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Q96J66 (ABCCB_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 100. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
ATP-binding cassette sub-family C member 11
Alternative name(s):
Multidrug resistance-associated protein 8
Gene names
Name:ABCC11
Synonyms:MRP8
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length1382 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Participates in physiological processes involving bile acids, conjugated steroids and cyclic nucleotides. Enhances the cellular extrusion of cAMP and cGMP. Stimulates the ATP-dependent uptake of a range of physiological and synthetic lipophilic anions, including the glutathione S-conjugates leukotriene C4 and dinitrophenyl S-glutathione, steroid sulfates such as dehydroepiandrosterone 3-sulfate (DHEAS) and estrone 3-sulfate, glucuronides such as estradiol 17-beta-D-glucuronide (E217betaG), the monoanionic bile acids glycocholate and taurocholate, and methotrexate. Probably functions to secrete earwax. Ref.4 Ref.5 Ref.6

Subcellular location

Membrane; Multi-pass membrane protein.

Tissue specificity

Expressed in many tissues. Not expressed in kidney, spleen and colon. Highly expressed in breast cancer. Expressed at moderate levels in normal breast and testis and at very low levels in liver, brain and placenta. Ref.1 Ref.3

Polymorphism

The allele with Arg-184 is responsible for the dry earwax phenotype [MIM:117800]. Human earwax is a Mendelian trait consisting of wet and dry types. The wet earwax is brownish and sticky, whereas the dry type lacks cerumen. The wet cerumen phenotype is completely dominant. The dry type is seen frequently (80-95%) among East Asians, but uncommon (0-3%) in populations of European and African origins. Intermediate frequencies (30-50%) of the dry type are seen in populations of Southern Asia, the Pacific Islands, Central Asia and Asia Minor, as well as among the Native North American and Inuit of Asian ancestry.

Sequence similarities

Belongs to the ABC transporter superfamily. ABCC family. Conjugate transporter (TC 3.A.1.208) subfamily. [View classification]

Contains 2 ABC transmembrane type-1 domains.

Contains 2 ABC transporter domains.

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q96J66-1)

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: Q96J66-2)

Also known as: Isoform A;

The sequence of this isoform differs from the canonical sequence as follows:
     1261-1298: Missing.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 13821382ATP-binding cassette sub-family C member 11
PRO_0000225594

Regions

Topological domain1 – 163163Cytoplasmic Potential
Transmembrane164 – 18421Helical; Potential
Transmembrane195 – 21521Helical; Potential
Transmembrane271 – 29121Helical; Potential
Transmembrane297 – 31721Helical; Potential
Transmembrane384 – 40421Helical; Potential
Transmembrane418 – 43821Helical; Potential
Topological domain439 – 806368Cytoplasmic Potential
Transmembrane807 – 82721Helical; Potential
Transmembrane864 – 88421Helical; Potential
Transmembrane931 – 95121Helical; Potential
Transmembrane1050 – 107021Helical; Potential
Topological domain1071 – 1382312Cytoplasmic Potential
Domain163 – 443281ABC transmembrane type-1 1
Domain508 – 732225ABC transporter 1
Domain806 – 1105300ABC transmembrane type-1 2
Domain1141 – 1375235ABC transporter 2
Nucleotide binding544 – 5518ATP 1 Potential
Nucleotide binding1175 – 11828ATP 2 Potential

Amino acid modifications

Glycosylation8381N-linked (GlcNAc...) Potential
Glycosylation8441N-linked (GlcNAc...) Potential
Glycosylation9921N-linked (GlcNAc...) Potential

Natural variations

Alternative sequence1261 – 129838Missing in isoform 2.
VSP_017351
Natural variant191R → H.
Corresponds to variant rs16945988 [ dbSNP | Ensembl ].
VAR_025437
Natural variant1801G → R in dry earwax phenotype; reduced transport activity. Ref.6
Corresponds to variant rs17822931 [ dbSNP | Ensembl ].
VAR_025438
Natural variant3171A → E. Ref.3
Corresponds to variant rs11863236 [ dbSNP | Ensembl ].
VAR_048144
Natural variant5461T → M.
Corresponds to variant rs17822471 [ dbSNP | Ensembl ].
VAR_048145
Natural variant6481V → I.
Corresponds to variant rs16945930 [ dbSNP | Ensembl ].
VAR_048146
Natural variant6871V → I.
Corresponds to variant rs16945928 [ dbSNP | Ensembl ].
VAR_048147
Natural variant7351K → R.
Corresponds to variant rs16945926 [ dbSNP | Ensembl ].
VAR_048148
Natural variant13441H → R. Ref.3
Corresponds to variant rs16945916 [ dbSNP | Ensembl ].
VAR_048149

Experimental info

Sequence conflict1991V → A in AAK58869. Ref.2
Sequence conflict1991V → A in AAL99902. Ref.2
Sequence conflict3111L → P in AAK19755. Ref.3
Sequence conflict3631K → E in AAK58869. Ref.2
Sequence conflict3631K → E in AAL99902. Ref.2
Sequence conflict3951T → A in AAK19755. Ref.3
Sequence conflict6321L → P in AAK19755. Ref.3
Sequence conflict6881L → Q in AAK19755. Ref.3
Sequence conflict7021I → V in AAK19755. Ref.3
Sequence conflict9821K → E in AAK19755. Ref.3

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified December 1, 2001. Version 1.
Checksum: 0F3C17DC69AE97F4

FASTA1,382154,301
        10         20         30         40         50         60 
MTRKRTYWVP NSSGGLVNRG IDIGDDMVSG LIYKTYTLQD GPWSQQERNP EAPGRAAVPP 

        70         80         90        100        110        120 
WGKYDAALRT MIPFRPKPRF PAPQPLDNAG LFSYLTVSWL TPLMIQSLRS RLDENTIPPL 

       130        140        150        160        170        180 
SVHDASDKNV QRLHRLWEEE VSRRGIEKAS VLLVMLRFQR TRLIFDALLG ICFCIASVLG 

       190        200        210        220        230        240 
PILIIPKILE YSEEQLGNVV HGVGLCFALF LSECVKSLSF SSSWIINQRT AIRFRAAVSS 

       250        260        270        280        290        300 
FAFEKLIQFK SVIHITSGEA ISFFTGDVNY LFEGVCYGPL VLITCASLVI CSISSYFIIG 

       310        320        330        340        350        360 
YTAFIAILCY LLVFPLAVFM TRMAVKAQHH TSEVSDQRIR VTSEVLTCIK LIKMYTWEKP 

       370        380        390        400        410        420 
FAKIIEDLRR KERKLLEKCG LVQSLTSITL FIIPTVATAV WVLIHTSLKL KLTASMAFSM 

       430        440        450        460        470        480 
LASLNLLRLS VFFVPIAVKG LTNSKSAVMR FKKFFLQESP VFYVQTLQDP SKALVFEEAT 

       490        500        510        520        530        540 
LSWQQTCPGI VNGALELERN GHASEGMTRP RDALGPEEEG NSLGPELHKI NLVVSKGMML 

       550        560        570        580        590        600 
GVCGNTGSGK SSLLSAILEE MHLLEGSVGV QGSLAYVPQQ AWIVSGNIRE NILMGGAYDK 

       610        620        630        640        650        660 
ARYLQVLHCC SLNRDLELLP FGDMTEIGER GLNLSGGQKQ RISLARAVYS DRQIYLLDDP 

       670        680        690        700        710        720 
LSAVDAHVGK HIFEECIKKT LRGKTVVLVT HQLQYLEFCG QIILLENGKI CENGTHSELM 

       730        740        750        760        770        780 
QKKGKYAQLI QKMHKEATSD MLQDTAKIAE KPKVESQALA TSLEESLNGN AVPEHQLTQE 

       790        800        810        820        830        840 
EEMEEGSLSW RVYHHYIQAA GGYMVSCIIF FFVVLIVFLT IFSFWWLSYW LEQGSGTNSS 

       850        860        870        880        890        900 
RESNGTMADL GNIADNPQLS FYQLVYGLNA LLLICVGVCS SGIFTKVTRK ASTALHNKLF 

       910        920        930        940        950        960 
NKVFRCPMSF FDTIPIGRLL NCFAGDLEQL DQLLPIFSEQ FLVLSLMVIA VLLIVSVLSP 

       970        980        990       1000       1010       1020 
YILLMGAIIM VICFIYYMMF KKAIGVFKRL ENYSRSPLFS HILNSLQGLS SIHVYGKTED 

      1030       1040       1050       1060       1070       1080 
FISQFKRLTD AQNNYLLLFL SSTRWMALRL EIMTNLVTLA VALFVAFGIS STPYSFKVMA 

      1090       1100       1110       1120       1130       1140 
VNIVLQLASS FQATARIGLE TEAQFTAVER ILQYMKMCVS EAPLHMEGTS CPQGWPQHGE 

      1150       1160       1170       1180       1190       1200 
IIFQDYHMKY RDNTPTVLHG INLTIRGHEV VGIVGRTGSG KSSLGMALFR LVEPMAGRIL 

      1210       1220       1230       1240       1250       1260 
IDGVDICSIG LEDLRSKLSV IPQDPVLLSG TIRFNLDPFD RHTDQQIWDA LERTFLTKAI 

      1270       1280       1290       1300       1310       1320 
SKFPKKLHTD VVENGGNFSV GERQLLCIAR AVLRNSKIIL IDEATASIDM ETDTLIQRTI 

      1330       1340       1350       1360       1370       1380 
REAFQGCTVL VIAHRVTTVL NCDHILVMGN GKVVEFDRPE VLRKKPGSLF AALMATATSS 


LR 

« Hide

Isoform 2 (Isoform A) [UniParc].

Checksum: 4859DCC95569B2C7
Show »

FASTA1,344150,093

References

[1]"Two new genes from the human ATP-binding cassette transporter superfamily, ABCC11 and ABCC12, tandemly duplicated on chromosome 16q12."
Tammur J., Prades C., Arnould I., Rzhetsky A., Hutchinson A., Adachi M., Schuetz J.D., Swoboda K.J., Ptacek L.J., Rosier M., Dean M., Allikmets R.
Gene 273:89-96(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY.
Tissue: Testis.
[2]"Multiple splicing variants of two new human ATP-binding cassette transporters, ABCC11 and ABCC12."
Yabuuchi H., Shimizu H., Takayanagi S., Ishikawa T.
Biochem. Biophys. Res. Commun. 288:933-939(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2).
Tissue: Liver.
[3]"MRP8, a new member of ABC transporter superfamily, identified by EST database mining and gene prediction program, is highly expressed in breast cancer."
Bera T.K., Lee S., Salvatore G., Lee B.K., Pastan I.H.
Mol. Med. 7:509-516(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY, VARIANTS GLU-317 AND ARG-1344.
Tissue: Mammary gland.
[4]"MRP8, ATP-binding cassette C11 (ABCC11), is a cyclic nucleotide efflux pump and a resistance factor for fluoropyrimidines 2',3'-dideoxycytidine and 9'-(2'-phosphonylmethoxyethyl)adenine."
Guo Y., Kotova E., Chen Z.S., Lee K., Hopper-Borge E., Belinsky M.G., Kruh G.D.
J. Biol. Chem. 278:29509-29514(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN CYCLIC NUCLEOTIDE EFFLUX.
[5]"Transport of bile acids, sulfated steroids, estradiol 17-beta-D-glucuronide, and leukotriene C4 by human multidrug resistance protein 8 (ABCC11)."
Chen Z.S., Guo Y., Belinsky M.G., Kotova E., Kruh G.D.
Mol. Pharmacol. 67:545-557(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[6]"A SNP in the ABCC11 gene is the determinant of human earwax type."
Yoshiura K., Kinoshita A., Ishida T., Ninokata A., Ishikawa T., Kaname T., Bannai M., Tokunaga K., Sonoda S., Komaki R., Ihara M., Saenko V.A., Alipov G.K., Sekine I., Komatsu K., Takahashi H., Nakashima M., Sosonkina N. expand/collapse author list , Mapendano C.K., Ghadami M., Nomura M., Liang D.-S., Miwa N., Kim D.-K., Garidkhuu A., Natsume N., Ohta T., Tomita H., Kaneko A., Kikuchi M., Russomando G., Hirayama K., Ishibashi M., Takahashi A., Saitou N., Murray J.C., Saito S., Nakamura Y., Niikawa N.
Nat. Genet. 38:324-330(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT ARG-180, CHARACTERIZATION OF VARIANT ARG-180, FUNCTION IN SECRETION OF EARWAX.
+Additional computationally mapped references.

Web resources

Protein Spotlight

Of earwax and migration - Issue 67 of February 2006

ABCMdb

Database for mutations in ABC proteins

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AY040219 mRNA. Translation: AAK76739.1.
AF367202 mRNA. Translation: AAK58869.1.
AF411579 mRNA. Translation: AAL99902.1.
AF352582 mRNA. Translation: AAK19755.1.
RefSeqNP_115972.2. NM_032583.3.
NP_149163.2. NM_033151.3.
NP_660187.1. NM_145186.2.
UniGeneHs.652267.

3D structure databases

ProteinModelPortalQ96J66.
SMRQ96J66. Positions 446-733, 778-1378.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

STRING9606.ENSP00000349017.

Chemistry

ChEMBLCHEMBL2073702.

Protein family/group databases

TCDB3.A.1.208.13. the atp-binding cassette (abc) superfamily.

PTM databases

PhosphoSiteQ96J66.

Polymorphism databases

DMDM74762666.

Proteomic databases

PaxDbQ96J66.
PRIDEQ96J66.

Protocols and materials databases

DNASU85320.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000353782; ENSP00000311326; ENSG00000121270. [Q96J66-2]
ENST00000356608; ENSP00000349017; ENSG00000121270. [Q96J66-1]
ENST00000394747; ENSP00000378230; ENSG00000121270. [Q96J66-1]
ENST00000394748; ENSP00000378231; ENSG00000121270. [Q96J66-1]
GeneID85320.
KEGGhsa:85320.
UCSCuc002eff.1. human. [Q96J66-1]
uc002efh.1. human. [Q96J66-2]

Organism-specific databases

CTD85320.
GeneCardsGC16M048249.
HGNCHGNC:14639. ABCC11.
HPAHPA031980.
MIM117800. phenotype.
607040. gene.
neXtProtNX_Q96J66.
PharmGKBPA24393.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG1132.
HOVERGENHBG108314.
InParanoidQ96J66.
KOK05671.
OMAWRTMIPF.
OrthoDBEOG7MWGW0.
PhylomeDBQ96J66.
TreeFamTF352085.

Enzyme and pathway databases

ReactomeREACT_15518. Transmembrane transport of small molecules.

Gene expression databases

ArrayExpressQ96J66.
BgeeQ96J66.
CleanExHS_ABCC11.
GenevestigatorQ96J66.

Family and domain databases

Gene3D3.40.50.300. 2 hits.
InterProIPR003593. AAA+_ATPase.
IPR011527. ABC1_TM_dom.
IPR003439. ABC_transporter-like.
IPR017871. ABC_transporter_CS.
IPR001140. ABC_transptr_TM_dom.
IPR027417. P-loop_NTPase.
[Graphical view]
PfamPF00664. ABC_membrane. 2 hits.
PF00005. ABC_tran. 2 hits.
[Graphical view]
SMARTSM00382. AAA. 2 hits.
[Graphical view]
SUPFAMSSF52540. SSF52540. 2 hits.
SSF90123. SSF90123. 2 hits.
PROSITEPS50929. ABC_TM1F. 2 hits.
PS00211. ABC_TRANSPORTER_1. 2 hits.
PS50893. ABC_TRANSPORTER_2. 2 hits.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiABCC11.
GenomeRNAi85320.
NextBio75831.
PROQ96J66.
SOURCESearch...

Entry information

Entry nameABCCB_HUMAN
AccessionPrimary (citable) accession number: Q96J66
Secondary accession number(s): Q8TDJ0, Q96JA6, Q9BX80
Entry history
Integrated into UniProtKB/Swiss-Prot: March 7, 2006
Last sequence update: December 1, 2001
Last modified: April 16, 2014
This is version 100 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

Protein Spotlight

Protein Spotlight articles and cited UniProtKB/Swiss-Prot entries

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 16

Human chromosome 16: entries, gene names and cross-references to MIM