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Protein

Methionine aminopeptidase 1D, mitochondrial

Gene

METAP1D

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Removes the N-terminal methionine from nascent proteins. The N-terminal methionine is often cleaved when the second residue in the primary sequence is small and uncharged (Met-Ala-, Cys, Gly, Pro, Ser, Thr, or Val). Requires deformylation of the N(alpha)-formylated initiator methionine before it can be hydrolyzed (By similarity). May play a role in colon tumorigenesis.UniRule annotation1 Publication

Catalytic activityi

Release of N-terminal amino acids, preferentially methionine, from peptides and arylamides.UniRule annotation

Cofactori

Co2+UniRule annotation, Zn2+UniRule annotation, Mn2+UniRule annotation, Fe2+UniRule annotationNote: Binds 2 divalent metal cations per subunit. Has a high-affinity and a low affinity metal-binding site. The true nature of the physiological cofactor is under debate. The enzyme is active with cobalt, zinc, manganese or divalent iron ions. Most likely, methionine aminopeptidases function as mononuclear Fe2+-metalloproteases under physiological conditions, and the catalytically relevant metal-binding site has been assigned to the histidine-containing high-affinity site.UniRule annotation

Kineticsi

  1. KM=573 µM for Met-pro-p-nitroanilide (at pH 8)1 Publication

    pH dependencei

    Optimum pH is 7.5-8.0.1 Publication

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Binding sitei161 – 1611SubstrateUniRule annotation
    Metal bindingi178 – 1781Divalent metal cation 1UniRule annotation
    Metal bindingi189 – 1891Divalent metal cation 1UniRule annotation
    Metal bindingi189 – 1891Divalent metal cation 2; catalyticUniRule annotation
    Metal bindingi252 – 2521Divalent metal cation 2; catalytic; via tele nitrogenUniRule annotation
    Binding sitei259 – 2591SubstrateUniRule annotation
    Metal bindingi284 – 2841Divalent metal cation 2; catalyticUniRule annotation
    Metal bindingi315 – 3151Divalent metal cation 1UniRule annotation
    Metal bindingi315 – 3151Divalent metal cation 2; catalyticUniRule annotation

    GO - Molecular functioni

    • aminopeptidase activity Source: UniProtKB
    • metal ion binding Source: UniProtKB-HAMAP
    • metalloaminopeptidase activity Source: UniProtKB-HAMAP
    • metalloexopeptidase activity Source: UniProtKB

    GO - Biological processi

    • N-terminal protein amino acid modification Source: HGNC
    • peptidyl-methionine modification Source: HGNC
    • protein initiator methionine removal Source: UniProtKB-HAMAP
    Complete GO annotation...

    Keywords - Molecular functioni

    Aminopeptidase, Hydrolase, Protease

    Keywords - Ligandi

    Metal-binding

    Enzyme and pathway databases

    BRENDAi3.4.11.18. 2681.
    SABIO-RKQ6UB28.

    Protein family/group databases

    MEROPSiM24.028.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Methionine aminopeptidase 1D, mitochondrialUniRule annotation (EC:3.4.11.18UniRule annotation)
    Short name:
    MAP 1DUniRule annotation
    Short name:
    MetAP 1DUniRule annotation
    Alternative name(s):
    Methionyl aminopeptidase type 1D, mitochondrial
    Peptidase M 1DUniRule annotation
    Gene namesi
    Name:METAP1D
    Synonyms:MAP1D
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640 Componenti: Chromosome 2

    Organism-specific databases

    HGNCiHGNC:32583. METAP1D.

    Subcellular locationi

    • Mitochondrion UniRule annotation1 Publication

    GO - Cellular componenti

    • mitochondrion Source: HGNC
    Complete GO annotation...

    Keywords - Cellular componenti

    Mitochondrion

    Pathology & Biotechi

    Polymorphism and mutation databases

    BioMutaiMETAP1D.
    DMDMi74710242.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transit peptidei1 – 1919MitochondrionUniRule annotationAdd
    BLAST
    Chaini20 – 335316Methionine aminopeptidase 1D, mitochondrialPRO_0000314126Add
    BLAST

    Proteomic databases

    MaxQBiQ6UB28.
    PaxDbiQ6UB28.
    PRIDEiQ6UB28.

    PTM databases

    PhosphoSiteiQ6UB28.

    Expressioni

    Tissue specificityi

    Overexpressed in colon cancer cell lines and colon tumors as compared to normal tissues (at protein level).1 Publication

    Gene expression databases

    BgeeiQ6UB28.
    GenevisibleiQ6UB28. HS.

    Organism-specific databases

    HPAiHPA030298.
    HPA030299.

    Interactioni

    Protein-protein interaction databases

    BioGridi129008. 1 interaction.
    STRINGi9606.ENSP00000315152.

    Structurei

    3D structure databases

    ProteinModelPortaliQ6UB28.
    SMRiQ6UB28. Positions 63-330.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Sequence similaritiesi

    Belongs to the peptidase M24A family. Methionine aminopeptidase type 1 subfamily.UniRule annotation

    Keywords - Domaini

    Transit peptide

    Phylogenomic databases

    eggNOGiCOG0024.
    GeneTreeiENSGT00390000002284.
    HOGENOMiHOG000030427.
    HOVERGENiHBG067178.
    InParanoidiQ6UB28.
    KOiK01265.
    OMAiLNHIYLH.
    OrthoDBiEOG786H38.
    PhylomeDBiQ6UB28.
    TreeFamiTF325318.

    Family and domain databases

    Gene3Di3.90.230.10. 1 hit.
    HAMAPiMF_01974. MetAP_1.
    InterProiIPR001714. Pept_M24_MAP.
    IPR000994. Pept_M24_structural-domain.
    IPR002467. Pept_M24A_MAP1.
    [Graphical view]
    PfamiPF00557. Peptidase_M24. 1 hit.
    [Graphical view]
    PRINTSiPR00599. MAPEPTIDASE.
    SUPFAMiSSF55920. SSF55920. 1 hit.
    TIGRFAMsiTIGR00500. met_pdase_I. 1 hit.
    PROSITEiPS00680. MAP_1. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    Sequence processingi: The displayed sequence is further processed into a mature form.

    Q6UB28-1 [UniParc]FASTAAdd to basket

    « Hide

            10         20         30         40         50
    MAAPSGVHLL VRRGSHRIFS SPLNHIYLHK QSSSQQRRNF FFRRQRDISH
    60 70 80 90 100
    SIVLPAAVSS AHPVPKHIKK PDYVTTGIVP DWGDSIEVKN EDQIQGLHQA
    110 120 130 140 150
    CQLARHVLLL AGKSLKVDMT TEEIDALVHR EIISHNAYPS PLGYGGFPKS
    160 170 180 190 200
    VCTSVNNVLC HGIPDSRPLQ DGDIINIDVT VYYNGYHGDT SETFLVGNVD
    210 220 230 240 250
    ECGKKLVEVA RRCRDEAIAA CRAGAPFSVI GNTISHITHQ NGFQVCPHFV
    260 270 280 290 300
    GHGIGSYFHG HPEIWHHAND SDLPMEEGMA FTIEPIITEG SPEFKVLEDA
    310 320 330
    WTVVSLDNQR SAQFEHTVLI TSRGAQILTK LPHEA
    Length:335
    Mass (Da):37,088
    Last modified:July 5, 2004 - v1
    Checksum:i2EB90946DC983D7B
    GO

    Sequence cautioni

    The sequence AAY55948.1 differs from that shown. Reason: Erroneous initiation. Curated

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti14 – 141G → V.1 Publication
    Corresponds to variant rs10497377 [ dbSNP | Ensembl ].
    VAR_050273

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    AY374142 mRNA. Translation: AAR27795.1.
    DQ005576 mRNA. Translation: AAY55948.1. Different initiation.
    CH471058 Genomic DNA. Translation: EAX11190.1.
    BC113644 mRNA. Translation: AAI13645.1.
    CCDSiCCDS2246.1.
    RefSeqiNP_954697.1. NM_199227.1.
    UniGeneiHs.298250.

    Genome annotation databases

    EnsembliENST00000315796; ENSP00000315152; ENSG00000172878.
    GeneIDi254042.
    KEGGihsa:254042.
    UCSCiuc002uhk.3. human.

    Keywords - Coding sequence diversityi

    Polymorphism

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    AY374142 mRNA. Translation: AAR27795.1.
    DQ005576 mRNA. Translation: AAY55948.1. Different initiation.
    CH471058 Genomic DNA. Translation: EAX11190.1.
    BC113644 mRNA. Translation: AAI13645.1.
    CCDSiCCDS2246.1.
    RefSeqiNP_954697.1. NM_199227.1.
    UniGeneiHs.298250.

    3D structure databases

    ProteinModelPortaliQ6UB28.
    SMRiQ6UB28. Positions 63-330.
    ModBaseiSearch...
    MobiDBiSearch...

    Protein-protein interaction databases

    BioGridi129008. 1 interaction.
    STRINGi9606.ENSP00000315152.

    Protein family/group databases

    MEROPSiM24.028.

    PTM databases

    PhosphoSiteiQ6UB28.

    Polymorphism and mutation databases

    BioMutaiMETAP1D.
    DMDMi74710242.

    Proteomic databases

    MaxQBiQ6UB28.
    PaxDbiQ6UB28.
    PRIDEiQ6UB28.

    Protocols and materials databases

    DNASUi254042.
    Structural Biology KnowledgebaseSearch...

    Genome annotation databases

    EnsembliENST00000315796; ENSP00000315152; ENSG00000172878.
    GeneIDi254042.
    KEGGihsa:254042.
    UCSCiuc002uhk.3. human.

    Organism-specific databases

    CTDi254042.
    GeneCardsiGC02P172865.
    HGNCiHGNC:32583. METAP1D.
    HPAiHPA030298.
    HPA030299.
    MIMi610267. gene.
    neXtProtiNX_Q6UB28.
    GenAtlasiSearch...

    Phylogenomic databases

    eggNOGiCOG0024.
    GeneTreeiENSGT00390000002284.
    HOGENOMiHOG000030427.
    HOVERGENiHBG067178.
    InParanoidiQ6UB28.
    KOiK01265.
    OMAiLNHIYLH.
    OrthoDBiEOG786H38.
    PhylomeDBiQ6UB28.
    TreeFamiTF325318.

    Enzyme and pathway databases

    BRENDAi3.4.11.18. 2681.
    SABIO-RKQ6UB28.

    Miscellaneous databases

    ChiTaRSiMETAP1D. human.
    GenomeRNAii254042.
    NextBioi92234.
    PROiQ6UB28.
    SOURCEiSearch...

    Gene expression databases

    BgeeiQ6UB28.
    GenevisibleiQ6UB28. HS.

    Family and domain databases

    Gene3Di3.90.230.10. 1 hit.
    HAMAPiMF_01974. MetAP_1.
    InterProiIPR001714. Pept_M24_MAP.
    IPR000994. Pept_M24_structural-domain.
    IPR002467. Pept_M24A_MAP1.
    [Graphical view]
    PfamiPF00557. Peptidase_M24. 1 hit.
    [Graphical view]
    PRINTSiPR00599. MAPEPTIDASE.
    SUPFAMiSSF55920. SSF55920. 1 hit.
    TIGRFAMsiTIGR00500. met_pdase_I. 1 hit.
    PROSITEiPS00680. MAP_1. 1 hit.
    [Graphical view]
    ProtoNetiSearch...

    Publicationsi

    « Hide 'large scale' publications
    1. "An unusual peptide deformylase features in the human mitochondrial N-terminal methionine excision pathway."
      Serero A., Giglione C., Sardini A., Martinez-Sanz J., Meinnel T.
      J. Biol. Chem. 278:52953-52963(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA], SUBCELLULAR LOCATION.
    2. "MAP1D, a novel methionine aminopeptidase family member is overexpressed in colon cancer."
      Leszczyniecka M., Bhatia U., Cueto M., Nirmala N.R., Towbin H., Vattay A., Wang B., Zabludoff S., Phillips P.E.
      Oncogene 25:3471-3478(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, TISSUE SPECIFICITY, VARIANT VAL-14.
    3. 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] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
      Tissue: Brain.
    5. "Kinetic and mutational studies of the number of interacting divalent cations required by bacterial and human methionine aminopeptidases."
      Hu X.V., Chen X., Han K.C., Mildvan A.S., Liu J.O.
      Biochemistry 46:12833-12843(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: COFACTOR, BIOPHYSICOCHEMICAL PROPERTIES.

    Entry informationi

    Entry nameiMAP12_HUMAN
    AccessioniPrimary (citable) accession number: Q6UB28
    Secondary accession number(s): Q1WNX3
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: January 15, 2008
    Last sequence update: July 5, 2004
    Last modified: July 22, 2015
    This is version 98 of the entry and version 1 of the sequence. [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

    Caution

    It is uncertain whether Met-1 or a Met upstream of this sequence is the initiator.Curated

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. Human chromosome 2
      Human chromosome 2: entries, gene names and cross-references to MIM
    2. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    3. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    4. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    5. Peptidase families
      Classification of peptidase families and list of entries
    6. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3

    Similar proteinsi

    Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
    100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
    90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
    50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.