ALX1_HUMAN
ID ALX1_HUMAN Reviewed; 326 AA.
AC Q15699; Q546C8; Q96FH4;
DT 15-JUL-1998, integrated into UniProtKB/Swiss-Prot.
DT 07-MAR-2006, sequence version 2.
DT 03-AUG-2022, entry version 186.
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|HGNC:HGNC:1494};
GN Synonyms=CART1 {ECO:0000303|PubMed:9753625};
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBCELLULAR LOCATION, AND TISSUE
RP SPECIFICITY.
RX PubMed=8756334; DOI=10.1089/dna.1996.15.531;
RA Gordon D.F., Wagner J., Atkinson B.L., Chiono M., Berry R., Sikela J.,
RA Gutierrez-Hartmann A.;
RT "Human Cart-1: structural organization, chromosomal localization, and
RT functional analysis of a cartilage-specific homeodomain cDNA.";
RL DNA Cell Biol. 15:531-541(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RA Felder B., Stegmann K., Ermert A., Koch M.C.;
RT "SNPs of transcription factor CART1 in cases with neural tube defects.";
RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
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 [4]
RP FUNCTION, SUBUNIT, AND SUBCELLULAR LOCATION.
RX PubMed=9753625; DOI=10.1006/bbrc.1998.9257;
RA Cai R.L.;
RT "Human CART1, a paired-class homeodomain protein, activates transcription
RT through palindromic binding sites.";
RL Biochem. Biophys. Res. Commun. 250:305-311(1998).
RN [5]
RP INVOLVEMENT IN FND3, AND FUNCTION.
RX PubMed=20451171; DOI=10.1016/j.ajhg.2010.04.002;
RA Uz E., Alanay Y., Aktas D., Vargel I., Gucer S., Tuncbilek G.,
RA von Eggeling F., Yilmaz E., Deren O., Posorski N., Ozdag H., Liehr T.,
RA Balci S., Alikasifoglu M., Wollnik B., Akarsu N.A.;
RT "Disruption of ALX1 causes extreme microphthalmia and severe facial
RT clefting: expanding the spectrum of autosomal-recessive ALX-related
RT frontonasal dysplasia.";
RL Am. J. Hum. Genet. 86:789-796(2010).
RN [6]
RP FUNCTION.
RX PubMed=23288509; DOI=10.1158/0008-5472.can-12-2377;
RA Yuan H., Kajiyama H., Ito S., Yoshikawa N., Hyodo T., Asano E.,
RA Hasegawa H., Maeda M., Shibata K., Hamaguchi M., Kikkawa F., Senga T.;
RT "ALX1 induces snail expression to promote epithelial-to-mesenchymal
RT transition and invasion of ovarian cancer cells.";
RL Cancer Res. 73:1581-1590(2013).
RN [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-12; SER-69 AND SER-306, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
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:9753625, PubMed:8756334).
CC Most probably regulates the expression of genes involved in the
CC development of mesenchyme-derived craniofacial structures. Early on in
CC development, it plays a role in forebrain mesenchyme survival
CC (PubMed:20451171). May also induce epithelial to mesenchymal transition
CC (EMT) through the expression of SNAI1 (PubMed:23288509).
CC {ECO:0000269|PubMed:20451171, ECO:0000269|PubMed:23288509,
CC ECO:0000269|PubMed:8756334, ECO:0000269|PubMed:9753625}.
CC -!- SUBUNIT: Binds DNA as a homodimer; required for transcriptional
CC activation (PubMed:9753625). Interacts (via homeobox domain) with
CC EP300; acetylates ALX1 and stimulates its transcriptional activity.
CC {ECO:0000250|UniProtKB:Q63087, ECO:0000269|PubMed:9753625}.
CC -!- INTERACTION:
CC Q15699; P02743: APCS; NbExp=3; IntAct=EBI-750671, EBI-2115799;
CC Q15699; O95833: CLIC3; NbExp=3; IntAct=EBI-750671, EBI-10192241;
CC Q15699; P29692-2: EEF1D; NbExp=3; IntAct=EBI-750671, EBI-5280572;
CC Q15699; P07492: GRP; NbExp=3; IntAct=EBI-750671, EBI-12821367;
CC Q15699; O94829: IPO13; NbExp=2; IntAct=EBI-750671, EBI-747310;
CC Q15699; Q92993: KAT5; NbExp=3; IntAct=EBI-750671, EBI-399080;
CC Q15699; Q9BYR3: KRTAP4-4; NbExp=3; IntAct=EBI-750671, EBI-11958132;
CC Q15699; Q8NGH7: OR52L1; NbExp=3; IntAct=EBI-750671, EBI-13330637;
CC Q15699; Q8N7B6-2: PACRGL; NbExp=3; IntAct=EBI-750671, EBI-10694433;
CC Q15699; P10276: RARA; NbExp=3; IntAct=EBI-750671, EBI-413374;
CC Q15699; Q8IUH3-3: RBM45; NbExp=3; IntAct=EBI-750671, EBI-10964453;
CC Q15699; Q96N76: UROC1; NbExp=3; IntAct=EBI-750671, EBI-13073486;
CC Q15699; Q96RE9-3: ZNF300; NbExp=3; IntAct=EBI-750671, EBI-12902696;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:8756334,
CC ECO:0000269|PubMed:9753625}.
CC -!- TISSUE SPECIFICITY: Cartilage and cervix tissue.
CC {ECO:0000269|PubMed:8756334}.
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:0000250|UniProtKB:Q8C8B0}.
CC -!- DISEASE: Frontonasal dysplasia 3 (FND3) [MIM:613456]: The term
CC frontonasal dysplasia describes an array of abnormalities affecting the
CC eyes, forehead and nose and linked to midfacial dysraphia. The clinical
CC picture is highly variable. Major findings include true ocular
CC hypertelorism; broadening of the nasal root; median facial cleft
CC affecting the nose and/or upper lip and palate; unilateral or bilateral
CC clefting of the alae nasi; lack of formation of the nasal tip; anterior
CC cranium bifidum occultum; a V-shaped or widow's peak frontal hairline.
CC {ECO:0000269|PubMed:20451171}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the paired homeobox family. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=Protein Spotlight; Note=The makings of a face
CC - Issue 173 of November 2015;
CC URL="https://web.expasy.org/spotlight/back_issues/173/";
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DR EMBL; U31986; AAB08960.1; -; mRNA.
DR EMBL; AJ558236; CAD90155.1; -; Genomic_DNA.
DR EMBL; AJ558237; CAD90155.1; JOINED; Genomic_DNA.
DR EMBL; BC010923; AAH10923.1; -; mRNA.
DR CCDS; CCDS9028.1; -.
DR RefSeq; NP_008913.2; NM_006982.2.
DR AlphaFoldDB; Q15699; -.
DR SMR; Q15699; -.
DR BioGRID; 113764; 17.
DR IntAct; Q15699; 16.
DR STRING; 9606.ENSP00000315417; -.
DR iPTMnet; Q15699; -.
DR PhosphoSitePlus; Q15699; -.
DR BioMuta; ALX1; -.
DR DMDM; 90111820; -.
DR jPOST; Q15699; -.
DR MassIVE; Q15699; -.
DR PaxDb; Q15699; -.
DR PeptideAtlas; Q15699; -.
DR PRIDE; Q15699; -.
DR ProteomicsDB; 60707; -.
DR Antibodypedia; 891; 176 antibodies from 25 providers.
DR DNASU; 8092; -.
DR Ensembl; ENST00000316824.4; ENSP00000315417.3; ENSG00000180318.4.
DR GeneID; 8092; -.
DR KEGG; hsa:8092; -.
DR MANE-Select; ENST00000316824.4; ENSP00000315417.3; NM_006982.3; NP_008913.2.
DR CTD; 8092; -.
DR DisGeNET; 8092; -.
DR GeneCards; ALX1; -.
DR HGNC; HGNC:1494; ALX1.
DR HPA; ENSG00000180318; Tissue enhanced (epididymis, kidney).
DR MalaCards; ALX1; -.
DR MIM; 601527; gene.
DR MIM; 613456; phenotype.
DR neXtProt; NX_Q15699; -.
DR OpenTargets; ENSG00000180318; -.
DR Orphanet; 306542; Frontonasal dysplasia-severe microphthalmia-severe facial clefting syndrome.
DR PharmGKB; PA162376294; -.
DR VEuPathDB; HostDB:ENSG00000180318; -.
DR eggNOG; KOG0490; Eukaryota.
DR GeneTree; ENSGT00940000158251; -.
DR HOGENOM; CLU_047013_0_1_1; -.
DR InParanoid; Q15699; -.
DR OMA; SSPCGDQ; -.
DR OrthoDB; 738339at2759; -.
DR PhylomeDB; Q15699; -.
DR TreeFam; TF350743; -.
DR PathwayCommons; Q15699; -.
DR SignaLink; Q15699; -.
DR BioGRID-ORCS; 8092; 12 hits in 1092 CRISPR screens.
DR ChiTaRS; ALX1; human.
DR GeneWiki; ALX1; -.
DR GenomeRNAi; 8092; -.
DR Pharos; Q15699; Tbio.
DR PRO; PR:Q15699; -.
DR Proteomes; UP000005640; Chromosome 12.
DR RNAct; Q15699; protein.
DR Bgee; ENSG00000180318; Expressed in metanephros cortex and 57 other tissues.
DR ExpressionAtlas; Q15699; baseline and differential.
DR Genevisible; Q15699; HS.
DR GO; GO:0000785; C:chromatin; ISA:NTNU_SB.
DR GO; GO:0005794; C:Golgi apparatus; IDA:HPA.
DR GO; GO:0016604; C:nuclear body; IDA:HPA.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; IDA:NTNU_SB.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; ISA:NTNU_SB.
DR GO; GO:0000977; F:RNA polymerase II transcription regulatory region sequence-specific DNA binding; IDA:NTNU_SB.
DR GO; GO:1990837; F:sequence-specific double-stranded DNA binding; IDA:ARUK-UCL.
DR GO; GO:0048704; P:embryonic skeletal system morphogenesis; IBA:GO_Central.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IDA:MGI.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; IBA:GO_Central.
DR GO; GO:0001755; P:neural crest cell migration; IEA:InterPro.
DR GO; GO:0010718; P:positive regulation of epithelial to mesenchymal transition; IMP:UniProtKB.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:NTNU_SB.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IDA:UniProtKB.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
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_0000048855"
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:0007744|PubMed:23186163"
FT MOD_RES 69
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 131
FT /note="N6-acetyllysine; by EP300"
FT /evidence="ECO:0000250|UniProtKB:Q8C8B0"
FT MOD_RES 306
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT CONFLICT 125
FT /note="S -> T (in Ref. 1; AAB08960)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 326 AA; 36961 MW; 9EB7374DE42E041B CRC64;
MEFLSEKFAL KSPPSKNSDF YMGAGGPLEH VMETLDNESF YSKASAGKCV QAFGPLPRAE
HHVRLERTSP CQDSSVNYGI TKVEGQPLHT ELNRAMDNCN SLRMSPVKGM QEKGELDELG
DKCDSNVSSS KKRRHRTTFT SLQLEELEKV FQKTHYPDVY VREQLALRTE LTEARVQVWF
QNRRAKWRKR ERYGQIQQAK SHFAATYDIS VLPRTDSYPQ IQNNLWAGNA SGGSVVTSCM
LPRDTSSCMT PYSHSPRTDS SYTGFSNHQN QFSHVPLNNF FTDSLLTGAT NGHAFETKPE
FERRSSSIAV LRMKAKEHTA NISWAM
