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Protein

Aminopeptidase O

Gene

AOPEP

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

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.1 Publication

Cofactori

Zn2+By similarityNote: Binds 1 zinc ion per subunit.By similarity

Activity regulationi

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.1 Publication

Kineticsi

  1. KM=6 µM for Arg-AMC1 Publication

    Sites

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Metal bindingi479Zinc; catalyticBy similarity1
    Active sitei480Proton acceptorBy similarity1
    Metal bindingi483Zinc; catalyticBy similarity1
    Metal bindingi502Zinc; catalyticBy similarity1
    Sitei586Transition state stabilizerBy similarity1

    GO - Molecular functioni

    GO - Biological processi

    Keywordsi

    Molecular functionAminopeptidase, Hydrolase, Metalloprotease, Protease
    LigandMetal-binding, Zinc

    Enzyme and pathway databases

    ReactomeiR-HSA-2022377 Metabolism of Angiotensinogen to Angiotensins
    SABIO-RKiQ8N6M6

    Protein family/group databases

    MEROPSiM01.028

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Aminopeptidase O (EC:3.4.11.-)
    Short name:
    AP-O
    Gene namesi
    Name:AOPEP
    Synonyms:C9orf3, ONPEP
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    Proteomesi
    • UP000005640 Componenti: Chromosome 9

    Organism-specific databases

    EuPathDBiHostDB:ENSG00000148120.14
    HGNCiHGNC:1361 C9orf3
    neXtProtiNX_Q8N6M6

    Subcellular locationi

    Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

    Keywords - Cellular componenti

    Cytoplasm

    Pathology & Biotechi

    Organism-specific databases

    DisGeNETi84909
    OpenTargetsiENSG00000148120
    PharmGKBiPA25978

    Chemistry databases

    ChEMBLiCHEMBL3831223

    Polymorphism and mutation databases

    BioMutaiAOPEP
    DMDMi61211648

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    ChainiPRO_00000950911 – 819Aminopeptidase OAdd BLAST819

    Proteomic databases

    PaxDbiQ8N6M6
    PeptideAtlasiQ8N6M6
    PRIDEiQ8N6M6
    ProteomicsDBi72195
    72196 [Q8N6M6-2]
    72197 [Q8N6M6-3]
    72198 [Q8N6M6-4]

    PTM databases

    iPTMnetiQ8N6M6
    PhosphoSitePlusiQ8N6M6

    Expressioni

    Tissue specificityi

    Predominantly expressed in pancreas, placenta, liver, testis and heart. Expressed at lower level in brain, lung and kidney.1 Publication

    Gene expression databases

    BgeeiENSG00000148120 Expressed in 226 organ(s), highest expression level in thoracic aorta
    CleanExiHS_C9orf3
    ExpressionAtlasiQ8N6M6 baseline and differential
    GenevisibleiQ8N6M6 HS

    Organism-specific databases

    HPAiHPA004633
    HPA072729

    Interactioni

    Protein-protein interaction databases

    BioGridi124346, 9 interactors
    IntActiQ8N6M6, 9 interactors
    MINTiQ8N6M6
    STRINGi9606.ENSP00000364464

    Structurei

    3D structure databases

    ProteinModelPortaliQ8N6M6
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Sequence similaritiesi

    Belongs to the peptidase M1 family.Curated

    Phylogenomic databases

    eggNOGiKOG1047 Eukaryota
    COG0308 LUCA
    GeneTreeiENSGT00530000063003
    HOVERGENiHBG050496
    InParanoidiQ8N6M6
    KOiK09606
    OMAiIFQDWLE
    OrthoDBiEOG091G0243
    PhylomeDBiQ8N6M6
    TreeFamiTF332004

    Family and domain databases

    Gene3Di1.25.40.320, 1 hit
    InterProiView protein in InterPro
    IPR033577 AOPep
    IPR016024 ARM-type_fold
    IPR038502 M1_LTA-4_hydro/amino_C_sf
    IPR001930 Peptidase_M1
    IPR015211 Peptidase_M1_C
    IPR014782 Peptidase_M1_N
    PANTHERiPTHR11533 PTHR11533, 1 hit
    PTHR11533:SF175 PTHR11533:SF175, 1 hit
    PfamiView protein in Pfam
    PF09127 Leuk-A4-hydro_C, 1 hit
    PF01433 Peptidase_M1, 1 hit
    SMARTiView protein in SMART
    SM01263 Leuk-A4-hydro_C, 1 hit
    SUPFAMiSSF48371 SSF48371, 1 hit

    Sequences (4+)i

    Sequence statusi: Complete.

    This entry describes 4 isoformsi produced by alternative splicing. AlignAdd to basket

    This entry has 4 described isoforms and 6 potential isoforms that are computationally mapped.Show allAlign All

    Isoform 1 (identifier: Q8N6M6-1) [UniParc]FASTAAdd to basket

    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.

    « Hide
            10         20         30         40         50
    MDIQLDPARD DLPLMANTSH ILVKHYVLDL DVDFESQVIE GTIVLFLEDG
    60 70 80 90 100
    NRFKKQNSSI EEACQSESNK ACKFGMPEPC HIPVTNARTF SSEMEYNDFA
    110 120 130 140 150
    ICSKGEKDTS DKDGNHDNQE HASGISSSKY CCDTGNHGSE DFLLVLDCCD
    160 170 180 190 200
    LSVLKVEEVD VAAVPGLEKF TRSPELTVVS EEFRNQIVRE LVTLPANRWR
    210 220 230 240 250
    EQLDYYARCS QAPGCGELLF DTDTWSLQIR KTGAQTATDF PHAIRIWYKT
    260 270 280 290 300
    KPEGRSVTWT SDQSGRPCVY TVGSPINNRA LFPCQEPPVA MSTWQATVRA
    310 320 330 340 350
    AASFVVLMSG ENSAKPTQLW EECSSWYYYV TMPMPASTFT IAVGCWTEMK
    360 370 380 390 400
    METWSSNDLA TERPFSPSEA NFRHVGVCSH MEYPCRFQNA SATTQEIIPH
    410 420 430 440 450
    RVFAPVCLTG ACQETLLRLI PPCLSAAHSV LGAHPFSRLD VLIVPANFPS
    460 470 480 490 500
    LGMASPHIMF LSQSILTGGN HLCGTRLCHE IAHAWFGLAI GARDWTEEWL
    510 520 530 540 550
    SEGFATHLED VFWATAQQLA PYEAREQQEL RACLRWRRLQ DEMQCSPEEM
    560 570 580 590 600
    QVLRPSKDKT GHTSDSGASV IKHGLNPEKI FMQVHYLKGY FLLRFLAKRL
    610 620 630 640 650
    GDETYFSFLR KFVHTFHGQL ILSQDFLQML LENIPEEKRL ELSVENIYQD
    660 670 680 690 700
    WLESSGIPKP LQRERRAGAE CGLARQVRAE VTKWIGVNRR PRKRKRREKE
    710 720 730 740 750
    EVFEKLLPDQ LVLLLEHLLE QKTLSPRTLQ SLQRTYHLQD QDAEVRHRWC
    760 770 780 790 800
    ELIVKHKFTK AYKSVERFLQ EDQAMGVYLY GELMVSEDAR QQQLARRCFE
    810
    RTKEQMDRSS AQVVAEMLF
    Length:819
    Mass (Da):93,572
    Last modified:March 15, 2005 - v2
    Checksum:i9EB4F19295B92674
    GO
    Isoform 2 (identifier: Q8N6M6-2) [UniParc]FASTAAdd to basket

    The sequence of this isoform differs from the canonical sequence as follows:
         455-553: Missing.

    Show »
    Length:720
    Mass (Da):82,105
    Checksum:i12A6A6169C56A627
    GO
    Isoform 3 (identifier: Q8N6M6-3) [UniParc]FASTAAdd to basket

    The sequence of this isoform differs from the canonical sequence as follows:
         555-565: PSKDKTGHTSD → FPHVGGCSGSFS
         566-819: Missing.

    Note: No experimental confirmation available.
    Show »
    Length:566
    Mass (Da):63,363
    Checksum:i3E9D4D00E45C2A46
    GO
    Isoform 4 (identifier: Q8N6M6-4) [UniParc]FASTAAdd to basket

    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.
    Show »
    Length:685
    Mass (Da):77,937
    Checksum:i57667BB61D258FD2
    GO

    Computationally mapped potential isoform sequencesi

    There are 6 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
    EntryEntry nameProtein names
    Gene namesLengthAnnotation
    H0Y7M4H0Y7M4_HUMAN
    Chromosome 9 open reading frame 3
    C9orf3
    184Annotation score:
    H0YCM2H0YCM2_HUMAN
    Chromosome 9 open reading frame 3
    C9orf3
    180Annotation score:
    A0A0A0MSU0A0A0A0MSU0_HUMAN
    Chromosome 9 open reading frame 3
    C9orf3
    508Annotation score:
    A0A0A0MST7A0A0A0MST7_HUMAN
    Chromosome 9 open reading frame 3
    C9orf3
    601Annotation score:
    H0Y7A8H0Y7A8_HUMAN
    Chromosome 9 open reading frame 3
    C9orf3
    145Annotation score:
    X6RBX4X6RBX4_HUMAN
    Chromosome 9 open reading frame 3
    C9orf3
    140Annotation score:

    Sequence cautioni

    The sequence AAH20194 differs from that shown. Reason: Erroneous initiation.Curated
    The sequence BAB55210 differs from that shown. Reason: Erroneous initiation.Curated

    Natural variant

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Natural variantiVAR_021511179V → A. Corresponds to variant dbSNP:rs16911679Ensembl.1
    Natural variantiVAR_057053179V → I. Corresponds to variant dbSNP:rs16911679Ensembl.1
    Natural variantiVAR_057054255R → Q. Corresponds to variant dbSNP:rs16911681Ensembl.1
    Natural variantiVAR_057055386R → C. Corresponds to variant dbSNP:rs34557833Ensembl.1

    Alternative sequence

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Alternative sequenceiVSP_013161455 – 553Missing in isoform 2 and isoform 4. 2 PublicationsAdd BLAST99
    Alternative sequenceiVSP_013162555 – 565PSKDKTGHTSD → FPHVGGCSGSFS in isoform 3. 1 PublicationAdd BLAST11
    Alternative sequenceiVSP_013163566 – 819Missing in isoform 3. 1 PublicationAdd BLAST254
    Alternative sequenceiVSP_013164774 – 784AMGVYLYGELM → VGVIFQQMGIL in isoform 4. 1 PublicationAdd BLAST11
    Alternative sequenceiVSP_013165785 – 819Missing in isoform 4. 1 PublicationAdd BLAST35

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    AJ560639 mRNA Translation: CAD90259.1
    AK027581 mRNA Translation: BAB55210.1 Different initiation.
    AK057450 mRNA Translation: BAB71491.1
    AL157936 Genomic DNA No translation available.
    AL353768 Genomic DNA No translation available.
    AL354893 Genomic DNA No translation available.
    BC020194 mRNA Translation: AAH20194.1 Different initiation.
    BC029616 mRNA Translation: AAH29616.1
    CCDSiCCDS55327.1 [Q8N6M6-3]
    CCDS55328.1 [Q8N6M6-1]
    CCDS6713.1 [Q8N6M6-2]
    RefSeqiNP_001180258.1, NM_001193329.1 [Q8N6M6-1]
    NP_001180260.1, NM_001193331.2 [Q8N6M6-3]
    NP_116212.3, NM_032823.5 [Q8N6M6-2]
    XP_006717369.1, XM_006717306.1 [Q8N6M6-1]
    XP_016870719.1, XM_017015230.1 [Q8N6M6-1]
    XP_016870720.1, XM_017015231.1 [Q8N6M6-2]
    UniGeneiHs.434253
    Hs.655466
    Hs.675327

    Genome annotation databases

    EnsembliENST00000277198; ENSP00000277198; ENSG00000148120 [Q8N6M6-3]
    ENST00000297979; ENSP00000297979; ENSG00000148120 [Q8N6M6-2]
    ENST00000375315; ENSP00000364464; ENSG00000148120 [Q8N6M6-1]
    GeneIDi84909
    KEGGihsa:84909
    UCSCiuc004aux.3 human [Q8N6M6-1]

    Keywords - Coding sequence diversityi

    Alternative splicing, Polymorphism

    Similar proteinsi

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    AJ560639 mRNA Translation: CAD90259.1
    AK027581 mRNA Translation: BAB55210.1 Different initiation.
    AK057450 mRNA Translation: BAB71491.1
    AL157936 Genomic DNA No translation available.
    AL353768 Genomic DNA No translation available.
    AL354893 Genomic DNA No translation available.
    BC020194 mRNA Translation: AAH20194.1 Different initiation.
    BC029616 mRNA Translation: AAH29616.1
    CCDSiCCDS55327.1 [Q8N6M6-3]
    CCDS55328.1 [Q8N6M6-1]
    CCDS6713.1 [Q8N6M6-2]
    RefSeqiNP_001180258.1, NM_001193329.1 [Q8N6M6-1]
    NP_001180260.1, NM_001193331.2 [Q8N6M6-3]
    NP_116212.3, NM_032823.5 [Q8N6M6-2]
    XP_006717369.1, XM_006717306.1 [Q8N6M6-1]
    XP_016870719.1, XM_017015230.1 [Q8N6M6-1]
    XP_016870720.1, XM_017015231.1 [Q8N6M6-2]
    UniGeneiHs.434253
    Hs.655466
    Hs.675327

    3D structure databases

    ProteinModelPortaliQ8N6M6
    ModBaseiSearch...
    MobiDBiSearch...

    Protein-protein interaction databases

    BioGridi124346, 9 interactors
    IntActiQ8N6M6, 9 interactors
    MINTiQ8N6M6
    STRINGi9606.ENSP00000364464

    Chemistry databases

    ChEMBLiCHEMBL3831223

    Protein family/group databases

    MEROPSiM01.028

    PTM databases

    iPTMnetiQ8N6M6
    PhosphoSitePlusiQ8N6M6

    Polymorphism and mutation databases

    BioMutaiAOPEP
    DMDMi61211648

    Proteomic databases

    PaxDbiQ8N6M6
    PeptideAtlasiQ8N6M6
    PRIDEiQ8N6M6
    ProteomicsDBi72195
    72196 [Q8N6M6-2]
    72197 [Q8N6M6-3]
    72198 [Q8N6M6-4]

    Protocols and materials databases

    Structural Biology KnowledgebaseSearch...

    Genome annotation databases

    EnsembliENST00000277198; ENSP00000277198; ENSG00000148120 [Q8N6M6-3]
    ENST00000297979; ENSP00000297979; ENSG00000148120 [Q8N6M6-2]
    ENST00000375315; ENSP00000364464; ENSG00000148120 [Q8N6M6-1]
    GeneIDi84909
    KEGGihsa:84909
    UCSCiuc004aux.3 human [Q8N6M6-1]

    Organism-specific databases

    CTDi84909
    DisGeNETi84909
    EuPathDBiHostDB:ENSG00000148120.14
    GeneCardsiC9orf3
    HGNCiHGNC:1361 C9orf3
    HPAiHPA004633
    HPA072729
    neXtProtiNX_Q8N6M6
    OpenTargetsiENSG00000148120
    PharmGKBiPA25978
    GenAtlasiSearch...

    Phylogenomic databases

    eggNOGiKOG1047 Eukaryota
    COG0308 LUCA
    GeneTreeiENSGT00530000063003
    HOVERGENiHBG050496
    InParanoidiQ8N6M6
    KOiK09606
    OMAiIFQDWLE
    OrthoDBiEOG091G0243
    PhylomeDBiQ8N6M6
    TreeFamiTF332004

    Enzyme and pathway databases

    ReactomeiR-HSA-2022377 Metabolism of Angiotensinogen to Angiotensins
    SABIO-RKiQ8N6M6

    Miscellaneous databases

    ChiTaRSiC9orf3 human
    GenomeRNAii84909
    PROiPR:Q8N6M6

    Gene expression databases

    BgeeiENSG00000148120 Expressed in 226 organ(s), highest expression level in thoracic aorta
    CleanExiHS_C9orf3
    ExpressionAtlasiQ8N6M6 baseline and differential
    GenevisibleiQ8N6M6 HS

    Family and domain databases

    Gene3Di1.25.40.320, 1 hit
    InterProiView protein in InterPro
    IPR033577 AOPep
    IPR016024 ARM-type_fold
    IPR038502 M1_LTA-4_hydro/amino_C_sf
    IPR001930 Peptidase_M1
    IPR015211 Peptidase_M1_C
    IPR014782 Peptidase_M1_N
    PANTHERiPTHR11533 PTHR11533, 1 hit
    PTHR11533:SF175 PTHR11533:SF175, 1 hit
    PfamiView protein in Pfam
    PF09127 Leuk-A4-hydro_C, 1 hit
    PF01433 Peptidase_M1, 1 hit
    SMARTiView protein in SMART
    SM01263 Leuk-A4-hydro_C, 1 hit
    SUPFAMiSSF48371 SSF48371, 1 hit
    ProtoNetiSearch...

    Entry informationi

    Entry nameiAMPO_HUMAN
    AccessioniPrimary (citable) accession number: Q8N6M6
    Secondary accession number(s): Q5T9B1
    , Q5T9B3, Q5T9B4, Q8WUL6, Q96M23, Q96SS1
    Entry historyiIntegrated into UniProtKB/Swiss-Prot: March 15, 2005
    Last sequence update: March 15, 2005
    Last modified: November 7, 2018
    This is version 135 of the entry and version 2 of the sequence. See complete history.
    Entry statusiReviewed (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.

    Miscellaneousi

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. SIMILARITY comments
      Index of protein domains and families
    2. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    3. Peptidase families
      Classification of peptidase families and list of entries
    4. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    5. Human chromosome 9
      Human chromosome 9: entries, gene names and cross-references to MIM
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