Q969G6 (RIFK_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Riboflavin kinase
EC=2.7.1.26

Alternative name(s):
ATP:riboflavin 5'-phosphotransferase
Flavokinase

Gene names

Name:

RFK

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	155 AA.
Sequence status	Complete.
Protein existence	Evidence 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.

Ontologies

Keywords
Cellular component	Cytoplasm
Ligand	ATP-binding FMN Magnesium Metal-binding Nucleotide-binding Zinc
Molecular function	Kinase Transferase
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	FMN biosynthetic process Inferred from electronic annotation. Source: UniProtKB-UniPathway riboflavin biosynthetic process Non-traceable author statement Ref.6. Source: UniProtKB
Cellular_component	cytosol Traceable author statement. Source: Reactome mitochondrion Inferred from electronic annotation. Source: Compara
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW riboflavin kinase activity Non-traceable author statement Ref.6. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 155

155

Riboflavin kinase

PRO_0000194148

Sites

Active site

79

1

Nucleophile By similarity

Metal binding

27

1

Magnesium

Binding site

15

1

ATP; via amide nitrogen

Binding site

21

1

ATP; via amide nitrogen

Binding site

27

1

ATP; via amide nitrogen

Binding site

29

1

ATP

Binding site

82

1

ATP; via amide nitrogen and carbonyl oxygen

Binding site

84

1

ATP; via carbonyl oxygen

Binding site

91

1

ATP

Binding site

104

1

FMN

Binding site

107

1

FMN; via amide nitrogen and carbonyl oxygen

Binding site

109

1

FMN; via amide nitrogen

Experimental info

Mutagenesis

79

1

E → Q: Loss of kinase activity. No effect on TNFRSF1A- and CYBA-binding. Ref.4

Sequence conflict

96

1

N → S in BAA92033. Ref.1

Secondary structure

1

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155

Helix Strand Turn

Details...

Beta strand

5 – 11

7

Beta strand

16 – 18

3

Helix

20 – 23

4

Helix

32 – 36

5

Beta strand

44 – 53

10

Beta strand

59 – 67

9

Beta strand

69 – 74

6

Beta strand

76 – 84

9

Beta strand

93 – 104

12

Helix

112 – 129

18

Helix

133 – 136

4

Helix

137 – 140

4

Helix

142 – 146

5

Sequences

	Sequence		Length	Mass (Da)
	Q969G6 [UniParc]. Last modified October 14, 2008. Version 2. Checksum: 3E038E487E164EBA	FASTA	155	17,623
	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

References

	« Hide 'large scale' referencesShow '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. , 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. , 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.

IPI

IPI00099995.

RefSeq

NP_060809.3. NM_018339.5.

UniGene

Hs.37558.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1NB0	X-ray	1.70	A	2-148	[»]
1NB9	X-ray	1.70	A	2-148	[»]
1P4M	X-ray	1.80	A	2-148	[»]
1Q9S	X-ray	2.42	A	7-148	[»]

ProteinModelPortal

Q969G6.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q969G6. 3 interactions.

MINT

MINT-1401441.

STRING

9606.ENSP00000257452.

PTM databases

PhosphoSite

Q969G6.

Polymorphism databases

DMDM

209572667.

Proteomic databases

PaxDb

Q969G6.

PRIDE

Q969G6.

Protocols and materials databases

DNASU

55312.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000376736; ENSP00000365926; ENSG00000135002.

GeneID

55312.

KEGG

hsa:55312.

UCSC

uc004akd.2. human.

Organism-specific databases

CTD

55312.

GeneCards

GC09M079000.

H-InvDB

HIX0169330.

HGNC

HGNC:30324. RFK.

MIM

613010. gene.

neXtProt

NX_Q969G6.

PharmGKB

PA134916697.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG0196.

HOGENOM

HOG000260803.

HOVERGEN

HBG049989.

InParanoid

Q969G6.

KO

K00861.

OrthoDB

EOG4RV2SP.

Enzyme and pathway databases

BioCyc

MetaCyc:HS05938-MONOMER.

Reactome

REACT_111217. Metabolism.

UniPathway

UPA00276; UER00406.

Gene expression databases

ArrayExpress

Q969G6.

Bgee

Q969G6.

CleanEx

HS_RFK.

Genevestigator

Q969G6.

GermOnline

ENSG00000135002. Homo sapiens.

Family and domain databases

Gene3D

2.40.30.30. 1 hit.

InterPro

IPR023468. Riboflavin_kinase.
IPR015865. Riboflavin_kinase_bac/euk.
IPR023465. Riboflavin_kinase_domain.
[Graphical view]

PANTHER

PTHR22749. PTHR22749. 1 hit.

Pfam

PF01687. Flavokinase. 1 hit.
[Graphical view]

SMART

SM00904. Flavokinase. 1 hit.
[Graphical view]

SUPFAM

SSF82114. Riboflavin_kinase. 1 hit.

ProtoNet

Search...

Other

DrugBank

DB00140. Riboflavin.

EvolutionaryTrace

Q969G6.

GenomeRNAi

55312.

NextBio

59546.

SOURCE

Search...

Entry information

Entry name

RIFK_HUMAN

Accession

Primary (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:	May 1, 2013
This is version 112 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.