ALX3_HUMAN
ID ALX3_HUMAN Reviewed; 343 AA.
AC O95076; O95075; Q5T8M4;
DT 27-APR-2001, integrated into UniProtKB/Swiss-Prot.
DT 25-NOV-2008, sequence version 2.
DT 03-AUG-2022, entry version 173.
DE RecName: Full=Homeobox protein aristaless-like 3;
DE AltName: Full=Proline-rich transcription factor ALX3;
GN Name=ALX3;
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], AND NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-92.
RC TISSUE=Neuroblastoma;
RX PubMed=11807986; DOI=10.1002/gcc.10030;
RA Wimmer K., Zhu X.-X., Rouillard J.-M., Ambros P.F., Lamb B.J., Kuick R.,
RA Eckart M., Weinhausl A., Fonatsch C., Hanash S.M.;
RT "Combined restriction landmark genomic scanning and virtual genome scans
RT identify a novel human homeobox gene, ALX3, that is hypermethylated in
RT neuroblastoma.";
RL Genes Chromosomes Cancer 33:285-294(2002).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
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 [5]
RP VARIANTS FND1 VAL-168; TRP-183; TRP-196 AND SER-203.
RX PubMed=19409524; DOI=10.1016/j.ajhg.2009.04.009;
RA Twigg S.R.F., Versnel S.L., Nuernberg G., Lees M.M., Bhat M., Hammond P.,
RA Hennekam R.C.M., Hoogeboom A.J., Hurst J.A., Johnson D., Robinson A.A.,
RA Scambler P.J., Gerrelli D., Nuernberg P., Mathijssen I.M.J., Wilkie A.O.M.;
RT "Frontorhiny, a distinctive presentation of frontonasal dysplasia caused by
RT recessive mutations in the ALX3 homeobox gene.";
RL Am. J. Hum. Genet. 84:698-705(2009).
CC -!- FUNCTION: Transcriptional regulator with a possible role in patterning
CC of mesoderm during development. {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000255|PROSITE-ProRule:PRU00108}.
CC -!- DISEASE: Frontonasal dysplasia 1 (FND1) [MIM:136760]: 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:19409524}. 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}.
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DR EMBL; AF008202; AAD01417.2; -; Genomic_DNA.
DR EMBL; AF008203; AAD01418.1; -; mRNA.
DR EMBL; AL160006; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471122; EAW56430.1; -; Genomic_DNA.
DR EMBL; BC112007; AAI12008.1; -; mRNA.
DR EMBL; BC113428; AAI13429.1; -; mRNA.
DR CCDS; CCDS819.1; -.
DR RefSeq; NP_006483.2; NM_006492.2.
DR AlphaFoldDB; O95076; -.
DR SMR; O95076; -.
DR BioGRID; 106755; 21.
DR IntAct; O95076; 16.
DR STRING; 9606.ENSP00000358807; -.
DR iPTMnet; O95076; -.
DR PhosphoSitePlus; O95076; -.
DR BioMuta; ALX3; -.
DR MassIVE; O95076; -.
DR PaxDb; O95076; -.
DR PeptideAtlas; O95076; -.
DR PRIDE; O95076; -.
DR Antibodypedia; 33780; 130 antibodies from 27 providers.
DR DNASU; 257; -.
DR Ensembl; ENST00000647563.2; ENSP00000497310.1; ENSG00000156150.9.
DR GeneID; 257; -.
DR KEGG; hsa:257; -.
DR MANE-Select; ENST00000647563.2; ENSP00000497310.1; NM_006492.3; NP_006483.2.
DR UCSC; uc001dzb.4; human.
DR CTD; 257; -.
DR DisGeNET; 257; -.
DR GeneCards; ALX3; -.
DR HGNC; HGNC:449; ALX3.
DR HPA; ENSG00000156150; Tissue enhanced (skin).
DR MalaCards; ALX3; -.
DR MIM; 136760; phenotype.
DR MIM; 606014; gene.
DR neXtProt; NX_O95076; -.
DR OpenTargets; ENSG00000156150; -.
DR Orphanet; 391474; Frontorhiny.
DR PharmGKB; PA24754; -.
DR VEuPathDB; HostDB:ENSG00000156150; -.
DR eggNOG; KOG0490; Eukaryota.
DR GeneTree; ENSGT00940000160669; -.
DR HOGENOM; CLU_059011_0_0_1; -.
DR InParanoid; O95076; -.
DR OMA; GSHFYEG; -.
DR OrthoDB; 738339at2759; -.
DR PhylomeDB; O95076; -.
DR TreeFam; TF350743; -.
DR PathwayCommons; O95076; -.
DR SignaLink; O95076; -.
DR BioGRID-ORCS; 257; 51 hits in 1097 CRISPR screens.
DR ChiTaRS; ALX3; human.
DR GenomeRNAi; 257; -.
DR Pharos; O95076; Tbio.
DR PRO; PR:O95076; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; O95076; protein.
DR Bgee; ENSG00000156150; Expressed in adenohypophysis and 50 other tissues.
DR ExpressionAtlas; O95076; baseline and differential.
DR Genevisible; O95076; HS.
DR GO; GO:0000785; C:chromatin; ISA:NTNU_SB.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
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; IBA:GO_Central.
DR GO; GO:1990837; F:sequence-specific double-stranded DNA binding; IDA:ARUK-UCL.
DR GO; GO:0048701; P:embryonic cranial skeleton morphogenesis; IEA:InterPro.
DR GO; GO:0035115; P:embryonic forelimb morphogenesis; IEA:Ensembl.
DR GO; GO:0035116; P:embryonic hindlimb morphogenesis; IEA:Ensembl.
DR GO; GO:0007389; P:pattern specification process; IEA:Ensembl.
DR GO; GO:0042981; P:regulation of apoptotic process; IEA:Ensembl.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR CDD; cd00086; homeodomain; 1.
DR InterPro; IPR033211; ALX3.
DR InterPro; IPR009057; Homeobox-like_sf.
DR InterPro; IPR017970; Homeobox_CS.
DR InterPro; IPR001356; Homeobox_dom.
DR PANTHER; PTHR24329:SF340; PTHR24329:SF340; 1.
DR Pfam; PF00046; Homeodomain; 1.
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 Developmental protein; Disease variant; DNA-binding; Homeobox; Nucleus;
KW Reference proteome; Transcription; Transcription regulation.
FT CHAIN 1..343
FT /note="Homeobox protein aristaless-like 3"
FT /id="PRO_0000048812"
FT DNA_BIND 153..212
FT /note="Homeobox"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00108"
FT REGION 1..104
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 29..49
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VARIANT 168
FT /note="L -> V (in FND1; dbSNP:rs121908167)"
FT /evidence="ECO:0000269|PubMed:19409524"
FT /id="VAR_063226"
FT VARIANT 183
FT /note="R -> W (in FND1; dbSNP:rs121908168)"
FT /evidence="ECO:0000269|PubMed:19409524"
FT /id="VAR_063227"
FT VARIANT 196
FT /note="R -> W (in FND1; dbSNP:rs121908170)"
FT /evidence="ECO:0000269|PubMed:19409524"
FT /id="VAR_063228"
FT VARIANT 203
FT /note="N -> S (in FND1; dbSNP:rs121908166)"
FT /evidence="ECO:0000269|PubMed:19409524"
FT /id="VAR_063229"
FT VARIANT 234
FT /note="P -> A (in dbSNP:rs12749726)"
FT /id="VAR_047475"
FT CONFLICT 72
FT /note="L -> M (in Ref. 1; AAD01417)"
FT /evidence="ECO:0000305"
FT CONFLICT 86
FT /note="F -> L (in Ref. 1; AAD01417)"
FT /evidence="ECO:0000305"
FT CONFLICT 249
FT /note="S -> G (in Ref. 1; AAD01418)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 343 AA; 36935 MW; 0BB20630D5CB817B CRC64;
MDPEHCAPFR VGPAPGPYVA SGDEPPGPQG TPAAAPHLHP APPRGPRLTR FPACGPLEPY
LPEPAKPPAK YLQDLGPGPA LNGGHFYEGP AEAEEKTSKA ASFPQLPLDC RGGPRDGPSN
LQGSPGPCLA SLHLPLSPGL PDSMELAKNK SKKRRNRTTF STFQLEELEK VFQKTHYPDV
YAREQLALRT DLTEARVQVW FQNRRAKWRK RERYGKIQEG RNPFTAAYDI SVLPRTDSHP
QLQNSLWASP GSGSPGGPCL VSPEGIPSPC MSPYSHPHGS VAGFMGVPAP SAAHPGIYSI
HGFPPTLGGH SFEPSSDGDY KSPSLVSLRV KPKEPPGLLN WTT
