HXA9_HUMAN
ID HXA9_HUMAN Reviewed; 272 AA.
AC P31269; O43369; O43429; Q99820;
DT 01-JUL-1993, integrated into UniProtKB/Swiss-Prot.
DT 15-JUL-1999, sequence version 4.
DT 03-AUG-2022, entry version 209.
DE RecName: Full=Homeobox protein Hox-A9;
DE AltName: Full=Homeobox protein Hox-1G;
GN Name=HOXA9; Synonyms=HOX1G;
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=Bone marrow;
RA Rozenfeld S., Sauvageau G., Largman C.;
RL Submitted (DEC-1996) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=9880515; DOI=10.1074/jbc.274.3.1415;
RA Patel C.V., Sharangpani R., Bandyopadhyay S., DiCorleto P.E.;
RT "Endothelial cells express a novel, tumor necrosis factor-alpha-regulated
RT variant of HOXA9.";
RL J. Biol. Chem. 274:1415-1422(1999).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor vector.";
RL Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases.
RN [4]
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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Colon;
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 NUCLEOTIDE SEQUENCE [MRNA] OF 195-272, AND CHROMOSOMAL TRANSLOCATION WITH
RP NUP98.
RX PubMed=8563754; DOI=10.1038/ng0296-159;
RA Borrow J., Shearman A.M., Stanton V.P., Becher R., Collins T.,
RA Williams A.J., Dube I., Katz F., Kwong Y.L., Morris C., Ohyashiki K.,
RA Toyama K., Rowley J., Housman D.E.;
RT "The t(7;11)(p15;p15) translocation in acute myeloid leukaemia fuses the
RT genes for nucleoporin NUP98 and class I homeoprotein HOXA9.";
RL Nat. Genet. 12:159-167(1996).
RN [7]
RP NUCLEOTIDE SEQUENCE OF 206-271.
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 [8]
RP CHROMOSOMAL TRANSLOCATION WITH MSI2.
RX PubMed=12649177;
RA Barbouti A., Hoeglund M., Johansson B., Lassen C., Nilsson P.-G.,
RA Hagemeijer A., Mitelman F., Fioretos T.;
RT "A novel gene, MSI2, encoding a putative RNA-binding protein is recurrently
RT rearranged at disease progression of chronic myeloid leukemia and forms a
RT fusion gene with HOXA9 as a result of the cryptic t(7;17)(p15;q23).";
RL Cancer Res. 63:1202-1206(2003).
RN [9]
RP FUNCTION, INTERACTION WITH PRMT5, METHYLATION AT ARG-140, MUTAGENESIS OF
RP ARG-140, AND IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=22269951; DOI=10.1128/mcb.05977-11;
RA Bandyopadhyay S., Harris D.P., Adams G.N., Lause G.E., McHugh A.,
RA Tillmaand E.G., Money A., Willard B., Fox P.L., Dicorleto P.E.;
RT "HOXA9 methylation by PRMT5 is essential for endothelial cell expression of
RT leukocyte adhesion molecules.";
RL Mol. Cell. Biol. 32:1202-1213(2012).
RN [10]
RP DISEASE, AND CHROMOSOMAL TRANSLOCATION WITH NUP98.
RX PubMed=8563753; DOI=10.1038/ng0296-154;
RA Nakamura T., Largaespada D.A., Lee M.P., Johnson L.A., Ohyashiki K.,
RA Toyama K., Chen S.J., Willman C.L., Chen I.M., Feinberg A.P., Jenkins N.A.,
RA Copeland N.G., Shaughnessy J.D. Jr.;
RT "Fusion of the nucleoporin gene NUP98 to HOXA9 by the chromosome
RT translocation t(7;11)(p15;p15) in human myeloid leukaemia.";
RL Nat. Genet. 12:154-158(1996).
RN [11]
RP CHARACTERIZATION OF CHROMOSOMAL TRANSLOCATION WITH NUP98.
RX PubMed=34163069; DOI=10.1038/s41586-021-03662-5;
RA Ahn J.H., Davis E.S., Daugird T.A., Zhao S., Quiroga I.Y., Uryu H., Li J.,
RA Storey A.J., Tsai Y.H., Keeley D.P., Mackintosh S.G., Edmondson R.D.,
RA Byrum S.D., Cai L., Tackett A.J., Zheng D., Legant W.R., Phanstiel D.H.,
RA Wang G.G.;
RT "Phase separation drives aberrant chromatin looping and cancer
RT development.";
RL Nature 595:591-595(2021).
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. Required for
CC induction of E-selectin and VCAM-1, on the endothelial cells surface at
CC sites of inflammation. {ECO:0000269|PubMed:22269951}.
CC -!- SUBUNIT: Transiently interacts with PRMT5 in TNF-alpha stimulated
CC endothelial cells. {ECO:0000269|PubMed:22269951}.
CC -!- INTERACTION:
CC P31269; Q9BYQ3: KRTAP9-3; NbExp=3; IntAct=EBI-742314, EBI-1043191;
CC P31269; O14744: PRMT5; NbExp=4; IntAct=EBI-742314, EBI-351098;
CC P31269; Q15654: TRIP6; NbExp=4; IntAct=EBI-742314, EBI-742327;
CC -!- SUBCELLULAR LOCATION: Nucleus.
CC -!- PTM: Methylated on Arg-140 by PRMT5; methylation is critical for E-
CC selectin induction. {ECO:0000269|PubMed:22269951}.
CC -!- DISEASE: Note=A chromosomal aberration involving HOXA9 is found in a
CC form of acute myeloid leukemia. Translocation t(7;11)(p15;p15) with
CC NUP98 (PubMed:8563753). The chimera includes NUP98 intrinsic disordered
CC regions which contribute to aberrant liquid-liquid phase separation
CC puncta of the chimera in the nucleus. This phase-separation enhances
CC the chimera genomic targeting and induces organization of aberrant
CC three-dimensional chromatin structures leading to tumourous
CC transformation (PubMed:34163069). {ECO:0000269|PubMed:34163069,
CC ECO:0000269|PubMed:8563753}.
CC -!- DISEASE: Note=A chromosomal aberration involving HOXA9 may contribute
CC to disease progression in chronic myeloid leukemia. Translocation
CC t(7;17)(p15;q23) with MSI2.
CC -!- SIMILARITY: Belongs to the Abd-B homeobox family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAC50364.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/HOXA9ID61.html";
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DR EMBL; U82759; AAB40867.1; -; mRNA.
DR EMBL; AF010258; AAD08713.1; -; Genomic_DNA.
DR EMBL; BT006990; AAP35636.1; -; mRNA.
DR EMBL; AC004080; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC006537; AAH06537.1; -; mRNA.
DR EMBL; BC010023; AAH10023.1; -; mRNA.
DR EMBL; U41813; AAC50364.1; ALT_INIT; mRNA.
DR CCDS; CCDS5409.1; -.
DR PIR; S14929; S14929.
DR RefSeq; NP_689952.1; NM_152739.3.
DR AlphaFoldDB; P31269; -.
DR SMR; P31269; -.
DR BioGRID; 109445; 27.
DR CORUM; P31269; -.
DR IntAct; P31269; 8.
DR MINT; P31269; -.
DR STRING; 9606.ENSP00000343619; -.
DR iPTMnet; P31269; -.
DR PhosphoSitePlus; P31269; -.
DR BioMuta; HOXA9; -.
DR DMDM; 6166219; -.
DR EPD; P31269; -.
DR jPOST; P31269; -.
DR MassIVE; P31269; -.
DR MaxQB; P31269; -.
DR PaxDb; P31269; -.
DR PeptideAtlas; P31269; -.
DR PRIDE; P31269; -.
DR ProteomicsDB; 54770; -.
DR Antibodypedia; 12395; 352 antibodies from 40 providers.
DR DNASU; 3205; -.
DR Ensembl; ENST00000343483.7; ENSP00000343619.6; ENSG00000078399.19.
DR GeneID; 3205; -.
DR KEGG; hsa:3205; -.
DR MANE-Select; ENST00000343483.7; ENSP00000343619.6; NM_152739.4; NP_689952.1.
DR UCSC; uc003syt.4; human.
DR CTD; 3205; -.
DR DisGeNET; 3205; -.
DR GeneCards; HOXA9; -.
DR HGNC; HGNC:5109; HOXA9.
DR HPA; ENSG00000078399; Tissue enhanced (kidney).
DR MIM; 142956; gene.
DR neXtProt; NX_P31269; -.
DR OpenTargets; ENSG00000078399; -.
DR PharmGKB; PA29386; -.
DR VEuPathDB; HostDB:ENSG00000078399; -.
DR eggNOG; KOG0487; Eukaryota.
DR GeneTree; ENSGT00940000161864; -.
DR HOGENOM; CLU_071854_0_0_1; -.
DR InParanoid; P31269; -.
DR OMA; HHQAPMA; -.
DR OrthoDB; 976319at2759; -.
DR PhylomeDB; P31269; -.
DR TreeFam; TF317819; -.
DR PathwayCommons; P31269; -.
DR SignaLink; P31269; -.
DR SIGNOR; P31269; -.
DR BioGRID-ORCS; 3205; 39 hits in 1098 CRISPR screens.
DR GeneWiki; HOXA9; -.
DR GenomeRNAi; 3205; -.
DR Pharos; P31269; Tbio.
DR PRO; PR:P31269; -.
DR Proteomes; UP000005640; Chromosome 7.
DR RNAct; P31269; protein.
DR Bgee; ENSG00000078399; Expressed in renal glomerulus and 146 other tissues.
DR ExpressionAtlas; P31269; baseline and differential.
DR Genevisible; P31269; HS.
DR GO; GO:0000785; C:chromatin; ISA:NTNU_SB.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:LIFEdb.
DR GO; GO:0005667; C:transcription regulator complex; IEA:Ensembl.
DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; IEA:Ensembl.
DR GO; GO:0003700; F:DNA-binding transcription factor activity; IBA:GO_Central.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; ISA:NTNU_SB.
DR GO; GO:0019899; F:enzyme binding; IPI:UniProtKB.
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; IBA:GO_Central.
DR GO; GO:0060216; P:definitive hemopoiesis; IEA:Ensembl.
DR GO; GO:0035115; P:embryonic forelimb morphogenesis; IEA:Ensembl.
DR GO; GO:0048704; P:embryonic skeletal system morphogenesis; IBA:GO_Central.
DR GO; GO:0042118; P:endothelial cell activation; IMP:UniProtKB.
DR GO; GO:0008584; P:male gonad development; IEA:Ensembl.
DR GO; GO:0030879; P:mammary gland development; IEA:Ensembl.
DR GO; GO:0045638; P:negative regulation of myeloid cell differentiation; ISS:UniProtKB.
DR GO; GO:0030850; P:prostate gland development; IEA:Ensembl.
DR GO; GO:0009954; P:proximal/distal pattern formation; IBA:GO_Central.
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:0007338; P:single fertilization; IEA:Ensembl.
DR GO; GO:0007283; P:spermatogenesis; IEA:Ensembl.
DR GO; GO:0006351; P:transcription, DNA-templated; IEA:InterPro.
DR GO; GO:0060065; P:uterus 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; IPR020479; Homeobox_metazoa.
DR InterPro; IPR006711; Hox9_activation_N.
DR InterPro; IPR017112; HXA9/HXB9/HXC9.
DR Pfam; PF00046; Homeodomain; 1.
DR Pfam; PF04617; Hox9_act; 1.
DR PIRSF; PIRSF037109; Homeobox_Hox9; 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 1: Evidence at protein level;
KW Chromosomal rearrangement; Developmental protein; DNA-binding; Homeobox;
KW Methylation; Nucleus; Proto-oncogene; Reference proteome; Transcription;
KW Transcription regulation.
FT CHAIN 1..272
FT /note="Homeobox protein Hox-A9"
FT /id="PRO_0000200081"
FT DNA_BIND 206..265
FT /note="Homeobox"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00108"
FT REGION 155..198
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT SITE 163..164
FT /note="Breakpoint for translocation to form MSI2/HOXA9
FT fusion protein"
FT SITE 163..164
FT /note="Breakpoint for translocation to form the NUP98-HOXA9
FT fusion protein"
FT /evidence="ECO:0000269|PubMed:8563753"
FT MOD_RES 140
FT /note="Symmetric dimethylarginine"
FT /evidence="ECO:0000269|PubMed:22269951"
FT MUTAGEN 140
FT /note="R->A: Results in loss of methylation."
FT /evidence="ECO:0000269|PubMed:22269951"
FT CONFLICT 64
FT /note="G -> V (in Ref. 1; AAB40867)"
FT /evidence="ECO:0000305"
FT CONFLICT 67
FT /note="W -> R (in Ref. 2; AAD08713)"
FT /evidence="ECO:0000305"
FT CONFLICT 80
FT /note="Missing (in Ref. 1; AAB40867)"
FT /evidence="ECO:0000305"
FT CONFLICT 243
FT /note="L -> F (in Ref. 1; AAB40867)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 272 AA; 30172 MW; 823A1A22BB07A881 CRC64;
MATTGALGNY YVDSFLLGAD AADELSVGRY APGTLGQPPR QAATLAEHPD FSPCSFQSKA
TVFGASWNPV HAAGANAVPA AVYHHHHHHP YVHPQAPVAA AAPDGRYMRS WLEPTPGALS
FAGLPSSRPY GIKPEPLSAR RGDCPTLDTH TLSLTDYACG SPPVDREKQP SEGAFSENNA
ENESGGDKPP IDPNNPAANW LHARSTRKKR CPYTKHQTLE LEKEFLFNMY LTRDRRYEVA
RLLNLTERQV KIWFQNRRMK MKKINKDRAK DE
