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Protein

Puromycin-sensitive aminopeptidase

Gene

pam-1

Organism
Caenorhabditis elegans
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Aminopeptidase (PubMed:12930831). Required for the exit from meiosis, probably upstream of cyclin cyb-3 (PubMed:17021038). Involved in the establishment of the anterior-posterior polarity at the embryonic 1-cell stage by regulating the dynamics of sperm-donated centrosomes (PubMed:17021038, PubMed:20599902, PubMed:28065742). Plays a role in oocyte maturation (PubMed:24663498). Required for embryonic development (PubMed:12930831).5 Publications

Catalytic activityi

Release of an N-terminal amino acid, preferentially alanine, from a wide range of peptides, amides and arylamides.1 Publication

Cofactori

Zn2+UniRule annotation1 PublicationNote: Binds 1 zinc ion per subunit. Can also use Ni2+ and Co2+ (PubMed:12930831).UniRule annotation1 Publication

Enzyme regulationi

Inhibited by chelating agent 1,10-phenanthroline, aminopeptidase inhibitors actinonin, amastatin, and leuhistin, and to a lesser extent by puromycin.1 Publication

Kineticsi

  1. KM=34 µM for L-Arg-AMC1 Publication
  2. KM=59 µM for L-Met-AMC1 Publication
  3. KM=63 µM for L-Leu-AMC1 Publication
  4. KM=73 µM for L-Tyr-AMC1 Publication
  5. KM=78 µM for L-Lys-AMC1 Publication
  6. KM=97 µM for L-Ala-AMC1 Publication
  7. KM=160 µM for L-Phe-AMC1 Publication
  8. KM=390 µM for L-Gly-AMC1 Publication
  9. KM=840 µM for L-Ser-AMC1 Publication

    Sites

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Binding sitei206SubstrateBy similarity1
    Metal bindingi377Zinc; catalyticPROSITE-ProRule annotation1
    Active sitei378Proton acceptorPROSITE-ProRule annotation1
    Metal bindingi381Zinc; catalyticPROSITE-ProRule annotation1
    Metal bindingi400Zinc; catalyticBy similarity1
    Sitei463Transition state stabilizerBy similarity1

    GO - Molecular functioni

    • metalloaminopeptidase activity Source: WormBase
    • peptide binding Source: GO_Central
    • zinc ion binding Source: GO_Central

    GO - Biological processi

    • anterior/posterior axis specification, embryo Source: UniProtKB
    • embryo development ending in birth or egg hatching Source: UniProtKB
    • exit from meiosis Source: UniProtKB
    • first cell cycle pseudocleavage Source: UniProtKB
    • maintenance of centrosome location Source: UniProtKB
    • peptide catabolic process Source: WormBase
    • positive regulation of oocyte maturation Source: UniProtKB
    • regulation of meiotic cell cycle process involved in oocyte maturation Source: UniProtKB
    • regulation of oviposition Source: UniProtKB

    Keywordsi

    Molecular functionAminopeptidase, Hydrolase, Metalloprotease, Protease
    Biological processDifferentiation, Meiosis, Oogenesis
    LigandMetal-binding, Zinc

    Enzyme and pathway databases

    ReactomeiR-CEL-983168. Antigen processing: Ubiquitination & Proteasome degradation.

    Protein family/group databases

    MEROPSiM01.A28.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Puromycin-sensitive aminopeptidase1 Publication (EC:3.4.11.141 Publication)
    Short name:
    PSACurated
    Alternative name(s):
    Cytosol alanyl aminopeptidaseCurated
    Short name:
    AAP-SCurated
    Gene namesi
    Name:pam-11 PublicationImported
    ORF Names:F49E8.3Imported
    OrganismiCaenorhabditis elegansImported
    Taxonomic identifieri6239 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaEcdysozoaNematodaChromadoreaRhabditidaRhabditoideaRhabditidaePeloderinaeCaenorhabditis
    Proteomesi
    • UP000001940 Componenti: Chromosome IV

    Organism-specific databases

    WormBaseiF49E8.3a; CE10790; WBGene00003914; pam-1.
    F49E8.3b; CE37649; WBGene00003914; pam-1.

    Subcellular locationi

    GO - Cellular componenti

    • condensed chromosome Source: UniProtKB
    • cytoplasm Source: WormBase
    • mitotic spindle pole Source: UniProtKB

    Keywords - Cellular componenti

    Chromosome, Cytoplasm, Cytoskeleton

    Pathology & Biotechi

    Disruption phenotypei

    RNAi-mediated knockdown causes an arrest at the gastrulation stage in 30 percent of embryos (PubMed:12930831). The surviving adults lay a substantial number of unfertilized oocytes (PubMed:12930831). However, brood size is only slightly reduced (PubMed:24663498). In the gonads, the pachytene zone is expanded in 15 percent of animals and oocyte nucleolus disassembly is delayed (PubMed:24663498). Mutant 1-cell embryos have a delay in meiotic exit during which chromosomes fail to decondense after polar body extrusion and oocyte and sperm pronuclear envelope formation is delayed (PubMed:17021038). In addition, 33 percent of 1-cell embryos have impaired chromosome segregation at meiotic anaphase II (PubMed:17021038). During meiotic exit delay, sperm pronucleus/centrosome complex (SPCC) dissociates prematurely from the posterior cortex resulting in a failure to establish anterior-posterior polarity subsequently leading to a symmetric division in half of the 1-cell embryos (PubMed:17021038, PubMed:20599902, PubMed:28065742). Premature microtubule nucleation prior to the sperm pronuclear appearance occurs (PubMed:17021038, PubMed:20599902). Cortical flows, pseudocleavage and asymmetric localization of par-1, par-2, par-3 and par-6 are absent, and cytoplasmic P granules and pie-1 are mislocalized prior to the first mitotic division (PubMed:17021038, PubMed:20599902, PubMed:28065742). In addition, non-muscle myosin nmy-2 foci fails to clear from the posterior part during polarization in half of the 1-cell embryos (PubMed:28065742). Simultaneous RNAi-mediated knockdown of cyclin cyb-3, causes a failure to extrude the second polar body and prevents anaphase entry in some of the 1-cel embryos (PubMed:17021038). Also restores normal timing for meiotic exit but not the establishment of AP axis polarity (PubMed:17021038). Simultaneous RNAi-mediated knockdown of dynein heavy chain dhc-1, restores anterior-posterior polarity, par-1, par2 and par-6 asymmetric localization and pseudocleavage formation (PubMed:20599902).5 Publications

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    ChainiPRO_00004408621 – 948Puromycin-sensitive aminopeptidaseAdd BLAST948

    Proteomic databases

    EPDiQ4TT88.
    PaxDbiQ4TT88.
    PeptideAtlasiQ4TT88.

    Expressioni

    Tissue specificityi

    Expressed mainly in intestinal cells in the posterior part of the intestine and in amphid sensory neurons and nerve ring neurons (PubMed:12930831). Expressed in neurons in the male tail (PubMed:12930831). Expressed in mature spermatids (at protein level) (PubMed:20599902).2 Publications

    Developmental stagei

    Expressed in the 1-cell embryos (at protein level) (PubMed:20599902). Expressed during gastrulation and throughout the larval stage and in adults (PubMed:12930831).2 Publications

    Gene expression databases

    BgeeiWBGene00003914.
    ExpressionAtlasiQ4TT88. baseline.

    Interactioni

    Protein-protein interaction databases

    IntActiQ20627. 1 interactor.
    STRINGi6239.F49E8.3b.

    Structurei

    3D structure databases

    ProteinModelPortaliQ4TT88.
    SMRiQ4TT88.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Region

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Regioni341 – 345Substrate bindingBy similarity5

    Sequence similaritiesi

    Belongs to the peptidase M1 family.UniRule annotation

    Phylogenomic databases

    eggNOGiKOG1046. Eukaryota.
    COG0308. LUCA.
    GeneTreeiENSGT00760000119082.
    HOGENOMiHOG000106482.
    InParanoidiQ4TT88.
    KOiK08776.
    OMAiPNESHLD.
    OrthoDBiEOG091G01GH.
    PhylomeDBiQ4TT88.

    Family and domain databases

    CDDicd09601. M1_APN_2. 1 hit.
    InterProiView protein in InterPro
    IPR024571. ERAP1-like_C_dom.
    IPR034016. M1_APN-typ.
    IPR001930. Peptidase_M1.
    IPR014782. Peptidase_M1_N.
    PANTHERiPTHR11533. PTHR11533. 1 hit.
    PfamiView protein in Pfam
    PF11838. ERAP1_C. 1 hit.
    PF01433. Peptidase_M1. 1 hit.
    PRINTSiPR00756. ALADIPTASE.
    PROSITEiView protein in PROSITE
    PS00142. ZINC_PROTEASE. 1 hit.

    Sequences (2)i

    Sequence statusi: Complete.

    This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

    Isoform bImported (identifier: Q4TT88-1) [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
    MLGRLAVRQA VRCSKASIKP VNTHQLCLRN FSAIRRLSFV AGAQCRPYHT
    60 70 80 90 100
    TANMLHRTAR GEHGMAACGN PSAAVKFERL PTFAEPTHYN VRLSPCLNQF
    110 120 130 140 150
    SFDGHATIDV TIKEATDVLK VHAQSLLIQS VSLITQPGDA SKSLETSYDD
    160 170 180 190 200
    KLNILTIKLP TTMQPQKVQL DFKFVGELND KMRGFYRSQY KDKNGTEKFL
    210 220 230 240 250
    ASTQFESTYA RYAFPCFDEP IYKATFDVTL EVENHLTALS NMNVISETPT
    260 270 280 290 300
    ADGKRKAVTF ATSPKMSSYL VAFAVGELEY ISAQTKSGVE MRVYTVPGKK
    310 320 330 340 350
    EQGQYSLDLS VKCIDWYNEW FDIKYPLPKC DLIAIPDFSM GAMENWGLVT
    360 370 380 390 400
    YREIALLVDP GVTSTRQKSR VALVVAHELA HLWFGNLVTM KWWTDLWLKE
    410 420 430 440 450
    GFASFMEYMF VGANCPEFKI WLHFLNDELA SGMGLDALRN SHPIEVEIDN
    460 470 480 490 500
    PNELDEIYDS ITYAKSNSVN RMLCYYLSEP VFQKGLRLYL KRFQYSNAVT
    510 520 530 540 550
    QDLWTALSEA SGQNVNELMS GWTQQMGFPV LKVSQRQDGN NRILTVEQRR
    560 570 580 590 600
    FISDGGEDPK NSQWQVPITV AVGSSPSDVK ARFLLKEKQQ EFTIEGVAPG
    610 620 630 640 650
    EWVKLNSGTT GFYRVEYSDE MLTAMLPDIA SRRMPVLDRF GLINDLSALL
    660 670 680 690 700
    NTGRVSIAQF VQVAASSAKE DEYVVWGAID EGMSKLLACA REMSEDTLKS
    710 720 730 740 750
    AKQLVVKMFE QTGAELGFAE QAGEDSQKMM LRSLVQARLA RAGHQPTIDK
    760 770 780 790 800
    FTQMFNDFLE KGTPIHPDIR LATFGVVARY GGKEGFDKLM NLRETTTFQE
    810 820 830 840 850
    IERQTMVAMS QTPEESLLAQ LFEYGFEKNK VRPQDQLYLF LGTGATHMGQ
    860 870 880 890 900
    QYAWKYFCEH IKEFLDKYGG ANSSLFQRCL KFAGESFGNE KRAVEFQDFF
    910 920 930 940
    CNCNVLSDTD RQTLARPIGQ TVEAIRLNAR LLESNRQIIE NLLKQSNV
    Note: No experimental confirmation available.Curated
    Length:948
    Mass (Da):107,150
    Last modified:July 19, 2005 - v1
    Checksum:i9E5F2D2A4FA71454
    GO
    Isoform aImported (identifier: Q4TT88-2) [UniParc]FASTAAdd to basket

    The sequence of this isoform differs from the canonical sequence as follows:
         1-64: Missing.

    Show »
    Length:884
    Mass (Da):100,009
    Checksum:i69A77B1A55558FF0
    GO

    Alternative sequence

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Alternative sequenceiVSP_0590001 – 64Missing in isoform a. CuratedAdd BLAST64

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    BX284604 Genomic DNA. Translation: CCD70444.1.
    BX284604 Genomic DNA. Translation: CCD70445.1.
    PIRiT29637.
    RefSeqiNP_001023210.1. NM_001028039.1.
    UniGeneiCel.34182.

    Genome annotation databases

    EnsemblMetazoaiF49E8.3b; F49E8.3b; WBGene00003914.
    GeneIDi177528.
    KEGGicel:CELE_F49E8.3.
    UCSCiF49E8.3a.1. c. elegans.

    Keywords - Coding sequence diversityi

    Alternative splicing

    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 one 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.

    Entry informationi

    Entry nameiPSA_CAEEL
    AccessioniPrimary (citable) accession number: Q4TT88
    Secondary accession number(s): Q20627
    Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 5, 2017
    Last sequence update: July 19, 2005
    Last modified: July 5, 2017
    This is version 92 of the entry and version 1 of the sequence. See complete history.
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programCaenorhabditis annotation project

    Miscellaneousi

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. Caenorhabditis elegans
      Caenorhabditis elegans: entries, gene names and cross-references to WormBase
    2. Peptidase families
      Classification of peptidase families and list of entries
    3. SIMILARITY comments
      Index of protein domains and families