PSA_CAEEL
ID PSA_CAEEL Reviewed; 948 AA.
AC Q4TT88; Q20627;
DT 05-JUL-2017, integrated into UniProtKB/Swiss-Prot.
DT 19-JUL-2005, sequence version 1.
DT 03-AUG-2022, entry version 118.
DE RecName: Full=Puromycin-sensitive aminopeptidase {ECO:0000303|PubMed:12930831};
DE Short=PSA {ECO:0000305};
DE EC=3.4.11.14 {ECO:0000305|PubMed:12930831};
DE AltName: Full=Cytosol alanyl aminopeptidase {ECO:0000305};
DE Short=AAP-S {ECO:0000305};
GN Name=pam-1 {ECO:0000303|PubMed:12930831, ECO:0000312|WormBase:F49E8.3b};
GN ORFNames=F49E8.3 {ECO:0000312|WormBase:F49E8.3b};
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, COFACTOR, ACTIVITY REGULATION,
RP BIOPHYSICOCHEMICAL PROPERTIES, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, AND
RP DISRUPTION PHENOTYPE.
RX PubMed=12930831; DOI=10.1074/jbc.m306216200;
RA Brooks D.R., Hooper N.M., Isaac R.E.;
RT "The Caenorhabditis elegans orthologue of mammalian puromycin-sensitive
RT aminopeptidase has roles in embryogenesis and reproduction.";
RL J. Biol. Chem. 278:42795-42801(2003).
RN [3] {ECO:0000305}
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=17021038; DOI=10.1242/dev.02615;
RA Lyczak R., Zweier L., Group T., Murrow M.A., Snyder C., Kulovitz L.,
RA Beatty A., Smith K., Bowerman B.;
RT "The puromycin-sensitive aminopeptidase PAM-1 is required for meiotic exit
RT and anteroposterior polarity in the one-cell Caenorhabditis elegans
RT embryo.";
RL Development 133:4281-4292(2006).
RN [4] {ECO:0000305}
RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE,
RP AND DISRUPTION PHENOTYPE.
RX PubMed=20599902; DOI=10.1016/j.ydbio.2010.06.016;
RA Fortin S.M., Marshall S.L., Jaeger E.C., Greene P.E., Brady L.K.,
RA Isaac R.E., Schrandt J.C., Brooks D.R., Lyczak R.;
RT "The PAM-1 aminopeptidase regulates centrosome positioning to ensure
RT anterior-posterior axis specification in one-cell C. elegans embryos.";
RL Dev. Biol. 344:992-1000(2010).
RN [5] {ECO:0000305}
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=24663498; DOI=10.1007/s00427-014-0470-3;
RA Althoff M.J., Flick K., Trzepacz C.;
RT "Collaboration within the M1 aminopeptidase family promotes reproductive
RT success in Caenorhabditis elegans.";
RL Dev. Genes Evol. 224:137-146(2014).
RN [6] {ECO:0000305}
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=28065742; DOI=10.1016/j.ydbio.2016.12.025;
RA Saturno D.M., Castanzo D.T., Williams M., Parikh D.A., Jaeger E.C.,
RA Lyczak R.;
RT "Sustained centrosome-cortical contact ensures robust polarization of the
RT one-cell C. elegans embryo.";
RL Dev. Biol. 422:135-145(2017).
CC -!- FUNCTION: Aminopeptidase (PubMed:12930831). Required for the exit from
CC meiosis, probably upstream of cyclin cyb-3 (PubMed:17021038). Involved
CC in the establishment of the anterior-posterior polarity at the
CC embryonic 1-cell stage by regulating the dynamics of sperm-donated
CC centrosomes (PubMed:17021038, PubMed:20599902, PubMed:28065742). Plays
CC a role in oocyte maturation (PubMed:24663498). Required for embryonic
CC development (PubMed:12930831). {ECO:0000269|PubMed:12930831,
CC ECO:0000269|PubMed:17021038, ECO:0000269|PubMed:20599902,
CC ECO:0000269|PubMed:24663498, ECO:0000269|PubMed:28065742}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Release of an N-terminal amino acid, preferentially alanine,
CC from a wide range of peptides, amides and arylamides.; EC=3.4.11.14;
CC Evidence={ECO:0000305|PubMed:12930831};
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000255|RuleBase:RU364040,
CC ECO:0000269|PubMed:12930831};
CC Note=Binds 1 zinc ion per subunit. Can also use Ni(2+) and Co(2+)
CC (PubMed:12930831). {ECO:0000255|RuleBase:RU364040,
CC ECO:0000269|PubMed:12930831};
CC -!- ACTIVITY REGULATION: Inhibited by chelating agent 1,10-phenanthroline,
CC aminopeptidase inhibitors actinonin, amastatin, and leuhistin, and to a
CC lesser extent by puromycin. {ECO:0000269|PubMed:12930831}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=34 uM for L-Arg-AMC {ECO:0000269|PubMed:12930831};
CC KM=59 uM for L-Met-AMC {ECO:0000269|PubMed:12930831};
CC KM=63 uM for L-Leu-AMC {ECO:0000269|PubMed:12930831};
CC KM=73 uM for L-Tyr-AMC {ECO:0000269|PubMed:12930831};
CC KM=78 uM for L-Lys-AMC {ECO:0000269|PubMed:12930831};
CC KM=97 uM for L-Ala-AMC {ECO:0000269|PubMed:12930831};
CC KM=160 uM for L-Phe-AMC {ECO:0000269|PubMed:12930831};
CC KM=390 uM for L-Gly-AMC {ECO:0000269|PubMed:12930831};
CC KM=840 uM for L-Ser-AMC {ECO:0000269|PubMed:12930831};
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:20599902}.
CC Cytoplasm, cell cortex {ECO:0000269|PubMed:20599902}. Chromosome
CC {ECO:0000269|PubMed:20599902}. Cytoplasm, cytoskeleton, spindle pole
CC {ECO:0000269|PubMed:20599902}. Note=During meiosis I, localizes to the
CC cell cortex. During meiosis II, localizes to the cytoplasm. During
CC embryonic mitosis, localizes around mitotic chromosomes at metaphase
CC and anaphase and near the spindle poles. In spermatids, excluded from
CC the chromosomes. {ECO:0000269|PubMed:20599902}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=b {ECO:0000312|WormBase:F49E8.3b};
CC IsoId=Q4TT88-1; Sequence=Displayed;
CC Name=a {ECO:0000312|WormBase:F49E8.3a};
CC IsoId=Q4TT88-2; Sequence=VSP_059000;
CC -!- TISSUE SPECIFICITY: Expressed mainly in intestinal cells in the
CC posterior part of the intestine and in amphid sensory neurons and nerve
CC ring neurons (PubMed:12930831). Expressed in neurons in the male tail
CC (PubMed:12930831). Expressed in mature spermatids (at protein level)
CC (PubMed:20599902). {ECO:0000269|PubMed:12930831,
CC ECO:0000269|PubMed:20599902}.
CC -!- DEVELOPMENTAL STAGE: Expressed in the 1-cell embryos (at protein level)
CC (PubMed:20599902). Expressed during gastrulation and throughout the
CC larval stage and in adults (PubMed:12930831).
CC {ECO:0000269|PubMed:12930831, ECO:0000269|PubMed:20599902}.
CC -!- DISRUPTION PHENOTYPE: RNAi-mediated knockdown causes an arrest at the
CC gastrulation stage in 30 percent of embryos (PubMed:12930831). The
CC surviving adults lay a substantial number of unfertilized oocytes
CC (PubMed:12930831). However, brood size is only slightly reduced
CC (PubMed:24663498). In the gonads, the pachytene zone is expanded in 15
CC percent of animals and oocyte nucleolus disassembly is delayed
CC (PubMed:24663498). Mutant 1-cell embryos have a delay in meiotic exit
CC during which chromosomes fail to decondense after polar body extrusion
CC and oocyte and sperm pronuclear envelope formation is delayed
CC (PubMed:17021038). In addition, 33 percent of 1-cell embryos have
CC impaired chromosome segregation at meiotic anaphase II
CC (PubMed:17021038). During meiotic exit delay, sperm
CC pronucleus/centrosome complex (SPCC) dissociates prematurely from the
CC posterior cortex resulting in a failure to establish anterior-posterior
CC polarity subsequently leading to a symmetric division in half of the 1-
CC cell embryos (PubMed:17021038, PubMed:20599902, PubMed:28065742).
CC Premature microtubule nucleation prior to the sperm pronuclear
CC appearance occurs (PubMed:17021038, PubMed:20599902). Cortical flows,
CC pseudocleavage and asymmetric localization of par-1, par-2, par-3 and
CC par-6 are absent, and cytoplasmic P granules and pie-1 are mislocalized
CC prior to the first mitotic division (PubMed:17021038, PubMed:20599902,
CC PubMed:28065742). In addition, non-muscle myosin nmy-2 foci fails to
CC clear from the posterior part during polarization in half of the 1-cell
CC embryos (PubMed:28065742). Simultaneous RNAi-mediated knockdown of
CC cyclin cyb-3, causes a failure to extrude the second polar body and
CC prevents anaphase entry in some of the 1-cel embryos (PubMed:17021038).
CC Also restores normal timing for meiotic exit but not the establishment
CC of AP axis polarity (PubMed:17021038). Simultaneous RNAi-mediated
CC knockdown of dynein heavy chain dhc-1, restores anterior-posterior
CC polarity, par-1, par2 and par-6 asymmetric localization and
CC pseudocleavage formation (PubMed:20599902).
CC {ECO:0000269|PubMed:12930831, ECO:0000269|PubMed:17021038,
CC ECO:0000269|PubMed:20599902, ECO:0000269|PubMed:24663498,
CC ECO:0000269|PubMed:28065742}.
CC -!- SIMILARITY: Belongs to the peptidase M1 family.
CC {ECO:0000255|RuleBase:RU364040}.
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DR EMBL; BX284604; CCD70444.1; -; Genomic_DNA.
DR EMBL; BX284604; CCD70445.1; -; Genomic_DNA.
DR PIR; T29637; T29637.
DR RefSeq; NP_001023209.1; NM_001028038.4. [Q4TT88-2]
DR RefSeq; NP_001023210.1; NM_001028039.1. [Q4TT88-1]
DR AlphaFoldDB; Q4TT88; -.
DR SMR; Q4TT88; -.
DR IntAct; Q4TT88; 1.
DR STRING; 6239.F49E8.3b; -.
DR MEROPS; M01.A28; -.
DR EPD; Q4TT88; -.
DR PaxDb; Q4TT88; -.
DR PeptideAtlas; Q4TT88; -.
DR EnsemblMetazoa; F49E8.3a.1; F49E8.3a.1; WBGene00003914. [Q4TT88-2]
DR EnsemblMetazoa; F49E8.3a.2; F49E8.3a.2; WBGene00003914. [Q4TT88-2]
DR EnsemblMetazoa; F49E8.3a.3; F49E8.3a.3; WBGene00003914. [Q4TT88-2]
DR EnsemblMetazoa; F49E8.3b.1; F49E8.3b.1; WBGene00003914. [Q4TT88-1]
DR GeneID; 177528; -.
DR KEGG; cel:CELE_F49E8.3; -.
DR UCSC; F49E8.3a.1; c. elegans.
DR CTD; 177528; -.
DR WormBase; F49E8.3a; CE10790; WBGene00003914; pam-1. [Q4TT88-2]
DR WormBase; F49E8.3b; CE37649; WBGene00003914; pam-1. [Q4TT88-1]
DR eggNOG; KOG1046; Eukaryota.
DR GeneTree; ENSGT00940000155246; -.
DR InParanoid; Q4TT88; -.
DR OMA; MMEYVAI; -.
DR OrthoDB; 110058at2759; -.
DR PhylomeDB; Q4TT88; -.
DR Reactome; R-CEL-6798695; Neutrophil degranulation.
DR Reactome; R-CEL-983168; Antigen processing: Ubiquitination & Proteasome degradation.
DR Reactome; R-CEL-983170; Antigen Presentation: Folding, assembly and peptide loading of class I MHC.
DR PRO; PR:Q4TT88; -.
DR Proteomes; UP000001940; Chromosome IV.
DR Bgee; WBGene00003914; Expressed in adult organism and 4 other tissues.
DR GO; GO:0005938; C:cell cortex; IEA:UniProtKB-SubCell.
DR GO; GO:0000793; C:condensed chromosome; IDA:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IDA:WormBase.
DR GO; GO:0097431; C:mitotic spindle pole; IDA:UniProtKB.
DR GO; GO:0070006; F:metalloaminopeptidase activity; IDA:WormBase.
DR GO; GO:0042277; F:peptide binding; IBA:GO_Central.
DR GO; GO:0008270; F:zinc ion binding; IBA:GO_Central.
DR GO; GO:0008595; P:anterior/posterior axis specification, embryo; IMP:UniProtKB.
DR GO; GO:0009792; P:embryo development ending in birth or egg hatching; IMP:UniProtKB.
DR GO; GO:1990947; P:exit from meiosis; IMP:UniProtKB.
DR GO; GO:0030590; P:first cell cycle pseudocleavage; IMP:UniProtKB.
DR GO; GO:0051661; P:maintenance of centrosome location; IMP:UniProtKB.
DR GO; GO:0048477; P:oogenesis; IEA:UniProtKB-KW.
DR GO; GO:0043171; P:peptide catabolic process; IDA:WormBase.
DR GO; GO:1900195; P:positive regulation of oocyte maturation; IMP:UniProtKB.
DR GO; GO:0006508; P:proteolysis; IBA:GO_Central.
DR GO; GO:1903538; P:regulation of meiotic cell cycle process involved in oocyte maturation; IMP:UniProtKB.
DR GO; GO:0046662; P:regulation of oviposition; IMP:UniProtKB.
DR CDD; cd09601; M1_APN-Q_like; 1.
DR Gene3D; 1.10.390.10; -; 1.
DR Gene3D; 2.60.40.1730; -; 1.
DR InterPro; IPR045357; Aminopeptidase_N-like_N.
DR InterPro; IPR042097; Aminopeptidase_N-like_N_sf.
DR InterPro; IPR024571; ERAP1-like_C_dom.
DR InterPro; IPR034016; M1_APN-typ.
DR InterPro; IPR001930; Peptidase_M1.
DR InterPro; IPR014782; Peptidase_M1_dom.
DR InterPro; IPR027268; Peptidase_M4/M1_CTD_sf.
DR Pfam; PF11838; ERAP1_C; 1.
DR Pfam; PF01433; Peptidase_M1; 1.
DR Pfam; PF17900; Peptidase_M1_N; 1.
DR PRINTS; PR00756; ALADIPTASE.
DR SUPFAM; SSF63737; SSF63737; 1.
DR PROSITE; PS00142; ZINC_PROTEASE; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Aminopeptidase; Chromosome; Cytoplasm; Cytoskeleton;
KW Differentiation; Hydrolase; Meiosis; Metal-binding; Metalloprotease;
KW Oogenesis; Protease; Reference proteome; Zinc.
FT CHAIN 1..948
FT /note="Puromycin-sensitive aminopeptidase"
FT /id="PRO_0000440862"
FT ACT_SITE 378
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10095"
FT BINDING 206
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q6P179"
FT BINDING 341..345
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P15144"
FT BINDING 377
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10095"
FT BINDING 381
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10095"
FT BINDING 400
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:P15144"
FT SITE 463
FT /note="Transition state stabilizer"
FT /evidence="ECO:0000250|UniProtKB:P15144"
FT VAR_SEQ 1..64
FT /note="Missing (in isoform a)"
FT /evidence="ECO:0000305"
FT /id="VSP_059000"
SQ SEQUENCE 948 AA; 107150 MW; 9E5F2D2A4FA71454 CRC64;
MLGRLAVRQA VRCSKASIKP VNTHQLCLRN FSAIRRLSFV AGAQCRPYHT TANMLHRTAR
GEHGMAACGN PSAAVKFERL PTFAEPTHYN VRLSPCLNQF SFDGHATIDV TIKEATDVLK
VHAQSLLIQS VSLITQPGDA SKSLETSYDD KLNILTIKLP TTMQPQKVQL DFKFVGELND
KMRGFYRSQY KDKNGTEKFL ASTQFESTYA RYAFPCFDEP IYKATFDVTL EVENHLTALS
NMNVISETPT ADGKRKAVTF ATSPKMSSYL VAFAVGELEY ISAQTKSGVE MRVYTVPGKK
EQGQYSLDLS VKCIDWYNEW FDIKYPLPKC DLIAIPDFSM GAMENWGLVT YREIALLVDP
GVTSTRQKSR VALVVAHELA HLWFGNLVTM KWWTDLWLKE GFASFMEYMF VGANCPEFKI
WLHFLNDELA SGMGLDALRN SHPIEVEIDN PNELDEIYDS ITYAKSNSVN RMLCYYLSEP
VFQKGLRLYL KRFQYSNAVT QDLWTALSEA SGQNVNELMS GWTQQMGFPV LKVSQRQDGN
NRILTVEQRR FISDGGEDPK NSQWQVPITV AVGSSPSDVK ARFLLKEKQQ EFTIEGVAPG
EWVKLNSGTT GFYRVEYSDE MLTAMLPDIA SRRMPVLDRF GLINDLSALL NTGRVSIAQF
VQVAASSAKE DEYVVWGAID EGMSKLLACA REMSEDTLKS AKQLVVKMFE QTGAELGFAE
QAGEDSQKMM LRSLVQARLA RAGHQPTIDK FTQMFNDFLE KGTPIHPDIR LATFGVVARY
GGKEGFDKLM NLRETTTFQE IERQTMVAMS QTPEESLLAQ LFEYGFEKNK VRPQDQLYLF
LGTGATHMGQ QYAWKYFCEH IKEFLDKYGG ANSSLFQRCL KFAGESFGNE KRAVEFQDFF
CNCNVLSDTD RQTLARPIGQ TVEAIRLNAR LLESNRQIIE NLLKQSNV
