RIFK_MOUSE
ID RIFK_MOUSE Reviewed; 155 AA.
AC Q8CFV9; O35471; O35472; Q9CQ95;
DT 03-OCT-2003, integrated into UniProtKB/Swiss-Prot.
DT 03-OCT-2003, sequence version 2.
DT 03-AUG-2022, entry version 146.
DE RecName: Full=Riboflavin kinase {ECO:0000250|UniProtKB:Q969G6};
DE EC=2.7.1.26 {ECO:0000250|UniProtKB:Q969G6};
DE AltName: Full=ATP:riboflavin 5'-phosphotransferase;
DE AltName: Full=Flavokinase;
DE AltName: Full=KOI-4;
GN Name=Rfk;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Embryonic stem cell, Kidney, and Small intestine;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Olfactory epithelium, and Retina;
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 NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 79-112 AND 114-155.
RC STRAIN=129/Sv;
RA Abrantes E.F., Silva A.M., Reis L.F.L.;
RL Submitted (OCT-1997) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP INTERACTION WITH CYBA; TNFRSF1A AND TRADD, AND DISRUPTION PHENOTYPE.
RX PubMed=19641494; DOI=10.1038/nature08206;
RA Yazdanpanah B., Wiegmann K., Tchikov V., Krut O., Pongratz C., Schramm M.,
RA Kleinridders A., Wunderlich T., Kashkar H., Utermoehlen O., Bruening J.C.,
RA Schuetze S., Kroenke M.;
RT "Riboflavin kinase couples TNF receptor 1 to NADPH oxidase.";
RL Nature 460:1159-1163(2009).
RN [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Lung, Pancreas, and Spleen;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
CC -!- FUNCTION: Catalyzes the phosphorylation of riboflavin (vitamin B2) to
CC form flavin-mononucleotide (FMN), hence rate-limiting enzyme in the
CC synthesis of FAD. Essential for TNF-induced reactive oxygen species
CC (ROS) production. Through its interaction with both TNFRSF1A and CYBA,
CC physically and functionally couples TNFRSF1A to NADPH oxidase. TNF-
CC activation of RFK may enhance the incorporation of FAD in NADPH
CC oxidase, a critical step for the assembly and activation of NADPH
CC oxidase (By similarity). {ECO:0000250|UniProtKB:Q969G6}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + riboflavin = ADP + FMN + H(+); Xref=Rhea:RHEA:14357,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:57986,
CC ChEBI:CHEBI:58210, ChEBI:CHEBI:456216; EC=2.7.1.26;
CC Evidence={ECO:0000250|UniProtKB:Q969G6};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:14358;
CC Evidence={ECO:0000250|UniProtKB:Q969G6};
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105; Evidence={ECO:0000250};
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000250|UniProtKB:Q969G6};
CC Note=Zinc or magnesium. {ECO:0000250};
CC -!- PATHWAY: Cofactor biosynthesis; FMN biosynthesis; FMN from riboflavin
CC (ATP route): step 1/1. {ECO:0000250|UniProtKB:Q969G6}.
CC -!- SUBUNIT: Monomer (By similarity). Directly interacts with TNFRSF1A
CC death domain; this interaction may be supported by TRADD
CC (PubMed:19641494). In the absence of TNFRSF1A, interacts with TRADD
CC (PubMed:19641494). Independently of TNFRSF1A, interacts with the NADPH
CC oxidase subunit CYBA (PubMed:19641494). {ECO:0000250|UniProtKB:Q969G6,
CC ECO:0000269|PubMed:19641494}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}.
CC -!- DISRUPTION PHENOTYPE: Mutant embryos die in utero before 7.5 dpc.
CC {ECO:0000269|PubMed:19641494}.
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DR EMBL; AK010607; BAB27057.1; -; mRNA.
DR EMBL; AK002806; BAB22372.1; -; mRNA.
DR EMBL; AK008352; BAB25622.1; -; mRNA.
DR EMBL; BC033521; AAH33521.2; -; mRNA.
DR EMBL; BC051021; AAH51021.1; -; mRNA.
DR EMBL; AF031380; AAB86494.1; -; Genomic_DNA.
DR EMBL; AF031381; AAB86495.1; -; Genomic_DNA.
DR CCDS; CCDS29688.1; -.
DR RefSeq; NP_062310.1; NM_019437.3.
DR AlphaFoldDB; Q8CFV9; -.
DR SMR; Q8CFV9; -.
DR BioGRID; 207641; 4.
DR DIP; DIP-60455N; -.
DR IntAct; Q8CFV9; 3.
DR STRING; 10090.ENSMUSP00000025617; -.
DR PhosphoSitePlus; Q8CFV9; -.
DR EPD; Q8CFV9; -.
DR MaxQB; Q8CFV9; -.
DR PaxDb; Q8CFV9; -.
DR PeptideAtlas; Q8CFV9; -.
DR PRIDE; Q8CFV9; -.
DR ProteomicsDB; 253242; -.
DR Antibodypedia; 27259; 156 antibodies from 24 providers.
DR DNASU; 54391; -.
DR Ensembl; ENSMUST00000025617; ENSMUSP00000025617; ENSMUSG00000024712.
DR GeneID; 54391; -.
DR KEGG; mmu:54391; -.
DR UCSC; uc008gxo.2; mouse.
DR CTD; 55312; -.
DR MGI; MGI:1914688; Rfk.
DR VEuPathDB; HostDB:ENSMUSG00000024712; -.
DR eggNOG; KOG3110; Eukaryota.
DR GeneTree; ENSGT00390000015537; -.
DR HOGENOM; CLU_048437_3_3_1; -.
DR InParanoid; Q8CFV9; -.
DR OMA; EVYKMVL; -.
DR OrthoDB; 1534271at2759; -.
DR PhylomeDB; Q8CFV9; -.
DR TreeFam; TF313786; -.
DR Reactome; R-MMU-196843; Vitamin B2 (riboflavin) metabolism.
DR UniPathway; UPA00276; UER00406.
DR BioGRID-ORCS; 54391; 26 hits in 74 CRISPR screens.
DR ChiTaRS; Rfk; mouse.
DR PRO; PR:Q8CFV9; -.
DR Proteomes; UP000000589; Chromosome 19.
DR RNAct; Q8CFV9; protein.
DR Bgee; ENSMUSG00000024712; Expressed in right colon and 261 other tissues.
DR Genevisible; Q8CFV9; MM.
DR GO; GO:0005739; C:mitochondrion; HDA:MGI.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0008531; F:riboflavin kinase activity; ISS:UniProtKB.
DR GO; GO:0006915; P:apoptotic process; ISO:MGI.
DR GO; GO:0009398; P:FMN biosynthetic process; IBA:GO_Central.
DR GO; GO:0016310; P:phosphorylation; IEA:UniProtKB-KW.
DR GO; GO:0033864; P:positive regulation of NAD(P)H oxidase activity; IGI:MGI.
DR GO; GO:0072593; P:reactive oxygen species metabolic process; IGI:MGI.
DR GO; GO:0009231; P:riboflavin biosynthetic process; IEA:InterPro.
DR GO; GO:0006771; P:riboflavin metabolic process; ISS:UniProtKB.
DR Gene3D; 2.40.30.30; -; 1.
DR InterPro; IPR023468; Riboflavin_kinase.
DR InterPro; IPR015865; Riboflavin_kinase_bac/euk.
DR InterPro; IPR023465; Riboflavin_kinase_dom_sf.
DR PANTHER; PTHR22749; PTHR22749; 1.
DR Pfam; PF01687; Flavokinase; 1.
DR SMART; SM00904; Flavokinase; 1.
DR SUPFAM; SSF82114; SSF82114; 1.
PE 1: Evidence at protein level;
KW ATP-binding; Cytoplasm; Flavoprotein; FMN; Kinase; Magnesium;
KW Metal-binding; Nucleotide-binding; Reference proteome; Transferase; Zinc.
FT CHAIN 1..155
FT /note="Riboflavin kinase"
FT /id="PRO_0000194149"
FT ACT_SITE 79
FT /note="Nucleophile"
FT /evidence="ECO:0000250"
FT BINDING 15
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q969G6"
FT BINDING 21
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q969G6"
FT BINDING 27
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q969G6"
FT BINDING 27
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:Q969G6"
FT BINDING 29
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q969G6"
FT BINDING 29
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:Q969G6"
FT BINDING 82
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q969G6"
FT BINDING 84
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q969G6"
FT BINDING 91
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q969G6"
FT BINDING 104
FT /ligand="FMN"
FT /ligand_id="ChEBI:CHEBI:58210"
FT /evidence="ECO:0000250|UniProtKB:Q969G6"
FT BINDING 107
FT /ligand="FMN"
FT /ligand_id="ChEBI:CHEBI:58210"
FT /evidence="ECO:0000250|UniProtKB:Q969G6"
FT BINDING 109
FT /ligand="FMN"
FT /ligand_id="ChEBI:CHEBI:58210"
FT /evidence="ECO:0000250|UniProtKB:Q969G6"
SQ SEQUENCE 155 AA; 17437 MW; AE6577023E3D34CF CRC64;
MRSLPFFCRG QVVRGFGRGS KQLGIPTANF PEQVVDNLPA DVSTGIYYGW ASVGSGDVHK
MVVSIGWNPY YKNVKKSMET HIIHTFKEDF YGEILNVAIV GYLRPEKNFD SLESLISAIQ
GDIEEAKKQL DLPEHLKLKD DNFFQVSKGK IMNGH
