PAN_METJA
ID PAN_METJA Reviewed; 430 AA.
AC Q58576;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 03-AUG-2022, entry version 136.
DE RecName: Full=Proteasome-activating nucleotidase {ECO:0000255|HAMAP-Rule:MF_00553};
DE Short=PAN {ECO:0000255|HAMAP-Rule:MF_00553};
DE AltName: Full=Proteasomal ATPase {ECO:0000255|HAMAP-Rule:MF_00553};
DE AltName: Full=Proteasome regulatory ATPase {ECO:0000255|HAMAP-Rule:MF_00553};
DE AltName: Full=Proteasome regulatory particle {ECO:0000255|HAMAP-Rule:MF_00553};
GN Name=pan {ECO:0000255|HAMAP-Rule:MF_00553}; OrderedLocusNames=MJ1176;
OS Methanocaldococcus jannaschii (strain ATCC 43067 / DSM 2661 / JAL-1 / JCM
OS 10045 / NBRC 100440) (Methanococcus jannaschii).
OC Archaea; Euryarchaeota; Methanomada group; Methanococci; Methanococcales;
OC Methanocaldococcaceae; Methanocaldococcus.
OX NCBI_TaxID=243232;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 43067 / DSM 2661 / JAL-1 / JCM 10045 / NBRC 100440;
RX PubMed=8688087; DOI=10.1126/science.273.5278.1058;
RA Bult C.J., White O., Olsen G.J., Zhou L., Fleischmann R.D., Sutton G.G.,
RA Blake J.A., FitzGerald L.M., Clayton R.A., Gocayne J.D., Kerlavage A.R.,
RA Dougherty B.A., Tomb J.-F., Adams M.D., Reich C.I., Overbeek R.,
RA Kirkness E.F., Weinstock K.G., Merrick J.M., Glodek A., Scott J.L.,
RA Geoghagen N.S.M., Weidman J.F., Fuhrmann J.L., Nguyen D., Utterback T.R.,
RA Kelley J.M., Peterson J.D., Sadow P.W., Hanna M.C., Cotton M.D.,
RA Roberts K.M., Hurst M.A., Kaine B.P., Borodovsky M., Klenk H.-P.,
RA Fraser C.M., Smith H.O., Woese C.R., Venter J.C.;
RT "Complete genome sequence of the methanogenic archaeon, Methanococcus
RT jannaschii.";
RL Science 273:1058-1073(1996).
RN [2]
RP PROTEIN SEQUENCE OF N-TERMINUS, FUNCTION AS AN ATPASE, BIOPHYSICOCHEMICAL
RP PROPERTIES, ACTIVITY REGULATION, SUBUNIT, AND INTERACTION WITH THE
RP PROTEASOME.
RX PubMed=10692374; DOI=10.1128/jb.182.6.1680-1692.2000;
RA Wilson H.L., Ou M.S., Aldrich H.C., Maupin-Furlow J.;
RT "Biochemical and physical properties of the Methanococcus jannaschii 20S
RT proteasome and PAN, a homolog of the ATPase (Rpt) subunits of the eucaryal
RT 26S proteasome.";
RL J. Bacteriol. 182:1680-1692(2000).
RN [3]
RP FUNCTION IN THE PROTEASOME DEGRADATION PATHWAY, ATPASE ACTIVITY, NUCLEOTIDE
RP SPECIFICITY, AND ACTIVITY REGULATION.
RX PubMed=10473546; DOI=10.1074/jbc.274.37.26008;
RA Zwickl P., Ng D., Woo K.M., Klenk H.-P., Goldberg A.L.;
RT "An archaebacterial ATPase, homologous to ATPases in the eukaryotic 26 S
RT proteasome, activates protein breakdown by 20 S proteasomes.";
RL J. Biol. Chem. 274:26008-26014(1999).
RN [4]
RP CHAPERONE ACTIVITY.
RX PubMed=11056539; DOI=10.1038/35041081;
RA Benaroudj N., Goldberg A.L.;
RT "PAN, the proteasome-activating nucleotidase from archaebacteria, is a
RT protein-unfolding molecular chaperone.";
RL Nat. Cell Biol. 2:833-839(2000).
RN [5]
RP FUNCTION, INTERACTION WITH THE PROTEASOME, AND SUBUNIT.
RX PubMed=16337593; DOI=10.1016/j.molcel.2005.10.019;
RA Smith D.M., Kafri G., Cheng Y., Ng D., Walz T., Goldberg A.L.;
RT "ATP binding to PAN or the 26S ATPases causes association with the 20S
RT proteasome, gate opening, and translocation of unfolded proteins.";
RL Mol. Cell 20:687-698(2005).
RN [6]
RP FUNCTION, ROLE OF C-TERMINUS IN GATE OPENING, AND MUTAGENESIS OF LEU-428;
RP TYR-429 AND ARG-430.
RX PubMed=17803938; DOI=10.1016/j.molcel.2007.06.033;
RA Smith D.M., Chang S.C., Park S., Finley D., Cheng Y., Goldberg A.L.;
RT "Docking of the proteasomal ATPases' carboxyl termini in the 20S
RT proteasome's alpha ring opens the gate for substrate entry.";
RL Mol. Cell 27:731-744(2007).
RN [7]
RP FUNCTION, UNFOLDING AND TRANSLOCATION MECHANISM, AND MUTAGENESIS OF
RP GLY-113; ASP-153; ALA-156; LYS-157; PHE-244; ILE-245; GLY-246;
RP 250-SER-LEU-251; GLU-271; GLY-285 AND GLY-286.
RX PubMed=19481528; DOI=10.1016/j.molcel.2009.04.022;
RA Zhang F., Wu Z., Zhang P., Tian G., Finley D., Shi Y.;
RT "Mechanism of substrate unfolding and translocation by the regulatory
RT particle of the proteasome from Methanocaldococcus jannaschii.";
RL Mol. Cell 34:485-496(2009).
RN [8]
RP X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 74-430 IN COMPLEX WITH ADP, AND
RP DOMAIN.
RX PubMed=19481527; DOI=10.1016/j.molcel.2009.04.021;
RA Zhang F., Hu M., Tian G., Zhang P., Finley D., Jeffrey P.D., Shi Y.;
RT "Structural insights into the regulatory particle of the proteasome from
RT Methanocaldococcus jannaschii.";
RL Mol. Cell 34:473-484(2009).
RN [9]
RP X-RAY CRYSTALLOGRAPHY (4.0 ANGSTROMS) OF 424-430 IN COMPLEX WITH THE
RP PROTEASOME OF T.ACIDOPHILUM.
RX PubMed=20019667; DOI=10.1038/emboj.2009.382;
RA Yu Y., Smith D.M., Kim H.M., Rodriguez V., Goldberg A.L., Cheng Y.;
RT "Interactions of PAN's C-termini with archaeal 20S proteasome and
RT implications for the eukaryotic proteasome-ATPase interactions.";
RL EMBO J. 29:692-702(2010).
CC -!- FUNCTION: ATPase which is responsible for recognizing, binding,
CC unfolding and translocation of substrate proteins into the archaeal 20S
CC proteasome core particle. Is essential for opening the gate of the 20S
CC proteasome via an interaction with its C-terminus, thereby allowing
CC substrate entry and access to the site of proteolysis. Thus, the C-
CC termini of the proteasomal ATPase function like a 'key in a lock' to
CC induce gate opening and therefore regulate proteolysis. Unfolding
CC activity requires energy from ATP hydrolysis, whereas ATP binding alone
CC promotes ATPase-20S proteasome association which triggers gate opening,
CC and supports translocation of unfolded substrates. In addition to ATP,
CC is able to cleave other nucleotide triphosphates such as CTP, GTP and
CC UTP, but hydrolysis of these other nucleotides is less effective in
CC promoting proteolysis than ATP. Moreover, PAN by itself can function as
CC a chaperone in vitro. {ECO:0000255|HAMAP-Rule:MF_00553,
CC ECO:0000269|PubMed:10473546, ECO:0000269|PubMed:10692374,
CC ECO:0000269|PubMed:16337593, ECO:0000269|PubMed:17803938,
CC ECO:0000269|PubMed:19481528}.
CC -!- ACTIVITY REGULATION: ATPase activity is inhibited by EDTA, N-
CC ethylmaleimide (NEM) and p-chloromercuriphenyl-sulfonic acid (PCMS) in
CC vitro. {ECO:0000269|PubMed:10473546, ECO:0000269|PubMed:10692374}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=497 uM for ATP {ECO:0000269|PubMed:10692374};
CC KM=307 uM for CTP {ECO:0000269|PubMed:10692374};
CC Vmax=3.5 umol/min/mg enzyme for ATPase activity
CC {ECO:0000269|PubMed:10692374};
CC Vmax=5.8 umol/min/mg enzyme for CTPase activity
CC {ECO:0000269|PubMed:10692374};
CC pH dependence:
CC Optimum pH is 7-8 for ATPase activity. Is more active at pH 8 to 10
CC than at pH 5.5. {ECO:0000269|PubMed:10692374};
CC Temperature dependence:
CC Optimum temperature is 80 degrees Celsius for ATPase activity.
CC {ECO:0000269|PubMed:10692374};
CC -!- SUBUNIT: Homohexamer. The hexameric complex has a two-ring architecture
CC resembling a top hat that caps the 20S proteasome core at one or both
CC ends. Alone, can form a complex composed of two stacked hexameric rings
CC in vitro. Upon ATP-binding, the C-terminus of PAN interacts with the
CC alpha-rings of the proteasome core by binding to the intersubunit
CC pockets. {ECO:0000269|PubMed:10692374, ECO:0000269|PubMed:16337593,
CC ECO:0000269|PubMed:19481527, ECO:0000269|PubMed:20019667}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm.
CC -!- DOMAIN: Consists of three main regions, an N-terminal coiled-coil
CC domain that may assist in substrate recognition, an interdomain
CC involved in PAN hexamerization, and a C-terminal ATPase domain of the
CC AAA type. {ECO:0000255|HAMAP-Rule:MF_00553,
CC ECO:0000269|PubMed:19481527}.
CC -!- SIMILARITY: Belongs to the AAA ATPase family. {ECO:0000255|HAMAP-
CC Rule:MF_00553}.
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DR EMBL; L77117; AAB99179.1; -; Genomic_DNA.
DR PIR; G64446; G64446.
DR RefSeq; WP_010870689.1; NC_000909.1.
DR PDB; 3H43; X-ray; 2.10 A; A/B/C/D/E/F/G/H/I/J/K/L=74-150.
DR PDB; 3H4M; X-ray; 3.11 A; A/B/C=155-430.
DR PDB; 3IPM; X-ray; 4.00 A; O/P/Q/R/S/T/U=424-430.
DR PDBsum; 3H43; -.
DR PDBsum; 3H4M; -.
DR PDBsum; 3IPM; -.
DR AlphaFoldDB; Q58576; -.
DR SMR; Q58576; -.
DR STRING; 243232.MJ_1176; -.
DR PRIDE; Q58576; -.
DR EnsemblBacteria; AAB99179; AAB99179; MJ_1176.
DR GeneID; 1452074; -.
DR KEGG; mja:MJ_1176; -.
DR eggNOG; arCOG01306; Archaea.
DR HOGENOM; CLU_000688_2_1_2; -.
DR InParanoid; Q58576; -.
DR OMA; YNMTTFE; -.
DR OrthoDB; 30571at2157; -.
DR PhylomeDB; Q58576; -.
DR BRENDA; 5.6.1.5; 3260.
DR SABIO-RK; Q58576; -.
DR EvolutionaryTrace; Q58576; -.
DR Proteomes; UP000000805; Chromosome.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0008540; C:proteasome regulatory particle, base subcomplex; IBA:GO_Central.
DR GO; GO:0022623; C:proteasome-activating nucleotidase complex; IDA:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-UniRule.
DR GO; GO:0016887; F:ATP hydrolysis activity; IDA:UniProtKB.
DR GO; GO:0043273; F:CTPase activity; IDA:UniProtKB.
DR GO; GO:0003924; F:GTPase activity; IDA:UniProtKB.
DR GO; GO:0036402; F:proteasome-activating activity; IBA:GO_Central.
DR GO; GO:0010498; P:proteasomal protein catabolic process; IDA:UniProtKB.
DR GO; GO:0043161; P:proteasome-mediated ubiquitin-dependent protein catabolic process; IBA:GO_Central.
DR GO; GO:0043335; P:protein unfolding; IDA:UniProtKB.
DR Gene3D; 2.40.50.140; -; 1.
DR Gene3D; 3.40.50.300; -; 1.
DR HAMAP; MF_00553; PAN; 1.
DR InterPro; IPR005937; 26S_Psome_P45-like.
DR InterPro; IPR003593; AAA+_ATPase.
DR InterPro; IPR041569; AAA_lid_3.
DR InterPro; IPR003959; ATPase_AAA_core.
DR InterPro; IPR003960; ATPase_AAA_CS.
DR InterPro; IPR012340; NA-bd_OB-fold.
DR InterPro; IPR023501; Nucleotidase_PAN.
DR InterPro; IPR027417; P-loop_NTPase.
DR InterPro; IPR032501; Prot_ATP_ID_OB_C.
DR Pfam; PF00004; AAA; 1.
DR Pfam; PF17862; AAA_lid_3; 1.
DR Pfam; PF16450; Prot_ATP_ID_OB; 1.
DR SMART; SM00382; AAA; 1.
DR SUPFAM; SSF52540; SSF52540; 1.
DR TIGRFAMs; TIGR01242; 26Sp45; 1.
DR PROSITE; PS00674; AAA; 1.
PE 1: Evidence at protein level;
KW 3D-structure; ATP-binding; Chaperone; Coiled coil; Cytoplasm;
KW Direct protein sequencing; Nucleotide-binding; Proteasome;
KW Reference proteome.
FT CHAIN 1..430
FT /note="Proteasome-activating nucleotidase"
FT /id="PRO_0000084743"
FT REGION 428..430
FT /note="Docks into pockets in the proteasome alpha-ring to
FT cause gate opening"
FT COILED 9..89
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00553"
FT BINDING 214..219
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT BINDING 353
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT MUTAGEN 113
FT /note="G->W: 7% of wild-type unfolding activity."
FT /evidence="ECO:0000269|PubMed:19481528"
FT MUTAGEN 153
FT /note="D->A: 2% of wild-type unfolding activity."
FT /evidence="ECO:0000269|PubMed:19481528"
FT MUTAGEN 156
FT /note="A->D: 1.5% of wild-type unfolding activity."
FT /evidence="ECO:0000269|PubMed:19481528"
FT MUTAGEN 157
FT /note="K->G: 4% of wild-type unfolding activity."
FT /evidence="ECO:0000269|PubMed:19481528"
FT MUTAGEN 244
FT /note="F->A: 1% of wild-type unfolding activity."
FT /evidence="ECO:0000269|PubMed:19481528"
FT MUTAGEN 245
FT /note="I->A,W: 4% of wild-type unfolding activity."
FT /evidence="ECO:0000269|PubMed:19481528"
FT MUTAGEN 246
FT /note="G->A: 5% of wild-type unfolding activity."
FT /evidence="ECO:0000269|PubMed:19481528"
FT MUTAGEN 250..251
FT /note="SL->AA: 4% of wild-type unfolding activity."
FT /evidence="ECO:0000269|PubMed:19481528"
FT MUTAGEN 271
FT /note="E->K: 9% of wild-type unfolding activity."
FT /evidence="ECO:0000269|PubMed:19481528"
FT MUTAGEN 285
FT /note="G->W: 1.6% of wild-type unfolding activity."
FT /evidence="ECO:0000269|PubMed:19481528"
FT MUTAGEN 286
FT /note="G->A: No effect on unfolding activity."
FT /evidence="ECO:0000269|PubMed:19481528"
FT MUTAGEN 286
FT /note="G->L,W: 4% of wild-type unfolding activity."
FT /evidence="ECO:0000269|PubMed:19481528"
FT MUTAGEN 428
FT /note="L->A,V,F: Markedly decreased PAN's ability to
FT stimulate gate opening."
FT /evidence="ECO:0000269|PubMed:17803938"
FT MUTAGEN 428
FT /note="L->I,Y,W: Slightly decreased PAN's ability to
FT stimulate gate opening."
FT /evidence="ECO:0000269|PubMed:17803938"
FT MUTAGEN 428
FT /note="L->R,D,C,P: Loss of PAN's ability to stimulate gate
FT opening. Fails to associate with the proteasome."
FT /evidence="ECO:0000269|PubMed:17803938"
FT MUTAGEN 429
FT /note="Y->A,V,I,L,F,W,R,D: Loss of PAN's ability to
FT stimulate gate opening. Fails to associate with the
FT proteasome."
FT /evidence="ECO:0000269|PubMed:17803938"
FT MUTAGEN 430
FT /note="R->A,W: No effect on PAN's ability to stimulate gate
FT opening. Still associates with the proteasome."
FT /evidence="ECO:0000269|PubMed:17803938"
FT MUTAGEN 430
FT /note="R->D: Loss of PAN's ability to stimulate gate
FT opening."
FT /evidence="ECO:0000269|PubMed:17803938"
FT MUTAGEN 430
FT /note="R->G: Slightly decreased PAN's ability to stimulate
FT gate opening."
FT /evidence="ECO:0000269|PubMed:17803938"
FT MUTAGEN 430
FT /note="R->L: Markedly decreased PAN's ability to stimulate
FT gate opening."
FT /evidence="ECO:0000269|PubMed:17803938"
FT MUTAGEN 430
FT /note="R->RA: Loss of PAN's ability to stimulate gate
FT opening. Fails to associate with the proteasome."
FT /evidence="ECO:0000269|PubMed:17803938"
FT MUTAGEN 430
FT /note="Missing: Loss of PAN's ability to stimulate gate
FT opening. Fails to associate with the proteasome."
FT /evidence="ECO:0000269|PubMed:17803938"
FT HELIX 75..88
FT /evidence="ECO:0007829|PDB:3H43"
FT STRAND 92..102
FT /evidence="ECO:0007829|PDB:3H43"
FT STRAND 105..110
FT /evidence="ECO:0007829|PDB:3H43"
FT STRAND 113..120
FT /evidence="ECO:0007829|PDB:3H43"
FT HELIX 126..128
FT /evidence="ECO:0007829|PDB:3H43"
FT STRAND 134..137
FT /evidence="ECO:0007829|PDB:3H43"
FT TURN 139..141
FT /evidence="ECO:0007829|PDB:3H43"
FT STRAND 144..147
FT /evidence="ECO:0007829|PDB:3H43"
FT STRAND 159..164
FT /evidence="ECO:0007829|PDB:3H4M"
FT HELIX 169..171
FT /evidence="ECO:0007829|PDB:3H4M"
FT HELIX 176..185
FT /evidence="ECO:0007829|PDB:3H4M"
FT HELIX 187..191
FT /evidence="ECO:0007829|PDB:3H4M"
FT HELIX 193..199
FT /evidence="ECO:0007829|PDB:3H4M"
FT STRAND 205..216
FT /evidence="ECO:0007829|PDB:3H4M"
FT HELIX 217..227
FT /evidence="ECO:0007829|PDB:3H4M"
FT STRAND 231..236
FT /evidence="ECO:0007829|PDB:3H4M"
FT HELIX 237..240
FT /evidence="ECO:0007829|PDB:3H4M"
FT HELIX 247..261
FT /evidence="ECO:0007829|PDB:3H4M"
FT STRAND 264..270
FT /evidence="ECO:0007829|PDB:3H4M"
FT HELIX 273..276
FT /evidence="ECO:0007829|PDB:3H4M"
FT STRAND 280..282
FT /evidence="ECO:0007829|PDB:3H4M"
FT HELIX 285..288
FT /evidence="ECO:0007829|PDB:3H4M"
FT HELIX 289..302
FT /evidence="ECO:0007829|PDB:3H4M"
FT STRAND 306..315
FT /evidence="ECO:0007829|PDB:3H4M"
FT HELIX 319..321
FT /evidence="ECO:0007829|PDB:3H4M"
FT HELIX 324..327
FT /evidence="ECO:0007829|PDB:3H4M"
FT STRAND 331..337
FT /evidence="ECO:0007829|PDB:3H4M"
FT HELIX 343..354
FT /evidence="ECO:0007829|PDB:3H4M"
FT HELIX 365..371
FT /evidence="ECO:0007829|PDB:3H4M"
FT HELIX 377..393
FT /evidence="ECO:0007829|PDB:3H4M"
FT STRAND 397..399
FT /evidence="ECO:0007829|PDB:3H4M"
FT HELIX 401..415
FT /evidence="ECO:0007829|PDB:3H4M"
SQ SEQUENCE 430 AA; 48690 MW; 3FD2E94A68D483DD CRC64;
MVFEEFISTE LKKEKKAFTE EFKEEKEIND NSNLKNDLLK EELQEKARIA ELESRILKLE
LEKKELEREN LQLMKENEIL RRELDRMRVP PLIVGTVVDK VGERKVVVKS STGPSFLVNV
SHFVNPDDLA PGKRVCLNQQ TLTVVDVLPE NKDYRAKAME VDERPNVRYE DIGGLEKQMQ
EIREVVELPL KHPELFEKVG IEPPKGILLY GPPGTGKTLL AKAVATETNA TFIRVVGSEL
VKKFIGEGAS LVKDIFKLAK EKAPSIIFID EIDAIAAKRT DALTGGDREV QRTLMQLLAE
MDGFDARGDV KIIGATNRPD ILDPAILRPG RFDRIIEVPA PDEKGRLEIL KIHTRKMNLA
EDVNLEEIAK MTEGCVGAEL KAICTEAGMN AIRELRDYVT MDDFRKAVEK IMEKKKVKVK
EPAHLDVLYR
