RBCC Red Blood Cell Collection

ABCB6 (MTABC3, PRP, UMAT) [Confidence: high (a blood group or CD marker)]
ATP-binding cassette sub-family B member 6, mitochondrial (Mitochondrial ABC transporter 3; Mt-ABC transporter 3; P-glycoprotein-related protein; Ubiquitously-expressed mammalian ABC half transporter)

hRBCD IPI00014555
IPI00014555 ATP-binding cassette, sub-family B, member 6, mitochondrial precursor ATP-binding cassette, sub-family B, member 6, mitochondrial precursor membrane 2 1 8 4 9 4 6 3 2 n/a 11 1 2 7 4 6 4 3 2 4 mitochondrial transmembrane n/a expected molecular weight found in band between 49-62 kDa

BGMUT lan
1332 lan ABCB6 LAN 1533dup10nt 1533-1543 dupCGGCTCCCTGC L515fs coding sequence gDNA and cDNA Lan(-) very rare; found in Japan 22246506 Helias et al. Nature Genetics 2012 44 170-173 Blumenfeld OO. 2012-02-08 18:06:19.710 NA

UniProt Q9NP58
ID ABCB6_HUMAN Reviewed; 842 AA.
AC Q9NP58; O75542; Q49A66; Q59GQ5; Q6ZME6; Q96ME8; Q9HAQ6; Q9HAQ7;
read moreDT 21-FEB-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2000, sequence version 1.
DT 22-JAN-2014, entry version 136.
DE RecName: Full=ATP-binding cassette sub-family B member 6, mitochondrial;
DE AltName: Full=Mitochondrial ABC transporter 3;
DE Short=Mt-ABC transporter 3;
DE AltName: Full=P-glycoprotein-related protein;
DE AltName: Full=Ubiquitously-expressed mammalian ABC half transporter;
GN Name=ABCB6; Synonyms=MTABC3, PRP, UMAT;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 1), FUNCTION, TISSUE
RP SPECIFICITY, AND SUBCELLULAR LOCATION.
RX PubMed=10837493; DOI=10.1074/jbc.275.23.17536;
RA Mitsuhashi N., Miki T., Senbongi H., Yokoi N., Yano H., Miyazaki M.,
RA Nakajima N., Iwanaga T., Yokoyama Y., Shibata T., Seino S.;
RT "MTABC3, a novel mitochondrial ATP-binding cassette protein involved
RT in iron homeostasis.";
RL J. Biol. Chem. 275:17536-17540(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND NUCLEOTIDE SEQUENCE
RP [GENOMIC DNA] OF 1-229.
RC TISSUE=Colon, and Liver;
RX PubMed=11955620; DOI=10.1016/S0167-4781(01)00340-2;
RA Emadi-Konjin H.-P., Zhang H., Anandan V., Sun D., Schuetz J.D.,
RA Furuya K.N.;
RT "Isolation of a genomic clone containing the promoter region of the
RT human ATP binding cassette (ABC) transporter, ABCB6.";
RL Biochim. Biophys. Acta 1574:117-130(2002).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RA Hirsch-Ernst K.I., Schaefer A., Ernst B.-P., Schmitz-Salue C.,
RA Awuah D., Kahl G.F.;
RT "Subcellular localization of the ABC transporter umat.";
RL Submitted (JUL-2000) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), AND NUCLEOTIDE
RP SEQUENCE [LARGE SCALE MRNA] OF 112-842 (ISOFORM 1).
RC TISSUE=Hepatoma, and Neuroepithelium;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain;
RA Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S.,
RA Ohara O., Nagase T., Kikuno R.F.;
RL Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 332-842 (ISOFORM 1).
RC TISSUE=Brain;
RA Yu W., Gibbs R.A.;
RL Submitted (JUN-1998) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP FUNCTION, DEVELOPMENTAL STAGE, INDUCTION BY CELLULAR PORPHYRINS,
RP SUBUNIT, SUBCELLULAR LOCATION, AND INTERACTION WITH HEMIN.
RX PubMed=17006453; DOI=10.1038/nature05125;
RA Krishnamurthy P.C., Du G., Fukuda Y., Sun D., Sampath J., Mercer K.E.,
RA Wang J., Sosa-Pineda B., Murti K.G., Schuetz J.D.;
RT "Identification of a mammalian mitochondrial porphyrin transporter.";
RL Nature 443:586-589(2006).
RN [9]
RP SUBCELLULAR LOCATION.
RX PubMed=17661442; DOI=10.1021/bi700015m;
RA Paterson J.K., Shukla S., Black C.M., Tachiwada T., Garfield S.,
RA Wincovitch S., Ernst D.N., Agadir A., Li X., Ambudkar S.V.,
RA Szakacs G., Akiyama S., Gottesman M.M.;
RT "Human ABCB6 localizes to both the outer mitochondrial membrane and
RT the plasma membrane.";
RL Biochemistry 46:9443-9452(2007).
RN [10]
RP SUBCELLULAR LOCATION.
RX PubMed=18279659; DOI=10.1016/j.bbrc.2008.02.027;
RA Tsuchida M., Emi Y., Kida Y., Sakaguchi M.;
RT "Human ABC transporter isoform B6 (ABCB6) localizes primarily in the
RT Golgi apparatus.";
RL Biochem. Biophys. Res. Commun. 369:369-375(2008).
RN [11]
RP SUBCELLULAR LOCATION, TISSUE SPECIFICITY, VARIANTS MCOPCB7 THR-57 AND
RP VAL-811, AND CHARACTERIZATION OF VARIANTS MCOPCB7 THR-57 AND VAL-811.
RX PubMed=22226084; DOI=10.1016/j.ajhg.2011.11.026;
RA Wang L., He F., Bu J., Liu X., Du W., Dong J., Cooney J.D.,
RA Dubey S.K., Shi Y., Gong B., Li J., McBride P.F., Jia Y., Lu F.,
RA Soltis K.A., Lin Y., Namburi P., Liang C., Sundaresan P., Paw B.H.,
RA Li D.Y., Phillips J.D., Yang Z.;
RT "ABCB6 mutations cause ocular coloboma.";
RL Am. J. Hum. Genet. 90:40-48(2012).
RN [12]
RP INVOLVEMENT IN LANGEREIS BLOOD GROUP SYSTEM.
RX PubMed=22246506; DOI=10.1038/ng.1069;
RA Helias V., Saison C., Ballif B.A., Peyrard T., Takahashi J.,
RA Takahashi H., Tanaka M., Deybach J.C., Puy H., Le Gall M., Sureau C.,
RA Pham B.N., Le Pennec P.Y., Tani Y., Cartron J.P., Arnaud L.;
RT "ABCB6 is dispensable for erythropoiesis and specifies the new blood
RT group system Langereis.";
RL Nat. Genet. 44:170-173(2012).
RN [13]
RP STRUCTURE BY NMR OF 558-842 IN COMPLEX WITH ADP.
RX PubMed=16791740; DOI=10.1007/s10858-006-9000-6;
RA Kurashima-Ito K., Ikeya T., Senbongi H., Tochio H., Mikawa T.,
RA Shibata T., Ito Y.;
RT "Heteronuclear multidimensional NMR and homology modelling studies of
RT the C-terminal nucleotide-binding domain of the human mitochondrial
RT ABC transporter ABCB6.";
RL J. Biomol. NMR 35:53-71(2006).
RN [14]
RP VARIANT [LARGE SCALE ANALYSIS] GLY-69.
RX PubMed=16959974; DOI=10.1126/science.1133427;
RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D.,
RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S.,
RA Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J.,
RA Dawson D., Willson J.K.V., Gazdar A.F., Hartigan J., Wu L., Liu C.,
RA Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N.,
RA Vogelstein B., Kinzler K.W., Velculescu V.E.;
RT "The consensus coding sequences of human breast and colorectal
RT cancers.";
RL Science 314:268-274(2006).
CC -!- FUNCTION: Binds heme and porphyrins and functions in their ATP-
CC dependent uptake into the mitochondria. Plays a crucial role in
CC heme synthesis.
CC -!- SUBUNIT: Homodimer.
CC -!- SUBCELLULAR LOCATION: Cell membrane. Mitochondrion outer membrane;
CC Multi-pass membrane protein. Endoplasmic reticulum. Golgi
CC apparatus.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9NP58-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9NP58-4; Sequence=VSP_021973;
CC Note=Ref.4 (BAB71347) sequence differs from that shown due to
CC splicing through aberrant splice sites;
CC -!- TISSUE SPECIFICITY: Widely expressed. High expression is detected
CC in the retinal epithelium.
CC -!- DEVELOPMENTAL STAGE: Highly expressed in fetal liver.
CC -!- INDUCTION: Up-regulated by cellular porphyrins (at protein level).
CC -!- POLYMORPHISM: Genetic variations in ABCB6 define the Langereis
CC blood group system (LAN) [MIM:111600]. Individuals with Lan(-)
CC blood group lack the Lan antigen on their red blood cells. These
CC individuals may have anti-Lan antibodies in their serum, which can
CC cause transfusion reactions or hemolytic disease of the fetus or
CC newborn. The Lan(-) blood group is only clinically significant in
CC transfusion settings or during pregnancy; otherwise Lan(-)
CC individuals have no clinical features.
CC -!- DISEASE: Microphthalmia, isolated, with coloboma, 7 (MCOPCB7)
CC [MIM:614497]: A disorder of eye formation, ranging from small size
CC of a single eye to complete bilateral absence of ocular tissues.
CC Ocular abnormalities like opacities of the cornea and lens,
CC scaring of the retina and choroid, and other abnormalities may
CC also be present. Ocular colobomas are a set of malformations
CC resulting from abnormal morphogenesis of the optic cup and stalk,
CC and the fusion of the fetal fissure (optic fissure). Note=The
CC disease is caused by mutations affecting the gene represented in
CC this entry.
CC -!- MISCELLANEOUS: Depletion of Abcb6 by RNAi abrogates heme
CC biosynthesis. Overexpression enhances porphyrin biosynthesis.
CC -!- SIMILARITY: Belongs to the ABC transporter superfamily. ABCB
CC family. Heavy Metal importer (TC 3.A.1.210) subfamily.
CC -!- SIMILARITY: Contains 1 ABC transmembrane type-1 domain.
CC -!- SIMILARITY: Contains 1 ABC transporter domain.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAG33617.1; Type=Erroneous initiation;
CC Sequence=AAG33618.1; Type=Erroneous initiation;
CC Sequence=AAH43423.1; Type=Miscellaneous discrepancy; Note=Intron retention;
CC Sequence=BAD18782.1; Type=Erroneous termination; Positions=168; Note=Translated as Trp;
CC Sequence=BAD92291.1; Type=Miscellaneous discrepancy; Note=Chimeric cDNA;
CC -!- WEB RESOURCE: Name=ABCMdb; Note=Database for mutations in ABC
CC proteins;
CC URL="http://abcmutations.hegelab.org/proteinDetails?uniprot_id=Q9NP58";
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DR EMBL; AB039371; BAA96733.1; -; Genomic_DNA.
DR EMBL; AF076775; AAF75107.1; -; mRNA.
DR EMBL; AF308472; AAG33617.1; ALT_INIT; mRNA.
DR EMBL; AF308473; AAG33618.1; ALT_INIT; Genomic_DNA.
DR EMBL; AJ289233; CAB95766.2; -; mRNA.
DR EMBL; AK057026; BAB71347.1; ALT_SEQ; mRNA.
DR EMBL; AK172812; BAD18782.1; ALT_SEQ; mRNA.
DR EMBL; AB209054; BAD92291.1; ALT_SEQ; mRNA.
DR EMBL; BC000559; AAH00559.1; -; mRNA.
DR EMBL; BC043423; AAH43423.1; ALT_SEQ; mRNA.
DR EMBL; AF070598; AAC28653.1; -; mRNA.
DR RefSeq; NP_005680.1; NM_005689.2.
DR RefSeq; XP_005246272.1; XM_005246215.1.
DR UniGene; Hs.107911; -.
DR PDB; 3NH6; X-ray; 2.00 A; A=558-842.
DR PDB; 3NH9; X-ray; 2.10 A; A=558-842.
DR PDB; 3NHA; X-ray; 2.10 A; A=558-842.
DR PDB; 3NHB; X-ray; 2.15 A; A=558-842.
DR PDBsum; 3NH6; -.
DR PDBsum; 3NH9; -.
DR PDBsum; 3NHA; -.
DR PDBsum; 3NHB; -.
DR ProteinModelPortal; Q9NP58; -.
DR SMR; Q9NP58; 239-828.
DR IntAct; Q9NP58; 3.
DR MINT; MINT-3071268; -.
DR STRING; 9606.ENSP00000265316; -.
DR BindingDB; Q9NP58; -.
DR ChEMBL; CHEMBL2007630; -.
DR TCDB; 3.A.1.210.6; the atp-binding cassette (abc) superfamily.
DR PhosphoSite; Q9NP58; -.
DR DMDM; 13123949; -.
DR PaxDb; Q9NP58; -.
DR PRIDE; Q9NP58; -.
DR DNASU; 10058; -.
DR Ensembl; ENST00000265316; ENSP00000265316; ENSG00000115657.
DR Ensembl; ENST00000439002; ENSP00000394333; ENSG00000115657.
DR GeneID; 10058; -.
DR KEGG; hsa:10058; -.
DR UCSC; uc002vkc.2; human.
DR CTD; 10058; -.
DR GeneCards; GC02M220038; -.
DR HGNC; HGNC:47; ABCB6.
DR HPA; HPA046723; -.
DR MIM; 111600; phenotype.
DR MIM; 605452; gene.
DR MIM; 614497; phenotype.
DR neXtProt; NX_Q9NP58; -.
DR Orphanet; 98938; Colobomatous microphthalmia.
DR Orphanet; 194; Ocular coloboma.
DR PharmGKB; PA24388; -.
DR eggNOG; COG5265; -.
DR HOVERGEN; HBG080810; -.
DR InParanoid; Q9NP58; -.
DR KO; K05661; -.
DR OMA; KPQTMER; -.
DR OrthoDB; EOG7Z69BT; -.
DR PhylomeDB; Q9NP58; -.
DR Reactome; REACT_15518; Transmembrane transport of small molecules.
DR ChiTaRS; ABCB6; human.
DR EvolutionaryTrace; Q9NP58; -.
DR GeneWiki; ABCB6; -.
DR GenomeRNAi; 10058; -.
DR NextBio; 38003; -.
DR PRO; PR:Q9NP58; -.
DR ArrayExpress; Q9NP58; -.
DR Bgee; Q9NP58; -.
DR CleanEx; HS_ABCB6; -.
DR Genevestigator; Q9NP58; -.
DR GO; GO:0043190; C:ATP-binding cassette (ABC) transporter complex; NAS:UniProtKB.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:UniProtKB.
DR GO; GO:0005794; C:Golgi apparatus; IDA:UniProtKB.
DR GO; GO:0031307; C:integral to mitochondrial outer membrane; IDA:UniProtKB.
DR GO; GO:0005774; C:vacuolar membrane; IBA:RefGenome.
DR GO; GO:0005524; F:ATP binding; IDA:MGI.
DR GO; GO:0015562; F:efflux transmembrane transporter activity; IDA:UniProtKB.
DR GO; GO:0020037; F:heme binding; IDA:UniProtKB.
DR GO; GO:0015439; F:heme-transporting ATPase activity; IMP:UniProtKB.
DR GO; GO:0007420; P:brain development; IMP:UniProtKB.
DR GO; GO:0070574; P:cadmium ion transmembrane transport; IBA:RefGenome.
DR GO; GO:0006879; P:cellular iron ion homeostasis; NAS:UniProtKB.
DR GO; GO:0071585; P:detoxification of cadmium ion; IBA:RefGenome.
DR GO; GO:0006779; P:porphyrin-containing compound biosynthetic process; IDA:UniProtKB.
DR GO; GO:0043588; P:skin development; IMP:UniProtKB.
DR InterPro; IPR003593; AAA+_ATPase.
DR InterPro; IPR011527; ABC1_TM_dom.
DR InterPro; IPR003439; ABC_transporter-like.
DR InterPro; IPR017871; ABC_transporter_CS.
DR InterPro; IPR001140; ABC_transptr_TM_dom.
DR InterPro; IPR027417; P-loop_NTPase.
DR Pfam; PF00664; ABC_membrane; 1.
DR Pfam; PF00005; ABC_tran; 1.
DR SMART; SM00382; AAA; 1.
DR SUPFAM; SSF52540; SSF52540; 1.
DR SUPFAM; SSF90123; SSF90123; 1.
DR PROSITE; PS50929; ABC_TM1F; 1.
DR PROSITE; PS00211; ABC_TRANSPORTER_1; 1.
DR PROSITE; PS50893; ABC_TRANSPORTER_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; ATP-binding; Cell membrane;
KW Complete proteome; Disease mutation; Endoplasmic reticulum;
KW Golgi apparatus; Membrane; Microphthalmia; Mitochondrion;
KW Mitochondrion outer membrane; Nucleotide-binding; Polymorphism;
KW Reference proteome; Transmembrane; Transmembrane helix; Transport.
FT CHAIN 1 842 ATP-binding cassette sub-family B member
FT 6, mitochondrial.
FT /FTId=PRO_0000000248.
FT TRANSMEM 27 47 Helical; (Potential).
FT TRANSMEM 73 93 Helical; (Potential).
FT TRANSMEM 107 127 Helical; (Potential).
FT TRANSMEM 148 168 Helical; (Potential).
FT TRANSMEM 186 206 Helical; (Potential).
FT TRANSMEM 265 285 Helical; (Potential).
FT TRANSMEM 376 396 Helical; (Potential).
FT TRANSMEM 409 431 Helical; (Potential).
FT TRANSMEM 502 522 Helical; (Potential).
FT TRANSMEM 530 550 Helical; (Potential).
FT DOMAIN 265 556 ABC transmembrane type-1.
FT DOMAIN 590 824 ABC transporter.
FT NP_BIND 623 630 ATP (Potential).
FT VAR_SEQ 183 228 Missing (in isoform 2).
FT /FTId=VSP_021973.
FT VARIANT 57 57 A -> T (in MCOPCB7; hypomorphic
FT mutation).
FT /FTId=VAR_067394.
FT VARIANT 69 69 R -> G (in a breast cancer sample;
FT somatic mutation).
FT /FTId=VAR_035732.
FT VARIANT 293 293 L -> V (in dbSNP:rs13018440).
FT /FTId=VAR_047552.
FT VARIANT 343 343 R -> Q (in dbSNP:rs60322991).
FT /FTId=VAR_060986.
FT VARIANT 648 648 R -> Q (in dbSNP:rs13402964).
FT /FTId=VAR_029749.
FT VARIANT 811 811 L -> V (in MCOPCB7; hypomorphic
FT mutation).
FT /FTId=VAR_067395.
FT CONFLICT 170 170 S -> N (in Ref. 2; AAG33618).
FT CONFLICT 320 320 T -> S (in Ref. 4; BAD18782).
FT CONFLICT 413 413 F -> S (in Ref. 4; BAD18782).
FT CONFLICT 616 616 G -> E (in Ref. 4; BAD18782).
FT CONFLICT 638 638 R -> L (in Ref. 4; BAD18782).
FT HELIX 561 572
FT STRAND 590 600
FT STRAND 604 613
FT STRAND 618 625
FT HELIX 628 636
FT STRAND 643 649
FT HELIX 654 656
FT HELIX 659 664
FT STRAND 666 669
FT STRAND 677 679
FT HELIX 680 685
FT HELIX 693 702
FT HELIX 706 711
FT HELIX 715 717
FT STRAND 719 721
FT HELIX 729 743
FT STRAND 746 751
FT HELIX 759 773
FT STRAND 776 781
FT HELIX 785 789
FT STRAND 792 798
FT STRAND 801 806
FT HELIX 808 814
FT HELIX 817 826
SQ SEQUENCE 842 AA; 93886 MW; E63A7D59DCE5B9ED CRC64;
MVTVGNYCEA EGPVGPAWMQ DGLSPCFFFT LVPSTRMALG TLALVLALPC RRRERPAGAD
SLSWGAGPRI SPYVLQLLLA TLQAALPLAG LAGRVGTARG APLPSYLLLA SVLESLAGAC
GLWLLVVERS QARQRLAMGI WIKFRHSPGL LLLWTVAFAA ENLALVSWNS PQWWWARADL
GQQVQFSLWV LRYVVSGGLF VLGLWAPGLR PQSYTLQVHE EDQDVERSQV RSAAQQSTWR
DFGRKLRLLS GYLWPRGSPA LQLVVLICLG LMGLERALNV LVPIFYRNIV NLLTEKAPWN
SLAWTVTSYV FLKFLQGGGT GSTGFVSNLR TFLWIRVQQF TSRRVELLIF SHLHELSLRW
HLGRRTGEVL RIADRGTSSV TGLLSYLVFN VIPTLADIII GIIYFSMFFN AWFGLIVFLC
MSLYLTLTIV VTEWRTKFRR AMNTQENATR ARAVDSLLNF ETVKYYNAES YEVERYREAI
IKYQGLEWKS SASLVLLNQT QNLVIGLGLL AGSLLCAYFV TEQKLQVGDY VLFGTYIIQL
YMPLNWFGTY YRMIQTNFID MENMFDLLKE ETEVKDLPGA GPLRFQKGRI EFENVHFSYA
DGRETLQDVS FTVMPGQTLA LVGPSGAGKS TILRLLFRFY DISSGCIRID GQDISQVTQA
SLRSHIGVVP QDTVLFNDTI ADNIRYGRVT AGNDEVEAAA QAAGIHDAIM AFPEGYRTQV
GERGLKLSGG EKQRVAIART ILKAPGIILL DEATSALDTS NERAIQASLA KVCANRTTIV
VAHRLSTVVN ADQILVIKDG CIVERGRHEA LLSRGGVYAD MWQLQQGQEE TSEDTKPQTM
ER
//

MIM 111600
*RECORD*
*FIELD* NO
111600
*FIELD* TI
#111600 BLOOD GROUP, LANGEREIS SYSTEM; LAN
*FIELD* TX
A number sign (#) is used with this entry because the Lan(-) blood group
read morephenotype is caused by homozygous or compound heterozygous mutation in
the ABCB6 gene (605452) on chromosome 2q36.

DESCRIPTION

Individuals with Lan(-) blood group lack the Lan antigen on their red
blood cells. These individuals may have anti-Lan antibodies in their
serum, which can cause transfusion reactions or hemolytic disease of the
fetus or newborn. The Lan(-) blood group is only clinically significant
in transfusion settings or during pregnancy; otherwise Lan(-)
individuals have no clinical features (summary by Helias et al., 2012).

CLINICAL FEATURES

Smith et al. (1969) reported a 26-year-old Caucasian woman with 1 child
and a history of blood transfusion who developed anti-Lan IgG antibodies
that were detected during a second pregnancy. She was found to have the
Lan(-) blood group. Due to low hemoglobin, she was transfused with her
brother's blood, which also lacked the Lan antigen. The infant developed
mild hemolytic anemia of the newborn due to the presence of maternal
anti-Lan antibodies, but recovered with time.

Page (1983) reported a 29-year-old Caucasian woman of Italian descent
who was transfused during her first pregnancy and developed anti-Lan
antibodies, which were detected during her second pregnancy. She and her
sister were found to have the Lan(-) blood group. A Lan(+) girl was born
to the proband, and the direct antiglobin test was weakly positive. The
daughter developed mild anemia, increased serum bilirubin, and jaundice,
but recovered well. There was a history of consanguinity in the family,
indicating autosomal recessive inheritance of the blood group Lan(-).

Okubo et al. (1984) reported 3 unrelated Japanese individuals with the
Lan(-) blood group phenotype who had anti-Lan antibodies. One was a man
with ulcerative colitis who had a history of being transfused; 1 was a
woman who had been pregnant 4 times; and the third was a woman with a
history of being transfused. All had anti IgG anti-Lan antibodies in
their serum, and their red cells were found to lack the Lan antigen.

INHERITANCE

The Lan(-) blood group is transmitted as an autosomal recessive trait
(Helias et al., 2012).

MOLECULAR GENETICS

In 12 individuals with the Langereis(-) blood group phenotype, Helias et
al. (2012) identified 10 different truncating mutations in the ABCB6
gene (see, e.g., 605452.0001-605452.0005). All mutations were present in
the homozygous or compound heterozygous state, indicating autosomal
recessive inheritance of the trait. None of the individuals had anemia,
abnormal erythropoiesis, or signs of porphyria, but some of the women
developed anti-Lan antibodies during pregnancy and/or in response to
transfusion with Lan(+) blood. Helias et al. (2012) suggested that
Lan(-) individuals may have altered pharmacokinetics with regard to
certain drugs potentially transported by ABCB6.

*FIELD* RF
1. Helias, V.; Saison, C.; Ballif, B. A.; Peyrard, T.; Takahashi,
J.; Takahashi, H.; Tanaka, M.; Deybach, J.-C.; Puy, H.; Le Gall, M.;
Sureau, C.; Pham, B.-N.; Le Pennec, P.-Y.; Tani, Y.; Cartron, J.-P.;
Arnaud, L.: ABCB6 is dispensable for erythropoiesis and specifies
the new blood group system Langereis. Nature Genet. 44: 170-173,
2012.

2. Okubo, Y.; Yamaguchi, H.; Seno, T.; Araki, Y.; Noguchi, M.; Shioda,
K.; Takai, M.; Daniels, G. L.: The rare red cell phenotype Lan negative
in Japanese. Transfusion 24: 534-535, 1984.

3. Page, P. L.: Hemolytic disease of the newborn due to anti-Lan. Transfusion 23:
256-257, 1983.

4. Smith, D. S.; Stratton, F.; Johnson, T.; Brown, R.; Howell, P.;
Riches, R.: Haemolytic disease of the newborn caused by anti-Lan
antibody. Brit. Med. J. 3: 90-92, 1969.

*FIELD* CN
Cassandra L. Kniffin - updated: 2/22/2012

*FIELD* CD
Victor A. McKusick: 6/4/1986

*FIELD* ED
terry: 02/24/2012
carol: 2/23/2012
ckniffin: 2/22/2012
jason: 7/5/1994
supermim: 3/16/1992
carol: 3/4/1992
supermim: 3/20/1990
carol: 3/6/1990
ddp: 10/26/1989

MIM 605452
*RECORD*
*FIELD* NO
605452
*FIELD* TI
*605452 ATP-BINDING CASSETTE, SUBFAMILY B, MEMBER 6; ABCB6
;;MITOCHONDRIAL ABC PROTEIN 3; MTABC3
read more*FIELD* TX

DESCRIPTION

For background information on the ATP-binding cassette (ABC) family of
transporter proteins, see ABCA4 (601691). In addition to the 'full' ABC
transporters with 2 transmembrane domains and 2 nucleotide-binding
domains, there are 'half' proteins that contain only 1 of each domain
(e.g., ABCB1, 171050). Full transporters are usually found in the plasma
membrane, whereas half transporters are found in subcellular organelles.
ABCB6 is located in the outer mitochondrial membrane and is required for
mitochondrial porphyrin uptake (Krishnamurthy et al., 2006).

CLONING

By searching an EST database and screening a liver cDNA library,
Mitsuhashi et al. (2000) obtained a cDNA encoding ABCB6, which they
called MTABC3. The predicted 842-amino acid ABCB6 protein, which is 34%
identical to the half transporter ABCB7 (300135), has 8
membrane-spanning regions. Northern blot analysis detected a 3.4-kb
transcript in all tissues tested, with highest expression in heart and
skeletal muscles. Immunoblot, confocal microscopy, and electron
immunohistochemical analyses demonstrated that ABCB6 is expressed as an
80-kD mitochondrial membrane protein. Analysis of mutant yeast
mitochondria suggested that ABCB6 may help maintain respiratory function
and may also transport Fe/S clusters from mitochondria to the cytosol,
thereby helping to prevent iron accumulation and DNA damage in the
organelle.

In zebrafish, Wang et al. (2012) demonstrated expression of abcb6 in the
eye and central nervous system. Using RT-PCR in human cell lines and
tissues, they observed much higher expression of ABCB6 in retinal and
retinal pigment epithelium cells than in other tissues studied.

By immunohistochemical staining of normal human skin, Zhang et al.
(2013) demonstrated that ABCB6 localizes to the epidermis and has
diffuse cytoplasmic distribution. Western blot analysis confirmed
expression of ABCB6 in human keratinocytes (HaCaT cell line) and
melanocytes (A375 cells).

GENE STRUCTURE

Mitsuhashi et al. (2000) determined that the ABCB6 gene spans 11 kb and
contains 19 exons in the protein-coding region.

MAPPING

Using FISH, Mitsuhashi et al. (2000) mapped the ABCB6 gene to 2q36,
close to the locus for lethal neonatal metabolic syndrome (603358), a
disorder of mitochondrial function associated with iron metabolism.

GENE FUNCTION

Transport of porphyrins into isolated mitochondria is energy-dependent,
as expected for the movement of anions into a negatively charged
environment. ATP-binding cassette transporters actively facilitate the
transmembrane movement of substances. Krishnamurthy et al. (2006) found
that the mitochondrial ATP-binding cassette transporter ABCB6 is
upregulated (mRNA and protein in human and mouse cells) by elevation of
cellular porphyrins and postulated that ABCB6 has a function in
porphyrin transport. The authors also predicted that ABCB6 is
functionally linked to heme biosynthesis, because its mRNA is found in
both human bone marrow and CD71+ early erythroid cells (by database
searching), and because ABCB6 is highly expressed in human fetal liver,
and Abcb6 in mouse embryonic liver. Krishnamurthy et al. (2006)
demonstrated that ABCB6 is uniquely located in the outer mitochondrial
membrane and is required for mitochondrial porphyrin uptake. After ABCB6
is upregulated in response to increased intracellular porphyrin,
mitochondrial porphyrin uptake activates de novo porphyrin biosynthesis.
This process was blocked when the Abcb6 gene in mice was silenced.
Krishnamurthy et al. (2006) concluded that their results challenged
previous assumptions about the intracellular movement of porphyrins and
the factors controlling heme biosynthesis.

Helias et al. (2012) identified ABCB6 as the genetic basis of the
Langereis (Lan) blood group antigen (see 111600). ABCB6 was demonstrated
to be present at the plasma membrane of erythrocytes, and the protein
was shown to play a role in export of porphyrin from red blood cells.
The Lan antigen was also present on HepG2 hepatocellular carcinoma
cells, but not on several other cancer cell lines.

MOLECULAR GENETICS

- Lan(-) Blood Group Phenotype

In 12 individuals with the Langereis(-) blood group phenotype (111600),
Helias et al. (2012) identified 10 different truncating mutations in the
ABCB6 gene (see, e.g., 605452.0001-605452.0005). All mutations were
present in the homozygous or compound heterozygous state, indicating
autosomal recessive inheritance of the trait. None of the individuals
had anemia, abnormal erythropoiesis, or signs of porphyria, but some of
the women developed anti-Lan antibodies during pregnancy and/or in
response to transfusion with Lan(+) blood. Helias et al. (2012)
suggested that Lan(-) individuals may have altered pharmacokinetics with
regard to certain drugs potentially transported by ABCB6.

- Isolated Microphthalmia with Coloboma 7

In a 3-generation Chinese family, originally reported by Dong et al.
(2009), with autosomal dominant iris and chorioretinal coloboma (614497)
mapping to chromosome 2q35 and known to be negative for mutation in
coloboma-associated genes, Wang et al. (2012) sequenced the exons of 76
candidate genes and identified a heterozygous missense mutation in the
ABCB6 gene (L811V; 605452.0006) that segregated with the disease.
Subsequent analysis of ABCB6 in 116 sporadic Indian patients with
coloboma who were negative for mutation in 9 known coloboma genes
revealed heterozygosity for a different missense mutation (A57T;
605452.0007) in 3 unrelated patients with microphthalmia and coloboma
(MCOPCB7; 614497).

- Dyschromatosis Universalis Hereditaria 3

In a 5-generation Chinese family segregating autosomal dominant
dyschromatosis universalis hereditaria (DUH3; 615402) mapping to
chromosome 2q33.1-q36.1, Zhang et al. (2013) performed whole-exome and
Sanger sequencing and identified a heterozygous missense mutation in the
ABCB6 gene (L356P; 605452.0008) that segregated with disease in the
family and was not found in 500 geographically matched controls.
Screening of the ABCB6 gene in 6 sporadic DUH patients revealed
heterozygosity for missense mutations (S170G, 605452.0009; G579E,
605452.0010) in 2 patients. Immunofluorescence analysis of transfected
B16 cell lines demonstrated that mutant ABCB6 is retained in the Golgi
apparatus, whereas wildtype protein accumulates in the dendrites.

ANIMAL MODEL

Wang et al. (2012) performed morpholino knockdown of abcb6 in zebrafish
and observed coloboma and retarded development. The phenotypes could be
rescued by wildtype ABCB6 mRNA, but could not be rescued by injection of
human mRNA containing either the L811V (605452.0006) or the A57T
(605452.0007) mutation.

*FIELD* AV
.0001
LANGEREIS BLOOD GROUP SYSTEM, LAN(-) PHENOTYPE
ABCB6, GLN239TER

In a Belgian woman with the Lan(-) blood group phenotype (111600),
Helias et al. (2012) identified a homozygous 717G-A transition in exon 3
of the ABCB6 gene, resulting in a gln239-to-ter (Q239X) substitution.

.0002
LANGEREIS BLOOD GROUP SYSTEM, LAN(-) PHENOTYPE
ABCB6, 2-BP DEL, 1690AT

In a Japanese woman with the Lan(-) blood group phenotype (111600),
Helias et al. (2012) identified a homozygous 2-bp deletion (1690delAT)
in exon 11 of the ABCB6 gene, resulting in a frameshift and premature
termination.

.0003
LANGEREIS BLOOD GROUP SYSTEM, LAN(-) PHENOTYPE
ABCB6, ARG648TER

In 3 unrelated patients, 2 females and 1 male, with the Lan(-) blood
group phenotype (111600), Helias et al. (2012) identified a homozygous
1942C-T transition in exon 14 of the ABCB6 gene, resulting in an
arg648-to-ter (R648X) substitution. One patient was of Greek descent,
another from northern France, and the third from Maghreb.

.0004
LANGEREIS BLOOD GROUP SYSTEM, LAN(-) PHENOTYPE
ABCB6, 2-BP DEL, 1985TC

In a man from northern France with the Lan(-) blood group phenotype
(111600), Helias et al. (2012) identified a homozygous 2-bp deletion
(1985delTC) in exon 15 of the ABCB6 gene, resulting in a frameshift and
premature termination.

.0005
LANGEREIS BLOOD GROUP SYSTEM, LAN(-) PHENOTYPE
ABCB6, IVS16DS, T-G, +2

In 2 individuals from northeastern France with the Lan(-) blood group
phenotype (111600), Helias et al. (2012) identified a homozygous T-to-G
transversion in intron 16 (2256+2T-G), resulting in a splice site
defect.

.0006
MICROPHTHALMIA, ISOLATED, WITH COLOBOMA 7
ABCB6, LEU811VAL

In 7 affected members of a 3-generation Chinese family segregating
autosomal dominant iris and chorioretinal coloboma (614497), originally
reported by Dong et al. (2009), Wang et al. (2012) identified
heterozygosity for a 2431C-G transition in the ABCB6 gene, resulting in
a leu811-to-val (L811V) substitution at a highly conserved residue. The
mutation was not found in unaffected family members or in 600 DNA
samples from ethnically matched controls.

.0007
MICROPHTHALMIA, ISOLATED, WITH COLOBOMA 7
ABCB6, ALA57THR

In 3 unrelated Indian patients with microphthalmia and coloboma
(MCOPCB7; 614497), Wang et al. (2012) identified heterozygosity for a
169G-A transition in exon 1 of the ABCB6 gene, resulting in an
ala57-to-thr (A57T) substitution at a highly conserved residue. The
mutation was not found in 200 ethnically matched control DNA samples.

.0008
DYSCHROMATOSIS UNIVERSALIS HEREDITARIA 3
ABCB6, LEU356PRO

In 10 affected members over 5 generations of a Chinese family with
dyschromatosis universalis hereditaria (DUH3; 615402), Zhang et al.
(2013) identified heterozygosity for a c.1067T-C transition in exon 5 of
the ABCB6 gene, resulting in a leu356-to-pro (L356P) substitution at a
highly conserved residue. The mutation was not found in unaffected
family members or in 500 geographically matched controls.
Immunofluorescence analysis of transfected mouse B16 cell lines
demonstrated that the L356P mutant is largely retained in the Golgi
apparatus, whereas wildtype ABCB6 accumulates in the dendrites.

.0009
DYSCHROMATOSIS UNIVERSALIS HEREDITARIA 3
ABCB6, SER170GLY

In a sporadic patient with dyschromatosis universalis hereditaria (DUH3;
615402), Zhang et al. (2013) identified heterozygosity for a c.508A-G
transition in exon 1 of the ABCB6 gene, resulting in a ser170-to-gly
(S170G) substitution at a highly conserved residue. The mutation was not
found in 400 controls or in the 1000 Genomes Project or UCSC Genome
Browser databases. Immunofluorescence analysis of transfected mouse B16
cell lines demonstrated that the S170G mutant is largely retained in the
Golgi apparatus, whereas wildtype ABCB6 accumulates in the dendrites.

.0010
DYSCHROMATOSIS UNIVERSALIS HEREDITARIA 3
ABCB6, GLY579GLU

In a sporadic patient with dyschromatosis universalis hereditaria (DUH3;
615402), Zhang et al. (2013) identified heterozygosity for a c.1736G-A
transition in exon 12 of the ABCB6 gene, resulting in a gly579-to-glu
(G579E) substitution at a highly conserved residue. The mutation was not
found in 400 controls or in the 1000 Genomes Project or UCSC Genome
Browser databases. Immunofluorescence analysis of transfected mouse B16
cell lines demonstrated that the G579E mutant is largely retained in the
Golgi apparatus, whereas wildtype ABCB6 accumulates in the dendrites.

*FIELD* RF
1. Dong, J.; Bu, J.; Li, J.; Zhuo, Y.; Wang, L.: [Linkage analysis
of a Chinese family with autosomal dominant congenital retinaochoroidal
coloboma.] Chinese J. Med. Genet. 26: 263-266, 2009. Note: Article
in Chinese.

2. Helias, V.; Saison, C.; Ballif, B. A.; Peyrard, T.; Takahashi,
J.; Takahashi, H.; Tanaka, M.; Deybach, J.-C.; Puy, H.; Le Gall, M.;
Sureau, C.; Pham, B.-N.; Le Pennec, P.-Y.; Tani, Y.; Cartron, J.-P.;
Arnaud, L.: ABCB6 is dispensable for erythropoiesis and specifies
the new blood group system Langereis. Nature Genet. 44: 170-173,
2012.

3. Krishnamurthy, P. C.; Du, G.; Fukuda, Y.; Sun, D.; Sampath, J.;
Mercer, K. E.; Wang, J.; Sosa-Pineda, B.; Murti, K. G.; Schuetz, J.
D.: Identification of a mammalian mitochondrial porphyrin transporter. Nature 443:
586-589, 2006.

4. Mitsuhashi, N.; Miki, T.; Senbongi, H.; Yokoi, N.; Yano, H.; Miyazaki,
M.; Nakajima, N.; Iwanaga, T.; Yokoyama, Y.; Shibata, T.; Seino, S.
: MTABC3, a novel mitochondrial ATP-binding cassette protein involved
in iron homeostasis. J. Biol. Chem. 275: 17536-17540, 2000.

5. Wang, L.; He, F.; Bu, J.; Zhen, Y.; Liu, X.; Du, W.; Dong, J.;
Cooney, J. D.; Dubey, S. K.; Shi, Y.; Gong, B.; Li, J.; and 13 others
: ABCB6 mutations cause ocular coloboma. Am. J. Hum. Genet. 90:
40-48, 2012. Note: Erratum: Am. J. Hum. Genet. 91: 397 only, 2012.

6. Zhang, C.; Li, D.; Zhang, J.; Chen, X.; Huang, M.; Archacki, S.;
Tian, Y.; Ren, W.; Mei, A.; Zhang, Q.; Fang, M.; Su, Z.; and 10 others
: Mutations in ABCB6 cause dyschromatosis universalis hereditaria. J.
Invest. Derm. 133: 2221-2228, 2013.

*FIELD* CN
Marla J. F. O'Neill - updated: 9/6/2013
Marla J. F. O'Neill - updated: 2/24/2012
Cassandra L. Kniffin - updated: 2/22/2012
Ada Hamosh - updated: 10/24/2006

*FIELD* CD
Paul J. Converse: 12/5/2000

*FIELD* ED
carol: 09/16/2013
carol: 9/9/2013
tpirozzi: 9/9/2013
tpirozzi: 9/6/2013
carol: 9/11/2012
carol: 2/27/2012
terry: 2/24/2012
carol: 2/24/2012
ckniffin: 2/22/2012
alopez: 11/6/2006
terry: 10/24/2006
mgross: 12/5/2000

MIM 614497
*RECORD*
*FIELD* NO
614497
*FIELD* TI
#614497 MICROPHTHALMIA, ISOLATED, WITH COLOBOMA 7; MCOPCB7
*FIELD* TX
A number sign (#) is used with this entry because of evidence that
read moremicrophthalmia with coloboma can be caused by heterozygous mutation in
the ABCB6 gene (605452) on chromosome 2q35.

For a discussion of genetic heterogeneity of isolated colobomatous
microphthalmia, see MCOPCB1 (300345).

MAPPING

In members of a 3-generation Chinese family with autosomal dominant iris
and chorioretinal coloboma who were negative for mutation in known
coloboma-associated genes, Wang et al. (2012) performed genomewide
linkage analysis and found linkage to chromosome 2q35. This family was
originally reported by Dong et al. (2009).

MOLECULAR GENETICS

In a 3-generation Chinese family with autosomal dominant iris and
chorioretinal coloboma mapping to chromosome 2q35 and known to be
negative for mutation in known coloboma-associated genes, Wang et al.
(2012) sequenced the exons of 76 candidate genes and identified a
heterozygous missense mutation in the ABCB6 gene (L811V; 605452.0006)
that segregated with disease in the family and was not found in DNA
samples from 600 ethnically matched controls. Subsequent analysis of
ABCB6 in 116 sporadic Indian coloboma patients, 63 of whom had
microphthalmia and coloboma, 21 isolated coloboma, and 32 aniridia, who
were all negative for mutation in 9 known coloboma genes, revealed
heterozygosity for a different missense mutation (A57T; 605452.0007) in
3 unrelated patients with microphthalmia and coloboma; the mutation was
not found in DNA samples from 200 ethnically matched controls.

*FIELD* RF
1. Dong, J.; Bu, J.; Li, J.; Zhuo, Y.; Wang, L.: [Linkage analysis
of a Chinese family with autosomal dominant congenital retinaochoroidal
coloboma.] Chinese J. Med. Genet. 26: 263-266, 2009. Note: Article
in Chinese.

2. Wang, L.; He, F.; Bu, J.; Zhen, Y.; Liu, X.; Du, W.; Dong, J.;
Cooney, J. D.; Dubey, S. K.; Shi, Y.; Gong, B.; Li, J.; and 13 others
: ABCB6 mutations cause ocular coloboma. Am. J. Hum. Genet. 90:
40-48, 2012. Note: Erratum: Am. J. Hum. Genet. 91: 397 only, 2012.

*FIELD* CS
INHERITANCE:
Autosomal dominant

HEAD AND NECK:
[Eyes];
Coloboma, iris;
Coloboma, chorioretinal;
Microphthalmia (in some patients)

MOLECULAR BASIS:
Caused by mutation in the ATP-binding cassette, subfamily B, member
6 gene (ABCB6, 605452.0001)

*FIELD* CD
Marla J. F. O'Neill: 2/28/2012

*FIELD* ED
joanna: 02/28/2012

*FIELD* CD
Marla J. F. O'Neill: 2/27/2012

*FIELD* ED
carol: 09/11/2012
terry: 3/5/2012
carol: 2/27/2012