Sedoheptulokinase (SHPK)

The protein contains 478 amino acids for an estimated molecular weight of 51491 Da.

 

Acts as a modulator of macrophage activation through control of glucose metabolism. (updated: March 4, 2015)

Protein identification was indicated in the following studies:

  1. Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
  2. Hegedűs and co-workers. (2015) Inconsistencies in the red blood cell membrane proteome analysis: generation of a database for research and diagnostic applications. Database (Oxford) 1-8.
  3. Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
  4. D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.

Methods

The following articles were analysed to gather the proteome content of erythrocytes.

The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.

PublicationIdentification 1Uniprot mapping 2Not mapped /
Obsolete		TrEMBLSwiss-Prot
Goodman (2013)2289 (gene list)227853205992269
Lange (2014)123412347281224
Hegedus (2015)2638262202352387
Wilson (2016)165815281702911068
d'Alessandro (2017)18261817201815
Bryk (2017)20902060101081942
Chu (2018)18531804553621387

1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry

The compilation of older studies can be retrieved from the Red Blood Cell Collection database.

The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.

No sequence conservation computed yet.
Protein sequence (FASTA)
Protein coevolution profile (FreeContact)
Multiple Sequence Alignment (Muscle)

Interpro domains
Total structural coverage: 0%
Model score: 0
No model available.

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VariantDescription
dbSNP:rs150857
dbSNP:rs224496
dbSNP:rs36125540

No binding partner found

The reference OMIM entry for this protein is 605060

Sedoheptulokinase; shpk
Shk
Carbohydrate kinase-like; carkl

DESCRIPTION

Carbohydrate kinases, including sedoheptulokinase (EC 2.7.1.14), are a class of proteins involved in the phosphorylation of sugars as they enter a cell, inhibiting return across the cell membrane (Touchman et al., 2000).

CLONING

Touchman et al. (2000) sequenced 200 kb surrounding the gene encoding cystinosin (CTNS; 606272), which is mutated in nephropathic cystinosis (219800), on chromosome 17p13. They found that genomic sequence in this region matched known ESTs. Using PCR primers to amplify a human fetal kidney cDNA library, the authors cloned SHPK, which they designated CARKL. The deduced 478-amino acid protein contains motifs showing weak similarity to 2 domains of the FGGY family of carbohydrate kinases. It does not appear to contain a signal sequence, suggesting that it is localized in the cytoplasm. Northern blot analysis detected expression of a 3.9-kb transcript predominantly in liver, kidney, and pancreas, with weaker expression in heart, placenta, brain, and lung. Additionally, a 2.7-kb transcript was detected in liver and, to a lesser extent, in heart.

GENE STRUCTURE

Touchman et al. (2000) determined that the SHPK gene contains 7 exons. Phornphutkul et al. (2001) found that the promoter region of the CTNS gene shares 41 nucleotides with the promoter region of the SHPK gene, whose start site is 501 bp from the CTNS start site. SHPK is aligned on the other DNA strand in the opposite direction. Phornphutkul et al. (2001) identified disease-causing mutations in the promoter region of the CTNS gene in patients with cystinosis, but found that these mutations had no effect on SHPK promoter activity.

MAPPING

By sequence analysis, Touchman et al. (2000) determined that the SHPK gene maps to chromosome 17p13 within the telomeric end of a 57-kb deletion including the CTNS gene (606272.0005) that is commonly deleted in cystinosis. They hypothesized that SHPK may be a modifier for the cystinosis phenotype.

GENE FUNCTION

Wamelink et al. (2008) found that cystinosis patients homozygous for a deletion that includes the SHPK gene had increased urinary sedoheptulose and erythritol compared to patients with other CTNS mutations. Enzyme studies of cultured fibroblasts revealed an 80% reduction in sedoheptulose phosphorylating activity compared to cystinosis patients with other mutations and controls. Sedoheptulose-7-phosphate is a key intermediate in the pentose phosphate pathway. The findings indicated that sedoheptulokinase is responsible for conversion of sedoheptulose and ATP to sedoheptulose-7-phosphate and ADP. By screening for novel human regulators of macrophage activation, Haschemi et al. (2012) identified nonprotein kinases of glucose metabolism, including CARKL, as candidate immune modulators. Upon lipopolysaccharide stimulation, CARKL was rapidly downregulated in vitro and in vivo in mice and humans. Mouse Carkl functioned as a sedoheptulose kinase, catalyzing an orphan reaction in the pentose phosphate pathway and refocusing cellular metabolism to a high-redox state upon physiologic or artificial downregulation. Haschemi et al. (2012) concluded that CARKL-dependent metabolic reprogramming is required for proper polarization of M1- and M2-like macrophages involved in pro- and antiinflammatory immune responses. ... More on the omim web site

Subscribe to this protein entry history

Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated

Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated

March 16, 2016: Protein entry updated
Automatic update: OMIM entry 605060 was added.