P00480 (OTC_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Ornithine carbamoyltransferase, mitochondrial
EC=2.1.3.3

Alternative name(s):
Ornithine transcarbamylase
Short name=OTCase

Gene names

Name:

OTC

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	354 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)

Catalytic activity	Carbamoyl phosphate + L-ornithine = phosphate + L-citrulline.
Enzyme regulation	Negatively regulated by lysine acetylation. Ref.10
Pathway	Nitrogen metabolism; urea cycle; L-citrulline from L-ornithine and carbamoyl phosphate: step 1/1.
Subunit structure	Homotrimer.
Subcellular location	Mitochondrion matrix.
Tissue specificity	Mainly expressed in liver and intestinal mucosa.
Post-translational modification	Acetylation at Lys-88 negatively regulates ornithine carbamoyltransferase activity in response to nutrient signals.
Involvement in disease	Ornithine carbamoyltransferase deficiency (OTCD) [MIM:311250]: An X-linked disorder of the urea cycle which causes a form of hyperammonemia. Mutations with no residual enzyme activity are always expressed in hemizygote males by a very severe neonatal hyperammonemic coma that generally proves to be fatal. Heterozygous females are either asymptomatic or express orotic aciduria spontaneously or after protein intake. The disorder is treatable with supplemental dietary arginine and low protein diet. The arbitrary classification of patients into the 'neonatal' group (clinical hyperammonemia in the first few days of life) and 'late' onset (clinical presentation after the neonatal period) has been used to differentiate severe from mild forms. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.9 Ref.16 Ref.17 Ref.18 Ref.19 Ref.20 Ref.21 Ref.22 Ref.23 Ref.24 Ref.25 Ref.26 Ref.27 Ref.28 Ref.29 Ref.30 Ref.31 Ref.32 Ref.33 Ref.34 Ref.35 Ref.36 Ref.37 Ref.38 Ref.39 Ref.40 Ref.41 Ref.42 Ref.43 Ref.44
Sequence similarities	Belongs to the ATCase/OTCase family.

Ontologies

Keywords
Biological process	Amino-acid biosynthesis Arginine biosynthesis Urea cycle
Cellular component	Mitochondrion
Coding sequence diversity	Polymorphism
Disease	Disease mutation
Domain	Transit peptide
Molecular function	Transferase
PTM	Acetylation
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	anion homeostasis Inferred from electronic annotation. Source: Compara arginine biosynthetic process Non-traceable author statement. Source: UniProtKB citrulline biosynthetic process Inferred from electronic annotation. Source: Compara liver development Inferred from electronic annotation. Source: Compara midgut development Inferred from electronic annotation. Source: Compara protein homotrimerization Inferred from electronic annotation. Source: Compara response to biotin Inferred from electronic annotation. Source: Compara response to drug Inferred from electronic annotation. Source: Compara response to insulin stimulus Inferred from electronic annotation. Source: Compara response to zinc ion Inferred from electronic annotation. Source: Compara urea cycle Non-traceable author statement. Source: UniProtKB
Cellular_component	mitochondrial inner membrane Inferred from electronic annotation. Source: Compara mitochondrial matrix Non-traceable author statement Ref.1. Source: UniProtKB ornithine carbamoyltransferase complex Non-traceable author statement. Source: UniProtKB
Molecular_function	amino acid binding Inferred from electronic annotation. Source: Compara ornithine carbamoyltransferase activity Non-traceable author statement. Source: UniProtKB phosphate ion binding Inferred from electronic annotation. Source: Compara phospholipid binding Inferred from electronic annotation. Source: Compara
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Transit peptide

1 – 32

32

Mitochondrion

Chain

33 – 354

322

Ornithine carbamoyltransferase, mitochondrial

PRO_0000020334

Regions

Region

90 – 94

5

Ornithine and carbamoyl phosphate binding

Region

168 – 171

4

Ornithine and carbamoyl phosphate binding

Region

263 – 267

5

Ornithine binding

Region

302 – 305

4

Ornithine binding By similarity

Sites

Active site

303

1

By similarity

Binding site

141

1

Carbamoyl phosphate

Binding site

141

1

Ornithine

Binding site

199

1

Ornithine

Binding site

330

1

Carbamoyl phosphate

Binding site

330

1

Ornithine

Amino acid modifications

Modified residue

88

1

N6-acetyllysine Ref.10

Modified residue

231

1

N6-acetyllysine By similarity

Modified residue

238

1

N6-acetyllysine By similarity

Natural variations

Natural variant

26

1

R → Q in OTCD. Ref.17

VAR_004843

Natural variant

39

1

G → C in OTCD; late onset. Ref.38

VAR_004844

Natural variant

40

1

R → C in OTCD; late onset.

VAR_004845

Natural variant

40

1

R → H in OTCD; late onset. Ref.25 Ref.29

VAR_004846

Natural variant

43

1

L → F. Ref.35

VAR_004847

Natural variant

44

1

T → I in OTCD. Ref.32

VAR_004848

Natural variant

45

1

L → P in OTCD. Ref.17

VAR_004849

Natural variant

45

1

L → V in OTCD.

VAR_004850

Natural variant

46

1

K → R. Ref.6 Ref.17
Corresponds to variant rs1800321 [ dbSNP | Ensembl ].

VAR_004851

Natural variant

47

1

N → I in OTCD; neonatal.

VAR_004852

Natural variant

50

1

G → R in OTCD; late onset.

VAR_004853

Natural variant

55

1

Y → D in OTCD; late onset. Ref.39

VAR_004854

Natural variant

56

1

M → T in OTCD; late onset.

VAR_004855

Natural variant

60

1

S → L in OTCD.

VAR_004856

Natural variant

63

1

L → P in OTCD; late onset. Ref.35

VAR_004857

Natural variant

79

1

G → E in OTCD. Ref.21

VAR_004858

Natural variant

82

1

Missing in OTCD.

VAR_004859

Natural variant

83

1

G → D in OTCD. Ref.40

VAR_004860

Natural variant

83

1

G → R in OTCD; neonatal.

VAR_004861

Natural variant

87

1

E → K in OTCD.

VAR_004862

Natural variant

88

1

K → N in OTCD; late onset. Ref.29 Ref.30

VAR_004863

Natural variant

90

1

S → R in OTCD.

VAR_004864

Natural variant

92

1

R → Q in OTCD. Ref.19

VAR_004865

Natural variant

93

1

T → A in OTCD; late onset.

VAR_004866

Natural variant

94

1

R → T in OTCD. Ref.21

VAR_004867

Natural variant

100

1

G → D in OTCD; late onset. Ref.35

VAR_004868

Natural variant

101

1

F → L. Ref.2 Ref.32

VAR_004869

Natural variant

102

1

A → E in OTCD.

VAR_004870

Natural variant

111

1

L → P. Ref.1 Ref.19
Corresponds to variant rs1800324 [ dbSNP | Ensembl ].

VAR_004871

Natural variant

117

1

H → L in OTCD. Ref.23

VAR_004872

Natural variant

117

1

H → R in OTCD; late onset.

VAR_004873

Natural variant

125

1

T → M in OTCD; neonatal. Ref.28

VAR_004874

Natural variant

126

1

D → G in OTCD; 0.9% of wild-type activity; early onset. Ref.24

VAR_004875

Natural variant

129

1

R → H in OTCD; 2.1% of wild-type activity; early onset. Ref.24 Ref.25

VAR_004876

Natural variant

139

1

L → S in OTCD.

VAR_004877

Natural variant

140

1

A → P in OTCD; late onset. Ref.22

VAR_010605

Natural variant

141

1

R → P in OTCD.

VAR_004878

Natural variant

141

1

R → Q in OTCD; activity is 100-fold lower; most common point mutation. Ref.16 Ref.32

VAR_004879

Natural variant

148

1

L → F in OTCD.

VAR_004880

Natural variant

159

1

I → T in OTCD. Ref.26

VAR_004881

Natural variant

160

1

I → S in OTCD. Ref.44

VAR_012651

Natural variant

161

1

N → S in OTCD.

VAR_004882

Natural variant

162

1

G → R in OTCD.

VAR_004883

Natural variant

168

1

H → Q in OTCD; late onset.

VAR_004884

Natural variant

168

1

H → R in OTCD; late onset.

VAR_004885

Natural variant

172

1

I → F in OTCD. Ref.41

VAR_009233

Natural variant

172

1

I → M in OTCD; no activity; early onset. Ref.24

VAR_004886

Natural variant

174

1

A → P in OTCD.

VAR_004887

Natural variant

175

1

D → V in OTCD.

VAR_004888

Natural variant

176

1

Y → C in OTCD; late onset. Ref.30

VAR_004889

Natural variant

178 – 179

2

Missing in OTCD; neonatal.

VAR_004891

Natural variant

178

1

T → M in OTCD; neonatal.

VAR_004890

Natural variant

180

1

Q → H in OTCD. Ref.37

VAR_004892

Natural variant

181

1

E → G in OTCD; neonatal.

VAR_004893

Natural variant

182

1

H → L in OTCD. Ref.23

VAR_004894

Natural variant

183

1

Y → C in OTCD.

VAR_004895

Natural variant

183

1

Y → D in OTCD; late onset. Ref.35

VAR_004896

Natural variant

188

1

G → R in OTCD; neonatal. Ref.28

VAR_004897

Natural variant

188

1

G → V in OTCD. Ref.41

VAR_009234

Natural variant

191

1

L → F in OTCD. Ref.44

VAR_012652

Natural variant

192

1

S → R in OTCD; neonatal.

VAR_004898

Natural variant

195

1

G → R in OTCD; no activity. Ref.25

VAR_004899

Natural variant

196

1

D → V in OTCD; neonatal; 3.7% activity.

VAR_004900

Natural variant

196

1

D → Y in OTCD; neonatal.

VAR_004901

Natural variant

197

1

G → E in OTCD.

VAR_004902

Natural variant

197

1

G → R in OTCD. Ref.41

VAR_009235

Natural variant

198

1

N → K in OTCD. Ref.42

VAR_010606

Natural variant

201

1

L → P in OTCD; neonatal. Ref.37

VAR_004903

Natural variant

202

1

H → Y in OTCD. Ref.29

VAR_004904

Natural variant

203

1

S → C in OTCD. Ref.23

VAR_004905

Natural variant

206

1

M → I in OTCD. Ref.44

VAR_012653

Natural variant

206

1

M → R in OTCD; neonatal.

VAR_004906

Natural variant

207

1

S → R in OTCD; neonatal. Ref.37

VAR_004907

Natural variant

208

1

A → T in OTCD; late onset.

VAR_004908

Natural variant

209

1

A → V in OTCD; neonatal. Ref.26 Ref.28 Ref.42

VAR_004909

Natural variant

213

1

M → K in OTCD; late onset. Ref.35

VAR_004910

Natural variant

214

1

H → Y in OTCD; neonatal. Ref.32

VAR_010607

Natural variant

216

1

Q → E in OTCD. Ref.17

VAR_004911

Natural variant

220

1

P → A in OTCD; late onset. Ref.30

VAR_004912

Natural variant

225

1

P → L in OTCD. Ref.20

VAR_004913

Natural variant

225

1

P → R in OTCD; neonatal.

VAR_004914

Natural variant

225

1

P → T in OTCD; late onset. Ref.25

VAR_004915

Natural variant

242

1

T → I in OTCD; late onset.

VAR_004916

Natural variant

244

1

L → Q in OTCD; late onset. Ref.38

VAR_004917

Natural variant

247

1

T → K in OTCD; neonatal/late onset.

VAR_004918

Natural variant

255

1

H → P in OTCD.

VAR_004919

Natural variant

262

1

T → K in OTCD; mild. Ref.43

VAR_010608

Natural variant

263

1

D → G in OTCD.

VAR_004920

Natural variant

263

1

D → N in OTCD. Ref.29

VAR_004921

Natural variant

264

1

T → A in OTCD; late onset 8.9% activity. Ref.43

VAR_004922

Natural variant

264

1

T → I in OTCD; late onset. Ref.37

VAR_004923

Natural variant

265

1

W → L in OTCD; mild. Ref.43

VAR_010609

Natural variant

267

1

S → R in OTCD. Ref.37

VAR_004924

Natural variant

268

1

M → T in OTCD; late onset.

VAR_004925

Natural variant

269

1

G → E in OTCD; neonatal. Ref.27

VAR_004926

Natural variant

270

1

Q → R in about 5% of population. Ref.1 Ref.42 Ref.45
Corresponds to variant rs1800328 [ dbSNP | Ensembl ].

VAR_004927

Natural variant

272

1

Missing in OTCD; late onset. Ref.31

VAR_004928

Natural variant

277

1

R → Q in OTCD; late onset. Ref.9 Ref.25

VAR_004929

Natural variant

277

1

R → W in OTCD; late onset. Ref.18 Ref.34

VAR_004930

Natural variant

301

1

L → F in OTCD. Ref.44

VAR_012654

Natural variant

302

1

H → L in OTCD; female; late onset. Ref.28

VAR_004931

Natural variant

302

1

H → Q in OTCD; late onset.

VAR_004932

Natural variant

302

1

H → Y in OTCD; neonatal. Ref.30

VAR_004933

Natural variant

303

1

C → R in OTCD; neonatal. Ref.38

VAR_004934

Natural variant

303

1

C → Y in OTCD.

VAR_004935

Natural variant

304

1

L → F in OTCD. Ref.21

VAR_004936

Natural variant

305

1

P → H in OTCD. Ref.44

VAR_012655

Natural variant

309

1

Missing in OTCD; late onset. Ref.25

VAR_004937

Natural variant

320

1

R → L in OTCD. Ref.19

VAR_004938

Natural variant

326

1

E → K in OTCD. Ref.42

VAR_010610

Natural variant

330

1

R → G in OTCD.

VAR_004939

Natural variant

333

1

T → A. Ref.44

VAR_012656

Natural variant

336

1

A → S in OTCD; late onset.

VAR_004940

Natural variant

337

1

V → L in OTCD; late onset.

VAR_004941

Natural variant

339

1

V → L in OTCD; neonatal.

VAR_004942

Natural variant

340

1

S → P in OTCD; late onset. Ref.35

VAR_004943

Natural variant

341

1

L → P in OTCD. Ref.44

VAR_012657

Natural variant

343

1

T → K in OTCD; late onset. Ref.30

VAR_004944

Natural variant

345

1

Y → C in OTCD; neonatal.

VAR_004946

Natural variant

345

1

Y → D in OTCD. Ref.21

VAR_004947

Natural variant

354

1

F → C in OTCD; late onset.

VAR_004948

Experimental info

Sequence conflict

193 – 194

2

WI → CF in AAA59975. Ref.1

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

354

Helix Strand Turn

Details...

Helix

45 – 47

3

Helix

50 – 68

19

Turn

76 – 79

4

Beta strand

81 – 88

8

Helix

92 – 103

12

Beta strand

107 – 112

6

Turn

113 – 115

3

Turn

119 – 121

3

Helix

124 – 134

11

Beta strand

136 – 141

6

Helix

145 – 154

10

Beta strand

159 – 162

4

Helix

169 – 183

15

Beta strand

190 – 195

6

Helix

199 – 205

7

Turn

206 – 208

3

Helix

209 – 211

3

Beta strand

214 – 218

5

Helix

227 – 240

14

Beta strand

244 – 248

5

Helix

250 – 254

5

Beta strand

258 – 262

5

Helix

271 – 273

3

Helix

274 – 280

7

Turn

281 – 283

3

Helix

288 – 292

5

Beta strand

299 – 302

4

Turn

308 – 310

3

Helix

313 – 316

4

Helix

323 – 342

20

Sequences

	Sequence		Length	Mass (Da)
	P00480 [UniParc]. Last modified December 20, 2005. Version 3. Checksum: AE15B734F6E27A3B	FASTA	354	39,935
	10 20 30 40 50 60 MLFNLRILLN NAAFRNGHNF MVRNFRCGQP LQNKVQLKGR DLLTLKNFTG EEIKYMLWLS 70 80 90 100 110 120 ADLKFRIKQK GEYLPLLQGK SLGMIFEKRS TRTRLSTETG FALLGGHPCF LTTQDIHLGV 130 140 150 160 170 180 NESLTDTARV LSSMADAVLA RVYKQSDLDT LAKEASIPII NGLSDLYHPI QILADYLTLQ 190 200 210 220 230 240 EHYSSLKGLT LSWIGDGNNI LHSIMMSAAK FGMHLQAATP KGYEPDASVT KLAEQYAKEN 250 260 270 280 290 300 GTKLLLTNDP LEAAHGGNVL ITDTWISMGQ EEEKKKRLQA FQGYQVTMKT AKVAASDWTF 310 320 330 340 350 LHCLPRKPEE VDDEVFYSPR SLVFPEAENR KWTIMAVMVS LLTDYSPQLQ KPKF

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Structure and expression of a complementary DNA for the nuclear coded precursor of human mitochondrial ornithine transcarbamylase." Horwich A.L., Fenton W.A., Williams K.R., Kalousek F., Kraus J.P., Doolittle R.F., Konigsberg W., Rosenberg L.E. Science 224:1068-1074(1984) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANTS PRO-111 AND ARG-270. Tissue: Liver.
[2]	"Structure of the human ornithine transcarbamylase gene." Hata A., Tsuzuki T., Shimada K., Takiguchi M., Mori M., Matsuda I. J. Biochem. 103:302-308(1988) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT LEU-101. Tissue: Liver.
[3]	"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: Liver.
[4]	"The DNA sequence of the human X chromosome." Ross M.T., Grafham D.V., Coffey A.J., Scherer S., McLay K., Muzny D., Platzer M., Howell G.R., Burrows C., Bird C.P., Frankish A., Lovell F.L., Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G., Jones M.C. , Hurles M.E., Andrews T.D., Scott C.E., Searle S., Ramser J., Whittaker A., Deadman R., Carter N.P., Hunt S.E., Chen R., Cree A., Gunaratne P., Havlak P., Hodgson A., Metzker M.L., Richards S., Scott G., Steffen D., Sodergren E., Wheeler D.A., Worley K.C., Ainscough R., Ambrose K.D., Ansari-Lari M.A., Aradhya S., Ashwell R.I., Babbage A.K., Bagguley C.L., Ballabio A., Banerjee R., Barker G.E., Barlow K.F., Barrett I.P., Bates K.N., Beare D.M., Beasley H., Beasley O., Beck A., Bethel G., Blechschmidt K., Brady N., Bray-Allen S., Bridgeman A.M., Brown A.J., Brown M.J., Bonnin D., Bruford E.A., Buhay C., Burch P., Burford D., Burgess J., Burrill W., Burton J., Bye J.M., Carder C., Carrel L., Chako J., Chapman J.C., Chavez D., Chen E., Chen G., Chen Y., Chen Z., Chinault C., Ciccodicola A., Clark S.Y., Clarke G., Clee C.M., Clegg S., Clerc-Blankenburg K., Clifford K., Cobley V., Cole C.G., Conquer J.S., Corby N., Connor R.E., David R., Davies J., Davis C., Davis J., Delgado O., Deshazo D., Dhami P., Ding Y., Dinh H., Dodsworth S., Draper H., Dugan-Rocha S., Dunham A., Dunn M., Durbin K.J., Dutta I., Eades T., Ellwood M., Emery-Cohen A., Errington H., Evans K.L., Faulkner L., Francis F., Frankland J., Fraser A.E., Galgoczy P., Gilbert J., Gill R., Gloeckner G., Gregory S.G., Gribble S., Griffiths C., Grocock R., Gu Y., Gwilliam R., Hamilton C., Hart E.A., Hawes A., Heath P.D., Heitmann K., Hennig S., Hernandez J., Hinzmann B., Ho S., Hoffs M., Howden P.J., Huckle E.J., Hume J., Hunt P.J., Hunt A.R., Isherwood J., Jacob L., Johnson D., Jones S., de Jong P.J., Joseph S.S., Keenan S., Kelly S., Kershaw J.K., Khan Z., Kioschis P., Klages S., Knights A.J., Kosiura A., Kovar-Smith C., Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L., Liu W., Lloyd C., Lloyd D.M., Loulseged H., Loveland J.E., Lovell J.D., Lozado R., Lu J., Lyne R., Ma J., Maheshwari M., Matthews L.H., McDowall J., McLaren S., McMurray A., Meidl P., Meitinger T., Milne S., Miner G., Mistry S.L., Morgan M., Morris S., Mueller I., Mullikin J.C., Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N., Okwuonu G., Palmer S., Pandian R., Parker D., Parrish J., Pasternak S., Patel D., Pearce A.V., Pearson D.M., Pelan S.E., Perez L., Porter K.M., Ramsey Y., Reichwald K., Rhodes S., Ridler K.A., Schlessinger D., Schueler M.G., Sehra H.K., Shaw-Smith C., Shen H., Sheridan E.M., Shownkeen R., Skuce C.D., Smith M.L., Sotheran E.C., Steingruber H.E., Steward C.A., Storey R., Swann R.M., Swarbreck D., Tabor P.E., Taudien S., Taylor T., Teague B., Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S., Tromans A.C., d'Urso M., Verduzco D., Villasana D., Waldron L., Wall M., Wang Q., Warren J., Warry G.L., Wei X., West A., Whitehead S.L., Whiteley M.N., Wilkinson J.E., Willey D.L., Williams G., Williams L., Williamson A., Williamson H., Wilming L., Woodmansey R.L., Wray P.W., Yen J., Zhang J., Zhou J., Zoghbi H., Zorilla S., Buck D., Reinhardt R., Poustka A., Rosenthal A., Lehrach H., Meindl A., Minx P.J., Hillier L.W., Willard H.F., Wilson R.K., Waterston R.H., Rice C.M., Vaudin M., Coulson A., Nelson D.L., Weinstock G., Sulston J.E., Durbin R.M., Hubbard T., Gibbs R.A., Beck S., Rogers J., Bentley D.R. Nature 434:325-337(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	"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], VARIANT ARG-46. Tissue: Brain.
[7]	"Arginine in the leader peptide is required for both import and proteolytic cleavage of a mitochondrial precursor." Horwich A.L., Kalousek F., Rosenberg L.E. Proc. Natl. Acad. Sci. U.S.A. 82:4930-4933(1985) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-36.
[8]	"Isolation and characterization of the human ornithine transcarbamylase gene: structure of the 5'-end region." Hata A., Tsuzuki T., Shimada K., Takiguchi M., Mori M., Matsuda I. J. Biochem. 100:717-725(1986) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-26.
[9]	"A novel arginine (245) to glutamine change in exon 8 of the ornithine carbamoyl transferase gene in two unrelated children presenting with late onset deficiency and showing the same enzymatic pattern." Gilbert-Dussardier B., Rabier D., Strautnieks S., Segues B., Bonnefont J.-P., Munnich A. Hum. Mol. Genet. 3:831-832(1994) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 269-289, VARIANT OTCD GLN-277.
[10]	"Lysine 88 acetylation negatively regulates ornithine carbamoyltransferase activity in response to nutrient signals." Yu W., Lin Y., Yao J., Huang W., Lei Q., Xiong Y., Zhao S., Guan K.L. J. Biol. Chem. 284:13669-13675(2009) [PubMed] [Europe PMC] [Abstract] Cited for: ACETYLATION AT LYS-88, ENZYME REGULATION.
[11]	"1.85-A resolution crystal structure of human ornithine transcarbamoylase complexed with N-phosphonacetyl-L-ornithine. Catalytic mechanism and correlation with inherited deficiency." Shi D., Morizono H., Ha Y., Aoyagi M., Tuchman M., Allewell N.M. J. Biol. Chem. 273:34247-34254(1998) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.85 ANGSTROMS) IN COMPLEX WITH SUBSTRATE ANALOG.
[12]	"Crystal structure of human ornithine transcarbamylase complexed with carbamoyl phosphate and L-norvaline at 1.9 A resolution." Shi D., Morizono H., Aoyagi M., Tuchman M., Allewell N.M. Proteins 39:271-277(2000) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) IN COMPLEX WITH SUBSTRATE.
[13]	"Mutations and polymorphisms in the human ornithine transcarbamylase gene." Tuchman M. Hum. Mutat. 2:174-178(1993) [PubMed] [Europe PMC] [Abstract] Cited for: REVIEW ON VARIANTS.
[14]	"Mutations and polymorphisms in the human ornithine transcarbamylase gene: mutation update addendum." Tuchman M., Plante R.J. Hum. Mutat. 5:293-295(1995) [PubMed] [Europe PMC] [Abstract] Cited for: REVIEW ON VARIANTS.
[15]	"The molecular basis of ornithine transcarbamylase deficiency: modelling the human enzyme and the effects of mutations." Tuchman M., Morizono H., Reish O., Yuan X., Allewell N.M. J. Med. Genet. 32:680-688(1995) [PubMed] [Europe PMC] [Abstract] Cited for: REVIEW ON VARIANTS, 3D-STRUCTURE MODELING.
[16]	"Characterization of point mutations in the same arginine codon in three unrelated patients with ornithine transcarbamylase deficiency." Maddalena A., Spence J.E., O'Brien W.E., Nussbaum R.L. J. Clin. Invest. 82:1353-1358(1988) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT OTCD GLN-141.
[17]	"Scanning detection of mutations in human ornithine transcarbamoylase by chemical mismatch cleavage." Grompe M., Muzny D.M., Caskey C.T. Proc. Natl. Acad. Sci. U.S.A. 86:5888-5892(1989) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS OTCD GLN-26; PRO-45 AND GLU-216, VARIANT ARG-46.
[18]	"Use of denaturing gradient gel electrophoresis for detection of mutation and prospective diagnosis in late onset ornithine transcarbamylase deficiency." Finkelstein J.E., Francomano C.A., Brusilow S.W., Traystman M.D. Genomics 7:167-172(1990) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT OTCD TRP-277.
[19]	"Improved molecular diagnostics for ornithine transcarbamylase deficiency." Grompe M., Caskey C.T., Fenwick R.G. Jr. Am. J. Hum. Genet. 48:212-222(1991) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS OTCD GLN-92 AND LEU-320, VARIANT PRO-111.
[20]	"Fatal hyperammonemia resulting from a C-to-T mutation at a MspI site of the ornithine transcarbamylase gene." Hentzen D., Pelet A., Feldman D., Rabier D., Berthelot J., Munnich A. Hum. Genet. 88:153-156(1991) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT OTCD LEU-225.
[21]	"Six new mutations in the ornithine transcarbamylase gene detected by single-strand conformational polymorphism." Tuchman M., Holzknecht R.A., Gueron A.B., Berry S.A., Tsai M.Y. Pediatr. Res. 32:600-604(1992) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS OTCD GLU-79; THR-94; PHE-304 AND ASP-345.
[22]	"Single-strand conformational polymorphism and direct sequencing applied to carrier testing in families with ornithine transcarbamylase deficiency." Tsai M.Y., Holzknecht R.A., Tuchman M. Hum. Genet. 91:321-325(1993) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT OTCD PRO-140.
[23]	"The ornithine transcarbamylase gene: new 'private' mutations in four patients and study of a polymorphism." Tuchman M., Plante R.J., Giguere Y., Lemieux B. Hum. Mutat. 3:318-320(1994) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS OTCD LEU-117; LEU-182 AND CYS-203.
[24]	"Four newly identified ornithine transcarbamylase (OTC) mutations (D126G, R129H, I172M and W332X) in Japanese male patients with early-onset OTC deficiency." Matsuura T., Hoshide R., Kiwaki K., Komaki S., Koike E., Endo F., Oyanagi K., Suzuki Y., Kato I., Ishikawa K., Yoda H., Kamitani S., Sakaki Y., Matsuda I. Hum. Mutat. 3:402-406(1994) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS OTCD GLY-126; HIS-129 AND MET-172.
[25]	"Seven new mutations in the human ornithine transcarbamylase gene." Tuchman M., Plante R.J., McCann M.T., Qureshi A.A. Hum. Mutat. 4:57-60(1994) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS OTCD HIS-40; HIS-129; ARG-195; THR-225; GLN-277 AND GLU-309 DEL.
[26]	"A splicing mutation, a nonsense mutation (Y167X) and two missense mutations (I159T and A209V) in Spanish patients with ornithine transcarbamylase deficiency." Garcia-Perez M.A., Sanjurjo P., Briones P., Garcia-Munoz M.J., Rubio V. Hum. Genet. 96:549-551(1995) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS OTCD THR-159 AND VAL-209.
[27]	"A novel point mutation at codon 269 of the ornithine transcarbamylase (OTC) gene causing neonatal onset of OTC deficiency." Zimmer K.P., Matsuura T., Colombo J.-P., Koch H.G., Ullrich K., Deufel T., Harms E., Matsuda I. J. Inherit. Metab. Dis. 18:356-357(1995) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT OTCD GLU-269.
[28]	"Partial duplication [dup. TCAC (178)] and novel point mutations (T125M, G188R, A209V, and H302L) of the ornithine transcarbamylase gene in congenital hyperammonemia." Gilbert-Dussardier B., Segues B., Rozet J.-M., Rabier D., Calvas P., de Lumley L., Bonnefont J.-P., Munnich A. Hum. Mutat. 8:74-76(1996) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS OTCD MET-125; ARG-188; VAL-209 AND LEU-302.
[29]	"Genotype-phenotype correlations in ornithine transcarbamylase deficiency." Guardamagna O., Gatti E., Parini R., Plante R.J., Tuchman M. Enzyme Protein 49:191-191(1996) Cited for: VARIANTS OTCD HIS-40; ASN-88; TYR-202 AND ASN-263.
[30]	"Ornithine transcarbamylase deficiency: characterization of gene mutations and polymorphisms." Leibundgut E.O., Wermuth B., Colombo J.-P., Liechti-Gallati S. Hum. Mutat. 8:333-339(1996) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS OTCD ASN-88; CYS-176; ALA-220; TYR-302 AND LYS-343.
[31]	"A 3-base pair in-frame deletion in exon 8 (delGlu272/273) of the ornithine transcarbamylase gene in late-onset hyperammonemic coma." Segues B., Saugier Veber P., Rabier D., Calvas P., Saudubray J.-M., Gilbert-Dussardier B., Bonnefont J.-P., Munnich A. Hum. Mutat. 8:373-374(1996) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT OTCD GLU-272 DEL.
[32]	"Identification of new mutations in the ornithine transcarbamylase (OTC) gene in Korean families." Yoo H.-W., Kim G.-H., Lee D.-H. J. Inherit. Metab. Dis. 19:31-42(1996) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS OTCD ILE-44; GLN-141 AND TYR-214, VARIANT LEU-101.
[33]	"The ornithine transcarbamylase (OTC) gene: mutations in 50 Japanese families with OTC deficiency." Matsuda I., Tanase S. Am. J. Med. Genet. 71:378-383(1997) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS OTCD.
[34]	"Expression, purification and kinetic characterization of wild-type human ornithine transcarbamylase and a recurrent mutant that produces 'late onset' hyperammonaemia." Morizono H., Tuchman M., Rajagopal B.S., McCann M.T., Listrom C.D., Yuan X., Venugopal D., Barany G., Allewell N.M. Biochem. J. 322:625-631(1997) [PubMed] [Europe PMC] [Abstract] Cited for: CHARACTERIZATION OF VARIANT OTCD TRP-277.
[35]	"Ornithine transcarbamylase deficiency: ten new mutations and high proportion of de novo mutations in heterozygous females." Oppliger Leibundgut E., Liechti-Gallati S., Colombo J.-P., Wermuth B. Hum. Mutat. 9:409-411(1997) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS OTCD PRO-63; ASP-100; ASP-183; LYS-213 AND PRO-340, VARIANT PHE-43.
[36]	"Identification of 'private' mutations in patients with ornithine transcarbamylase deficiency." Tuchman M., Morizono H., Rajagopal B.S., Plante R.J., Allewell N.M. J. Inherit. Metab. Dis. 20:525-527(1997) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS OTCD.
[37]	"Ten novel mutations of the ornithine transcarbamylase (OTC) gene in OTC deficiency." Shimadzu M., Matsumoto H., Matsuura T., Kobayashi K., Komaki S., Kiwaki K., Hoshide R., Endo F., Saheki T., Matsuda I. Hum. Mutat. Suppl. 1:S5-S7(1998) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS OTCD 178-THE-LEU-179 DEL; HIS-180; PRO-201; ARG-207; ILE-264 AND ARG-267.
[38]	"Novel intragenic deletions and point mutations of the ornithine transcarbamylase gene in congenital hyperammonemia." Calvas P., Seques B., Rozet J.-M., Rabier D., Bonnefont J.-P., Munnich A. Hum. Mutat. Suppl. 1:S81-S84(1998) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS OTCD CYS-39; GLN-244 AND ARG-303.
[39]	"Y55D mutation in ornithine transcarbamylase associated with late-onset hyperammonemia in a male." Nishiyori A., Yoshino M., Tananari Y., Matsuura T., Hoshide R., Matsuda I., Mori M., Kato H. Hum. Mutat. Suppl. 1:S131-S133(1998) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT OTCD ASP-55.
[40]	"A novel missense mutation in the human ornithine transcarbamylase gene." Bartholomew D.W., McClellan J. Hum. Mutat. 12:220-220(1998) Cited for: VARIANT OTCD ASP-83.
[41]	"Identification of a cytogenetic deletion and of four novel mutations (Q69X, I172F, G188V, G197R) affecting the gene for ornithine transcarbamylase (OTC) in Spanish patients with OTC deficiency." Climent C., Garcia-Perez M.A., Sanjurjo P., Ruiz-Sanz J.-I., Vilaseca M.A., Pineda M., Campistol J., Rubio V. Hum. Mutat. 14:352-353(1999) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS OTCD PHE-172; VAL-188 AND ARG-197.
[42]	"Three novel and one recurrent ornithine carbamoyltransferase gene mutations in Polish patients." Popowska E., Ciara E., Rokicki D., Pronicka E. J. Inherit. Metab. Dis. 22:92-93(1999) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS OTCD LYS-198; VAL-209 AND LYS-326, VARIANT ARG-270.
[43]	"Lymphocyte mRNA analysis of the ornithine transcarbamylase gene in Italian OTCD male patients and manifesting carriers: identification of novel mutations." Giorgi M., Morrone A., Donati M.A., Ciani F., Bardelli T., Biasucci G., Zammarchi E. Hum. Mutat. 15:380-381(2000) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS OTCD LYS-262; ALA-264 AND LEU-265.
[44]	"Identification of seven novel missense mutations, two splice-site mutations, two microdeletions and a polymorphic amino acid substitution in the gene for ornithine transcarbamylase (OTC) in patients with OTC deficiency." Climent C., Rubio V. Hum. Mutat. 19:185-186(2002) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS OTCD SER-160; PHE-191; ILE-206; PHE-301; HIS-305 AND PRO-341, VARIANT ALA-333.
[45]	"The consensus coding sequences of human breast and colorectal cancers." Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V. , Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., Velculescu V.E. Science 314:268-274(2006) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT [LARGE SCALE ANALYSIS] ARG-270.
+	Additional computationally mapped references.

Web resources

GeneReviews

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

K02100 mRNA. Translation: AAA59975.1.
D00230 Genomic DNA. Translation: BAA00161.1.
AK292757 mRNA. Translation: BAF85446.1.
AL607040, AF241726, AL606748 Genomic DNA. Translation: CAI95193.1.
AL606748, AL607040, AF241726 Genomic DNA. Translation: CAI95408.1.
CH471141 Genomic DNA. Translation: EAW59439.1.
CH471141 Genomic DNA. Translation: EAW59440.1.
BC074745 mRNA. Translation: AAH74745.1.
BC107153 mRNA. Translation: AAI07154.1.
BC107154 mRNA. Translation: AAI07155.1.
BC114496 mRNA. Translation: AAI14497.1.
M11235 Genomic DNA. Translation: AAA59976.1.
D00095 Genomic DNA. Translation: BAA00058.1.
X04443 Genomic DNA. Translation: CAA28039.1.
S73640 Genomic DNA. Translation: AAB31859.1.

IPI

IPI00295363.

PIR

OWHU. A41444.

RefSeq

NP_000522.3. NM_000531.5.

UniGene

Hs.117050.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1C9Y	X-ray	1.90	A	34-354	[»]
1EP9	X-ray	2.40	A	34-354	[»]
1FVO	X-ray	2.60	A/B	34-354	[»]
1OTH	X-ray	1.85	A	34-354	[»]

ProteinModelPortal

P00480.

ModBase

Search...

Protein-protein interaction databases

STRING

9606.ENSP00000039007.

PTM databases

PhosphoSite

P00480.

Polymorphism databases

DMDM

84028235.

2D gel databases

REPRODUCTION-2DPAGE

P00480.

Proteomic databases

PaxDb

P00480.

PRIDE

P00480.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000039007; ENSP00000039007; ENSG00000036473.

GeneID

5009.

KEGG

hsa:5009.

UCSC

uc004def.4. human.

Organism-specific databases

CTD

5009.

GeneCards

GC0XP038211.

HGNC

HGNC:8512. OTC.

HPA

HPA000243.
HPA000570.

MIM

300461. gene.
311250. phenotype.

neXtProt

NX_P00480.

Orphanet

664. Ornithine transcarbamylase deficiency.

PharmGKB

PA32840.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG0078.

HOGENOM

HOG000022686.

HOVERGEN

HBG007881.

InParanoid

P00480.

KO

K00611.

OMA

AHPCQTL.

OrthoDB

EOG4GB76C.

PhylomeDB

P00480.

Enzyme and pathway databases

BioCyc

MetaCyc:HS00516-MONOMER.

Reactome

REACT_111217. Metabolism.

SABIO-RK

P00480.

UniPathway

UPA00158; UER00271.

Gene expression databases

Bgee

P00480.

CleanEx

HS_OTC.

Genevestigator

P00480.

GermOnline

ENSG00000036473. Homo sapiens.

Family and domain databases

InterPro

IPR006132. Asp/Orn_carbamoyltranf_P-bd.
IPR006130. Asp/Orn_carbamoylTrfase.
IPR006131. Asp_carbamoyltransf_Asp/Orn-bd.
IPR002292. Orn/put_carbamltrans.
[Graphical view]

Pfam

PF00185. OTCace. 1 hit.
PF02729. OTCace_N. 1 hit.
[Graphical view]

PRINTS

PR00100. AOTCASE.
PR00102. OTCASE.

SUPFAM

SSF53671. Asp/Orn_carbamoyltranf. 1 hit.

TIGRFAMs

TIGR00658. orni_carb_tr. 1 hit.

PROSITE

PS00097. CARBAMOYLTRANSFERASE. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

BindingDB

P00480.

ChEMBL

CHEMBL2222.

DrugBank

DB00155. L-Citrulline.
DB00129. L-Ornithine.

EvolutionaryTrace

P00480.

GenomeRNAi

5009.

NextBio

19288.

PMAP-CutDB

P00480.

SOURCE

Search...

Entry information

Entry name

OTC_HUMAN

Accession

Primary (citable) accession number: P00480
Secondary accession number(s): A8K9P2 , D3DWB0, Q3KNR1, Q6B0I1, Q9NYJ5

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 21, 1986
Last sequence update:	December 20, 2005
Last modified:	May 1, 2013
This is version 167 of the entry and version 3 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.