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Q96J66

- ABCCB_HUMAN

UniProt

Q96J66 - ABCCB_HUMAN

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Protein
ATP-binding cassette sub-family C member 11
Gene
ABCC11, MRP8
Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5 - Experimental evidence at protein leveli

Functioni

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.3 Publications

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi544 – 5518ATP 1 Reviewed prediction
Nucleotide bindingi1175 – 11828ATP 2 Reviewed prediction

GO - Molecular functioni

  1. ATP binding Source: UniProtKB-KW
  2. ATPase activity, coupled to transmembrane movement of substances Source: InterPro
  3. organic anion transmembrane transporter activity Source: UniProt
  4. purine nucleotide transmembrane transporter activity Source: UniProt
Complete GO annotation...

GO - Biological processi

  1. organic anion transport Source: UniProt
  2. purine nucleotide transport Source: UniProt
  3. transmembrane transport Source: Reactome
Complete GO annotation...

Keywords - Biological processi

Transport

Keywords - Ligandi

ATP-binding, Nucleotide-binding

Enzyme and pathway databases

ReactomeiREACT_15480. ABC-family proteins mediated transport.

Protein family/group databases

TCDBi3.A.1.208.13. the atp-binding cassette (abc) superfamily.

Names & Taxonomyi

Protein namesi
Recommended name:
ATP-binding cassette sub-family C member 11
Alternative name(s):
Multidrug resistance-associated protein 8
Gene namesi
Name:ABCC11
Synonyms:MRP8
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 16

Organism-specific databases

HGNCiHGNC:14639. ABCC11.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 163163Cytoplasmic Reviewed prediction
Add
BLAST
Transmembranei164 – 18421Helical; Reviewed prediction
Add
BLAST
Transmembranei195 – 21521Helical; Reviewed prediction
Add
BLAST
Transmembranei271 – 29121Helical; Reviewed prediction
Add
BLAST
Transmembranei297 – 31721Helical; Reviewed prediction
Add
BLAST
Transmembranei384 – 40421Helical; Reviewed prediction
Add
BLAST
Transmembranei418 – 43821Helical; Reviewed prediction
Add
BLAST
Topological domaini439 – 806368Cytoplasmic Reviewed prediction
Add
BLAST
Transmembranei807 – 82721Helical; Reviewed prediction
Add
BLAST
Transmembranei864 – 88421Helical; Reviewed prediction
Add
BLAST
Transmembranei931 – 95121Helical; Reviewed prediction
Add
BLAST
Transmembranei1050 – 107021Helical; Reviewed prediction
Add
BLAST
Topological domaini1071 – 1382312Cytoplasmic Reviewed prediction
Add
BLAST

GO - Cellular componenti

  1. extracellular vesicular exosome Source: UniProt
  2. integral component of plasma membrane Source: UniProt
  3. plasma membrane Source: Reactome
Complete GO annotation...

Keywords - Cellular componenti

Membrane

Pathology & Biotechi

Organism-specific databases

MIMi117800. phenotype.
PharmGKBiPA24393.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 13821382ATP-binding cassette sub-family C member 11
PRO_0000225594Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi838 – 8381N-linked (GlcNAc...) Reviewed prediction
Glycosylationi844 – 8441N-linked (GlcNAc...) Reviewed prediction
Glycosylationi992 – 9921N-linked (GlcNAc...) Reviewed prediction

Keywords - PTMi

Glycoprotein

Proteomic databases

PaxDbiQ96J66.
PRIDEiQ96J66.

PTM databases

PhosphoSiteiQ96J66.

Expressioni

Tissue specificityi

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.2 Publications

Gene expression databases

ArrayExpressiQ96J66.
BgeeiQ96J66.
CleanExiHS_ABCC11.
GenevestigatoriQ96J66.

Organism-specific databases

HPAiHPA031980.

Interactioni

Protein-protein interaction databases

STRINGi9606.ENSP00000349017.

Structurei

3D structure databases

ProteinModelPortaliQ96J66.
SMRiQ96J66. Positions 525-731, 806-1379.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini163 – 443281ABC transmembrane type-1 1
Add
BLAST
Domaini508 – 732225ABC transporter 1
Add
BLAST
Domaini806 – 1105300ABC transmembrane type-1 2
Add
BLAST
Domaini1141 – 1375235ABC transporter 2
Add
BLAST

Sequence similaritiesi

Keywords - Domaini

Repeat, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiCOG1132.
HOVERGENiHBG108314.
InParanoidiQ96J66.
KOiK05671.
OMAiWRTMIPF.
OrthoDBiEOG7MWGW0.
PhylomeDBiQ96J66.
TreeFamiTF352085.

Family and domain databases

Gene3Di3.40.50.300. 2 hits.
InterProiIPR003593. 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]
PfamiPF00664. ABC_membrane. 2 hits.
PF00005. ABC_tran. 2 hits.
[Graphical view]
SMARTiSM00382. AAA. 2 hits.
[Graphical view]
SUPFAMiSSF52540. SSF52540. 2 hits.
SSF90123. SSF90123. 2 hits.
PROSITEiPS50929. ABC_TM1F. 2 hits.
PS00211. ABC_TRANSPORTER_1. 2 hits.
PS50893. ABC_TRANSPORTER_2. 2 hits.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. Align

Isoform 1 (identifier: Q96J66-1) [UniParc]FASTAAdd to Basket

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.

« Hide

MTRKRTYWVP NSSGGLVNRG IDIGDDMVSG LIYKTYTLQD GPWSQQERNP     50
EAPGRAAVPP WGKYDAALRT MIPFRPKPRF PAPQPLDNAG LFSYLTVSWL 100
TPLMIQSLRS RLDENTIPPL SVHDASDKNV QRLHRLWEEE VSRRGIEKAS 150
VLLVMLRFQR TRLIFDALLG ICFCIASVLG PILIIPKILE YSEEQLGNVV 200
HGVGLCFALF LSECVKSLSF SSSWIINQRT AIRFRAAVSS FAFEKLIQFK 250
SVIHITSGEA ISFFTGDVNY LFEGVCYGPL VLITCASLVI CSISSYFIIG 300
YTAFIAILCY LLVFPLAVFM TRMAVKAQHH TSEVSDQRIR VTSEVLTCIK 350
LIKMYTWEKP FAKIIEDLRR KERKLLEKCG LVQSLTSITL FIIPTVATAV 400
WVLIHTSLKL KLTASMAFSM LASLNLLRLS VFFVPIAVKG LTNSKSAVMR 450
FKKFFLQESP VFYVQTLQDP SKALVFEEAT LSWQQTCPGI VNGALELERN 500
GHASEGMTRP RDALGPEEEG NSLGPELHKI NLVVSKGMML GVCGNTGSGK 550
SSLLSAILEE MHLLEGSVGV QGSLAYVPQQ AWIVSGNIRE NILMGGAYDK 600
ARYLQVLHCC SLNRDLELLP FGDMTEIGER GLNLSGGQKQ RISLARAVYS 650
DRQIYLLDDP LSAVDAHVGK HIFEECIKKT LRGKTVVLVT HQLQYLEFCG 700
QIILLENGKI CENGTHSELM QKKGKYAQLI QKMHKEATSD MLQDTAKIAE 750
KPKVESQALA TSLEESLNGN AVPEHQLTQE EEMEEGSLSW RVYHHYIQAA 800
GGYMVSCIIF FFVVLIVFLT IFSFWWLSYW LEQGSGTNSS RESNGTMADL 850
GNIADNPQLS FYQLVYGLNA LLLICVGVCS SGIFTKVTRK ASTALHNKLF 900
NKVFRCPMSF FDTIPIGRLL NCFAGDLEQL DQLLPIFSEQ FLVLSLMVIA 950
VLLIVSVLSP YILLMGAIIM VICFIYYMMF KKAIGVFKRL ENYSRSPLFS 1000
HILNSLQGLS SIHVYGKTED FISQFKRLTD AQNNYLLLFL SSTRWMALRL 1050
EIMTNLVTLA VALFVAFGIS STPYSFKVMA VNIVLQLASS FQATARIGLE 1100
TEAQFTAVER ILQYMKMCVS EAPLHMEGTS CPQGWPQHGE IIFQDYHMKY 1150
RDNTPTVLHG INLTIRGHEV VGIVGRTGSG KSSLGMALFR LVEPMAGRIL 1200
IDGVDICSIG LEDLRSKLSV IPQDPVLLSG TIRFNLDPFD RHTDQQIWDA 1250
LERTFLTKAI SKFPKKLHTD VVENGGNFSV GERQLLCIAR AVLRNSKIIL 1300
IDEATASIDM ETDTLIQRTI REAFQGCTVL VIAHRVTTVL NCDHILVMGN 1350
GKVVEFDRPE VLRKKPGSLF AALMATATSS LR 1382
Length:1,382
Mass (Da):154,301
Last modified:December 1, 2001 - v1
Checksum:i0F3C17DC69AE97F4
GO
Isoform 2 (identifier: Q96J66-2) [UniParc]FASTAAdd to Basket

Also known as: Isoform A

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

Show »
Length:1,344
Mass (Da):150,093
Checksum:i4859DCC95569B2C7
GO

Polymorphismi

The allele with Arg-184 is responsible for the dry earwax phenotype [MIMi: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.

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti19 – 191R → H.
Corresponds to variant rs16945988 [ dbSNP | Ensembl ].
VAR_025437
Natural varianti180 – 1801G → R in dry earwax phenotype; reduced transport activity. 1 Publication
Corresponds to variant rs17822931 [ dbSNP | Ensembl ].
VAR_025438
Natural varianti317 – 3171A → E.1 Publication
Corresponds to variant rs11863236 [ dbSNP | Ensembl ].
VAR_048144
Natural varianti546 – 5461T → M.
Corresponds to variant rs17822471 [ dbSNP | Ensembl ].
VAR_048145
Natural varianti648 – 6481V → I.
Corresponds to variant rs16945930 [ dbSNP | Ensembl ].
VAR_048146
Natural varianti687 – 6871V → I.
Corresponds to variant rs16945928 [ dbSNP | Ensembl ].
VAR_048147
Natural varianti735 – 7351K → R.
Corresponds to variant rs16945926 [ dbSNP | Ensembl ].
VAR_048148
Natural varianti1344 – 13441H → R.1 Publication
Corresponds to variant rs16945916 [ dbSNP | Ensembl ].
VAR_048149

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1261 – 129838Missing in isoform 2.
VSP_017351Add
BLAST

Sequence conflict

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti199 – 1991V → A in AAK58869. 1 Publication
Sequence conflicti199 – 1991V → A in AAL99902. 1 Publication
Sequence conflicti311 – 3111L → P in AAK19755. 1 Publication
Sequence conflicti363 – 3631K → E in AAK58869. 1 Publication
Sequence conflicti363 – 3631K → E in AAL99902. 1 Publication
Sequence conflicti395 – 3951T → A in AAK19755. 1 Publication
Sequence conflicti632 – 6321L → P in AAK19755. 1 Publication
Sequence conflicti688 – 6881L → Q in AAK19755. 1 Publication
Sequence conflicti702 – 7021I → V in AAK19755. 1 Publication
Sequence conflicti982 – 9821K → E in AAK19755. 1 Publication

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
AY040219 mRNA. Translation: AAK76739.1.
AF367202 mRNA. Translation: AAK58869.1.
AF411579 mRNA. Translation: AAL99902.1.
AF352582 mRNA. Translation: AAK19755.1.
CCDSiCCDS10732.1. [Q96J66-1]
CCDS10733.1. [Q96J66-2]
RefSeqiNP_115972.2. NM_032583.3. [Q96J66-1]
NP_149163.2. NM_033151.3. [Q96J66-1]
NP_660187.1. NM_145186.2. [Q96J66-2]
UniGeneiHs.652267.

Genome annotation databases

EnsembliENST00000353782; ENSP00000311326; ENSG00000121270. [Q96J66-2]
ENST00000356608; ENSP00000349017; ENSG00000121270. [Q96J66-1]
ENST00000394747; ENSP00000378230; ENSG00000121270. [Q96J66-1]
ENST00000394748; ENSP00000378231; ENSG00000121270. [Q96J66-1]
GeneIDi85320.
KEGGihsa:85320.
UCSCiuc002eff.1. human. [Q96J66-1]
uc002efh.1. human. [Q96J66-2]

Polymorphism databases

DMDMi74762666.

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Web resourcesi

Protein Spotlight

Of earwax and migration - Issue 67 of February 2006

ABCMdb

Database for mutations in ABC proteins

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
AY040219 mRNA. Translation: AAK76739.1 .
AF367202 mRNA. Translation: AAK58869.1 .
AF411579 mRNA. Translation: AAL99902.1 .
AF352582 mRNA. Translation: AAK19755.1 .
CCDSi CCDS10732.1. [Q96J66-1 ]
CCDS10733.1. [Q96J66-2 ]
RefSeqi NP_115972.2. NM_032583.3. [Q96J66-1 ]
NP_149163.2. NM_033151.3. [Q96J66-1 ]
NP_660187.1. NM_145186.2. [Q96J66-2 ]
UniGenei Hs.652267.

3D structure databases

ProteinModelPortali Q96J66.
SMRi Q96J66. Positions 525-731, 806-1379.
ModBasei Search...

Protein-protein interaction databases

STRINGi 9606.ENSP00000349017.

Chemistry

ChEMBLi CHEMBL2073702.

Protein family/group databases

TCDBi 3.A.1.208.13. the atp-binding cassette (abc) superfamily.

PTM databases

PhosphoSitei Q96J66.

Polymorphism databases

DMDMi 74762666.

Proteomic databases

PaxDbi Q96J66.
PRIDEi Q96J66.

Protocols and materials databases

DNASUi 85320.
Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000353782 ; ENSP00000311326 ; ENSG00000121270 . [Q96J66-2 ]
ENST00000356608 ; ENSP00000349017 ; ENSG00000121270 . [Q96J66-1 ]
ENST00000394747 ; ENSP00000378230 ; ENSG00000121270 . [Q96J66-1 ]
ENST00000394748 ; ENSP00000378231 ; ENSG00000121270 . [Q96J66-1 ]
GeneIDi 85320.
KEGGi hsa:85320.
UCSCi uc002eff.1. human. [Q96J66-1 ]
uc002efh.1. human. [Q96J66-2 ]

Organism-specific databases

CTDi 85320.
GeneCardsi GC16M048249.
HGNCi HGNC:14639. ABCC11.
HPAi HPA031980.
MIMi 117800. phenotype.
607040. gene.
neXtProti NX_Q96J66.
PharmGKBi PA24393.
GenAtlasi Search...

Phylogenomic databases

eggNOGi COG1132.
HOVERGENi HBG108314.
InParanoidi Q96J66.
KOi K05671.
OMAi WRTMIPF.
OrthoDBi EOG7MWGW0.
PhylomeDBi Q96J66.
TreeFami TF352085.

Enzyme and pathway databases

Reactomei REACT_15480. ABC-family proteins mediated transport.

Miscellaneous databases

GeneWikii ABCC11.
GenomeRNAii 85320.
NextBioi 75831.
PROi Q96J66.
SOURCEi Search...

Gene expression databases

ArrayExpressi Q96J66.
Bgeei Q96J66.
CleanExi HS_ABCC11.
Genevestigatori Q96J66.

Family and domain databases

Gene3Di 3.40.50.300. 2 hits.
InterProi IPR003593. 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 ]
Pfami PF00664. ABC_membrane. 2 hits.
PF00005. ABC_tran. 2 hits.
[Graphical view ]
SMARTi SM00382. AAA. 2 hits.
[Graphical view ]
SUPFAMi SSF52540. SSF52540. 2 hits.
SSF90123. SSF90123. 2 hits.
PROSITEi PS50929. ABC_TM1F. 2 hits.
PS00211. ABC_TRANSPORTER_1. 2 hits.
PS50893. ABC_TRANSPORTER_2. 2 hits.
[Graphical view ]
ProtoNeti Search...

Publicationsi

  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. Cited for: VARIANT ARG-180, CHARACTERIZATION OF VARIANT ARG-180, FUNCTION IN SECRETION OF EARWAX.

Entry informationi

Entry nameiABCCB_HUMAN
AccessioniPrimary (citable) accession number: Q96J66
Secondary accession number(s): Q8TDJ0, Q96JA6, Q9BX80
Entry historyi
Integrated into UniProtKB/Swiss-Prot: March 7, 2006
Last sequence update: December 1, 2001
Last modified: September 3, 2014
This is version 104 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 16
    Human chromosome 16: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. Protein Spotlight
    Protein Spotlight articles and cited UniProtKB/Swiss-Prot entries
  6. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

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