ID   KMT5A_XENTR             Reviewed;         336 AA.
AC   Q0V9E9;
DT   05-FEB-2008, integrated into UniProtKB/Swiss-Prot.
DT   05-SEP-2006, sequence version 1.
DT   03-AUG-2022, entry version 90.
DE   RecName: Full=N-lysine methyltransferase KMT5A {ECO:0000305};
DE            EC=2.1.1.- {ECO:0000250|UniProtKB:Q9NQR1};
DE   AltName: Full=Histone-lysine N-methyltransferase KMT5A;
DE            EC=2.1.1.361 {ECO:0000250|UniProtKB:Q9NQR1};
DE   AltName: Full=Lysine-specific methylase 5A {ECO:0000250|UniProtKB:Q9NQR1};
DE   AltName: Full=SET domain-containing protein 8;
GN   Name=kmt5a {ECO:0000250|UniProtKB:Q9NQR1}; Synonyms=setd8;
OS   Xenopus tropicalis (Western clawed frog) (Silurana tropicalis).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Amphibia;
OC   Batrachia; Anura; Pipoidea; Pipidae; Xenopodinae; Xenopus; Silurana.
OX   NCBI_TaxID=8364;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=N6; TISSUE=Ovary;
RG   NIH - Xenopus Gene Collection (XGC) project;
RL   Submitted (AUG-2006) to the EMBL/GenBank/DDBJ databases.
CC   -!- FUNCTION: Protein-lysine N-methyltransferase that monomethylates both
CC       histones and non-histone proteins. Specifically monomethylates 'Lys-20'
CC       of histone H4 (H4K20me1). H4K20me1 is enriched during mitosis and
CC       represents a specific tag for epigenetic transcriptional repression.
CC       Mainly functions in euchromatin regions, thereby playing a central role
CC       in the silencing of euchromatic genes. Required for cell proliferation,
CC       probably by contributing to the maintenance of proper higher-order
CC       structure of DNA during mitosis. Involved in chromosome condensation
CC       and proper cytokinesis. Nucleosomes are preferred as substrate compared
CC       to free histones. Mediates monomethylation of p53/TP53 at 'Lys-382',
CC       leading to repress p53/TP53-target genes. Plays a negative role in TGF-
CC       beta response regulation and a positive role in cell migration.
CC       {ECO:0000250|UniProtKB:Q9NQR1}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=L-lysyl(20)-[histone H4] + S-adenosyl-L-methionine = H(+) +
CC         N(6)-methyl-L-lysyl(20)-[histone H4] + S-adenosyl-L-homocysteine;
CC         Xref=Rhea:RHEA:60344, Rhea:RHEA-COMP:15554, Rhea:RHEA-COMP:15555,
CC         ChEBI:CHEBI:15378, ChEBI:CHEBI:29969, ChEBI:CHEBI:57856,
CC         ChEBI:CHEBI:59789, ChEBI:CHEBI:61929; EC=2.1.1.361;
CC         Evidence={ECO:0000250|UniProtKB:Q9NQR1, ECO:0000255|PROSITE-
CC         ProRule:PRU00904};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=L-lysyl-[protein] + S-adenosyl-L-methionine = H(+) + N(6)-
CC         methyl-L-lysyl-[protein] + S-adenosyl-L-homocysteine;
CC         Xref=Rhea:RHEA:51736, Rhea:RHEA-COMP:9752, Rhea:RHEA-COMP:13053,
CC         ChEBI:CHEBI:15378, ChEBI:CHEBI:29969, ChEBI:CHEBI:57856,
CC         ChEBI:CHEBI:59789, ChEBI:CHEBI:61929;
CC         Evidence={ECO:0000250|UniProtKB:Q9NQR1};
CC   -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:Q9NQR1}.
CC       Chromosome {ECO:0000250|UniProtKB:Q9NQR1}. Note=Specifically localizes
CC       to mitotic chromosomes. Associates with silent chromatin on euchromatic
CC       arms (By similarity). {ECO:0000250|UniProtKB:Q9NQR1}.
CC   -!- SIMILARITY: Belongs to the class V-like SAM-binding methyltransferase
CC       superfamily. Histone-lysine methyltransferase family. PR/SET subfamily.
CC       {ECO:0000255|PROSITE-ProRule:PRU00904}.
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DR   EMBL; BC121601; AAI21602.1; -; mRNA.
DR   RefSeq; NP_001072815.1; NM_001079347.1.
DR   AlphaFoldDB; Q0V9E9; -.
DR   SMR; Q0V9E9; -.
DR   STRING; 8364.ENSXETP00000004789; -.
DR   PaxDb; Q0V9E9; -.
DR   DNASU; 780276; -.
DR   GeneID; 780276; -.
DR   KEGG; xtr:780276; -.
DR   CTD; 387893; -.
DR   Xenbase; XB-GENE-489177; kmt5a.
DR   eggNOG; KOG1085; Eukaryota.
DR   HOGENOM; CLU_047978_0_1_1; -.
DR   InParanoid; Q0V9E9; -.
DR   OMA; THHEAKC; -.
DR   OrthoDB; 1460495at2759; -.
DR   PhylomeDB; Q0V9E9; -.
DR   TreeFam; TF335181; -.
DR   Reactome; R-XTR-2299718; Condensation of Prophase Chromosomes.
DR   Reactome; R-XTR-3214841; PKMTs methylate histone lysines.
DR   Proteomes; UP000008143; Chromosome 1.
DR   Proteomes; UP000790000; Unplaced.
DR   Bgee; ENSXETG00000005820; Expressed in ovary and 20 other tissues.
DR   ExpressionAtlas; Q0V9E9; baseline.
DR   GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR   GO; GO:0005700; C:polytene chromosome; IBA:GO_Central.
DR   GO; GO:0042799; F:histone methyltransferase activity (H4-K20 specific); IBA:GO_Central.
DR   GO; GO:0018024; F:histone-lysine N-methyltransferase activity; ISS:UniProtKB.
DR   GO; GO:0007049; P:cell cycle; IEA:UniProtKB-KW.
DR   GO; GO:0051301; P:cell division; IEA:UniProtKB-KW.
DR   GO; GO:0006325; P:chromatin organization; IEA:UniProtKB-KW.
DR   GO; GO:0034771; P:histone H4-K20 monomethylation; IBA:GO_Central.
DR   GO; GO:0043516; P:regulation of DNA damage response, signal transduction by p53 class mediator; IBA:GO_Central.
DR   GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR   Gene3D; 2.170.270.10; -; 1.
DR   InterPro; IPR016858; Hist_H4-K20_MeTrfase.
DR   InterPro; IPR001214; SET_dom.
DR   InterPro; IPR046341; SET_dom_sf.
DR   Pfam; PF00856; SET; 1.
DR   PIRSF; PIRSF027717; Histone_H4-K20_mtfrase; 1.
DR   SMART; SM00317; SET; 1.
DR   SUPFAM; SSF82199; SSF82199; 1.
DR   PROSITE; PS51571; SAM_MT43_PR_SET; 1.
DR   PROSITE; PS50280; SET; 1.
PE   2: Evidence at transcript level;
KW   Cell cycle; Cell division; Chromatin regulator; Chromosome;
KW   Methyltransferase; Mitosis; Nucleus; Reference proteome; Repressor;
KW   S-adenosyl-L-methionine; Transcription; Transcription regulation;
KW   Transferase.
FT   CHAIN           1..336
FT                   /note="N-lysine methyltransferase KMT5A"
FT                   /id="PRO_0000317002"
FT   DOMAIN          200..321
FT                   /note="SET"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00190"
FT   REGION          1..112
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        48..62
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        65..97
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        98..112
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   BINDING         210..212
FT                   /ligand="S-adenosyl-L-methionine"
FT                   /ligand_id="ChEBI:CHEBI:59789"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00904"
FT   BINDING         255
FT                   /ligand="S-adenosyl-L-methionine"
FT                   /ligand_id="ChEBI:CHEBI:59789"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00190,
FT                   ECO:0000255|PROSITE-ProRule:PRU00904"
FT   BINDING         282..283
FT                   /ligand="S-adenosyl-L-methionine"
FT                   /ligand_id="ChEBI:CHEBI:59789"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00904"
SQ   SEQUENCE   336 AA;  38237 MW;  422D7B38C168DCA1 CRC64;
     MGRGKKMSKP GDGRSGDVPD TGRTGGTNEN HPKINGEVAH LGQPKIYSFM SPTKSPSARP
     PLQEENSVAH HESKCPGKPL TETRKKAEVE KKRISSGTEL SVKPSEQRET ECNSIGEFLD
     PKQEQTDVRR NIALPPADKL NHQKMVKDKP LRRKAQRKKS PNRKLTDYYP VRRSCRKSKT
     ELESEEKKRI DELIQTGKEE GMKMDMITGK GRGVIATRDF QRGEFVVEYH GDLIEITDAK
     RREATYAQDS NTGCYMYYFQ YLNKTYCIDA TRETGRLGRL INHSKSGNCH TKLHNINNVP
     HLILVASRDI NVGEELLYDY GDRRKSSLEA HPWLKN