MIXL1_HUMAN
ID MIXL1_HUMAN Reviewed; 232 AA.
AC Q9H2W2; B7ZLF9;
DT 13-NOV-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2001, sequence version 1.
DT 03-AUG-2022, entry version 178.
DE RecName: Full=Homeobox protein MIXL1;
DE AltName: Full=Homeodomain protein MIX;
DE Short=hMix;
DE AltName: Full=MIX1 homeobox-like protein 1;
DE AltName: Full=Mix.1 homeobox-like protein;
GN Name=MIXL1; Synonyms=MIXL;
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] (ISOFORM 1), SUBCELLULAR LOCATION, AND TISSUE
RP SPECIFICITY.
RX PubMed=12070013; DOI=10.1182/blood.v100.1.89;
RA Guo W., Chan A.P., Liang H., Wieder E.D., Molldrem J.J., Etkin L.D.,
RA Nagarajan L.;
RT "A human Mix-like homeobox gene MIXL shows functional similarity to Xenopus
RT Mix.1.";
RL Blood 100:89-95(2002).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=11084649;
RX DOI=10.1002/1097-0177(2000)9999:9999<::aid-dvdy1070>3.0.co;2-o;
RA Robb L., Hartley L., Begley C.G., Brodnicki T.C., Copeland N.G.,
RA Gilbert D.J., Jenkins N.A., Elefanty A.G.;
RT "Cloning, expression analysis, and chromosomal localization of murine and
RT human homologues of a Xenopus mix gene.";
RL Dev. Dyn. 219:497-504(2000).
RN [3]
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 [4]
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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
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 [6]
RP TISSUE SPECIFICITY.
RX PubMed=16433620; DOI=10.1089/scd.2005.14.656;
RA Mossman A.K., Sourris K., Ng E., Stanley E.G., Elefanty A.G.;
RT "Mixl1 and oct4 proteins are transiently co-expressed in differentiating
RT mouse and human embryonic stem cells.";
RL Stem Cells Dev. 14:656-663(2005).
RN [7]
RP PHOSPHORYLATION AT TYR-20.
RX PubMed=17224082; DOI=10.1186/1750-2187-1-6;
RA Guo W., Nagarajan L.;
RT "Amino terminal tyrosine phosphorylation of human MIXL1.";
RL J. Mol. Signal. 1:6-6(2006).
RN [8]
RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=17303500; DOI=10.1016/j.humpath.2006.09.020;
RA Drakos E., Rassidakis G.Z., Leventaki V., Guo W., Medeiros L.J.,
RA Nagarajan L.;
RT "Differential expression of the human MIXL1 gene product in non-Hodgkin and
RT Hodgkin lymphomas.";
RL Hum. Pathol. 38:500-507(2007).
CC -!- FUNCTION: Transcription factor that play a central role in proper axial
CC mesendoderm morphogenesis and endoderm formation. Required for
CC efficient differentiation of cells from the primitive streak stage to
CC blood, by acting early in the recruitment and/or expansion of
CC mesodermal progenitors to the hemangioblastic and hematopoietic
CC lineages. Also involved in the morphogenesis of the heart and the gut
CC during embryogenesis. Acts as a negative regulator of brachyury
CC expression (By similarity). {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000255|PROSITE-ProRule:PRU00108,
CC ECO:0000269|PubMed:12070013, ECO:0000269|PubMed:17303500}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9H2W2-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9H2W2-2; Sequence=VSP_054305;
CC -!- TISSUE SPECIFICITY: Restricted to progenitors and secondary lymph
CC tissues. In normal hematopoiesis, it is restricted to immature B- and
CC T-lymphoid cells. Present in differentiating embryonic stem cells (at
CC protein level). {ECO:0000269|PubMed:12070013,
CC ECO:0000269|PubMed:16433620, ECO:0000269|PubMed:17303500}.
CC -!- PTM: Phosphorylated at multiple sites. {ECO:0000269|PubMed:17224082}.
CC -!- SIMILARITY: Belongs to the paired homeobox family. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/MIXL1ID47624ch1q42.html";
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DR EMBL; AF211891; AAG35776.1; -; mRNA.
DR EMBL; AF218357; AAK01479.1; -; Genomic_DNA.
DR EMBL; AL592045; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471098; EAW69778.1; -; Genomic_DNA.
DR EMBL; BC111974; AAI11975.1; -; mRNA.
DR EMBL; BC113441; AAI13442.1; -; mRNA.
DR EMBL; BC143784; AAI43785.1; -; mRNA.
DR CCDS; CCDS1552.1; -. [Q9H2W2-1]
DR CCDS; CCDS60432.1; -. [Q9H2W2-2]
DR RefSeq; NP_001269331.1; NM_001282402.1. [Q9H2W2-2]
DR RefSeq; NP_114150.1; NM_031944.2. [Q9H2W2-1]
DR AlphaFoldDB; Q9H2W2; -.
DR SMR; Q9H2W2; -.
DR IntAct; Q9H2W2; 1.
DR STRING; 9606.ENSP00000442439; -.
DR iPTMnet; Q9H2W2; -.
DR PhosphoSitePlus; Q9H2W2; -.
DR BioMuta; MIXL1; -.
DR DMDM; 74762734; -.
DR MassIVE; Q9H2W2; -.
DR PaxDb; Q9H2W2; -.
DR PeptideAtlas; Q9H2W2; -.
DR PRIDE; Q9H2W2; -.
DR ProteomicsDB; 7224; -.
DR ProteomicsDB; 80609; -. [Q9H2W2-1]
DR Antibodypedia; 20764; 152 antibodies from 31 providers.
DR DNASU; 83881; -.
DR Ensembl; ENST00000366810.6; ENSP00000355775.4; ENSG00000185155.12. [Q9H2W2-1]
DR Ensembl; ENST00000542034.5; ENSP00000442439.1; ENSG00000185155.12. [Q9H2W2-2]
DR GeneID; 83881; -.
DR KEGG; hsa:83881; -.
DR MANE-Select; ENST00000366810.6; ENSP00000355775.4; NM_031944.3; NP_114150.1.
DR UCSC; uc010pvm.4; human. [Q9H2W2-1]
DR CTD; 83881; -.
DR DisGeNET; 83881; -.
DR GeneCards; MIXL1; -.
DR HGNC; HGNC:13363; MIXL1.
DR HPA; ENSG00000185155; Tissue enhanced (lymphoid).
DR MIM; 609852; gene.
DR neXtProt; NX_Q9H2W2; -.
DR OpenTargets; ENSG00000185155; -.
DR PharmGKB; PA134976348; -.
DR VEuPathDB; HostDB:ENSG00000185155; -.
DR eggNOG; KOG0849; Eukaryota.
DR GeneTree; ENSGT00940000162190; -.
DR HOGENOM; CLU_104890_0_0_1; -.
DR InParanoid; Q9H2W2; -.
DR OMA; HHSACET; -.
DR OrthoDB; 1270742at2759; -.
DR PhylomeDB; Q9H2W2; -.
DR TreeFam; TF334098; -.
DR PathwayCommons; Q9H2W2; -.
DR SignaLink; Q9H2W2; -.
DR BioGRID-ORCS; 83881; 38 hits in 1095 CRISPR screens.
DR GenomeRNAi; 83881; -.
DR Pharos; Q9H2W2; Tbio.
DR PRO; PR:Q9H2W2; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; Q9H2W2; protein.
DR Bgee; ENSG00000185155; Expressed in oocyte and 85 other tissues.
DR ExpressionAtlas; Q9H2W2; baseline and differential.
DR Genevisible; Q9H2W2; HS.
DR GO; GO:0000785; C:chromatin; ISS:BHF-UCL.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0000987; F:cis-regulatory region sequence-specific DNA binding; ISS:BHF-UCL.
DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; ISS:BHF-UCL.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; ISA:NTNU_SB.
DR GO; GO:0042803; F:protein homodimerization activity; ISS:BHF-UCL.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; ISS:BHF-UCL.
DR GO; GO:0061629; F:RNA polymerase II-specific DNA-binding transcription factor binding; IPI:BHF-UCL.
DR GO; GO:1990837; F:sequence-specific double-stranded DNA binding; IDA:ARUK-UCL.
DR GO; GO:0042074; P:cell migration involved in gastrulation; IEA:Ensembl.
DR GO; GO:0048565; P:digestive tract development; ISS:BHF-UCL.
DR GO; GO:0007492; P:endoderm development; ISS:BHF-UCL.
DR GO; GO:0001706; P:endoderm formation; IBA:GO_Central.
DR GO; GO:0035987; P:endodermal cell differentiation; ISS:BHF-UCL.
DR GO; GO:0007369; P:gastrulation; ISS:BHF-UCL.
DR GO; GO:0007507; P:heart development; ISS:BHF-UCL.
DR GO; GO:0002244; P:hematopoietic progenitor cell differentiation; ISS:BHF-UCL.
DR GO; GO:1901533; P:negative regulation of hematopoietic progenitor cell differentiation; ISS:BHF-UCL.
DR GO; GO:2000382; P:positive regulation of mesoderm development; ISS:BHF-UCL.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISS:BHF-UCL.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR CDD; cd00086; homeodomain; 1.
DR InterPro; IPR009057; Homeobox-like_sf.
DR InterPro; IPR017970; Homeobox_CS.
DR InterPro; IPR001356; Homeobox_dom.
DR InterPro; IPR042917; MIXL1.
DR PANTHER; PTHR47656; PTHR47656; 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 Alternative splicing; Developmental protein; Differentiation; DNA-binding;
KW Homeobox; Nucleus; Phosphoprotein; Reference proteome; Transcription;
KW Transcription regulation.
FT CHAIN 1..232
FT /note="Homeobox protein MIXL1"
FT /id="PRO_0000311333"
FT DNA_BIND 86..145
FT /note="Homeobox"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00108"
FT REGION 22..92
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 28..48
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 59..73
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 20
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000269|PubMed:17224082"
FT VAR_SEQ 130
FT /note="I -> IQLLFSPLF (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_054305"
SQ SEQUENCE 232 AA; 24659 MW; 2E8A6A811799A8F0 CRC64;
MATAESRALQ FAEGAAFPAY RAPHAGGALL PPPSPAAALL PAPPAGPGPA TFAGFLGRDP
GPAPPPPASL GSPAPPKGAA APSASQRRKR TSFSAEQLQL LELVFRRTRY PDIHLRERLA
ALTLLPESRI QVWFQNRRAK SRRQSGKSFQ PLARPEIILN HCAPGTETKC LKPQLPLEVD
VNCLPEPNGV GGGISDSSSQ GQNFETCSPL SEDIGSKLDS WEEHIFSAFG NF
