Membrane transport protein XK (XK)

The protein contains 444 amino acids for an estimated molecular weight of 50902 Da.

 

May be involved in sodium-dependent transport of neutral amino acids or oligopeptides. (updated: March 4, 2015)

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.
Protein sequence (FASTA)
Protein coevolution profile (FreeContact)
Multiple Sequence Alignment (Muscle)

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

Topcons

Interpro domains
Total structural coverage: 24%
Model score: 28
MODL_I-TASSER-2.1

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VariantDescription
MLS
MLS
MLS; atypical without hematologic, neuromuscular, or cerebral involvement

No binding partner found

The reference OMIM entry for this protein is 300842

Mcleod syndrome; mclds
Mcleod phenotype
Neuroacanthocytosis, mcleod type mcleod syndrome with chronic granulomatous disease, included

A number sign (#) is used with this entry because the McLeod phenotype is caused by mutation in the XK gene (314850), encoding an antigen of the Kell blood group system (see 110900).

DESCRIPTION

Hematologically, McLeod syndrome is characterized by the absence of red blood cell Kx antigen, weak expression of Kell red blood cell antigens, acanthocytosis, and compensated hemolysis. Most carriers of this McLeod blood group phenotype have acanthocytosis and elevated serum creatine kinase levels and are prone to develop a severe neurologic disorder resembling Huntington disease (143100). Onset of neurologic symptoms ranges between 25 and 60 years (mean onset 30-40 years), and penetrance appears to be high. Additional symptoms include generalized seizures, neuromuscular symptoms leading to weakness and atrophy, and cardiomyopathy mainly manifesting with atrial fibrillation, malignant arrhythmias, and dilated cardiomyopathy (summary by Jung et al., 2007). The cooccurrence of McLeod syndrome and chronic granulomatous disease (CGD; 306400) results from a contiguous gene deletion (Francke et al., 1985).

CLINICAL FEATURES

The McLeod phenotype was described by Allen et al. (1961) in a man of that surname. His red cells showed unaccountably weak reactivity to Kell antisera. In 1970, his red cells were noted to be acanthocytic in the absence of abetalipoproteinemia. The precursor missing in McLeod's red cells is called Kx. The X-linked locus determining this substance is called Xk. McLeod had a compensated hemolytic state (Wimer et al., 1976). He did not have CGD. Evidence for X-linkage of Xk was provided by mosaicism in females for both acanthocytosis and red cell Kx. The observations showed that some blood group antigenic substances are important to both structure and function of cell membranes. Jung et al. (2007) stated that Hugh McLeod, the original propositus, died at the age of 69 after developing all major McLeod syndrome manifestations. Symmans et al. (1979) described the second example of the McLeod phenotype in the absence of CGD and the first example of a rare blood group being recognized because of a morphologic abnormality of red cells. Heterozygous females showed mosaicism with a normal and an acanthocytic red cell population. Thus, lyonization of this locus occurs even though nonlyonization holds for the Xg (314700) and ichthyosis (steroid sulfatase) loci (308100) which are in the same small segment of Xp. All cases of X-linked CGD that had been studied had Kx-negative leukocytes (Marsh, 1979). At least two Xg:XK recombinants are known (Tippett, 1981). Danek et al. (2001) remarked that, like other erythrocyte phenotypes, the peculiar pattern of weakly expressed Kell antigens received its name from the propositus. Acanthocytosis was noted much later (Wimer et al., 1977). The diagnosis of the McLeod phenotype in a boy with chronic anemia from a large New Zealand family led to the recognition of features such as hemolysis, hepatomegaly, and splenomegaly (Symmans et al., 1979) and proved the previous assumption of X-linked inheritance. It was Marsh et al. (1981) who recognized muscle involvement and proposed the designation 'McLeod syndrome.' Schwartz et al. (1982) reported areflexia and chorea in the New Zealand family. Faillace et al. (1982) noted the presence of McLeod red cells in a patient with amyotrophic chorea and acanthocytosis. Densen et al. (1981) reported a highly informative family in which 4 of 8 brothers ... More on the omim web site

The reference OMIM entry for this protein is 314850

Kell blood group protein, mcleod syndrome-associated; xk
Kell blood group precursor
Xk locus
Precursor substance, kell blood group; kx
Kell complex, 37-kd component

DESCRIPTION

The XK gene encodes a putative membrane transporter that is expressed ubiquitously, but found mainly in nervous tissue, heart, and red blood cells. In red blood cells XK is covalently linked to Kell glycoprotein (613883) through a disulfide bond, forming a complex on the cell surface. There is a correlation between expression of Kell and XK; thus, XK levels are reduced when Kell is absent and vice versa (summary by Dubielecka et al., 2011).

CLONING

Ho et al. (1994) assembled a cosmid contig of 360 kb that encompassed the XK locus and, by screening DNA from patients with radiolabeled whole cosmids, detected a 50-kb deletion. Two transcription units were identified within this deletion. The mRNA expression pattern of one of them, designated XK, correlated closely with the McLeod phenotype (300842). Two unrelated patients with no deletions or rearrangements detected on pulsed field gel electrophoresis and Southern blot analysis were examined for the presence of point mutations. The strategy involved direct sequence analysis of PCR products derived from genomic DNA samples that were isolated from patients' leukocytes. In 1 patient, a mutation was found in the donor splice site of intron 2, and in the second, a mutation in the acceptor splice site of intron 2. The predicted protein product of XK is composed of 444 amino acids with a calculated molecular weight of 50,913 daltons. The protein shared structural characteristics with membrane transport proteins of prokaryotes and eukaryotes. The neurologic abnormalities in McLeod syndrome correlate well with the high levels of expression of XK in the brain. Striatal degeneration with the development of chorea in McLeod syndrome can probably be explained thereby. Late-onset muscular dystrophy and cardiomyopathy also correlate well with a high expression of XK in skeletal and cardiac muscle. Stanfield and Horvitz (2000) found that the 458-amino acid Ced8 transmembrane protein of C. elegans is weakly similar to the human XK protein. The Ced8 and XK proteins share 19% amino acid identity, have similar hydropathy plots, and both contain 10 hydrophobic predicted membrane-spanning segments. The authors showed that loss-of-function mutations in the Ced8 gene lead to the late appearance of cell corpses during embryonic development in C. elegans. Ced8 functions downstream of or in parallel to the regulatory cell death gene Ced9 and may function as a cell death effector downstream of the caspase encoded by the programmed cell death killer gene Ced3. Stanfield and Horvitz (2000) suggested that in Ced8 mutants, embryonic programmed cell death probably initiates normally but proceeds slowly. The Ced8 protein appeared to be localized to the plasma membrane.

GENE STRUCTURE

The XK gene contains 3 exons (Ho et al., 1994).

MAPPING

Marsh (1977) showed that the XK locus, which controls synthesis of the Kell blood group 'precursor substance' (Kx), is X-linked. The XK locus is inactivated by lyonization. The XK and Xg (314700) loci are closely linked (Densen et al., 1981). Marsh (1978) reported a total lod score of 3.426 for theta of 0.0. Ho et al. (1992) constructed a long-range restriction map of Xp21, encompassing the gene loci for McLeod and chronic granulomatous disease (CGD; 306400). Multiple CpG islands were found clustered in a 700-kb region. Using a new marker, DXS709, they limited the McLeod syndrome region to a 150- to 380-kb segment. Within this interv ... More on the omim web site

Subscribe to this protein entry history

July 2, 2021: Protein entry updated
Automatic update: OMIM entry 300842 was added.

July 2, 2021: Protein entry updated
Automatic update: OMIM entry 314850 was added.

April 11, 2021: Protein entry updated
Automatic update: OMIM entry 300842 was added.

April 11, 2021: Protein entry updated
Automatic update: OMIM entry 314850 was added.

Feb. 17, 2021: Protein entry updated
Automatic update: OMIM entry 300842 was added.

Feb. 17, 2021: Protein entry updated
Automatic update: OMIM entry 314850 was added.

Oct. 21, 2020: Protein entry updated
Automatic update: OMIM entry 300842 was added.

Oct. 21, 2020: Protein entry updated
Automatic update: OMIM entry 314850 was added.

Aug. 25, 2020: Protein entry updated
Automatic update: OMIM entry 300842 was added.

Aug. 25, 2020: Protein entry updated
Automatic update: OMIM entry 314850 was added.

June 30, 2020: Protein entry updated
Automatic update: OMIM entry 300842 was added.

June 30, 2020: Protein entry updated
Automatic update: OMIM entry 314850 was added.

April 26, 2020: Protein entry updated
Automatic update: OMIM entry 300842 was added.

April 26, 2020: Protein entry updated
Automatic update: OMIM entry 314850 was added.

March 4, 2020: Protein entry updated
Automatic update: OMIM entry 300842 was added.

March 4, 2020: Protein entry updated
Automatic update: OMIM entry 314850 was added.

Jan. 23, 2020: Protein entry updated
Automatic update: OMIM entry 300842 was added.

Jan. 23, 2020: Protein entry updated
Automatic update: OMIM entry 314850 was added.

Dec. 3, 2019: Protein entry updated
Automatic update: OMIM entry 300842 was added.

Dec. 3, 2019: Protein entry updated
Automatic update: OMIM entry 314850 was added.

Oct. 28, 2019: Protein entry updated
Automatic update: OMIM entry 300842 was added.

Oct. 28, 2019: Protein entry updated
Automatic update: OMIM entry 314850 was added.

Sept. 23, 2019: Protein entry updated
Automatic update: OMIM entry 300842 was added.

Sept. 23, 2019: Protein entry updated
Automatic update: OMIM entry 314850 was added.

Aug. 20, 2019: Protein entry updated
Automatic update: OMIM entry 300842 was added.

Aug. 20, 2019: Protein entry updated
Automatic update: OMIM entry 314850 was added.

July 5, 2019: Protein entry updated
Automatic update: OMIM entry 300842 was added.

July 5, 2019: Protein entry updated
Automatic update: OMIM entry 314850 was added.

June 7, 2019: Protein entry updated
Automatic update: OMIM entry 300842 was added.

June 7, 2019: Protein entry updated
Automatic update: OMIM entry 314850 was added.

May 12, 2019: Protein entry updated
Automatic update: OMIM entry 300842 was added.

May 12, 2019: Protein entry updated
Automatic update: OMIM entry 314850 was added.

Jan. 21, 2019: Protein entry updated
Automatic update: OMIM entry 300842 was added.

Jan. 21, 2019: Protein entry updated
Automatic update: OMIM entry 314850 was added.

Nov. 17, 2018: Protein entry updated
Automatic update: OMIM entry 300842 was added.

Nov. 17, 2018: Protein entry updated
Automatic update: OMIM entry 314850 was added.

Oct. 20, 2018: Protein entry updated
Automatic update: OMIM entry 300842 was added.

Oct. 20, 2018: Protein entry updated
Automatic update: OMIM entry 314850 was added.

Oct. 2, 2018: Protein entry updated
Automatic update: OMIM entry 300842 was added.

Oct. 2, 2018: Protein entry updated
Automatic update: OMIM entry 314850 was added.

July 7, 2018: Protein entry updated
Automatic update: OMIM entry 300842 was added.

July 7, 2018: Protein entry updated
Automatic update: OMIM entry 314850 was added.

July 5, 2018: Protein entry updated
Automatic update: OMIM entry 300842 was added.

July 5, 2018: Protein entry updated
Automatic update: OMIM entry 314850 was added.

July 5, 2018: Protein entry updated
Automatic update: OMIM entry 300842 was added.

July 5, 2018: Protein entry updated
Automatic update: OMIM entry 314850 was added.

July 4, 2018: Protein entry updated
Automatic update: OMIM entry 300842 was added.

July 4, 2018: Protein entry updated
Automatic update: OMIM entry 314850 was added.

July 3, 2018: Protein entry updated
Automatic update: OMIM entry 300842 was added.

July 3, 2018: Protein entry updated
Automatic update: OMIM entry 314850 was added.

May 27, 2018: Protein entry updated
Automatic update: OMIM entry 300842 was added.

May 27, 2018: Protein entry updated
Automatic update: OMIM entry 314850 was added.

April 27, 2018: Protein entry updated
Automatic update: OMIM entry 300842 was added.

April 27, 2018: Protein entry updated
Automatic update: OMIM entry 314850 was added.

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 25, 2017: Additional information
No protein expression data in P. Mayeux work for XK

March 16, 2016: Protein entry updated
Automatic update: OMIM entry 300842 was added.

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