Summary: Carbohydrate kinase
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CARKD Edit Wikipedia article
|, LP3298, CARKD, NAD(P)HX dehydratase|
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. The protein is conserved throughout many species, and has predicted orthologs through eukaryotes, bacteria, and archea.
- COL4A2: A2 Subunit of type IV collagen
- RAB20: Potential regulator of Connexin 43 trafficking.
- CARS2: Mitochondrial Cystienyl-tRNA Synthetase 2
- ING1: Tumor-Suppressor 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 (Pfam PF01256). This family is related to Pfam PF02210 and Pfam PF00294 implying that it also is a carbohydrate kinase.
The following properties of CARKD were predicted using bioinformatic analysis:
- Molecular Weight: 41.4 KDal
- Isoelectric point: 9.377
- CARKD orthologs have highly variable isoelectric points.
- Post-translational modification: Three post-translational modifications are predicted:
- A Signal Peptide and signal peptide cleavage site was predicted.
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. 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.
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.
Based on allele-specific expression of CARKD, CARKD may play a role in acute lymphoblastic leukemia. In addition, microarray data indicates that CARKD is up-regulated in Glioblastoma multiforme tumors.
- GRCh38: Ensembl release 89: ENSG00000213995 - Ensembl, May 2017
- GRCm38: Ensembl release 89: ENSMUSG00000031505 - Ensembl, May 2017
- "Human PubMed Reference:".
- "Mouse PubMed Reference:".
- "Structure of Bacillus subtilis YXKO--a member of the UPF0031 family and a putative kinase". Journal of Structural Biology. 139 (3): 161–70. doi:10.1016/S1047-8477(02)00532-4. PMC . PMID 12457846.; Zhang RG, Grembecka J, Vinokour E, Collart F, Dementieva I, Minor W, Joachimiak A (September 2002).
- Marbaix, AY; Tyteca, D; Niehaus, TD; Hanson, AD; Linster, CL; Van Schaftingen, E (15 May 2014). "Occurrence and subcellular distribution of the NADPHX repair system in mammals". The Biochemical Journal. 460 (1): 49–58. doi:10.1042/bj20131482. PMID 24611804.
- "UCSC Genome Browser: CARKD".
- "CDD: Conserved Domain Database (NCBI)".
- Brendel V, Bucher P, Nourbakhsh IR, Blaisdell BE, Karlin S (March 1992). "Methods and algorithms for statistical analysis of protein sequences". Proceedings of the National Academy of Sciences of the United States of America. 89 (6): 2002–6. doi:10.1073/pnas.89.6.2002. PMC . PMID 1549558.
- "PI Program (Isoelectric Point Prediction)". Archived from the original on 2008-10-26.
- "UniProt Database".
- Bendtsen JD, Nielsen H, von Heijne G, Brunak S (July 2004). "Improved prediction of signal peptides: SignalP 3.0". Journal of Molecular Biology. 340 (4): 783–95. doi:10.1016/j.jmb.2004.05.028. PMID 15223320.
- "Unigene (EST profile viewer) Human CARKD".
- "Unigene (EST profile viewer) Mouse CARKD".
- Nielsen JA, Maric D, Lau P, Barker JL, Hudson LD (September 2006). "Identification of a novel oligodendrocyte cell adhesion protein using gene expression profiling". Journal of Neuroscience. 26 (39): 9881–91. doi:10.1523/JNEUROSCI.2246-06.2006. PMC . PMID 17005852.
- "STRING: Known and Predicted Protein-Protein Interactions".
- Date SV (2008). "The Rosetta stone method". Methods Mol Biol. 453: 169–80.
- Milani L, Lundmark A, Nordlund J, Kiialainen A, Flaegstad T, Jonmundsson G, Kanerva J, Schmiegelow K, Gunderson KL, Lönnerholm G, Syvänen AC (January 2009). "Allele-specific gene expression patterns in primary leukemic cells reveal regulation of gene expression by CpG site methylation". Genome Research. 19 (1): 1–11. doi:10.1101/gr.083931.108. PMC . PMID 18997001.
- Ruano Y, Mollejo M, Ribalta T, Fiaño C, Camacho FI, Gómez E, de Lope AR, Hernández-Moneo JL, Martínez P, Meléndez B (2006). "Identification of novel candidate target genes in amplicons of Glioblastoma multiforme tumors detected by expression and CGH microarray profiling". Molecular Cancer. 5 (1): 39. doi:10.1186/1476-4598-5-39. PMC . PMID 17002787.
This tab holds the annotation information that is stored in the Pfam database. As we move to using Wikipedia as our main source of annotation, the contents of this tab will be gradually replaced by the Wikipedia tab.
Carbohydrate kinase Provide feedback
Internal database links
|SCOOP:||HK PfkB Phos_pyr_kin|
|Similarity to PfamA using HHSearch:||HK Phos_pyr_kin|
External database links
This tab holds annotation information from the InterPro database.
InterPro entry IPR000631
Hydration of NAD(P)H to NAD(P)HX, which inhibits several dehydrogenases, is corrected by an ATP-dependent dehydratase and an epimerase. The ATP-dependent dehydratase has been identified as the product of the vertebrate Carkd (carbohydrate kinase domain) gene [PUBMED:24611804]. In E. coli, it is found as the C-terminal domain of a bifunctional enzyme (YjeF) that also includes the epimerase and uses ADP instead of ATP [PUBMED:21994945]. These enzymes are widespread in eukaryotes, prokaryotes, and archaea.
The mapping between Pfam and Gene Ontology is provided by InterPro. If you use this data please cite InterPro.
|Molecular function||ADP-dependent NAD(P)H-hydrate dehydratase activity (GO:0052855)|
Below is a listing of the unique domain organisations or architectures in which this domain is found. More...
The graphic that is shown by default represents the longest sequence with a given architecture. Each row contains the following information:
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All of these enzymes are phosphotransferases that have an alcohol group as an acceptor (EC:2.7.1.-). However, 4-amino-5-hydroxymethyl-2-methylpyrimidine phosphate kinase (HMPP kinase) catalyses two phosphorylation reactions: one to a hydroxymethyl group of hydroxymethyl pyrimidine (HMP) and the second to the phosphomethyl group of HMPP . The common structural feature for the enzymes in this superfamily is a central eight-stranded sheet that is flanked by eight structurally conserved helices, five on one side and three on the other . The active site is located in a shallow groove along one edge of the sheet, with the phosphate acceptor hydroxyl group and -phosphate of ATP close together in the middle of the groove, and substrate and ATP binding at the ends .
The clan contains the following 5 members:ADP_PFK_GK Carb_kinase HK PfkB Phos_pyr_kin
We store a range of different sequence alignments for families. As well as the seed alignment from which the family is built, we provide the full alignment, generated by searching the sequence database (reference proteomes) using the family HMM. We also generate alignments using four representative proteomes (RP) sets, the UniProtKB sequence database, the NCBI sequence database, and our metagenomics sequence database. More...
There are various ways to view or download the sequence alignments that we store. We provide several sequence viewers and a plain-text Stockholm-format file for download.
We make a range of alignments for each Pfam-A family:
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- Representative Proteomes (RPs) at 15%, 35%, 55% and 75% co-membership thresholds
- alignment generated by searching the UniProtKB sequence database using the family HMM
- alignment generated by searching the NCBI sequence database using the family HMM
- alignment generated by searching the metagenomics sequence database using the family HMM
You can see the alignments as HTML or in three different sequence viewers:
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You can download (or view in your browser) a text representation of a Pfam alignment in various formats:
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We make a range of alignments for each Pfam-A family. You can see a description of each above. You can view these alignments in various ways but please note that some types of alignment are never generated while others may not be available for all families, most commonly because the alignments are too large to handle.
1Cannot generate PP/Heatmap alignments for seeds; no PP data available
Key: available, not generated, — not available.
Format an alignment
We make all of our alignments available in Stockholm format. You can download them here as raw, plain text files or as gzip-compressed files.
You can also download a FASTA format file containing the full-length sequences for all sequences in the full alignment.
HMM logos is one way of visualising profile HMMs. Logos provide a quick overview of the properties of an HMM in a graphical form. You can see a more detailed description of HMM logos and find out how you can interpret them here. More...
If you find these logos useful in your own work, please consider citing the following article:
This page displays the phylogenetic tree for this family's seed alignment. We use FastTree to calculate neighbour join trees with a local bootstrap based on 100 resamples (shown next to the tree nodes). FastTree calculates approximately-maximum-likelihood phylogenetic trees from our seed alignment.
Note: You can also download the data file for the tree.
Curation and family details
This section shows the detailed information about the Pfam family. You can see the definitions of many of the terms in this section in the glossary and a fuller explanation of the scoring system that we use in the scores section of the help pages.
|Previous IDs:||UPF0031; carb_kinase;|
|Author:||Finn RD, Bateman A, Yeats C|
|Number in seed:||9|
|Number in full:||4848|
|Average length of the domain:||239.40 aa|
|Average identity of full alignment:||27 %|
|Average coverage of the sequence by the domain:||57.13 %|
|HMM build commands:||
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 26740544 -E 1000 --cpu 4 HMM pfamseq
|Family (HMM) version:||16|
|Download:||download the raw HMM for this family|
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This visualisation provides a simple graphical representation of the distribution of this family across species. You can find the original interactive tree in the More....
This chart is a modified "sunburst" visualisation of the species tree for this family. It shows each node in the tree as a separate arc, arranged radially with the superkingdoms at the centre and the species arrayed around the outermost ring.
How the sunburst is generated
The tree is built by considering the taxonomic lineage of each sequence that has a match to this family. For each node in the resulting tree, we draw an arc in the sunburst. The radius of the arc, its distance from the root node at the centre of the sunburst, shows the taxonomic level ("superkingdom", "kingdom", etc). The length of the arc represents either the number of sequences represented at a given level, or the number of species that are found beneath the node in the tree. The weighting scheme can be changed using the sunburst controls.
In order to reduce the complexity of the representation, we reduce the number of taxonomic levels that we show. We consider only the following eight major taxonomic levels:
Colouring and labels
Segments of the tree are coloured approximately according to their superkingdom. For example, archeal branches are coloured with shades of orange, eukaryotes in shades of purple, etc. The colour assignments are shown under the sunburst controls. Where space allows, the name of the taxonomic level will be written on the arc itself.
As you move your mouse across the sunburst, the current node will be highlighted. In the top section of the controls panel we show a summary of the lineage of the currently highlighed node. If you pause over an arc, a tooltip will be shown, giving the name of the taxonomic level in the title and a summary of the number of sequences and species below that node in the tree.
Anomalies in the taxonomy tree
There are some situations that the sunburst tree cannot easily handle and for which we have work-arounds in place.
Missing taxonomic levels
Some species in the taxonomic tree may not have one or more of the main eight levels that we display. For example, Bos taurus is not assigned an order in the NCBI taxonomic tree. In such cases we mark the omitted level with, for example, "No order", in both the tooltip and the lineage summary.
Unmapped species names
The tree is built by looking at each sequence in the full alignment for the family. We take the name of the species given by UniProt and try to map that to the full taxonomic tree from NCBI. In some cases, the name chosen by UniProt does not map to any node in the NCBI tree, perhaps because the chosen name is listed as a synonym or a misspelling in the NCBI taxonomy.
So that these nodes are not simply omitted from the sunburst tree, we group them together in a separate branch (or segment of the sunburst tree). Since we cannot determine the lineage for these unmapped species, we show all levels between the superkingdom and the species as "uncategorised".
Since we reduce the species tree to only the eight main taxonomic levels, sequences that are mapped to the sub-species level in the tree would not normally be shown. Rather than leave out these species, we map them instead to their parent species. So, for example, for sequences belonging to one of the Vibrio cholerae sub-species in the NCBI taxonomy, we show them instead as belonging to the species Vibrio cholerae.
Too many species/sequences
For large species trees, you may see blank regions in the outer layers of the sunburst. These occur when there are large numbers of arcs to be drawn in a small space. If an arc is less than approximately one pixel wide, it will not be drawn and the space will be left blank. You may still be able to get some information about the species in that region by moving your mouse across the area, but since each arc will be very small, it will be difficult to accurately locate a particular species.
The tree shows the occurrence of this domain across different species. More...
We show the species tree in one of two ways. For smaller trees we try to show an interactive representation, which allows you to select specific nodes in the tree and view them as an alignment or as a set of Pfam domain graphics.
Unfortunately we have found that there are problems viewing the interactive tree when the it becomes larger than a certain limit. Furthermore, we have found that Internet Explorer can become unresponsive when viewing some trees, regardless of their size. We therefore show a text representation of the species tree when the size is above a certain limit or if you are using Internet Explorer to view the site.
If you are using IE you can still load the interactive tree by clicking the "Generate interactive tree" button, but please be aware of the potential problems that the interactive species tree can cause.
For all of the domain matches in a full alignment, we count the number that are found on all sequences in the alignment. This total is shown in the purple box.
We also count the number of unique sequences on which each domain is found, which is shown in green. Note that a domain may appear multiple times on the same sequence, leading to the difference between these two numbers.
Finally, we group sequences from the same organism according to the NCBI code that is assigned by UniProt, allowing us to count the number of distinct sequences on which the domain is found. This value is shown in the pink boxes.
We use the NCBI species tree to group organisms according to their taxonomy and this forms the structure of the displayed tree. Note that in some cases the trees are too large (have too many nodes) to allow us to build an interactive tree, but in most cases you can still view the tree in a plain text, non-interactive representation. Those species which are represented in the seed alignment for this domain are highlighted.
You can use the tree controls to manipulate how the interactive tree is displayed:
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Please note: for large trees this can take some time. While the tree is loading, you can safely switch away from this tab but if you browse away from the family page entirely, the tree will not be loaded.
There are 2 interactions for this family. More...
We determine these interactions using iPfam, which considers the interactions between residues in three-dimensional protein structures and maps those interactions back to Pfam families. You can find more information about the iPfam algorithm in the journal article that accompanies the website.
For those sequences which have a structure in the Protein DataBank, we use the mapping between UniProt, PDB and Pfam coordinate systems from the PDBe group, to allow us to map Pfam domains onto UniProt sequences and three-dimensional protein structures. The table below shows the structures on which the Carb_kinase domain has been found. There are 36 instances of this domain found in the PDB. Note that there may be multiple copies of the domain in a single PDB structure, since many structures contain multiple copies of the same protein sequence.
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