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 residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respo ...

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 Cho or CHO may refer to: People * Chief Happiness Officer Surnames * Cho (Korean surname), one romanization of the common Korean surname * Zhuo (), romanized Cho in Wade–Giles, Chinese surname * Cho, a Minnan romanization of the Chinese sur ...

(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 Cell (biology), cells of most Eukaryotes, such as animals, plants and Fungus, fungi. Mitochondria have a double lipid bilayer, membrane structure and use aerobic respiration to generate adenosi ...

and the

endoplasmic reticulum The endoplasmic reticulum (ER) is, in essence, the transportation system of the eukaryotic cell, and has many other important functions such as protein folding. It is a type of organelle made up of two subunits – rough endoplasmic reticulum ( ...

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 spec ...

s through

eukaryote Eukaryotes () are organisms whose cells have a nucleus. All animals, plants, fungi, and many unicellular organisms, are Eukaryotes. They belong to the group of organisms Eukaryota or Eukarya, which is one of the three domains of life. Bacte ...

bacteria Bacteria (; singular: bacterium) are ubiquitous, mostly free-living organisms often consisting of one biological cell. They constitute a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria were among ...

, and

archea Archaea ( ; singular archaeon ) is a domain of single-celled organisms. These microorganisms lack cell nuclei and are therefore prokaryotes. Archaea were initially classified as bacteria, receiving the name archaebacteria (in the Archaeb ...

. __TOC__

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 ...

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 114 million base pairs (the building material of DNA) and represents between 3.5 and 4% of the total DNA ...

at q34. The following genes are near CARKD on the chromosome: *

COL4A2 Collagen alpha-2(IV) chain is a protein that in humans is encoded by the ''COL4A2'' gene. This gene encodes one of the six subunits of type IV collagen, the major structural component of basement membranes. The C-terminal portion of the protein, ...

: A2 Subunit of type IV collagen * RAB20: Potential regulator of Connexin 43 trafficking. * CARS2: Mitochondrial Cystienyl-tRNA Synthetase 2 *

ING1 Inhibitor of growth protein 1 is a protein that in humans is encoded by the ''ING1'' gene. Function This gene encodes a tumor suppressor protein that can induce cell growth arrest and apoptosis. The encoded protein is a nuclear protein that ph ...

: Tumor-Suppressor Protein

Protein

This protein is part of the phosphomethylpyrimidine kinase:

ribokinase In enzymology, a ribokinase () is an enzyme that catalyzes the chemical reaction :ATP + -ribose ⇌ ADP + -ribose 5-phosphate Thus, the two substrates of this enzyme are ATP and -ribose, whereas its two products are ADP and -ribose 5-phosp ...

/ pfkB superfamily. This family is characterized by the presence of a

domain Domain may refer to: Mathematics *Domain of a function, the set of input values for which the (total) function is defined **Domain of definition of a partial function **Natural domain of a partial function **Domain of holomorphy of a function * Do ...

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 electrical charge or is electrically neutral in the statistical mean. The standard nomenclature to represent the isoelectric point is pH(I). However, pI is also u ...

: 9.377 ** CARKD orthologs have highly variable isoelectric points. *

Post-translational modification Post-translational modification (PTM) is the covalent and generally enzymatic modification of proteins following protein biosynthesis. This process occurs in the endoplasmic reticulum and the golgi apparatus. Proteins are synthesized by ribosome ...

: Three post-translational modifications are predicted: ** Modified

Phosphotyrosine -Tyrosine or tyrosine (symbol Tyr or Y) or 4-hydroxyphenylalanine is one of the 20 standard amino acids that are used by cells to synthesize proteins. It is a non-essential amino acid with a polar side group. The word "tyrosine" is from the Gr ...

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), ...

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 N-ter ...

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

, indicate its expression in almost all tissues. One peculiar expression pattern of CARKD is its differential expression through the development of

oligodendrocyte Oligodendrocytes (), or oligodendroglia, are a type of neuroglia whose main functions are to provide support and insulation to axons in the central nervous system of jawed vertebrates, equivalent to the function performed by Schwann cells in the ...

s. Its expression is lower in oligodendrocyte progenitor cells than in mature oligodendrocytes.

Binding partners

The human protein apolipoprotein A-1 binding precursor (

APOA1BP Apolipoprotein A-I-binding protein also known as APOA1BP is a protein that in humans is encoded by the ''APOA1BP'' gene. Function APOA1BP binds to APOA1, APOA2, and high-density lipoprotein High-density lipoprotein (HDL) is one of the five m ...

) 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 lymphoid line of blood cells characterized by the development of large numbers of immature lymphocytes. Symptoms may include feeling tired, pale skin color, fever, easy bleeding or bruisin ...

. In addition,

microarray A microarray is a multiplex lab-on-a-chip. Its purpose is to simultaneously detect the expression of thousands of genes from a sample (e.g. from a tissue). It is a two-dimensional array on a solid substrate—usually a glass slide or silicon t ...

data indicates that CARKD is up-regulated in

Glioblastoma multiforme Glioblastoma, previously known as glioblastoma multiforme (GBM), is one of the most aggressive types of cancer that begin within the brain. Initially, signs and symptoms of glioblastoma are nonspecific. They may include headaches, personality ch ...

tumors.

References

External links

* {{UCSC gene info, CARKD