SHPK_HUMAN
ID SHPK_HUMAN Reviewed; 478 AA.
AC Q9UHJ6; B2R640; Q8WUH3;
DT 27-APR-2001, integrated into UniProtKB/Swiss-Prot.
DT 23-FEB-2022, sequence version 4.
DT 03-AUG-2022, entry version 157.
DE RecName: Full=Sedoheptulokinase {ECO:0000305};
DE Short=SHK;
DE EC=2.7.1.14 {ECO:0000269|PubMed:18186520};
DE AltName: Full=Carbohydrate kinase-like protein;
GN Name=SHPK {ECO:0000312|HGNC:HGNC:1492}; Synonyms=CARKL;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA], TISSUE SPECIFICITY, AND VARIANT
RP LYS-215.
RC TISSUE=Fetal kidney;
RX PubMed=10673275; DOI=10.1101/gr.10.2.165;
RA Touchman J.W., Anikster Y., Dietrich N.L., Maduro V.V.B., McDowell G.,
RA Shotelersuk V., Bouffard G.G., Beckstrom-Sternberg S.M., Gahl W.A.,
RA Green E.D.;
RT "The genomic region encompassing the nephropathic cystinosis gene (CTNS):
RT complete sequencing of a 200-kb segment and discovery of a novel gene
RT within the common cystinosis-causing deletion.";
RL Genome Res. 10:165-173(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Melanoma;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16625196; DOI=10.1038/nature04689;
RA Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R.,
RA Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A.,
RA Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J.,
RA Chang J.L., Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J.,
RA DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., Gnerre S.,
RA Goldstein S., Grafham D.V., Grocock R., Hafez N., Hagopian D.S., Hart E.,
RA Norman C.H., Humphray S., Jaffe D.B., Jones M., Kamal M., Khodiyar V.K.,
RA LaButti K., Laird G., Lehoczky J., Liu X., Lokyitsang T., Loveland J.,
RA Lui A., Macdonald P., Major J.E., Matthews L., Mauceli E., McCarroll S.A.,
RA Mihalev A.H., Mudge J., Nguyen C., Nicol R., O'Leary S.B., Osoegawa K.,
RA Schwartz D.C., Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D.,
RA Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A.,
RA Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C.;
RT "DNA sequence of human chromosome 17 and analysis of rearrangement in the
RT human lineage.";
RL Nature 440:1045-1049(2006).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Liver;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [7]
RP CATALYTIC ACTIVITY, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=18186520; DOI=10.1002/humu.20685;
RA Wamelink M.M., Struys E.A., Jansen E.E., Levtchenko E.N., Zijlstra F.S.,
RA Engelke U., Blom H.J., Jakobs C., Wevers R.A.;
RT "Sedoheptulokinase deficiency due to a 57-kb deletion in cystinosis
RT patients causes urinary accumulation of sedoheptulose: elucidation of the
RT CARKL gene.";
RL Hum. Mutat. 29:532-536(2008).
RN [8]
RP INDUCTION.
RX PubMed=22682222; DOI=10.1016/j.cmet.2012.04.023;
RA Haschemi A., Kosma P., Gille L., Evans C.R., Burant C.F., Starkl P.,
RA Knapp B., Haas R., Schmid J.A., Jandl C., Amir S., Lubec G., Park J.,
RA Esterbauer H., Bilban M., Brizuela L., Pospisilik J.A., Otterbein L.E.,
RA Wagner O.;
RT "The sedoheptulose kinase CARKL directs macrophage polarization through
RT control of glucose metabolism.";
RL Cell Metab. 15:813-826(2012).
RN [9]
RP INVOLVEMENT IN SHPKD.
RX PubMed=25647543; DOI=10.1007/s10545-014-9809-1;
RA Wamelink M.M., Ramos R.J., van den Elzen A.P., Ruijter G.J., Bonte R.,
RA Diogo L., Garcia P., Neves N., Nota B., Haschemi A., Tavares de Almeida I.,
RA Salomons G.S.;
RT "First two unrelated cases of isolated sedoheptulokinase deficiency: A
RT benign disorder?";
RL J. Inherit. Metab. Dis. 38:889-894(2015).
CC -!- FUNCTION: Acts as a modulator of macrophage activation through control
CC of glucose metabolism. {ECO:0000250}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + sedoheptulose = ADP + D-sedoheptulose 7-phosphate +
CC H(+); Xref=Rhea:RHEA:23844, ChEBI:CHEBI:15378, ChEBI:CHEBI:16802,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:57483, ChEBI:CHEBI:456216;
CC EC=2.7.1.14; Evidence={ECO:0000269|PubMed:18186520};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=0.06 mM for sedoheptulose {ECO:0000269|PubMed:18186520};
CC pH dependence:
CC Optimum pH is 8.5. {ECO:0000269|PubMed:18186520};
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Strongly expressed in liver, kidney and pancreas.
CC Expressed at lower levels in placenta and heart. Very weakly expressed
CC in lung and brain. {ECO:0000269|PubMed:10673275}.
CC -!- INDUCTION: Down-regulated by LPS. {ECO:0000269|PubMed:22682222}.
CC -!- DISEASE: Sedoheptulokinase deficiency (SHPKD) [MIM:617213]: An
CC autosomal recessive metabolic disease characterized by increased
CC urinary erythritol and sedoheptulose. Neonatal cholestasis,
CC hypoglycemia, anemia, congenital arthrogryposis multiplex, multiple
CC contractures and dysmorphisms have been reported in SHPKD patients, but
CC the relationship of these features to the SHPKD is unclear.
CC {ECO:0000269|PubMed:25647543}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the FGGY kinase family. {ECO:0000305}.
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DR EMBL; AF163573; AAF24936.1; -; mRNA.
DR EMBL; AF168787; AAF43103.1; -; Genomic_DNA.
DR EMBL; AK312428; BAG35337.1; -; mRNA.
DR EMBL; AL832420; CAH10646.1; -; mRNA.
DR EMBL; AC027796; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471108; EAW90501.1; -; Genomic_DNA.
DR EMBL; BC020543; AAH20543.1; -; mRNA.
DR CCDS; CCDS11030.1; -.
DR RefSeq; NP_037408.2; NM_013276.2.
DR AlphaFoldDB; Q9UHJ6; -.
DR SMR; Q9UHJ6; -.
DR BioGRID; 117235; 35.
DR IntAct; Q9UHJ6; 7.
DR STRING; 9606.ENSP00000225519; -.
DR iPTMnet; Q9UHJ6; -.
DR PhosphoSitePlus; Q9UHJ6; -.
DR BioMuta; SHPK; -.
DR DMDM; 296452959; -.
DR EPD; Q9UHJ6; -.
DR jPOST; Q9UHJ6; -.
DR MassIVE; Q9UHJ6; -.
DR MaxQB; Q9UHJ6; -.
DR PaxDb; Q9UHJ6; -.
DR PeptideAtlas; Q9UHJ6; -.
DR PRIDE; Q9UHJ6; -.
DR ProteomicsDB; 84364; -.
DR TopDownProteomics; Q9UHJ6; -.
DR Antibodypedia; 10891; 224 antibodies from 27 providers.
DR DNASU; 23729; -.
DR Ensembl; ENST00000225519.5; ENSP00000225519.3; ENSG00000197417.9.
DR GeneID; 23729; -.
DR KEGG; hsa:23729; -.
DR MANE-Select; ENST00000225519.5; ENSP00000225519.3; NM_013276.4; NP_037408.2.
DR UCSC; uc002fvz.1; human.
DR CTD; 23729; -.
DR DisGeNET; 23729; -.
DR GeneCards; SHPK; -.
DR HGNC; HGNC:1492; SHPK.
DR HPA; ENSG00000197417; Low tissue specificity.
DR MalaCards; SHPK; -.
DR MIM; 605060; gene.
DR MIM; 617213; phenotype.
DR neXtProt; NX_Q9UHJ6; -.
DR OpenTargets; ENSG00000197417; -.
DR OpenTargets; ENSG00000262304; -.
DR Orphanet; 440713; Isolated sedoheptulokinase deficiency.
DR PharmGKB; PA162403312; -.
DR VEuPathDB; HostDB:ENSG00000197417; -.
DR eggNOG; KOG2517; Eukaryota.
DR GeneTree; ENSGT01000000214434; -.
DR HOGENOM; CLU_021676_1_1_1; -.
DR InParanoid; Q9UHJ6; -.
DR OrthoDB; 1027013at2759; -.
DR PhylomeDB; Q9UHJ6; -.
DR TreeFam; TF315140; -.
DR BioCyc; MetaCyc:G66-33950-MON; -.
DR BRENDA; 2.7.1.14; 2681.
DR PathwayCommons; Q9UHJ6; -.
DR Reactome; R-HSA-71336; Pentose phosphate pathway.
DR SignaLink; Q9UHJ6; -.
DR SIGNOR; Q9UHJ6; -.
DR BioGRID-ORCS; 23729; 10 hits in 1082 CRISPR screens.
DR GenomeRNAi; 23729; -.
DR Pharos; Q9UHJ6; Tbio.
DR PRO; PR:Q9UHJ6; -.
DR Proteomes; UP000005640; Chromosome 17.
DR RNAct; Q9UHJ6; protein.
DR Bgee; ENSG00000197417; Expressed in right lobe of liver and 120 other tissues.
DR Genevisible; Q9UHJ6; HS.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0016773; F:phosphotransferase activity, alcohol group as acceptor; IBA:GO_Central.
DR GO; GO:0050277; F:sedoheptulokinase activity; IDA:UniProtKB.
DR GO; GO:0005975; P:carbohydrate metabolic process; IDA:UniProtKB.
DR GO; GO:0035963; P:cellular response to interleukin-13; ISS:UniProtKB.
DR GO; GO:0071353; P:cellular response to interleukin-4; ISS:UniProtKB.
DR GO; GO:0071222; P:cellular response to lipopolysaccharide; IDA:UniProtKB.
DR GO; GO:0006071; P:glycerol metabolic process; IBA:GO_Central.
DR GO; GO:0006098; P:pentose-phosphate shunt; TAS:Reactome.
DR GO; GO:0009052; P:pentose-phosphate shunt, non-oxidative branch; ISS:UniProtKB.
DR GO; GO:0016310; P:phosphorylation; IDA:UniProtKB.
DR GO; GO:0050727; P:regulation of inflammatory response; ISS:UniProtKB.
DR GO; GO:0043030; P:regulation of macrophage activation; ISS:UniProtKB.
DR CDD; cd07777; FGGY_SHK_like; 1.
DR InterPro; IPR043129; ATPase_NBD.
DR InterPro; IPR018484; Carb_kinase_FGGY_N.
DR InterPro; IPR042027; SHK.
DR Pfam; PF00370; FGGY_N; 1.
DR SUPFAM; SSF53067; SSF53067; 2.
PE 1: Evidence at protein level;
KW ATP-binding; Cytoplasm; Kinase; Nucleotide-binding; Reference proteome;
KW Transferase.
FT CHAIN 1..478
FT /note="Sedoheptulokinase"
FT /id="PRO_0000059564"
FT VARIANT 215
FT /note="E -> K (in dbSNP:rs150857)"
FT /evidence="ECO:0000269|PubMed:10673275"
FT /id="VAR_042580"
FT VARIANT 421
FT /note="E -> D (in dbSNP:rs224496)"
FT /id="VAR_048591"
FT VARIANT 434
FT /note="L -> M (in dbSNP:rs36125540)"
FT /id="VAR_048592"
SQ SEQUENCE 478 AA; 51505 MW; 0C930B380826AC1E CRC64;
MAARPITLGI DLGTTSVKAA LLRAAPDDPS GFAVLASCAR AARAEAAVES AVAGPQGREQ
DVSRILQALH ECLAALPRPQ LRSVVGIGVS GQMHGVVFWK TGQGCEWTEG GITPVFEPRA
VSHLVTWQDG RCSSEFLASL PQPKSHLSVA TGFGCATIFW LLKYRPEFLK SYDAAGTIHD
YVVAMLCGLP RPLMSDQNAA SWGYFNTQSQ SWNVETLRSS GFPVHLLPDI AEPGSVAGRT
SHMWFEIPKG TQVGVALGDL QASVYSCMAQ RTDAVLNIST SVQLAASMPS GFQPAQTPDP
TAPVAYFPYF NRTYLGVAAS LNGGNVLATF VHMLVQWMAD LGLEVEESTV YSRMIQAAVQ
QRDTHLTITP TVLGERHLPD QLASVTRISS SDLSLGHVTR ALCRGIVQNL HSMLPIQQLQ
EWGVERVMGS GSALSRNDVL KQEVQRAFPL PMSFGQDVDA AVGAALVMLR RHLNQKES
