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Q969G6 (RIFK_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 122. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (4) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Riboflavin kinase

EC=2.7.1.26
Alternative name(s):
ATP:riboflavin 5'-phosphotransferase
Flavokinase
Gene names
Name:RFK
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length155 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Catalyzes the phosphorylation of riboflavin (vitamin B2) to form flavin-mononucleotide (FMN), hence rate-limiting enzyme in the synthesis of FAD. Essential for TNF-induced reactive oxygen species (ROS) production. Through its interaction with both TNFRSF1A and CYBA, physically and functionally couples TNFRSF1A to NADPH oxidase. TNF-activation of RFK may enhance the incorporation of FAD in NADPH oxidase, a critical step for the assembly and activation of NADPH oxidase. Ref.4

Catalytic activity

ATP + riboflavin = ADP + FMN.

Cofactor

Zinc or magnesium.

Pathway

Cofactor biosynthesis; FMN biosynthesis; FMN from riboflavin (ATP route): step 1/1.

Subunit structure

Monomer. Directly interacts with TNFRSF1A death domain. TNFRSF1A-binding may be supported by TRADD. In the absence of TNFRSF1A, interacts with TRADD. Independently of TNFRSF1A, interacts with the NADPH oxidase subunit CYBA. Ref.4

Subcellular location

Cytoplasm By similarity.

Tissue specificity

Detected in brain, placenta and urinary bladder.

Sequence caution

The sequence AAH07069.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.

The sequence BAA92033.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 155155Riboflavin kinase
PRO_0000194148

Sites

Active site791Nucleophile By similarity
Metal binding271Magnesium
Binding site151ATP; via amide nitrogen
Binding site211ATP; via amide nitrogen
Binding site271ATP; via amide nitrogen
Binding site291ATP
Binding site821ATP; via amide nitrogen and carbonyl oxygen
Binding site841ATP; via carbonyl oxygen
Binding site911ATP
Binding site1041FMN
Binding site1071FMN; via amide nitrogen and carbonyl oxygen
Binding site1091FMN; via amide nitrogen

Experimental info

Mutagenesis791E → Q: Loss of kinase activity. No effect on TNFRSF1A- and CYBA-binding. Ref.4
Sequence conflict961N → S in BAA92033. Ref.1

Secondary structure

.......................... 155
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Q969G6 [UniParc].

Last modified October 14, 2008. Version 2.
Checksum: 3E038E487E164EBA

FASTA15517,623
        10         20         30         40         50         60 
MRHLPYFCRG QVVRGFGRGS KQLGIPTANF PEQVVDNLPA DISTGIYYGW ASVGSGDVHK 

        70         80         90        100        110        120 
MVVSIGWNPY YKNTKKSMET HIMHTFKEDF YGEILNVAIV GYLRPEKNFD SLESLISAIQ 

       130        140        150 
GDIEEAKKRL ELPEHLKIKE DNFFQVSKSK IMNGH 

« Hide

References

« Hide 'large scale' references
[1]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Placenta.
[2]"DNA sequence and analysis of human chromosome 9."
Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L., Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R., Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S., Bagguley C.L. expand/collapse author list , Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y., Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E., Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M., Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J., Frankish A., Frankland J.A., French L., Fricker D.G., Garner P., Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S., Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E., Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D., Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E., Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K., Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J., Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E., McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V., Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S., Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K., Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J., Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M., West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L., Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M., Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J., Dunham I.
Nature 429:369-374(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Urinary bladder.
[4]"Riboflavin kinase couples TNF receptor 1 to NADPH oxidase."
Yazdanpanah B., Wiegmann K., Tchikov V., Krut O., Pongratz C., Schramm M., Kleinridders A., Wunderlich T., Kashkar H., Utermoehlen O., Bruening J.C., Schuetze S., Kroenke M.
Nature 460:1159-1163(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH CYBA; TNFRSF1A AND TRADD, MUTAGENESIS OF GLU-79.
[5]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[6]"Crystal structure of human riboflavin kinase reveals a beta barrel fold and a novel active site arch."
Karthikeyan S., Zhou Q., Mseeh F., Grishin N.V., Osterman A.L., Zhang H.
Structure 11:265-273(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) OF 2-148 IN COMPLEX WITH MG-ADP AND RIBOFLAVIN NUCLEOTIDE.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AK002011 mRNA. Translation: BAA92033.1. Different initiation.
AL391868 Genomic DNA. Translation: CAI40676.1.
BC007069 mRNA. Translation: AAH07069.1. Different initiation.
CCDSCCDS35044.2.
RefSeqNP_060809.3. NM_018339.5.
UniGeneHs.37558.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1NB0X-ray1.70A2-148[»]
1NB9X-ray1.70A2-148[»]
1P4MX-ray1.80A2-148[»]
1Q9SX-ray2.42A1-148[»]
ProteinModelPortalQ969G6.
SMRQ969G6. Positions 2-148.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid120594. 3 interactions.
DIPDIP-60454N.
IntActQ969G6. 3 interactions.
MINTMINT-1401441.
STRING9606.ENSP00000257452.

Chemistry

DrugBankDB00140. Riboflavin.

PTM databases

PhosphoSiteQ969G6.

Polymorphism databases

DMDM209572667.

Proteomic databases

MaxQBQ969G6.
PaxDbQ969G6.
PRIDEQ969G6.

Protocols and materials databases

DNASU55312.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000376736; ENSP00000365926; ENSG00000135002.
GeneID55312.
KEGGhsa:55312.
UCSCuc004akd.2. human.

Organism-specific databases

CTD55312.
GeneCardsGC09M079000.
H-InvDBHIX0169330.
HGNCHGNC:30324. RFK.
HPAHPA057163.
MIM613010. gene.
neXtProtNX_Q969G6.
PharmGKBPA134916697.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0196.
HOGENOMHOG000260803.
HOVERGENHBG049989.
InParanoidQ969G6.
KOK00861.
OMASLPYFCR.
OrthoDBEOG7K3TP0.
PhylomeDBQ969G6.
TreeFamTF313786.

Enzyme and pathway databases

BioCycMetaCyc:HS05938-MONOMER.
ReactomeREACT_111217. Metabolism.
REACT_116125. Disease.
UniPathwayUPA00276; UER00406.

Gene expression databases

ArrayExpressQ969G6.
BgeeQ969G6.
CleanExHS_RFK.
GenevestigatorQ969G6.

Family and domain databases

Gene3D2.40.30.30. 1 hit.
InterProIPR023468. Riboflavin_kinase.
IPR015865. Riboflavin_kinase_bac/euk.
IPR023465. Riboflavin_kinase_domain.
[Graphical view]
PANTHERPTHR22749. PTHR22749. 1 hit.
PfamPF01687. Flavokinase. 1 hit.
[Graphical view]
SMARTSM00904. Flavokinase. 1 hit.
[Graphical view]
SUPFAMSSF82114. SSF82114. 1 hit.
ProtoNetSearch...

Other

EvolutionaryTraceQ969G6.
GenomeRNAi55312.
NextBio59546.
PROQ969G6.
SOURCESearch...

Entry information

Entry nameRIFK_HUMAN
AccessionPrimary (citable) accession number: Q969G6
Secondary accession number(s): Q5JSG9, Q9NUT7
Entry history
Integrated into UniProtKB/Swiss-Prot: October 3, 2003
Last sequence update: October 14, 2008
Last modified: July 9, 2014
This is version 122 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

PATHWAY comments

Index of metabolic and biosynthesis pathways

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human chromosome 9

Human chromosome 9: entries, gene names and cross-references to MIM