{{Short description|Protein-coding gene in humans}} {{cs1 config|name-list-style=vanc}} {{Infobox_gene}} {{Pfam_box | Symbol = Carb_kinase | Name = Carbohydrate kinase | image = Carbohydrate_kinase_1KYH.png | width = | caption = Crystallographic structure of a putative ''Bacillus subtilis'' carbohydrate kinase (rainbow colored, N-terminus = blue, C-terminus = red).<ref name="pmid12457846">{{PDB|1kyh}}; {{cite journal |vauthors=Zhang RG, Grembecka J, Vinokour E, Collart F, Dementieva I, Minor W, Joachimiak A | title = Structure of Bacillus subtilis YXKO--a member of the UPF0031 family and a putative kinase | journal = Journal of Structural Biology | volume = 139 | issue = 3 | pages = 161–70 |date=September 2002 | pmid = 12457846 | doi = 10.1016/S1047-8477(02)00532-4 | pmc = 2793413 }}</ref> | Pfam = PF01256 | Pfam_clan = CL0118 | InterPro = IPR000631 | SMART = | PROSITE = PDOC00806 | SCOP = 1kyh | TCDB = | OPM family = | OPM protein = | PDB = {{PDB2|1kyh}}, {{PDB2|2ax3}} }} '''Carbohydrate kinase domain containing protein''' (abbreviated as '''CARKD'''), encoded by '''CARKD''' gene, is a human protein 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, whereas mCARKD and spCARKD are targeted to the mitochondria and the endoplasmic reticulum respectively.<ref name="pmid24611804">{{cite journal|last1=Marbaix|first1=AY|last2=Tyteca|first2=D|last3=Niehaus|first3=TD|last4=Hanson|first4=AD|last5=Linster|first5=CL|last6=Van Schaftingen|first6=E|title=Occurrence and subcellular distribution of the NADPHX repair system in mammals.|journal=The Biochemical Journal|date=15 May 2014|volume=460|issue=1|pages=49–58|pmid=24611804|doi=10.1042/bj20131482}}</ref> The protein is conserved throughout many species, and has predicted orthologs through eukaryotes, bacteria, and archea. __TOC__
== Structure ==
=== Gene ===
Human CARKD gene has 10 exons and resides on Chromosome 13 at q34. The following genes are near CARKD on the chromosome:<ref name=UCSC>{{cite web |title= UCSC Genome Browser: CARKD |url= http://genome.ucsc.edu/cgi-bin/hgTracks?position=chr13:110066009-110090343&hgsid=130989312&refGene=pack&hgFind.matches=NM_018210, }}</ref> * 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.<ref name=CDD>{{cite web |title= CDD: Conserved Domain Database (NCBI) |url=https://www.ncbi.nlm.nih.gov/cdd?linkname=gene_cdd&from_uid=55739 }}</ref> CARKD contains a carbohydrate kinase domain ({{pfam|PF01256}}).<ref name=CDD /> This family is related to {{pfam|PF02210}} and {{pfam|PF00294}} 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<ref name="SAPS">{{cite journal |vauthors=Brendel V, Bucher P, Nourbakhsh IR, Blaisdell BE, Karlin S | title = Methods and algorithms for statistical analysis of protein sequences | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 89 | issue = 6 | pages = 2002–6 |date=March 1992 | pmid = 1549558 | pmc = 48584 | doi = 10.1073/pnas.89.6.2002| bibcode = 1992PNAS...89.2002B | doi-access = free }}</ref> * Isoelectric point: 9.377<ref name=PI>{{cite web |title= PI Program (Isoelectric Point Prediction) |url= http://www.embl-heidelberg.de/cgi/pi-wrapper.pl |url-status= dead |archive-url= https://web.archive.org/web/20081026062821/http://www.embl-heidelberg.de/cgi/pi-wrapper.pl |archive-date= 2008-10-26 }}</ref> ** CARKD orthologs have highly variable isoelectric points.<ref name=PI/> * Post-translational modification: Three post-translational modifications are predicted: ** Modified Phosphotyrosine Residue<ref name=Uniprot>{{cite web |title=UniProt Database |url=https://www.uniprot.org/uniprot/Q8IW45}}</ref> ** Two N-Linked Glycosylation Sites<ref name=Uniprot/> * A Signal Peptide and signal peptide cleavage site was predicted.<ref name="SignalP">{{cite journal |vauthors=Bendtsen JD, Nielsen H, von Heijne G, Brunak S | title = Improved prediction of signal peptides: SignalP 3.0 | journal = Journal of Molecular Biology | volume = 340 | issue = 4 | pages = 783–95 |date=July 2004 | pmid = 15223320 | doi = 10.1016/j.jmb.2004.05.028 | citeseerx = 10.1.1.165.2784 }}</ref>
== Function ==
=== Tissue distribution ===
CARKD appears to be ubiquitously expressed at high levels. Expression data in the human protein, and the mouse ortholog, indicate its expression in almost all tissues.<ref name=ESTHuman>{{cite web |title=Unigene (EST profile viewer) Human CARKD |url= https://www.ncbi.nlm.nih.gov/UniGene/ESTProfileViewer.cgi?uglist=Hs.408324|archive-url= https://web.archive.org/web/20121114065919/http://www.ncbi.nlm.nih.gov/UniGene/ESTProfileViewer.cgi?uglist=Hs.408324|url-status= dead|archive-date= November 14, 2012}}</ref><ref name=CARKDmouse>{{cite web |title=Unigene (EST profile viewer) Mouse CARKD |url=https://www.ncbi.nlm.nih.gov/UniGene/ESTProfileViewer.cgi?uglist=Mm.64911|archive-url=https://web.archive.org/web/20121114065932/http://www.ncbi.nlm.nih.gov/UniGene/ESTProfileViewer.cgi?uglist=Mm.64911|url-status=dead|archive-date=November 14, 2012}}</ref> One peculiar expression pattern of CARKD is its differential expression through the development of oligodendrocytes. Its expression is lower in oligodendrocyte progenitor cells than in mature oligodendrocytes.<ref name="pmid17005852">{{cite journal |vauthors=Nielsen JA, Maric D, Lau P, Barker JL, Hudson LD | title = Identification of a novel oligodendrocyte cell adhesion protein using gene expression profiling | journal = Journal of Neuroscience | volume = 26 | issue = 39 | pages = 9881–91 |date=September 2006 | pmid = 17005852 | pmc = 1613258 | doi = 10.1523/JNEUROSCI.2246-06.2006 }}</ref>
=== Binding partners ===
The human protein apolipoprotein A-1 binding precursor (APOA1BP) was predicted to be a binding partner for CARKD.<ref name=String>{{cite web |title= STRING: Known and Predicted Protein-Protein Interactions |url=http://string.embl.de/}}</ref> 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,<ref>{{cite book | vauthors = Date SV | title = Bioinformatics | year = 2008 | chapter = The Rosetta Stone Method | volume = 453 | pages = 169–80 | doi = 10.1007/978-1-60327-429-6_7 | pmid = 18712302 | series = Methods in Molecular Biology | publisher = Humana Press | location = Totowa, NJ | isbn = 978-1-60327-428-9 }}</ref> 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.<ref name="pmid18997001">{{cite journal |vauthors=Milani L, Lundmark A, Nordlund J, Kiialainen A, Flaegstad T, Jonmundsson G, Kanerva J, Schmiegelow K, Gunderson KL, Lönnerholm G, Syvänen AC | title = Allele-specific gene expression patterns in primary leukemic cells reveal regulation of gene expression by CpG site methylation | journal = Genome Research | volume = 19 | issue = 1 | pages = 1–11 |date=January 2009 | pmid = 18997001 | pmc = 2612957 | doi = 10.1101/gr.083931.108 }}</ref> In addition, microarray data indicates that CARKD is up-regulated in Glioblastoma multiforme tumors.<ref name="pmid17002787">{{cite journal |vauthors=Ruano Y, Mollejo M, Ribalta T, Fiaño C, Camacho FI, Gómez E, de Lope AR, Hernández-Moneo JL, Martínez P, Meléndez B | title = Identification of novel candidate target genes in amplicons of Glioblastoma multiforme tumors detected by expression and CGH microarray profiling | journal = Molecular Cancer | volume = 5 | issue = 1| pages = 39 | year = 2006 | pmid = 17002787 | pmc = 1592108 | doi = 10.1186/1476-4598-5-39 | doi-access = free }}</ref>
Mutations of the NAXD gene cause the rare disease early-onset progressive encephalopathy with brain edema and/or leukoencephalopathy-2 (PEBEL2).
== References == {{Reflist}}
==External links== * {{UCSC gene info|CARKD}}