Reviewed, UniProtKB/Swiss-Prot P11413 (G6PD_HUMAN)

Names and origin

Protein names

Recommended name:
    Glucose-6-phosphate 1-dehydrogenase
      Short name=G6PD
    EC=1.1.1.49

Gene names

Name:

G6PD

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	515 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	Produces pentose sugars for nucleic acid synthesis and main producer of NADPH reducing power.
Catalytic activity	D-glucose 6-phosphate + NADP(+) = D-glucono-1,5-lactone 6-phosphate + NADPH.
Pathway	Carbohydrate degradation; pentose phosphate pathway; D-ribulose 5-phosphate from D-glucose 6-phosphate (oxidative stage): step 1/3.
Subunit structure	Homodimer or homotetramer.
Tissue specificity	The long isoform is found in lymphoblasts, granulocytes and sperm.
Polymorphism	The sequence shown is that of variant B, the most common variant.
Involvement in disease	Defects in G6PD are the cause of chronic non-spherocytic hemolytic anemia (CNSHA) [MIM:305900]. Deficiency of G6PD is associated with hemolytic anemia in two different situations. First, in areas in which malaria has been endemic, G6PD-deficiency alleles have reached high frequencies (1% to 50%) and deficient individuals, though essentially asymptomatic in the steady state, have a high risk of acute hemolytic attacks. Secondly, sporadic cases of G6PD deficiency occur at a very low frequencies, and they usually present a more severe phenotype. Several types of CNSHA are recognized. Class-I variants are associated with severe NSHA; class-II have an activity <10% of normal; class-III have an activity of 10% to 60% of normal; class-IV have near normal activity.
Miscellaneous	Has NADP both as cofactor (bound to the N-terminal domain) and as structural element bound to the C-terminal domain.
Sequence similarities	Belongs to the glucose-6-phosphate dehydrogenase family.

Ontologies

Keywords
Biological process	Carbohydrate metabolism Glucose metabolism
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Disease mutation Hereditary hemolytic anemia
Ligand	NADP
Molecular function	Oxidoreductase
PTM	Acetylation Phosphoprotein
Technical term	3D-structure Direct protein sequencing
Gene Ontology (GO)
Biological process	cellular response to oxidative stress Inferred from mutant phenotype. Source: UniProtKB cholesterol biosynthetic process Inferred from mutant phenotype. Source: UniProtKB erythrocyte maturation Inferred from mutant phenotype. Source: UniProtKB glucose 6-phosphate utilization Inferred from mutant phenotype. Source: UniProtKB glutathione metabolic process Inferred from mutant phenotype. Source: UniProtKB oxidation reduction Inferred from electronic annotation. Source: UniProtKB-KW pentose-phosphate shunt, oxidative branch Inferred from mutant phenotype. Source: UniProtKB regulation of protein modification process Inferred from mutant phenotype. Source: UniProtKB ribose phosphate biosynthetic process Inferred from mutant phenotype. Source: UniProtKB
Cellular component	centrosome Inferred from direct assay. Source: HPA cytosol Inferred from direct assay. Source: UniProtKB internal side of plasma membrane Inferred from direct assay. Source: UniProtKB intracellular membrane-bounded organelle Inferred from direct assay. Source: HPA
Molecular function	NADP binding Inferred from direct assay. Source: UniProtKB glucose binding Inferred from direct assay. Source: UniProtKB glucose-6-phosphate dehydrogenase activity Inferred from electronic annotation. Source: InterPro protein homodimerization activity Inferred from physical interaction. Source: UniProtKB
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform Short (identifier: P11413-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform Long (identifier: P11413-2)

The sequence of this isoform differs from the canonical sequence as follows:
     257-257: R → RGPGRQGGSGSESCSLSLGSLVWGPHALEPGEQGGELRRALASSVPR

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Initiator methionine

1

1

Removed

Chain

2 – 515

514

Glucose-6-phosphate 1-dehydrogenase

PRO_0000068083

Regions

Nucleotide binding

39 – 45

7

NADP By similarity

Sites

Active site

263

1

Proton acceptor By similarity

Binding site

40

1

NADP By similarity

Binding site

72

1

NADP By similarity

Binding site

201

1

Substrate By similarity

Binding site

205

1

Substrate By similarity

Binding site

238

1

NADP

Binding site

357

1

NADP

Binding site

487

1

NADP

Amino acid modifications

Modified residue

2

1

N-acetylalanine

Modified residue

401

1

Phosphotyrosine

Modified residue

503

1

Phosphotyrosine

Modified residue

507

1

Phosphotyrosine

Natural variations

Alternative sequence

257

1

R → RGPGRQGGSGSESCSLSLGS LVWGPHALEPGEQGGELRRA LASSVPR in isoform Long.

VSP_001592

Natural variant

12

1

V → L in Sinnai.

VAR_002450

Natural variant

32

1

H → R in CSNA; Gahoe; class III; frequent in Chinese.

VAR_002451

Natural variant

35

1

Missing in CNSHA; Sunderland; class I.

VAR_002452

Natural variant

44

1

A → G in Orissa; class III; frequent in Indian tribal populations.

VAR_002453

Natural variant

48

1

I → T in Aures; class II.

VAR_002454

Natural variant

58

1

D → N in Metaponto; class III.

VAR_002455

Natural variant

68

1

V → M in A(-) type I; class III; frequent in African population. dbSNP rs1050828.

VAR_002456

Natural variant

70

1

Y → H in Namoru; 4% activity.

VAR_002457

Natural variant

75

1

L → P in Swansea; class I.

VAR_002458

Natural variant

81

1

R → C in Konan/Ube; class III.

VAR_002460

Natural variant

81

1

R → H in Lagosanto; class III.

VAR_002459

Natural variant

106

1

S → C in Vancouver; class I.

VAR_002461

Natural variant

126

1

N → D in A(+), A(-), Santa Maria; class IV and in Mount Sinai; class I. dbSNP rs1050829.

VAR_002462

Natural variant

128

1

L → P in Vanua Lava; 4% activity.

VAR_002463

Natural variant

131

1

G → V in Chinese-4.

VAR_002464

Natural variant

156

1

E → K in Ilesha; class III.

VAR_002465

Natural variant

163

1

G → D in Plymouth; class I.

VAR_002467

Natural variant

163

1

G → S in Mahidol; class III.

VAR_002466

Natural variant

165

1

N → D in Chinese-3; class II.

VAR_002468

Natural variant

166

1

R → H in Naone; 1% activity.

VAR_002469

Natural variant

176

1

D → G in Shinshu; class I.

VAR_002470

Natural variant

181

1

D → V in Santa Maria; class I.

VAR_002471

Natural variant

182

1

R → W in Vancouver; class I.

VAR_002472

Natural variant

188

1

S → F in Sassari/Cagliari; class II; frequent in the Mediterranean.

VAR_002473

Natural variant

198

1

R → C in Coimbra; class II.

VAR_002474

Natural variant

198

1

R → P in CNSHA; Santiago; class I.

VAR_002475

Natural variant

212

1

M → V in Sibari; class III.

VAR_002476

Natural variant

213

1

V → L in Minnesota; class I.

VAR_002477

Natural variant

216

1

F → L in Harilaou; class I.

VAR_002478

Natural variant

227

1

R → L in A- type 2; class III.

VAR_002480

Natural variant

227

1

R → Q in Mexico City; class III.

VAR_002479

Natural variant

242 – 243

2

Missing in Stonybrook; class I.

VAR_002481

Natural variant

257

1

R → G in Wayne; class I.

VAR_002482

Natural variant

274

1

E → K in Corum; class I.

VAR_002483

Natural variant

278

1

S → F in Wexham; class I.

VAR_002484

Natural variant

279

1

T → S in Chinese-1; class II.

VAR_002485

Natural variant

282

1

D → H in Seattle; class III.

VAR_002486

Natural variant

285

1

R → H in Montalbano; class III.

VAR_002487

Natural variant

291

1

V → M in Viangchan/Jammu; class II.

VAR_002488

Natural variant

317

1

E → K in Kalyan/Kerala; class III.

VAR_002489

Natural variant

322

1

Y → H in Rehovot.

VAR_020535

Natural variant

323

1

L → P in A- type 3; class III.

VAR_002490

Natural variant

335

1

A → T in Chatham; class III.

VAR_002491

Natural variant

342

1

L → F in Chinese-5.

VAR_002492

Natural variant

353

1

P → S in Ierapetra; class II.

VAR_002493

Natural variant

363

1

N → K in Loma Linda; class I.

VAR_002494

Natural variant

385

1

C → R in Tomah; class I.

VAR_002495

Natural variant

386

1

K → E in Iowa; class I.

VAR_002496

Natural variant

387

1

R → C in CNSHA; Guadajalara and Mount Sinai; class I.

VAR_002498

Natural variant

387

1

R → H in Beverly Hills; class I.

VAR_002497

Natural variant

393

1

R → H in Nashville/Anaheim; class I.

VAR_002499

Natural variant

394

1

V → L in CNSHA; Alhambra; class I.

VAR_002500

Natural variant

396

1

P → L in Bari; class I.

VAR_002501

Natural variant

398

1

E → K in Puerto Limon; class I.

VAR_002502

Natural variant

410

1

G → C in Riverside; class I.

VAR_002503

Natural variant

410

1

G → D in CNSHA; Japan; class I.

VAR_002504

Natural variant

416

1

E → K in Tokyo; class I.

VAR_002505

Natural variant

439

1

R → P in CNSHA; Pawnee; class I.

VAR_002506

Natural variant

440

1

L → F in Telti/Kobe; class I.

VAR_002507

Natural variant

447

1

G → R in Santiago de Cuba; class I.

VAR_002508

Natural variant

449

1

Q → H in Cassano; class II.

VAR_002509

Natural variant

454

1

R → C in Chinese-II/Maewo/Union; class II, <1% activity.

VAR_002510

Natural variant

454

1

R → H in Andalus; class I.

VAR_002511

Natural variant

459

1

R → L in Canton; class II; frequent in China.

VAR_002512

Natural variant

459

1

R → P in Cosenza; class II.

VAR_002513

Natural variant

463

1

R → H in Kaiping; class II.

VAR_002514

Natural variant

488

1

G → V in Campinas; class I.

VAR_002515

Experimental info

Sequence conflict

11

1

Q → H Ref.1 Ref.2 Ref.3 Ref.4 Ref.6 Ref.9

Sequence conflict

435 – 436

2

DA → EP Ref.12

Secondary structure

1

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