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   02-SEP-2026, entry version 198.
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_006735.4.
DR   AlphaFoldDB; O43364; -.
DR   SMR; O43364; -.
DR   BioGRID; 109439; 17.
DR   FunCoup; O43364; 1111.
DR   IntAct; O43364; 13.
DR   STRING; 9606.ENSP00000222718; -.
DR   iPTMnet; O43364; -.
DR   PhosphoSitePlus; O43364; -.
DR   BioMuta; HOXA2; -.
DR   MassIVE; O43364; -.
DR   PaxDb; 9606-ENSP00000222718; -.
DR   PeptideAtlas; O43364; -.
DR   Antibodypedia; 12364; 163 antibodies from 28 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   AGR; HGNC:5103; -.
DR   ClinPGx; PA29380; -.
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   OpenTargets; ENSG00000105996; -.
DR   Orphanet; 140963; Bilateral microtia-deafness-cleft palate syndrome.
DR   Orphanet; 83463; Microtia.
DR   VEuPathDB; HostDB:ENSG00000105996; -.
DR   eggNOG; KOG0489; Eukaryota.
DR   GeneTree; ENSGT00940000162533; -.
DR   HOGENOM; CLU_048378_0_0_1; -.
DR   InParanoid; O43364; -.
DR   OMA; IHDFQPF; -.
DR   OrthoDB; 6159439at2759; -.
DR   PAN-GO; O43364; 4 GO annotations based on evolutionary models.
DR   PhylomeDB; O43364; -.
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   Agora; ENSG00000105996; -.
DR   BioGRID-ORCS; 3199; 6 hits in 1169 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 81 other cell types or tissues.
DR   GO; GO:0000785; C:chromatin; ISA:NTNU_SB.
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:0048706; P:embryonic skeletal system development; IEA:Ensembl.
DR   GO; GO:0061061; P:muscle structure development; IEA:Ensembl.
DR   GO; GO:0060037; P:pharyngeal system development; IEA:Ensembl.
DR   GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR   CDD; cd00086; homeodomain; 1.
DR   FunFam; 1.10.10.60:FF:000145; homeobox protein Hox-A2; 1.
DR   Gene3D; 1.10.10.60; Homeodomain-like; 1.
DR   InterPro; IPR001356; HD.
DR   InterPro; IPR020479; HD_metazoa.
DR   InterPro; IPR001827; Homeobox_Antennapedia_CS.
DR   InterPro; IPR017970; Homeobox_CS.
DR   InterPro; IPR009057; Homeodomain-like_sf.
DR   PANTHER; PTHR45664:SF3; HOMEOBOX PROTEIN HOX-A2; 1.
DR   PANTHER; PTHR45664; PROTEIN ZERKNUELLT 1-RELATED; 1.
DR   Pfam; PF00046; Homeodomain; 1.
DR   PRINTS; PR00024; HOMEOBOX.
DR   SMART; SM00389; HOX; 1.
DR   SUPFAM; SSF46689; Homeodomain-like; 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   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
//