IPPK_HUMAN
ID IPPK_HUMAN Reviewed; 491 AA.
AC Q9H8X2; Q5T9F7; Q9H7V8;
DT 06-DEC-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2001, sequence version 1.
DT 03-AUG-2022, entry version 159.
DE RecName: Full=Inositol-pentakisphosphate 2-kinase;
DE EC=2.7.1.158;
DE AltName: Full=IPK1 homolog;
DE AltName: Full=Inositol-1,3,4,5,6-pentakisphosphate 2-kinase;
DE AltName: Full=Ins(1,3,4,5,6)P5 2-kinase;
DE Short=InsP5 2-kinase;
GN Name=IPPK; Synonyms=C9orf12;
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 [MRNA], FUNCTION, ENZYME ACTIVITY, BIOPHYSICOCHEMICAL
RP PROPERTIES, AND TISSUE SPECIFICITY.
RX PubMed=12084730; DOI=10.1074/jbc.m205682200;
RA Verbsky J.W., Wilson M.P., Kisseleva M.V., Majerus P.W., Wente S.R.;
RT "The synthesis of inositol hexakisphosphate. Characterization of human
RT inositol 1,3,4,5,6-pentakisphosphate 2-kinase.";
RL J. Biol. Chem. 277:31857-31862(2002).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Spinal cord;
RA Hulme D.J., Dawkins J.L., Nicholson G.A.;
RT "Characterization of a novel gene, C9orf12, and exclusion as the gene
RT causing hereditary sensory neuropathy type I by mutation analysis.";
RL Submitted (FEB-2001) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Teratocarcinoma;
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15164053; DOI=10.1038/nature02465;
RA Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L.,
RA Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R.,
RA Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S.,
RA Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K.,
RA Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y.,
RA Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C.,
RA Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E.,
RA Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M.,
RA Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J.,
RA Frankish A., Frankland J.A., French L., Fricker D.G., Garner P.,
RA Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S.,
RA Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E.,
RA Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D.,
RA Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E.,
RA Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K.,
RA Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S.,
RA Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J.,
RA Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E.,
RA McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V.,
RA Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S.,
RA Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K.,
RA Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J.,
RA Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M.,
RA West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L.,
RA Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M.,
RA Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J.,
RA Dunham I.;
RT "DNA sequence and analysis of human chromosome 9.";
RL Nature 429:369-374(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Testis;
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 [6]
RP FUNCTION.
RX PubMed=15967797; DOI=10.1074/jbc.m503366200;
RA Verbsky J., Majerus P.W.;
RT "Increased levels of inositol hexakisphosphate (InsP6) protect HEK293 cells
RT from tumor necrosis factor (alpha)- and Fas-induced apoptosis.";
RL J. Biol. Chem. 280:29263-29268(2005).
RN [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-282, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
CC -!- FUNCTION: Phosphorylates Ins(1,3,4,5,6)P5 at position 2 to form
CC Ins(1,2,3,4,5,6)P6 (InsP6 or phytate). InsP6 is involved in many
CC processes such as mRNA export, non-homologous end-joining, endocytosis,
CC ion channel regulation. It also protects cells from TNF-alpha-induced
CC apoptosis. {ECO:0000269|PubMed:12084730, ECO:0000269|PubMed:15967797}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1D-myo-inositol 1,3,4,5,6-pentakisphosphate + ATP = 1D-myo-
CC inositol hexakisphosphate + ADP + H(+); Xref=Rhea:RHEA:20313,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:57733,
CC ChEBI:CHEBI:58130, ChEBI:CHEBI:456216; EC=2.7.1.158;
CC Evidence={ECO:0000269|PubMed:12084730};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=0.43 uM for Ins(1,3,4,5,6)P5 {ECO:0000269|PubMed:12084730};
CC KM=21 uM for ATP {ECO:0000269|PubMed:12084730};
CC Vmax=31 nmol/min/mg enzyme {ECO:0000269|PubMed:12084730};
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}. Nucleus {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Ubiquitously expressed, with high expression in
CC heart, brain, testis and placenta. {ECO:0000269|PubMed:12084730}.
CC -!- DOMAIN: The EXKPK motif is conserved in inositol-pentakisphosphate 2-
CC kinases of both family 1 and 2.
CC -!- SIMILARITY: Belongs to the IPK1 type 2 family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAB14866.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; AF520811; AAM75353.1; -; mRNA.
DR EMBL; AF351202; AAK69692.1; -; mRNA.
DR EMBL; AK023225; BAB14476.1; -; mRNA.
DR EMBL; AK024267; BAB14866.1; ALT_INIT; mRNA.
DR EMBL; AL137074; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL157827; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC026154; AAH26154.1; -; mRNA.
DR CCDS; CCDS6699.1; -.
DR RefSeq; NP_073592.1; NM_022755.5.
DR AlphaFoldDB; Q9H8X2; -.
DR SMR; Q9H8X2; -.
DR BioGRID; 122279; 109.
DR IntAct; Q9H8X2; 98.
DR STRING; 9606.ENSP00000287996; -.
DR MoonProt; Q9H8X2; -.
DR iPTMnet; Q9H8X2; -.
DR PhosphoSitePlus; Q9H8X2; -.
DR BioMuta; IPPK; -.
DR DMDM; 74752731; -.
DR EPD; Q9H8X2; -.
DR jPOST; Q9H8X2; -.
DR MassIVE; Q9H8X2; -.
DR MaxQB; Q9H8X2; -.
DR PaxDb; Q9H8X2; -.
DR PeptideAtlas; Q9H8X2; -.
DR PRIDE; Q9H8X2; -.
DR ProteomicsDB; 81252; -.
DR Antibodypedia; 13762; 116 antibodies from 25 providers.
DR DNASU; 64768; -.
DR Ensembl; ENST00000287996.8; ENSP00000287996.3; ENSG00000127080.10.
DR GeneID; 64768; -.
DR KEGG; hsa:64768; -.
DR MANE-Select; ENST00000287996.8; ENSP00000287996.3; NM_022755.6; NP_073592.1.
DR UCSC; uc004asl.1; human.
DR CTD; 64768; -.
DR DisGeNET; 64768; -.
DR GeneCards; IPPK; -.
DR HGNC; HGNC:14645; IPPK.
DR HPA; ENSG00000127080; Tissue enhanced (esophagus).
DR MIM; 619043; gene.
DR neXtProt; NX_Q9H8X2; -.
DR OpenTargets; ENSG00000127080; -.
DR PharmGKB; PA25970; -.
DR VEuPathDB; HostDB:ENSG00000127080; -.
DR eggNOG; KOG4749; Eukaryota.
DR GeneTree; ENSGT00390000010053; -.
DR HOGENOM; CLU_033188_1_0_1; -.
DR InParanoid; Q9H8X2; -.
DR OMA; NCVHCGE; -.
DR OrthoDB; 1195478at2759; -.
DR PhylomeDB; Q9H8X2; -.
DR TreeFam; TF106142; -.
DR BioCyc; MetaCyc:HS05071-MON; -.
DR BRENDA; 2.7.1.158; 2681.
DR PathwayCommons; Q9H8X2; -.
DR Reactome; R-HSA-1855167; Synthesis of pyrophosphates in the cytosol.
DR Reactome; R-HSA-1855191; Synthesis of IPs in the nucleus.
DR SABIO-RK; Q9H8X2; -.
DR SignaLink; Q9H8X2; -.
DR BioGRID-ORCS; 64768; 170 hits in 1085 CRISPR screens.
DR ChiTaRS; IPPK; human.
DR GenomeRNAi; 64768; -.
DR Pharos; Q9H8X2; Tbio.
DR PRO; PR:Q9H8X2; -.
DR Proteomes; UP000005640; Chromosome 9.
DR RNAct; Q9H8X2; protein.
DR Bgee; ENSG00000127080; Expressed in lower esophagus mucosa and 169 other tissues.
DR ExpressionAtlas; Q9H8X2; baseline and differential.
DR Genevisible; Q9H8X2; HS.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005730; C:nucleolus; IMP:CAFA.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0035299; F:inositol pentakisphosphate 2-kinase activity; IDA:HGNC-UCL.
DR GO; GO:0060090; F:molecular adaptor activity; IMP:CAFA.
DR GO; GO:0032958; P:inositol phosphate biosynthetic process; IBA:GO_Central.
DR GO; GO:0043647; P:inositol phosphate metabolic process; TAS:Reactome.
DR GO; GO:0052746; P:inositol phosphorylation; IDA:BHF-UCL.
DR GO; GO:1901838; P:positive regulation of transcription of nucleolar large rRNA by RNA polymerase I; IMP:CAFA.
DR Gene3D; 3.30.200.110; -; 1.
DR InterPro; IPR009286; Ins_P5_2-kin.
DR InterPro; IPR043001; IP5_2-K_N_lobe.
DR PANTHER; PTHR14456; PTHR14456; 1.
DR Pfam; PF06090; Ins_P5_2-kin; 1.
PE 1: Evidence at protein level;
KW ATP-binding; Cytoplasm; Kinase; Nucleotide-binding; Nucleus;
KW Phosphoprotein; Reference proteome; Transferase.
FT CHAIN 1..491
FT /note="Inositol-pentakisphosphate 2-kinase"
FT /id="PRO_0000110529"
FT MOTIF 136..140
FT /note="EXKPK motif"
FT MOD_RES 282
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT VARIANT 277
FT /note="R -> W (in dbSNP:rs2277168)"
FT /id="VAR_049641"
FT VARIANT 376
FT /note="L -> F (in dbSNP:rs2277170)"
FT /id="VAR_049642"
FT CONFLICT 264
FT /note="V -> A (in Ref. 3; BAB14866)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 491 AA; 56017 MW; AE7A125F3BD709C0 CRC64;
MEEGKMDENE WGYHGEGNKS LVVAHAQRCV VLRFLKFPPN RKKTSEEIFQ HLQNIVDFGK
NVMKEFLGEN YVHYGEVVQL PLEFVKQLCL KIQSERPESR CDKDLDTLSG YAMCLPNLTR
LQTYRFAEHR PILCVEIKPK CGFIPFSSDV THEMKHKVCR YCMHQHLKVA TGKWKQISKY
CPLDLYSGNK QRMHFALKSL LQEAQNNLKI FKNGELIYGC KDARSPVADW SELAHHLKPF
FFPSNGLASG PHCTRAVIRE LVHVITRVLL SGSDKGRAGT LSPGLGPQGP RVCEASPFSR
SLRCQGKNTP ERSGLPKGCL LYKTLQVQML DLLDIEGLYP LYNRVERYLE EFPEERKTLQ
IDGPYDEAFY QKLLDLSTED DGTVAFALTK VQQYRVAMTA KDCSIMIALS PCLQDASSDQ
RPVVPSSRSR FAFSVSVLDL DLKPYESIPH QYKLDGKIVN YYSKTVRAKD NAVMSTRFKE
SEDCTLVLHK V