Summary: Carbohydrate kinase
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CARKD Edit Wikipedia article
| Carbohydrate kinase | |||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
 Crystallographic structure of a putative Bacillus subtilis carbohydrate kinase (rainbow colored, N-terminus = blue, C-terminus = red).[5] | |||||||||||
| Identifiers | |||||||||||
| Symbol | Carb_kinase | ||||||||||
| Pfam | PF01256 | ||||||||||
| Pfam clan | CL0118 | ||||||||||
| InterPro | IPR000631 | ||||||||||
| PROSITE | PDOC00806 | ||||||||||
| SCOPe | 1kyh / SUPFAM | ||||||||||
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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.[6] The protein is conserved throughout many species, and has predicted orthologs through eukaryotes, bacteria, and archea.
Contents
Structure
Gene
Human CARKD gene has 10 exons and resides on Chromosome 13 at q34. The following genes are near CARKD on the chromosome:[7]
- 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.[8] CARKD contains a carbohydrate kinase domain (Pfam PF01256).[8] 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[9]
- Isoelectric point: 9.377[10]
- CARKD orthologs have highly variable isoelectric points.[10]
- Post-translational modification: Three post-translational modifications are predicted:
- Modified Phosphotyrosine Residue[11]
- Two N-Linked Glycosylation Sites[11]
- A Signal Peptide and signal peptide cleavage site was predicted.[12]
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.[13][14] 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.[15]
Binding partners
The human protein apolipoprotein A-1 binding precursor (APOA1BP) was predicted to be a binding partner for CARKD.[16] 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,[17] 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.[18] In addition, microarray data indicates that CARKD is up-regulated in Glioblastoma multiforme tumors.[19]
References
- ^ a b c GRCh38: Ensembl release 89: ENSG00000213995 - Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000031505 - Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ PDB: 1kyh; Zhang RG, Grembecka J, Vinokour E, Collart F, Dementieva I, Minor W, Joachimiak A (September 2002). "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 2793413. PMID 12457846.
- ^ 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".
- ^ a b "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 48584. PMID 1549558.
- ^ a b "PI Program (Isoelectric Point Prediction)". Archived from the original on 2008-10-26.
- ^ a b "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. CiteSeerX 10.1.1.165.2784. 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 1613258. PMID 17005852.
- ^ "STRING: Known and Predicted Protein-Protein Interactions".
- ^ Date SV (2008). The Rosetta stone method. Methods Mol Biol. Methods in Molecular Biology™. 453. pp. 169–80. doi:10.1007/978-1-60327-429-6_7. ISBN 978-1-60327-428-9. PMID 18712302.
- ^ 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 2612957. PMID 18997001.
- ^ Ruano Y, Mollejo M, Ribalta T, Fiaño C, Camacho FI, Gómez E, de Lope AR, Hernández-Moneo JL, MartÃnez 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 1592108. PMID 17002787.
External links
- Human CARKD genome location and CARKD gene details page in the UCSC Genome Browser.
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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
This family is related to PF02110 and PF00294 implying that it also is a carbohydrate kinase. (personal obs Yeats C).
Internal database links
| SCOOP: | HK PfkB Phos_pyr_kin |
| Similarity to PfamA using HHSearch: | HK Phos_pyr_kin |
External database links
| PROSITE: | PDOC00806 |
| SCOP: | 1kyh |
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.
Gene Ontology
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) |
Domain organisation
Below is a listing of the unique domain organisations or architectures in which this domain is found. More...
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Pfam Clan
This family is a member of clan Ribokinase (CL0118), which has the following description:
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 [1]. 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 [1]. 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 [1].
The clan contains the following 5 members:
ADP_PFK_GK Carb_kinase HK PfkB Phos_pyr_kinAlignments
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...
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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.
| Seed (9) |
Full (8103) |
Representative proteomes | UniProt (35552) |
NCBI (84706) |
Meta (1618) |
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| RP15 (1147) |
RP35 (3847) |
RP55 (7706) |
RP75 (13135) |
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| HTML | |||||||||
| PP/heatmap | 1 | ||||||||
1Cannot generate PP/Heatmap alignments for seeds; no PP data available
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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.
| Seed (9) |
Full (8103) |
Representative proteomes | UniProt (35552) |
NCBI (84706) |
Meta (1618) |
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| RP15 (1147) |
RP35 (3847) |
RP55 (7706) |
RP75 (13135) |
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| Raw Stockholm | |||||||||
| Gzipped | |||||||||
You can also download a FASTA format file containing the full-length sequences for all sequences in the full alignment.
HMM logo
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...
Trees
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.
Curation
| Seed source: | Prosite |
| Previous IDs: | UPF0031; carb_kinase; |
| Type: | Family |
| Sequence Ontology: | SO:0100021 |
| Author: |
Finn RD  , Bateman A , Yeats C
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| Number in seed: | 9 |
| Number in full: | 8103 |
| Average length of the domain: | 241.20 aa |
| Average identity of full alignment: | 29 % |
| Average coverage of the sequence by the domain: | 56.05 % |
HMM information
| HMM build commands: |
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 47079205 -E 1000 --cpu 4 HMM pfamseq
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| Model details: |
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| Model length: | 244 | ||||||||||||
| Family (HMM) version: | 18 | ||||||||||||
| Download: | download the raw HMM for this family |
Species distribution
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Colour assignments
Archea
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Eukaryota
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Interactions
Structures
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 38 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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