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MEOX1_MOUSE
ID   MEOX1_MOUSE             Reviewed;         253 AA.
AC   P32442; Q543E8;
DT   01-OCT-1993, integrated into UniProtKB/Swiss-Prot.
DT   01-OCT-1993, sequence version 1.
DT   03-AUG-2022, entry version 159.
DE   RecName: Full=Homeobox protein MOX-1;
DE   AltName: Full=Mesenchyme homeobox 1;
GN   Name=Meox1; Synonyms=Mox-1, Mox1;
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, TISSUE SPECIFICITY, AND DEVELOPMENTAL
RP   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 [LARGE SCALE MRNA].
RC   STRAIN=C57BL/6J {ECO:0000312|EMBL:BAC34961.1};
RC   TISSUE=Heart {ECO:0000312|EMBL:BAC34961.1};
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   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA   Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL   Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=C57BL/6J; TISSUE=Mammary gland;
RX   PubMed=15489334; DOI=10.1101/gr.2596504;
RG   The MGC Project Team;
RT   "The status, quality, and expansion of the NIH full-length cDNA project:
RT   the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [5]
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   [6]
RP   FUNCTION.
RX   PubMed=15039437; DOI=10.1074/jbc.m312612200;
RA   Petropoulos H., Gianakopoulos P.J., Ridgeway A.G., Skerjanc I.S.;
RT   "Disruption of Meox or Gli activity ablates skeletal myogenesis in P19
RT   cells.";
RL   J. Biol. Chem. 279:23874-23881(2004).
RN   [7]
RP   FUNCTION.
RX   PubMed=15024065; DOI=10.1128/mcb.24.7.2757-2766.2004;
RA   Rodrigo I., Bovolenta P., Mankoo B.S., Imai K.;
RT   "Meox homeodomain proteins are required for Bapx1 expression in the
RT   sclerotome and activate its transcription by direct binding to its
RT   promoter.";
RL   Mol. Cell. Biol. 24:2757-2766(2004).
RN   [8]
RP   FUNCTION.
RX   PubMed=18417617; DOI=10.1242/dev.020958;
RA   Wasteson P., Johansson B.R., Jukkola T., Breuer S., Akyurek L.M.,
RA   Partanen J., Lindahl P.;
RT   "Developmental origin of smooth muscle cells in the descending aorta in
RT   mice.";
RL   Development 135:1823-1832(2008).
RN   [9]
RP   FUNCTION, DNA-BINDING, AND DISRUPTION PHENOTYPE.
RX   PubMed=19520072; DOI=10.1016/j.ydbio.2009.06.006;
RA   Skuntz S., Mankoo B., Nguyen M.T., Hustert E., Nakayama A.,
RA   Tournier-Lasserve E., Wright C.V., Pachnis V., Bharti K., Arnheiter H.;
RT   "Lack of the mesodermal homeodomain protein MEOX1 disrupts sclerotome
RT   polarity and leads to a remodeling of the cranio-cervical joints of the
RT   axial skeleton.";
RL   Dev. Biol. 332:383-395(2009).
RN   [10]
RP   FUNCTION, SUBCELLULAR LOCATION, AND MUTAGENESIS OF GLN-219.
RX   PubMed=22206000; DOI=10.1371/journal.pone.0029099;
RA   Douville J.M., Cheung D.Y., Herbert K.L., Moffatt T., Wigle J.T.;
RT   "Mechanisms of MEOX1 and MEOX2 regulation of the cyclin dependent kinase
RT   inhibitors p21 and p16 in vascular endothelial cells.";
RL   PLoS ONE 6:E29099-E29099(2011).
CC   -!- FUNCTION: Mesodermal transcription factor that plays a key role in
CC       somitogenesis and is specifically required for sclerotome development.
CC       Required for maintenance of the sclerotome polarity and formation of
CC       the cranio-cervical joints (PubMed:19520072). Binds specifically to the
CC       promoter of target genes and regulates their expression. Activates
CC       expression of NKX3-2 in the sclerotome (PubMed:15024065). Activates
CC       expression of CDKN1A and CDKN2A in endothelial cells, acting as a
CC       regulator of vascular cell proliferation. While it activates CDKN1A in
CC       a DNA-dependent manner, it activates CDKN2A in a DNA-independent manner
CC       (PubMed:22206000). Required for hematopoietic stem cell (HSCs)
CC       induction via its role in somitogenesis: specification of HSCs occurs
CC       via the deployment of a specific endothelial precursor population,
CC       which arises within a sub-compartment of the somite named endotome (By
CC       similarity). {ECO:0000250|UniProtKB:F1Q4R9,
CC       ECO:0000269|PubMed:12925591, ECO:0000269|PubMed:1363541,
CC       ECO:0000269|PubMed:15024065, ECO:0000269|PubMed:15039437,
CC       ECO:0000269|PubMed:18417617, ECO:0000269|PubMed:19520072,
CC       ECO:0000269|PubMed:22206000}.
CC   -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:22206000}. Cytoplasm
CC       {ECO:0000269|PubMed:22206000}. Note=Localizes predominantly in the
CC       nucleus. {ECO:0000269|PubMed:22206000}.
CC   -!- TISSUE SPECIFICITY: Heart, lateral plate derivatives, kidney, loose
CC       connective tissue at sites of bone formation and skeletal muscle-
CC       connective tissue apposition. {ECO:0000269|PubMed:1363541}.
CC   -!- DEVELOPMENTAL STAGE: After 7 dpc it is expressed in mesoderm lying
CC       posterior of the future primordial head and heart. Between 7.5 and 9.5
CC       dpc it is expressed in presomitic mesoderm, epithelial and
CC       differentiating somites and in lateral plate mesoderm. In the body of
CC       mid-gestation embryos it is restricted to loose undifferentiated
CC       mesenchyme. {ECO:0000269|PubMed:1363541}.
CC   -!- DISRUPTION PHENOTYPE: Mice display mild defects in sclerotome derived
CC       vertebral and rib bones (PubMed:12925591). Abnormalities are restricted
CC       to the sclerotome and its derivatives and are characterized by a
CC       remodeling of the cranio-cervical joints, leading to the assimilation
CC       of the atlas into the basioccipital bone so that the skull rests on the
CC       axis (PubMed:19520072). Mice lacking Meox1 and Meox2 show extremely
CC       disrupted somite morphogenesis, patterning and differentiation. They
CC       lack an axial skeleton and skeletal muscles are severely deficient
CC       (PubMed:12925591). {ECO:0000269|PubMed:12925591,
CC       ECO:0000269|PubMed:19520072}.
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DR   EMBL; Z15103; CAA78812.1; -; mRNA.
DR   EMBL; AK052370; BAC34961.1; -; mRNA.
DR   EMBL; CH466558; EDL34069.1; -; Genomic_DNA.
DR   EMBL; BC011082; AAH11082.1; -; mRNA.
DR   CCDS; CCDS25480.1; -.
DR   PIR; A49122; A49122.
DR   RefSeq; NP_034921.1; NM_010791.3.
DR   AlphaFoldDB; P32442; -.
DR   SMR; P32442; -.
DR   BioGRID; 201394; 3.
DR   STRING; 10090.ENSMUSP00000051158; -.
DR   PhosphoSitePlus; P32442; -.
DR   PaxDb; P32442; -.
DR   PRIDE; P32442; -.
DR   ProteomicsDB; 296000; -.
DR   Antibodypedia; 17286; 416 antibodies from 31 providers.
DR   DNASU; 17285; -.
DR   Ensembl; ENSMUST00000057054; ENSMUSP00000051158; ENSMUSG00000001493.
DR   GeneID; 17285; -.
DR   KEGG; mmu:17285; -.
DR   UCSC; uc007lpx.1; mouse.
DR   CTD; 4222; -.
DR   MGI; MGI:103220; Meox1.
DR   VEuPathDB; HostDB:ENSMUSG00000001493; -.
DR   eggNOG; KOG0489; Eukaryota.
DR   GeneTree; ENSGT00940000154018; -.
DR   HOGENOM; CLU_081326_1_0_1; -.
DR   InParanoid; P32442; -.
DR   OMA; CMRSPQP; -.
DR   OrthoDB; 1522857at2759; -.
DR   PhylomeDB; P32442; -.
DR   TreeFam; TF351603; -.
DR   BioGRID-ORCS; 17285; 2 hits in 74 CRISPR screens.
DR   ChiTaRS; Meox1; mouse.
DR   PRO; PR:P32442; -.
DR   Proteomes; UP000000589; Chromosome 11.
DR   RNAct; P32442; protein.
DR   Bgee; ENSMUSG00000001493; Expressed in somite and 135 other tissues.
DR   Genevisible; P32442; MM.
DR   GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR   GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR   GO; GO:0003682; F:chromatin binding; IDA:MGI.
DR   GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; IDA:NTNU_SB.
DR   GO; GO:0003700; F:DNA-binding transcription factor activity; IDA:UniProtKB.
DR   GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; IBA:GO_Central.
DR   GO; GO:0071837; F:HMG box domain binding; IPI:UniProtKB.
DR   GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IDA:UniProtKB.
DR   GO; GO:0043565; F:sequence-specific DNA binding; IMP:UniProtKB.
DR   GO; GO:1990837; F:sequence-specific double-stranded DNA binding; ISO:MGI.
DR   GO; GO:0060218; P:hematopoietic stem cell differentiation; ISS:UniProtKB.
DR   GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:NTNU_SB.
DR   GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR   GO; GO:0061056; P:sclerotome development; IMP:UniProtKB.
DR   GO; GO:0061053; P:somite development; IMP:UniProtKB.
DR   GO; GO:0001757; P:somite specification; IGI:MGI.
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   InterPro; IPR042634; MOX-1/MOX-2.
DR   PANTHER; PTHR24328; PTHR24328; 1.
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   Activator; Cytoplasm; Developmental protein; DNA-binding; Homeobox;
KW   Nucleus; Reference proteome; Repressor; Transcription;
KW   Transcription regulation.
FT   CHAIN           1..253
FT                   /note="Homeobox protein MOX-1"
FT                   /id="PRO_0000049196"
FT   DNA_BIND        170..229
FT                   /note="Homeobox"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00108"
FT   REGION          1..44
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          139..177
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          226..253
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        26..43
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        142..177
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MUTAGEN         219
FT                   /note="Q->E: Abolishes DNA-binding. Does not affect ability
FT                   to activate expression of CDKN2A."
FT                   /evidence="ECO:0000269|PubMed:22206000"
SQ   SEQUENCE   253 AA;  27980 MW;  5B8757EFE503EDDF CRC64;
     MDPVANSCVR NPQPPAPVWG CLRNPHSEDS SASGLSHYPP TPFSFHQKSD FPATAAYPDF
     SASCLAATPH SLPRTERIFN EQHPAFPQTP DWHFPISEAG QRLNLGPAGS AREMGAGSPG
     LVDGTAGLGE DCMVLGTIAN ETEKKSSRRK KERSDNQENG GGKPEGSSKA RKERTAFTKE
     QLRELEAEFA HHNYLTRLRR YEIAVNLDLS ERQVKVWFQN RRMKWKRVKG GQPVSPQEQD
     REDGDSAASP SSE
 
 
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