HMX1_HUMAN
ID HMX1_HUMAN Reviewed; 348 AA.
AC Q9NP08;
DT 20-FEB-2007, integrated into UniProtKB/Swiss-Prot.
DT 22-SEP-2009, sequence version 2.
DT 03-AUG-2022, entry version 148.
DE RecName: Full=Homeobox protein HMX1;
DE AltName: Full=Homeobox protein H6;
GN Name=HMX1; Synonyms=H6;
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].
RC TISSUE=Craniofacial;
RX PubMed=1360670; DOI=10.1073/pnas.89.23.11579;
RA Stadler H.S., Padanilam B.J., Buetow K., Murray J.C., Solursh M.;
RT "Identification and genetic mapping of a homeobox gene to the 4p16.1 region
RT of human chromosome 4.";
RL Proc. Natl. Acad. Sci. U.S.A. 89:11579-11583(1992).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT 4.";
RL Nature 434:724-731(2005).
RN [3]
RP FUNCTION.
RX PubMed=10206974; DOI=10.1074/jbc.274.17.11635;
RA Amendt B.A., Sutherland L.B., Russo A.F.;
RT "Transcriptional antagonism between Hmx1 and Nkx2.5 for a shared DNA-
RT binding site.";
RL J. Biol. Chem. 274:11635-11642(1999).
RN [4]
RP INVOLVEMENT IN OCACS.
RX PubMed=18423520; DOI=10.1016/j.ajhg.2008.03.007;
RA Schorderet D.F., Nichini O., Boisset G., Polok B., Tiab L., Mayeur H.,
RA Raji B., de la Houssaye G., Abitbol M.M., Munier F.L.;
RT "Mutation in the human homeobox gene NKX5-3 causes an oculo-auricular
RT syndrome.";
RL Am. J. Hum. Genet. 82:1178-1184(2008).
CC -!- FUNCTION: DNA-binding protein that binds to the 5'-CAAG-3' core
CC sequence. May function as a transcriptional repressor. Seems to act as
CC a transcriptional antagonist of NKX2-5. May play an important role in
CC the development of craniofacial structures such as the eye and ear.
CC {ECO:0000269|PubMed:10206974}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000305}.
CC -!- DISEASE: Oculoauricular syndrome (OCACS) [MIM:612109]: A syndrome
CC characterized by microphthalmia, microcornea, anterior segment
CC dysgenesis, cataract, ocular coloboma, retinal pigment epithelium
CC abnormalities, rod-cone dystrophy, and anomalies of the external ear.
CC {ECO:0000269|PubMed:18423520}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the HMX homeobox family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAF70205.1; Type=Frameshift; Evidence={ECO:0000305};
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; M99587; AAF70205.1; ALT_FRAME; mRNA.
DR EMBL; AC116612; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR CCDS; CCDS47018.1; -.
DR PIR; A47234; A47234.
DR RefSeq; NP_001293071.1; NM_001306142.1.
DR RefSeq; NP_061815.2; NM_018942.2.
DR AlphaFoldDB; Q9NP08; -.
DR SMR; Q9NP08; -.
DR BioGRID; 109409; 1.
DR STRING; 9606.ENSP00000383516; -.
DR GlyGen; Q9NP08; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q9NP08; -.
DR PhosphoSitePlus; Q9NP08; -.
DR BioMuta; HMX1; -.
DR DMDM; 259016250; -.
DR jPOST; Q9NP08; -.
DR MassIVE; Q9NP08; -.
DR PaxDb; Q9NP08; -.
DR PeptideAtlas; Q9NP08; -.
DR PRIDE; Q9NP08; -.
DR ProteomicsDB; 81880; -.
DR Antibodypedia; 4687; 51 antibodies from 16 providers.
DR DNASU; 3166; -.
DR Ensembl; ENST00000400677.5; ENSP00000383516.3; ENSG00000215612.8.
DR Ensembl; ENST00000673238.1; ENSP00000499825.1; ENSG00000288204.1.
DR GeneID; 3166; -.
DR KEGG; hsa:3166; -.
DR MANE-Select; ENST00000400677.5; ENSP00000383516.3; NM_018942.3; NP_061815.2.
DR UCSC; uc003izz.2; human.
DR CTD; 3166; -.
DR DisGeNET; 3166; -.
DR GeneCards; HMX1; -.
DR HGNC; HGNC:5017; HMX1.
DR HPA; ENSG00000215612; Tissue enhanced (brain, retina, testis).
DR MalaCards; HMX1; -.
DR MIM; 142992; gene.
DR MIM; 612109; phenotype.
DR neXtProt; NX_Q9NP08; -.
DR OpenTargets; ENSG00000215612; -.
DR Orphanet; 157962; Oculoauricular syndrome, Schorderet type.
DR PharmGKB; PA29344; -.
DR VEuPathDB; HostDB:ENSG00000215612; -.
DR eggNOG; KOG0485; Eukaryota.
DR GeneTree; ENSGT00940000162580; -.
DR HOGENOM; CLU_064096_2_0_1; -.
DR InParanoid; Q9NP08; -.
DR OMA; TMEWYRR; -.
DR OrthoDB; 1313583at2759; -.
DR PhylomeDB; Q9NP08; -.
DR TreeFam; TF320562; -.
DR PathwayCommons; Q9NP08; -.
DR BioGRID-ORCS; 3166; 14 hits in 1092 CRISPR screens.
DR GenomeRNAi; 3166; -.
DR Pharos; Q9NP08; Tbio.
DR PRO; PR:Q9NP08; -.
DR Proteomes; UP000005640; Chromosome 4.
DR RNAct; Q9NP08; protein.
DR Bgee; ENSG00000215612; Expressed in amygdala and 27 other tissues.
DR ExpressionAtlas; Q9NP08; baseline and differential.
DR Genevisible; Q9NP08; HS.
DR GO; GO:0000785; C:chromatin; ISA:NTNU_SB.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0003677; F:DNA binding; IMP:UniProtKB.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; ISA:NTNU_SB.
DR GO; GO:0001227; F:DNA-binding transcription repressor activity, RNA polymerase II-specific; IEA:Ensembl.
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:0045892; P:negative regulation of transcription, DNA-templated; IMP:UniProtKB.
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; IPR020479; Homeobox_metazoa.
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 2: Evidence at transcript level;
KW Cataract; Developmental protein; DNA-binding; Homeobox; Microphthalmia;
KW Nucleus; Reference proteome; Repressor; Transcription;
KW Transcription regulation.
FT CHAIN 1..348
FT /note="Homeobox protein HMX1"
FT /id="PRO_0000278453"
FT DNA_BIND 203..262
FT /note="Homeobox"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00108"
FT REGION 29..203
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 263..273
FT /note="HMX family specific domain 1"
FT MOTIF 276..289
FT /note="HMX family specific domain 2"
FT CONFLICT 277
FT /note="Q -> A (in Ref. 1; AAF70205)"
FT /evidence="ECO:0000305"
FT CONFLICT 308..310
FT /note="PAA -> RR (in Ref. 1; AAF70205)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 348 AA; 36155 MW; 7B2AE7662699B15A CRC64;
MPDELTEPGR ATPARASSFL IENLLAAEAK GAGRATQGDG SREDEEEDDD DPEDEDAEQA
RRRRLQRRRQ LLAGTGPGGE ARARALLGPG ALGLGPRPPP GPGPPFALGC GGAARWYPRA
HGGYGGGLSP DTSDRDSPET GEEMGRAEGA WPRGPGPGAV QREAAELAAR GPAAGTEEAS
ELAEVPAAAG ETRGGVGVGG GRKKKTRTVF SRSQVFQLES TFDLKRYLSS AERAGLAASL
QLTETQVKIW FQNRRNKWKR QLAAELEAAS LSPPGAQRLV RVPVLYHESP PAAAAAGPPA
TLPFPLAPAA PAPPPPLLGF SGALAYPLAA FPAAASVPFL RAQMPGLV
