PFA4_CRYNH
ID PFA4_CRYNH Reviewed; 456 AA.
AC J9VJ99;
DT 09-DEC-2015, integrated into UniProtKB/Swiss-Prot.
DT 09-DEC-2015, sequence version 2.
DT 25-MAY-2022, entry version 51.
DE RecName: Full=Palmitoyltransferase PFA4 {ECO:0000255|HAMAP-Rule:MF_03199, ECO:0000305|PubMed:25970403};
DE EC=2.3.1.225 {ECO:0000255|HAMAP-Rule:MF_03199};
DE AltName: Full=Protein S-acyltransferase {ECO:0000255|HAMAP-Rule:MF_03199, ECO:0000303|PubMed:25970403};
DE Short=PAT {ECO:0000255|HAMAP-Rule:MF_03199};
DE AltName: Full=Protein fatty acyltransferase 4 {ECO:0000255|HAMAP-Rule:MF_03199};
GN Name=PFA4 {ECO:0000255|HAMAP-Rule:MF_03199, ECO:0000303|PubMed:25970403};
GN ORFNames=CNAG_03981;
OS Cryptococcus neoformans var. grubii serotype A (strain H99 / ATCC 208821 /
OS CBS 10515 / FGSC 9487) (Filobasidiella neoformans var. grubii).
OC Eukaryota; Fungi; Dikarya; Basidiomycota; Agaricomycotina; Tremellomycetes;
OC Tremellales; Cryptococcaceae; Cryptococcus;
OC Cryptococcus neoformans species complex.
OX NCBI_TaxID=235443;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=H99 / ATCC 208821 / CBS 10515 / FGSC 9487;
RX PubMed=24743168; DOI=10.1371/journal.pgen.1004261;
RA Janbon G., Ormerod K.L., Paulet D., Byrnes E.J. III, Yadav V.,
RA Chatterjee G., Mullapudi N., Hon C.-C., Billmyre R.B., Brunel F.,
RA Bahn Y.-S., Chen W., Chen Y., Chow E.W.L., Coppee J.-Y., Floyd-Averette A.,
RA Gaillardin C., Gerik K.J., Goldberg J., Gonzalez-Hilarion S., Gujja S.,
RA Hamlin J.L., Hsueh Y.-P., Ianiri G., Jones S., Kodira C.D., Kozubowski L.,
RA Lam W., Marra M., Mesner L.D., Mieczkowski P.A., Moyrand F., Nielsen K.,
RA Proux C., Rossignol T., Schein J.E., Sun S., Wollschlaeger C., Wood I.A.,
RA Zeng Q., Neuveglise C., Newlon C.S., Perfect J.R., Lodge J.K., Idnurm A.,
RA Stajich J.E., Kronstad J.W., Sanyal K., Heitman J., Fraser J.A.,
RA Cuomo C.A., Dietrich F.S.;
RT "Analysis of the genome and transcriptome of Cryptococcus neoformans var.
RT grubii reveals complex RNA expression and microevolution leading to
RT virulence attenuation.";
RL PLoS Genet. 10:E1004261-E1004261(2014).
RN [2]
RP FUNCTION, DISRUPTION PHENOTYPE, AND MUTAGENESIS OF 124-HIS-CYS-125.
RC STRAIN=H99 / ATCC 208821 / CBS 10515 / FGSC 9487;
RX PubMed=25970403; DOI=10.1371/journal.ppat.1004908;
RA Santiago-Tirado F.H., Peng T., Yang M., Hang H.C., Doering T.L.;
RT "A single protein S-acyl transferase acts through diverse substrates to
RT determine cryptococcal morphology, stress tolerance, and pathogenic
RT outcome.";
RL PLoS Pathog. 11:E1004908-E1004908(2015).
CC -!- FUNCTION: Mediates the reversible addition of palmitate to target
CC proteins, thereby regulating their membrane association and biological
CC function. Responsible for the modification of a subset of proteins that
CC are critical in cryptococcal pathogenesis, with substrates involved in
CC cell wall synthesis, signal transduction, and membrane trafficking.
CC Palmitoylates chitin synthase CHS3. {ECO:0000255|HAMAP-Rule:MF_03199,
CC ECO:0000269|PubMed:25970403}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=hexadecanoyl-CoA + L-cysteinyl-[protein] = CoA + S-
CC hexadecanoyl-L-cysteinyl-[protein]; Xref=Rhea:RHEA:36683, Rhea:RHEA-
CC COMP:10131, Rhea:RHEA-COMP:11032, ChEBI:CHEBI:29950,
CC ChEBI:CHEBI:57287, ChEBI:CHEBI:57379, ChEBI:CHEBI:74151;
CC EC=2.3.1.225; Evidence={ECO:0000255|HAMAP-Rule:MF_03199};
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000255|HAMAP-Rule:MF_03199}; Multi-pass membrane protein
CC {ECO:0000255|HAMAP-Rule:MF_03199}.
CC -!- DOMAIN: The DHHC domain is required for palmitoyltransferase activity.
CC {ECO:0000255|HAMAP-Rule:MF_03199}.
CC -!- DISRUPTION PHENOTYPE: Displays morphological changes and shows
CC increases in adherence to and engulfment by host macrophages. Causes
CC dramatic defects in cryptococcal morphology, stress tolerance, and
CC virulence. {ECO:0000269|PubMed:25970403}.
CC -!- SIMILARITY: Belongs to the DHHC palmitoyltransferase family. PFA4
CC subfamily. {ECO:0000255|HAMAP-Rule:MF_03199}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AFR93481.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305|PubMed:25970403};
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DR EMBL; CP003821; AFR93481.1; ALT_SEQ; Genomic_DNA.
DR RefSeq; XP_012047592.1; XM_012192202.1.
DR AlphaFoldDB; J9VJ99; -.
DR SMR; J9VJ99; -.
DR EnsemblFungi; AFR93481; AFR93481; CNAG_03981.
DR GeneID; 23887432; -.
DR HOGENOM; CLU_027721_9_0_1; -.
DR PHI-base; PHI:4785; -.
DR PHI-base; PHI:6585; -.
DR Proteomes; UP000010091; Chromosome 2.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0016409; F:palmitoyltransferase activity; IMP:UniProtKB.
DR GO; GO:0019706; F:protein-cysteine S-palmitoyltransferase activity; IEA:UniProtKB-UniRule.
DR GO; GO:0061951; P:establishment of protein localization to plasma membrane; IMP:UniProtKB.
DR GO; GO:0018345; P:protein palmitoylation; IEA:UniProtKB-UniRule.
DR HAMAP; MF_03199; DHHC_PAT_PFA4; 1.
DR InterPro; IPR001594; Palmitoyltrfase_DHHC.
DR InterPro; IPR033682; PFA4.
DR Pfam; PF01529; DHHC; 1.
DR PROSITE; PS50216; DHHC; 1.
PE 1: Evidence at protein level;
KW Acyltransferase; Endoplasmic reticulum; Lipoprotein; Membrane; Palmitate;
KW Transferase; Transmembrane; Transmembrane helix.
FT CHAIN 1..456
FT /note="Palmitoyltransferase PFA4"
FT /id="PRO_0000435134"
FT TOPO_DOM 1..9
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03199"
FT TRANSMEM 10..30
FT /note="Helical"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03199"
FT TOPO_DOM 31..37
FT /note="Lumenal"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03199"
FT TRANSMEM 38..58
FT /note="Helical"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03199"
FT TOPO_DOM 59..138
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03199"
FT TRANSMEM 139..159
FT /note="Helical"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03199"
FT TOPO_DOM 160..176
FT /note="Lumenal"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03199"
FT TRANSMEM 177..197
FT /note="Helical"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03199"
FT TOPO_DOM 198..456
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03199"
FT DOMAIN 95..145
FT /note="DHHC"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00067"
FT REGION 284..377
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 287..301
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 307..325
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 326..349
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 125
FT /note="S-palmitoyl cysteine intermediate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03199"
FT MUTAGEN 124..125
FT /note="HC->AS: Renders protein unable to complement a null
FT mutant, probably due to a lack of PAT enzymatic activity."
FT /evidence="ECO:0000269|PubMed:25970403"
SQ SEQUENCE 456 AA; 52295 MW; 4F95A24B32419CF6 CRC64;
MAARNWSRVW VGGTVILISF IAFSSQIFVI WPWYGREISL DLLMLLVPLN LAAFMIFWNY
RLCVITSPGT VPEGWRPNIG AMDGMEVKKG THTPRYCKNC AHYKPPRAHH CRQCKTCWLK
LDHHCPWIGN CVGFYNQGHF IRFLLWVDIG TTFHLIIMVR RVLYIAEYYH EPTLADVLFL
VFNFATCVPV WLCVGMFSIY HVYLACGNST TIEGWEKDKV ATLIRRGKIK EVKYPYNIGI
YKNIKSVLGP NPLLWLWPQK MQGDGLSFPV NPSAGDHMTQ YFWPPQDPSR LPNPPPIPAH
ASPFVYGNNG FNPNLRPTNS LRARRSSTPR IDEDEYSHEQ GRHYSSGDER DNGSISASSS
PEPYLSDYDH YDEGPMYPGE RMTTLVPRVR RGSEGWEVAP GGGWNAYAGM MDEEVGWDDE
AGYDEAPGED PYVERPWEMR GRYNVYDPEE ESGYTH
