PACC_EMENI
ID PACC_EMENI Reviewed; 678 AA.
AC Q00202; C8VJC9; Q5B9C5;
DT 21-JUN-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 25-MAY-2022, entry version 125.
DE RecName: Full=pH-response transcription factor pacC/RIM101;
DE Contains:
DE RecName: Full=pH-response transcription factor pacC/RIM101 closed form;
DE Contains:
DE RecName: Full=pH-response transcription factor pacC/RIM101 open form 1;
DE Contains:
DE RecName: Full=pH-response transcription factor pacC/RIM101 open form 2;
DE Flags: Precursor;
GN Name=pacC; ORFNames=AN2855;
OS Emericella nidulans (strain FGSC A4 / ATCC 38163 / CBS 112.46 / NRRL 194 /
OS M139) (Aspergillus nidulans).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC Eurotiomycetidae; Eurotiales; Aspergillaceae; Aspergillus;
OC Aspergillus subgen. Nidulantes.
OX NCBI_TaxID=227321;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, INDUCTION, DNA-BINDING, AND
RP MUTAGENESIS.
RC STRAIN=FGSC A4 / ATCC 38163 / CBS 112.46 / NRRL 194 / M139;
RX PubMed=7882981; DOI=10.1002/j.1460-2075.1995.tb07056.x;
RA Tilburn J., Sarkar S., Widdick D.A., Espeso E.A., Orejas M., Mungroo J.,
RA Penalva M.A., Arst H.N. Jr.;
RT "The Aspergillus PacC zinc finger transcription factor mediates regulation
RT of both acid- and alkaline-expressed genes by ambient pH.";
RL EMBO J. 14:779-790(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=FGSC A4 / ATCC 38163 / CBS 112.46 / NRRL 194 / M139;
RX PubMed=16372000; DOI=10.1038/nature04341;
RA Galagan J.E., Calvo S.E., Cuomo C., Ma L.-J., Wortman J.R., Batzoglou S.,
RA Lee S.-I., Bastuerkmen M., Spevak C.C., Clutterbuck J., Kapitonov V.,
RA Jurka J., Scazzocchio C., Farman M.L., Butler J., Purcell S., Harris S.,
RA Braus G.H., Draht O., Busch S., D'Enfert C., Bouchier C., Goldman G.H.,
RA Bell-Pedersen D., Griffiths-Jones S., Doonan J.H., Yu J., Vienken K.,
RA Pain A., Freitag M., Selker E.U., Archer D.B., Penalva M.A., Oakley B.R.,
RA Momany M., Tanaka T., Kumagai T., Asai K., Machida M., Nierman W.C.,
RA Denning D.W., Caddick M.X., Hynes M., Paoletti M., Fischer R., Miller B.L.,
RA Dyer P.S., Sachs M.S., Osmani S.A., Birren B.W.;
RT "Sequencing of Aspergillus nidulans and comparative analysis with A.
RT fumigatus and A. oryzae.";
RL Nature 438:1105-1115(2005).
RN [3]
RP GENOME REANNOTATION.
RC STRAIN=FGSC A4 / ATCC 38163 / CBS 112.46 / NRRL 194 / M139;
RX PubMed=19146970; DOI=10.1016/j.fgb.2008.12.003;
RA Wortman J.R., Gilsenan J.M., Joardar V., Deegan J., Clutterbuck J.,
RA Andersen M.R., Archer D., Bencina M., Braus G., Coutinho P., von Dohren H.,
RA Doonan J., Driessen A.J., Durek P., Espeso E., Fekete E., Flipphi M.,
RA Estrada C.G., Geysens S., Goldman G., de Groot P.W., Hansen K.,
RA Harris S.D., Heinekamp T., Helmstaedt K., Henrissat B., Hofmann G.,
RA Homan T., Horio T., Horiuchi H., James S., Jones M., Karaffa L.,
RA Karanyi Z., Kato M., Keller N., Kelly D.E., Kiel J.A., Kim J.M.,
RA van der Klei I.J., Klis F.M., Kovalchuk A., Krasevec N., Kubicek C.P.,
RA Liu B., Maccabe A., Meyer V., Mirabito P., Miskei M., Mos M., Mullins J.,
RA Nelson D.R., Nielsen J., Oakley B.R., Osmani S.A., Pakula T., Paszewski A.,
RA Paulsen I., Pilsyk S., Pocsi I., Punt P.J., Ram A.F., Ren Q., Robellet X.,
RA Robson G., Seiboth B., van Solingen P., Specht T., Sun J.,
RA Taheri-Talesh N., Takeshita N., Ussery D., vanKuyk P.A., Visser H.,
RA van de Vondervoort P.J., de Vries R.P., Walton J., Xiang X., Xiong Y.,
RA Zeng A.P., Brandt B.W., Cornell M.J., van den Hondel C.A., Visser J.,
RA Oliver S.G., Turner G.;
RT "The 2008 update of the Aspergillus nidulans genome annotation: a community
RT effort.";
RL Fungal Genet. Biol. 46:S2-13(2009).
RN [4]
RP FUNCTION, AND PROTEOLYTIC PROCESSING.
RX PubMed=7628696; DOI=10.1101/gad.9.13.1622;
RA Orejas M., Espeso E.A., Tilburn J., Sarkar S., Arst H.N. Jr., Penalva M.A.;
RT "Activation of the Aspergillus PacC transcription factor in response to
RT alkaline ambient pH requires proteolysis of the carboxy-terminal moiety.";
RL Genes Dev. 9:1622-1632(1995).
RN [5]
RP DNA-BINDING.
RX PubMed=9417928; DOI=10.1006/jmbi.1997.1428;
RA Espeso E.A., Tilburn J., Sanchez-Pulido L., Brown C.V., Valencia A.,
RA Arst H.N. Jr., Penalva M.A.;
RT "Specific DNA recognition by the Aspergillus nidulans three zinc finger
RT transcription factor PacC.";
RL J. Mol. Biol. 274:466-480(1997).
RN [6]
RP IDENTIFICATION OF PROBABLE INITIATION SITE, AND MUTAGENESIS OF LEU-259;
RP LEU-266 AND LEU-340.
RX PubMed=9891072; DOI=10.1128/mcb.19.2.1390;
RA Mingot J.-M., Tilburn J., Diez E., Bignell E., Orejas M., Widdick D.A.,
RA Sarkar S., Brown C.V., Caddick M.X., Espeso E.A., Arst H.N. Jr.,
RA Penalva M.A.;
RT "Specificity determinants of proteolytic processing of Aspergillus PacC
RT transcription factor are remote from the processing site, and processing
RT occurs in yeast if pH signalling is bypassed.";
RL Mol. Cell. Biol. 19:1390-1400(1999).
RN [7]
RP INTRAMOLECULAR INTERACTION, AND MUTAGENESIS OF LEU-340; ARG-573 AND
RP ARG-579.
RX PubMed=10675341; DOI=10.1093/emboj/19.4.719;
RA Espeso E.A., Roncal T., Diez E., Rainbow L., Bignell E., Alvaro J.,
RA Suarez T., Denison S.H., Tilburn J., Arst H.N. Jr., Penalva M.A.;
RT "On how a transcription factor can avoid its proteolytic activation in the
RT absence of signal transduction.";
RL EMBO J. 19:719-728(2000).
RN [8]
RP SUBCELLULAR LOCATION.
RX PubMed=11238906; DOI=10.1128/mcb.21.5.1688-1699.2001;
RA Mingot J.-M., Espeso E.A., Diez E., Penalva M.A.;
RT "Ambient pH signaling regulates nuclear localization of the Aspergillus
RT nidulans PacC transcription factor.";
RL Mol. Cell. Biol. 21:1688-1699(2001).
RN [9]
RP PROTEOLYTIC PROCESSING, AND MUTAGENESIS OF LEU-498.
RX PubMed=11889040; DOI=10.1093/emboj/21.6.1350;
RA Diez E., Alvaro J., Espeso E.A., Rainbow L., Suarez T., Tilburn J.,
RA Arst H.N. Jr., Penalva M.A.;
RT "Activation of the Aspergillus PacC zinc finger transcription factor
RT requires two proteolytic steps.";
RL EMBO J. 21:1350-1359(2002).
RN [10]
RP DNA-BINDING, AND DOMAINS.
RX PubMed=14636595; DOI=10.1016/j.jmb.2003.09.072;
RA Fernandez-Martinez J., Brown C.V., Diez E., Tilburn J., Arst H.N. Jr.,
RA Penalva M.A., Espeso E.A.;
RT "Overlap of nuclear localisation signal and specific DNA-binding residues
RT within the zinc finger domain of PacC.";
RL J. Mol. Biol. 334:667-684(2003).
RN [11]
RP INTERACTION WITH PALA, AND MUTAGENESIS OF TYR-455 AND TYR-662.
RX PubMed=12588984; DOI=10.1128/mcb.23.5.1647-1655.2003;
RA Vincent O., Rainbow L., Tilburn J., Arst H.N. Jr., Penalva M.A.;
RT "YPXL/I is a protein interaction motif recognized by Aspergillus PalA and
RT its human homologue, AIP1/Alix.";
RL Mol. Cell. Biol. 23:1647-1655(2003).
RN [12]
RP FUNCTION IN VIRULENCE.
RX PubMed=15686555; DOI=10.1111/j.1365-2958.2004.04472.x;
RA Bignell E., Negrete-Urtasun S., Calcagno A.M., Haynes K., Arst H.N. Jr.,
RA Rogers T.;
RT "The Aspergillus pH-responsive transcription factor PacC regulates
RT virulence.";
RL Mol. Microbiol. 55:1072-1084(2005).
CC -!- FUNCTION: Transcription factor that mediates regulation of both
CC acid- and alkaline-expressed genes in response to ambient pH. At
CC alkaline ambient pH, activates transcription of alkaline-expressed
CC genes (including pacC itself) and represses transcription of acid-
CC expressed genes. Specifically recognizes and binds the consensus
CC sequence 5'-GCCARG-3'. Required for virulence in invasive pulmonary
CC aspergillosis (IPA). {ECO:0000269|PubMed:15686555,
CC ECO:0000269|PubMed:7628696, ECO:0000269|PubMed:7882981}.
CC -!- SUBUNIT: Binds to DNA. Interacts with palA, which binds to the two
CC YPX[LI] motifs and is required for proteolytic processing.
CC {ECO:0000269|PubMed:12588984}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:11238906}. Nucleus
CC {ECO:0000269|PubMed:11238906}. Note=Cytoplasmic at acidic ambient pH,
CC and nuclear in its processed form at alkaline ambient pH.
CC -!- INDUCTION: By alkaline conditions. {ECO:0000269|PubMed:7882981}.
CC -!- DOMAIN: Only zinc fingers 2 and 3 contact DNA. Zinc finger 1 interacts
CC with zinc finger 2. {ECO:0000269|PubMed:14636595}.
CC -!- DOMAIN: Interacting regions A, B and C form intramolecular interactions
CC in the full-length translation product at acidic ambient pH, keeping
CC the protein in a 'closed' conformation preventing proteolytic cleavage
CC by the processing protease. {ECO:0000269|PubMed:14636595}.
CC -!- PTM: Activated by C-terminal proteolytic cleavage. At neutral to
CC alkaline ambient pH, the signaling protease (probably palB) cleaves
CC pacC within the conserved 24-residue signaling protease box, removing
CC the C-terminal interacting region C and producing a 53 kDa 'open'
CC conformation intermediate protein, which is committed to further
CC processing. In an ambient pH-independent reaction, the processing
CC protease (probably the proteasome) removes additional C-terminal
CC residues to yield the 27 kDa functional form.
CC {ECO:0000269|PubMed:11889040, ECO:0000269|PubMed:7628696}.
CC -!- SIMILARITY: Belongs to the pacC/RIM101 family. {ECO:0000305}.
CC -!- CAUTION: Met-5 is the major initiator, but Met-1 may also be used.
CC {ECO:0000305}.
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DR EMBL; Z47081; CAA87390.1; -; Genomic_DNA.
DR EMBL; AACD01000051; EAA63426.1; -; Genomic_DNA.
DR EMBL; BN001306; CBF83867.1; -; Genomic_DNA.
DR PIR; S54308; S54308.
DR RefSeq; XP_660459.1; XM_655367.1.
DR AlphaFoldDB; Q00202; -.
DR ELM; Q00202; -.
DR STRING; 162425.CADANIAP00010235; -.
DR EnsemblFungi; EAA63426; EAA63426; AN2855.2.
DR GeneID; 2873843; -.
DR KEGG; ani:AN2855.2; -.
DR eggNOG; KOG1721; Eukaryota.
DR HOGENOM; CLU_012842_1_0_1; -.
DR InParanoid; Q00202; -.
DR OrthoDB; 507875at2759; -.
DR PHI-base; PHI:398; -.
DR Proteomes; UP000000560; Chromosome VI.
DR Proteomes; UP000005890; Unassembled WGS sequence.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0003677; F:DNA binding; IEA:UniProtKB-KW.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR InterPro; IPR036236; Znf_C2H2_sf.
DR InterPro; IPR013087; Znf_C2H2_type.
DR Pfam; PF00096; zf-C2H2; 1.
DR SMART; SM00355; ZnF_C2H2; 3.
DR SUPFAM; SSF57667; SSF57667; 2.
DR PROSITE; PS00028; ZINC_FINGER_C2H2_1; 2.
DR PROSITE; PS50157; ZINC_FINGER_C2H2_2; 2.
PE 1: Evidence at protein level;
KW Activator; Cytoplasm; DNA-binding; Metal-binding; Nucleus;
KW Reference proteome; Repeat; Repressor; Transcription;
KW Transcription regulation; Zinc; Zinc-finger.
FT CHAIN 1..678
FT /note="pH-response transcription factor pacC/RIM101 closed
FT form"
FT /id="PRO_0000046832"
FT CHAIN 1..?493
FT /note="pH-response transcription factor pacC/RIM101 open
FT form 2"
FT /id="PRO_0000312590"
FT CHAIN 1..?252
FT /note="pH-response transcription factor pacC/RIM101 open
FT form 1"
FT /id="PRO_0000312589"
FT PROPEP ?253..?493
FT /note="Removed in open form 1; by processing protease"
FT /id="PRO_0000312591"
FT PROPEP ?494..678
FT /note="Removed in open form 2; by signaling protease"
FT /id="PRO_0000312592"
FT ZN_FING 76..101
FT /note="C2H2-type 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT ZN_FING 112..136
FT /note="C2H2-type 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT ZN_FING 142..164
FT /note="C2H2-type 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT REGION 1..31
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 51..70
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 169..301
FT /note="Interacting region A"
FT REGION 252..254
FT /note="Processing protease cleavage"
FT REGION 334..410
FT /note="Interacting region B"
FT REGION 377..565
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 479..502
FT /note="Signaling protease box"
FT REGION 493..500
FT /note="Signaling protease cleavage"
FT REGION 529..592
FT /note="Interacting region C"
FT REGION 590..678
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 158..164
FT /note="Nuclear localization signal"
FT MOTIF 455..458
FT /note="YPX[LI] motif 1"
FT MOTIF 662..665
FT /note="YPX[LI] motif 2"
FT COMPBIAS 16..31
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 378..438
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 455..477
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 593..611
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 624..640
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MUTAGEN 259
FT /note="L->R: Prevents intramolecular interactions,
FT resulting in the 'open' conformation protein committed to
FT processing independent on ambient pH."
FT /evidence="ECO:0000269|PubMed:9891072"
FT MUTAGEN 266
FT /note="L->F: Prevents intramolecular interactions,
FT resulting in the 'open' conformation protein committed to
FT processing independent on ambient pH."
FT /evidence="ECO:0000269|PubMed:9891072"
FT MUTAGEN 340
FT /note="L->S: Prevents intramolecular interactions,
FT resulting in the 'open' conformation protein committed to
FT processing independent on ambient pH."
FT /evidence="ECO:0000269|PubMed:10675341,
FT ECO:0000269|PubMed:9891072"
FT MUTAGEN 455
FT /note="Y->D: Abolishes interaction with palA. Severely
FT reduces proteolytic processing of the full-length
FT translation product by signaling protease, causing a
FT stringent loss-of-function, acidity-mimicking phenotype."
FT /evidence="ECO:0000269|PubMed:12588984"
FT MUTAGEN 498
FT /note="L->F: Partially reduces proteolytic cleavage of the
FT full-length translation product by signaling protease."
FT /evidence="ECO:0000269|PubMed:11889040"
FT MUTAGEN 498
FT /note="L->S: Completely prevents proteolytic cleavage of
FT the full-length translation product by signaling protease."
FT /evidence="ECO:0000269|PubMed:11889040"
FT MUTAGEN 573
FT /note="R->W: Prevents intramolecular interactions,
FT resulting in the 'open' conformation protein committed to
FT processing independent on ambient pH."
FT /evidence="ECO:0000269|PubMed:10675341"
FT MUTAGEN 579
FT /note="R->G,T: Prevents intramolecular interactions,
FT resulting in the 'open' conformation protein committed to
FT processing independent on ambient pH."
FT /evidence="ECO:0000269|PubMed:10675341"
FT MUTAGEN 662
FT /note="Y->N: Abolishes interaction with palA. Partially
FT reduces proteolytic processing of the full-length
FT translation product by signaling protease, causing a weak
FT loss-of-function phenotype."
FT /evidence="ECO:0000269|PubMed:12588984"
FT CONFLICT 189
FT /note="G -> F (in Ref. 2; EAA63426/CBF83867)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 678 AA; 72939 MW; 7B626632C8366342 CRC64;
MLGAMAEEAV APVAVPTTQE QPTSQPAAAQ VTTVTSPSVT ATAAAATAAV ASPQANGNAA
SPVAPASSTS RPAEELTCMW QGCSEKLPTP ESLYEHVCER HVGRKSTNNL NLTCQWGSCR
TTTVKRDHIT SHIRVHVPLK PHKCDFCGKA FKRPQDLKKH VKTHADDSVL VRSPEPGSRN
PDMMFGGNGK GYAAAHYFEP ALNPVPSQGY AHGPPQYYQA HHAPQPSNPS YGNVYYALNT
GPEPHQASYE SKKRGYDALN EFFGDLKRRQ FDPNSYAAVG QRLLSLQNLS LPVLTAAPLP
EYQAMPAPVA VASGPYGGGP HPAPAYHLPP MSNVRTKNDL INIDQFLQQM QDTIYENDDN
VAAAGVAQPG AHYIHNGISY RTTHSPPTQL PSAHATTQTT AGPIISNTSA HSPSSSTPAL
TPPSSAQSYT SGRSPISLPS AHRVSPPHES GSSMYPRLPS ATDGMTSGYT AASSAAPPST
LGGIFDNDER RRYTGGTLQR ARPASRAASE SMDLSSDDKE SGERTPKQIS ASLIDPALHS
GSPGEDDVTR TAKAATEVAE RSDVQSEWVE KVRLIEYLRN YIANRLERGE FSDDSEQEQD
QEQEQDQEQE QDQEQGQDRV SRSPVSKADV DMEGVERDSL PRSPRTVPIK TDGESAEDSV
MYPTLRGLDE DGDSKMPS
