DPAP1_PLAF7
ID DPAP1_PLAF7 Reviewed; 700 AA.
AC Q8IIJ9; A0A144A2G5;
DT 26-APR-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2003, sequence version 1.
DT 03-AUG-2022, entry version 124.
DE RecName: Full=Dipeptidyl aminopeptidase 1 {ECO:0000303|PubMed:15304495};
DE AltName: Full=Cathepsin C homolog {ECO:0000305};
DE EC=3.4.14.1 {ECO:0000269|PubMed:15304495, ECO:0000269|PubMed:20833209};
DE Contains:
DE RecName: Full=Dipeptidyl aminopeptidase 1 exclusion domain chain {ECO:0000303|PubMed:15304495};
DE Contains:
DE RecName: Full=Dipeptidyl aminopeptidase 1 heavy chain {ECO:0000303|PubMed:15304495};
DE Contains:
DE RecName: Full=Dipeptidyl aminopeptidase 1 light chain {ECO:0000303|PubMed:15304495};
DE Flags: Precursor;
GN Name=DPAP1 {ECO:0000303|PubMed:15304495};
GN ORFNames=PF11_0174, PF3D7_1116700;
OS Plasmodium falciparum (isolate 3D7).
OC Eukaryota; Sar; Alveolata; Apicomplexa; Aconoidasida; Haemosporida;
OC Plasmodiidae; Plasmodium; Plasmodium (Laverania).
OX NCBI_TaxID=36329;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=3D7;
RX PubMed=12368864; DOI=10.1038/nature01097;
RA Gardner M.J., Hall N., Fung E., White O., Berriman M., Hyman R.W.,
RA Carlton J.M., Pain A., Nelson K.E., Bowman S., Paulsen I.T., James K.D.,
RA Eisen J.A., Rutherford K.M., Salzberg S.L., Craig A., Kyes S., Chan M.-S.,
RA Nene V., Shallom S.J., Suh B., Peterson J., Angiuoli S., Pertea M.,
RA Allen J., Selengut J., Haft D., Mather M.W., Vaidya A.B., Martin D.M.A.,
RA Fairlamb A.H., Fraunholz M.J., Roos D.S., Ralph S.A., McFadden G.I.,
RA Cummings L.M., Subramanian G.M., Mungall C., Venter J.C., Carucci D.J.,
RA Hoffman S.L., Newbold C., Davis R.W., Fraser C.M., Barrell B.G.;
RT "Genome sequence of the human malaria parasite Plasmodium falciparum.";
RL Nature 419:498-511(2002).
RN [2]
RP IDENTIFICATION BY MASS SPECTROMETRY, PROTEIN SEQUENCE OF 410-417, AND
RP SULFATION AT THR-416.
RX PubMed=14752058; DOI=10.1074/mcp.m300140-mcp200;
RA Medzihradszky K.F., Darula Z., Perlson E., Fainzilber M., Chalkley R.J.,
RA Ball H., Greenbaum D., Bogyo M., Tyson D.R., Bradshaw R.A.,
RA Burlingame A.L.;
RT "O-sulfonation of serine and threonine: mass spectrometric detection and
RT characterization of a new posttranslational modification in diverse
RT proteins throughout the eukaryotes.";
RL Mol. Cell. Proteomics 3:429-440(2004).
RN [3]
RP FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, DEVELOPMENTAL STAGE,
RP AND PROTEOLYTIC CLEAVAGE.
RX PubMed=15304495; DOI=10.1074/jbc.m408123200;
RA Klemba M., Gluzman I., Goldberg D.E.;
RT "A Plasmodium falciparum dipeptidyl aminopeptidase I participates in
RT vacuolar hemoglobin degradation.";
RL J. Biol. Chem. 279:43000-43007(2004).
RN [4]
RP FUNCTION, CATALYTIC ACTIVITY, COFACTOR, BIOPHYSICOCHEMICAL PROPERTIES, AND
RP SUBUNIT.
RX PubMed=20833209; DOI=10.1016/j.molbiopara.2010.08.004;
RA Wang F., Krai P., Deu E., Bibb B., Lauritzen C., Pedersen J., Bogyo M.,
RA Klemba M.;
RT "Biochemical characterization of Plasmodium falciparum dipeptidyl
RT aminopeptidase 1.";
RL Mol. Biochem. Parasitol. 175:10-20(2011).
CC -!- FUNCTION: Thiol protease that cleaves dipeptides from the N-terminus of
CC protein substrates (PubMed:15304495, PubMed:20833209). Active against a
CC broad range of dipeptide substrates composed of both polar and
CC hydrophobic amino acids (PubMed:20833209). Proline cannot occupy the P1
CC position and arginine or lysine cannot occupy the P2 position of the
CC substrate (PubMed:20833209). Involved in host hemoglobin degradation by
CC generating dipeptides from hemoglobin-derived oligopeptides
CC (PubMed:15304495). {ECO:0000269|PubMed:15304495,
CC ECO:0000269|PubMed:20833209}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Release of an N-terminal dipeptide, Xaa-Yaa-|-Zaa-, except
CC when Xaa is Arg or Lys, or Yaa or Zaa is Pro.; EC=3.4.14.1;
CC Evidence={ECO:0000269|PubMed:15304495, ECO:0000269|PubMed:20833209};
CC -!- COFACTOR:
CC Name=chloride; Xref=ChEBI:CHEBI:17996;
CC Evidence={ECO:0000269|PubMed:20833209};
CC Note=Binds 1 Cl(-) ion per heavy chain. {ECO:0000250|UniProtKB:P53634};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC pH dependence:
CC Optimum pH is 6-6.5. {ECO:0000269|PubMed:20833209};
CC -!- SUBUNIT: Monomer. {ECO:0000269|PubMed:20833209}.
CC -!- SUBCELLULAR LOCATION: Vacuole lumen {ECO:0000269|PubMed:15304495}.
CC Parasitophorous vacuole lumen {ECO:0000269|PubMed:15304495}. Note=In
CC schizonts, the immature form localizes to the parasitophorous vacuole
CC (PubMed:15304495). In trophozoites, the mature form localizes to the
CC digestive (or food) vacuole, an acidic vacuole where host hemoglobin is
CC digested (PubMed:15304495). {ECO:0000269|PubMed:15304495}.
CC -!- DEVELOPMENTAL STAGE: Expressed during the asexual blood stage including
CC in trophozoites and schizonts (at protein level).
CC {ECO:0000269|PubMed:15304495}.
CC -!- SIMILARITY: Belongs to the peptidase C1 family. {ECO:0000305}.
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DR EMBL; LN999945; CZT98828.1; -; Genomic_DNA.
DR RefSeq; XP_001347845.1; XM_001347809.1.
DR AlphaFoldDB; Q8IIJ9; -.
DR BioGRID; 1206117; 3.
DR IntAct; Q8IIJ9; 3.
DR STRING; 5833.PF11_0174; -.
DR ChEMBL; CHEMBL1250372; -.
DR DrugBank; DB11638; Artenimol.
DR PRIDE; Q8IIJ9; -.
DR EnsemblProtists; CZT98828; CZT98828; PF3D7_1116700.
DR GeneID; 810721; -.
DR KEGG; pfa:PF3D7_1116700; -.
DR VEuPathDB; PlasmoDB:PF3D7_1116700; -.
DR HOGENOM; CLU_462725_0_0_1; -.
DR InParanoid; Q8IIJ9; -.
DR OMA; CYIASQM; -.
DR PhylomeDB; Q8IIJ9; -.
DR BioCyc; MetaCyc:MON-15382; -.
DR Reactome; R-PFA-204005; COPII-mediated vesicle transport.
DR Reactome; R-PFA-2132295; MHC class II antigen presentation.
DR Reactome; R-PFA-5694530; Cargo concentration in the ER.
DR Reactome; R-PFA-6798695; Neutrophil degranulation.
DR PRO; PR:Q8IIJ9; -.
DR Proteomes; UP000001450; Chromosome 11.
DR GO; GO:0005615; C:extracellular space; IBA:GO_Central.
DR GO; GO:0020020; C:food vacuole; IDA:GeneDB.
DR GO; GO:0005764; C:lysosome; IBA:GO_Central.
DR GO; GO:0020003; C:symbiont-containing vacuole; IDA:GeneDB.
DR GO; GO:0005775; C:vacuolar lumen; IEA:UniProtKB-SubCell.
DR GO; GO:0004197; F:cysteine-type endopeptidase activity; IBA:GO_Central.
DR GO; GO:0008239; F:dipeptidyl-peptidase activity; IDA:UniProtKB.
DR GO; GO:0051603; P:proteolysis involved in protein catabolic process; IDA:UniProtKB.
DR CDD; cd02621; Peptidase_C1A_CathepsinC; 1.
DR Gene3D; 2.40.128.80; -; 1.
DR InterPro; IPR039412; CatC.
DR InterPro; IPR014882; CathepsinC_exc.
DR InterPro; IPR036496; CathepsinC_exc_dom_sf.
DR InterPro; IPR038765; Papain-like_cys_pep_sf.
DR InterPro; IPR025661; Pept_asp_AS.
DR InterPro; IPR025660; Pept_his_AS.
DR InterPro; IPR000668; Peptidase_C1A_C.
DR Pfam; PF08773; CathepsinC_exc; 1.
DR Pfam; PF00112; Peptidase_C1; 2.
DR SMART; SM00645; Pept_C1; 1.
DR SUPFAM; SSF54001; SSF54001; 1.
DR SUPFAM; SSF75001; SSF75001; 1.
DR PROSITE; PS00640; THIOL_PROTEASE_ASN; 1.
DR PROSITE; PS00639; THIOL_PROTEASE_HIS; 1.
PE 1: Evidence at protein level;
KW Chloride; Direct protein sequencing; Disulfide bond; Glycoprotein;
KW Hydrolase; Protease; Reference proteome; Signal; Sulfation; Thiol protease;
KW Vacuole; Zymogen.
FT SIGNAL 1..27
FT /evidence="ECO:0000255"
FT CHAIN 28..?209
FT /note="Dipeptidyl aminopeptidase 1 exclusion domain chain"
FT /evidence="ECO:0000305|PubMed:15304495"
FT /id="PRO_0000026355"
FT PROPEP ?210..?369
FT /evidence="ECO:0000305|PubMed:15304495"
FT /id="PRO_0000026354"
FT CHAIN ?370..?599
FT /note="Dipeptidyl aminopeptidase 1 heavy chain"
FT /evidence="ECO:0000305|PubMed:15304495"
FT /id="PRO_0000454586"
FT CHAIN ?600..700
FT /note="Dipeptidyl aminopeptidase 1 light chain"
FT /evidence="ECO:0000305|PubMed:15304495"
FT /id="PRO_0000454587"
FT ACT_SITE 398
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10088"
FT ACT_SITE 624
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10089"
FT ACT_SITE 648
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10090"
FT BINDING 450
FT /ligand="chloride"
FT /ligand_id="ChEBI:CHEBI:17996"
FT /evidence="ECO:0000250|UniProtKB:P53634"
FT BINDING 452
FT /ligand="chloride"
FT /ligand_id="ChEBI:CHEBI:17996"
FT /evidence="ECO:0000250|UniProtKB:P53634"
FT BINDING 549
FT /ligand="chloride"
FT /ligand_id="ChEBI:CHEBI:17996"
FT /evidence="ECO:0000250|UniProtKB:P53634"
FT MOD_RES 416
FT /note="Sulfothreonine"
FT /evidence="ECO:0000269|PubMed:14752058"
FT CARBOHYD 52
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 144
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 265
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 337
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 373
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 481
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 490
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 507
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 615
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 667
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 395..446
FT /evidence="ECO:0000250|UniProtKB:P53634"
FT DISULFID 439..478
FT /evidence="ECO:0000250|UniProtKB:P53634"
SQ SEQUENCE 700 AA; 80412 MW; EFD504796C8D377B CRC64;
MAKRIFSVSF LLVLLNVLHI CIKFSVADLP THVETKNLLG KWKILRTKTS PNLTTCGSSQ
PNKNTYNVGI TDYKKYLLEN NYEFVSELNV ILSDDYVLYG DIYNTQDNEH RSKWKVLAVY
DENKRVIGTW TTICDEGFEI KIGNETYAAL MHYEPNGKCG PVSDEDSLDS NGDTDCYTTS
FSKIRYGWLD VENEKNEHLH GCFYAERIFD NVNEIKHLDS FTIDKDSQNV LQTFTYDTKL
NNILNSNNML YKFGNLQKPT FTKRNNTNVQ FNSELNWHRM KHHGKKKPLK KSMLDASRQT
YACPCNANEV VDNVINKGDS DNPVSPTLIQ LNNNLKNTTQ TGNKDTNEMD LENYEDTLNS
PKRELEINEL PKNFTWGDPW NKNTREYEVT NQLLCGSCYI ASQLYAFKRR IEVALTKKLD
RKYLNNFDDQ LSIQTVLSCS FYDQGCNGGF PYLVSKLAKL QGIPLNVYFP YSATEETCPY
NISKHPNDMN GSAKLREINA IFNSNNNMST YNNINNDHHQ LGVYANTASS QEQHGISEEN
RWYAKDFNYV GGCYGCNQCN GEKIMMNEIY RNGPIVSSFE ASPDFYDYAD GVYFVEDFPH
ARRCTIEPKN DGVYNITGWD RVNHAIVLLG WGEEEINGKL YKYWIGRNSW GNGWGKEGYF
KILRGQNFSG IESQSLFIEP DFSRGAGKIL LEKMQKELGN
