HMX_CAEEL
ID HMX_CAEEL Reviewed; 341 AA.
AC Q18533;
DT 02-DEC-2020, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2002, sequence version 2.
DT 03-AUG-2022, entry version 154.
DE RecName: Full=Homeobox protein mls-2 {ECO:0000303|PubMed:16107479};
DE AltName: Full=Mesodermal lineage specification protein 2 {ECO:0000303|PubMed:16107479, ECO:0000312|WormBase:C39E6.4};
GN Name=mls-2 {ECO:0000303|PubMed:16107479, ECO:0000312|WormBase:C39E6.4};
GN ORFNames=C39E6.4 {ECO:0000312|WormBase:C39E6.4};
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|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 [2] {ECO:0000305}
RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE,
RP AND MUTAGENESIS OF 26-GLN--MET-341.
RX PubMed=16107479; DOI=10.1242/dev.01967;
RA Jiang Y., Horner V., Liu J.;
RT "The HMX homeodomain protein MLS-2 regulates cleavage orientation, cell
RT proliferation and cell fate specification in the C. elegans postembryonic
RT mesoderm.";
RL Development 132:4119-4130(2005).
RN [3] {ECO:0000305}
RP FUNCTION, SUBCELLULAR LOCATION, AND DEVELOPMENTAL STAGE.
RX PubMed=18508862; DOI=10.1242/dev.019547;
RA Yoshimura S., Murray J.I., Lu Y., Waterston R.H., Shaham S.;
RT "mls-2 and vab-3 Control glia development, hlh-17/Olig expression and glia-
RT dependent neurite extension in C. elegans.";
RL Development 135:2263-2275(2008).
RN [4] {ECO:0000305}
RP TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE.
RX PubMed=18316179; DOI=10.1016/j.mod.2008.01.009;
RA Jiang Y., Shi H., Amin N.M., Sultan I., Liu J.;
RT "Mesodermal expression of the C. elegans HMX homolog mls-2 requires the PBC
RT homolog CEH-20.";
RL Mech. Dev. 125:451-461(2008).
RN [5] {ECO:0000305}
RP FUNCTION, DEVELOPMENTAL STAGE, MUTAGENESIS OF 26-GLN--MET-341, AND
RP MUTAGENESIS OF SER-209.
RX PubMed=20150279; DOI=10.1242/dev.044719;
RA Kim K., Kim R., Sengupta P.;
RT "The HMX/NKX homeodomain protein MLS-2 specifies the identity of the AWC
RT sensory neuron type via regulation of the ceh-36 Otx gene in C. elegans.";
RL Development 137:963-974(2010).
RN [6] {ECO:0000305}
RP FUNCTION, DEVELOPMENTAL STAGE, MUTAGENESIS OF 26-GLN--MET-341, AND
RP MUTAGENESIS OF 250-GLN--MET-341.
RX PubMed=22537498; DOI=10.1016/j.ydbio.2012.03.015;
RA Abdus-Saboor I., Stone C.E., Murray J.I., Sundaram M.V.;
RT "The Nkx5/HMX homeodomain protein MLS-2 is required for proper tube cell
RT shape in the C. elegans excretory system.";
RL Dev. Biol. 366:298-307(2012).
RN [7] {ECO:0000305}
RP DEVELOPMENTAL STAGE, AND MUTAGENESIS OF 250-GLN--MET-341.
RX PubMed=25738873; DOI=10.1371/journal.pgen.1005003;
RA Walton T., Preston E., Nair G., Zacharias A.L., Raj A., Murray J.I.;
RT "The Bicoid class homeodomain factors ceh-36/OTX and unc-30/PITX cooperate
RT in C. elegans embryonic progenitor cells to regulate robust development.";
RL PLoS Genet. 11:e1005003-e1005003(2015).
CC -!- FUNCTION: Transcription factor that binds to the promoter of target
CC genes (PubMed:20150279). Regulates fate specification and/or
CC differentiation of multiple cell types arising from the embryonic
CC mesodermal (M) lineage and the ABp(l/r)paa precursors (PubMed:20150279,
CC PubMed:16107479). In the postembryonic M lineage, regulates cleavage
CC orientation, cell proliferation and cell fate specification
CC (PubMed:16107479). Regulates hlh-1 expression to specify coelomocyte
CC fate in the mesodermal (M) lineage (PubMed:16107479). In AWC neurons,
CC initiates expression of ceh-36, leading to the expression of terminal
CC differentiation genes (PubMed:20150279). Regulates ventral cephalic
CC sheath (CEPsh) glia differentiation and expression of transcription
CC factor hlh-17 in CEPsh glia (PubMed:18508862). Promotes terminal
CC differentiation and morphogenesis of the epithelial duct and pore cells
CC (PubMed:22537498). In the duct cell, cooperates with the EGF-Ras-ERK
CC pathway in turning on the terminal differentiation gene lin-48
CC (PubMed:22537498). {ECO:0000269|PubMed:16107479,
CC ECO:0000269|PubMed:18508862, ECO:0000269|PubMed:20150279,
CC ECO:0000269|PubMed:22537498}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000255|PROSITE-ProRule:PRU00108,
CC ECO:0000255|RuleBase:RU000682, ECO:0000269|PubMed:16107479,
CC ECO:0000269|PubMed:18508862}.
CC -!- TISSUE SPECIFICITY: Expressed in a subset of head neurons, including
CC AIM and ASK (at protein level). {ECO:0000269|PubMed:16107479,
CC ECO:0000269|PubMed:18316179}.
CC -!- DEVELOPMENTAL STAGE: First expressed around the 50-cell stage of
CC embryogenesis in proliferating cells that are primarily located at the
CC anterior of the embryo in the early M lineage (at protein level)
CC (PubMed:16107479, PubMed:18316179, PubMed:22537498). During
CC morphogenesis, expression becomes restricted to a small subset of head
CC neuronal precursors, including AIM and ASK (at protein level)
CC (PubMed:16107479, PubMed:18316179). Expressed in precursor cells of the
CC left and right ventral CEPsh glia, ABplpaaapap and ABprpaaapap,
CC respectively and also in precursors of dorsal CEPsh glia
CC (PubMed:18508862). Expressed in the duct and pore lineages, persisting
CC through the stages of ventral enclosure and 1.5-folds of embryonic
CC development, but not detectable by the L1 larval stage, when duct and
CC pore cells achieve mature morphology (PubMed:22537498,
CC PubMed:25738873). Expressed in ABpxp descendants that give rise to the
CC excretory system (PubMed:25738873). Transiently expressed in AWC
CC neurons in L1 larvae until abolished shortly after hatching
CC (PubMed:20150279). During the L2 and L3 larval stages, expressed in a
CC group of proliferating cells surrounding the gonad (PubMed:18316179).
CC {ECO:0000269|PubMed:16107479, ECO:0000269|PubMed:18316179,
CC ECO:0000269|PubMed:18508862, ECO:0000269|PubMed:20150279,
CC ECO:0000269|PubMed:22537498, ECO:0000269|PubMed:25738873}.
CC -!- SIMILARITY: Belongs to the HMX homeobox family. {ECO:0000305}.
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DR EMBL; BX284606; CCD67080.1; -; Genomic_DNA.
DR RefSeq; NP_508815.2; NM_076414.5.
DR AlphaFoldDB; Q18533; -.
DR SMR; Q18533; -.
DR IntAct; Q18533; 20.
DR STRING; 6239.C39E6.4; -.
DR EPD; Q18533; -.
DR PaxDb; Q18533; -.
DR EnsemblMetazoa; C39E6.4.1; C39E6.4.1; WBGene00003377.
DR GeneID; 180751; -.
DR KEGG; cel:CELE_C39E6.4; -.
DR UCSC; C39E6.4; c. elegans.
DR CTD; 180751; -.
DR WormBase; C39E6.4; CE30891; WBGene00003377; mls-2.
DR eggNOG; KOG0485; Eukaryota.
DR GeneTree; ENSGT00940000162580; -.
DR HOGENOM; CLU_837412_0_0_1; -.
DR InParanoid; Q18533; -.
DR OMA; IDMTTMS; -.
DR OrthoDB; 1313583at2759; -.
DR SignaLink; Q18533; -.
DR Proteomes; UP000001940; Chromosome X.
DR Bgee; WBGene00003377; Expressed in embryo and 3 other tissues.
DR GO; GO:0005634; C:nucleus; IDA:WormBase.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; IBA:GO_Central.
DR GO; GO:0000977; F:RNA polymerase II transcription regulatory region sequence-specific DNA binding; IDA:WormBase.
DR GO; GO:0000132; P:establishment of mitotic spindle orientation; IMP:WormBase.
DR GO; GO:0002119; P:nematode larval development; IMP:WormBase.
DR GO; GO:0003387; P:neuron differentiation involved in amphid sensory organ development; IMP:WormBase.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; IMP:WormBase.
DR GO; GO:0045687; P:positive regulation of glial cell differentiation; IMP:UniProtKB.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IMP:WormBase.
DR GO; GO:0042661; P:regulation of mesodermal cell fate specification; IMP:WormBase.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR CDD; cd00086; homeodomain; 1.
DR InterPro; IPR009057; Homeobox-like_sf.
DR InterPro; IPR017970; Homeobox_CS.
DR InterPro; IPR001356; Homeobox_dom.
DR InterPro; IPR020479; Homeobox_metazoa.
DR Pfam; PF00046; Homeodomain; 1.
DR PRINTS; PR00024; HOMEOBOX.
DR SMART; SM00389; HOX; 1.
DR SUPFAM; SSF46689; SSF46689; 1.
DR PROSITE; PS00027; HOMEOBOX_1; 1.
DR PROSITE; PS50071; HOMEOBOX_2; 1.
PE 1: Evidence at protein level;
KW DNA-binding; Homeobox; Nucleus; Reference proteome; Transcription;
KW Transcription regulation.
FT CHAIN 1..341
FT /note="Homeobox protein mls-2"
FT /id="PRO_0000451455"
FT DNA_BIND 201..260
FT /note="Homeobox"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00108"
FT REGION 1..78
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 139..209
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1..23
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 42..62
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 63..78
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 147..167
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MUTAGEN 26..341
FT /note="Missing: In cc615; approximately 30% larval and
FT adult lethality. Abnormal cell cleavage orientation, under-
FT proliferation and cell fate transformation in the
FT mesodermal (M) lineage. Abolishes M-lineage specific
FT expression of hlh-1. At late L1 stage, animals contain a
FT reduced number of M lineage descendants. Defects in
FT expression of ceh-36 and odr-1 in AWC neurons. Abnormal
FT excretory duct and pore development in early L1 larvae."
FT /evidence="ECO:0000269|PubMed:16107479,
FT ECO:0000269|PubMed:20150279, ECO:0000269|PubMed:22537498"
FT MUTAGEN 209
FT /note="S->N: In oy88; multiple morphological defects of AWC
FT sensory neurons, including truncated dendrites, abnormal
FT axonal branching and axonal trajectories and altered cell
FT body positions. Altered expression of ceh-36 homeobox gene
FT and odr-1 receptor-type guanylate cyclase in AWC neurons
FT and altered expression of differention markers in ASH, ASK
FT and AIM neurons."
FT /evidence="ECO:0000269|PubMed:20150279"
FT MUTAGEN 250..341
FT /note="Missing: In cs71; abnormal excretory duct and pore
FT development in early L1 larvae, leading to abnormal duct
FT and pore shape."
FT /evidence="ECO:0000269|PubMed:22537498,
FT ECO:0000269|PubMed:25738873"
SQ SEQUENCE 341 AA; 38241 MW; 2A5AE7CF3BA931A3 CRC64;
MPTSVMNLPI DMTTMSSQER LEKMSQLPKI ELMEEEEEEE MKPSSDNKIK FNISELLEDD
RKPTTQSSPS ASSEDSTNEI EQTAFNFNFD PKMNPISALL QLQQTFLNVG NQQNMISPLT
MFPFFGLPTA QLMHFKNMSN PDVNIQSDNG EEKDEKSEGK DGETRDSTGG SPLESDAEDD
DDIGRGSDDE ANSSDPSQNR KKKTRTVFSR SQVSQLEMMF ECKRYLSSQE RSNLAQKLHL
TETQVKIWFQ NRRNKFKRQA QTDDTNISLQ MHRANVFSIP ATTALTSPIL TIPTTSAGVN
MRNMISSPMD ASATAAARFL FGFGTLQAQQ NLNASAQAQN M
