ALX1_MOUSE
ID ALX1_MOUSE Reviewed; 326 AA.
AC Q8C8B0; Q8C370;
DT 07-JUN-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2003, sequence version 1.
DT 03-AUG-2022, entry version 149.
DE RecName: Full=ALX homeobox protein 1 {ECO:0000305};
DE AltName: Full=Cartilage homeoprotein 1 {ECO:0000250|UniProtKB:Q63087};
DE Short=CART-1 {ECO:0000250|UniProtKB:Q63087};
GN Name=Alx1 {ECO:0000312|MGI:MGI:104621};
GN Synonyms=Cart1 {ECO:0000303|PubMed:12929931};
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 [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Head;
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 [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Limb;
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 [3]
RP FUNCTION, DISRUPTION PHENOTYPE, AND DEVELOPMENTAL STAGE.
RX PubMed=8673125; DOI=10.1038/ng0796-275;
RA Zhao Q., Behringer R.R., deCrombrugghe B.;
RT "Prenatal folic acid treatment suppresses acrania and meroanencephaly in
RT mice mutant for the Cart1 homeobox gene.";
RL Nat. Genet. 13:275-283(1996).
RN [4]
RP FUNCTION, SUBCELLULAR LOCATION, ACETYLATION AT LYS-131, INTERACTION WITH
RP EP300, AND MUTAGENESIS OF LYS-131.
RX PubMed=12929931; DOI=10.1359/jbmr.2003.18.8.1419;
RA Iioka T., Furukawa K., Yamaguchi A., Shindo H., Yamashita S., Tsukazaki T.;
RT "P300/CBP acts as a coactivator to cartilage homeoprotein-1 (Cart1),
RT paired-like homeoprotein, through acetylation of the conserved lysine
RT residue adjacent to the homeodomain.";
RL J. Bone Miner. Res. 18:1419-1429(2003).
CC -!- FUNCTION: Sequence-specific DNA-binding transcription factor that binds
CC palindromic sequences within promoters and may activate or repress the
CC transcription of a subset of genes (PubMed:12929931). Most probably
CC regulates the expression of genes involved in the development of
CC mesenchyme-derived craniofacial structures. Early on in development, it
CC plays a role in forebrain mesenchyme survival (PubMed:8673125). May
CC also induce epithelial to mesenchymal transition (EMT) through the
CC expression of SNAI1 (By similarity). {ECO:0000250|UniProtKB:Q15699,
CC ECO:0000269|PubMed:12929931, ECO:0000269|PubMed:8673125}.
CC -!- SUBUNIT: Binds DNA as a homodimer; required for transcriptional
CC activation (By similarity). Interacts (via homeobox domain) with EP300;
CC acetylates ALX1 and stimulates its transcriptional activity
CC (PubMed:12929931). {ECO:0000250|UniProtKB:Q63087,
CC ECO:0000269|PubMed:12929931}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:12929931}.
CC -!- DEVELOPMENTAL STAGE: At 8.5 dpc and 9.5 dpc expression is restricted to
CC forebrain mesenchymal cells. {ECO:0000269|PubMed:8673125}.
CC -!- DOMAIN: The OAR motif may negatively regulate DNA-binding and therefore
CC transcriptional activity. It is found in the C-terminal transactivation
CC domain that stimulates transcription. {ECO:0000250|UniProtKB:Q63087}.
CC -!- PTM: Acetylated at Lys-131 by EP300; increases interaction with EP300
CC and stimulates ALX1 transcriptional activity.
CC {ECO:0000269|PubMed:12929931}.
CC -!- DISRUPTION PHENOTYPE: Mice lacking Alx1 die within 24 hours of birth.
CC The overt phenotype is acrania and degeneration of unprotected brain
CC tissues. This is most probably the cause of the death since no other
CC abnormality in limbs and visceral tissues is observed. The defect in
CC cranial bone formation may be a consequence of extensive loss of
CC forebrain head mesenchyme due to cell death and neural tube closure
CC defects earlier during development. The penetrance of the
CC acrania/meroanencephaly phenotype is variable between mice strains.
CC Heterozygous mice appear normal and fertile.
CC {ECO:0000269|PubMed:8673125}.
CC -!- SIMILARITY: Belongs to the paired homeobox family. {ECO:0000305}.
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DR EMBL; AK047846; BAC33173.1; -; mRNA.
DR EMBL; AK086731; BAC39730.1; -; mRNA.
DR EMBL; BC052200; AAH52200.1; -; mRNA.
DR CCDS; CCDS24155.1; -.
DR RefSeq; NP_766141.1; NM_172553.4.
DR RefSeq; XP_006513592.1; XM_006513529.2.
DR AlphaFoldDB; Q8C8B0; -.
DR SMR; Q8C8B0; -.
DR STRING; 10090.ENSMUSP00000129230; -.
DR iPTMnet; Q8C8B0; -.
DR PhosphoSitePlus; Q8C8B0; -.
DR MaxQB; Q8C8B0; -.
DR PaxDb; Q8C8B0; -.
DR PRIDE; Q8C8B0; -.
DR ProteomicsDB; 282077; -.
DR Antibodypedia; 891; 176 antibodies from 25 providers.
DR DNASU; 216285; -.
DR Ensembl; ENSMUST00000040859; ENSMUSP00000042512; ENSMUSG00000036602.
DR Ensembl; ENSMUST00000167156; ENSMUSP00000129230; ENSMUSG00000036602.
DR Ensembl; ENSMUST00000218282; ENSMUSP00000151776; ENSMUSG00000036602.
DR Ensembl; ENSMUST00000219194; ENSMUSP00000152018; ENSMUSG00000036602.
DR GeneID; 216285; -.
DR KEGG; mmu:216285; -.
DR UCSC; uc007gyg.1; mouse.
DR CTD; 8092; -.
DR MGI; MGI:104621; Alx1.
DR VEuPathDB; HostDB:ENSMUSG00000036602; -.
DR eggNOG; KOG0490; Eukaryota.
DR GeneTree; ENSGT00940000158251; -.
DR HOGENOM; CLU_047013_0_1_1; -.
DR InParanoid; Q8C8B0; -.
DR OMA; SSPCGDQ; -.
DR OrthoDB; 738339at2759; -.
DR PhylomeDB; Q8C8B0; -.
DR TreeFam; TF350743; -.
DR BioGRID-ORCS; 216285; 2 hits in 76 CRISPR screens.
DR ChiTaRS; Traf4; mouse.
DR PRO; PR:Q8C8B0; -.
DR Proteomes; UP000000589; Chromosome 10.
DR RNAct; Q8C8B0; protein.
DR Bgee; ENSMUSG00000036602; Expressed in frontonasal prominence and 101 other tissues.
DR ExpressionAtlas; Q8C8B0; baseline and differential.
DR Genevisible; Q8C8B0; MM.
DR GO; GO:0005794; C:Golgi apparatus; ISO:MGI.
DR GO; GO:0016604; C:nuclear body; ISO:MGI.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0005667; C:transcription regulator complex; IDA:MGI.
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; IDA:MGI.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; IBA:GO_Central.
DR GO; GO:0042803; F:protein homodimerization activity; ISO:MGI.
DR GO; GO:0000977; F:RNA polymerase II transcription regulatory region sequence-specific DNA binding; ISO:MGI.
DR GO; GO:0043565; F:sequence-specific DNA binding; IDA:MGI.
DR GO; GO:1990837; F:sequence-specific double-stranded DNA binding; ISO:MGI.
DR GO; GO:0009952; P:anterior/posterior pattern specification; IGI:MGI.
DR GO; GO:0030326; P:embryonic limb morphogenesis; IGI:MGI.
DR GO; GO:0048704; P:embryonic skeletal system morphogenesis; IGI:MGI.
DR GO; GO:0014031; P:mesenchymal cell development; IMP:MGI.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; ISO:MGI.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; ISO:MGI.
DR GO; GO:0001755; P:neural crest cell migration; IEA:InterPro.
DR GO; GO:0001843; P:neural tube closure; IMP:MGI.
DR GO; GO:0010718; P:positive regulation of epithelial to mesenchymal transition; ISS:UniProtKB.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:MGI.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; ISS:UniProtKB.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0060021; P:roof of mouth development; IGI:MGI.
DR GO; GO:0048864; P:stem cell development; IMP:MGI.
DR CDD; cd00086; homeodomain; 1.
DR InterPro; IPR033209; ALX1.
DR InterPro; IPR009057; Homeobox-like_sf.
DR InterPro; IPR017970; Homeobox_CS.
DR InterPro; IPR001356; Homeobox_dom.
DR InterPro; IPR003654; OAR_dom.
DR PANTHER; PTHR24329:SF359; PTHR24329:SF359; 1.
DR Pfam; PF00046; Homeodomain; 1.
DR Pfam; PF03826; OAR; 1.
DR SMART; SM00389; HOX; 1.
DR SUPFAM; SSF46689; SSF46689; 1.
DR PROSITE; PS00027; HOMEOBOX_1; 1.
DR PROSITE; PS50071; HOMEOBOX_2; 1.
DR PROSITE; PS50803; OAR; 1.
PE 1: Evidence at protein level;
KW Acetylation; Activator; Developmental protein; DNA-binding; Homeobox;
KW Nucleus; Phosphoprotein; Reference proteome; Repressor; Transcription;
KW Transcription regulation.
FT CHAIN 1..326
FT /note="ALX homeobox protein 1"
FT /id="PRO_0000048856"
FT DNA_BIND 132..191
FT /note="Homeobox"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00108"
FT REGION 192..326
FT /note="Transactivation domain"
FT /evidence="ECO:0000250|UniProtKB:Q63087"
FT MOTIF 306..319
FT /note="OAR"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00138"
FT MOD_RES 12
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q15699"
FT MOD_RES 69
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q15699"
FT MOD_RES 131
FT /note="N6-acetyllysine; by EP300"
FT /evidence="ECO:0000269|PubMed:12929931"
FT MOD_RES 306
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q15699"
FT MUTAGEN 131
FT /note="K->R: Loss of acetylation. Decreased binding
FT affinity to EP300. Loss of EP300-mediated transcriptional
FT coactivation."
FT /evidence="ECO:0000269|PubMed:12929931"
SQ SEQUENCE 326 AA; 36931 MW; 71FF257E137EF4BF CRC64;
MEFLSEKFAL KSPPSKNSDF YMGTGGALEH VMETLDNESF YGKATAGKCV QAFGPLPRAE
HHVRLDRTSP CQDSSVNYGI TKVEGQPLHT ELNRAMDNCN NLRMSPVKGM PEKSELDELG
DKCDSNVSSS KKRRHRTTFT SLQLEELEKV FQKTHYPDVY VREQLALRTE LTEARVQVWF
QNRRAKWRKR ERYGQIQQAK SHFAATYDIS VLPRTDSYPQ IQNNLWAGNA SGGSVVTSCM
LPRDASSCMT PYSHSPRTDS SYTGFSNHQN QFSHVPLNNF FTDSLLTGAT NGHAFETKPE
FERRSSSIAV LRMKAKEHTA NISWAM