View source for ABCC11

{{Infobox_gene}}
'''ATP-binding cassette transporter sub-family C member 11''' is a [[protein]] that in humans is encoded by the ''ABCC11'' [[gene]].<ref name="pmid11483364">{{cite journal | vauthors = Tammur J, Prades C, Arnould I, Rzhetsky A, Hutchinson A, Adachi M, Schuetz JD, Swoboda KJ, Ptácek LJ, Rosier M, Dean M, Allikmets R | title = Two new genes from the human ATP-binding cassette transporter superfamily, ABCC11 and ABCC12, tandemly duplicated on chromosome 16q12 | journal = Gene | volume = 273 | issue = 1 | pages = 89–96 | date = Jul 2001 | pmid = 11483364 | pmc =  | doi = 10.1016/S0378-1119(01)00572-8 }}</ref><ref name="pmid11435397">{{cite journal | vauthors = Dean M, Rzhetsky A, Allikmets R | title = The human ATP-binding cassette (ABC) transporter superfamily | journal = Genome Research | volume = 11 | issue = 7 | pages = 1156–66 | date = Jul 2001 | pmid = 11435397 | pmc =  | doi = 10.1101/gr.184901 }}</ref><ref name="entrez"/>

The gene is responsible for determination of human [[Earwax|cerumen]] type (wet or dry ear wax) and presence of underarm [[osmidrosis]] (odor associated with [[Perspiration|sweat]] caused by excessive [[apocrine]] secretion).

== Function ==

The protein encoded by this gene is a member of the superfamily of ATP-binding cassette (ABC) transporters. ABC proteins transport various molecules across extra- and intra-cellular membranes. ABC genes are divided into seven distinct subfamilies (ABC1, MDR/TAP, MRP, ALD, OABP, GCN20, White). This ABC full transporter is a member of the MRP subfamily which is involved in multi-drug resistance. The product of this gene participates in physiological processes involving bile acids, conjugated steroids, and cyclic nucleotides. In addition, a SNP in this gene is responsible for determination of human [[earwax]] type and presence of underarm odour. This gene and family member ABCC12 are determined to be derived by duplication and are both localized to chromosome 16q12.1. Multiple alternatively spliced transcript variants have been described for this gene.<ref name="entrez">{{cite web | title = Entrez Gene: ABCC11 ATP-binding cassette, sub-family C (CFTR/MRP), member 11| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=85320| accessdate = }}</ref>

== Molecular genetics ==
The ''ABCC11'' [[gene]] is present in the [[human genome]] as two [[allele]]s, differing in one [[nucleotide]] also known as a [[Single-nucleotide polymorphism|single nucleotide polymorphism (SNP)]].<ref name="Toyoda_2009">{{cite journal | vauthors = Toyoda Y, Sakurai A, Mitani Y, Nakashima M, Yoshiura K, Nakagawa H, Sakai Y, Ota I, Lezhava A, Hayashizaki Y, Niikawa N, Ishikawa T | title = Earwax, osmidrosis, and breast cancer: why does one SNP (538G>A) in the human ABC transporter ABCC11 gene determine earwax type? | journal = FASEB Journal | volume = 23 | issue = 6 | pages = 2001–13 | date = Jun 2009 | pmid = 19383836 | doi = 10.1096/fj.09-129098 }}</ref> A SNP in the ''ABCC11'' gene on [[Chromosome 16 (human)|chromosome 16]] at [[Nucleobase|base]] position 538 of either a [[guanine]] or [[adenine]] controls for multiple distinct [[phenotype]]s.<ref name="Toyoda_2009" /><ref name="Yoshiura_2006" /> These respectively code for [[glycine]] and [[arginine]] in the gene's [[protein]] product. [[Heredity|Dominant inheritance]] of the GG or GA [[genotype]] is observed while the AA genotype is recessive. The phenotypes expressed by the genotypes include [[Earwax|cerumen]] type (wet or dry ear wax), [[osmidrosis]] (odor associated with [[Perspiration|sweat]] caused by excessive [[apocrine]] secretion), and [[breast cancer]] risk, although there is ongoing debate on whether if there is a real correlation of the wet ear wax phenotype to breast cancer susceptibility.<ref name="Rodriguez_2013">{{cite journal | vauthors = Rodriguez S, Steer CD, Farrow A, Golding J, Day IN | title = Dependence of deodorant usage on ABCC11 genotype: scope for personalized genetics in personal hygiene | journal = The Journal of Investigative Dermatology | volume = 133 | issue = 7 | pages = 1760–7 | date = Jul 2013 | pmid = 23325016 | pmc = 3674910 | doi = 10.1038/jid.2012.480 }}</ref><ref>{{cite journal | vauthors = Park YJ, Shin MS | title = What is the best method for treating osmidrosis? | journal = Annals of Plastic Surgery | volume = 47 | issue = 3 | pages = 303–9 | date = Sep 2001 | pmid = 11562036 | doi=10.1097/00000637-200109000-00014}}</ref> The GG or GA genotype produces the wet ear wax phenotype (sticky and brown colored) and acrid sweat odor and is the dominant allele.<ref name="Rodriguez_2013"/> Note this phenotype requires only the presence of one guanine. The [[homozygous]] recessive AA genotype produces the dry ear wax phenotype (dry and flaky) and mildly odored sweat.<ref name="Rodriguez_2013" />

The alleles containing a guanine produce a protein that is [[Glycosylation|glycosylated]] but alleles containing an adenine are not glycosylated. The resulting protein is only partially degraded by [[proteasome]]s.<ref name="Toyoda_2009"/> This effect is localized to [[ceruminous gland]] membranes.<ref name="Toyoda_2009" /> Because the adenine containing allele protein product is only partially degraded, the remaining functional protein is located on the cell surface membrane which ''ABCC11'' gene's role in sweat odor is likely in part due to the quantitative dosage of ABCC11 protein.<ref name="Toyoda_2009" />

From an [[evolution]]ary perspective, the implications of cerumen type on [[Fitness (biology)|fitness]] are unknown although odorless sweat in ancient Northern [[Eurasia]]n populations have been postulated to have an [[Adaptation|adaptive]] advantage for cold weather.<ref name="Yoshiura_2006" /> In some nonhuman [[mammal]]s, [[mating]] signals via release of an odor enhanced by increased apocrine secretion may be a factor in [[sexual selection]].<ref name="Yoshiura_2006" />

Physical [[human]] traits that are controlled by a single gene are [[Human genetics#Human traits with simple inheritance patterns|uncommon]]. Most human characteristics are controlled by multiple genes ([[polygene]]s) although ''ABCC11'' is a peculiar example of a gene with unambiguous phenotypes that is controlled by a SNP. Additionally, it is considered a [[Pleiotropy|pleiotropic]] gene.

== Demographics ==
The history of the migration of humans can be traced back using the ''ABCC11'' gene alleles. The variation between ear wax and body odor in [[Ethnic group|ethnicities]] around the world are specifically due to the ''ABCC11'' gene alleles.<ref name="Yoshiura_2006" />  It is hypothesized that 40,000 years ago, an ancient [[Mongoloid]] tribe evolved the dry ear wax phenotype that followed a spread of the dry ear wax allele to other regions of Asia via migration of the ancient tribe.<ref name="Ishikawa_2012">{{cite journal | vauthors = Ishikawa T, Toyoda Y, Yoshiura K, Niikawa N | title = Pharmacogenetics of human ABC transporter ABCC11: new insights into apocrine gland growth and metabolite secretion | journal = Frontiers in Genetics | volume = 3 | pages = 306 | date = 2012-01-01 | pmid = 23316210 | pmc = 3539816 | doi = 10.3389/fgene.2012.00306 }}</ref> The gene spread as a result of it being a beneficial [[Adaptation|adaption]] or through an evolutionary neutral [[mutation]] mechanism that went through [[genetic drift]] events.<ref name="Ishikawa_2012" />

The frequency of alleles for dry ear wax and odorless sweat is most concentrated in East- and Northeast [[Asia]], most notably [[Korea]], [[China]], [[Mongolia]], and western [[Japan]].<ref name="Yoshiura_2006">{{cite journal | vauthors = Yoshiura K, Kinoshita A, Ishida T, Ninokata A, Ishikawa T, Kaname T, Bannai M, Tokunaga K, Sonoda S, Komaki R, Ihara M, Saenko VA, Alipov GK, Sekine I, Komatsu K, Takahashi H, Nakashima M, Sosonkina N, Mapendano CK, Ghadami M, Nomura M, Liang DS, Miwa N, Kim DK, Garidkhuu A, Natsume N, Ohta T, Tomita H, Kaneko A, Kikuchi M, Russomando G, Hirayama K, Ishibashi M, Takahashi A, Saitou N, Murray JC, Saito S, Nakamura Y, Niikawa N | display-authors = 6 | title = A SNP in the ABCC11 gene is the determinant of human earwax type | journal = Nature Genetics | volume = 38 | issue = 3 | pages = 324–30 | date = Mar 2006 | pmid = 16444273 | doi = 10.1038/ng1733 }}</ref> Conversely the frequency of the allele for wet ear wax and odored sweat are highest in [[African Americans|African-American]] and [[Sub-Saharan Africans|sub-saharan]] populations.<ref name="Yoshiura_2006" /> A downward gradient of dry ear wax allele phenotypes can be drawn from northern China to southern Asia and a east-west gradient can also be drawn from eastern Siberia to western Europe.<ref name="Yoshiura_2006" /> The [[Allele frequency|allele frequencies]] within ethnicities continued to be maintained because the ''ABCC11'' gene is inherited as a [[haplotype]], a group of genes or alleles that tend to be inherited as a single unit<ref name="Yoshiura_2006" /><ref>{{cite journal | vauthors = Prokop-Prigge KA, Mansfield CJ, Parker MR, Thaler E, Grice EA, Wysocki CJ, Preti G | title = Ethnic/racial and genetic influences on cerumen odorant profiles | journal = Journal of Chemical Ecology | volume = 41 | issue = 1 | pages = 67–74 | date = Jan 2015 | pmid = 25501636 | pmc = 4304888 | doi = 10.1007/s10886-014-0533-y }}</ref>[[Haplotype|.]]

== See also ==
* [[ATP-binding cassette transporter]]

== References ==
{{Reflist|33em}}

== Further reading ==
{{refbegin|33em}}
* {{cite journal | vauthors = Bera TK, Lee S, Salvatore G, Lee B, Pastan I | title = MRP8, a new member of ABC transporter superfamily, identified by EST database mining and gene prediction program, is highly expressed in breast cancer | journal = Molecular Medicine | volume = 7 | issue = 8 | pages = 509–16 | date = Aug 2001 | pmid = 11591886 | pmc = 1950066 | doi =  }}
* {{cite journal | vauthors = Yabuuchi H, Shimizu H, Takayanagi S, Ishikawa T | title = Multiple splicing variants of two new human ATP-binding cassette transporters, ABCC11 and ABCC12 | journal = Biochemical and Biophysical Research Communications | volume = 288 | issue = 4 | pages = 933–9 | date = Nov 2001 | pmid = 11688999 | doi = 10.1006/bbrc.2001.5865 }}
* {{cite journal | vauthors = Lai L, Tan TM | title = Role of glutathione in the multidrug resistance protein 4 (MRP4/ABCC4)-mediated efflux of cAMP and resistance to purine analogues | journal = The Biochemical Journal | volume = 361 | issue = Pt 3 | pages = 497–503 | date = Feb 2002 | pmid = 11802779 | pmc = 1222332 | doi = 10.1042/0264-6021:3610497 }}
* {{cite journal | vauthors = Stríz I, Jaresová M, Lácha J, Sedlácek J, Vítko S | title = MRP 8/14 and procalcitonin serum levels in organ transplantations | journal = Annals of Transplantation | volume = 6 | issue = 2 | pages = 6–9 | year = 2002 | pmid = 11803621 | doi =  }}
* {{cite journal | vauthors = Tomita H, Yamada K, Ghadami M, Ogura T, Yanai Y, Nakatomi K, Sadamatsu M, Masui A, Kato N, Niikawa N | title = Mapping of the wet/dry earwax locus to the pericentromeric region of chromosome 16 | journal = Lancet | volume = 359 | issue = 9322 | pages = 2000–2 | date = Jun 2002 | pmid = 12076558 | doi = 10.1016/S0140-6736(02)08835-9 }}
* {{cite journal | vauthors = Turriziani O, Schuetz JD, Focher F, Scagnolari C, Sampath J, Adachi M, Bambacioni F, Riva E, Antonelli G | title = Impaired 2',3'-dideoxy-3'-thiacytidine accumulation in T-lymphoblastoid cells as a mechanism of acquired resistance independent of multidrug resistant protein 4 with a possible role for ATP-binding cassette C11 | journal = The Biochemical Journal | volume = 368 | issue = Pt 1 | pages = 325–32 | date = Nov 2002 | pmid = 12133003 | pmc = 1222956 | doi = 10.1042/BJ20020494 }}
* {{cite journal | vauthors = Guo Y, Kotova E, Chen ZS, Lee K, Hopper-Borge E, Belinsky MG, Kruh GD | title = 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 | journal = The Journal of Biological Chemistry | volume = 278 | issue = 32 | pages = 29509–14 | date = Aug 2003 | pmid = 12764137 | doi = 10.1074/jbc.M304059200 }}
* {{cite journal | vauthors = Bouma G, Lam-Tse WK, Wierenga-Wolf AF, Drexhage HA, Versnel MA | title = Increased serum levels of MRP-8/14 in type 1 diabetes induce an increased expression of CD11b and an enhanced adhesion of circulating monocytes to fibronectin | journal = Diabetes | volume = 53 | issue = 8 | pages = 1979–86 | date = Aug 2004 | pmid = 15277376 | doi = 10.2337/diabetes.53.8.1979 }}
* {{cite journal | vauthors = Vogl T, Ludwig S, Goebeler M, Strey A, Thorey IS, Reichelt R, Foell D, Gerke V, Manitz MP, Nacken W, Werner S, Sorg C, Roth J | title = MRP8 and MRP14 control microtubule reorganization during transendothelial migration of phagocytes | journal = Blood | volume = 104 | issue = 13 | pages = 4260–8 | date = Dec 2004 | pmid = 15331440 | doi = 10.1182/blood-2004-02-0446 }}
* {{cite journal | vauthors = Chen ZS, Guo Y, Belinsky MG, Kotova E, Kruh GD | title = Transport of bile acids, sulfated steroids, estradiol 17-beta-D-glucuronide, and leukotriene C4 by human multidrug resistance protein 8 (ABCC11) | journal = Molecular Pharmacology | volume = 67 | issue = 2 | pages = 545–57 | date = Feb 2005 | pmid = 15537867 | doi = 10.1124/mol.104.007138 }}
* {{cite journal | vauthors = Bortfeld M, Rius M, König J, Herold-Mende C, Nies AT, Keppler D | title = Human multidrug resistance protein 8 (MRP8/ABCC11), an apical efflux pump for steroid sulfates, is an axonal protein of the CNS and peripheral nervous system | journal = Neuroscience | volume = 137 | issue = 4 | pages = 1247–57 | year = 2006 | pmid = 16359813 | doi = 10.1016/j.neuroscience.2005.10.025 }}
* {{cite journal | vauthors = Viemann D, Barczyk K, Vogl T, Fischer U, Sunderkötter C, Schulze-Osthoff K, Roth J | title = MRP8/MRP14 impairs endothelial integrity and induces a caspase-dependent and -independent cell death program | journal = Blood | volume = 109 | issue = 6 | pages = 2453–60 | date = Mar 2007 | pmid = 17095618 | doi = 10.1182/blood-2006-08-040444 }}
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== External links ==
* {{MeshName|ABCC11+protein,+human}}
* {{UCSC gene info|ABCC11}}

{{NLM content}}
{{ABC transporters}}

{{DEFAULTSORT:Abcc11}}
[[Category:ABC transporters]]