ATP-binding cassette sub-family B member 6 (ABCB6)

The protein contains 842 amino acids for an estimated molecular weight of 93886 Da.

 

ATP-dependent transporter that catalyzes the transport of a broad-spectrum of porphyrins from the cytoplasm to the extracellular space through the plasma membrane or into the vesicle lumen (PubMed:33007128, PubMed:27507172, PubMed:17661442, PubMed:23792964). May also function as an ATP-dependent importer of porphyrins from the cytoplasm into the mitochondria, in turns may participate in the de novo heme biosynthesis regulation and in the coordination of heme and iron homeostasis during phenylhydrazine stress (PubMed:17006453, PubMed:10837493, PubMed:23792964, PubMed:33007128). May also play a key role in the early steps of melanogenesis producing PMEL amyloid fibrils (PubMed:29940187). In vitro, it confers to cells a resistance to toxic metal such as arsenic and cadmium and against chemotherapeutics agent such as 5-fluorouracil, SN-38 and vincristin (PubMed:25202056, PubMed:21266531, PubMed:31053883). In addition may play a role in the transition metal homeostasis (By similarity). (updated: June 2, 2021)

Protein identification was indicated in the following studies:

  1. Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
  2. Lange and co-workers. (2014) Annotating N termini for the human proteome project: N termini and Nα-acetylation status differentiate stable cleaved protein species from degradation remnants in the human erythrocyte proteome. J Proteome Res. 13(4), 2028-2044.
  3. Hegedűs and co-workers. (2015) Inconsistencies in the red blood cell membrane proteome analysis: generation of a database for research and diagnostic applications. Database (Oxford) 1-8.
  4. Wilson and co-workers. (2016) Comparison of the Proteome of Adult and Cord Erythroid Cells, and Changes in the Proteome Following Reticulocyte Maturation. Mol Cell Proteomics. 15(6), 1938-1946.
  5. Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
  6. D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
  7. Chu and co-workers. (2018) Quantitative mass spectrometry of human reticulocytes reveal proteome-wide modifications during maturation. Br J Haematol. 180(1), 118-133.

Methods

The following articles were analysed to gather the proteome content of erythrocytes.

The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.

PublicationIdentification 1Uniprot mapping 2Not mapped /
Obsolete
TrEMBLSwiss-Prot
Goodman (2013)2289 (gene list)227853205992269
Lange (2014)123412347281224
Hegedus (2015)2638262202352387
Wilson (2016)165815281702911068
d'Alessandro (2017)18261817201815
Bryk (2017)20902060101081942
Chu (2018)18531804553621387

1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry

The compilation of older studies can be retrieved from the Red Blood Cell Collection database.

The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.

No sequence conservation computed yet.

This protein is annotated as membranous in Gene Ontology, is annotated as membranous in UniProt, is predicted to be membranous by TOPCONS.


Interpro domains
Total structural coverage: 36%
Model score: 38

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VariantDescription
MCOPCB7
a breast cancer sample; somatic mutation
DUH3
dbSNP:rs13018440
dbSNP:rs60322991
DUH3
PSHK2
PSHK2
DUH3
DUH3
DUH3
dbSNP:rs13402964
MCOPCB7
DUH3
DUH3
PSHK2
Decrease expression; does not affect susbtrate binding; does not affect ATP-binding; loss of plasma membrane expression
May be a modifier of disease severity in porphyria patients; loss of expression
May be a modifier of disease severity in porphyria patients; increases expression; does not affect susbtrate binding; impairs ATP-binding; Loss of ATP
May be a modifier of disease severity in porphyria patients; loss of expression
May be a modifier of disease severity in porphyria patients; loss of expression
May be a modifier of disease severity in porphyria patients; loss of expression

The reference OMIM entry for this protein is 111600

Blood group, langereis system; lan

A number sign (#) is used with this entry because the Lan(-) blood group phenotype 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. ... More on the omim web site

Subscribe to this protein entry history

July 1, 2021: Protein entry updated
Automatic update: Entry updated from uniprot information.

Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated

Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated

Nov. 23, 2017: Protein entry updated
Automatic update: Uniprot description updated

March 16, 2016: Protein entry updated
Automatic update: OMIM entry 111600 was added.

Feb. 24, 2016: Protein entry updated
Automatic update: model status changed

Jan. 27, 2016: Protein entry updated
Automatic update: model status changed

Jan. 24, 2016: Protein entry updated
Automatic update: model status changed