HXA13_HUMAN
ID HXA13_HUMAN Reviewed; 388 AA.
AC P31271; A4D188; O43371;
DT 01-JUL-1993, integrated into UniProtKB/Swiss-Prot.
DT 17-OCT-2006, sequence version 3.
DT 03-AUG-2022, entry version 200.
DE RecName: Full=Homeobox protein Hox-A13;
DE AltName: Full=Homeobox protein Hox-1J;
GN Name=HOXA13; Synonyms=HOX1J;
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 [GENOMIC DNA].
RX PubMed=9020844; DOI=10.1038/ng0297-179;
RA Mortlock D.P., Innis J.W.;
RT "Mutation of HOXA13 in hand-foot-genital syndrome.";
RL Nat. Genet. 15:179-180(1997).
RN [2]
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 [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 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 [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 322-387.
RX PubMed=2574852; DOI=10.1093/nar/17.24.10385;
RA Acampora D., D'Esposito M., Faiella A., Pannese M., Migliaccio E.,
RA Morelli F., Stornaiuolo A., Nigro V., Simeone A., Boncinelli E.;
RT "The human HOX gene family.";
RL Nucleic Acids Res. 17:10385-10402(1989).
RN [6]
RP STRUCTURE BY NMR OF 322-388 IN COMPLEX WITH DNA, AND SUBUNIT.
RX PubMed=21829694; DOI=10.1371/journal.pone.0023069;
RA Zhang Y., Larsen C.A., Stadler H.S., Ames J.B.;
RT "Structural basis for sequence specific DNA binding and protein
RT dimerization of HOXA13.";
RL PLoS ONE 6:E23069-E23069(2011).
RN [7]
RP VARIANTS HFG HIS-372 AND ALA-ALA-ALA-ALA-ALA-ALA-ALA-ALA-129 INS.
RX PubMed=10839976; DOI=10.1086/302961;
RA Goodman F.R., Bacchelli C., Brady A.F., Brueton L.A., Fryns J.-P.,
RA Mortlock D.P., Innis J.W., Holmes L.B., Donnenfeld A.E., Feingold M.,
RA Beemer F.A., Hennekam R.C.M., Scambler P.J.;
RT "Novel HOXA13 mutations and the phenotypic spectrum of hand-foot-genital
RT syndrome.";
RL Am. J. Hum. Genet. 67:197-202(2000).
RN [8]
RP VARIANT HFG ALA-ALA-ALA-ALA-ALA-ALA-125 INS.
RX PubMed=12073020; DOI=10.1007/s00439-002-0712-8;
RA Utsch B., Becker K., Brock D., Lentze M.J., Bidlingmaier F., Ludwig M.;
RT "A novel stable polyalanine [poly(A)] expansion in the HOXA13 gene
RT associated with hand-foot-genital syndrome: proper function of poly(A)-
RT harbouring transcription factors depends on a critical repeat length?";
RL Hum. Genet. 110:488-494(2002).
RN [9]
RP VARIANT GUTTS LEU-371.
RX PubMed=11968094; DOI=10.1002/humu.9036;
RA Innis J.W., Goodman F.R., Bacchelli C., Williams T.M., Mortlock D.P.,
RA Sateesh P., Scambler P.J., McKinnon W., Guttmacher A.E.;
RT "A HOXA13 allele with a missense mutation in the homeobox and a
RT dinucleotide deletion in the promoter underlies Guttmacher syndrome.";
RL Hum. Mutat. 19:573-574(2002).
RN [10]
RP VARIANT HFG PHE-368.
RX PubMed=24934387; DOI=10.1002/ajmg.a.36648;
RA Imagawa E., Kayserili H., Nishimura G., Nakashima M., Tsurusaki Y.,
RA Saitsu H., Ikegawa S., Matsumoto N., Miyake N.;
RT "Severe manifestations of hand-foot-genital syndrome associated with a
RT novel HOXA13 mutation.";
RL Am. J. Med. Genet. A 164A:2398-2402(2014).
RN [11]
RP VARIANT HFG PHE-375.
RX PubMed=26590955; DOI=10.1002/ajmg.a.37478;
RA Wallis M., Tsurusaki Y., Burgess T., Borzi P., Matsumoto N., Miyake N.,
RA True D., Patel C.;
RT "Dual genetic diagnoses: Atypical hand-foot-genital syndrome and
RT developmental delay due to de novo mutations in HOXA13 and NRXN1.";
RL Am. J. Med. Genet. A 170:717-724(2016).
CC -!- FUNCTION: Sequence-specific, AT-rich binding transcription factor which
CC is part of a developmental regulatory system that provides cells with
CC specific positional identities on the anterior-posterior axis.
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 -!- SUBUNIT: Binds DNA as a homodimer. Interacts with MEIS1, MEIS2 and
CC MEIS3 (By similarity). {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Nucleus.
CC -!- DISEASE: Hand-foot-genital syndrome (HFG) [MIM:140000]: A disorder
CC characterized by limb and genitourinary anomalies. Clinical features
CC include small feet with unusually short great toes and abnormal thumbs.
CC Females with the disorder have duplication of the genital tract.
CC {ECO:0000269|PubMed:10839976, ECO:0000269|PubMed:12073020,
CC ECO:0000269|PubMed:24934387, ECO:0000269|PubMed:26590955}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- DISEASE: Guttmacher syndrome (GUTTS) [MIM:176305]: Dominantly inherited
CC combination of distal limb and genital tract abnormalities. It has
CC several features in common with hand-foot-genital syndrome, including
CC hypoplastic first digits and hypospadias. Typical features not seen in
CC hand-foot-genital syndrome include postaxial polydactyly of the hands
CC and uniphalangeal second toes with absent nails.
CC {ECO:0000269|PubMed:11968094}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the Abd-B homeobox family. {ECO:0000305}.
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DR EMBL; U82827; AAC50993.1; -; Genomic_DNA.
DR EMBL; AC004080; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471073; EAW93890.1; -; Genomic_DNA.
DR EMBL; CH236948; EAL24218.1; -; Genomic_DNA.
DR CCDS; CCDS5412.1; -.
DR PIR; S14932; S14932.
DR RefSeq; NP_000513.2; NM_000522.4.
DR PDB; 2L7Z; NMR; -; A=322-388.
DR PDBsum; 2L7Z; -.
DR AlphaFoldDB; P31271; -.
DR BMRB; P31271; -.
DR SMR; P31271; -.
DR BioGRID; 109449; 8.
DR IntAct; P31271; 3.
DR STRING; 9606.ENSP00000222753; -.
DR iPTMnet; P31271; -.
DR PhosphoSitePlus; P31271; -.
DR BioMuta; HOXA13; -.
DR DMDM; 116242513; -.
DR EPD; P31271; -.
DR jPOST; P31271; -.
DR MassIVE; P31271; -.
DR MaxQB; P31271; -.
DR PaxDb; P31271; -.
DR PeptideAtlas; P31271; -.
DR PRIDE; P31271; -.
DR ProteomicsDB; 54772; -.
DR Antibodypedia; 12410; 150 antibodies from 25 providers.
DR DNASU; 3209; -.
DR Ensembl; ENST00000649031.1; ENSP00000497112.1; ENSG00000106031.9.
DR GeneID; 3209; -.
DR KEGG; hsa:3209; -.
DR MANE-Select; ENST00000649031.1; ENSP00000497112.1; NM_000522.5; NP_000513.2.
DR UCSC; uc003szb.2; human.
DR CTD; 3209; -.
DR DisGeNET; 3209; -.
DR GeneCards; HOXA13; -.
DR GeneReviews; HOXA13; -.
DR HGNC; HGNC:5102; HOXA13.
DR HPA; ENSG00000106031; Tissue enhanced (cervix, placenta, prostate, seminal vesicle).
DR MalaCards; HOXA13; -.
DR MIM; 140000; phenotype.
DR MIM; 142959; gene.
DR MIM; 176305; phenotype.
DR neXtProt; NX_P31271; -.
DR OpenTargets; ENSG00000106031; -.
DR Orphanet; 2957; Guttmacher syndrome.
DR Orphanet; 2438; Hand-foot-genital syndrome.
DR PharmGKB; PA29379; -.
DR VEuPathDB; HostDB:ENSG00000106031; -.
DR eggNOG; KOG0487; Eukaryota.
DR GeneTree; ENSGT00940000162322; -.
DR HOGENOM; CLU_059940_1_0_1; -.
DR InParanoid; P31271; -.
DR OMA; YMDTAAS; -.
DR OrthoDB; 1190384at2759; -.
DR PhylomeDB; P31271; -.
DR TreeFam; TF330813; -.
DR PathwayCommons; P31271; -.
DR SignaLink; P31271; -.
DR SIGNOR; P31271; -.
DR BioGRID-ORCS; 3209; 56 hits in 1095 CRISPR screens.
DR GeneWiki; HOXA13; -.
DR GenomeRNAi; 3209; -.
DR Pharos; P31271; Tbio.
DR PRO; PR:P31271; -.
DR Proteomes; UP000005640; Chromosome 7.
DR RNAct; P31271; protein.
DR Bgee; ENSG00000106031; Expressed in endocervix and 61 other tissues.
DR Genevisible; P31271; HS.
DR GO; GO:0000785; C:chromatin; ISA:NTNU_SB.
DR GO; GO:0005694; C:chromosome; IDA:HPA.
DR GO; GO:0045111; C:intermediate filament cytoskeleton; IDA:HPA.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0003677; F:DNA binding; TAS:ProtInc.
DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; IEA:Ensembl.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; ISA:NTNU_SB.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IBA:GO_Central.
DR GO; GO:0043565; F:sequence-specific DNA binding; IDA:NTNU_SB.
DR GO; GO:1990837; F:sequence-specific double-stranded DNA binding; IDA:ARUK-UCL.
DR GO; GO:0048844; P:artery morphogenesis; IEA:Ensembl.
DR GO; GO:0060442; P:branching involved in prostate gland morphogenesis; IEA:Ensembl.
DR GO; GO:0035115; P:embryonic forelimb morphogenesis; IEA:Ensembl.
DR GO; GO:0048619; P:embryonic hindgut morphogenesis; IEA:Ensembl.
DR GO; GO:0060847; P:endothelial cell fate specification; IEA:Ensembl.
DR GO; GO:0001886; P:endothelial cell morphogenesis; IEA:Ensembl.
DR GO; GO:0048839; P:inner ear development; IEA:Ensembl.
DR GO; GO:0030539; P:male genitalia development; IEA:Ensembl.
DR GO; GO:0097152; P:mesenchymal cell apoptotic process; IEA:Ensembl.
DR GO; GO:0140014; P:mitotic nuclear division; IEA:Ensembl.
DR GO; GO:2001055; P:positive regulation of mesenchymal cell apoptotic process; IEA:Ensembl.
DR GO; GO:0045840; P:positive regulation of mitotic nuclear division; IEA:Ensembl.
DR GO; GO:0030510; P:regulation of BMP signaling pathway; IEA:Ensembl.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0033574; P:response to testosterone; IEA:Ensembl.
DR GO; GO:0001501; P:skeletal system development; TAS:ProtInc.
DR GO; GO:0001894; P:tissue homeostasis; IEA:Ensembl.
DR GO; GO:0006366; P:transcription by RNA polymerase II; IEA:Ensembl.
DR GO; GO:0001570; P:vasculogenesis; IEA:Ensembl.
DR GO; GO:0003281; P:ventricular septum development; IEA:Ensembl.
DR CDD; cd00086; homeodomain; 1.
DR InterPro; IPR009057; Homeobox-like_sf.
DR InterPro; IPR017970; Homeobox_CS.
DR InterPro; IPR001356; Homeobox_dom.
DR InterPro; IPR022067; HoxA13_N.
DR Pfam; PF00046; Homeodomain; 1.
DR Pfam; PF12284; HoxA13_N; 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 3D-structure; Developmental protein; Disease variant; DNA-binding;
KW Homeobox; Nucleus; Reference proteome; Transcription;
KW Transcription regulation.
FT CHAIN 1..388
FT /note="Homeobox protein Hox-A13"
FT /id="PRO_0000200101"
FT DNA_BIND 322..381
FT /note="Homeobox"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00108"
FT VARIANT 125
FT /note="A -> AAAAAAA (in HFG)"
FT /evidence="ECO:0000269|PubMed:12073020"
FT /id="VAR_017773"
FT VARIANT 129
FT /note="A -> AAAAAAAAA (in HFG)"
FT /id="VAR_017774"
FT VARIANT 368
FT /note="I -> F (in HFG; severe phenotype overlapping with
FT Guttmacher syndrome)"
FT /evidence="ECO:0000269|PubMed:24934387"
FT /id="VAR_075341"
FT VARIANT 371
FT /note="Q -> L (in GUTTS)"
FT /evidence="ECO:0000269|PubMed:11968094"
FT /id="VAR_017775"
FT VARIANT 372
FT /note="N -> H (in HFG; severe; dbSNP:rs121912542)"
FT /evidence="ECO:0000269|PubMed:10839976"
FT /id="VAR_017776"
FT VARIANT 375
FT /note="V -> F (in HFG)"
FT /evidence="ECO:0000269|PubMed:26590955"
FT /id="VAR_075342"
FT CONFLICT 146
FT /note="G -> A (in Ref. 1; AAC50993)"
FT /evidence="ECO:0000305"
FT CONFLICT 187
FT /note="H -> P (in Ref. 1; AAC50993)"
FT /evidence="ECO:0000305"
FT CONFLICT 195
FT /note="A -> P (in Ref. 1; AAC50993)"
FT /evidence="ECO:0000305"
FT CONFLICT 198
FT /note="A -> P (in Ref. 1; AAC50993)"
FT /evidence="ECO:0000305"
FT HELIX 331..343
FT /evidence="ECO:0007829|PDB:2L7Z"
FT HELIX 349..359
FT /evidence="ECO:0007829|PDB:2L7Z"
FT HELIX 364..377
FT /evidence="ECO:0007829|PDB:2L7Z"
FT STRAND 380..385
FT /evidence="ECO:0007829|PDB:2L7Z"
SQ SEQUENCE 388 AA; 39727 MW; 3512E7622FA931C4 CRC64;
MTASVLLHPR WIEPTVMFLY DNGGGLVADE LNKNMEGAAA AAAAAAAAAA AGAGGGGFPH
PAAAAAGGNF SVAAAAAAAA AAAANQCRNL MAHPAPLAPG AASAYSSAPG EAPPSAAAAA
AAAAAAAAAA AAASSSGGPG PAGPAGAEAA KQCSPCSAAA QSSSGPAALP YGYFGSGYYP
CARMGPHPNA IKSCAQPASA AAAAAFADKY MDTAGPAAEE FSSRAKEFAF YHQGYAAGPY
HHHQPMPGYL DMPVVPGLGG PGESRHEPLG LPMESYQPWA LPNGWNGQMY CPKEQAQPPH
LWKSTLPDVV SHPSDASSYR RGRKKRVPYT KVQLKELERE YATNKFITKD KRRRISATTN
LSERQVTIWF QNRRVKEKKV INKLKTTS
