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Protein

Riboflavin kinase

Gene

RFK

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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.1 Publication

Catalytic activityi

ATP + riboflavin = ADP + FMN.

Cofactori

Zn2+, Mg2+Note: Zinc or magnesium.

Pathwayi: FMN biosynthesis

This protein is involved in step 1 of the subpathway that synthesizes FMN from riboflavin (ATP route).
Proteins known to be involved in this subpathway in this organism are:
  1. Riboflavin kinase (RFK)
This subpathway is part of the pathway FMN biosynthesis, which is itself part of Cofactor biosynthesis.
View all proteins of this organism that are known to be involved in the subpathway that synthesizes FMN from riboflavin (ATP route), the pathway FMN biosynthesis and in Cofactor biosynthesis.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei15ATP; via amide nitrogen1
Binding sitei21ATP; via amide nitrogen1
Metal bindingi27Magnesium1
Binding sitei27ATP; via amide nitrogen1
Binding sitei29ATP1
Active sitei79NucleophileBy similarity1
Binding sitei82ATP; via amide nitrogen and carbonyl oxygen1
Binding sitei84ATP; via carbonyl oxygen1
Binding sitei91ATP1
Binding sitei104FMN1
Binding sitei107FMN; via amide nitrogen and carbonyl oxygen1
Binding sitei109FMN; via amide nitrogen1

GO - Molecular functioni

GO - Biological processi

  • apoptotic process Source: MGI
  • FMN biosynthetic process Source: UniProtKB-UniPathway
  • positive regulation of NAD(P)H oxidase activity Source: MGI
  • reactive oxygen species metabolic process Source: Ensembl
  • riboflavin biosynthetic process Source: UniProtKB
  • riboflavin metabolic process Source: Reactome

Keywordsi

Molecular functionKinase, Transferase
LigandATP-binding, Flavoprotein, FMN, Magnesium, Metal-binding, Nucleotide-binding, Zinc

Enzyme and pathway databases

BioCyciMetaCyc:HS05938-MONOMER.
BRENDAi2.7.1.26. 2681.
ReactomeiR-HSA-196843. Vitamin B2 (riboflavin) metabolism.
UniPathwayiUPA00276; UER00406.

Names & Taxonomyi

Protein namesi
Recommended name:
Riboflavin kinase (EC:2.7.1.26)
Alternative name(s):
ATP:riboflavin 5'-phosphotransferase
Flavokinase
Gene namesi
Name:RFK
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 9

Organism-specific databases

HGNCiHGNC:30324. RFK.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: UniProtKB
  • cytosol Source: Reactome
  • mitochondrion Source: Ensembl

Keywords - Cellular componenti

Cytoplasm

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi79E → Q: Loss of kinase activity. No effect on TNFRSF1A- and CYBA-binding. 1 Publication1

Organism-specific databases

DisGeNETi55312.
OpenTargetsiENSG00000135002.
PharmGKBiPA134916697.

Chemistry databases

DrugBankiDB00140. Riboflavin.
DB03247. Riboflavin Monophosphate.

Polymorphism and mutation databases

BioMutaiRFK.
DMDMi209572667.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001941481 – 155Riboflavin kinaseAdd BLAST155

Proteomic databases

EPDiQ969G6.
MaxQBiQ969G6.
PaxDbiQ969G6.
PeptideAtlasiQ969G6.
PRIDEiQ969G6.

PTM databases

iPTMnetiQ969G6.
PhosphoSitePlusiQ969G6.

Expressioni

Tissue specificityi

Detected in brain, placenta and urinary bladder.

Gene expression databases

BgeeiENSG00000135002.
CleanExiHS_RFK.
ExpressionAtlasiQ969G6. baseline and differential.
GenevisibleiQ969G6. HS.

Organism-specific databases

HPAiCAB033887.
HPA023259.
HPA057163.

Interactioni

Subunit structurei

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.2 Publications

Protein-protein interaction databases

BioGridi120594. 8 interactors.
DIPiDIP-60454N.
IntActiQ969G6. 3 interactors.
MINTiMINT-1401441.
STRINGi9606.ENSP00000365926.

Structurei

Secondary structure

1155
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi5 – 11Combined sources7
Beta strandi16 – 18Combined sources3
Helixi20 – 23Combined sources4
Helixi32 – 36Combined sources5
Beta strandi44 – 53Combined sources10
Beta strandi59 – 67Combined sources9
Beta strandi69 – 74Combined sources6
Beta strandi76 – 84Combined sources9
Beta strandi93 – 104Combined sources12
Helixi112 – 129Combined sources18
Helixi133 – 136Combined sources4
Helixi137 – 140Combined sources4
Helixi142 – 146Combined sources5

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1NB0X-ray1.70A2-148[»]
1NB9X-ray1.70A2-148[»]
1P4MX-ray1.80A2-148[»]
1Q9SX-ray2.42A1-148[»]
ProteinModelPortaliQ969G6.
SMRiQ969G6.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ969G6.

Family & Domainsi

Phylogenomic databases

eggNOGiKOG3110. Eukaryota.
COG0196. LUCA.
GeneTreeiENSGT00390000015537.
HOGENOMiHOG000260803.
HOVERGENiHBG049989.
InParanoidiQ969G6.
KOiK00861.
OMAiGKDLGCP.
OrthoDBiEOG091G0Z4E.
PhylomeDBiQ969G6.
TreeFamiTF313786.

Family and domain databases

Gene3Di2.40.30.30. 1 hit.
InterProiView protein in InterPro
IPR023468. Riboflavin_kinase.
IPR015865. Riboflavin_kinase_bac/euk.
IPR023465. Riboflavin_kinase_domain.
PANTHERiPTHR22749. PTHR22749. 1 hit.
PfamiView protein in Pfam
PF01687. Flavokinase. 1 hit.
SMARTiView protein in SMART
SM00904. Flavokinase. 1 hit.
SUPFAMiSSF82114. SSF82114. 1 hit.

Sequencei

Sequence statusi: Complete.

Q969G6-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MRHLPYFCRG QVVRGFGRGS KQLGIPTANF PEQVVDNLPA DISTGIYYGW
60 70 80 90 100
ASVGSGDVHK MVVSIGWNPY YKNTKKSMET HIMHTFKEDF YGEILNVAIV
110 120 130 140 150
GYLRPEKNFD SLESLISAIQ GDIEEAKKRL ELPEHLKIKE DNFFQVSKSK

IMNGH
Length:155
Mass (Da):17,623
Last modified:October 14, 2008 - v2
Checksum:i3E038E487E164EBA
GO

Sequence cautioni

The sequence AAH07069 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated
The sequence BAA92033 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti96N → S in BAA92033 (PubMed:14702039).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK002011 mRNA. Translation: BAA92033.1. Different initiation.
AL391868 Genomic DNA. No translation available.
BC007069 mRNA. Translation: AAH07069.1. Different initiation.
CCDSiCCDS35044.2.
RefSeqiNP_060809.3. NM_018339.5.
UniGeneiHs.37558.

Genome annotation databases

EnsembliENST00000376736; ENSP00000365926; ENSG00000135002.
GeneIDi55312.
KEGGihsa:55312.
UCSCiuc004akd.3. human.

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.

Entry informationi

Entry nameiRIFK_HUMAN
AccessioniPrimary (citable) accession number: Q969G6
Secondary accession number(s): Q5JSG9, Q9NUT7
Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 3, 2003
Last sequence update: October 14, 2008
Last modified: June 7, 2017
This is version 149 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 9
    Human chromosome 9: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  4. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references