KMT5A_BOVIN
ID KMT5A_BOVIN Reviewed; 352 AA.
AC Q2YDJ8;
DT 21-MAR-2006, integrated into UniProtKB/Swiss-Prot.
DT 20-DEC-2005, sequence version 1.
DT 03-AUG-2022, entry version 110.
DE RecName: Full=N-lysine methyltransferase KMT5A {ECO:0000305};
DE EC=2.1.1.- {ECO:0000250|UniProtKB:Q9NQR1};
DE AltName: Full=H4-K20-HMTase KMT5A;
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=PR/SET domain-containing protein 07;
DE Short=PR-Set7;
DE Short=PR/SET07;
DE AltName: Full=SET domain-containing protein 8;
GN Name=KMT5A {ECO:0000250|UniProtKB:Q9NQR1}; Synonyms=SETD8;
OS Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Crossbred X Angus; TISSUE=Liver;
RG NIH - Mammalian Gene Collection (MGC) project;
RL Submitted (NOV-2005) 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 -!- SUBUNIT: Interacts with L3MBTL1. Interacts with SIRT2 (phosphorylated
CC form); the interaction is direct, stimulates KMT5A-mediated
CC methyltransferase activity at histone H4 'Lys-20' (H4K20me1) and is
CC increased in a H(2)O(2)-induced oxidative stress-dependent manner (By
CC similarity). {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. Colocalized with SIRT2 at mitotic foci. Associates with
CC chromosomes during mitosis; association is increased in a H(2)O(2)-
CC induced oxidative stress-dependent manner. Not associated with
CC constitutive heterochromatin (By similarity).
CC {ECO:0000250|UniProtKB:Q9NQR1}.
CC -!- DOMAIN: Although the SET domain contains the active site of enzymatic
CC activity, both sequences upstream and downstream of the SET domain are
CC required for methyltransferase activity.
CC {ECO:0000250|UniProtKB:Q9NQR1}.
CC -!- PTM: Acetylated at Lys-131; does not change methyltransferase activity.
CC Deacetylated at Lys-131 by SIRT2; does not change methyltransferase
CC activity (By similarity). {ECO:0000250|UniProtKB:Q9NQR1}.
CC -!- PTM: Ubiquitinated and degraded by the DCX(DTL) complex. {ECO:0000305}.
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; BC110189; AAI10190.1; -; mRNA.
DR RefSeq; NP_001039795.1; NM_001046330.1.
DR AlphaFoldDB; Q2YDJ8; -.
DR SMR; Q2YDJ8; -.
DR STRING; 9913.ENSBTAP00000055591; -.
DR PaxDb; Q2YDJ8; -.
DR PRIDE; Q2YDJ8; -.
DR Ensembl; ENSBTAT00000063474; ENSBTAP00000055591; ENSBTAG00000000139.
DR GeneID; 532622; -.
DR KEGG; bta:532622; -.
DR CTD; 387893; -.
DR VEuPathDB; HostDB:ENSBTAG00000000139; -.
DR VGNC; VGNC:53910; KMT5A.
DR eggNOG; KOG1085; Eukaryota.
DR GeneTree; ENSGT00940000160030; -.
DR InParanoid; Q2YDJ8; -.
DR OMA; THHEAKC; -.
DR OrthoDB; 1460495at2759; -.
DR Proteomes; UP000009136; Chromosome 17.
DR Bgee; ENSBTAG00000000139; Expressed in trachea and 102 other tissues.
DR ExpressionAtlas; Q2YDJ8; baseline and differential.
DR GO; GO:0005829; C:cytosol; IEA:Ensembl.
DR GO; GO:0005654; C:nucleoplasm; IEA:Ensembl.
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:0002039; F:p53 binding; ISS:UniProtKB.
DR GO; GO:0016279; F:protein-lysine N-methyltransferase activity; ISS:UniProtKB.
DR GO; GO:0003714; F:transcription corepressor activity; IEA:Ensembl.
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:0000122; P:negative regulation of transcription by RNA polymerase II; ISS:UniProtKB.
DR GO; GO:0018026; P:peptidyl-lysine monomethylation; ISS:UniProtKB.
DR GO; GO:0043516; P:regulation of DNA damage response, signal transduction by p53 class mediator; ISS:UniProtKB.
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 Acetylation; Cell cycle; Cell division; Chromatin regulator; Chromosome;
KW Methyltransferase; Mitosis; Nucleus; Phosphoprotein; Reference proteome;
KW Repressor; S-adenosyl-L-methionine; Transcription;
KW Transcription regulation; Transferase; Ubl conjugation.
FT CHAIN 1..352
FT /note="N-lysine methyltransferase KMT5A"
FT /id="PRO_0000228688"
FT DOMAIN 216..337
FT /note="SET"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00190"
FT REGION 21..51
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 87..202
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 89..103
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 135..150
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 161..175
FT /note="Basic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 185..202
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 226..228
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00904"
FT BINDING 271
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 298..299
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00904"
FT MOD_RES 59
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9NQR1"
FT MOD_RES 131
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q9NQR1"
FT MOD_RES 140
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q9NQR1"
SQ SEQUENCE 352 AA; 39277 MW; 98BBD07941AAE9BE CRC64;
MARGRKMSKP RAVEAAAAAA AVAATAPGPE MVERRGPGRP RTNGENVFTG QSKIYTYMSP
NKCSGMRSPL QEENSVAQYE VKCQGKPLAG IYRKRDEKRN SGNAIRSSMK AEEQKIKDAR
RGPLAPFPNQ KSEAAEPPKT PTSSCDTPNA AAAKQGLKKP VRGKQAPRKK AQGKTQQNRK
LTDFYPVRRS SRKSKAELQS EERKRIDELI ESGKEEGMKI DLIDGKGRGV IATKQFSRGE
FVVEYHGDLI EITDAKKREA LYAQDPSTGC YMYYFQYLSK TYCVDATRET NRLGRLINHS
KCGNCQTKLH DIDGVPHLIL IASRDIEAGE ELLYDYGDRS RASIEAYPWL KH
