Carbohydrate kinase domain containing protein (abbreviated as CARKD), encoded by CARKD gene, is a human
protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...
of unknown function. The CARKD gene encodes proteins with a predicted mitochondrial propeptide (mCARKD), a signal peptide (spCARKD) or neither of them (cCARKD). Confocal microscopy analysis of transfected
CHO (Chinese-hamster ovary) cells indicated that cCARKD remains in the
cytosol
The cytosol, also known as cytoplasmic matrix or groundplasm, is one of the liquids found inside cells ( intracellular fluid (ICF)). It is separated into compartments by membranes. For example, the mitochondrial matrix separates the mitochondri ...
, whereas mCARKD and spCARKD are targeted to the
mitochondria
A mitochondrion () is an organelle found in the cells of most eukaryotes, such as animals, plants and fungi. Mitochondria have a double membrane structure and use aerobic respiration to generate adenosine triphosphate (ATP), which is us ...
and the
endoplasmic reticulum
The endoplasmic reticulum (ER) is a part of a transportation system of the eukaryote, eukaryotic cell, and has many other important functions such as protein folding. The word endoplasmic means "within the cytoplasm", and reticulum is Latin for ...
respectively.
The protein is conserved throughout many species, and has predicted
ortholog
Sequence homology is the biological homology between DNA, RNA, or protein sequences, defined in terms of shared ancestry in the evolutionary history of life. Two segments of DNA can have shared ancestry because of three phenomena: either a speci ...
s through
eukaryote
The eukaryotes ( ) constitute the Domain (biology), domain of Eukaryota or Eukarya, organisms whose Cell (biology), cells have a membrane-bound cell nucleus, nucleus. All animals, plants, Fungus, fungi, seaweeds, and many unicellular organisms ...
s,
bacteria
Bacteria (; : bacterium) are ubiquitous, mostly free-living organisms often consisting of one Cell (biology), biological cell. They constitute a large domain (biology), domain of Prokaryote, prokaryotic microorganisms. Typically a few micr ...
, and
archea.
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Structure
Gene
Human CARKD gene has 10
exons
An exon is any part of a gene that will form a part of the final mature RNA produced by that gene after introns have been removed by RNA splicing. The term ''exon'' refers to both the DNA sequence within a gene and to the corresponding sequence i ...
and resides on
Chromosome 13
Chromosome 13 is one of the 23 pairs of chromosomes in humans. People normally have two copies of this chromosome. Chromosome 13 spans about 113 million base pairs (the building material of DNA) and represents between 3.5 and 4% of the total DNA i ...
at q34. The following genes are near CARKD on the chromosome:
*
COL4A2: A2 Subunit of type IV collagen
* RAB20: Potential regulator of Connexin 43 trafficking.
* CARS2: Mitochondrial Cystienyl-tRNA Synthetase 2
*
ING1: Tumor-Suppressor Protein
Protein
This protein is part of the
phosphomethylpyrimidine kinase:
ribokinase / pfkB superfamily. This family is characterized by the presence of a
domain shared by the family.
CARKD contains a carbohydrate kinase domain ().
This family is related to and implying that it also is a carbohydrate kinase.
Predicted properties
The following properties of CARKD were predicted using
bioinformatic analysis:
* Molecular Weight: 41.4 KDal
*
Isoelectric point
The isoelectric point (pI, pH(I), IEP), is the pH at which a molecule carries no net electric charge, electrical charge or is electrically neutral in the statistical mean. The standard nomenclature to represent the isoelectric point is pH(I). Howe ...
: 9.377
** CARKD orthologs have highly variable isoelectric points.
[
* ]Post-translational modification
In molecular biology, post-translational modification (PTM) is the covalent process of changing proteins following protein biosynthesis. PTMs may involve enzymes or occur spontaneously. Proteins are created by ribosomes, which translation (biolog ...
: Three post-translational modifications are predicted:
** Modified Phosphotyrosine Residue
** Two N-Linked Glycosylation
''N''-linked glycosylation is the attachment of an oligosaccharide, a carbohydrate consisting of several sugar molecules, sometimes also referred to as glycan, to a nitrogen atom (the amide nitrogen of an asparagine (Asn) residue of a protein), i ...
Sites[
* A ]Signal Peptide
A signal peptide (sometimes referred to as signal sequence, targeting signal, localization signal, localization sequence, transit peptide, leader sequence or leader peptide) is a short peptide (usually 16–30 amino acids long) present at the ...
and signal peptide cleavage site was predicted.
Function
Tissue distribution
CARKD appears to be ubiquitously expressed at high levels. Expression data in the human protein, and the mouse ortholog
Sequence homology is the biological homology between DNA, RNA, or protein sequences, defined in terms of shared ancestry in the evolutionary history of life. Two segments of DNA can have shared ancestry because of three phenomena: either a speci ...
, indicate its expression in almost all tissues. One peculiar expression pattern of CARKD is its differential expression through the development of oligodendrocyte
Oligodendrocytes (), also known as oligodendroglia, are a type of neuroglia whose main function is to provide the myelin sheath to neuronal axons in the central nervous system (CNS). Myelination gives metabolic support to, and insulates the axons ...
s. Its expression is lower in oligodendrocyte progenitor cells than in mature oligodendrocytes.
Binding partners
The human protein apolipoprotein A-1 binding precursor ( APOA1BP) was predicted to be a binding partner for CARKD. This prediction is based on co-occurrence across genomes and co-expression. In addition to these data, the orthologs of CARKD in ''E. coli'' contain a domain similar to APOA1BP. This indicates that the two proteins are likely to have originated from a common evolutionary ancestor and, according to Rosetta stone analysis theory, are likely interaction partners even in species such as humans where the two proteins are not produced as a single polypeptide.
Clinical significance
Based on allele-specific expression of CARKD, CARKD may play a role in acute lymphoblastic leukemia
Acute lymphoblastic leukemia (ALL) is a cancer of the Lymphocyte, lymphoid line of blood cells characterized by the development of large numbers of lymphoblast, immature lymphocytes. Symptoms may include feeling tired, pale skin color, fever, ...
. In addition, microarray
A microarray is a multiplex (assay), multiplex lab-on-a-chip. Its purpose is to simultaneously detect the expression of thousands of biological interactions. It is a two-dimensional array on a Substrate (materials science), solid substrate—usu ...
data indicates that CARKD is up-regulated in Glioblastoma multiforme
Glioblastoma, previously known as glioblastoma multiforme (GBM), is the most aggressive and most common type of cancer that originates in the brain, and has a very poor prognosis for survival. Initial signs and symptoms of glioblastoma are nons ...
tumors.
References
External links
* {{UCSC gene info, CARKD