CLR4_CRYNH
ID CLR4_CRYNH Reviewed; 1820 AA.
AC J9VWH9;
DT 22-APR-2020, integrated into UniProtKB/Swiss-Prot.
DT 13-NOV-2013, sequence version 2.
DT 03-AUG-2022, entry version 54.
DE RecName: Full=Histone-lysine N-methyltransferase, H3 lysine-9 specific {ECO:0000305};
DE EC=2.1.1.- {ECO:0000305|PubMed:25533783};
DE EC=2.1.1.367 {ECO:0000305|PubMed:25533783};
DE AltName: Full=Histone H3-K9 methyltransferase;
DE Short=H3-K9-HMTase;
GN Name=CLR4 {ECO:0000303|PubMed:25533783}; ORFNames=CNAG_05404;
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.
RX PubMed=25533783; DOI=10.1016/j.cell.2014.11.039;
RA Dumesic P.A., Homer C.M., Moresco J.J., Pack L.R., Shanle E.K., Coyle S.M.,
RA Strahl B.D., Fujimori D.G., Yates J.R. III, Madhani H.D.;
RT "Product binding enforces the genomic specificity of a yeast polycomb
RT repressive complex.";
RL Cell 160:204-218(2015).
RN [3]
RP INDUCTION.
RX PubMed=29581526; DOI=10.1038/s41598-018-21965-y;
RA Brandao F., Esher S.K., Ost K.S., Pianalto K., Nichols C.B., Fernandes L.,
RA Bocca A.L., Pocas-Fonseca M.J., Alspaugh J.A.;
RT "HDAC genes play distinct and redundant roles in Cryptococcus neoformans
RT virulence.";
RL Sci. Rep. 8:5209-5209(2018).
RN [4]
RP DISRUPTION PHENOTYPE.
RX PubMed=31955845; DOI=10.1016/j.cell.2019.12.012;
RA Catania S., Dumesic P.A., Pimentel H., Nasif A., Stoddard C.I., Burke J.E.,
RA Diedrich J.K., Cook S., Shea T., Geinger E., Lintner R., Yates J.R. III,
RA Hajkova P., Narlikar G.J., Cuomo C.A., Pritchard J.K., Madhani H.D.;
RT "Evolutionary Persistence of DNA Methylation for Millions of Years after
RT Ancient Loss of a De Novo Methyltransferase.";
RL Cell 180:263.277.e20-263.277.e20(2020).
CC -!- FUNCTION: Histone methyltransferase that specifically dimethylates
CC histone H3 to form H3K9me2 (PubMed:25533783). H3K9me2 represents a
CC specific tag for epigenetic transcriptional repression by recruiting
CC HP1 proteins to methylated histones (By similarity). Mainly functions
CC in heterochromatin regions, thereby playing a central role in the
CC establishment of constitutive heterochromatin at centromeric regions
CC (Probable). {ECO:0000250|UniProtKB:O60016, ECO:0000269|PubMed:25533783,
CC ECO:0000305|PubMed:25533783}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=N(6)-methyl-L-lysyl(9)-[histone H3] + S-adenosyl-L-methionine
CC = H(+) + N(6),N(6)-dimethyl-L-lysyl(9)-[histone H3] + S-adenosyl-L-
CC homocysteine; Xref=Rhea:RHEA:60284, Rhea:RHEA-COMP:15541, Rhea:RHEA-
CC COMP:15542, ChEBI:CHEBI:15378, ChEBI:CHEBI:57856, ChEBI:CHEBI:59789,
CC ChEBI:CHEBI:61929, ChEBI:CHEBI:61976;
CC Evidence={ECO:0000305|PubMed:25533783};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=L-lysyl(9)-[histone H3] + S-adenosyl-L-methionine = H(+) +
CC N(6)-methyl-L-lysyl(9)-[histone H3] + S-adenosyl-L-homocysteine;
CC Xref=Rhea:RHEA:60280, Rhea:RHEA-COMP:15542, Rhea:RHEA-COMP:15546,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:29969, ChEBI:CHEBI:57856,
CC ChEBI:CHEBI:59789, ChEBI:CHEBI:61929; EC=2.1.1.367;
CC Evidence={ECO:0000305|PubMed:25533783};
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:O60016}.
CC Chromosome {ECO:0000250|UniProtKB:O60016}.
CC -!- INDUCTION: Transcriptionally repressed in an HDA1-dependent manner.
CC {ECO:0000269|PubMed:29581526}.
CC -!- DOMAIN: In the pre-SET domain, Cys residues bind 3 zinc ions that are
CC arranged in a triangular cluster; some of these Cys residues contribute
CC to the binding of two zinc ions within the cluster.
CC {ECO:0000250|UniProtKB:O60016}.
CC -!- DISRUPTION PHENOTYPE: Severely decreases localization of DMT5 to DNA
CC (PubMed:31955845). Decreases methylation of the fifth carbon of
CC cytosine (5mC) in DNA; simultaneous disruption of UHF1 exacerbates the
CC effect (PubMed:31955845). {ECO:0000269|PubMed:31955845}.
CC -!- SIMILARITY: Belongs to the class V-like SAM-binding methyltransferase
CC superfamily. Histone-lysine methyltransferase family. Suvar3-9
CC subfamily. {ECO:0000255|PROSITE-ProRule:PRU00190}.
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DR EMBL; CP003833; AFR98832.2; -; Genomic_DNA.
DR RefSeq; XP_012053594.1; XM_012198204.1.
DR AlphaFoldDB; J9VWH9; -.
DR SMR; J9VWH9; -.
DR EnsemblFungi; AFR98832; AFR98832; CNAG_05404.
DR GeneID; 23888722; -.
DR VEuPathDB; FungiDB:CNAG_05404; -.
DR Proteomes; UP000010091; Chromosome 14.
DR GO; GO:0005694; C:chromosome; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0018024; F:histone-lysine N-methyltransferase activity; IEA:InterPro.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0034968; P:histone lysine methylation; IEA:InterPro.
DR Gene3D; 2.170.270.10; -; 1.
DR InterPro; IPR003616; Post-SET_dom.
DR InterPro; IPR007728; Pre-SET_dom.
DR InterPro; IPR001214; SET_dom.
DR InterPro; IPR046341; SET_dom_sf.
DR Pfam; PF05033; Pre-SET; 1.
DR Pfam; PF00856; SET; 1.
DR SMART; SM00468; PreSET; 1.
DR SMART; SM00317; SET; 1.
DR SUPFAM; SSF82199; SSF82199; 1.
DR PROSITE; PS50868; POST_SET; 1.
DR PROSITE; PS50867; PRE_SET; 1.
DR PROSITE; PS50280; SET; 1.
PE 2: Evidence at transcript level;
KW Chromosome; Metal-binding; Methyltransferase; Nucleus;
KW S-adenosyl-L-methionine; Transferase; Zinc.
FT CHAIN 1..1820
FT /note="Histone-lysine N-methyltransferase, H3 lysine-9
FT specific"
FT /id="PRO_0000449276"
FT DOMAIN 1516..1585
FT /note="Pre-SET"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00157"
FT DOMAIN 1590..1750
FT /note="SET"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00190"
FT DOMAIN 1800..1816
FT /note="Post-SET"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00155"
FT REGION 1..54
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 74..251
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 284..618
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 634..681
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 804..836
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 850..893
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 911..944
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 966..996
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1063..1126
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1183..1270
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1296..1335
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1385..1407
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1756..1794
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 74..88
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 110..126
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 157..235
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 302..321
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 337..362
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 372..462
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 465..479
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 480..534
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 548..618
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 634..666
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 966..983
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1069..1089
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1094..1113
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1222..1255
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1385..1405
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 1518
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:O60016"
FT BINDING 1518
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:O60016"
FT BINDING 1520
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:O60016"
FT BINDING 1524
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:O60016"
FT BINDING 1524
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:O60016"
FT BINDING 1531
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:O60016"
FT BINDING 1533
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:O60016"
FT BINDING 1567
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:O60016"
FT BINDING 1567
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:O60016"
FT BINDING 1571
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:O60016"
FT BINDING 1573
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:O60016"
FT BINDING 1577
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:O60016"
FT BINDING 1600..1602
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:O60016"
FT BINDING 1643
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00190"
FT BINDING 1704
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00190"
FT BINDING 1707..1708
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:O60016"
FT BINDING 1710
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="4"
FT /evidence="ECO:0000250|UniProtKB:O60016"
FT BINDING 1804
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="4"
FT /evidence="ECO:0000250|UniProtKB:O60016"
FT BINDING 1806
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="4"
FT /evidence="ECO:0000250|UniProtKB:O60016"
FT BINDING 1811
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="4"
FT /evidence="ECO:0000250|UniProtKB:O60016"
SQ SEQUENCE 1820 AA; 194979 MW; 35048CD7A8A31FB4 CRC64;
MPGARSEAGG VDNPLVLDSS DSDDNLSGLP LNGRVKRIDG NDRSYKKKSL TSMRKSTVVD
LTLSDSDEAV ESVNLLPGSS STPDRAAQAG ISDKQPSLRR RPRPFMSIAD SSSPPENQNV
ISFLGNHSQE IGELPSPPLV EDRAAPNKME LGGENIAGQN NEANAAQAAV PVSGTPSLTL
SSNRPQSVSG AQLVVASSSR SAINSPPRRT PSIPQQSPSS RATPCRSASI ASSRSRPPTP
PLPATQSTPV TVSRRLASPI LSPVQAVSSA IISPTIPSIP SHASLSDPTI LSPPSATSAP
PNSPIPSTST TVQTPAAALT YARPSTSAAP LPVMPISVTP ATTSPAGPGP SALQSASEAT
KSSDQKESPR KTNSKQPSSP SSTHGRWTDT RLFHTPSNLS ATSGKSSAAS SRSKSRAPLS
SRAAMSDNVA GPSKTTSVSS THPPSRASPS SLPSQSQRQV HPRPPSRDGV GKREKKSKTL
SSGTGQSTPS KFSLPTSDVA SNQKNKSTGL NALPKKPSST PTSSIPQRTS TLATAMAIRP
FVRSPTPPSP QSSSEASRSI QTSRGAVKAA QNQDKIHPLS TALSISSHSR EATTKATTLF
HTTSSPPSPS QSTSAPTKSH VVWNAQKLGT TVLSSERIHL SRGKSQTSDS VVAPAASQTA
ASLSYPAGTS GGAREADKKA VETSFHAGPS SADFEAFVQP STSAIAPTTV RPSVAPPEDA
PVLKSGSIIH PLFRAASAIG DQNAFTKTEA VGDVLSQGSK GRASSPRITT TGAVSHLAPH
VDLGSKIKPT AAPSLFASGV TTKNVDDQDS AQPQNQTPLP SAISVSSKKN HGSLSKESSI
KSAASFISSS STLGDSVSGL GRKSHHKSTQ SMPQSPLPTT NTNNSSGIEV NSWLNPQPFG
PSFAASHLSI HAKKKWKERE RGKEREKEKV REKEKAEEEN EQLRQRRIAD LEKLSANLEL
YKRRMDVESR TRSIPRADGE TRKRPPSPGI SVSTDAEVRV VKRSKPTWAI APEGGHVAPA
MEKESANVNK KAADAIKINH QPASSYAPAF ATPASPAKAT RTPLSVTAGL GPPVNSSSST
STPSLLSRSI NLGILRDKPK DHMDDDDGDD SAGGLPVRKT GKNGAVEEQV EQVRLDLDDV
SIHGSSPAAP LSIFTSRFRD VSITPSRIQK TLEESDNDVP IQRYAVKVNG KQKAQRSKDK
SYGSESENDV PLNWPSRKGK GRTAPEPQDS SETQRDDDDV NLGSGDGEER PSDDDSIPVP
PAPLFKDRTA HVRQPLQTLF KGGIVAKHSY QRPLAKASAV SPVPSANRPS PAPSAKADLL
PQKRKRRLKK ITSQQWQHIA QNSLSDVDDL LGESSKKRLS PENAEKLGAD LSKLTRPRVF
SIVSRSEPRT KREPIEEDNN EYFTDSDSHT SDVALFSQHP DPPPPPERIR EAKRNFDTRN
IDPWNRQKHT FRSNPALHRA IFEAYIMQST SMEESGGDDI KVTNDVDADG GPPDFEFVYS
DTMLYPDGIP PPELGLGCDC DGPCDPDSET CTCVKRQELY FYDLGLKGFA YDENGKIREN
SASIWECNEL CGCPPECMNR VIQRGRARDT GIEIFKTKEK GWGIRARSFI PSGTYIGSYT
GELIREAESE RRGVTYTAIG RTYVFDLDGW QIRHPPKGLE KIDKRAAELA EAVKMRARAA
MRESQEDAYN AYSVDAFHYG NFTRYFNHSC DPNLAITQAY VKDFHPERPL LVIFTRRDIK
KHEELCISYK GIPDDDDIPS PEPVKKKKGG KGKKQMSKTS ASAHPPEMTA LNSDKGLVEV
KDICRCGAKN CDGRMFNYGP
