ID   HXD4_HUMAN              Reviewed;         255 AA.
AC   P09016; B2R9R3; Q96AU0;
DT   01-NOV-1988, integrated into UniProtKB/Swiss-Prot.
DT   23-JAN-2002, sequence version 3.
DT   24-JAN-2024, entry version 213.
DE   RecName: Full=Homeobox protein Hox-D4;
DE   AltName: Full=Homeobox protein HHO.C13;
DE   AltName: Full=Homeobox protein Hox-4B;
DE   AltName: Full=Homeobox protein Hox-5.1;
GN   Name=HOXD4; Synonyms=HOX4B;
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], AND VARIANT PRO-123.
RX   PubMed=1975093; DOI=10.1093/nar/18.15.4361;
RA   Cianetti L., di Cristofaro A., Zappavigna V., Bottero L., Boccoli G.,
RA   Testa U., Russo G., Boncinelli E., Peschle C.;
RT   "Molecular mechanisms underlying the expression of the human HOX-5.1
RT   gene.";
RL   Nucleic Acids Res. 18:4361-4368(1990).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RX   PubMed=2879245; DOI=10.1038/324664a0;
RA   Mavilio F., Simeone A., Giampaolo A., Faiella A., Zappavigna V.,
RA   Acampora D., Poiana G., Russo G., Peschle C., Boncinelli E.;
RT   "Differential and stage-related expression in embryonic tissues of a new
RT   human homoeobox gene.";
RL   Nature 324:664-668(1986).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT PRO-123.
RC   TISSUE=Uterus;
RX   PubMed=14702039; DOI=10.1038/ng1285;
RA   Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA   Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA   Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA   Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA   Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA   Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA   Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA   Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA   Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA   Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA   Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA   Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA   Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA   Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA   Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA   Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA   Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA   Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA   Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA   Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA   Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA   Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA   Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA   Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA   Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA   Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA   Isogai T., Sugano S.;
RT   "Complete sequencing and characterization of 21,243 full-length human
RT   cDNAs.";
RL   Nat. Genet. 36:40-45(2004).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Kidney;
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   NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 154-219.
RX   PubMed=2576652; DOI=10.1139/g89-133;
RA   Boncinelli E., Acampora D., Pannese M., D'Esposito M., Somma R.,
RA   Gaudino G., Stornaiuolo A., Cafiero M., Faiella A., Simeone A.;
RT   "Organization of human class I homeobox genes.";
RL   Genome 31:745-756(1989).
RN   [6]
RP   INTERACTION WITH PBX1.
RX   PubMed=7791786; DOI=10.1128/mcb.15.7.3786;
RA   Lu Q., Knoepfler P.S., Scheele J., Wright D.D., Kamps M.P.;
RT   "Both Pbx1 and E2A-Pbx1 bind the DNA motif ATCAATCAA cooperatively with the
RT   products of multiple murine Hox genes, some of which are themselves
RT   oncogenes.";
RL   Mol. Cell. Biol. 15:3786-3795(1995).
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: Forms a DNA-binding heterodimer with transcription factor
CC       PBX1. {ECO:0000269|PubMed:7791786}.
CC   -!- INTERACTION:
CC       P09016; Q9NW38: FANCL; NbExp=3; IntAct=EBI-12822515, EBI-2339898;
CC       P09016; Q9BYU1: PBX4; NbExp=3; IntAct=EBI-12822515, EBI-10302990;
CC   -!- SUBCELLULAR LOCATION: Nucleus.
CC   -!- SIMILARITY: Belongs to the Antp homeobox family. Deformed subfamily.
CC       {ECO:0000305}.
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DR   EMBL; X17360; CAA35237.1; -; Genomic_DNA.
DR   EMBL; X04706; CAA28411.1; -; mRNA.
DR   EMBL; AK313885; BAG36610.1; -; mRNA.
DR   EMBL; BC016763; AAH16763.1; -; mRNA.
DR   EMBL; BC074797; AAH74797.1; -; mRNA.
DR   CCDS; CCDS2269.1; -.
DR   PIR; S10985; WJHU4B.
DR   RefSeq; NP_055436.2; NM_014621.2.
DR   AlphaFoldDB; P09016; -.
DR   SMR; P09016; -.
DR   BioGRID; 109473; 27.
DR   ELM; P09016; -.
DR   IntAct; P09016; 19.
DR   STRING; 9606.ENSP00000302548; -.
DR   iPTMnet; P09016; -.
DR   PhosphoSitePlus; P09016; -.
DR   BioMuta; HOXD4; -.
DR   DMDM; 20141491; -.
DR   MassIVE; P09016; -.
DR   MaxQB; P09016; -.
DR   PaxDb; 9606-ENSP00000302548; -.
DR   PeptideAtlas; P09016; -.
DR   ProteomicsDB; 52185; -.
DR   Pumba; P09016; -.
DR   Antibodypedia; 19523; 254 antibodies from 23 providers.
DR   DNASU; 3233; -.
DR   Ensembl; ENST00000306324.4; ENSP00000302548.3; ENSG00000170166.6.
DR   GeneID; 3233; -.
DR   KEGG; hsa:3233; -.
DR   MANE-Select; ENST00000306324.4; ENSP00000302548.3; NM_014621.3; NP_055436.2.
DR   UCSC; uc002uks.4; human.
DR   AGR; HGNC:5138; -.
DR   CTD; 3233; -.
DR   DisGeNET; 3233; -.
DR   GeneCards; HOXD4; -.
DR   HGNC; HGNC:5138; HOXD4.
DR   HPA; ENSG00000170166; Tissue enhanced (endometrium, epididymis).
DR   MIM; 142981; gene+phenotype.
DR   neXtProt; NX_P09016; -.
DR   OpenTargets; ENSG00000170166; -.
DR   PharmGKB; PA29412; -.
DR   VEuPathDB; HostDB:ENSG00000170166; -.
DR   eggNOG; KOG0489; Eukaryota.
DR   GeneTree; ENSGT00940000157270; -.
DR   HOGENOM; CLU_061398_0_0_1; -.
DR   InParanoid; P09016; -.
DR   OMA; QGVYPRS; -.
DR   OrthoDB; 728401at2759; -.
DR   PhylomeDB; P09016; -.
DR   TreeFam; TF352857; -.
DR   PathwayCommons; P09016; -.
DR   Reactome; R-HSA-5617472; Activation of anterior HOX genes in hindbrain development during early embryogenesis.
DR   SignaLink; P09016; -.
DR   BioGRID-ORCS; 3233; 7 hits in 1172 CRISPR screens.
DR   GeneWiki; HOXD4; -.
DR   GenomeRNAi; 3233; -.
DR   Pharos; P09016; Tbio.
DR   PRO; PR:P09016; -.
DR   Proteomes; UP000005640; Chromosome 2.
DR   RNAct; P09016; Protein.
DR   Bgee; ENSG00000170166; Expressed in body of uterus and 76 other cell types or tissues.
DR   GO; GO:0030054; C:cell junction; IDA:HPA.
DR   GO; GO:0000785; C:chromatin; ISA:NTNU_SB.
DR   GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR   GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; IDA:NTNU_SB.
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:0000977; F:RNA polymerase II transcription regulatory region sequence-specific DNA binding; IMP:NTNU_SB.
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:0048568; P:embryonic organ development; IEP:UniProtKB.
DR   GO; GO:0048704; P:embryonic skeletal system morphogenesis; IBA:GO_Central.
DR   GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:NTNU_SB.
DR   GO; GO:0048863; P:stem cell differentiation; IEA:Ensembl.
DR   CDD; cd00086; homeodomain; 1.
DR   Gene3D; 1.10.10.60; Homeodomain-like; 1.
DR   InterPro; IPR009057; Homeobox-like_sf.
DR   InterPro; IPR017995; Homeobox_antennapedia.
DR   InterPro; IPR001827; Homeobox_Antennapedia_CS.
DR   InterPro; IPR017970; Homeobox_CS.
DR   InterPro; IPR001356; Homeobox_dom.
DR   InterPro; IPR020479; Homeobox_metazoa.
DR   PANTHER; PTHR45771:SF5; HOMEOBOX PROTEIN HOX-D4; 1.
DR   PANTHER; PTHR45771; HOMEOTIC PROTEIN DEFORMED; 1.
DR   Pfam; PF00046; Homeodomain; 1.
DR   PRINTS; PR00025; ANTENNAPEDIA.
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.
DR   Genevisible; P09016; HS.
PE   1: Evidence at protein level;
KW   Developmental protein; DNA-binding; Homeobox; Nucleus; Reference proteome;
KW   Transcription; Transcription regulation.
FT   CHAIN           1..255
FT                   /note="Homeobox protein Hox-D4"
FT                   /id="PRO_0000200210"
FT   DNA_BIND        154..213
FT                   /note="Homeobox"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00108"
FT   REGION          31..127
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          212..255
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MOTIF           133..138
FT                   /note="Antp-type hexapeptide"
FT   COMPBIAS        92..109
FT                   /note="Pro residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        219..240
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   VARIANT         123
FT                   /note="S -> P (in dbSNP:rs34727427)"
FT                   /evidence="ECO:0000269|PubMed:14702039,
FT                   ECO:0000269|PubMed:1975093"
FT                   /id="VAR_067445"
FT   CONFLICT        142
FT                   /note="V -> A (in Ref. 2; CAA28411)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   255 AA;  27885 MW;  39205343CDB0142F CRC64;
     MVMSSYMVNS KYVDPKFPPC EEYLQGGYLG EQGADYYGGG AQGADFQPPG LYPRPDFGEQ
     PFGGSGPGPG SALPARGHGQ EPGGPGGHYA APGEPCPAPP APPPAPLPGA RAYSQSDPKQ
     PPSGTALKQP AVVYPWMKKV HVNSVNPNYT GGEPKRSRTA YTRQQVLELE KEFHFNRYLT
     RRRRIEIAHT LCLSERQIKI WFQNRRMKWK KDHKLPNTKG RSSSSSSSSS CSSSVAPSQH
     LQPMAKDHHT DLTTL
//