043101
	Natural variant	788	1	R → Q. Ref.2 Ref.14		VAR_024359
	Natural variant	934	1	A → T in GBD1. Ref.14		VAR_043102
	Natural variant	983	1	G → S in PFIC3. Ref.11 Corresponds to variant rs56187107 [ dbSNP | Ensembl ].		VAR_043103
	Natural variant	1082	1	L → Q in a heterozygous patient with amoxicillin/clavulanic acid-induced cholestasis. Ref.18		VAR_043104
	Natural variant	1161	1	Missing in GBD1.		VAR_043105
	Natural variant	1168	1	P → S in GBD1. Ref.12 Ref.14		VAR_023504

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified February 20, 2007. Version 2. Checksum: 9A9066F2292F2CCF	FASTA	1,286	141,523
	10 20 30 40 50 60 MDLEAAKNGT AWRPTSAEGD FELGISSKQK RKKTKTVKMI GVLTLFRYSD WQDKLFMSLG 70 80 90 100 110 120 TIMAIAHGSG LPLMMIVFGE MTDKFVDTAG NFSFPVNFSL SLLNPGKILE EEMTRYAYYY 130 140 150 160 170 180 SGLGAGVLVA AYIQVSFWTL AAGRQIRKIR QKFFHAILRQ EIGWFDINDT TELNTRLTDD 190 200 210 220 230 240 ISKISEGIGD KVGMFFQAVA TFFAGFIVGF IRGWKLTLVI MAISPILGLS AAVWAKILSA 250 260 270 280 290 300 FSDKELAAYA KAGAVAEEAL GAIRTVIAFG GQNKELERYQ KHLENAKEIG IKKAISANIS 310 320 330 340 350 360 MGIAFLLIYA SYALAFWYGS TLVISKEYTI GNAMTVFFSI LIGAFSVGQA APCIDAFANA 370 380 390 400 410 420 RGAAYVIFDI IDNNPKIDSF SERGHKPDSI KGNLEFNDVH FSYPSRANVK ILKGLNLKVQ 430 440 450 460 470 480 SGQTVALVGS SGCGKSTTVQ LIQRLYDPDE GTINIDGQDI RNFNVNYLRE IIGVVSQEPV 490 500 510 520 530 540 LFSTTIAENI CYGRGNVTMD EIKKAVKEAN AYEFIMKLPQ KFDTLVGERG AQLSGGQKQR 550 560 570 580 590 600 IAIARALVRN PKILLLDEAT SALDTESEAE VQAALDKARE GRTTIVIAHR LSTVRNADVI 610 620 630 640 650 660 AGFEDGVIVE QGSHSELMKK EGVYFKLVNM QTSGSQIQSE EFELNDEKAA TRMAPNGWKS 670 680 690 700 710 720 RLFRHSTQKN LKNSQMCQKS LDVETDGLEA NVPPVSFLKV LKLNKTEWPY FVVGTVCAIA 730 740 750 760 770 780 NGGLQPAFSV IFSEIIAIFG PGDDAVKQQK CNIFSLIFLF LGIISFFTFF LQGFTFGKAG 790 800 810 820 830 840 EILTRRLRSM AFKAMLRQDM SWFDDHKNST GALSTRLATD AAQVQGATGT RLALIAQNIA 850 860 870 880 890 900 NLGTGIIISF IYGWQLTLLL LAVVPIIAVS GIVEMKLLAG NAKRDKKELE AAGKIATEAI 910 920 930 940 950 960 ENIRTVVSLT QERKFESMYV EKLYGPYRNS VQKAHIYGIT FSISQAFMYF SYAGCFRFGA 970 980 990 1000 1010 1020 YLIVNGHMRF RDVILVFSAI VFGAVALGHA SSFAPDYAKA KLSAAHLFML FERQPLIDSY 1030 1040 1050 1060 1070 1080 SEEGLKPDKF EGNITFNEVV FNYPTRANVP VLQGLSLEVK KGQTLALVGS SGCGKSTVVQ 1090 1100 1110 1120 1130 1140 LLERFYDPLA GTVFVDFGFQ LLDGQEAKKL NVQWLRAQLG IVSQEPILFD CSIAENIAYG 1150 1160 1170 1180 1190 1200 DNSRVVSQDE IVSAAKAANI HPFIETLPHK YETRVGDKGT QLSGGQKQRI AIARALIRQP 1210 1220 1230 1240 1250 1260 QILLLDEATS ALDTESEKVV QEALDKAREG RTCIVIAHRL STIQNADLIV VFQNGRVKEH 1270 1280 GTHQQLLAQK GIYFSMVSVQ AGTQNL
	Isoform 2 [UniParc]. Checksum: 3D58C98B5C8D6087	FASTA	1,279	140,682
	10 20 30 40 50 60 MDLEAAKNGT AWRPTSAEGD FELGISSKQK RKKTKTVKMI GVLTLFRYSD WQDKLFMSLG 70 80 90 100 110 120 TIMAIAHGSG LPLMMIVFGE MTDKFVDTAG NFSFPVNFSL SLLNPGKILE EEMTRYAYYY 130 140 150 160 170 180 SGLGAGVLVA AYIQVSFWTL AAGRQIRKIR QKFFHAILRQ EIGWFDINDT TELNTRLTDD 190 200 210 220 230 240 ISKISEGIGD KVGMFFQAVA TFFAGFIVGF IRGWKLTLVI MAISPILGLS AAVWAKILSA 250 260 270 280 290 300 FSDKELAAYA KAGAVAEEAL GAIRTVIAFG GQNKELERYQ KHLENAKEIG IKKAISANIS 310 320 330 340 350 360 MGIAFLLIYA SYALAFWYGS TLVISKEYTI GNAMTVFFSI LIGAFSVGQA APCIDAFANA 370 380 390 400 410 420 RGAAYVIFDI IDNNPKIDSF SERGHKPDSI KGNLEFNDVH FSYPSRANVK ILKGLNLKVQ 430 440 450 460 470 480 SGQTVALVGS SGCGKSTTVQ LIQRLYDPDE GTINIDGQDI RNFNVNYLRE IIGVVSQEPV 490 500 510 520 530 540 LFSTTIAENI CYGRGNVTMD EIKKAVKEAN AYEFIMKLPQ KFDTLVGERG AQLSGGQKQR 550 560 570 580 590 600 IAIARALVRN PKILLLDEAT SALDTESEAE VQAALDKARE GRTTIVIAHR LSTVRNADVI 610 620 630 640 650 660 AGFEDGVIVE QGSHSELMKK EGVYFKLVNM QTSGSQIQSE EFELNDEKAA TRMAPNGWKS 670 680 690 700 710 720 RLFRHSTQKN LKNSQMCQKS LDVETDGLEA NVPPVSFLKV LKLNKTEWPY FVVGTVCAIA 730 740 750 760 770 780 NGGLQPAFSV IFSEIIAIFG PGDDAVKQQK CNIFSLIFLF LGIISFFTFF LQGFTFGKAG 790 800 810 820 830 840 EILTRRLRSM AFKAMLRQDM SWFDDHKNST GALSTRLATD AAQVQGATGT RLALIAQNIA 850 860 870 880 890 900 NLGTGIIISF IYGWQLTLLL LAVVPIIAVS GIVEMKLLAG NAKRDKKELE AAGKIATEAI 910 920 930 940 950 960 ENIRTVVSLT QERKFESMYV EKLYGPYRNS VQKAHIYGIT FSISQAFMYF SYAGCFRFGA 970 980 990 1000 1010 1020 YLIVNGHMRF RDVILVFSAI VFGAVALGHA SSFAPDYAKA KLSAAHLFML FERQPLIDSY 1030 1040 1050 1060 1070 1080 SEEGLKPDKF EGNITFNEVV FNYPTRANVP VLQGLSLEVK KGQTLALVGS SGCGKSTVVQ 1090 1100 1110 1120 1130 1140 LLERFYDPLA GTVLLDGQEA KKLNVQWLRA QLGIVSQEPI LFDCSIAENI AYGDNSRVVS 1150 1160 1170 1180 1190 1200 QDEIVSAAKA ANIHPFIETL PHKYETRVGD KGTQLSGGQK QRIAIARALI RQPQILLLDE 1210 1220 1230 1240 1250 1260 ATSALDTESE KVVQEALDKA REGRTCIVIA HRLSTIQNAD LIVVFQNGRV KEHGTHQQLL 1270 AQKGIYFSMV SVQAGTQNL
	Isoform 3 [UniParc]. Checksum: 48626DBEDA98930C	FASTA	1,232	135,259
	10 20 30 40 50 60 MDLEAAKNGT AWRPTSAEGD FELGISSKQK RKKTKTVKMI GVLTLFRYSD WQDKLFMSLG 70 80 90 100 110 120 TIMAIAHGSG LPLMMIVFGE MTDKFVDTAG NFSFPVNFSL SLLNPGKILE EEMTRYAYYY 130 140 150 160 170 180 SGLGAGVLVA AYIQVSFWTL AAGRQIRKIR QKFFHAILRQ EIGWFDINDT TELNTRLTDD 190 200 210 220 230 240 ISKISEGIGD KVGMFFQAVA TFFAGFIVGF IRGWKLTLVI MAISPILGLS AAVWAKILSA 250 260 270 280 290 300 FSDKELAAYA KAGAVAEEAL GAIRTVIAFG GQNKELERYQ KHLENAKEIG IKKAISANIS 310 320 330 340 350 360 MGIAFLLIYA SYALAFWYGS TLVISKEYTI GNAMTVFFSI LIGAFSVGQA APCIDAFANA 370 380 390 400 410 420 RGAAYVIFDI IDNNPKIDSF SERGHKPDSI KGNLEFNDVH FSYPSRANVK ILKGLNLKVQ 430 440 450 460 470 480 SGQTVALVGS SGCGKSTTVQ LIQRLYDPDE GTINIDGQDI RNFNVNYLRE IIGVVSQEPV 490 500 510 520 530 540 LFSTTIAENI CYGRGNVTMD EIKKAVKEAN AYEFIMKLPQ KFDTLVGERG AQLSGGQKQR 550 560 570 580 590 600 IAIARALVRN PKILLLDEAT SALDTESEAE VQAALDKARE GRTTIVIAHR LSTVRNADVI 610 620 630 640 650 660 AGFEDGVIVE QGSHSELMKK EGVYFKLVNM QTSGSQIQSE EFELNDEKAA TRMAPNGWKS 670 680 690 700 710 720 RLFRHSTQKN LKNSQMCQKS LDVETDGLEA NVPPVSFLKV LKLNKTEWPY FVVGTVCAIA 730 740 750 760 770 780 NGGLQPAFSV IFSEIIAIFG PGDDAVKQQK CNIFSLIFLF LGIISFFTFF LQGFTFGKAG 790 800 810 820 830 840 EILTRRLRSM AFKAMLRQDM SWFDDHKNST GALSTRLATD AAQVQGATGT RLALIAQNIA 850 860 870 880 890 900 NLGTGIIISF IYGWQLTLLL LAVVPIIAVS GIVEMKLLAG NAKRDKKELE AAGKIATEAI 910 920 930 940 950 960 ENIRTVVSLT QERKFESMYV EKLYGPYRVF SAIVFGAVAL GHASSFAPDY AKAKLSAAHL 970 980 990 1000 1010 1020 FMLFERQPLI DSYSEEGLKP DKFEGNITFN EVVFNYPTRA NVPVLQGLSL EVKKGQTLAL 1030 1040 1050 1060 1070 1080 VGSSGCGKST VVQLLERFYD PLAGTVLLDG QEAKKLNVQW LRAQLGIVSQ EPILFDCSIA 1090 1100 1110 1120 1130 1140 ENIAYGDNSR VVSQDEIVSA AKAANIHPFI ETLPHKYETR VGDKGTQLSG GQKQRIAIAR 1150 1160 1170 1180 1190 1200 ALIRQPQILL LDEATSALDT ESEKVVQEAL DKAREGRTCI VIAHRLSTIQ NADLIVVFQN 1210 1220 1230 GRVKEHGTHQ QLLAQKGIYF SMVSVQAGTQ NL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Sequence of mdr3 cDNA encoding a human P-glycoprotein." van der Bliek A.M., Kooiman P.M., Schneider C., Borst P. Gene 71:401-411(1988) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
[2]	NIEHS SNPs program Submitted (OCT-2006) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS VAL-238; VAL-263; ASP-528; GLN-590; ASN-651; GLY-652 AND GLN-788.
[3]	"The DNA sequence of human chromosome 7." Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H., Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K., Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A., Delehaunty K.D., Miner T.L. , Nash W.E., Cordes M., Du H., Sun H., Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A., Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P., Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M., Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S., Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R., Strowmatt C., Latreille P., Miller N., Johnson D., Murray J., Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W., Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A., Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E., Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E., Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A., Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A., Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R., McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H., Wilson R.K. Nature 424:157-164(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	"Human chromosome 7: DNA sequence and biology." Scherer S.W., Cheung J., MacDonald J.R., Osborne L.R., Nakabayashi K., Herbrick J.-A., Carson A.R., Parker-Katiraee L., Skaug J., Khaja R., Zhang J., Hudek A.K., Li M., Haddad M., Duggan G.E., Fernandez B.A., Kanematsu E., Gentles S. , Christopoulos C.C., Choufani S., Kwasnicka D., Zheng X.H., Lai Z., Nusskern D.R., Zhang Q., Gu Z., Lu F., Zeesman S., Nowaczyk M.J., Teshima I., Chitayat D., Shuman C., Weksberg R., Zackai E.H., Grebe T.A., Cox S.R., Kirkpatrick S.J., Rahman N., Friedman J.M., Heng H.H.Q., Pelicci P.G., Lo-Coco F., Belloni E., Shaffer L.G., Pober B., Morton C.C., Gusella J.F., Bruns G.A.P., Korf B.R., Quade B.J., Ligon A.H., Ferguson H., Higgins A.W., Leach N.T., Herrick S.R., Lemyre E., Farra C.G., Kim H.-G., Summers A.M., Gripp K.W., Roberts W., Szatmari P., Winsor E.J.T., Grzeschik K.-H., Teebi A., Minassian B.A., Kere J., Armengol L., Pujana M.A., Estivill X., Wilson M.D., Koop B.F., Tosi S., Moore G.E., Boright A.P., Zlotorynski E., Kerem B., Kroisel P.M., Petek E., Oscier D.G., Mould S.J., Doehner H., Doehner K., Rommens J.M., Vincent J.B., Venter J.C., Li P.W., Mural R.J., Adams M.D., Tsui L.-C. Science 300:767-772(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	"Characterization of the promoter region of the human MDR3 P-glycoprotein gene." Smit J.J., Mol C.A., van Deemter L., Wagenaar E., Schinkel A.H., Borst P. Biochim. Biophys. Acta 1261:44-56(1995) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1-72 (ISOFORM 1). Tissue: Liver.
[7]	"The human mdr3 gene encodes a novel P-glycoprotein homologue and gives rise to alternatively spliced mRNAs in liver." van der Bliek A.M., Baas F., ten Houte de Lange T., Kooiman P.M., van der Velde-Koerts T., Borst P. EMBO J. 6:3325-3331(1987) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 856-1286 (ISOFORM 1), ALTERNATIVE SPLICING.
[8]	"Structure of the human MDR3 gene and physical mapping of the human MDR locus." Lincke C.R., Smit J.J.M., van der Velde-Koerts T., Borst P. J. Biol. Chem. 266:5303-5310(1991) [PubMed] [Europe PMC] [Abstract] Cited for: GENE STRUCTURE.
[9]	"Mutations in the MDR3 gene cause progressive familial intrahepatic cholestasis." de Vree J.M.L., Jacquemin E., Sturm E., Cresteil D., Bosma P.J., Aten J., Deleuze J.-F., Desrochers M., Burdelski M., Bernard O., Oude Elferink R.P.J., Hadchouel M. Proc. Natl. Acad. Sci. U.S.A. 95:282-287(1998) [PubMed] [Europe PMC] [Abstract] Cited for: INVOLVEMENT IN PFIC3.
[10]	"Heterozygous MDR3 missense mutation associated with intrahepatic cholestasis of pregnancy: evidence for a defect in protein trafficking." Dixon P.H., Weerasekera N., Linton K.J., Donaldson O., Chambers J., Egginton E., Weaver J., Nelson-Piercy C., de Swiet M., Warnes G., Elias E., Higgins C.F., Johnston D.G., McCarthy M.I., Williamson C. Hum. Mol. Genet. 9:1209-1217(2000) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT ICP3 ASP-546, CHARACTERIZATION OF VARIANT ICP3 ASP-546.
[11]	"The wide spectrum of multidrug resistance 3 deficiency: from neonatal cholestasis to cirrhosis of adulthood." Jacquemin E., De Vree J.M.L., Cresteil D., Sokal E.M., Sturm E., Dumont M., Scheffer G.L., Paul M., Burdelski M., Bosma P.J., Bernard O., Hadchouel M., Elferink R.P. Gastroenterology 120:1448-1458(2001) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS PFIC3 ARG-138; ILE-346; GLY-395; ALA-424; MET-425; PHE-541; ARG-556; GLY-564; SER-711 AND SER-983, VARIANT GLY-652.
[12]	"MDR3 gene defect in adults with symptomatic intrahepatic and gallbladder cholesterol cholelithiasis." Rosmorduc O., Hermelin B., Poupon R. Gastroenterology 120:1459-1467(2001) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS GBD1 PHE-320 AND SER-1168, VARIANT ALA-175.
[13]	"A multidrug resistance 3 gene mutation causing cholelithiasis, cholestasis of pregnancy, and adulthood biliary cirrhosis." Lucena J.-F., Herrero J.I., Quiroga J., Sangro B., Garcia-Foncillas J., Zabalegui N., Sola J., Herraiz M., Medina J.F., Prieto J. Gastroenterology 124:1037-1042(2003) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT PFIC3 ASP-535.
[14]	"ABCB4 gene mutation-associated cholelithiasis in adults." Rosmorduc O., Hermelin B., Boelle P.Y., Parc R., Taboury J., Poupon R. Gastroenterology 125:452-459(2003) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS GBD1 ILE-165; THR-301; PHE-320; GLN-591; THR-934 AND SER-1168, VARIANTS ALA-175; ASP-528; GLN-590; GLY-652; SER-742 AND GLN-788.
[15]	"ABCB4 gene sequence variation in women with intrahepatic cholestasis of pregnancy." Muellenbach R., Linton K.J., Wiltshire S., Weerasekera N., Chambers J., Elias E., Higgins C.F., Johnston D.G., McCarthy M.I., Williamson C. J. Med. Genet. 40:E70-E70(2003) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT ICP3 LYS-150, VARIANT GLY-652.
[16]	"Sequence analysis of bile salt export pump (ABCB11) and multidrug resistance p-glycoprotein 3 (ABCB4, MDR3) in patients with intrahepatic cholestasis of pregnancy." Pauli-Magnus C., Lang T., Meier Y., Zodan-Marin T., Jung D., Breymann C., Zimmermann R., Kenngott S., Beuers U., Reichel C., Kerb R., Penger A., Meier P.J., Kullak-Ublick G.A. Pharmacogenetics 14:91-102(2004) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS ALA-175; ASP-528; GLY-652 AND MET-775, VARIANTS ICP3 PHE-320 AND GLU-762.
[17]	"Genetic variability, haplotype structures, and ethnic diversity of hepatic transporters MDR3 (ABCB4) and bile salt export pump (ABCB11)." Lang T., Haberl M., Jung D., Drescher A., Schlagenhaufer R., Keil A., Mornhinweg E., Stieger B., Kullak-Ublick G.A., Kerb R. Drug Metab. Dispos. 34:1582-1599(2006) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS GLU-87; SER-95; ALA-175; VAL-367; GLY-450; GLN-590 AND GLY-652.
[18]	"Mutations and polymorphisms in the bile salt export pump and the multidrug resistance protein 3 associated with drug-induced liver injury." Lang C., Meier Y., Stieger B., Beuers U., Lang T., Kerb R., Kullak-Ublick G.A., Meier P.J., Pauli-Magnus C. Pharmacogenet. Genomics 17:47-60(2007) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS ALA-175; GLN-590; GLY-652; LEU-764 AND GLN-1082.
+	Additional computationally mapped references.

Web resources

GeneReviews

NIEHS-SNPs

ABCMdb

Database for mutations in ABC proteins

Cross-references

Sequence databases
EMBL GenBank DDBJ	M23234 mRNA. Translation: AAA36207.1. EF034088 Genomic DNA. Translation: ABJ53424.1. AC005045 Genomic DNA. No translation available. AC005068 Genomic DNA. No translation available. AC006154 Genomic DNA. No translation available. CH236949 Genomic DNA. Translation: EAL24174.1. CH236949 Genomic DNA. Translation: EAL24175.1. CH236949 Genomic DNA. Translation: EAL24176.1. CH471091 Genomic DNA. Translation: EAW76946.1. CH471091 Genomic DNA. Translation: EAW76947.1. CH471091 Genomic DNA. Translation: EAW76948.1. CH471091 Genomic DNA. Translation: EAW76950.1. CH471091 Genomic DNA. Translation: EAW76951.1. CH471091 Genomic DNA. Translation: EAW76952.1. Z35284 mRNA. Translation: CAA84542.1. Sequence problems. X06181 mRNA. Translation: CAA29547.1.
IPI	IPI00042932. IPI00218731. IPI00927655.
PIR	DVHU3. JS0051.
RefSeq	NP_000434.1. NM_000443.3. NP_061337.1. NM_018849.2. NP_061338.1. NM_018850.2.
UniGene	Hs.654403.
3D structure databases
ProteinModelPortal	P21439.
ModBase	Search...
Protein-protein interaction databases
IntAct	P21439. 3 interactions.
STRING	9606.ENSP00000265723.
Protein family/group databases
TCDB	3.A.1.201.3. ATP-binding cassette (ABC) superfamily.
PTM databases
PhosphoSite	P21439.
Polymorphism databases
DMDM	126302568.
Proteomic databases
PaxDb	P21439.
PRIDE	P21439.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000265723; ENSP00000265723; ENSG00000005471. ENST00000358400; ENSP00000351172; ENSG00000005471. ENST00000359206; ENSP00000352135; ENSG00000005471. ENST00000453593; ENSP00000392983; ENSG00000005471. ENST00000545634; ENSP00000437465; ENSG00000005471.
GeneID	5244.
KEGG	hsa:5244.
UCSC	uc003uiv.1. human. uc003uiw.1. human.
Organism-specific databases
CTD	5244.
GeneCards	GC07M087031.
HGNC	HGNC:45. ABCB4.
HPA	CAB004498. HPA049395. HPA053288.
MIM	171060. gene. 600803. phenotype. 602347. phenotype. 614972. phenotype.
neXtProt	NX_P21439.
Orphanet	69665. Intrahepatic cholestasis of pregnancy. 69663. Low phospholipid associated cholelithiasis. 79305. Progressive familial intrahepatic cholestasis type 3.
PharmGKB	PA268.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG1132.
HOVERGEN	HBG080809.
InParanoid	P21439.
KO	K05659.
OMA	SIHAMAV.
PhylomeDB	P21439.
Enzyme and pathway databases
Reactome	REACT_111217. Metabolism.
Gene expression databases
ArrayExpress	P21439.
Bgee	P21439.
CleanEx	HS_ABCB4.
Genevestigator	P21439.
GermOnline	ENSG00000005471. Homo sapiens.
Family and domain databases
InterPro	IPR003593. AAA+_ATPase. IPR003439. ABC_transporter-like. IPR017871. ABC_transporter_CS. IPR017940. ABC_transporter_type1. IPR001140. ABC_transptr_TM_dom. IPR011527. ABC_transptrTM_dom_typ1. [Graphical view]
Pfam	PF00664. ABC_membrane. 2 hits. PF00005. ABC_tran. 2 hits. [Graphical view]
SMART	SM00382. AAA. 2 hits. [Graphical view]
SUPFAM	SSF90123. ABC_TM_1. 2 hits.
PROSITE	PS50929. ABC_TM1F. 2 hits. PS00211. ABC_TRANSPORTER_1. 2 hits. PS50893. ABC_TRANSPORTER_2. 2 hits. [Graphical view]
ProtoNet	Search...
Other
ChEMBL	CHEMBL1743129.
GenomeRNAi	5244.
NextBio	20258.
SOURCE	Search...

Entry information

Entry name

MDR3_HUMAN

Accession

Primary (citable) accession number: P21439
Secondary accession number(s): A0A2V7 , A4D1D3, A4D1D4, A4D1D5, D6W5P3, D6W5P4, Q14813

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 1, 1991
Last sequence update:	February 20, 2007
Last modified:	May 1, 2013
This is version 139 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.