ID MEOX2_MOUSE Reviewed; 303 AA.
AC P32443; Q544T6;
DT 01-OCT-1993, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1993, sequence version 1.
DT 24-JAN-2024, entry version 171.
DE RecName: Full=Homeobox protein MOX-2 {ECO:0000303|PubMed:1363541};
DE AltName: Full=Growth arrest-specific homeobox {ECO:0000303|PubMed:7623821};
DE AltName: Full=Mesenchyme homeobox 2 {ECO:0000303|PubMed:1363541};
GN Name=Meox2 {ECO:0000312|MGI:MGI:103219};
GN Synonyms=Gax {ECO:0000303|PubMed:7623821},
GN Mox-2 {ECO:0000303|PubMed:1363541}, Mox2 {ECO:0000303|PubMed:10403250,
GN ECO:0000303|PubMed:1363541};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, AND DEVELOPMENTAL STAGE.
RX PubMed=1363541; DOI=10.1242/dev.116.4.1123;
RA Candia A.F., Hu J., Crosby J., Lalley P.A., Noden D., Nadeau J.H.,
RA Wright C.V.E.;
RT "Mox-1 and Mox-2 define a novel homeobox gene subfamily and are
RT differentially expressed during early mesodermal patterning in mouse
RT embryos.";
RL Development 116:1123-1136(1992).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=7909944; DOI=10.1093/nar/21.21.4982;
RA Candia A.F., Kovalik J.-P., Wright C.V.E.;
RT "Amino acid sequence of Mox-2 and comparison to its Xenopus and rat
RT homologs.";
RL Nucleic Acids Res. 21:4982-4982(1993).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Forelimb, Heart, and Placenta;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-11.
RX PubMed=7623821; DOI=10.1128/mcb.15.8.4272;
RA Andres V., Fisher S., Wearsch P., Walsh K.;
RT "Regulation of Gax homeobox gene transcription by a combination of positive
RT factors including myocyte-specific enhancer factor 2.";
RL Mol. Cell. Biol. 15:4272-4281(1995).
RN [5]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=10403250; DOI=10.1038/21892;
RA Mankoo B.S., Collins N.S., Ashby P., Grigorieva E., Pevny L.H., Candia A.,
RA Wright C.V., Rigby P.W., Pachnis V.;
RT "Mox2 is a component of the genetic hierarchy controlling limb muscle
RT development.";
RL Nature 400:69-73(1999).
RN [6]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=12925591; DOI=10.1242/dev.00687;
RA Mankoo B.S., Skuntz S., Harrigan I., Grigorieva E., Candia A., Wright C.V.,
RA Arnheiter H., Pachnis V.;
RT "The concerted action of Meox homeobox genes is required upstream of
RT genetic pathways essential for the formation, patterning and
RT differentiation of somites.";
RL Development 130:4655-4664(2003).
RN [7]
RP FUNCTION.
RX PubMed=16116430; DOI=10.1038/nm1287;
RA Wu Z., Guo H., Chow N., Sallstrom J., Bell R.D., Deane R., Brooks A.I.,
RA Kanagala S., Rubio A., Sagare A., Liu D., Li F., Armstrong D.,
RA Gasiewicz T., Zidovetzki R., Song X., Hofman F., Zlokovic B.V.;
RT "Role of the MEOX2 homeobox gene in neurovascular dysfunction in Alzheimer
RT disease.";
RL Nat. Med. 11:959-965(2005).
RN [8]
RP DISRUPTION PHENOTYPE.
RX PubMed=16284941; DOI=10.1002/dvdy.20641;
RA Jin J.Z., Ding J.;
RT "Analysis of Meox-2 mutant mice reveals a novel postfusion-based cleft
RT palate.";
RL Dev. Dyn. 235:539-546(2006).
RN [9]
RP FUNCTION, AND INTERACTION WITH TCF15.
RX PubMed=25561514; DOI=10.1161/circulationaha.114.013721;
RA Coppiello G., Collantes M., Sirerol-Piquer M.S., Vandenwijngaert S.,
RA Schoors S., Swinnen M., Vandersmissen I., Herijgers P., Topal B.,
RA van Loon J., Goffin J., Prosper F., Carmeliet P., Garcia-Verdugo J.M.,
RA Janssens S., Penuelas I., Aranguren X.L., Luttun A.;
RT "Meox2/Tcf15 heterodimers program the heart capillary endothelium for
RT cardiac fatty acid uptake.";
RL Circulation 131:815-826(2015).
CC -!- FUNCTION: Mesodermal transcription factor that plays a key role in
CC somitogenesis and somitogenesis and limb muscle differentiation
CC (PubMed:12925591, PubMed:10403250, PubMed:1363541). Required during
CC limb development for normal appendicular muscle formation and for the
CC normal regulation of myogenic genes (PubMed:10403250). May have a
CC regulatory role when quiescent vascular smooth muscle cells reenter the
CC cell cycle (By similarity). Also acts as a negative regulator of
CC angiogenesis (PubMed:16116430). Activates expression of CDKN1A and
CC CDKN2A in endothelial cells, acting as a regulator of vascular cell
CC proliferation (By similarity). While it activates CDKN1A in a DNA-
CC dependent manner, it activates CDKN2A in a DNA-independent manner (By
CC similarity). Together with TCF15, regulates transcription in heart
CC endothelial cells to regulate fatty acid transport across heart
CC endothelial cells (PubMed:25561514). {ECO:0000250|UniProtKB:P39020,
CC ECO:0000250|UniProtKB:P50222, ECO:0000269|PubMed:10403250,
CC ECO:0000269|PubMed:12925591, ECO:0000269|PubMed:1363541,
CC ECO:0000269|PubMed:16116430, ECO:0000269|PubMed:25561514}.
CC -!- SUBUNIT: Interacts with RNF10 (By similarity). Interacts with TCF15
CC (PubMed:25561514). {ECO:0000250|UniProtKB:P50222,
CC ECO:0000269|PubMed:25561514}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:P50222}. Nucleus
CC speckle {ECO:0000250|UniProtKB:P50222}.
CC -!- DEVELOPMENTAL STAGE: It is not expressed before 8-8.5 dpc
CC (PubMed:1363541). At 8-8.5 dpc it is found on the entire epithelium of
CC the somite (PubMed:1363541). At 9.5 dpc its expression is restricted to
CC the sclerotome (PubMed:1363541). At 10.5 dpc it is found in
CC sclerotomally derived cells including the vertebral and costal
CC precursors (PubMed:1363541). {ECO:0000269|PubMed:1363541}.
CC -!- DOMAIN: The polyhistidine repeat may act as a targeting signal to
CC nuclear speckles. {ECO:0000250|UniProtKB:P50222}.
CC -!- DISRUPTION PHENOTYPE: Mice display defective differentiation and
CC morphogenesis of the limb muscles, characterized by an overall
CC reduction in muscle mass and elimination of specific muscles
CC (PubMed:10403250, PubMed:12925591). Embryos also display a cleft palate
CC phenotype at 15.5 dpc (PubMed:16284941). Mice lacking Meox1 and Meox2
CC show extremely disrupted somite morphogenesis, patterning and
CC differentiation (PubMed:12925591). They lack an axial skeleton and
CC skeletal muscles are severely deficient (PubMed:12925591).
CC {ECO:0000269|PubMed:10403250, ECO:0000269|PubMed:12925591,
CC ECO:0000269|PubMed:16284941}.
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DR EMBL; Z16406; CAA78899.1; -; mRNA.
DR EMBL; AK028352; BAC25898.1; -; mRNA.
DR EMBL; AK031152; BAC27282.1; -; mRNA.
DR EMBL; AK142690; BAE25163.1; -; mRNA.
DR EMBL; S79168; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR CCDS; CCDS25888.1; -.
DR PIR; B49122; B49122.
DR RefSeq; NP_032610.1; NM_008584.3.
DR AlphaFoldDB; P32443; -.
DR SMR; P32443; -.
DR BioGRID; 201395; 4.
DR IntAct; P32443; 2.
DR STRING; 10090.ENSMUSP00000043587; -.
DR iPTMnet; P32443; -.
DR PhosphoSitePlus; P32443; -.
DR PaxDb; 10090-ENSMUSP00000043587; -.
DR ProteomicsDB; 296001; -.
DR Antibodypedia; 11796; 443 antibodies from 35 providers.
DR DNASU; 17286; -.
DR Ensembl; ENSMUST00000041183.7; ENSMUSP00000043587.5; ENSMUSG00000036144.7.
DR GeneID; 17286; -.
DR KEGG; mmu:17286; -.
DR UCSC; uc007nkf.1; mouse.
DR AGR; MGI:103219; -.
DR CTD; 4223; -.
DR MGI; MGI:103219; Meox2.
DR VEuPathDB; HostDB:ENSMUSG00000036144; -.
DR eggNOG; KOG0489; Eukaryota.
DR GeneTree; ENSGT00940000154018; -.
DR HOGENOM; CLU_081326_0_0_1; -.
DR InParanoid; P32443; -.
DR OMA; QHHASWH; -.
DR OrthoDB; 728401at2759; -.
DR PhylomeDB; P32443; -.
DR TreeFam; TF351603; -.
DR BioGRID-ORCS; 17286; 2 hits in 77 CRISPR screens.
DR PRO; PR:P32443; -.
DR Proteomes; UP000000589; Chromosome 12.
DR RNAct; P32443; Protein.
DR Bgee; ENSMUSG00000036144; Expressed in left lung lobe and 188 other cell types or tissues.
DR Genevisible; P32443; MM.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0016607; C:nuclear speck; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; ISO:MGI.
DR GO; GO:0003700; F:DNA-binding transcription factor activity; ISS:UniProtKB.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; IBA:GO_Central.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; ISO:MGI.
DR GO; GO:0043565; F:sequence-specific DNA binding; ISS:UniProtKB.
DR GO; GO:1990837; F:sequence-specific double-stranded DNA binding; ISO:MGI.
DR GO; GO:0001525; P:angiogenesis; IMP:MGI.
DR GO; GO:0048144; P:fibroblast proliferation; ISO:MGI.
DR GO; GO:0060173; P:limb development; IMP:MGI.
DR GO; GO:0090051; P:negative regulation of cell migration involved in sprouting angiogenesis; ISO:MGI.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISO:MGI.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0060021; P:roof of mouth development; IMP:MGI.
DR GO; GO:0007519; P:skeletal muscle tissue development; IMP:MGI.
DR GO; GO:0061053; P:somite development; IBA:GO_Central.
DR GO; GO:0001757; P:somite specification; IGI:MGI.
DR CDD; cd00086; homeodomain; 1.
DR Gene3D; 1.10.10.60; Homeodomain-like; 1.
DR InterPro; IPR009057; Homeobox-like_sf.
DR InterPro; IPR017970; Homeobox_CS.
DR InterPro; IPR001356; Homeobox_dom.
DR InterPro; IPR020479; Homeobox_metazoa.
DR InterPro; IPR042634; MOX-1/MOX-2.
DR PANTHER; PTHR24328; HOMEOBOX PROTEIN MOX; 1.
DR PANTHER; PTHR24328:SF1; HOMEOBOX PROTEIN MOX-2; 1.
DR Pfam; PF00046; Homeodomain; 1.
DR PRINTS; PR00024; HOMEOBOX.
DR SMART; SM00389; HOX; 1.
DR SUPFAM; SSF46689; Homeodomain-like; 1.
DR PROSITE; PS00027; HOMEOBOX_1; 1.
DR PROSITE; PS50071; HOMEOBOX_2; 1.
PE 1: Evidence at protein level;
KW Activator; Developmental protein; DNA-binding; Homeobox; Nucleus;
KW Reference proteome; Transcription; Transcription regulation.
FT CHAIN 1..303
FT /note="Homeobox protein MOX-2"
FT /id="PRO_0000049198"
FT DNA_BIND 186..245
FT /note="Homeobox"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00108"
FT REGION 63..191
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 278..303
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 64..82
FT /note="Basic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 83..104
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 123..139
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 159..174
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 288..303
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
SQ SEQUENCE 303 AA; 33506 MW; 41BD05FC39AA4427 CRC64;
MEHPLFGCLR SPHATAQGLH PFSQSSLALH GRSDHMSYPE LSTSSSSCII AGYPNEEGMF
ASQHHRGHHH HHHHHHHHHQ QQQHQALQSN WHLPQMSSPP SAARHSLCLQ PDSGGPPELG
SSPPVLCSNS SSLGSSTPTG AACAPGDYGR QALSPADVEK RSGSKRKSDS SDSQEGNYKS
EVNSKPRKER TAFTKEQIRE LEAEFAHHNY LTRLRRYEIA VNLDLTERQV KVWFQNRRMK
WKRVKGGQQG AAAREKELVN VKKGTLLPSE LSGIGAATLQ QTGDSLANED SRDSDHSSEH
AHL
//
