MAP2_CAEEL
ID MAP2_CAEEL Reviewed; 468 AA.
AC H1UBK1; H1UBK2; Q9U2V9;
DT 16-OCT-2019, integrated into UniProtKB/Swiss-Prot.
DT 21-MAR-2012, sequence version 1.
DT 03-AUG-2022, entry version 86.
DE RecName: Full=Methionine aminopeptidase 2 {ECO:0000255|HAMAP-Rule:MF_03175};
DE Short=MAP 2 {ECO:0000255|HAMAP-Rule:MF_03175};
DE Short=MetAP 2 {ECO:0000255|HAMAP-Rule:MF_03175};
DE EC=3.4.11.18 {ECO:0000269|PubMed:15474045};
DE AltName: Full=Peptidase M {ECO:0000255|HAMAP-Rule:MF_03175};
GN Name=map-2 {ECO:0000303|PubMed:15474045, ECO:0000312|WormBase:Y116A8A.9b};
GN ORFNames=Y116A8A.9 {ECO:0000312|WormBase:Y116A8A.9b};
OS Caenorhabditis elegans.
OC Eukaryota; Metazoa; Ecdysozoa; Nematoda; Chromadorea; Rhabditida;
OC Rhabditina; Rhabditomorpha; Rhabditoidea; Rhabditidae; Peloderinae;
OC Caenorhabditis.
OX NCBI_TaxID=6239 {ECO:0000312|Proteomes:UP000001940};
RN [1] {ECO:0000312|Proteomes:UP000001940}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Bristol N2 {ECO:0000312|Proteomes:UP000001940};
RX PubMed=9851916; DOI=10.1126/science.282.5396.2012;
RG The C. elegans sequencing consortium;
RT "Genome sequence of the nematode C. elegans: a platform for investigating
RT biology.";
RL Science 282:2012-2018(1998).
RN [2] {ECO:0000305}
RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, AND DISRUPTION
RP PHENOTYPE.
RX PubMed=15474045; DOI=10.1016/j.febslet.2004.08.077;
RA Boxem M., Tsai C.W., Zhang Y., Saito R.M., Liu J.O.;
RT "The C. elegans methionine aminopeptidase 2 analog map-2 is required for
RT germ cell proliferation.";
RL FEBS Lett. 576:245-250(2004).
CC -!- FUNCTION: Cotranslationally removes the N-terminal methionine from
CC nascent proteins (PubMed:15474045). The N-terminal methionine is often
CC cleaved when the second residue in the primary sequence is small and
CC uncharged (Met-Ala-, Cys, Gly, Pro, Ser, Thr, or Val)
CC (PubMed:15474045). Required for germ cell proliferation and/or
CC differentiation (PubMed:15474045). {ECO:0000269|PubMed:15474045}.
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:0000269|PubMed:15474045};
CC -!- COFACTOR:
CC Name=Co(2+); Xref=ChEBI:CHEBI:48828;
CC Evidence={ECO:0000255|HAMAP-Rule:MF_03175,
CC ECO:0000255|RuleBase:RU003653};
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000255|HAMAP-Rule:MF_03175,
CC ECO:0000255|RuleBase:RU003653};
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC Evidence={ECO:0000255|HAMAP-Rule:MF_03175,
CC ECO:0000255|RuleBase:RU003653};
CC Name=Fe(2+); Xref=ChEBI:CHEBI:29033;
CC Evidence={ECO:0000255|HAMAP-Rule:MF_03175,
CC ECO:0000255|RuleBase:RU003653};
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_03175, ECO:0000255|RuleBase:RU003653};
CC -!- ACTIVITY REGULATION: Inhibited by the fumagillin analog, TNP-470.
CC {ECO:0000269|PubMed:15474045}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000255, ECO:0000255|HAMAP-
CC Rule:MF_03175}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=b {ECO:0000312|WormBase:Y116A8A.9b};
CC IsoId=H1UBK1-1; Sequence=Displayed;
CC Name=a {ECO:0000312|WormBase:Y116A8A.9a};
CC IsoId=H1UBK1-2; Sequence=VSP_060368;
CC Name=c {ECO:0000312|WormBase:Y116A8A.9c};
CC IsoId=H1UBK1-3; Sequence=VSP_060368, VSP_060369;
CC -!- DISRUPTION PHENOTYPE: RNAi-mediated knockdown causes sterility due to a
CC defect in germ cell proliferation and/or differentiation.
CC {ECO:0000269|PubMed:15474045}.
CC -!- SIMILARITY: Belongs to the peptidase M24A family. Methionine
CC aminopeptidase eukaryotic type 2 subfamily. {ECO:0000255,
CC ECO:0000255|HAMAP-Rule:MF_03175}.
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DR EMBL; BX284604; CAB55167.1; -; Genomic_DNA.
DR EMBL; BX284604; CCF23399.1; -; Genomic_DNA.
DR EMBL; BX284604; CCF23400.1; -; Genomic_DNA.
DR RefSeq; NP_001255905.1; NM_001268976.1.
DR RefSeq; NP_001255906.1; NM_001268977.1. [H1UBK1-2]
DR RefSeq; NP_001255907.1; NM_001268978.1. [H1UBK1-1]
DR AlphaFoldDB; H1UBK1; -.
DR SMR; H1UBK1; -.
DR STRING; 6239.Y116A8A.9b.2; -.
DR MEROPS; M24.002; -.
DR PaxDb; H1UBK1; -.
DR PeptideAtlas; H1UBK1; -.
DR EnsemblMetazoa; Y116A8A.9a.1; Y116A8A.9a.1; WBGene00003130. [H1UBK1-2]
DR EnsemblMetazoa; Y116A8A.9b.1; Y116A8A.9b.1; WBGene00003130. [H1UBK1-1]
DR EnsemblMetazoa; Y116A8A.9c.1; Y116A8A.9c.1; WBGene00003130. [H1UBK1-3]
DR GeneID; 178468; -.
DR UCSC; Y116A8A.9.2; c. elegans.
DR CTD; 178468; -.
DR WormBase; Y116A8A.9a; CE24146; WBGene00003130; map-2. [H1UBK1-2]
DR WormBase; Y116A8A.9b; CE47033; WBGene00003130; map-2. [H1UBK1-1]
DR WormBase; Y116A8A.9c; CE46993; WBGene00003130; map-2. [H1UBK1-3]
DR eggNOG; KOG2775; Eukaryota.
DR GeneTree; ENSGT00940000172436; -.
DR HOGENOM; CLU_015857_7_2_1; -.
DR InParanoid; H1UBK1; -.
DR OMA; MESHTVE; -.
DR OrthoDB; 601484at2759; -.
DR PhylomeDB; H1UBK1; -.
DR Reactome; R-CEL-2514859; Inactivation, recovery and regulation of the phototransduction cascade.
DR PRO; PR:H1UBK1; -.
DR Proteomes; UP000001940; Chromosome IV.
DR Bgee; WBGene00003130; Expressed in larva and 4 other tissues.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0004177; F:aminopeptidase activity; IBA:GO_Central.
DR GO; GO:0008238; F:exopeptidase activity; IDA:WormBase.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-UniRule.
DR GO; GO:0070006; F:metalloaminopeptidase activity; IEA:UniProtKB-UniRule.
DR GO; GO:0008235; F:metalloexopeptidase activity; IBA:GO_Central.
DR GO; GO:0036093; P:germ cell proliferation; IMP:WormBase.
DR GO; GO:0035551; P:protein initiator methionine removal involved in protein maturation; IBA:GO_Central.
DR CDD; cd01088; MetAP2; 1.
DR Gene3D; 1.10.10.10; -; 1.
DR Gene3D; 3.90.230.10; -; 1.
DR HAMAP; MF_03175; MetAP_2_euk; 1.
DR InterPro; IPR036005; Creatinase/aminopeptidase-like.
DR InterPro; IPR000994; Pept_M24.
DR InterPro; IPR001714; Pept_M24_MAP.
DR InterPro; IPR002468; Pept_M24A_MAP2.
DR InterPro; IPR036388; WH-like_DNA-bd_sf.
DR InterPro; IPR036390; WH_DNA-bd_sf.
DR Pfam; PF00557; Peptidase_M24; 1.
DR PRINTS; PR00599; MAPEPTIDASE.
DR SUPFAM; SSF46785; SSF46785; 1.
DR SUPFAM; SSF55920; SSF55920; 1.
DR TIGRFAMs; TIGR00501; met_pdase_II; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Aminopeptidase; Cytoplasm; Hydrolase; Metal-binding;
KW Protease; Reference proteome.
FT CHAIN 1..468
FT /note="Methionine aminopeptidase 2"
FT /id="PRO_0000448244"
FT REGION 63..87
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 219
FT /ligand="substrate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03175"
FT BINDING 239
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /ligand_label="1"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03175"
FT BINDING 250
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /ligand_label="1"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03175"
FT BINDING 250
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_03175"
FT BINDING 319
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_03175"
FT BINDING 327
FT /ligand="substrate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03175"
FT BINDING 352
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_03175"
FT BINDING 449
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /ligand_label="1"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03175"
FT BINDING 449
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_03175"
FT VAR_SEQ 18..41
FT /note="Missing (in isoform a and isoform c)"
FT /evidence="ECO:0000305"
FT /id="VSP_060368"
FT VAR_SEQ 237..427
FT /note="Missing (in isoform c)"
FT /evidence="ECO:0000305"
FT /id="VSP_060369"
SQ SEQUENCE 468 AA; 52375 MW; B0B988D8D697AE44 CRC64;
MPPANGKKGK KGGAAKAVRR IQYRPKSFKH SRFVKHAHFW SAAPEEDFDA ILAEMQLADA
KTAAKEATKK DAKGGKGKAN GSAAATAAPE EAKQAWQAEI AAMKPIDEQF PDGKFPHGID
ESPYYLKGKD GRVATDRESN EEKKALDISY EEVWQDYRRS AEAHRQVRKY VKSWIKPGMT
MIEICERLET TSRRLIKEQG LEAGLAFPTG CSLNHCAAHY TPNAGDTTVL QYGDVCKIDY
GIHVRGRLID SAFTVHFDPK FDPLVEAVRE ATNAGIKESG IDVRLCDVGE IVEEVMTSHE
VELDGKSYVV KPIRNLNGHS IAQYRIHAGK TVPIVKGGEQ TKMEENEIYA IETFGSTGKG
YVHDDMETSH YMKNFELADE KIPLRLQKSK GLLNLIDKNF ATLAFCRRWI DRLGETKYLM
ALKDLCDKGI VDPYPPLCDV KGCYTAQWEH TILMRPTVKE VVSRGDDY
