HXA2_HUMAN
ID HXA2_HUMAN Reviewed; 376 AA.
AC O43364; A1L4K3; B2RMW3;
DT 15-JUL-1999, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-1998, sequence version 1.
DT 03-AUG-2022, entry version 180.
DE RecName: Full=Homeobox protein Hox-A2;
DE AltName: Full=Homeobox protein Hox-1K;
GN Name=HOXA2; Synonyms=HOX1K;
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 [LARGE SCALE GENOMIC DNA].
RX PubMed=12853948; DOI=10.1038/nature01782;
RA Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H.,
RA Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K.,
RA Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A.,
RA Delehaunty K.D., Miner T.L., Nash W.E., Cordes M., Du H., Sun H.,
RA Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A.,
RA Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P.,
RA Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M.,
RA Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S.,
RA Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R.,
RA Strowmatt C., Latreille P., Miller N., Johnson D., Murray J.,
RA Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W.,
RA Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A.,
RA Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E.,
RA Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E.,
RA Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A.,
RA Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A.,
RA Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R.,
RA McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H.,
RA Wilson R.K.;
RT "The DNA sequence of human chromosome 7.";
RL Nature 424:157-164(2003).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=12690205; DOI=10.1126/science.1083423;
RA Scherer S.W., Cheung J., MacDonald J.R., Osborne L.R., Nakabayashi K.,
RA Herbrick J.-A., Carson A.R., Parker-Katiraee L., Skaug J., Khaja R.,
RA Zhang J., Hudek A.K., Li M., Haddad M., Duggan G.E., Fernandez B.A.,
RA Kanematsu E., Gentles S., Christopoulos C.C., Choufani S., Kwasnicka D.,
RA Zheng X.H., Lai Z., Nusskern D.R., Zhang Q., Gu Z., Lu F., Zeesman S.,
RA Nowaczyk M.J., Teshima I., Chitayat D., Shuman C., Weksberg R.,
RA Zackai E.H., Grebe T.A., Cox S.R., Kirkpatrick S.J., Rahman N.,
RA Friedman J.M., Heng H.H.Q., Pelicci P.G., Lo-Coco F., Belloni E.,
RA Shaffer L.G., Pober B., Morton C.C., Gusella J.F., Bruns G.A.P., Korf B.R.,
RA Quade B.J., Ligon A.H., Ferguson H., Higgins A.W., Leach N.T.,
RA Herrick S.R., Lemyre E., Farra C.G., Kim H.-G., Summers A.M., Gripp K.W.,
RA Roberts W., Szatmari P., Winsor E.J.T., Grzeschik K.-H., Teebi A.,
RA Minassian B.A., Kere J., Armengol L., Pujana M.A., Estivill X.,
RA Wilson M.D., Koop B.F., Tosi S., Moore G.E., Boright A.P., Zlotorynski E.,
RA Kerem B., Kroisel P.M., Petek E., Oscier D.G., Mould S.J., Doehner H.,
RA Doehner K., Rommens J.M., Vincent J.B., Venter J.C., Li P.W., Mural R.J.,
RA Adams M.D., Tsui L.-C.;
RT "Human chromosome 7: DNA sequence and biology.";
RL Science 300:767-772(2003).
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].
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 INVOLVEMENT IN MCRT.
RX PubMed=23775976; DOI=10.1002/humu.22367;
RA Brown K.K., Viana L.M., Helwig C.C., Artunduaga M.A., Quintanilla-Dieck L.,
RA Jarrin P., Osorno G., McDonough B., Depalma S.R., Eavey R.D., Seidman J.G.,
RA Seidman C.E.;
RT "HOXA2 haploinsufficiency in dominant bilateral microtia and hearing
RT loss.";
RL Hum. Mutat. 34:1347-1351(2013).
RN [6]
RP VARIANT MHICP LYS-186.
RX PubMed=18394579; DOI=10.1016/j.ajhg.2008.02.015;
RA Alasti F., Sadeghi A., Sanati M.H., Farhadi M., Stollar E., Somers T.,
RA Van Camp G.;
RT "A mutation in HOXA2 is responsible for autosomal-recessive microtia in an
RT Iranian family.";
RL Am. J. Hum. Genet. 82:982-991(2008).
RN [7]
RP ERRATUM OF PUBMED:18394579.
RA Alasti F., Sadeghi A., Sanati M.H., Farhadi M., Stollar E., Somers T.,
RA Van Camp G.;
RL Am. J. Hum. Genet. 83:424-424(2008).
CC -!- FUNCTION: Sequence-specific transcription factor which is part of a
CC developmental regulatory system that provides cells with specific
CC positional identities on the anterior-posterior axis.
CC -!- SUBCELLULAR LOCATION: Nucleus.
CC -!- DISEASE: Microtia, hearing impairment, and cleft palate (MHICP)
CC [MIM:612290]: A disease characterized by microtia, mixed symmetric
CC severe to profound hearing impairment, and partial cleft palate.
CC Microtia is a congenital deformity of the outer ear that is small and
CC abnormally shaped. In classic microtia, the pinna is essentially
CC absent, except for a vertical sausage-shaped skin remnant. The superior
CC aspect of this sausage-shaped skin remnant consists of underlying
CC unorganized cartilage, and the inferior aspect of this remnant consists
CC of a relatively well-formed lobule. Syndromic forms of microtia occur
CC in conjunction with other abnormalities including cleft palate, a
CC congenital fissure of the soft and/or hard palate due to faulty fusion.
CC {ECO:0000269|PubMed:18394579}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Microtia with or without hearing impairment (MCRT)
CC [MIM:612290]: Microtia is a congenital deformity of the outer ear that
CC is small and abnormally shaped. In classic microtia, the pinna is
CC essentially absent, except for a vertical sausage-shaped skin remnant.
CC The superior aspect of this sausage-shaped skin remnant consists of
CC underlying unorganized cartilage, and the inferior aspect of this
CC remnant consists of a relatively well-formed lobule.
CC {ECO:0000269|PubMed:23775976}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the Antp homeobox family. Proboscipedia
CC subfamily. {ECO:0000305}.
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DR EMBL; AC004079; AAS00375.1; -; Genomic_DNA.
DR EMBL; CH236948; EAL24227.1; -; Genomic_DNA.
DR EMBL; CH471073; EAW93864.1; -; Genomic_DNA.
DR EMBL; BC130571; AAI30572.1; -; mRNA.
DR EMBL; BC136500; AAI36501.1; -; mRNA.
DR CCDS; CCDS5403.1; -.
DR RefSeq; NP_006726.1; NM_006735.3.
DR AlphaFoldDB; O43364; -.
DR SMR; O43364; -.
DR BioGRID; 109439; 5.
DR IntAct; O43364; 13.
DR STRING; 9606.ENSP00000222718; -.
DR iPTMnet; O43364; -.
DR PhosphoSitePlus; O43364; -.
DR BioMuta; HOXA2; -.
DR jPOST; O43364; -.
DR MassIVE; O43364; -.
DR PaxDb; O43364; -.
DR PeptideAtlas; O43364; -.
DR PRIDE; O43364; -.
DR Antibodypedia; 12364; 167 antibodies from 27 providers.
DR DNASU; 3199; -.
DR Ensembl; ENST00000222718.7; ENSP00000222718.5; ENSG00000105996.7.
DR GeneID; 3199; -.
DR KEGG; hsa:3199; -.
DR MANE-Select; ENST00000222718.7; ENSP00000222718.5; NM_006735.4; NP_006726.1.
DR UCSC; uc003syh.4; human.
DR CTD; 3199; -.
DR DisGeNET; 3199; -.
DR GeneCards; HOXA2; -.
DR HGNC; HGNC:5103; HOXA2.
DR HPA; ENSG00000105996; Low tissue specificity.
DR MalaCards; HOXA2; -.
DR MIM; 604685; gene.
DR MIM; 612290; phenotype.
DR neXtProt; NX_O43364; -.
DR OpenTargets; ENSG00000105996; -.
DR Orphanet; 140963; Bilateral microtia-deafness-cleft palate syndrome.
DR Orphanet; 83463; Microtia.
DR PharmGKB; PA29380; -.
DR VEuPathDB; HostDB:ENSG00000105996; -.
DR eggNOG; KOG0489; Eukaryota.
DR GeneTree; ENSGT00940000162533; -.
DR HOGENOM; CLU_048378_0_0_1; -.
DR InParanoid; O43364; -.
DR OMA; ACLGHKE; -.
DR OrthoDB; 835724at2759; -.
DR PhylomeDB; O43364; -.
DR TreeFam; TF317730; -.
DR PathwayCommons; O43364; -.
DR Reactome; R-HSA-5617472; Activation of anterior HOX genes in hindbrain development during early embryogenesis.
DR Reactome; R-HSA-9010553; Regulation of expression of SLITs and ROBOs.
DR SignaLink; O43364; -.
DR SIGNOR; O43364; -.
DR BioGRID-ORCS; 3199; 6 hits in 1093 CRISPR screens.
DR GeneWiki; HOXA2; -.
DR GenomeRNAi; 3199; -.
DR Pharos; O43364; Tbio.
DR PRO; PR:O43364; -.
DR Proteomes; UP000005640; Chromosome 7.
DR RNAct; O43364; protein.
DR Bgee; ENSG00000105996; Expressed in mucosa of transverse colon and 80 other tissues.
DR Genevisible; O43364; HS.
DR GO; GO:0000785; C:chromatin; ISA:NTNU_SB.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:HPA.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
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:0000978; F:RNA polymerase II cis-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:0009952; P:anterior/posterior pattern specification; IEA:Ensembl.
DR GO; GO:0035284; P:brain segmentation; IEA:Ensembl.
DR GO; GO:0001709; P:cell fate determination; IEA:Ensembl.
DR GO; GO:0071300; P:cellular response to retinoic acid; IEA:Ensembl.
DR GO; GO:0009953; P:dorsal/ventral pattern formation; IEA:Ensembl.
DR GO; GO:0048703; P:embryonic viscerocranium morphogenesis; IEA:Ensembl.
DR GO; GO:0042474; P:middle ear morphogenesis; IEA:Ensembl.
DR GO; GO:0008045; P:motor neuron axon guidance; IEA:Ensembl.
DR GO; GO:0061061; P:muscle structure development; IEA:Ensembl.
DR GO; GO:0045665; P:negative regulation of neuron differentiation; IEA:Ensembl.
DR GO; GO:0045668; P:negative regulation of osteoblast differentiation; IEA:Ensembl.
DR GO; GO:0002076; P:osteoblast development; IEA:Ensembl.
DR GO; GO:0060037; P:pharyngeal system development; IEA:Ensembl.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IEA:Ensembl.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0021568; P:rhombomere 2 development; IEA:Ensembl.
DR GO; GO:0021658; P:rhombomere 3 morphogenesis; IEA:Ensembl.
DR GO; GO:0007379; P:segment specification; IEA:Ensembl.
DR CDD; cd00086; homeodomain; 1.
DR InterPro; IPR009057; Homeobox-like_sf.
DR InterPro; IPR001827; Homeobox_Antennapedia_CS.
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; PS00032; ANTENNAPEDIA; 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..376
FT /note="Homeobox protein Hox-A2"
FT /id="PRO_0000200036"
FT DNA_BIND 143..202
FT /note="Homeobox"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00108"
FT REGION 42..93
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 198..229
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 257..279
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 94..99
FT /note="Antp-type hexapeptide"
FT COMPBIAS 42..61
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 202..220
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VARIANT 186
FT /note="Q -> K (in MHICP; dbSNP:rs119489104)"
FT /evidence="ECO:0000269|PubMed:18394579"
FT /id="VAR_048023"
SQ SEQUENCE 376 AA; 41002 MW; 78EB388FE1EEAD72 CRC64;
MNYEFEREIG FINSQPSLAE CLTSFPPVAD TFQSSSIKTS TLSHSTLIPP PFEQTIPSLN
PGSHPRHGAG GRPKPSPAGS RGSPVPAGAL QPPEYPWMKE KKAAKKTALL PAAAAAATAA
ATGPACLSHK ESLEIADGSG GGSRRLRTAY TNTQLLELEK EFHFNKYLCR PRRVEIAALL
DLTERQVKVW FQNRRMKHKR QTQCKENQNS EGKCKSLEDS EKVEEDEEEK TLFEQALSVS
GALLEREGYT FQQNALSQQQ APNGHNGDSQ SFPVSPLTSN EKNLKHFQHQ SPTVPNCLST
MGQNCGAGLN NDSPEALEVP SLQDFSVFST DSCLQLSDAV SPSLPGSLDS PVDISADSLD
FFTDTLTTID LQHLNY
