MAP12_HUMAN
ID MAP12_HUMAN Reviewed; 335 AA.
AC Q6UB28; Q1WNX3;
DT 15-JAN-2008, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2004, sequence version 1.
DT 03-AUG-2022, entry version 140.
DE RecName: Full=Methionine aminopeptidase 1D, mitochondrial {ECO:0000255|HAMAP-Rule:MF_03174};
DE Short=MAP 1D {ECO:0000255|HAMAP-Rule:MF_03174};
DE Short=MetAP 1D {ECO:0000255|HAMAP-Rule:MF_03174};
DE EC=3.4.11.18 {ECO:0000255|HAMAP-Rule:MF_03174};
DE AltName: Full=Methionyl aminopeptidase type 1D, mitochondrial;
DE AltName: Full=Peptidase M 1D {ECO:0000255|HAMAP-Rule:MF_03174};
DE Flags: Precursor;
GN Name=METAP1D; Synonyms=MAP1D;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND SUBCELLULAR LOCATION.
RX PubMed=14532271; DOI=10.1074/jbc.m309770200;
RA Serero A., Giglione C., Sardini A., Martinez-Sanz J., Meinnel T.;
RT "An unusual peptide deformylase features in the human mitochondrial N-
RT terminal methionine excision pathway.";
RL J. Biol. Chem. 278:52953-52963(2003).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, TISSUE SPECIFICITY, AND VARIANT
RP VAL-14.
RX PubMed=16568094; DOI=10.1038/sj.onc.1209383;
RA Leszczyniecka M., Bhatia U., Cueto M., Nirmala N.R., Towbin H., Vattay A.,
RA Wang B., Zabludoff S., Phillips P.E.;
RT "MAP1D, a novel methionine aminopeptidase family member is overexpressed in
RT colon cancer.";
RL Oncogene 25:3471-3478(2006).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP COFACTOR, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=17929833; DOI=10.1021/bi701127x;
RA Hu X.V., Chen X., Han K.C., Mildvan A.S., Liu J.O.;
RT "Kinetic and mutational studies of the number of interacting divalent
RT cations required by bacterial and human methionine aminopeptidases.";
RL Biochemistry 46:12833-12843(2007).
RN [6]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25944712; DOI=10.1002/pmic.201400617;
RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT "N-terminome analysis of the human mitochondrial proteome.";
RL Proteomics 15:2519-2524(2015).
CC -!- FUNCTION: Removes the N-terminal methionine from nascent proteins. The
CC N-terminal methionine is often cleaved when the second residue in the
CC primary sequence is small and uncharged (Met-Ala-, Cys, Gly, Pro, Ser,
CC Thr, or Val). Requires deformylation of the N(alpha)-formylated
CC initiator methionine before it can be hydrolyzed (By similarity). May
CC play a role in colon tumorigenesis. {ECO:0000255|HAMAP-Rule:MF_03174,
CC ECO:0000269|PubMed:16568094}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Release of N-terminal amino acids, preferentially methionine,
CC from peptides and arylamides.; EC=3.4.11.18;
CC Evidence={ECO:0000255|HAMAP-Rule:MF_03174};
CC -!- COFACTOR:
CC Name=Co(2+); Xref=ChEBI:CHEBI:48828;
CC Evidence={ECO:0000255|HAMAP-Rule:MF_03174};
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000255|HAMAP-Rule:MF_03174};
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC Evidence={ECO:0000255|HAMAP-Rule:MF_03174};
CC Name=Fe(2+); Xref=ChEBI:CHEBI:29033;
CC Evidence={ECO:0000255|HAMAP-Rule:MF_03174};
CC Note=Binds 2 divalent metal cations per subunit. Has a high-affinity
CC and a low affinity metal-binding site. The true nature of the
CC physiological cofactor is under debate. The enzyme is active with
CC cobalt, zinc, manganese or divalent iron ions. Most likely, methionine
CC aminopeptidases function as mononuclear Fe(2+)-metalloproteases under
CC physiological conditions, and the catalytically relevant metal-binding
CC site has been assigned to the histidine-containing high-affinity site.
CC {ECO:0000255|HAMAP-Rule:MF_03174};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=573 uM for Met-pro-p-nitroanilide (at pH 8)
CC {ECO:0000269|PubMed:17929833};
CC pH dependence:
CC Optimum pH is 7.5-8.0. {ECO:0000269|PubMed:17929833};
CC -!- SUBCELLULAR LOCATION: Mitochondrion {ECO:0000255|HAMAP-Rule:MF_03174,
CC ECO:0000269|PubMed:14532271}.
CC -!- TISSUE SPECIFICITY: Overexpressed in colon cancer cell lines and colon
CC tumors as compared to normal tissues (at protein level).
CC {ECO:0000269|PubMed:16568094}.
CC -!- SIMILARITY: Belongs to the peptidase M24A family. Methionine
CC aminopeptidase type 1 subfamily. {ECO:0000255|HAMAP-Rule:MF_03174}.
CC -!- CAUTION: It is uncertain whether Met-1 or a Met upstream of this
CC sequence is the initiator. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAY55948.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; AY374142; AAR27795.1; -; mRNA.
DR EMBL; DQ005576; AAY55948.1; ALT_INIT; mRNA.
DR EMBL; CH471058; EAX11190.1; -; Genomic_DNA.
DR EMBL; BC113644; AAI13645.1; -; mRNA.
DR CCDS; CCDS2246.1; -.
DR RefSeq; NP_001309207.1; NM_001322278.1.
DR RefSeq; NP_001309208.1; NM_001322279.1.
DR RefSeq; NP_954697.1; NM_199227.2.
DR AlphaFoldDB; Q6UB28; -.
DR SMR; Q6UB28; -.
DR BioGRID; 129008; 13.
DR IntAct; Q6UB28; 6.
DR STRING; 9606.ENSP00000315152; -.
DR ChEMBL; CHEMBL3831223; -.
DR MEROPS; M24.028; -.
DR iPTMnet; Q6UB28; -.
DR PhosphoSitePlus; Q6UB28; -.
DR BioMuta; METAP1D; -.
DR DMDM; 74710242; -.
DR EPD; Q6UB28; -.
DR jPOST; Q6UB28; -.
DR MassIVE; Q6UB28; -.
DR MaxQB; Q6UB28; -.
DR PaxDb; Q6UB28; -.
DR PeptideAtlas; Q6UB28; -.
DR PRIDE; Q6UB28; -.
DR ProteomicsDB; 67401; -.
DR Antibodypedia; 33857; 115 antibodies from 18 providers.
DR DNASU; 254042; -.
DR Ensembl; ENST00000315796.5; ENSP00000315152.4; ENSG00000172878.14.
DR GeneID; 254042; -.
DR KEGG; hsa:254042; -.
DR MANE-Select; ENST00000315796.5; ENSP00000315152.4; NM_199227.3; NP_954697.1.
DR UCSC; uc002uhk.4; human.
DR CTD; 254042; -.
DR DisGeNET; 254042; -.
DR GeneCards; METAP1D; -.
DR HGNC; HGNC:32583; METAP1D.
DR HPA; ENSG00000172878; Low tissue specificity.
DR MIM; 610267; gene.
DR neXtProt; NX_Q6UB28; -.
DR OpenTargets; ENSG00000172878; -.
DR VEuPathDB; HostDB:ENSG00000172878; -.
DR eggNOG; KOG2738; Eukaryota.
DR GeneTree; ENSGT00940000157735; -.
DR HOGENOM; CLU_015857_1_1_1; -.
DR InParanoid; Q6UB28; -.
DR OMA; RGAESCY; -.
DR OrthoDB; 1002357at2759; -.
DR PhylomeDB; Q6UB28; -.
DR TreeFam; TF325318; -.
DR BRENDA; 3.4.11.18; 2681.
DR PathwayCommons; Q6UB28; -.
DR SABIO-RK; Q6UB28; -.
DR SignaLink; Q6UB28; -.
DR BioGRID-ORCS; 254042; 17 hits in 1078 CRISPR screens.
DR ChiTaRS; METAP1D; human.
DR GenomeRNAi; 254042; -.
DR Pharos; Q6UB28; Tbio.
DR PRO; PR:Q6UB28; -.
DR Proteomes; UP000005640; Chromosome 2.
DR RNAct; Q6UB28; protein.
DR Bgee; ENSG00000172878; Expressed in oviduct epithelium and 152 other tissues.
DR Genevisible; Q6UB28; HS.
DR GO; GO:0005739; C:mitochondrion; IDA:HGNC-UCL.
DR GO; GO:0004177; F:aminopeptidase activity; TAS:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-UniRule.
DR GO; GO:0070006; F:metalloaminopeptidase activity; IBA:GO_Central.
DR GO; GO:0008235; F:metalloexopeptidase activity; TAS:UniProtKB.
DR GO; GO:0031365; P:N-terminal protein amino acid modification; TAS:HGNC-UCL.
DR GO; GO:0018206; P:peptidyl-methionine modification; TAS:HGNC-UCL.
DR GO; GO:0070084; P:protein initiator methionine removal; IEA:UniProtKB-UniRule.
DR GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR CDD; cd01086; MetAP1; 1.
DR Gene3D; 3.90.230.10; -; 1.
DR HAMAP; MF_01974; MetAP_1; 1.
DR InterPro; IPR036005; Creatinase/aminopeptidase-like.
DR InterPro; IPR000994; Pept_M24.
DR InterPro; IPR001714; Pept_M24_MAP.
DR InterPro; IPR002467; Pept_M24A_MAP1.
DR Pfam; PF00557; Peptidase_M24; 1.
DR PRINTS; PR00599; MAPEPTIDASE.
DR SUPFAM; SSF55920; SSF55920; 1.
DR TIGRFAMs; TIGR00500; met_pdase_I; 1.
DR PROSITE; PS00680; MAP_1; 1.
PE 1: Evidence at protein level;
KW Aminopeptidase; Hydrolase; Metal-binding; Mitochondrion; Protease;
KW Reference proteome; Transit peptide.
FT TRANSIT 1..19
FT /note="Mitochondrion"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03174"
FT CHAIN 20..335
FT /note="Methionine aminopeptidase 1D, mitochondrial"
FT /id="PRO_0000314126"
FT BINDING 161
FT /ligand="substrate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03174"
FT BINDING 178
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /ligand_label="1"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03174"
FT BINDING 189
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /ligand_label="1"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03174"
FT BINDING 189
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /ligand_label="2"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03174"
FT BINDING 252
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /ligand_label="2"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03174"
FT BINDING 259
FT /ligand="substrate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03174"
FT BINDING 284
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /ligand_label="2"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03174"
FT BINDING 315
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /ligand_label="1"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03174"
FT BINDING 315
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /ligand_label="2"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03174"
FT VARIANT 14
FT /note="G -> V (in dbSNP:rs10497377)"
FT /evidence="ECO:0000269|PubMed:16568094"
FT /id="VAR_050273"
SQ SEQUENCE 335 AA; 37088 MW; 2EB90946DC983D7B CRC64;
MAAPSGVHLL VRRGSHRIFS SPLNHIYLHK QSSSQQRRNF FFRRQRDISH SIVLPAAVSS
AHPVPKHIKK PDYVTTGIVP DWGDSIEVKN EDQIQGLHQA CQLARHVLLL AGKSLKVDMT
TEEIDALVHR EIISHNAYPS PLGYGGFPKS VCTSVNNVLC HGIPDSRPLQ DGDIINIDVT
VYYNGYHGDT SETFLVGNVD ECGKKLVEVA RRCRDEAIAA CRAGAPFSVI GNTISHITHQ
NGFQVCPHFV GHGIGSYFHG HPEIWHHAND SDLPMEEGMA FTIEPIITEG SPEFKVLEDA
WTVVSLDNQR SAQFEHTVLI TSRGAQILTK LPHEA
