FN3K_HUMAN
ID FN3K_HUMAN Reviewed; 309 AA.
AC Q9H479;
DT 04-MAY-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2001, sequence version 1.
DT 03-AUG-2022, entry version 158.
DE RecName: Full=Fructosamine-3-kinase {ECO:0000303|PubMed:11016445};
DE EC=2.7.1.171 {ECO:0000269|PubMed:11016445, ECO:0000269|PubMed:11522682};
DE AltName: Full=Protein-psicosamine 3-kinase FN3K {ECO:0000305};
DE AltName: Full=Protein-ribulosamine 3-kinase FN3K {ECO:0000305};
DE EC=2.7.1.172 {ECO:0000269|PubMed:14633848};
GN Name=FN3K {ECO:0000303|PubMed:14633848, ECO:0000312|HGNC:HGNC:24822};
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], PROTEIN SEQUENCE OF 1-6; 30-41; 50-63; 76-92;
RP 103-116; 121-130 AND 173-190, ACETYLATION AT MET-1, FUNCTION, CATALYTIC
RP ACTIVITY, SUBUNIT, AND TISSUE SPECIFICITY.
RC TISSUE=Kidney;
RX PubMed=11016445; DOI=10.2337/diabetes.49.10.1627;
RA Delpierre G., Rider M.H., Collard F., Stroobant V., Vanstapel F.,
RA Santos H., Van Schaftingen E.;
RT "Identification, cloning, and heterologous expression of a mammalian
RT fructosamine-3-kinase.";
RL Diabetes 49:1627-1634(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
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 [3]
RP PROTEIN SEQUENCE OF 16-26; 30-41; 76-92; 103-116; 119-130; 132-142;
RP 173-187; 258-265; 270-276 AND 298-305, FUNCTION, CATALYTIC ACTIVITY, AND
RP TISSUE SPECIFICITY.
RX PubMed=11522682; DOI=10.2337/diabetes.50.9.2139;
RA Szwergold B.S., Howell S., Beisswenger P.J.;
RT "Human fructosamine-3-kinase: purification, sequencing, substrate
RT specificity, and evidence of activity in vivo.";
RL Diabetes 50:2139-2147(2001).
RN [4]
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., Buerckstuemmer T.,
RA 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 [5]
RP FUNCTION.
RX PubMed=11975663; DOI=10.1042/bj20020325;
RA Delpierre G., Collard F., Fortpied J., Van Schaftingen E.;
RT "Fructosamine 3-kinase is involved in an intracellular deglycation pathway
RT in human erythrocytes.";
RL Biochem. J. 365:801-808(2002).
RN [6]
RP FUNCTION, CATALYTIC ACTIVITY, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=14633848; DOI=10.2337/diabetes.52.12.2888;
RA Collard F., Delpierre G., Stroobant V., Matthijs G., Van Schaftingen E.;
RT "A mammalian protein homologous to fructosamine-3-kinase is a ketosamine-3-
RT kinase acting on psicosamines and ribulosamines but not on fructosamines.";
RL Diabetes 52:2888-2895(2003).
CC -!- FUNCTION: Fructosamine-3-kinase involved in protein deglycation by
CC mediating phosphorylation of fructoselysine residues on glycated
CC proteins, to generate fructoselysine-3 phosphate (PubMed:11016445,
CC PubMed:11522682, PubMed:11975663). Fructoselysine-3 phosphate adducts
CC are unstable and decompose under physiological conditions
CC (PubMed:11522682, PubMed:11975663). Involved in intracellular
CC deglycation in erythrocytes (PubMed:11975663). Involved in the response
CC to oxidative stress by mediating deglycation of NFE2L2/NRF2, glycation
CC impairing NFE2L2/NRF2 function (By similarity). Also able to
CC phosphorylate psicosamines and ribulosamines (PubMed:14633848).
CC {ECO:0000250|UniProtKB:Q9ER35, ECO:0000269|PubMed:11016445,
CC ECO:0000269|PubMed:11522682, ECO:0000269|PubMed:11975663,
CC ECO:0000269|PubMed:14633848}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + N(6)-(D-fructosyl)-L-lysyl-[protein] = ADP + H(+) +
CC N(6)-(3-O-phospho-D-fructosyl)-L-lysyl-[protein];
CC Xref=Rhea:RHEA:59832, Rhea:RHEA-COMP:15451, Rhea:RHEA-COMP:15452,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:143253,
CC ChEBI:CHEBI:143254, ChEBI:CHEBI:456216; EC=2.7.1.171;
CC Evidence={ECO:0000269|PubMed:11016445, ECO:0000269|PubMed:11522682};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:59833;
CC Evidence={ECO:0000269|PubMed:11016445, ECO:0000269|PubMed:11522682};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + N(6)-D-ribulosyl-L-lysyl-[protein] = ADP + H(+) + N(6)-
CC (3-O-phospho-D-ribulosyl)-L-lysyl-[protein]; Xref=Rhea:RHEA:48432,
CC Rhea:RHEA-COMP:12103, Rhea:RHEA-COMP:12104, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:90418, ChEBI:CHEBI:90420,
CC ChEBI:CHEBI:456216; EC=2.7.1.172;
CC Evidence={ECO:0000269|PubMed:14633848};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:48433;
CC Evidence={ECO:0000269|PubMed:14633848};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + N(6)-(D-psicosyl)-L-lysyl-[protein] = ADP + H(+) + N(6)-
CC (3-O-phospho-D-psicosyl)-L-lysyl-[protein]; Xref=Rhea:RHEA:61392,
CC Rhea:RHEA-COMP:15796, Rhea:RHEA-COMP:15797, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:144621, ChEBI:CHEBI:144622,
CC ChEBI:CHEBI:456216; Evidence={ECO:0000269|PubMed:14633848};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:61393;
CC Evidence={ECO:0000269|PubMed:14633848};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=10 uM for deoxymorpholinofructose {ECO:0000269|PubMed:14633848};
CC KM=160 uM for deoxymorpholinopsicose {ECO:0000269|PubMed:14633848};
CC KM=140 uM for Psicoselysine {ECO:0000269|PubMed:14633848};
CC KM=2.6 uM for deoxymorpholinoribulose {ECO:0000269|PubMed:14633848};
CC -!- SUBUNIT: Monomer. {ECO:0000269|PubMed:11016445}.
CC -!- TISSUE SPECIFICITY: Widely expressed (PubMed:11522682). Expressed in
CC erythrocytes (PubMed:11016445). {ECO:0000269|PubMed:11016445,
CC ECO:0000269|PubMed:11522682}.
CC -!- SIMILARITY: Belongs to the fructosamine kinase family. {ECO:0000305}.
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DR EMBL; AJ404615; CAC16393.1; -; mRNA.
DR EMBL; BC042680; AAH42680.1; -; mRNA.
DR CCDS; CCDS11818.1; -.
DR RefSeq; NP_071441.1; NM_022158.3.
DR AlphaFoldDB; Q9H479; -.
DR SMR; Q9H479; -.
DR BioGRID; 122075; 12.
DR IntAct; Q9H479; 4.
DR STRING; 9606.ENSP00000300784; -.
DR iPTMnet; Q9H479; -.
DR PhosphoSitePlus; Q9H479; -.
DR BioMuta; FN3K; -.
DR DMDM; 13959371; -.
DR EPD; Q9H479; -.
DR jPOST; Q9H479; -.
DR MassIVE; Q9H479; -.
DR MaxQB; Q9H479; -.
DR PaxDb; Q9H479; -.
DR PeptideAtlas; Q9H479; -.
DR PRIDE; Q9H479; -.
DR ProteomicsDB; 80792; -.
DR Antibodypedia; 33043; 174 antibodies from 26 providers.
DR DNASU; 64122; -.
DR Ensembl; ENST00000300784.8; ENSP00000300784.7; ENSG00000167363.14.
DR GeneID; 64122; -.
DR KEGG; hsa:64122; -.
DR MANE-Select; ENST00000300784.8; ENSP00000300784.7; NM_022158.4; NP_071441.1.
DR UCSC; uc010wvs.2; human.
DR CTD; 64122; -.
DR DisGeNET; 64122; -.
DR GeneCards; FN3K; -.
DR HGNC; HGNC:24822; FN3K.
DR HPA; ENSG00000167363; Tissue enhanced (brain).
DR MIM; 608425; gene.
DR neXtProt; NX_Q9H479; -.
DR OpenTargets; ENSG00000167363; -.
DR PharmGKB; PA134870460; -.
DR VEuPathDB; HostDB:ENSG00000167363; -.
DR eggNOG; KOG3021; Eukaryota.
DR GeneTree; ENSGT00390000005730; -.
DR HOGENOM; CLU_036517_0_1_1; -.
DR InParanoid; Q9H479; -.
DR OMA; QSDWPSF; -.
DR OrthoDB; 943202at2759; -.
DR PhylomeDB; Q9H479; -.
DR TreeFam; TF313452; -.
DR BioCyc; MetaCyc:ENSG00000167363-MON; -.
DR BRENDA; 2.7.1.171; 2681.
DR PathwayCommons; Q9H479; -.
DR Reactome; R-HSA-163841; Gamma carboxylation, hypusine formation and arylsulfatase activation.
DR SignaLink; Q9H479; -.
DR BioGRID-ORCS; 64122; 13 hits in 1078 CRISPR screens.
DR ChiTaRS; FN3K; human.
DR GeneWiki; FN3K; -.
DR GeneWiki; Fructosamine-3-kinase; -.
DR GenomeRNAi; 64122; -.
DR Pharos; Q9H479; Tbio.
DR PRO; PR:Q9H479; -.
DR Proteomes; UP000005640; Chromosome 17.
DR RNAct; Q9H479; protein.
DR Bgee; ENSG00000167363; Expressed in sural nerve and 90 other tissues.
DR Genevisible; Q9H479; HS.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0016301; F:kinase activity; IBA:GO_Central.
DR GO; GO:0102194; F:protein-fructosamine 3-kinase activity; IDA:UniProtKB.
DR GO; GO:0102193; F:protein-ribulosamine 3-kinase activity; IEA:UniProtKB-EC.
DR GO; GO:0030855; P:epithelial cell differentiation; IEP:UniProtKB.
DR GO; GO:0030389; P:fructosamine metabolic process; IBA:GO_Central.
DR GO; GO:0030393; P:fructoselysine metabolic process; NAS:UniProtKB.
DR GO; GO:0016310; P:phosphorylation; IEA:UniProtKB-KW.
DR GO; GO:0043687; P:post-translational protein modification; TAS:Reactome.
DR GO; GO:0036525; P:protein deglycation; IDA:UniProtKB.
DR InterPro; IPR016477; Fructo-/Ketosamine-3-kinase.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR PANTHER; PTHR12149; PTHR12149; 1.
DR Pfam; PF03881; Fructosamin_kin; 1.
DR PIRSF; PIRSF006221; Ketosamine-3-kinase; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
PE 1: Evidence at protein level;
KW Acetylation; ATP-binding; Direct protein sequencing; Kinase;
KW Nucleotide-binding; Reference proteome; Transferase.
FT CHAIN 1..309
FT /note="Fructosamine-3-kinase"
FT /id="PRO_0000216337"
FT ACT_SITE 217
FT /note="Proton acceptor"
FT /evidence="ECO:0000250|UniProtKB:P9WI99"
FT BINDING 89..91
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q9HA64"
FT MOD_RES 1
FT /note="N-acetylmethionine"
FT /evidence="ECO:0000269|PubMed:11016445"
SQ SEQUENCE 309 AA; 35171 MW; BA886A86655DE28F CRC64;
MEQLLRAELR TATLRAFGGP GAGCISEGRA YDTDAGPVFV KVNRRTQARQ MFEGEVASLE
ALRSTGLVRV PRPMKVIDLP GGGAAFVMEH LKMKSLSSQA SKLGEQMADL HLYNQKLREK
LKEEENTVGR RGEGAEPQYV DKFGFHTVTC CGFIPQVNEW QDDWPTFFAR HRLQAQLDLI
EKDYADREAR ELWSRLQVKI PDLFCGLEIV PALLHGDLWS GNVAEDDVGP IIYDPASFYG
HSEFELAIAL MFGGFPRSFF TAYHRKIPKA PGFDQRLLLY QLFNYLNHWN HFGREYRSPS
LGTMRRLLK
