O00757 (F16P2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Fructose-1,6-bisphosphatase isozyme 2
Short name=FBPase 2
EC=3.1.3.11

Alternative name(s):
D-fructose-1,6-bisphosphate 1-phosphohydrolase 2

Gene names

Name:

FBP2

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	339 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Catalytic activity	D-fructose 1,6-bisphosphate + H2O = D-fructose 6-phosphate + phosphate.
Cofactor	Binds 3 magnesium ions per subunit By similarity. Ref.5
Enzyme regulation	Subject to complex allosteric regulation. The enzyme can assume an active R-state, or an inactive T-state. Intermediate conformations may exist. AMP acts as allosteric inhibitor. Fructose-2,6-biphosphate acts as competitive inhibitor. Ref.5
Pathway	Carbohydrate biosynthesis; gluconeogenesis.
Subunit structure	Homotetramer By similarity.
Sequence similarities	Belongs to the FBPase class 1 family.
Biophysicochemical properties	Kinetic parameters: KM=1.3 µM for fructose-1,6-biphosphate Ref.5

Ontologies

Keywords
Biological process	Carbohydrate metabolism Gluconeogenesis
Coding sequence diversity	Polymorphism
Ligand	Magnesium Metal-binding
Molecular function	Hydrolase
PTM	Phosphoprotein
Technical term	3D-structure Allosteric enzyme Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	fructose metabolic process Traceable author statement. Source: ProtInc gluconeogenesis Traceable author statement. Source: Reactome
Cellular component	cytosol Traceable author statement. Source: Reactome
Molecular function	fructose 1,6-bisphosphate 1-phosphatase activity Inferred from electronic annotation. Source: EC fructose-2,6-bisphosphate 2-phosphatase activity Traceable author statement. Source: ProtInc metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 339

339

Fructose-1,6-bisphosphatase isozyme 2

PRO_0000200504

Regions

Nucleotide binding

18 – 22

5

AMP By similarity

Nucleotide binding

28 – 32

5

AMP By similarity

Nucleotide binding

113 – 114

2

AMP By similarity

Region

122 – 125

4

Substrate binding By similarity

Region

213 – 216

4

Substrate binding By similarity

Region

244 – 249

6

Substrate binding By similarity

Region

275 – 277

3

Substrate binding By similarity

Sites

Metal binding

69

1

Magnesium 1 By similarity

Metal binding

98

1

Magnesium 1 By similarity

Metal binding

98

1

Magnesium 2 By similarity

Metal binding

119

1

Magnesium 2 By similarity

Metal binding

119

1

Magnesium 3 By similarity

Metal binding

121

1

Magnesium 2; via carbonyl oxygen By similarity

Metal binding

122

1

Magnesium 3 By similarity

Metal binding

281

1

Magnesium 3 By similarity

Binding site

141

1

AMP By similarity

Binding site

265

1

Substrate By similarity

Amino acid modifications

Modified residue

216

1

Phosphotyrosine Ref.6

Natural variations

Natural variant

86

1

V → L. Ref.1 Ref.4
Corresponds to variant rs573212 [ dbSNP | Ensembl ].

VAR_024448

Experimental info

Mutagenesis

21

1

K → E: Reduces sensitivity to AMP; when associated with M-178 and C-180. Ref.5

Mutagenesis

178

1

T → M: Reduces sensitivity to AMP; when associated with E-21 and C-180. Ref.5

Mutagenesis

180

1

Q → C: Reduces sensitivity to AMP; when associated with E-21 and M-178. Ref.5

Secondary structure

1

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339

Helix Strand Turn

Details...

Helix

14 – 20

7

Helix

31 – 49

19

Turn

55 – 57

3

Helix

70 – 88

19

Beta strand

93 – 97

5

Helix

108 – 110

3

Beta strand

114 – 119

6

Helix

127 – 129

3

Beta strand

136 – 141

6

Helix

150 – 153

4

Beta strand

161 – 163

3

Beta strand

165 – 168

4

Beta strand

173 – 177

5

Beta strand

183 – 187

5

Beta strand

194 – 200

7

Helix

217 – 219

3

Helix

222 – 232

11

Helix

249 – 258

10

Beta strand

263 – 265

3

Turn

278 – 281

4

Helix

282 – 292

11

Helix

303 – 305

3

Beta strand

317 – 319

3

Helix

322 – 336

15

Sequences

	Sequence		Length	Mass (Da)
	O00757 [UniParc]. Last modified September 27, 2005. Version 2. Checksum: 196B06D744710BC4	FASTA	339	36,743
	10 20 30 40 50 60 MTDRSPFETD MLTLTRYVME KGRQAKGTGE LTQLLNSMLT AIKAISSAVR KAGLAHLYGI 70 80 90 100 110 120 AGSVNVTGDE VKKLDVLSNS LVINMVQSSY STCVLVSEEN KDAIITAKEK RGKYVVCFDP 130 140 150 160 170 180 LDGSSNIDCL ASIGTIFAIY RKTSEDEPSE KDALQCGRNI VAAGYALYGS ATLVALSTGQ 190 200 210 220 230 240 GVDLFMLDPA LGEFVLVEKD VKIKKKGKIY SLNEGYAKYF DAATTEYVQK KKFPEDGSAP 250 260 270 280 290 300 YGARYVGSMV ADVHRTLVYG GIFLYPANQK SPKGKLRLLY ECNPVAYIIE QAGGLATTGT 310 320 330 QPVLDVKPEA IHQRVPLILG SPEDVQEYLT CVQKNQAGS

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Isolation and characterization of an allelic cDNA for human muscle fructose-1,6-bisphosphatase." Tillman H., Eschrich K. Gene 212:295-304(1998) [PubMed: 9678974] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT LEU-86. Tissue: Skeletal muscle.
[2]	"Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)." Halleck A., Ebert L., Mkoundinya M., Schick M., Eisenstein S., Neubert P., Kstrang K., Schatten R., Shen B., Henze S., Mar W., Korn B., Zuo D., Hu Y., LaBaer J. Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[3]	"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: 15164053] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	"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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT LEU-86. Tissue: Colon.
[5]	"The origin of the high sensitivity of muscle fructose 1,6-bisphosphatase towards AMP." Rakus D., Maciaszczyk E., Wawrzycka D., Ulaszewski S., Eschrich K., Dzugaj A. FEBS Lett. 579:5577-5581(2005) [PubMed: 16213487] [Abstract] Cited for: ENZYME REGULATION, COFACTOR, MUTAGENESIS OF LYS-21; THR-178 AND GLN-180, BIOPHYSICOCHEMICAL PROPERTIES.
[6]	"Global survey of phosphotyrosine signaling identifies oncogenic kinases in lung cancer." Rikova K., Guo A., Zeng Q., Possemato A., Yu J., Haack H., Nardone J., Lee K., Reeves C., Li Y., Hu Y., Tan Z., Stokes M., Sullivan L., Mitchell J., Wetzel R., Macneill J., Ren J.M. , Yuan J., Bakalarski C.E., Villen J., Kornhauser J.M., Smith B., Li D., Zhou X., Gygi S.P., Gu T.-L., Polakiewicz R.D., Rush J., Comb M.J. Cell 131:1190-1203(2007) [PubMed: 18083107] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-216, MASS SPECTROMETRY. Tissue: Lung carcinoma.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

Y10812 mRNA. Translation: CAA71772.1.
CR536483 mRNA. Translation: CAG38722.1.
AL161728 Genomic DNA. Translation: CAH72694.1.
BC113632 mRNA. Translation: AAI13633.1.
BC117477 mRNA. Translation: AAI17478.1.

IPI

IPI00299456.

RefSeq

NP_003828.2. NM_003837.2.

UniGene

Hs.61255.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
3IFA	X-ray	1.93	A/B/C/D	2-339	[»]
3IFC	X-ray	1.97	A/B/C/D	2-339	[»]

ProteinModelPortal

O00757.

SMR

O00757. Positions 9-337.

ModBase

Search...

Protein-protein interaction databases

IntAct

O00757. 1 interaction.

MINT

MINT-1374932.

STRING

O00757.

PTM databases

PhosphoSite

O00757.

Proteomic databases

PRIDE

O00757.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000375337; ENSP00000364486; ENSG00000130957.

GeneID

8789.

KEGG

hsa:8789.

NMPDR

fig|9606.3.peg.31580.

UCSC

uc004auv.1. human.

Organism-specific databases

CTD

8789.

GeneCards

GC09M097321.

H-InvDB

HIX0034872.

HGNC

HGNC:3607. FBP2.

HPA

HPA012513.

MIM

603027. gene.

neXtProt

NX_O00757.

PharmGKB

PA28019.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG10983.

GeneTree

ENSGT00390000015513.

HOGENOM

HBG731261.

HOVERGEN

HBG005627.

InParanoid

O00757.

OMA

ITAKEKR.

OrthoDB

EOG4P8FJF.

PhylomeDB

O00757.

Enzyme and pathway databases

Reactome

REACT_474. Metabolism of carbohydrates.

Gene expression databases

ArrayExpress

O00757.

Bgee

O00757.

CleanEx

HS_FBP2.

Genevestigator

O00757.

GermOnline

ENSG00000130957. Homo sapiens.

Family and domain databases

InterPro

IPR000146. FBPase_class-1/SBPase.
IPR020548. Fructose_bisphosphatase_AS.
[Graphical view]

KO

K03841.

PANTHER

PTHR11556. In_FB_phphtase. 1 hit.

Pfam

PF00316. FBPase. 1 hit.
[Graphical view]

PIRSF

PIRSF000904. FBPtase_SBPase. 1 hit.

PRINTS

PR00115. F16BPHPHTASE.

PROSITE

PS00124. FBPASE. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

NextBio

32964.

SOURCE

Search...

Entry information

Entry name

F16P2_HUMAN

Accession

Primary (citable) accession number: O00757
Secondary accession number(s): Q17R39, Q6FI53

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 15, 1998
Last sequence update:	September 27, 2005
Last modified:	January 25, 2012
This is version 100 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.