ATG4_DICDI
ID ATG4_DICDI Reviewed; 745 AA.
AC Q557H7; Q86CR5;
DT 08-APR-2008, integrated into UniProtKB/Swiss-Prot.
DT 24-MAY-2005, sequence version 1.
DT 25-MAY-2022, entry version 99.
DE RecName: Full=Cysteine protease atg4 {ECO:0000305};
DE EC=3.4.22.- {ECO:0000250|UniProtKB:Q9Y4P1};
DE AltName: Full=Autophagy-related protein 4;
GN Name=atg4-1; Synonyms=apg4-1; ORFNames=DDB_G0273443;
GN and
GN Name=atg4-2; Synonyms=apg4-2; ORFNames=DDB_G0273553;
OS Dictyostelium discoideum (Slime mold).
OC Eukaryota; Amoebozoa; Evosea; Eumycetozoa; Dictyostelia; Dictyosteliales;
OC Dictyosteliaceae; Dictyostelium.
OX NCBI_TaxID=44689;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND FUNCTION.
RC STRAIN=AX3 / DH1;
RX PubMed=12626495; DOI=10.1074/jbc.m212467200;
RA Otto G.P., Wu M.Y., Kazgan N., Anderson O.R., Kessin R.H.;
RT "Macroautophagy is required for multicellular development of the social
RT amoeba Dictyostelium discoideum.";
RL J. Biol. Chem. 278:17636-17645(2003).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=AX4;
RX PubMed=12097910; DOI=10.1038/nature00847;
RA Gloeckner G., Eichinger L., Szafranski K., Pachebat J.A., Bankier A.T.,
RA Dear P.H., Lehmann R., Baumgart C., Parra G., Abril J.F., Guigo R.,
RA Kumpf K., Tunggal B., Cox E.C., Quail M.A., Platzer M., Rosenthal A.,
RA Noegel A.A.;
RT "Sequence and analysis of chromosome 2 of Dictyostelium discoideum.";
RL Nature 418:79-85(2002).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=AX4;
RX PubMed=15875012; DOI=10.1038/nature03481;
RA Eichinger L., Pachebat J.A., Gloeckner G., Rajandream M.A., Sucgang R.,
RA Berriman M., Song J., Olsen R., Szafranski K., Xu Q., Tunggal B.,
RA Kummerfeld S., Madera M., Konfortov B.A., Rivero F., Bankier A.T.,
RA Lehmann R., Hamlin N., Davies R., Gaudet P., Fey P., Pilcher K., Chen G.,
RA Saunders D., Sodergren E.J., Davis P., Kerhornou A., Nie X., Hall N.,
RA Anjard C., Hemphill L., Bason N., Farbrother P., Desany B., Just E.,
RA Morio T., Rost R., Churcher C.M., Cooper J., Haydock S., van Driessche N.,
RA Cronin A., Goodhead I., Muzny D.M., Mourier T., Pain A., Lu M., Harper D.,
RA Lindsay R., Hauser H., James K.D., Quiles M., Madan Babu M., Saito T.,
RA Buchrieser C., Wardroper A., Felder M., Thangavelu M., Johnson D.,
RA Knights A., Loulseged H., Mungall K.L., Oliver K., Price C., Quail M.A.,
RA Urushihara H., Hernandez J., Rabbinowitsch E., Steffen D., Sanders M.,
RA Ma J., Kohara Y., Sharp S., Simmonds M.N., Spiegler S., Tivey A.,
RA Sugano S., White B., Walker D., Woodward J.R., Winckler T., Tanaka Y.,
RA Shaulsky G., Schleicher M., Weinstock G.M., Rosenthal A., Cox E.C.,
RA Chisholm R.L., Gibbs R.A., Loomis W.F., Platzer M., Kay R.R.,
RA Williams J.G., Dear P.H., Noegel A.A., Barrell B.G., Kuspa A.;
RT "The genome of the social amoeba Dictyostelium discoideum.";
RL Nature 435:43-57(2005).
CC -!- FUNCTION: Cysteine protease that plays a key role in autophagy by
CC mediating both proteolytic activation and delipidation of ATG8 family
CC proteins (PubMed:12626495). The protease activity is required for
CC proteolytic activation of ATG8 family proteins: cleaves the C-terminal
CC amino acid of ATG8 proteins to reveal a C-terminal glycine (By
CC similarity). Exposure of the glycine at the C-terminus is essential for
CC ATG8 proteins conjugation to phosphatidylethanolamine (PE) and
CC insertion to membranes, which is necessary for autophagy (By
CC similarity). In addition to the protease activity, also mediates
CC delipidation of PE-conjugated ATG8 proteins (By similarity).
CC {ECO:0000250|UniProtKB:Q9Y4P1, ECO:0000269|PubMed:12626495}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=[protein]-C-terminal L-amino acid-glycyl-
CC phosphatidylethanolamide + H2O = [protein]-C-terminal L-amino acid-
CC glycine + a 1,2-diacyl-sn-glycero-3-phosphoethanolamine;
CC Xref=Rhea:RHEA:67548, Rhea:RHEA-COMP:17323, Rhea:RHEA-COMP:17324,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:64612, ChEBI:CHEBI:172940,
CC ChEBI:CHEBI:172941; Evidence={ECO:0000250|UniProtKB:Q9Y4P1};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:67549;
CC Evidence={ECO:0000250|UniProtKB:Q9Y4P1};
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q8BGE6}.
CC -!- SIMILARITY: Belongs to the peptidase C54 family. {ECO:0000305}.
CC -!- CAUTION: The gene for this protein is duplicated in strains AX3 and
CC AX4. These strains contain a duplication of a segment of 750 kb of
CC chromosome 2 compared to the corresponding sequence in strain AX2.
CC {ECO:0000305}.
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DR EMBL; AY191018; AAO39081.1; -; Genomic_DNA.
DR EMBL; AAFI02000010; EAL70676.1; -; Genomic_DNA.
DR EMBL; AAFI02000010; EAL70731.1; -; Genomic_DNA.
DR RefSeq; XP_644593.1; XM_639501.1.
DR RefSeq; XP_644658.1; XM_639566.1.
DR AlphaFoldDB; Q557H7; -.
DR SMR; Q557H7; -.
DR STRING; 44689.DDB0185148; -.
DR MEROPS; C54.A08; -.
DR PaxDb; Q557H7; -.
DR PRIDE; Q557H7; -.
DR EnsemblProtists; EAL70676; EAL70676; DDB_G0273443.
DR EnsemblProtists; EAL70731; EAL70731; DDB_G0273553.
DR GeneID; 8618957; -.
DR GeneID; 8619020; -.
DR KEGG; ddi:DDB_G0273443; -.
DR KEGG; ddi:DDB_G0273553; -.
DR dictyBase; DDB_G0273443; atg4-1.
DR dictyBase; DDB_G0273553; atg4-2.
DR eggNOG; KOG2674; Eukaryota.
DR HOGENOM; CLU_373181_0_0_1; -.
DR InParanoid; Q557H7; -.
DR OMA; KIMISFY; -.
DR PhylomeDB; Q557H7; -.
DR Reactome; R-DDI-1632852; Macroautophagy.
DR PRO; PR:Q557H7; -.
DR Proteomes; UP000002195; Chromosome 2.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0008234; F:cysteine-type peptidase activity; IEA:UniProtKB-KW.
DR GO; GO:0006914; P:autophagy; ISS:dictyBase.
DR GO; GO:0015031; P:protein transport; IEA:UniProtKB-KW.
DR GO; GO:0006508; P:proteolysis; ISS:dictyBase.
DR InterPro; IPR038765; Papain-like_cys_pep_sf.
DR InterPro; IPR005078; Peptidase_C54.
DR PANTHER; PTHR22624; PTHR22624; 1.
DR Pfam; PF03416; Peptidase_C54; 1.
DR SUPFAM; SSF54001; SSF54001; 1.
PE 3: Inferred from homology;
KW Autophagy; Cytoplasm; Hydrolase; Protease; Protein transport;
KW Reference proteome; Thiol protease; Transport; Ubl conjugation pathway.
FT CHAIN 1..745
FT /note="Cysteine protease atg4"
FT /id="PRO_0000327587"
FT REGION 29..68
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 192..215
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 344..363
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 439..480
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 686..745
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 688..733
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 262
FT /note="Nucleophile"
FT /evidence="ECO:0000250|UniProtKB:Q9Y4P1"
FT ACT_SITE 562
FT /evidence="ECO:0000250|UniProtKB:Q9Y4P1"
FT ACT_SITE 564
FT /evidence="ECO:0000250|UniProtKB:Q9Y4P1"
FT CONFLICT 713
FT /note="T -> N (in Ref. 1; AAO39081)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 745 AA; 86136 MW; 8F8BAE022A95C84C CRC64;
MFTKYSHHNG YQDGSHLQPF QYQQQTYNQQ SYLRQQQQAP QQISYGFNQP NSPTSSSSTP
SSSTAMGNSF QNQRQINLQQ QQQQEQFLQE QVFYQQQLLQ QQSQIKEQQR QKEQKQKTNI
LNIYKEGKQK IMMSFYNLYR NYPTEPPHFS PSPIWLMGRC YTSKDNNSNN NSNNNQVPQT
QPTQLQQSIG IFQNNNSNSN NNNNHNNNHN NNNNNLTTDL IYRPAIESGF LSDVASMIWF
SYRKDFPPIE NTNITTDIGW GCMLRTGQMI LARALIKHLY KENDMVPEIE RKKPHSNYSQ
VLAWFSDYPS KEHVYGIHQI VNKKQAMEKN NRKQQILREQ VISLNRGGGG SSKGKKKKEK
EEEINDNVEE WLAPTRISNI LRQLIKFQHL EDLEMYVPTD GVIYKDYINN LCNNSNTHNH
YQIIQQQLQH LREQQNIQQN NNKNNNNNNP TTTTTTTTTA TSSNNNNNQS PPSRVPNGYN
NQVFDDESLF DYNTAISSIP PKWKSLIIMI PLKLGADKLN STYIEKLKLL LKLPQSLGFI
GGKPKQSFYF IGFQDDQVIY LDPHFVQESV NPNSFDYSNT YSGCIPQKMP FTQLDPSLSI
GFYCRDQASF EDLCDRLSVI NNCEFPIISV CQKLPDYQIE CELVDDYAES ETTEMLAITI
ANGGNNHSCI PENIVVDDEE FIVHHHIPYN PNNNQNNNQN NNNNNNKNNN NNTNQQQTPN
YPPKLNTYQP DFSSDGEIDD FTMVG
