Protein: Histone-lysine N-methyltransferase SETD1A (EC 2.1.1.364) (Lysine N-methyltransferase 2F) (SET domain-containing protein 1A) (hSET1A) (Set1/Ash2 histone methyltransferase complex subunit SET1) (O15047)
Organism: Homo sapiens (Human)
Function: Histone methyltransferase that catalyzes methyl group transfer from S-adenosyl-L-methionine to the epsilon-amino group of 'Lys-4' of histone H3 (H3K4) via a non-processive mechanism. Part of chromatin remodeling machinery, forms H3K4me1, H3K4me2 and H3K4me3 methylation marks at active chromatin sites where transcription and DNA repair take place. Responsible for H3K4me3 enriched promoters and transcriptional programming of inner mass stem cells and neuron progenitors during embryogenesis (By similarity). Required for H3K4me1 mark at stalled replication forks. Mediates FANCD2-dependent nucleosome remodeling and RAD51 nucleofilaments stabilization at reversed forks, protecting them from nucleolytic degradation. Does not methylate 'Lys-4' of histone H3 if the neighboring 'Lys-9' residue is already methylated.
Subcellular location: Nucleus speckle {ECO:0000269|PubMed:17355966, ECO:0000269|PubMed:38003223}. Chromosome {ECO:0000269|PubMed:17355966}. Cytoplasm {ECO:0000269|PubMed:38003223}. Note=Localizes to a largely non-overlapping set of euchromatic nuclear speckles with SETD1B, suggesting that SETD1A and SETD1B each bind to a unique set of target genes (PubMed:17355966). Predominantly nuclear (PubMed:38003223). {ECO:0000269|PubMed:17355966, ECO:0000269|PubMed:38003223}.
Sequence: MDQEGGGDGQKAPSFQWRNYKLIVDPALDPALRRPSQKVYRYDGVHFSVNDSKYIPVEDLQDPRCHVRSKNRDFSLPVPKFKLDEFYIGQIPLKEVTFARLNDNVRETFLKDMCRKYGEVEEVEILLHPRTRKHLGLARVLFTSTRGAKETVKNLHLTSVMGNIIHAQLDIKGQQRMKYYELIVNGSYTPQTVPTGGKALSEKFQGSGAATETAESRRRSSSDTAAYPAGTTAVGTPGNGTPCSQDTSFSSSRQDTPSSFGQFTPQSSQGTPYTSRGSTPYSQDSAYSSSTTSTSFKPRRSENSYQDAFSRRHFSASSASTTASTAIAATTAATASSSASSSSLSSSSSSSSSSSSSQFRSSDANYPAYYESWNRYQRHTSYPPRRATREEPPGAPFAENTAERFPPSYTSYLPPEPSRPTDQDYRPPASEAPPPEPPEPGGGGGGGGPSPEREEVRTSPRPASPARSGSPAPETTNESVPFAQHSSLDSRIEMLLKEQRSKFSFLASDTEEEEENSSMVLGARDTGSEVPSGSGHGPCTPPPAPANFEDVAPTGSGEPGATRESPKANGQNQASPCSSGDDMEISDDDRGGSPPPAPTPPQQPPPPPPPPPPPPPYLASLPLGYPPHQPAYLLPPRPDGPPPPEYPPPPPPPPHIYDFVNSLELMDRLGAQWGGMPMSFQMQTQMLTRLHQLRQGKGLIAASAGPPGGAFGEAFLPFPPPQEAAYGLPYALYAQGQEGRGAYSREAYHLPMPMAAEPLPSSSVSGEEARLPPREEAELAEGKTLPTAGTVGRVLAMLVQEMKSIMQRDLNRKMVENVAFGAFDQWWESKEEKAKPFQNAAKQQAKEEDKEKTKLKEPGLLSLVDWAKSGGTTGIEAFAFGSGLRGALRLPSFKVKRKEPSEISEASEEKRPRPSTPAEEDEDDPEQEKEAGEPGRPGTKPPKRDEERGKTQGKHRKSFALDSEGEEASQESSSEKDEEDDEEDEEDEDREEAVDTTKKETEVSDGEDEESDSSSKCSLYADSDGENDSTSDSESSSSSSSSSSSSSSSSSSSSSSSSESSSEDEEEEERPAALPSASPPPREVPVPTPAPVEVPVPERVAGSPVTPLPEQEASPARPAGPTEESPPSAPLRPPEPPAGPPAPAPRPDERPSSPIPLLPPPKKRRKTVSFSAIEVVPAPEPPPATPPQAKFPGPASRKAPRGVERTIRNLPLDHASLVKSWPEEVSRGGRSRAGGRGRLTEEEEAEPGTEVDLAVLADLALTPARRGLPALPAVEDSEATETSDEAERPRPLLSHILLEHNYALAVKPTPPAPALRPPEPVPAPAALFSSPADEVLEAPEVVVAEAEEPKPQQLQQQREEGEEEGEEEGEEEEEESSDSSSSSDGEGALRRRSLRSHARRRRPPPPPPPPPPRAYEPRSEFEQMTILYDIWNSGLDSEDMSYLRLTYERLLQQTSGADWLNDTHWVHHTITNLTTPKRKRRPQDGPREHQTGSARSEGYYPISKKEKDKYLDVCPVSARQLEGVDTQGTNRVLSERRSEQRRLLSAIGTSAIMDSDLLKLNQLKFRKKKLRFGRSRIHEWGLFAMEPIAADEMVIEYVGQNIRQMVADMREKRYVQEGIGSSYLFRVDHDTIIDATKCGNLARFINHCCTPNCYAKVITIESQKKIVIYSKQPIGVDEEITYDYKFPLEDNKIPCLCGTESCRGSLN
InterPro domains: - IPR035979: RNA-binding domain superfamily (homologous_superfamily) [68-168]
- IPR012677: Nucleotide-binding alpha-beta plait domain superfamily (homologous_superfamily) [88-197]
- IPR037841: Histone-lysine N-methyltransferase SETD1A/B-like, SET domain (domain) [1556-1703]
- IPR034467: Set1A, RNA recognition motif (domain) [92-186]
- IPR046341: SET domain superfamily (homologous_superfamily) [1490-1707]
- IPR024657: COMPASS complex Set1 subunit, N-SET domain (domain) [1419-1562]
- IPR001214: SET domain (domain) [1568-1691]
- IPR000504: RNA recognition motif domain (domain) [84-172]
- IPR003616: Post-SET domain (domain) [1691-1707]
- IPR044570: Histone-lysine N-methyltransferase Set1-like (family) [562-1707]
Interaction partners: - WD repeat-containing protein 5
- Host cell factor 1
- Retinoblastoma-binding protein 5
- Set1/Ash2 histone methyltransferase complex subunit ASH2
- Protein dpy-30 homolog
- CXXC-type zinc finger protein 1
- WD repeat-containing protein 82
- Histone-lysine N-methyltransferase SETD1B
- Histone-lysine N-methyltransferase 2C
- Histone H3.1
Gene Ontology annotations:
Molecular Function (MF): GO:0003674 (molecular function), GO:0005488 (binding), GO:0003824 (catalytic activity), GO:0016740 (transferase activity), GO:0140096 (catalytic activity, acting on a protein), GO:0005515 (protein binding), GO:0016741 (transferase activity, transferring one-carbon groups), GO:0008276 (protein methyltransferase activity), GO:0016279 (protein-lysine N-methyltransferase activity), GO:0008168 (methyltransferase activity), GO:0042054 (histone methyltransferase activity), GO:0018024 (histone lysine N-methyltransferase activity), GO:0140938 (histone H3 methyltransferase activity), GO:0008757 (S-adenosylmethionine-dependent methyltransferase activity), GO:0008170 (N-methyltransferase activity), GO:0016278 (lysine N-methyltransferase activity), GO:0042800 (histone H3K4 methyltransferase activity)
Biological Process (BP): GO:0008150 (biological process), GO:0048518 (positive regulation of biological process), GO:0050789 (regulation of biological process), GO:0065007 (biological regulation), GO:0009987 (cellular process), GO:0008152 (metabolic process), GO:0048519 (negative regulation of biological process), GO:0006807 (nitrogen compound metabolic process), GO:0009892 (negative regulation of metabolic process), GO:0050794 (regulation of cellular process), GO:0048523 (negative regulation of cellular process), GO:0019222 (regulation of metabolic process), GO:0071704 (organic substance metabolic process), GO:0044237 (cellular metabolic process), GO:0009893 (positive regulation of metabolic process), GO:0044238 (primary metabolic process), GO:0048522 (positive regulation of cellular process), GO:0060255 (regulation of macromolecule metabolic process), GO:0006725 (cellular aromatic compound metabolic process), GO:1901360 (organic cyclic compound metabolic process), GO:0010605 (negative regulation of macromolecule metabolic process), GO:0051171 (regulation of nitrogen compound metabolic process), GO:0051128 (regulation of cellular component organization), GO:0051173 (positive regulation of nitrogen compound metabolic process), GO:0051172 (negative regulation of nitrogen compound metabolic process), GO:0010604 (positive regulation of macromolecule metabolic process), GO:0046483 (heterocycle metabolic process), GO:0051130 (positive regulation of cellular component organization), GO:0034641 (cellular nitrogen compound metabolic process), GO:0031324 (negative regulation of cellular metabolic process), GO:0043170 (macromolecule metabolic process), GO:0009891 (positive regulation of biosynthetic process), GO:0006139 (nucleobase-containing compound metabolic process), GO:0031325 (positive regulation of cellular metabolic process), GO:0009889 (regulation of biosynthetic process), GO:0031323 (regulation of cellular metabolic process), GO:0009890 (negative regulation of biosynthetic process), GO:0080090 (regulation of primary metabolic process), GO:0010556 (regulation of macromolecule biosynthetic process), GO:0010468 (regulation of gene expression), GO:0090304 (nucleic acid metabolic process), GO:1902275 (regulation of chromatin organization), GO:0031327 (negative regulation of cellular biosynthetic process), GO:0051252 (regulation of RNA metabolic process), GO:0051253 (negative regulation of RNA metabolic process), GO:0045934 (negative regulation of nucleobase-containing compound metabolic process), GO:0010467 (gene expression), GO:0016070 (RNA metabolic process), GO:0031445 (regulation of heterochromatin formation), GO:2001141 (regulation of RNA biosynthetic process), GO:0006355 (regulation of DNA-templated transcription), GO:2001252 (positive regulation of chromosome organization), GO:1902679 (negative regulation of RNA biosynthetic process), GO:0033044 (regulation of chromosome organization), GO:0120261 (regulation of heterochromatin organization), GO:1905269 (positive regulation of chromatin organization), GO:0120263 (positive regulation of heterochromatin organization), GO:0045892 (negative regulation of DNA-templated transcription), GO:1903507 (negative regulation of nucleic acid-templated transcription), GO:0090308 (regulation of DNA methylation-dependent heterochromatin formation), GO:1903506 (regulation of nucleic acid-templated transcription), GO:0006359 (regulation of transcription by RNA polymerase III)
Cellular Component (CC): GO:0005575 (cellular component), GO:0032991 (protein-containing complex), GO:0110165 (cellular anatomical entity), GO:0005622 (intracellular anatomical structure), GO:0043226 (organelle), GO:0000785 (chromatin), GO:1902494 (catalytic complex), GO:0140513 (nuclear protein-containing complex), GO:0031974 (membrane-enclosed lumen), GO:0005654 (nucleoplasm), GO:1990234 (transferase complex), GO:0043229 (intracellular organelle), GO:0034708 (methyltransferase complex), GO:0043228 (non-membrane-bounded organelle), GO:0043233 (organelle lumen), GO:0035097 (histone methyltransferase complex), GO:0043227 (membrane-bounded organelle), GO:0043231 (intracellular membrane-bounded organelle), GO:0043232 (intracellular non-membrane-bounded organelle), GO:0048188 (Set1C/COMPASS complex), GO:0070013 (intracellular organelle lumen), GO:0005634 (nucleus), GO:0031981 (nuclear lumen), GO:0005694 (chromosome)