P06745 (G6PI_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Glucose-6-phosphate isomerase
Short name=GPI
EC=5.3.1.9

Alternative name(s):
Autocrine motility factor
Short name=AMF
Neuroleukin
Short name=NLK
Phosphoglucose isomerase
Short name=PGI
Phosphohexose isomerase
Short name=PHI

Gene names

Name:	Gpi
Synonyms:	Gpi1

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Dipnotetrapodomorpha › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Boreoeutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	558 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Besides it's role as a glycolytic enzyme, mammalian GPI can function as a tumor-secreted cytokine and an angiogenic factor (AMF) that stimulates endothelial cell motility. GPI is also a neurotrophic factor (Neuroleukin) for spinal and sensory neurons. HAMAP-Rule MF_00473
Catalytic activity	D-glucose 6-phosphate = D-fructose 6-phosphate. HAMAP-Rule MF_00473
Pathway	Carbohydrate degradation; glycolysis; D-glyceraldehyde 3-phosphate and glycerone phosphate from D-glucose: step 2/4. HAMAP-Rule MF_00473
Subunit structure	Homodimer in the catalytically active form, monomer in the secreted form.
Subcellular location	Cytoplasm. Secreted HAMAP-Rule MF_00473.
Post-translational modification	ISGylated. Ref.10
Sequence similarities	Belongs to the GPI family.
Sequence caution	The sequence BAC36335.1 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
Biological process	Angiogenesis Gluconeogenesis Glycolysis
Cellular component	Cytoplasm Secreted
Molecular function	Cytokine Growth factor Isomerase
PTM	Acetylation Phosphoprotein Ubl conjugation
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	angiogenesis Inferred from electronic annotation. Source: UniProtKB-KW erythrocyte homeostasis Inferred from mutant phenotype PubMed 8417789. Source: MGI gluconeogenesis Inferred from electronic annotation. Source: UniProtKB-KW glucose homeostasis Inferred from mutant phenotype PubMed 8417789. Source: MGI glycolytic process Inferred from direct assay PubMed 15665293. Source: MGI in utero embryonic development Inferred from mutant phenotype PubMed 1582174. Source: MGI mesoderm formation Inferred from mutant phenotype PubMed 8922529. Source: MGI
Cellular_component	ciliary membrane Inferred from direct assay PubMed 22179047. Source: MGI cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell extracellular space Inferred from electronic annotation. Source: UniProtKB-KW plasma membrane Inferred from direct assay PubMed 22179047. Source: MGI
Molecular_function	glucose-6-phosphate isomerase activity Inferred from direct assay PubMed 1180875PubMed 1235912PubMed 15155459PubMed 1582174PubMed 204065PubMed 2344351PubMed 7277315PubMed 7323947PubMed 7444718PubMed 8417789. Source: MGI protein binding Inferred from physical interaction PubMed 17875708. Source: IntAct
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
Parp14	Q2EMV9	4	EBI-1534927,EBI-1534943

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Initiator methionine

1

1

Removed By similarity

Chain

2 – 558

557

Glucose-6-phosphate isomerase HAMAP-Rule MF_00473

PRO_0000180538

Sites

Active site

358

1

Proton donor Ref.12

Active site

389

1

Ref.12

Active site

519

1

Ref.12

Amino acid modifications

Modified residue

2

1

N-acetylalanine By similarity

Modified residue

12

1

N6-acetyllysine By similarity

Modified residue

109

1

Phosphothreonine By similarity

Modified residue

142

1

N6-acetyllysine Ref.11

Modified residue

185

1

Phosphoserine; by CK2 By similarity

Modified residue

454

1

N6-malonyllysine By similarity

Experimental info

Sequence conflict

95

1

N → D in AAA39825. Ref.1

Sequence conflict

95

1

N → D in BAE41301. Ref.1

Sequence conflict

119

1

M → K in BAE21866. Ref.2

Sequence conflict

191

1

H → R in BAE22329. Ref.2

Sequence conflict

238

1

A → E in AAC36515. Ref.6

Sequence conflict

264 – 266

3

FEF → LEL in AAC36515. Ref.6

Sequence conflict

285

1

A → V in AAC36515. Ref.6

Sequence conflict

303

1

M → T in AAC36515. Ref.6

Sequence conflict

313

1

E → G in BAE35416. Ref.2

Sequence conflict

357

1

M → V in AAC36515. Ref.6

Sequence conflict

372

1

D → N in AAC36515. Ref.6

Sequence conflict

380

1

W → L in AAC36515. Ref.6

Sequence conflict

499

1

F → L in BAE23502. Ref.2

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

558

Helix Strand Turn

Details...

Helix

3 – 6

4

Helix

8 – 20

13

Helix

21 – 23

3

Helix

26 – 32

7

Helix

36 – 39

4

Beta strand

41 – 45

5

Beta strand

50 – 54

5

Helix

62 – 74

13

Helix

77 – 85

9

Turn

92 – 95

4

Helix

100 – 103

4

Beta strand

116 – 118

3

Helix

119 – 137

19

Beta strand

151 – 155

5

Helix

158 – 160

3

Helix

162 – 170

9

Helix

172 – 175

4

Beta strand

180 – 184

5

Helix

189 – 196

8

Turn

201 – 203

3

Beta strand

204 – 209

6

Beta strand

211 – 213

3

Helix

216 – 233

18

Helix

236 – 241

6

Beta strand

243 – 248

6

Helix

250 – 256

7

Helix

260 – 262

3

Beta strand

263 – 265

3

Helix

272 – 274

3

Turn

276 – 278

3

Helix

279 – 281

3

Helix

282 – 288

7

Helix

290 – 309

20

Helix

312 – 314

3

Helix

316 – 329

14

Beta strand

335 – 341

7

Helix

343 – 345

3

Helix

348 – 360

13

Beta strand

378 – 380

3

Turn

384 – 387

4

Helix

388 – 397

10

Beta strand

404 – 411

8

Helix

417 – 419

3

Helix

420 – 438

19

Helix

442 – 451

10

Helix

456 – 462

7

Helix

463 – 466

4

Beta strand

474 – 481

8

Helix

484 – 505

22

Helix

513 – 515

3

Helix

516 – 525

10

Helix

526 – 529

4

Beta strand

530 – 533

4

Helix

540 – 552

13

Sequences

	Sequence		Length	Mass (Da)
	P06745 [UniParc]. Last modified May 1, 2007. Version 4. Checksum: 7299E98B12B4C375	FASTA	558	62,767
	10 20 30 40 50 60 MAALTRNPQF QKLLEWHRAN SANLKLRELF EADPERFNNF SLNLNTNHGH ILVDYSKNLV 70 80 90 100 110 120 NKEVMQMLVE LAKSRGVEAA RDNMFSGSKI NYTENRAVLH VALRNRSNTP IKVDGKDVMP 130 140 150 160 170 180 EVNRVLDKMK SFCQRVRSGD WKGYTGKSIT DIINIGIGGS DLGPLMVTEA LKPYSKGGPR 190 200 210 220 230 240 VWFVSNIDGT HIAKTLASLS PETSLFIIAS KTFTTQETIT NAETAKEWFL EAAKDPSAVA 250 260 270 280 290 300 KHFVALSTNT AKVKEFGIDP QNMFEFWDWV GGRYSLWSAI GLSIALHVGF DHFEQLLSGA 310 320 330 340 350 360 HWMDQHFLKT PLEKNAPVLL ALLGIWYINC YGCETHALLP YDQYMHRFAA YFQQGDMESN 370 380 390 400 410 420 GKYITKSGAR VDHQTGPIVW GEPGTNGQHA FYQLIHQGTK MIPCDFLIPV QTQHPIRKGL 430 440 450 460 470 480 HHKILLANFL AQTEALMKGK LPEEARKELQ AAGKSPEDLE KLLPHKVFEG NRPTNSIVFT 490 500 510 520 530 540 KLTPFILGAL IAMYEHKIFV QGIMWDINSF DQWGVELGKQ LAKKIEPELE GSSAVTSHDS 550 STNGLISFIK QQRDTKLE

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Molecular cloning and expression of neuroleukin, a neurotrophic factor for spinal and sensory neurons." Gurney M.E., Heinrich S.P., Lee M.R., Yin H.-S. Science 234:566-574(1986) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Salivary gland.
[2]	"The transcriptional landscape of the mammalian genome." Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y. Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Strain: C57BL/6J and NOD. Tissue: Bone marrow, Head, Heart, Olfactory bulb and Thymus.
[3]	"Lineage-specific biology revealed by a finished genome assembly of the mouse." Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X., Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y., Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S. , Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R., Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K., Eichler E.E., Ponting C.P. PLoS Biol. 7:E1000112-E1000112(2009) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: C57BL/6J.
[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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Strain: C57BL/6. Tissue: Brain.
[5]	Lubec G., Klug S., Kang S.U. Submitted (APR-2007) to UniProtKB Cited for: PROTEIN SEQUENCE OF 28-36; 63-73; 97-104; 107-124; 148-176; 181-234; 242-252; 255-273; 424-438; 455-461 AND 467-481, IDENTIFICATION BY MASS SPECTROMETRY. Strain: C57BL/6. Tissue: Brain and Hippocampus.
[6]	"Expressed genes in interleukin-4 treated B cells identified by cDNA representational difference analysis." Chu C.C., Paul W.E. Mol. Immunol. 35:487-502(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 235-393. Strain: BALB/c. Tissue: Spleen.
[7]	"Identification of a novel tandemly repeated sequence present in an intron of the glucose phosphate isomerase (GPI) gene in mouse and man." Faik P., Walker J.I., Morgan M.J. Genomics 21:122-127(1994) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 269-558.
[8]	"Quantitative allelic discrimination of GPI-c and GPI-a using molecular beacons." Bauchwitz R.P., Tyagi S., Marras S.A.E. Submitted (NOV-1998) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 417-543. Strain: 129.
[9]	"Mouse glucose-6-phosphate isomerase and neuroleukin have identical 3' sequences." Faik P., Walker J.I.H., Redmill A.A.M., Morgan M.J. Nature 332:455-456(1988) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTITY OF NEUROLEUKIN AS PGI.
[10]	"Proteomic identification of proteins conjugated to ISG15 in mouse and human cells." Giannakopoulos N.V., Luo J.K., Papov V., Zou W., Lenschow D.J., Jacobs B.S., Borden E.C., Li J., Virgin H.W., Zhang D.E. Biochem. Biophys. Res. Commun. 336:496-506(2005) [PubMed] [Europe PMC] [Abstract] Cited for: ISGYLATION.
[11]	"SIRT5-mediated lysine desuccinylation impacts diverse metabolic pathways." Park J., Chen Y., Tishkoff D.X., Peng C., Tan M., Dai L., Xie Z., Zhang Y., Zwaans B.M., Skinner M.E., Lombard D.B., Zhao Y. Mol. Cell 50:919-930(2013) [PubMed] [Europe PMC] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-142, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. Tissue: Embryonic fibroblast.
[12]	"The crystal structure of mouse phosphoglucose isomerase at 1.6A resolution and its complex with glucose 6-phosphate reveals the catalytic mechanism of sugar ring opening." Solomons J.T.G., Zimmerly E.M., Burns S., Krishnamurthy N., Swan M.K., Krings S., Muirhead H., Chirgwin J., Davies C. J. Mol. Biol. 342:847-860(2004) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.6 ANGSTROMS) IN COMPLEX WITH G6P, ACTIVE SITE.
[13]	"Tumor cell autocrine motility factor is the neuroleukin/phosphohexose isomerase polypeptide." Watanabe H., Takehana K., Date M., Shinozaki T., Raz A. Cancer Res. 56:2960-2963(1996) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTITY OF AMF AS PGI.
[14]	"Crystal structures of mouse autocrine motility factor in complex with carbohydrate phosphate inhibitors provide insight into structure-activity relationship of the inhibitors." Tanaka N., Haga A., Naba N., Shiraiwa K., Kusakabe Y., Hashimoto K., Funasaka T., Nagase H., Raz A., Nakamura K.T. J. Mol. Biol. 356:312-324(2006) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.4 ANGSTROMS) OF 1-557 IN COMPLEX WITH INHIBITORS.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

M14220 mRNA. Translation: AAA39825.1.
AK076424 mRNA. Translation: BAC36335.1. Different initiation.
AK133827 mRNA. Translation: BAE21866.1.
AK134890 mRNA. Translation: BAE22329.1.
AK137805 mRNA. Translation: BAE23502.1.
AK147124 mRNA. Translation: BAE27695.1.
AK150341 mRNA. Translation: BAE29481.1.
AK159838 mRNA. Translation: BAE35416.1.
AK169681 mRNA. Translation: BAE41301.1.
BX537302 Genomic DNA. Translation: CAM21756.1.
BC086640 mRNA. Translation: AAH86640.1.
BC088995 mRNA. Translation: AAH88995.1.
U89408 mRNA. Translation: AAC36515.1.
L09104 mRNA. Translation: AAA65641.1.
AF108354 mRNA. Translation: AAF28799.1.

CCDS

CCDS21138.1.

PIR

NUMS. A24439.

RefSeq

NP_032181.2. NM_008155.4.

UniGene

Mm.589.

3D structure databases

PDBe
RCSB-PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1U0E	X-ray	1.60	A/B	1-558	[»]
1U0F	X-ray	1.60	A/B	1-558	[»]
1U0G	X-ray	1.70	A/B	1-558	[»]
2CVP	X-ray	1.80	A/B	1-557	[»]
2CXN	X-ray	1.40	A/B	1-557	[»]
2CXO	X-ray	1.80	A/B	1-557	[»]
2CXP	X-ray	1.70	A/B	1-557	[»]
2CXQ	X-ray	1.50	A/B	1-557	[»]
2CXR	X-ray	1.70	A/B	1-557	[»]
2CXS	X-ray	1.50	A/B	1-557	[»]
2CXT	X-ray	1.50	A/B	1-557	[»]
2CXU	X-ray	1.65	A/B	1-557	[»]

ProteinModelPortal

P06745.

SMR

P06745. Positions 1-557.

ModBase

Search...

MobiDB

Search...

Protein-protein interaction databases

BioGrid

200021. 3 interactions.

IntAct

P06745. 6 interactions.

MINT

MINT-1869738.

PTM databases

PhosphoSite

P06745.

Proteomic databases

MaxQB

P06745.

PaxDb

P06745.

PRIDE

P06745.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENSMUST00000038027; ENSMUSP00000049355; ENSMUSG00000036427.

GeneID

14751.

KEGG

mmu:14751.

UCSC

uc009gix.2. mouse.

Organism-specific databases

CTD

14751.

MGI

MGI:95797. Gpi1.

Phylogenomic databases

eggNOG

COG0166.

GeneTree

ENSGT00390000000707.

HOVERGEN

HBG002877.

InParanoid

P06745.

KO

K01810.

OMA

NCHFVAN.

OrthoDB

EOG7FXZXV.

PhylomeDB

P06745.

TreeFam

TF300436.

Enzyme and pathway databases

SABIO-RK

P06745.

UniPathway

UPA00109; UER00181.

Gene expression databases

Bgee

P06745.

CleanEx

MM_GPI1.

Genevestigator

P06745.

Family and domain databases

Gene3D

1.10.1390.10. 1 hit.

HAMAP

MF_00473. G6P_isomerase.

InterPro

IPR001672. G6P_Isomerase.
IPR023096. G6P_Isomerase_C.
IPR018189. Phosphoglucose_isomerase_CS.
[Graphical view]

PANTHER

PTHR11469. PTHR11469. 1 hit.

Pfam

PF00342. PGI. 1 hit.
[Graphical view]

PRINTS

PR00662. G6PISOMERASE.

PROSITE

PS00765. P_GLUCOSE_ISOMERASE_1. 1 hit.
PS00174. P_GLUCOSE_ISOMERASE_2. 1 hit.
PS51463. P_GLUCOSE_ISOMERASE_3. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

P06745.

NextBio

286815.

PRO

P06745.

SOURCE

Search...

Entry information

Entry name

G6PI_MOUSE

Accession

Primary (citable) accession number: P06745
Secondary accession number(s): O89062 , Q3TEE7, Q3TW50, Q3UUX1, Q3UY84, Q3UZJ1, Q5RJI3, Q8C675, Q9JM07

Entry history

Integrated into UniProtKB/Swiss-Prot:	January 1, 1988
Last sequence update:	May 1, 2007
Last modified:	July 9, 2014
This is version 131 of the entry and version 4 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program