Reviewed, UniProtKB/Swiss-Prot Q92947 (GCDH_HUMAN)

Names and origin

Protein names

Recommended name:
    Glutaryl-CoA dehydrogenase, mitochondrial
      Short name=GCD
    EC=1.3.99.7

Gene names

Name:

GCDH

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	438 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	Catalyzes the oxidative decarboxylation of glutaryl-CoA to crotonyl-CoA and CO(2) in the degradative pathway of L-lysine, L-hydroxylysine, and L-tryptophan metabolism. It uses electron transfer flavoprotein as its electron acceptor. The short isoform is inactive.
Catalytic activity	Glutaryl-CoA + acceptor = crotonoyl-CoA + CO(2) + reduced acceptor.
Cofactor	FAD.
Pathway	Amino-acid metabolism; lysine degradation. Amino-acid metabolism; tryptophan metabolism.
Subunit structure	Homotetramer.
Subcellular location	Mitochondrion matrix.
Tissue specificity	The 2 isoforms have been found in fibroblasts and liver.
Involvement in disease	Defects in GCDH are the cause of glutaric acidemia type I (GA-I) [MIM:231670]. GA-I is an autosomal recessive metabolic disorder characterized by progressive dystonia and athetosis due to gliosis and neuronal loss in the basal ganglia. Macrocephaly is often seen at birth. Patients with the disorder accumulate and excrete glutaric, 3-hydroxyglutaric, and glutaconic acid.
Sequence similarities	Belongs to the acyl-CoA dehydrogenase family.

Ontologies

Keywords
Cellular component	Mitochondrion
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Disease mutation
Domain	Transit peptide
Ligand	FAD Flavoprotein
Molecular function	Oxidoreductase
Technical term	3D-structure
Gene Ontology (GO)
Biological process	oxidation reduction Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	mitochondrial matrix Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	FAD binding Inferred from electronic annotation. Source: InterPro electron carrier activity Inferred from electronic annotation. Source: InterPro glutaryl-CoA dehydrogenase activity Ref.2 Traceable author statement. Source: ProtInc
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
GRB2	P62993	1	EBI-1236978,EBI-401755

Alternative products

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

Isoform Long (identifier: Q92947-1)

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 Short (identifier: Q92947-2)

The sequence of this isoform differs from the canonical sequence as follows:
     415-438: GTHDIHALILGRAITGIQAFTASK → VVQMCSLKRRWNSL

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Transit peptide

1 – 44

44

Mitochondrion Potential

Chain

45 – 438

394

Glutaryl-CoA dehydrogenase, mitochondrial

PRO_0000000526

Sites

Active site

414

1

Proton acceptor Potential

Natural variations

Alternative sequence

415 – 438

24

GTHDI…FTASK → VVQMCSLKRRWNSL in isoform Short.

VSP_000145

Natural variant

88

1

R → C in GA-I.

VAR_000366

Natural variant

94

1

R → L in GA-I.

VAR_000367

Natural variant

101

1

G → R in GA-I.

VAR_000368

Natural variant

115

1

C → Y in GA-I.

VAR_000369

Natural variant

122

1

A → V in GA-I.

VAR_000370

Natural variant

128

1

R → G in GA-I.

VAR_000371

Natural variant

138

1

R → G in GA-I.

VAR_000372

Natural variant

139

1

S → L in GA-I.

VAR_000373

Natural variant

148

1

V → I in GA-I.

VAR_000374

Natural variant

161

1

R → Q in GA-I.

VAR_000375

Natural variant

178

1

G → R in GA-I.

VAR_000376

Natural variant

179

1

L → R in GA-I.

VAR_000377

Natural variant

191

1

M → T in GA-I.

VAR_000378

Natural variant

195

1

A → T in GA-I.

VAR_000379

Natural variant

227

1

R → P in GA-I.

VAR_000380

Natural variant

236

1

F → L in GA-I.

VAR_000381

Natural variant

257

1

R → Q in GA-I.

VAR_000382

Natural variant

257

1

R → W in GA-I.

VAR_000383

Natural variant

266

1

M → V in GA-I.

VAR_000384

Natural variant

278

1

P → S in GA-I.

VAR_000385

Natural variant

283

1

L → P in GA-I.

VAR_000386

Natural variant

293

1

A → T in GA-I.

VAR_000387

Natural variant

294

1

R → W in GA-I.

VAR_000388

Natural variant

295

1

Y → H in GA-I.

VAR_000389

Natural variant

298

1

A → T

VAR_000390

Natural variant

298

1

A → V

VAR_000391

Natural variant

305

1

S → L in GA-I.

VAR_000392

Natural variant

308

1

C → S in GA-I.

VAR_000393

Natural variant

309

1

L → W in GA-I.

VAR_000394

Natural variant

313

1

R → W in GA-I.

VAR_000395

Natural variant

333

1

Q → E in GA-I.

VAR_000396

Natural variant

349

1

A → T in GA-I.

VAR_000397

Natural variant

354

1

G → R in GA-I.

VAR_000398

Natural variant

354

1

G → S in GA-I.

VAR_000399

Natural variant

355

1

R → C in GA-I.

VAR_000400

Natural variant

355

1

R → H in GA-I.

VAR_000401

Natural variant

365

1

E → K in GA-I.

VAR_000402

Natural variant

375

1

C → R in GA-I.

VAR_000403

Natural variant

382

1

A → T in GA-I.

VAR_000404

Natural variant

383

1

R → C in GA-I.

VAR_000405

Natural variant

383

1

R → H in GA-I.

VAR_000406

Natural variant

386

1

R → Q in GA-I.

VAR_000407

Natural variant

390

1

G → A in GA-I.

VAR_000409

Natural variant

390

1

G → R in GA-I.

VAR_000408

Natural variant

392

1

N → D in GA-I.

VAR_000410

Natural variant

400

1

V → M in GA-I.

VAR_000411

Natural variant

402

1

R → Q in GA-I.

VAR_000413

Natural variant

402

1

R → W in GA-I; most common mutation identified.

VAR_000412

Natural variant

403

1

H → R in GA-I.

VAR_000414

Natural variant

406

1

N → K in GA-I.

VAR_000415

Natural variant

407

1

L → P in GA-I.

VAR_000416

Natural variant

414

1

E → K in GA-I.

VAR_000417

Natural variant

416

1

T → I in GA-I.

VAR_000418

Natural variant

421

1

A → T in GA-I.

VAR_000419

Natural variant

421

1

A → V in GA-I; impaired association of subunits.

VAR_000420

Natural variant

429

1

T → M in GA-I.

VAR_000421

Natural variant

433

1

A → E in GA-I.

VAR_000422

Experimental info

Sequence conflict

33

1

G → A in AAC52079. Ref.1

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

438

Helix Strand Turn

Details...

Helix

56 – 59

4

Helix

62 – 78

17

Helix

80 – 89

10

Helix

95 – 102

8

Helix

120 – 131

12

Helix

135 – 146

12

Helix

149 – 155

7

Helix

158 – 169

12

Beta strand

175 – 178

4

Beta strand

184 – 186

3

Helix

188 – 190

3

Beta strand

194 – 198

5

Turn

199 – 202

4

Beta strand

203 – 214

12

Helix

216 – 218

3

Beta strand

220 – 228

9

Beta strand

233 – 239

7

Beta strand

253 – 256

4

Beta strand

261 – 272

12

Helix

273 – 275

3

Helix

284 – 318

35

Helix

326 – 328

3