Reviewed,
UniProtKB/Swiss-Prot Q8N6M6 (AMPO_HUMAN)
Last modified
November 24, 2009.
Version 63.
History...
Clusters with 100%,
90%,
50% identity |
Documents (5) |
Third-party data |
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Names and origin
| Protein names | Recommended name: Aminopeptidase O Short name=AP-O EC=3.4.11.- | ||||
| Gene names |
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| Organism | Homo sapiens (Human) [Complete proteome] | ||||
| Taxonomic identifier | 9606 [NCBI] | ||||
| Taxonomic lineage | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Protein attributes
| Sequence length | 819 AA. |
| Sequence status | Complete. |
| Sequence processing | The displayed sequence is not processed. |
| Protein existence | Evidence at protein level. |
General annotation (Comments)
| Function | Aminopeptidases catalyze the hydrolysis of amino acid residues from the N-terminus of peptide or protein substrates. Able to cleave angiotensin III to generate angiotensin IV, a bioactive peptide of the renin-angiotensin pathway. Not able to cleave angiotensin I and angiotensin II. May play a role in the proteolytic processing of bioactive peptides in tissues such as testis and heart. Ref.1 |
| Cofactor | Binds 1 zinc ion per subunit By similarity. |
| Enzyme regulation | Strongly inhibited by ophenanthroline, a metalloprotease inhibitor. Inhibited by arphamenine A, a potent inhibitor of aminopeptidases. Not affected by AEBSF and E-64, which are common inhibitors of serine- and cysteine-proteases, respectively. Ref.1 |
| Subcellular location | Cytoplasm Potential. |
| Tissue specificity | Predominantly expressed in pancreas, placenta, liver, testis and heart. Expressed at lower level in brain, lung and kidney. Ref.1 |
| Sequence similarities | Belongs to the peptidase M1 family. |
| Biophysicochemical properties | Kinetic parameters: KM=6 µM for Asn-AMC |
Ontologies
| Keywords | |
|---|---|
| Cellular component | Cytoplasm |
| Coding sequence diversity | Alternative splicing Polymorphism |
| Ligand | Metal-binding Zinc |
| Molecular function | Aminopeptidase Hydrolase Metalloprotease Protease |
| Technical term | Complete proteome |
| Gene Ontology (GO) | |
| Biological process | leukotriene biosynthetic process Inferred from electronic annotation. Source: InterPro proteolysis Ref.1Inferred from direct assay. Source: UniProtKB |
| Cellular component | cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell |
| Molecular function | aminopeptidase activity Ref.1 Inferred from direct assay. Source: UniProtKB metallopeptidase activity Ref.1Inferred from direct assay. Source: UniProtKB zinc ion bindingInferred from electronic annotation. Source: UniProtKB-KW |
| Complete GO annotation... | |
Alternative products
| This entry describes 4 isoforms produced by alternative splicing. [Align] [Select] | ||||||
| Isoform 1 (identifier: Q8N6M6-1) 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 2 (identifier: Q8N6M6-2) The sequence of this isoform differs from the canonical sequence as follows: 455-553: Missing. | ||||||
| Isoform 3 (identifier: Q8N6M6-3) The sequence of this isoform differs from the canonical sequence as follows: 555-565: PSKDKTGHTSD → FPHVGGCSGSF 566-819: Missing. | ||||||
| Note: No experimental confirmation available. | ||||||
| Isoform 4 (identifier: Q8N6M6-4) The sequence of this isoform differs from the canonical sequence as follows: 455-553: Missing. 774-784: AMGVYLYGELM → VGVIFQQMGIL 785-819: Missing. | ||||||
| Note: No experimental confirmation available. |
Sequence annotation (Features)
| Feature key | Position(s) | Length | Description | Graphical view | Feature identifier | ||||
Molecule processing | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Chain | 1 – 819 | 819 | Aminopeptidase O | PRO_0000095091 | |||||
Sites | |||||||||
| Active site | 480 | 1 | By similarity | ||||||
| Active site | 586 | 1 | Proton donor By similarity | ||||||
| Metal binding | 479 | 1 | Zinc; catalytic By similarity | ||||||
| Metal binding | 483 | 1 | Zinc; catalytic By similarity | ||||||
| Metal binding | 502 | 1 | Zinc; catalytic By similarity | ||||||
Natural variations | |||||||||
| Alternative sequence | 455 – 553 | 99 | Missing in isoform 2 and isoform 4. | VSP_013161 | |||||
| Alternative sequence | 555 – 565 | 11 | PSKDKTGHTSD → FPHVGGCSGSF in isoform 3. | VSP_013162 | |||||
| Alternative sequence | 566 – 819 | 254 | Missing in isoform 3. | VSP_013163 | |||||
| Alternative sequence | 774 – 784 | 11 | AMGVYLYGELM → VGVIFQQMGIL in isoform 4. | VSP_013164 | |||||
| Alternative sequence | 785 – 819 | 35 | Missing in isoform 4. | VSP_013165 | |||||
| Natural variant | 179 | 1 | V → A: dbSNP rs16911679. | VAR_021511 | |||||
| Natural variant | 179 | 1 | V → I: dbSNP rs16911679. | VAR_057053 | |||||
| Natural variant | 255 | 1 | R → Q: dbSNP rs16911681. | VAR_057054 | |||||
| Natural variant | 386 | 1 | R → C: dbSNP rs34557833. | VAR_057055 | |||||
Sequences
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References
| [1] | "Identification of human aminopeptidase O, a novel metalloprotease with structural similarity to aminopeptidase B and leukotriene A4 hydrolase." Diaz-Perales A., Quesada V., Sanchez L.M., Ugalde A.P., Suarez M.F., Fueyo A., Lopez-Otin C. J. Biol. Chem. 280:14310-14317(2005) [PubMed: 15687497] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, ENZYME REGULATION, BIOPHYSICOCHEMICAL PROPERTIES, ENZYME ACTIVITY, TISSUE SPECIFICITY. Tissue: Brain. |
| [2] | "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. Sugano S.Nat. Genet. 36:40-45(2004) [PubMed: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3), NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 178-819 (ISOFORM 4). Tissue: Teratocarcinoma and Testis. |
| [3] | "DNA sequence and analysis of human chromosome 9." Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L., Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R., Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S., Bagguley C.L. Dunham I.Nature 429:369-374(2004) [PubMed: 15164053] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. |
| [4] | "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 219-819 (ISOFORM 1). Tissue: Lung and Muscle. |
Cross-references
Sequence databases | |
|---|---|
| AJ560639 mRNA. Translation: CAD90259.1. AK027581 mRNA. Translation: BAB55210.1. Different initiation. AK057450 mRNA. Translation: BAB71491.1. AL157936, AL353768, AL354893 Genomic DNA. Translation: CAI13040.1. AL353768, AL157936, AL354893 Genomic DNA. Translation: CAI41125.1. AL354893, AL157936, AL353768 Genomic DNA. Translation: CAI41325.1. AL157936, AL353768, AL354893 Genomic DNA. Translation: CAI13039.1. AL353768, AL157936, AL354893 Genomic DNA. Translation: CAI41126.1. AL354893, AL157936, AL353768 Genomic DNA. Translation: CAI41326.1. AL157936, AL353768 Genomic DNA. Translation: CAI13037.1. AL353768, AL157936 Genomic DNA. Translation: CAI41124.1. AL157936, AL353768, AL354893 Genomic DNA. Translation: CAI13041.1. AL353768, AL157936, AL354893 Genomic DNA. Translation: CAI41127.1. AL354893, AL157936, AL353768 Genomic DNA. Translation: CAI41327.1. AL157936 Genomic DNA. Translation: CAI13038.1. BC020194 mRNA. Translation: AAH20194.1. Different initiation. BC029616 mRNA. Translation: AAH29616.1. | |
| IPI | IPI00163493. IPI00171144. IPI00187032. IPI00554492. |
| RefSeq | NP_116212.3. |
| UniGene | Hs.434253 |
3D structure databases | |
| ModBase | Search... |
Protein-protein interaction databases | |
| STRING | Q8N6M6. |
Protein family/group databases | |
| MEROPS | M01.028. |
PTM databases | |
| PhosphoSite | Q8N6M6. |
Proteomic databases | |
| PRIDE | Q8N6M6. |
Genome annotation databases | |
| Ensembl | ENST00000375315; ENSP00000364464; ENSG00000148120; Homo sapiens. [Genome view] |
| GeneID | 84909. |
| KEGG | hsa:84909. |
| UCSC | uc004aux.1. human. uc004auy.1. human. uc004auz.1. human. uc004ava.1. human. |
Organism-specific databases | |
| CTD | 84909. |
| GeneCards | GC09P096528. |
| H-InvDB | HIX0008192. |
| HGNC | HGNC:1361. C9orf3. |
| HPA | HPA004633. |
| PharmGKB | PA25978. |
| GenAtlas | Search... |
Phylogenomic databases | |
| HOVERGEN | Q8N6M6. |
| OMA | FESQVIE |
Gene expression databases | |
| ArrayExpress | Q8N6M6. |
| Bgee | Q8N6M6. |
| CleanEx | HS_C9orf3. |
| Genevestigator | Q8N6M6. |
| GermOnline | ENSG00000148120. Homo sapiens. |
Family and domain databases | |
| InterPro | IPR016024. ARM-type_fold. IPR001930. Peptidase_M1. IPR015211. Peptidase_M1_C. IPR014782. Peptidase_M1_N. [Graphical view] |
| PANTHER | PTHR11533. Peptidase_M1. 1 hit. |
| Pfam | PF09127. Leuk-A4-hydro_C. 1 hit. PF01433. Peptidase_M1. 1 hit. [Graphical view] |
| PROSITE | PS00142. ZINC_PROTEASE. False negative. [Graphical view] |
| ProtoNet | Search... |
Other Resources | |
| NextBio | 75288. |
Entry information
| Entry name | AMPO_HUMAN | ||||||||
| Accession | Primary (citable) accession number: Q8N6M6 Secondary accession number(s): Q5T9B1 Q96SS1 | ||||||||
| Entry history |
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| Entry status | Reviewed (UniProtKB/Swiss-Prot) | ||||||||
| Annotation project | HPI (Human Proteome Initiative) | ||||||||
| 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. | ||||||||
Relevant documents
| Human chromosome 9 Human chromosome 9: entries, gene names and cross-references to MIM |
| Human entries with polymorphisms or disease mutations List of human entries with polymorphisms or disease mutations |
| Human polymorphisms and disease mutations Index of human polymorphisms and disease mutations |
| Peptidase families Classification of peptidase families and list of entries |
| SIMILARITY comments Index of protein domains and families |

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