Full text data of SHPK
SHPK
(CARKL)
[Confidence: low (only semi-automatic identification from reviews)]
Sedoheptulokinase; SHK; 2.7.1.14 (Carbohydrate kinase-like protein)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
Sedoheptulokinase; SHK; 2.7.1.14 (Carbohydrate kinase-like protein)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
UniProt
Q9UHJ6
ID SHPK_HUMAN Reviewed; 478 AA.
AC Q9UHJ6; B2R640; Q8WUH3;
DT 27-APR-2001, integrated into UniProtKB/Swiss-Prot.
read moreDT 18-MAY-2010, sequence version 3.
DT 22-JAN-2014, entry version 103.
DE RecName: Full=Sedoheptulokinase;
DE Short=SHK;
DE EC=2.7.1.14;
DE AltName: Full=Carbohydrate kinase-like protein;
GN Name=SHPK; Synonyms=CARKL;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA], TISSUE SPECIFICITY, AND
RP VARIANTS LYS-215 AND GLU-421.
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
RT (CTNS): complete sequencing of a 200-kb segment and discovery of a
RT novel gene within the common cystinosis-causing deletion.";
RL Genome Res. 10:165-173(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT GLU-421.
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.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA 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.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., 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], AND VARIANT GLU-421.
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.,
RA Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K.,
RA Ottenwaelder B., Poustka A., 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.,
RA Gnerre S., Goldstein S., Grafham D.V., Grocock R., Hafez N.,
RA Hagopian D.S., Hart E., Norman C.H., Humphray S., Jaffe D.B.,
RA Jones M., Kamal M., Khodiyar V.K., LaButti K., Laird G., Lehoczky J.,
RA Liu X., Lokyitsang T., Loveland J., Lui A., Macdonald P., Major J.E.,
RA Matthews L., Mauceli E., McCarroll S.A., Mihalev A.H., Mudge J.,
RA Nguyen C., Nicol R., O'Leary S.B., Osoegawa K., Schwartz D.C.,
RA 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
RT the human lineage.";
RL Nature 440:1045-1049(2006).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANT GLU-421.
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT GLU-421.
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
RT project: 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.,
RA Zijlstra F.S., 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
RT the CARKL gene.";
RL Hum. Mutat. 29:532-536(2008).
RN [8]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, MASS SPECTROMETRY, AND
RP CLEAVAGE OF INITIATOR METHIONINE.
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J.,
RA Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in
RT a refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [9]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [10]
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.,
RA Otterbein L.E., Wagner O.;
RT "The sedoheptulose kinase CARKL directs macrophage polarization
RT through control of glucose metabolism.";
RL Cell Metab. 15:813-826(2012).
CC -!- FUNCTION: Acts as a modulator of macrophage activation through
CC control of glucose metabolism (By similarity).
CC -!- CATALYTIC ACTIVITY: ATP + sedoheptulose = ADP + sedoheptulose 7-
CC phosphate.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=0.06 mM for sedoheptulose;
CC pH dependence:
CC Optimum pH is 8.5;
CC -!- SUBCELLULAR LOCATION: Cytoplasm (By similarity).
CC -!- TISSUE SPECIFICITY: Strongly expressed in liver, kidney and
CC pancreas. Expressed at lower levels in placenta and heart. Very
CC weakly expressed in lung and brain.
CC -!- INDUCTION: Down-regulated by LPS.
CC -!- SIMILARITY: Belongs to the FGGY kinase family.
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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 RefSeq; NP_037408.2; NM_013276.2.
DR UniGene; Hs.579217; -.
DR ProteinModelPortal; Q9UHJ6; -.
DR SMR; Q9UHJ6; 8-374.
DR IntAct; Q9UHJ6; 1.
DR STRING; 9606.ENSP00000225519; -.
DR PhosphoSite; Q9UHJ6; -.
DR DMDM; 296452959; -.
DR PaxDb; Q9UHJ6; -.
DR PRIDE; Q9UHJ6; -.
DR DNASU; 23729; -.
DR Ensembl; ENST00000225519; ENSP00000225519; ENSG00000197417.
DR GeneID; 23729; -.
DR KEGG; hsa:23729; -.
DR UCSC; uc002fvz.1; human.
DR CTD; 23729; -.
DR GeneCards; GC17M003514; -.
DR HGNC; HGNC:1492; SHPK.
DR HPA; HPA024361; -.
DR MIM; 605060; gene.
DR neXtProt; NX_Q9UHJ6; -.
DR PharmGKB; PA162403312; -.
DR eggNOG; COG1070; -.
DR HOGENOM; HOG000008078; -.
DR HOVERGEN; HBG050796; -.
DR InParanoid; Q9UHJ6; -.
DR KO; K11214; -.
DR OMA; FQCSVYS; -.
DR PhylomeDB; Q9UHJ6; -.
DR GenomeRNAi; 23729; -.
DR NextBio; 46633; -.
DR PRO; PR:Q9UHJ6; -.
DR Bgee; Q9UHJ6; -.
DR CleanEx; HS_SHPK; -.
DR Genevestigator; Q9UHJ6; -.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0050277; F:sedoheptulokinase activity; 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:0009052; P:pentose-phosphate shunt, non-oxidative branch; ISS:UniProtKB.
DR GO; GO:0050727; P:regulation of inflammatory response; ISS:UniProtKB.
DR GO; GO:0043030; P:regulation of macrophage activation; ISS:UniProtKB.
DR InterPro; IPR018484; Carb_kinase_FGGY_N.
DR InterPro; IPR028491; Sedoheptulokinase.
DR PANTHER; PTHR10196:SF22; PTHR10196:SF22; 1.
DR Pfam; PF00370; FGGY_N; 1.
DR PROSITE; PS00933; FGGY_KINASES_1; FALSE_NEG.
DR PROSITE; PS00445; FGGY_KINASES_2; FALSE_NEG.
PE 1: Evidence at protein level;
KW Acetylation; ATP-binding; Complete proteome; Cytoplasm; Kinase;
KW Nucleotide-binding; Polymorphism; Reference proteome; Transferase.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 478 Sedoheptulokinase.
FT /FTId=PRO_0000059564.
FT MOD_RES 2 2 N-acetylalanine.
FT VARIANT 215 215 E -> K (in dbSNP:rs150857).
FT /FTId=VAR_042580.
FT VARIANT 421 421 D -> E (in dbSNP:rs224496).
FT /FTId=VAR_048591.
FT VARIANT 434 434 L -> M (in dbSNP:rs36125540).
FT /FTId=VAR_048592.
SQ SEQUENCE 478 AA; 51491 MW; 0C920A380927AC1E 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
DWGVERVMGS GSALSRNDVL KQEVQRAFPL PMSFGQDVDA AVGAALVMLR RHLNQKES
//
ID SHPK_HUMAN Reviewed; 478 AA.
AC Q9UHJ6; B2R640; Q8WUH3;
DT 27-APR-2001, integrated into UniProtKB/Swiss-Prot.
read moreDT 18-MAY-2010, sequence version 3.
DT 22-JAN-2014, entry version 103.
DE RecName: Full=Sedoheptulokinase;
DE Short=SHK;
DE EC=2.7.1.14;
DE AltName: Full=Carbohydrate kinase-like protein;
GN Name=SHPK; Synonyms=CARKL;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA], TISSUE SPECIFICITY, AND
RP VARIANTS LYS-215 AND GLU-421.
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
RT (CTNS): complete sequencing of a 200-kb segment and discovery of a
RT novel gene within the common cystinosis-causing deletion.";
RL Genome Res. 10:165-173(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT GLU-421.
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.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA 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.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., 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], AND VARIANT GLU-421.
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.,
RA Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K.,
RA Ottenwaelder B., Poustka A., 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.,
RA Gnerre S., Goldstein S., Grafham D.V., Grocock R., Hafez N.,
RA Hagopian D.S., Hart E., Norman C.H., Humphray S., Jaffe D.B.,
RA Jones M., Kamal M., Khodiyar V.K., LaButti K., Laird G., Lehoczky J.,
RA Liu X., Lokyitsang T., Loveland J., Lui A., Macdonald P., Major J.E.,
RA Matthews L., Mauceli E., McCarroll S.A., Mihalev A.H., Mudge J.,
RA Nguyen C., Nicol R., O'Leary S.B., Osoegawa K., Schwartz D.C.,
RA 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
RT the human lineage.";
RL Nature 440:1045-1049(2006).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANT GLU-421.
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT GLU-421.
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
RT project: 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.,
RA Zijlstra F.S., 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
RT the CARKL gene.";
RL Hum. Mutat. 29:532-536(2008).
RN [8]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, MASS SPECTROMETRY, AND
RP CLEAVAGE OF INITIATOR METHIONINE.
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J.,
RA Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in
RT a refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [9]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [10]
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.,
RA Otterbein L.E., Wagner O.;
RT "The sedoheptulose kinase CARKL directs macrophage polarization
RT through control of glucose metabolism.";
RL Cell Metab. 15:813-826(2012).
CC -!- FUNCTION: Acts as a modulator of macrophage activation through
CC control of glucose metabolism (By similarity).
CC -!- CATALYTIC ACTIVITY: ATP + sedoheptulose = ADP + sedoheptulose 7-
CC phosphate.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=0.06 mM for sedoheptulose;
CC pH dependence:
CC Optimum pH is 8.5;
CC -!- SUBCELLULAR LOCATION: Cytoplasm (By similarity).
CC -!- TISSUE SPECIFICITY: Strongly expressed in liver, kidney and
CC pancreas. Expressed at lower levels in placenta and heart. Very
CC weakly expressed in lung and brain.
CC -!- INDUCTION: Down-regulated by LPS.
CC -!- SIMILARITY: Belongs to the FGGY kinase family.
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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 RefSeq; NP_037408.2; NM_013276.2.
DR UniGene; Hs.579217; -.
DR ProteinModelPortal; Q9UHJ6; -.
DR SMR; Q9UHJ6; 8-374.
DR IntAct; Q9UHJ6; 1.
DR STRING; 9606.ENSP00000225519; -.
DR PhosphoSite; Q9UHJ6; -.
DR DMDM; 296452959; -.
DR PaxDb; Q9UHJ6; -.
DR PRIDE; Q9UHJ6; -.
DR DNASU; 23729; -.
DR Ensembl; ENST00000225519; ENSP00000225519; ENSG00000197417.
DR GeneID; 23729; -.
DR KEGG; hsa:23729; -.
DR UCSC; uc002fvz.1; human.
DR CTD; 23729; -.
DR GeneCards; GC17M003514; -.
DR HGNC; HGNC:1492; SHPK.
DR HPA; HPA024361; -.
DR MIM; 605060; gene.
DR neXtProt; NX_Q9UHJ6; -.
DR PharmGKB; PA162403312; -.
DR eggNOG; COG1070; -.
DR HOGENOM; HOG000008078; -.
DR HOVERGEN; HBG050796; -.
DR InParanoid; Q9UHJ6; -.
DR KO; K11214; -.
DR OMA; FQCSVYS; -.
DR PhylomeDB; Q9UHJ6; -.
DR GenomeRNAi; 23729; -.
DR NextBio; 46633; -.
DR PRO; PR:Q9UHJ6; -.
DR Bgee; Q9UHJ6; -.
DR CleanEx; HS_SHPK; -.
DR Genevestigator; Q9UHJ6; -.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0050277; F:sedoheptulokinase activity; 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:0009052; P:pentose-phosphate shunt, non-oxidative branch; ISS:UniProtKB.
DR GO; GO:0050727; P:regulation of inflammatory response; ISS:UniProtKB.
DR GO; GO:0043030; P:regulation of macrophage activation; ISS:UniProtKB.
DR InterPro; IPR018484; Carb_kinase_FGGY_N.
DR InterPro; IPR028491; Sedoheptulokinase.
DR PANTHER; PTHR10196:SF22; PTHR10196:SF22; 1.
DR Pfam; PF00370; FGGY_N; 1.
DR PROSITE; PS00933; FGGY_KINASES_1; FALSE_NEG.
DR PROSITE; PS00445; FGGY_KINASES_2; FALSE_NEG.
PE 1: Evidence at protein level;
KW Acetylation; ATP-binding; Complete proteome; Cytoplasm; Kinase;
KW Nucleotide-binding; Polymorphism; Reference proteome; Transferase.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 478 Sedoheptulokinase.
FT /FTId=PRO_0000059564.
FT MOD_RES 2 2 N-acetylalanine.
FT VARIANT 215 215 E -> K (in dbSNP:rs150857).
FT /FTId=VAR_042580.
FT VARIANT 421 421 D -> E (in dbSNP:rs224496).
FT /FTId=VAR_048591.
FT VARIANT 434 434 L -> M (in dbSNP:rs36125540).
FT /FTId=VAR_048592.
SQ SEQUENCE 478 AA; 51491 MW; 0C920A380927AC1E 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
DWGVERVMGS GSALSRNDVL KQEVQRAFPL PMSFGQDVDA AVGAALVMLR RHLNQKES
//
MIM
605060
*RECORD*
*FIELD* NO
605060
*FIELD* TI
*605060 SEDOHEPTULOKINASE; SHPK
;;SHK;;
CARBOHYDRATE KINASE-LIKE; CARKL
*FIELD* TX
read more
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.
*FIELD* RF
1. Haschemi, A.; Kosma, P.; Gille, L.; Evans, C. R.; Burant, C. F.;
Starkl, P.; Knapp, B.; Haas, R.; Schmid, J. A.; Jandl, C.; Amir, S.;
Lubec, G.; Park, J.; Esterbauer, H.; Bilban, M.; Brizuela, L.; Pospisilik,
J. A.; Otterbein, L. E.; Wagner, O.: The sedoheptulose kinase CARKL
directs macrophage polarization through control of glucose metabolism. Cell
Metab. 15: 813-826, 2012.
2. Phornphutkul, C.; Anikster, Y.; Huizing, M.; Braun, P.; Brodie,
C.; Chou, J. Y.; Gahl, W. A.: The promoter of a lysosomal membrane
transporter gene, CTNS, binds Sp-1, shares sequences with the promoter
of an adjacent gene, CARKL, and causes cystinosis if mutated in a
critical region. Am. J. Hum. Genet. 69: 712-721, 2001.
3. Touchman, J. W.; Anikster, Y.; Dietrich, N. L.; Braden Maduro,
V. V.; McDowell, G.; Shotelersuk, V.; Bouffard, G. G.; Beckstrom-Sternberg,
S. M.; Gahl, W. A.; Green, E. D.: The genomic region encompassing
the nephropathic cystinosis gene (CTNS): complete sequencing of a
200-kb segment and discovery of a novel gene within the common cystinosis-causing
deletion. Genome Res. 10: 165-173, 2000.
4. Wamelink, M. M. C.; Struys, E. A.; Jansen, E. E. W.; Levtchenko,
E. N.; Zijlstra, F. S. M.; Engelke, U.; Blom, H. J.; Jakobs, C.; Wevers,
R. A.: Sedoheptulokinase deficiency due to a 57-kb deletion in cystinosis
patients causes urinary accumulation of sedoheptulose: elucidation
of the CARKL gene. Hum. Mutat. 29: 532-536, 2008.
*FIELD* CN
Paul J. Converse - updated: 9/24/2012
Cassandra L. Kniffin - updated: 7/28/2008
Deborah L. Stone - updated: 11/7/2001
*FIELD* CD
Dawn Watkins-Chow: 6/19/2000
*FIELD* ED
mgross: 09/25/2012
mgross: 9/25/2012
terry: 9/24/2012
wwang: 7/29/2008
ckniffin: 7/28/2008
carol: 11/7/2001
carol: 9/27/2001
carol: 6/20/2000
*RECORD*
*FIELD* NO
605060
*FIELD* TI
*605060 SEDOHEPTULOKINASE; SHPK
;;SHK;;
CARBOHYDRATE KINASE-LIKE; CARKL
*FIELD* TX
read more
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.
*FIELD* RF
1. Haschemi, A.; Kosma, P.; Gille, L.; Evans, C. R.; Burant, C. F.;
Starkl, P.; Knapp, B.; Haas, R.; Schmid, J. A.; Jandl, C.; Amir, S.;
Lubec, G.; Park, J.; Esterbauer, H.; Bilban, M.; Brizuela, L.; Pospisilik,
J. A.; Otterbein, L. E.; Wagner, O.: The sedoheptulose kinase CARKL
directs macrophage polarization through control of glucose metabolism. Cell
Metab. 15: 813-826, 2012.
2. Phornphutkul, C.; Anikster, Y.; Huizing, M.; Braun, P.; Brodie,
C.; Chou, J. Y.; Gahl, W. A.: The promoter of a lysosomal membrane
transporter gene, CTNS, binds Sp-1, shares sequences with the promoter
of an adjacent gene, CARKL, and causes cystinosis if mutated in a
critical region. Am. J. Hum. Genet. 69: 712-721, 2001.
3. Touchman, J. W.; Anikster, Y.; Dietrich, N. L.; Braden Maduro,
V. V.; McDowell, G.; Shotelersuk, V.; Bouffard, G. G.; Beckstrom-Sternberg,
S. M.; Gahl, W. A.; Green, E. D.: The genomic region encompassing
the nephropathic cystinosis gene (CTNS): complete sequencing of a
200-kb segment and discovery of a novel gene within the common cystinosis-causing
deletion. Genome Res. 10: 165-173, 2000.
4. Wamelink, M. M. C.; Struys, E. A.; Jansen, E. E. W.; Levtchenko,
E. N.; Zijlstra, F. S. M.; Engelke, U.; Blom, H. J.; Jakobs, C.; Wevers,
R. A.: Sedoheptulokinase deficiency due to a 57-kb deletion in cystinosis
patients causes urinary accumulation of sedoheptulose: elucidation
of the CARKL gene. Hum. Mutat. 29: 532-536, 2008.
*FIELD* CN
Paul J. Converse - updated: 9/24/2012
Cassandra L. Kniffin - updated: 7/28/2008
Deborah L. Stone - updated: 11/7/2001
*FIELD* CD
Dawn Watkins-Chow: 6/19/2000
*FIELD* ED
mgross: 09/25/2012
mgross: 9/25/2012
terry: 9/24/2012
wwang: 7/29/2008
ckniffin: 7/28/2008
carol: 11/7/2001
carol: 9/27/2001
carol: 6/20/2000