ASH2_CAEEL
ID ASH2_CAEEL Reviewed; 570 AA.
AC G5EFZ3;
DT 07-JUN-2017, integrated into UniProtKB/Swiss-Prot.
DT 14-DEC-2011, sequence version 1.
DT 03-AUG-2022, entry version 85.
DE RecName: Full=Set1/Ash2 histone methyltransferase complex subunit ash-2;
GN Name=ash-2 {ECO:0000312|WormBase:Y17G7B.2a};
GN ORFNames=Y17G7B.2 {ECO:0000312|WormBase:Y17G7B.2a};
OS Caenorhabditis elegans.
OC Eukaryota; Metazoa; Ecdysozoa; Nematoda; Chromadorea; Rhabditida;
OC Rhabditina; Rhabditomorpha; Rhabditoidea; Rhabditidae; Peloderinae;
OC Caenorhabditis.
OX NCBI_TaxID=6239 {ECO:0000312|Proteomes:UP000001940};
RN [1] {ECO:0000312|EMBL:ABW34919.1}
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Soete G., Betist M.C., Korswagen H.C.;
RT "The histone methyltransferase ash-2 controls Caenorhabditis elegans seam
RT and vulva development.";
RL Submitted (SEP-2007) to the EMBL/GenBank/DDBJ databases.
RN [2] {ECO:0000312|Proteomes:UP000001940}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Bristol N2 {ECO:0000312|Proteomes:UP000001940};
RX PubMed=9851916; DOI=10.1126/science.282.5396.2012;
RG The C. elegans sequencing consortium;
RT "Genome sequence of the nematode C. elegans: a platform for investigating
RT biology.";
RL Science 282:2012-2018(1998).
RN [3] {ECO:0000305}
RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE,
RP AND DISRUPTION PHENOTYPE.
RX PubMed=20555324; DOI=10.1038/nature09195;
RA Greer E.L., Maures T.J., Hauswirth A.G., Green E.M., Leeman D.S.,
RA Maro G.S., Han S., Banko M.R., Gozani O., Brunet A.;
RT "Members of the H3K4 trimethylation complex regulate lifespan in a
RT germline-dependent manner in C. elegans.";
RL Nature 466:383-387(2010).
RN [4] {ECO:0000305}
RP FUNCTION.
RX PubMed=22012258; DOI=10.1038/nature10572;
RA Greer E.L., Maures T.J., Ucar D., Hauswirth A.G., Mancini E., Lim J.P.,
RA Benayoun B.A., Shi Y., Brunet A.;
RT "Transgenerational epigenetic inheritance of longevity in Caenorhabditis
RT elegans.";
RL Nature 479:365-371(2011).
RN [5] {ECO:0000305}
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=21527717; DOI=10.1073/pnas.1019290108;
RA Xiao Y., Bedet C., Robert V.J., Simonet T., Dunkelbarger S.,
RA Rakotomalala C., Soete G., Korswagen H.C., Strome S., Palladino F.;
RT "Caenorhabditis elegans chromatin-associated proteins SET-2 and ASH-2 are
RT differentially required for histone H3 Lys 4 methylation in embryos and
RT adult germ cells.";
RL Proc. Natl. Acad. Sci. U.S.A. 108:8305-8310(2011).
RN [6] {ECO:0000305}
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=28379943; DOI=10.1038/nature21686;
RA Han S., Schroeder E.A., Silva-Garcia C.G., Hebestreit K., Mair W.B.,
RA Brunet A.;
RT "Mono-unsaturated fatty acids link H3K4me3 modifiers to C. elegans
RT lifespan.";
RL Nature 544:185-190(2017).
RN [7] {ECO:0000305}
RP IDENTIFICATION IN THE SET2 COMPLEX, INTERACTION WITH CFP-1 AND WDR-5.1, AND
RP IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=31602465; DOI=10.1093/nar/gkz880;
RA Beurton F., Stempor P., Caron M., Appert A., Dong Y., Chen R.A., Cluet D.,
RA Coute Y., Herbette M., Huang N., Polveche H., Spichty M., Bedet C.,
RA Ahringer J., Palladino F.;
RT "Physical and functional interaction between SET1/COMPASS complex component
RT CFP-1 and a Sin3S HDAC complex in C. elegans.";
RL Nucleic Acids Res. 47:11164-11180(2019).
CC -!- FUNCTION: Component of the set-2/ash-2 histone methyltransferase (HMT)
CC complex (Probable). Required for the di- and trimethylation at 'Lys-4'
CC of histone H3, a mark associated with epigenetic transcriptional
CC activation (PubMed:21527717, PubMed:20555324). Implicated in the
CC epigenetic inheritance of lifespan over several generations
CC (PubMed:22012258). Functions as transcriptional regulator
CC (PubMed:28379943). Acts in the germline to limit the longevity of the
CC soma, probably by regulating a lipid metabolism pathway that signals
CC from the germline to the intestine, thereby preventing accumulation of
CC mono-unsaturated fatty acids (PubMed:20555324, PubMed:22012258,
CC PubMed:28379943). {ECO:0000269|PubMed:20555324,
CC ECO:0000269|PubMed:21527717, ECO:0000269|PubMed:22012258,
CC ECO:0000269|PubMed:28379943, ECO:0000305}.
CC -!- SUBUNIT: Component of the SET2 complex (also known as the SET1/COMPASS
CC complex), which contains at least set-2, swd-2.1, cfp-1, rbbp-5, wdr-
CC 5.1, dpy-30 and ash-2 (Probable) (PubMed:31602465). Within the complex,
CC interacts with cfp-1 and wdr-5.1 (PubMed:31602465).
CC {ECO:0000269|PubMed:31602465, ECO:0000305|PubMed:20555324,
CC ECO:0000305|PubMed:21527717, ECO:0000305|PubMed:22012258,
CC ECO:0000305|PubMed:28379943}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:20555324}.
CC -!- TISSUE SPECIFICITY: Expressed in somatic and germline tissues (at
CC protein level). {ECO:0000269|PubMed:20555324}.
CC -!- DEVELOPMENTAL STAGE: Expressed throughout development and in adult
CC animals. {ECO:0000269|PubMed:20555324}.
CC -!- DISRUPTION PHENOTYPE: Decreased levels of tri- and dimethylated 'Lys-4'
CC of histone H3 in the somatic cells in embryos and young adult animals
CC (PubMed:21527717, PubMed:20555324). Increased dimethylated 'Lys-4' of
CC histone H3 in primordial germ cells (PubMed:21527717). Decreased
CC dimethylated 'Lys-4' of histone H3 in the distal region of the germline
CC (PubMed:21527717). Reduced fertility (PubMed:21527717). RNAi-mediated
CC knockdown results in the extension of lifespan (PubMed:20555324).
CC Decreased levels of trimethylated 'Lys-4' of histone H3 in L3 stage
CC larvae (PubMed:20555324). Leads to a deregulation of fat metabolism and
CC to an accumulation of mono-unsaturated fatty acids in the intestine
CC (PubMed:28379943). {ECO:0000269|PubMed:20555324,
CC ECO:0000269|PubMed:21527717, ECO:0000269|PubMed:28379943}.
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DR EMBL; EU178102; ABW34919.1; -; mRNA.
DR EMBL; BX284602; CAA19449.1; -; Genomic_DNA.
DR PIR; T26495; T26495.
DR RefSeq; NP_496555.1; NM_064154.1.
DR AlphaFoldDB; G5EFZ3; -.
DR SMR; G5EFZ3; -.
DR STRING; 6239.Y17G7B.2b; -.
DR EPD; G5EFZ3; -.
DR PeptideAtlas; G5EFZ3; -.
DR EnsemblMetazoa; Y17G7B.2a.1; Y17G7B.2a.1; WBGene00012458.
DR GeneID; 174838; -.
DR CTD; 174838; -.
DR WormBase; Y17G7B.2a; CE19035; WBGene00012458; ash-2.
DR eggNOG; KOG2626; Eukaryota.
DR HOGENOM; CLU_032370_2_0_1; -.
DR Reactome; R-CEL-201722; Formation of the beta-catenin:TCF transactivating complex.
DR Reactome; R-CEL-3214841; PKMTs methylate histone lysines.
DR Reactome; R-CEL-8936459; RUNX1 regulates genes involved in megakaryocyte differentiation and platelet function.
DR PRO; PR:G5EFZ3; -.
DR Proteomes; UP000001940; Chromosome II.
DR Bgee; WBGene00012458; Expressed in embryo and 4 other tissues.
DR ExpressionAtlas; G5EFZ3; baseline and differential.
DR GO; GO:0005634; C:nucleus; IDA:WormBase.
DR GO; GO:0048188; C:Set1C/COMPASS complex; IBA:GO_Central.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0000976; F:transcription cis-regulatory region binding; IBA:GO_Central.
DR GO; GO:0006325; P:chromatin organization; IEA:UniProtKB-KW.
DR GO; GO:0008340; P:determination of adult lifespan; IMP:WormBase.
DR GO; GO:0051568; P:histone H3-K4 methylation; IMP:WormBase.
DR GO; GO:0012501; P:programmed cell death; IMP:UniProtKB.
DR Gene3D; 2.60.120.920; -; 1.
DR InterPro; IPR037353; ASH2.
DR InterPro; IPR001870; B30.2/SPRY.
DR InterPro; IPR043136; B30.2/SPRY_sf.
DR InterPro; IPR013320; ConA-like_dom_sf.
DR InterPro; IPR003877; SPRY_dom.
DR InterPro; IPR019786; Zinc_finger_PHD-type_CS.
DR InterPro; IPR011011; Znf_FYVE_PHD.
DR PANTHER; PTHR10598; PTHR10598; 1.
DR Pfam; PF00622; SPRY; 1.
DR SMART; SM00449; SPRY; 1.
DR SUPFAM; SSF49899; SSF49899; 1.
DR SUPFAM; SSF57903; SSF57903; 1.
DR PROSITE; PS50188; B302_SPRY; 1.
DR PROSITE; PS01359; ZF_PHD_1; 1.
PE 1: Evidence at protein level;
KW Chromatin regulator; DNA-binding; Metal-binding; Nucleus;
KW Reference proteome; Transcription; Transcription regulation; Zinc;
KW Zinc-finger.
FT CHAIN 1..570
FT /note="Set1/Ash2 histone methyltransferase complex subunit
FT ash-2"
FT /id="PRO_0000440618"
FT DOMAIN 270..468
FT /note="B30.2/SPRY"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00548"
FT ZN_FING 19..76
FT /note="PHD-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00146"
FT REGION 201..242
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 201..231
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
SQ SEQUENCE 570 AA; 64496 MW; D55C341B6C35C07E CRC64;
MRSSKGGRGR QAAPKTAPTT VCYCDGKREL GSVEVVCSTC LKWFHGRCLK EFHELNSNGV
PFMICYTFTC KQCRPTAEDW KAKKADLVQM CVTVLATLSA ERLKADGKLS AEHVPEDFTY
LSLKDEIVPY MNENWYMLTA IKQKKEWHQN LAPTLLKEKN IFVQHNDDDD LFALAEKNLS
LLGPLHEAVK LIGKRPIERE NREPRHIELP PIEGPKTRGA SKRRHAEAPV TGKKQKLAAD
YSSTAAPNGV QIDIPFSKDN YRYYLTEVDP NVPEDPAWNQ NQSSAYVIPS FHYRELLNPT
VNVSSNDRAF QLSINGNSIT GFEGYSMARA SHGVSKGTWY FEVNFDDQPD DSHIRIGWSQ
SYASLQACVG YNKFSYGWRS KHGTKFHEAK GKKYHFGGFK QGDVLGCLIH LPVDKKLQIP
ANLPSEKYLP VSHKGFNLIS FKANYFFEVQ EESADIAKTL VEMPGSYIEF FHNGKSCGKA
YENIYAGAYY PSISIFKSAT ATMNLGPKFR NLPRGATGIH ARADEQQHEQ TLSDMLYLVS
KEVNLDHPPR VKREDDDDVK DIKKEIKQEI
