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 04-NOV-2026, entry version 182. 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}, Mox-2 GN {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:10403250, PubMed:12925591, 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}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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_008584.4. DR AlphaFoldDB; P32443; -. DR SMR; P32443; -. DR BioGRID; 201395; 4. DR FunCoup; P32443; 2211. DR IntAct; P32443; 2. DR STRING; 10090.ENSMUSP00000043587; -. DR iPTMnet; P32443; -. DR PhosphoSitePlus; P32443; -. DR PaxDb; 10090-ENSMUSP00000043587; -. DR ProteomicsDB; 296001; -. DR Antibodypedia; 11796; 447 antibodies from 38 providers. DR DNASU; 17286; -. DR Ensembl; ENSMPUT00000014146; ENSMPUP00000013925; ENSMPUG00000014031. 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; AHWHIPQ; -. DR OrthoDB; 6159439at2759; -. DR PhylomeDB; P32443; -. 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 GO; GO:0005737; C:cytoplasm; ISO:GO_Central. DR GO; GO:0016607; C:nuclear speck; ISS:UniProtKB. DR GO; GO:0005634; C:nucleus; ISS:UniProtKB. DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; ISO:GO_Central. 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:GO_Central. DR GO; GO:0043565; F:sequence-specific DNA binding; ISS:UniProtKB. DR GO; GO:1990837; F:sequence-specific double-stranded DNA binding; ISO:GO_Central. DR GO; GO:0001525; P:angiogenesis; IMP:MGI. DR GO; GO:0048144; P:fibroblast proliferation; ISO:GO_Central. DR GO; GO:0060173; P:limb development; IMP:MGI. DR GO; GO:0090051; P:negative regulation of cell migration involved in sprouting angiogenesis; ISO:GO_Central. DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISO:GO_Central. 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 FunFam; 1.10.10.60:FF:000109; Homeobox protein MOX-2; 1. DR Gene3D; 1.10.10.60; Homeodomain-like; 1. DR InterPro; IPR001356; HD. DR InterPro; IPR020479; HD_metazoa. DR InterPro; IPR017970; Homeobox_CS. DR InterPro; IPR009057; Homeodomain-like_sf. 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 63..81 FT /note="Basic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 86..100 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 111..136 FT /note="Low complexity" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 157..170 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 182..191 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 289..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 //