CBXH2_CAEEL
ID CBXH2_CAEEL Reviewed; 175 AA.
AC G5EDE2; G5EFS9; Q9U3C6;
DT 25-MAY-2022, integrated into UniProtKB/Swiss-Prot.
DT 14-DEC-2011, sequence version 1.
DT 03-AUG-2022, entry version 91.
DE RecName: Full=Chromobox protein homolog hpl-2 {ECO:0000305};
DE AltName: Full=HP1-like heterochromatin protein 2 {ECO:0000312|WormBase:K01G5.2a};
GN Name=hpl-2 {ECO:0000303|PubMed:11850401, ECO:0000312|WormBase:K01G5.2a};
GN Synonyms=K01G5.2a {ECO:0000312|EMBL:AAD21197.1};
GN ORFNames=K01G5.2 {ECO:0000312|WormBase:K01G5.2a};
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:AAD21196.1, ECO:0000312|EMBL:AAD21197.1}
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS A AND B).
RC STRAIN=Bristol N2 {ECO:0000312|EMBL:AAD21196.1};
RA Bahrami M., Schulze E.;
RT "A novel chromo-domain protein in Caenorhabditis elegans.";
RL Submitted (JAN-1999) 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, DEVELOPMENTAL STAGE, AND DISRUPTION
RP PHENOTYPE.
RX PubMed=11850401; DOI=10.1093/embo-reports/kvf051;
RA Couteau F., Guerry F., Muller F., Palladino F.;
RT "A heterochromatin protein 1 homologue in Caenorhabditis elegans acts in
RT germline and vulval development.";
RL EMBO Rep. 3:235-241(2002).
RN [4] {ECO:0000305}
RP FUNCTION, SUBUNIT(ISOFORM A), INTERACTION WITH LIN-13, SUBCELLULAR
RP LOCATION, AND DISRUPTION PHENOTYPE.
RX PubMed=16890929; DOI=10.1016/j.ydbio.2006.04.474;
RA Coustham V., Bedet C., Monier K., Schott S., Karali M., Palladino F.;
RT "The C. elegans HP1 homologue HPL-2 and the LIN-13 zinc finger protein form
RT a complex implicated in vulval development.";
RL Dev. Biol. 297:308-322(2006).
RN [5] {ECO:0000305}
RP FUNCTION, SUBCELLULAR LOCATION, DEVELOPMENTAL STAGE, AND DISRUPTION
RP PHENOTYPE.
RX PubMed=16905130; DOI=10.1016/j.ydbio.2006.06.039;
RA Schott S., Coustham V., Simonet T., Bedet C., Palladino F.;
RT "Unique and redundant functions of C. elegans HP1 proteins in post-
RT embryonic development.";
RL Dev. Biol. 298:176-187(2006).
RN [6] {ECO:0000305}
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=17967446; DOI=10.1016/j.ydbio.2007.09.035;
RA Simonet T., Dulermo R., Schott S., Palladino F.;
RT "Antagonistic functions of SET-2/SET1 and HPL/HP1 proteins in C. elegans
RT development.";
RL Dev. Biol. 312:367-383(2007).
RN [7] {ECO:0000305}
RP FUNCTION.
RX PubMed=19064713; DOI=10.1534/genetics.108.089276;
RA Schott S., Ramos F., Coustham V., Palladino F.;
RT "HPL-2/HP1 prevents inappropriate vulval induction in Caenorhabditis
RT elegans by acting in both HYP7 and vulval precursor cells.";
RL Genetics 181:797-801(2009).
RN [8] {ECO:0000305}
RP FUNCTION.
RX PubMed=22185090; DOI=10.1186/gb-2011-12-12-r123;
RA Meister P., Schott S., Bedet C., Xiao Y., Rohner S., Bodennec S., Hudry B.,
RA Molin L., Solari F., Gasser S.M., Palladino F.;
RT "Caenorhabditis elegans Heterochromatin protein 1 (HPL-2) links
RT developmental plasticity, longevity and lipid metabolism.";
RL Genome Biol. 12:R123.1-R123.18(2011).
RN [9] {ECO:0000305}
RP FUNCTION, AND INTERACTION WITH HIS-24 AND HPL-1.
RX PubMed=22083954; DOI=10.1128/mcb.05229-11;
RA Studencka M., Konzer A., Moneron G., Wenzel D., Opitz L.,
RA Salinas-Riester G., Bedet C., Krueger M., Hell S.W., Wisniewski J.R.,
RA Schmidt H., Palladino F., Schulze E., Jedrusik-Bode M.;
RT "Novel roles of Caenorhabditis elegans heterochromatin protein HP1 and
RT linker histone in the regulation of innate immune gene expression.";
RL Mol. Cell. Biol. 32:251-265(2012).
RN [10] {ECO:0000305}
RP FUNCTION, INTERACTION WITH HISTONE H3, AND DISRUPTION PHENOTYPE.
RX PubMed=23028351; DOI=10.1371/journal.pgen.1002940;
RA Studencka M., Wesolowski R., Opitz L., Salinas-Riester G., Wisniewski J.R.,
RA Jedrusik-Bode M.;
RT "Transcriptional repression of Hox genes by C. elegans HP1/HPL and H1/HIS-
RT 24.";
RL PLoS Genet. 8:e1002940-e1002940(2012).
RN [11] {ECO:0000305}
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=24715729; DOI=10.1073/pnas.1321698111;
RA Kozlowski L., Garvis S., Bedet C., Palladino F.;
RT "The Caenorhabditis elegans HP1 family protein HPL-2 maintains ER
RT homeostasis through the UPR and hormesis.";
RL Proc. Natl. Acad. Sci. U.S.A. 111:5956-5961(2014).
RN [12] {ECO:0000305}
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=25467431; DOI=10.1101/gr.180489.114;
RA Garrigues J.M., Sidoli S., Garcia B.A., Strome S.;
RT "Defining heterochromatin in C. elegans through genome-wide analysis of the
RT heterochromatin protein 1 homolog HPL-2.";
RL Genome Res. 25:76-88(2015).
RN [13] {ECO:0000305}
RP FUNCTION, INTERACTION WITH HISTONE H3, SUBCELLULAR LOCATION, AND DISRUPTION
RP PHENOTYPE.
RX PubMed=26476455; DOI=10.1093/nar/gkv1063;
RA Vandamme J., Sidoli S., Mariani L., Friis C., Christensen J., Helin K.,
RA Jensen O.N., Salcini A.E.;
RT "H3K23me2 is a new heterochromatic mark in Caenorhabditis elegans.";
RL Nucleic Acids Res. 43:9694-9710(2015).
RN [14] {ECO:0000305}
RP FUNCTION, INTERACTION WITH TDP-1, SUBCELLULAR LOCATION, AND DISRUPTION
RP PHENOTYPE.
RX PubMed=29760282; DOI=10.1128/mcb.00668-17;
RA Saldi T.K., Gonzales P., Garrido-Lecca A., Dostal V., Roberts C.M.,
RA Petrucelli L., Link C.D.;
RT "The Caenorhabditis elegans Ortholog of TDP-43 Regulates the Chromatin
RT Localization of the Heterochromatin Protein 1 Homolog HPL-2.";
RL Mol. Cell. Biol. 38:0-0(2018).
CC -!- FUNCTION: Seems to be involved in transcriptional silencing in
CC heterochromatin-like complexes (PubMed:11850401). Probably does not act
CC as global transcriptional repressor, instead targeting a subset of
CC genes (PubMed:23028351, PubMed:19064713, PubMed:22185090,
CC PubMed:25467431). Involved in RNA processing mediated by Tar DNA-
CC binding protein homolog tdp-1 (PubMed:29760282). Plays a role in
CC linking epigenetic regulation with the innate immune response
CC (PubMed:22083954). Involved in the endoplasmic reticulum (ER) stress
CC response via modulation of the unfolded protein response (UPR), acting
CC mainly through the IRE1-XBP1 pathway and perhaps, to a lesser extent,
CC through the autophagy pathway (PubMed:24715729). May act in a common
CC pathway with retinoblastoma-like protein homolog lin-35 and zinc finger
CC protein lin-13 to influence the ER stress response in the intestine
CC (PubMed:24715729). Plays a role in the formation of the vulva and in
CC fertility, acting together with a CoREST-like complex, and chromobox
CC protein homolog hpl-1 (PubMed:26476455, PubMed:16905130,
CC PubMed:16890929, PubMed:11850401). Acting in concert with hpl-1 and
CC histone H1 protein his-24, involved in reproduction, somatic gonad
CC development, male tail development and vulval cell fate specification;
CC perhaps as a result of modulating expression of Hox genes mab-5 and
CC egl-5 (PubMed:23028351, PubMed:16905130, PubMed:16890929,
CC PubMed:11850401, PubMed:19064713). In vulval cell fate specification
CC may act by repressing transcription, of EGF family gene lin-3 in
CC hypodermal hyp7, and of homeobox lin-39 in vulval precursor cells (VPC)
CC (PubMed:19064713). Role in growth and somatic gonad development is
CC antagonized by histone-lysine N-methyltransferase set-2/SET1
CC (PubMed:17967446). Required for larval development, acting redundantly
CC with hpl-1 (PubMed:16905130). Plays a role in regulation of the
CC developmentally arrested larval state known as dauer, longevity, and
CC lipid metabolism (PubMed:22185090). {ECO:0000269|PubMed:11850401,
CC ECO:0000269|PubMed:16890929, ECO:0000269|PubMed:16905130,
CC ECO:0000269|PubMed:17967446, ECO:0000269|PubMed:19064713,
CC ECO:0000269|PubMed:22083954, ECO:0000269|PubMed:22185090,
CC ECO:0000269|PubMed:23028351, ECO:0000269|PubMed:24715729,
CC ECO:0000269|PubMed:25467431, ECO:0000269|PubMed:26476455,
CC ECO:0000269|PubMed:29760282}.
CC -!- SUBUNIT: Interacts with histone H3 when di-, or tri-methylated at 'Lys-
CC 27' (H3K27me2/me3), or tri-methylated at 'Lys-9' (H3K9me3)
CC (PubMed:26476455, PubMed:23028351). Interacts with Tar DNA-binding
CC protein homolog tdp-1; interaction may maintain localization of hpl-2
CC to gene bodies (PubMed:29760282). Interacts with histone H1 his-24,
CC probably via interaction with hpl-1 (PubMed:22083954). Interacts with
CC chromobox protein homolog hpl-1 (PubMed:22083954).
CC {ECO:0000269|PubMed:22083954, ECO:0000269|PubMed:23028351,
CC ECO:0000269|PubMed:26476455, ECO:0000269|PubMed:29760282}.
CC -!- SUBUNIT: [Isoform a]: May form homodimers (PubMed:16890929). Interacts
CC (via chromo (shadow subtype) domain) with zinc finger protein lin-13
CC (via PLVPV motif); the interaction is direct and influences
CC localization of hpl-2 to nuclear foci (PubMed:16890929).
CC {ECO:0000269|PubMed:16890929}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:11850401,
CC ECO:0000269|PubMed:16890929, ECO:0000269|PubMed:16905130,
CC ECO:0000269|PubMed:25467431, ECO:0000269|PubMed:26476455,
CC ECO:0000269|PubMed:29760282}. Chromosome {ECO:0000269|PubMed:11850401,
CC ECO:0000269|PubMed:16890929, ECO:0000269|PubMed:16905130,
CC ECO:0000269|PubMed:25467431, ECO:0000269|PubMed:26476455}.
CC Note=Localizes to distinct nuclear foci, not overlapping significantly
CC with hpl-1, in embryonic cells (PubMed:26476455, PubMed:16905130).
CC Localization to nuclear foci overlaps partially with zinc finger
CC protein lin-13 (PubMed:16890929). Localizes to foci in a lin-13-
CC dependent manner (PubMed:16890929). Localization along chromosomal arms
CC correlates with localization of histone H3 methylated at 'Lys-9'
CC (H3K9me), however, hpl-2 can associate with chromatin in an H3K9me-
CC independent manner (PubMed:25467431). Localization on chromosome
CC correlates with sequences enriched in repetitive elements, or in well-
CC expressed genes (PubMed:25467431). Localized to gene bodies
CC (PubMed:29760282). {ECO:0000269|PubMed:16890929,
CC ECO:0000269|PubMed:16905130, ECO:0000269|PubMed:25467431,
CC ECO:0000269|PubMed:26476455, ECO:0000269|PubMed:29760282}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=a {ECO:0000312|WormBase:K01G5.2a};
CC IsoId=G5EDE2-1; Sequence=Displayed;
CC Name=b {ECO:0000312|WormBase:K01G5.2b};
CC IsoId=G5EDE2-2; Sequence=VSP_061516;
CC Name=c {ECO:0000312|WormBase:K01G5.2c};
CC IsoId=G5EDE2-3; Sequence=VSP_061517;
CC -!- DEVELOPMENTAL STAGE: Expressed in embryos at about the 20-50 cell stage
CC (PubMed:11850401, PubMed:16905130). Expression persists throughout
CC development and into adulthood (PubMed:11850401). Also expressed at
CC lower level in germ cells, developing oocytes and embryos starting at
CC the two-cell stage, before the onset of zygotic transcription,
CC suggesting that the protein is maternally inherited (PubMed:11850401).
CC Expressed in hyp7 hypodermal cells and vulval precursor cells of larval
CC L2 stage hermaphrodites (PubMed:19064713).
CC {ECO:0000269|PubMed:11850401, ECO:0000269|PubMed:16905130,
CC ECO:0000269|PubMed:19064713}.
CC -!- DISRUPTION PHENOTYPE: Causes ectopic up-regulation of transcription of
CC specific genes, such as lin-39 and lag-2 (PubMed:16890929). Causes
CC accumulation of double-stranded RNA transcripts (PubMed:29760282).
CC Splicing defects (PubMed:29760282). Results in increased levels of
CC spliced xbp-1 under basal conditions (PubMed:24715729). Increases
CC survival in response to ER stress inducers tunicamycin or
CC dithiothreitol (DTT), as compared to wild-type (PubMed:24715729).
CC Knockout in a chromobox protein homolog hpl-1 mutant background has no
CC effect on the distribution of monomethylated histone H3 'Lys-9'
CC (H3K9me3) in chromatin (PubMed:26476455). Germline nuclei differ in
CC size and morphology in a his-24 mutant background, probably as a result
CC of altered chromatin compaction (PubMed:23028351). Causes defects in
CC gonad elongation when grown at 25 degrees Celsius; phenotype
CC exacerbated in an hpl-1 mutant background (PubMed:16905130). Causes
CC vulva defects, infertility and larval lethality, in particular when
CC grown at 25 degrees Celsius; exacerbated in various mutant backgrounds,
CC such as hpl-1, or rcor-1 or his-24, or by simultaneous RNAi-mediated
CC knockdown of lin-15A, or lin-9 or lin-35 (PubMed:26476455,
CC PubMed:23028351, PubMed:16890929). Causes male tail defects in a his-24
CC mutant background (PubMed:23028351). Some knockout phenotypes are
CC suppressed by simultaneous RNAi-mediated knockdown of histone-lysine N-
CC methyltransferase set-2 (PubMed:17967446). RNAi-mediated knockdown
CC causes sterility and vulval defects; sterility exacerbated by
CC simultaneous RNAi-mediated knockdown of hpl-1. Defects in oocyte
CC morphology, perhaps due to abnormal maturation (PubMed:11850401).
CC {ECO:0000269|PubMed:11850401, ECO:0000269|PubMed:16890929,
CC ECO:0000269|PubMed:16905130, ECO:0000269|PubMed:17967446,
CC ECO:0000269|PubMed:23028351, ECO:0000269|PubMed:24715729,
CC ECO:0000269|PubMed:26476455, ECO:0000269|PubMed:29760282}.
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DR EMBL; AF123573; AAD21196.1; -; mRNA.
DR EMBL; AF123574; AAD21197.1; -; mRNA.
DR EMBL; BX284603; CAB07241.1; -; Genomic_DNA.
DR EMBL; BX284603; CAB07243.2; -; Genomic_DNA.
DR EMBL; BX284603; CAB54267.2; -; Genomic_DNA.
DR PIR; T23196; T23196.
DR PIR; T23198; T23198.
DR PIR; T23202; T23202.
DR RefSeq; NP_001022652.1; NM_001027481.4.
DR RefSeq; NP_001022653.1; NM_001027482.2.
DR RefSeq; NP_001022654.1; NM_001027483.2.
DR AlphaFoldDB; G5EDE2; -.
DR IntAct; G5EDE2; 3.
DR STRING; 6239.K01G5.2c; -.
DR EPD; G5EDE2; -.
DR PaxDb; G5EDE2; -.
DR PeptideAtlas; G5EDE2; -.
DR EnsemblMetazoa; K01G5.2a.1; K01G5.2a.1; WBGene00001996. [G5EDE2-1]
DR EnsemblMetazoa; K01G5.2b.1; K01G5.2b.1; WBGene00001996. [G5EDE2-2]
DR EnsemblMetazoa; K01G5.2c.1; K01G5.2c.1; WBGene00001996. [G5EDE2-3]
DR GeneID; 176506; -.
DR KEGG; cel:CELE_K01G5.2; -.
DR CTD; 176506; -.
DR WormBase; K01G5.2a; CE16191; WBGene00001996; hpl-2.
DR WormBase; K01G5.2b; CE25037; WBGene00001996; hpl-2.
DR WormBase; K01G5.2c; CE25038; WBGene00001996; hpl-2.
DR eggNOG; KOG1911; Eukaryota.
DR GeneTree; ENSGT00970000195943; -.
DR HOGENOM; CLU_045874_1_2_1; -.
DR InParanoid; G5EDE2; -.
DR OMA; KWQGFPL; -.
DR OrthoDB; 1628171at2759; -.
DR PhylomeDB; G5EDE2; -.
DR Proteomes; UP000001940; Chromosome III.
DR Bgee; WBGene00001996; Expressed in embryo and 4 other tissues.
DR ExpressionAtlas; G5EDE2; baseline and differential.
DR GO; GO:0000793; C:condensed chromosome; IBA:GO_Central.
DR GO; GO:0000792; C:heterochromatin; IEA:UniProt.
DR GO; GO:0005637; C:nuclear inner membrane; IBA:GO_Central.
DR GO; GO:0034399; C:nuclear periphery; IDA:WormBase.
DR GO; GO:0005634; C:nucleus; IDA:WormBase.
DR GO; GO:0003682; F:chromatin binding; IBA:GO_Central.
DR GO; GO:0035064; F:methylated histone binding; IBA:GO_Central.
DR GO; GO:0006325; P:chromatin organization; IEA:UniProtKB-KW.
DR GO; GO:0097240; P:chromosome attachment to the nuclear envelope; IBA:GO_Central.
DR GO; GO:0007281; P:germ cell development; IMP:WormBase.
DR GO; GO:0008406; P:gonad development; IMP:WormBase.
DR GO; GO:0046580; P:negative regulation of Ras protein signal transduction; IGI:WormBase.
DR GO; GO:0040027; P:negative regulation of vulval development; IMP:WormBase.
DR GO; GO:0002119; P:nematode larval development; IGI:WormBase.
DR GO; GO:0040010; P:positive regulation of growth rate; IMP:WormBase.
DR GO; GO:0045595; P:regulation of cell differentiation; IGI:WormBase.
DR GO; GO:0010468; P:regulation of gene expression; IBA:GO_Central.
DR GO; GO:0000003; P:reproduction; IMP:WormBase.
DR InterPro; IPR037948; Cec-4.
DR InterPro; IPR016197; Chromo-like_dom_sf.
DR InterPro; IPR000953; Chromo/chromo_shadow_dom.
DR InterPro; IPR017984; Chromo_dom_subgr.
DR InterPro; IPR023780; Chromo_domain.
DR InterPro; IPR008251; Chromo_shadow_dom.
DR PANTHER; PTHR10503; PTHR10503; 1.
DR Pfam; PF00385; Chromo; 1.
DR Pfam; PF01393; Chromo_shadow; 1.
DR PRINTS; PR00504; CHROMODOMAIN.
DR SMART; SM00298; CHROMO; 1.
DR SMART; SM00300; ChSh; 1.
DR SUPFAM; SSF54160; SSF54160; 2.
DR PROSITE; PS50013; CHROMO_2; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Chromatin regulator; Chromosome; Nucleus;
KW Reference proteome; Transcription; Transcription regulation.
FT CHAIN 1..175
FT /note="Chromobox protein homolog hpl-2"
FT /id="PRO_0000455643"
FT DOMAIN 19..78
FT /note="Chromo"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00053"
FT DOMAIN 115..172
FT /note="Chromo 2; shadow subtype"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00053"
FT REGION 71..109
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VAR_SEQ 154..175
FT /note="PSQVIRYYESKLTIQDPKADEL -> RPFVDAYGEFLKKKMERRHKRISEGK
FT KKRSIEEDDADDEWPEMPPGHRILTTEEHELQRRKESKISQDVEMTEAQTAADMLNDMH
FT MAANGDLLSSFPQDFLEDSGDGEVHEAAILSVFDDNSNSPPPCPIVVDTVPDDDDSLLF
FT PRNS (in isoform b)"
FT /evidence="ECO:0000305"
FT /id="VSP_061516"
FT VAR_SEQ 154..175
FT /note="PSQVIRYYESKLTIQDPKADEL -> RPFVDAYGEFLKKKMERRHKRISEGK
FT KKRSIEEDDADDEWPEMPPGHRILTTEEHELQRRKESKISQDVEMTEAFQQTAADMLND
FT MHMAANGDLLSSFPQDFLEDSGDGEVHEAAILSVFDDNSNSPPPCPIVVDTVPDDDDSL
FT LFPRNS (in isoform c)"
FT /evidence="ECO:0000305"
FT /id="VSP_061517"
SQ SEQUENCE 175 AA; 20427 MW; 5C3EA43D9E0407DF CRC64;
MSSKSTKRAK IEDPKDNVFM VEKVLDKRTG KAGRDEFLIQ WQGFPESDSS WEPRENLQCV
EMLDEFEREF SKREKPIRKR HSQKPEPSED QADPEEDKDE KKETNQNDKF SLEGKQLKCI
VGLTKGPGEL HFLCKFSDDT ARLLPAKEVN SRYPSQVIRY YESKLTIQDP KADEL
