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P00480 (OTC_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 177. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Ornithine carbamoyltransferase, mitochondrial

EC=2.1.3.3
Alternative name(s):
Ornithine transcarbamylase
Short name=OTCase
Gene names
Name:OTC
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length354 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence 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. Ref.10

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 processAmino-acid biosynthesis
Arginine biosynthesis
Urea cycle
   Cellular componentMitochondrion
   Coding sequence diversityPolymorphism
   DiseaseDisease mutation
   DomainTransit peptide
   Molecular functionTransferase
   PTMAcetylation
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processammonia homeostasis

Inferred from mutant phenotype PubMed 2556444PubMed 2575934. Source: BHF-UCL

arginine biosynthetic process

Inferred from electronic annotation. Source: UniProtKB-KW

cellular nitrogen compound metabolic process

Traceable author statement. Source: Reactome

citrulline biosynthetic process

Inferred from direct assay PubMed 2556444PubMed 8112735. Source: BHF-UCL

liver development

Inferred from electronic annotation. Source: Ensembl

midgut development

Inferred from electronic annotation. Source: Ensembl

ornithine catabolic process

Inferred from direct assay PubMed 2556444PubMed 8112735. Source: BHF-UCL

protein homotrimerization

Inferred from electronic annotation. Source: Ensembl

response to biotin

Inferred from electronic annotation. Source: Ensembl

response to drug

Inferred from electronic annotation. Source: Ensembl

response to insulin

Inferred from electronic annotation. Source: Ensembl

response to zinc ion

Inferred from electronic annotation. Source: Ensembl

small molecule metabolic process

Traceable author statement. Source: Reactome

urea cycle

Inferred from direct assay PubMed 2556444. Source: BHF-UCL

   Cellular_componentmitochondrial inner membrane

Inferred from electronic annotation. Source: Ensembl

mitochondrial matrix

Non-traceable author statement Ref.1. Source: UniProtKB

mitochondrion

Inferred from direct assay PubMed 3472484Ref.1. Source: BHF-UCL

   Molecular_functionamino acid binding

Inferred from electronic annotation. Source: Ensembl

ornithine carbamoyltransferase activity

Inferred from direct assay PubMed 2556444PubMed 8112735. Source: BHF-UCL

phosphate ion binding

Inferred from electronic annotation. Source: Ensembl

phospholipid binding

Inferred from electronic annotation. Source: Ensembl

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Transit peptide1 – 3232Mitochondrion
Chain33 – 354322Ornithine carbamoyltransferase, mitochondrial
PRO_0000020334

Regions

Region90 – 945Ornithine and carbamoyl phosphate binding
Region168 – 1714Ornithine and carbamoyl phosphate binding
Region263 – 2675Ornithine binding
Region302 – 3054Ornithine binding By similarity

Sites

Active site3031 By similarity
Binding site1411Carbamoyl phosphate
Binding site1411Ornithine
Binding site1991Ornithine
Binding site3301Carbamoyl phosphate
Binding site3301Ornithine

Amino acid modifications

Modified residue701N6-acetyllysine; alternate By similarity
Modified residue701N6-succinyllysine; alternate By similarity
Modified residue801N6-succinyllysine By similarity
Modified residue881N6-acetyllysine; alternate Ref.10
Modified residue881N6-succinyllysine; alternate By similarity
Modified residue1441N6-acetyllysine; alternate By similarity
Modified residue1441N6-succinyllysine; alternate By similarity
Modified residue2211N6-acetyllysine; alternate By similarity
Modified residue2211N6-succinyllysine; alternate By similarity
Modified residue2311N6-acetyllysine; alternate By similarity
Modified residue2311N6-succinyllysine; alternate By similarity
Modified residue2381N6-acetyllysine; alternate By similarity
Modified residue2381N6-succinyllysine; alternate By similarity
Modified residue2431N6-acetyllysine By similarity
Modified residue2741N6-succinyllysine By similarity
Modified residue2891N6-succinyllysine By similarity
Modified residue2921N6-acetyllysine; alternate By similarity
Modified residue2921N6-succinyllysine; alternate By similarity
Modified residue3071N6-acetyllysine; alternate By similarity
Modified residue3071N6-succinyllysine; alternate By similarity

Natural variations

Natural variant261R → Q in OTCD. Ref.17
VAR_004843
Natural variant391G → C in OTCD; late onset. Ref.38
VAR_004844
Natural variant401R → C in OTCD; late onset.
VAR_004845
Natural variant401R → H in OTCD; late onset. Ref.25 Ref.29
VAR_004846
Natural variant431L → F. Ref.35
VAR_004847
Natural variant441T → I in OTCD. Ref.32
VAR_004848
Natural variant451L → P in OTCD. Ref.17
VAR_004849
Natural variant451L → V in OTCD.
VAR_004850
Natural variant461K → R. Ref.6 Ref.17
Corresponds to variant rs1800321 [ dbSNP | Ensembl ].
VAR_004851
Natural variant471N → I in OTCD; neonatal.
VAR_004852
Natural variant501G → R in OTCD; late onset.
VAR_004853
Natural variant551Y → D in OTCD; late onset. Ref.39
VAR_004854
Natural variant561M → T in OTCD; late onset.
VAR_004855
Natural variant601S → L in OTCD.
VAR_004856
Natural variant631L → P in OTCD; late onset. Ref.35
VAR_004857
Natural variant791G → E in OTCD. Ref.21
VAR_004858
Natural variant821Missing in OTCD.
VAR_004859
Natural variant831G → D in OTCD. Ref.40
VAR_004860
Natural variant831G → R in OTCD; neonatal.
VAR_004861
Natural variant871E → K in OTCD.
VAR_004862
Natural variant881K → N in OTCD; late onset. Ref.29 Ref.30
VAR_004863
Natural variant901S → R in OTCD.
VAR_004864
Natural variant921R → Q in OTCD. Ref.19
VAR_004865
Natural variant931T → A in OTCD; late onset.
VAR_004866
Natural variant941R → T in OTCD. Ref.21
VAR_004867
Natural variant1001G → D in OTCD; late onset. Ref.35
VAR_004868
Natural variant1011F → L. Ref.2 Ref.32
VAR_004869
Natural variant1021A → E in OTCD.
VAR_004870
Natural variant1111L → P. Ref.1 Ref.19
Corresponds to variant rs1800324 [ dbSNP | Ensembl ].
VAR_004871
Natural variant1171H → L in OTCD. Ref.23
VAR_004872
Natural variant1171H → R in OTCD; late onset.
VAR_004873
Natural variant1251T → M in OTCD; neonatal. Ref.28
VAR_004874
Natural variant1261D → G in OTCD; 0.9% of wild-type activity; early onset. Ref.24
VAR_004875
Natural variant1291R → H in OTCD; 2.1% of wild-type activity; early onset. Ref.24 Ref.25
VAR_004876
Natural variant1391L → S in OTCD.
VAR_004877
Natural variant1401A → P in OTCD; late onset. Ref.22
VAR_010605
Natural variant1411R → P in OTCD.
VAR_004878
Natural variant1411R → Q in OTCD; activity is 100-fold lower; most common point mutation. Ref.16 Ref.32
VAR_004879
Natural variant1481L → F in OTCD.
VAR_004880
Natural variant1591I → T in OTCD. Ref.26
VAR_004881
Natural variant1601I → S in OTCD. Ref.44
VAR_012651
Natural variant1611N → S in OTCD.
VAR_004882
Natural variant1621G → R in OTCD.
VAR_004883
Natural variant1681H → Q in OTCD; late onset.
VAR_004884
Natural variant1681H → R in OTCD; late onset.
VAR_004885
Natural variant1721I → F in OTCD. Ref.41
VAR_009233
Natural variant1721I → M in OTCD; no activity; early onset. Ref.24
VAR_004886
Natural variant1741A → P in OTCD.
VAR_004887
Natural variant1751D → V in OTCD.
VAR_004888
Natural variant1761Y → C in OTCD; late onset. Ref.30
VAR_004889
Natural variant178 – 1792Missing in OTCD; neonatal.
VAR_004891
Natural variant1781T → M in OTCD; neonatal.
VAR_004890
Natural variant1801Q → H in OTCD. Ref.37
VAR_004892
Natural variant1811E → G in OTCD; neonatal.
VAR_004893
Natural variant1821H → L in OTCD. Ref.23
VAR_004894
Natural variant1831Y → C in OTCD.
VAR_004895
Natural variant1831Y → D in OTCD; late onset. Ref.35
VAR_004896
Natural variant1881G → R in OTCD; neonatal. Ref.28
VAR_004897
Natural variant1881G → V in OTCD. Ref.41
VAR_009234
Natural variant1911L → F in OTCD. Ref.44
VAR_012652
Natural variant1921S → R in OTCD; neonatal.
VAR_004898
Natural variant1951G → R in OTCD; no activity. Ref.25
VAR_004899
Natural variant1961D → V in OTCD; neonatal; 3.7% activity.
VAR_004900
Natural variant1961D → Y in OTCD; neonatal.
VAR_004901
Natural variant1971G → E in OTCD.
VAR_004902
Natural variant1971G → R in OTCD. Ref.41
VAR_009235
Natural variant1981N → K in OTCD. Ref.42
VAR_010606
Natural variant2011L → P in OTCD; neonatal. Ref.37
VAR_004903
Natural variant2021H → Y in OTCD. Ref.29
VAR_004904
Natural variant2031S → C in OTCD. Ref.23
VAR_004905
Natural variant2061M → I in OTCD. Ref.44
VAR_012653
Natural variant2061M → R in OTCD; neonatal.
VAR_004906
Natural variant2071S → R in OTCD; neonatal. Ref.37
VAR_004907
Natural variant2081A → T in OTCD; late onset.
VAR_004908
Natural variant2091A → V in OTCD; neonatal. Ref.26 Ref.28 Ref.42
VAR_004909
Natural variant2131M → K in OTCD; late onset. Ref.35
VAR_004910
Natural variant2141H → Y in OTCD; neonatal. Ref.32
VAR_010607
Natural variant2161Q → E in OTCD. Ref.17
VAR_004911
Natural variant2201P → A in OTCD; late onset. Ref.30
VAR_004912
Natural variant2251P → L in OTCD. Ref.20
VAR_004913
Natural variant2251P → R in OTCD; neonatal.
VAR_004914
Natural variant2251P → T in OTCD; late onset. Ref.25
VAR_004915
Natural variant2421T → I in OTCD; late onset.
VAR_004916
Natural variant2441L → Q in OTCD; late onset. Ref.38
VAR_004917
Natural variant2471T → K in OTCD; neonatal/late onset.
VAR_004918
Natural variant2551H → P in OTCD.
VAR_004919
Natural variant2621T → K in OTCD; mild. Ref.43
VAR_010608
Natural variant2631D → G in OTCD.
VAR_004920
Natural variant2631D → N in OTCD. Ref.29
VAR_004921
Natural variant2641T → A in OTCD; late onset; 8.9% activity. Ref.43
VAR_004922
Natural variant2641T → I in OTCD; late onset. Ref.37
VAR_004923
Natural variant2651W → L in OTCD; mild. Ref.43
VAR_010609
Natural variant2671S → R in OTCD. Ref.37
VAR_004924
Natural variant2681M → T in OTCD; late onset.
VAR_004925
Natural variant2691G → E in OTCD; neonatal. Ref.27
VAR_004926
Natural variant2701Q → R in about 5% of population. Ref.1 Ref.42 Ref.45
Corresponds to variant rs1800328 [ dbSNP | Ensembl ].
VAR_004927
Natural variant2721Missing in OTCD; late onset. Ref.31
VAR_004928
Natural variant2771R → Q in OTCD; late onset. Ref.9 Ref.25
VAR_004929
Natural variant2771R → W in OTCD; late onset. Ref.18 Ref.34
VAR_004930
Natural variant3011L → F in OTCD. Ref.44
VAR_012654
Natural variant3021H → L in OTCD; female; late onset. Ref.28
VAR_004931
Natural variant3021H → Q in OTCD; late onset.
VAR_004932
Natural variant3021H → Y in OTCD; neonatal. Ref.30
VAR_004933
Natural variant3031C → R in OTCD; neonatal. Ref.38
VAR_004934
Natural variant3031C → Y in OTCD.
VAR_004935
Natural variant3041L → F in OTCD. Ref.21
VAR_004936
Natural variant3051P → H in OTCD. Ref.44
VAR_012655
Natural variant3091Missing in OTCD; late onset. Ref.25
VAR_004937
Natural variant3201R → L in OTCD. Ref.19
VAR_004938
Natural variant3261E → K in OTCD. Ref.42
VAR_010610
Natural variant3301R → G in OTCD.
VAR_004939
Natural variant3331T → A. Ref.44
VAR_012656
Natural variant3361A → S in OTCD; late onset.
VAR_004940
Natural variant3371V → L in OTCD; late onset.
VAR_004941
Natural variant3391V → L in OTCD; neonatal.
VAR_004942
Natural variant3401S → P in OTCD; late onset. Ref.35
VAR_004943
Natural variant3411L → P in OTCD. Ref.44
VAR_012657
Natural variant3431T → K in OTCD; late onset. Ref.30
VAR_004944
Natural variant3451Y → C in OTCD; neonatal.
VAR_004946
Natural variant3451Y → D in OTCD. Ref.21
VAR_004947
Natural variant3541F → C in OTCD; late onset.
VAR_004948

Experimental info

Sequence conflict193 – 1942WI → CF in AAA59975. Ref.1

Secondary structure

........................................................ 354
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P00480 [UniParc].

Last modified December 20, 2005. Version 3.
Checksum: AE15B734F6E27A3B

FASTA35439,935
        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 

« Hide

References

« Hide '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. expand/collapse author list , 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. expand/collapse author list , 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. expand/collapse author list , 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. expand/collapse author list , 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

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.
PIROWHU. A41444.
RefSeqNP_000522.3. NM_000531.5.
UniGeneHs.117050.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1C9YX-ray1.90A34-354[»]
1EP9X-ray2.40A34-354[»]
1FVOX-ray2.60A/B34-354[»]
1OTHX-ray1.85A34-354[»]
ProteinModelPortalP00480.
SMRP00480. Positions 34-354.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid111050. 2 interactions.
STRING9606.ENSP00000039007.

Chemistry

BindingDBP00480.
ChEMBLCHEMBL2222.
DrugBankDB00155. L-Citrulline.
DB00129. L-Ornithine.

PTM databases

PhosphoSiteP00480.

Polymorphism databases

DMDM84028235.

2D gel databases

REPRODUCTION-2DPAGEP00480.

Proteomic databases

PaxDbP00480.
PRIDEP00480.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000039007; ENSP00000039007; ENSG00000036473.
GeneID5009.
KEGGhsa:5009.
UCSCuc004def.4. human.

Organism-specific databases

CTD5009.
GeneCardsGC0XP038211.
HGNCHGNC:8512. OTC.
HPAHPA000243.
HPA000570.
MIM300461. gene.
311250. phenotype.
neXtProtNX_P00480.
Orphanet664. Ornithine transcarbamylase deficiency.
PharmGKBPA32840.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0078.
HOGENOMHOG000022686.
HOVERGENHBG007881.
InParanoidP00480.
KOK00611.
OMAGNNVCNS.
OrthoDBEOG7D85XC.
PhylomeDBP00480.
TreeFamTF352580.

Enzyme and pathway databases

BioCycMetaCyc:HS00516-MONOMER.
ReactomeREACT_111217. Metabolism.
SABIO-RKP00480.
UniPathwayUPA00158; UER00271.

Gene expression databases

BgeeP00480.
CleanExHS_OTC.
GenevestigatorP00480.

Family and domain databases

Gene3D3.40.50.1370. 2 hits.
InterProIPR006132. Asp/Orn_carbamoyltranf_P-bd.
IPR006130. Asp/Orn_carbamoylTrfase.
IPR006131. Asp_carbamoyltransf_Asp/Orn-bd.
IPR002292. Orn/put_carbamltrans.
[Graphical view]
PfamPF00185. OTCace. 1 hit.
PF02729. OTCace_N. 1 hit.
[Graphical view]
PRINTSPR00100. AOTCASE.
PR00102. OTCASE.
SUPFAMSSF53671. SSF53671. 1 hit.
TIGRFAMsTIGR00658. orni_carb_tr. 1 hit.
PROSITEPS00097. CARBAMOYLTRANSFERASE. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceP00480.
GeneWikiOrnithine_transcarbamylase.
GenomeRNAi5009.
NextBio19288.
PMAP-CutDBP00480.
PROP00480.
SOURCESearch...

Entry information

Entry nameOTC_HUMAN
AccessionPrimary (citable) accession number: P00480
Secondary accession number(s): A8K9P2 expand/collapse secondary AC list , D3DWB0, Q3KNR1, Q6B0I1, Q9NYJ5
Entry history
Integrated into UniProtKB/Swiss-Prot: July 21, 1986
Last sequence update: December 20, 2005
Last modified: April 16, 2014
This is version 177 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

PATHWAY comments

Index of metabolic and biosynthesis pathways

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome X

Human chromosome X: entries, gene names and cross-references to MIM