ID   HXD8_HUMAN              Reviewed;         290 AA.
AC   P13378; F8WBG7; Q5BL00; Q8IXZ1;
DT   01-JAN-1990, integrated into UniProtKB/Swiss-Prot.
DT   21-FEB-2001, sequence version 2.
DT   07-OCT-2020, entry version 186.
DE   RecName: Full=Homeobox protein Hox-D8;
DE   AltName: Full=Homeobox protein Hox-4E;
DE   AltName: Full=Homeobox protein Hox-5.4;
GN   Name=HOXD8; Synonyms=HOX4E;
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=11857506; DOI=10.1002/tera.10009;
RA   Kosaki K., Kosaki R., Suzuki T., Yoshihashi H., Takahashi T., Sasaki K.,
RA   Tomita M., McGinnis W., Matsuo N.;
RT   "Complete mutation analysis panel of the 39 human HOX genes.";
RL   Teratology 65:50-62(2002).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
RC   TISSUE=Neuroblastoma;
RA   Li W.B., Gruber C., Jessee J., Polayes D.;
RT   "Full-length cDNA libraries and normalization.";
RL   Submitted (APR-2003) to the EMBL/GenBank/DDBJ databases.
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=15815621; DOI=10.1038/nature03466;
RA   Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA   Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA   Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA   Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA   Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA   Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA   Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA   Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA   Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA   McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA   Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA   Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA   Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA   Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA   Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA   Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA   Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA   Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA   Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA   Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA   Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA   Wilson R.K.;
RT   "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT   4.";
RL   Nature 434:724-731(2005).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC   TISSUE=Kidney, and PNS;
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 193-287.
RX   PubMed=2568311; DOI=10.1101/gad.3.5.641;
RA   Oliver G., Sidell N., Fiske N., Heinzmann C., Mohandas T., Sparkes R.S.,
RA   De Robertis E.M.;
RT   "Complementary homeo protein gradients in developing limb buds.";
RL   Genes Dev. 3:641-650(1989).
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   -!- INTERACTION:
CC       P13378; Q9UQB8-6: BAIAP2; NbExp=3; IntAct=EBI-7098661, EBI-9092016;
CC       P13378; Q5SW96: LDLRAP1; NbExp=3; IntAct=EBI-7098661, EBI-747813;
CC       P13378; O43639: NCK2; NbExp=3; IntAct=EBI-7098661, EBI-713635;
CC   -!- SUBCELLULAR LOCATION: Nucleus.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=3;
CC       Name=1;
CC         IsoId=P13378-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=P13378-2; Sequence=VSP_042856;
CC       Name=3;
CC         IsoId=P13378-3; Sequence=VSP_045862, VSP_045863;
CC   -!- SIMILARITY: Belongs to the Antp homeobox family. {ECO:0000305}.
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DR   EMBL; AY014304; AAG42152.1; -; Genomic_DNA.
DR   EMBL; AY014303; AAG42152.1; JOINED; Genomic_DNA.
DR   EMBL; AL520835; -; NOT_ANNOTATED_CDS; mRNA.
DR   EMBL; AC009336; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; BC038709; AAH38709.1; -; mRNA.
DR   EMBL; BC090853; AAH90853.1; -; mRNA.
DR   EMBL; X15507; CAA33529.1; -; Genomic_DNA.
DR   CCDS; CCDS2268.1; -. [P13378-1]
DR   CCDS; CCDS56148.1; -. [P13378-2]
DR   PIR; B32830; B32830.
DR   RefSeq; NP_001186675.1; NM_001199746.1. [P13378-2]
DR   RefSeq; NP_062458.1; NM_019558.3. [P13378-1]
DR   SMR; P13378; -.
DR   BioGRID; 109474; 9.
DR   IntAct; P13378; 8.
DR   MINT; P13378; -.
DR   STRING; 9606.ENSP00000315949; -.
DR   iPTMnet; P13378; -.
DR   PhosphoSitePlus; P13378; -.
DR   BioMuta; HOXD8; -.
DR   DMDM; 13124737; -.
DR   jPOST; P13378; -.
DR   MassIVE; P13378; -.
DR   MaxQB; P13378; -.
DR   PaxDb; P13378; -.
DR   PeptideAtlas; P13378; -.
DR   PRIDE; P13378; -.
DR   ProteomicsDB; 30803; -.
DR   ProteomicsDB; 52907; -. [P13378-1]
DR   ProteomicsDB; 52908; -. [P13378-2]
DR   Antibodypedia; 33911; 267 antibodies.
DR   Ensembl; ENST00000313173; ENSP00000315949; ENSG00000175879. [P13378-1]
DR   Ensembl; ENST00000450510; ENSP00000409026; ENSG00000175879. [P13378-2]
DR   GeneID; 3234; -.
DR   KEGG; hsa:3234; -.
DR   UCSC; uc002uko.4; human. [P13378-1]
DR   CTD; 3234; -.
DR   DisGeNET; 3234; -.
DR   EuPathDB; HostDB:ENSG00000175879.8; -.
DR   GeneCards; HOXD8; -.
DR   HGNC; HGNC:5139; HOXD8.
DR   HPA; ENSG00000175879; Tissue enhanced (ductus deferens, epididymis).
DR   MIM; 142985; gene.
DR   neXtProt; NX_P13378; -.
DR   OpenTargets; ENSG00000175879; -.
DR   PharmGKB; PA29413; -.
DR   eggNOG; KOG0489; Eukaryota.
DR   GeneTree; ENSGT00940000161653; -.
DR   InParanoid; P13378; -.
DR   KO; K09308; -.
DR   OMA; QEYFHPG; -.
DR   OrthoDB; 976319at2759; -.
DR   PhylomeDB; P13378; -.
DR   TreeFam; TF316310; -.
DR   PathwayCommons; P13378; -.
DR   BioGRID-ORCS; 3234; 3 hits in 894 CRISPR screens.
DR   GeneWiki; HOXD8; -.
DR   GenomeRNAi; 3234; -.
DR   Pharos; P13378; Tbio.
DR   PRO; PR:P13378; -.
DR   Proteomes; UP000005640; Chromosome 2.
DR   RNAct; P13378; protein.
DR   Bgee; ENSG00000175879; Expressed in metanephros and 143 other tissues.
DR   ExpressionAtlas; P13378; baseline and differential.
DR   Genevisible; P13378; HS.
DR   GO; GO:0000790; C:nuclear chromatin; ISA:NTNU_SB.
DR   GO; GO:0005634; C:nucleus; NAS:UniProtKB.
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:0000977; F:RNA polymerase II transcription regulatory region sequence-specific DNA binding; IDA:NTNU_SB.
DR   GO; GO:1990837; F:sequence-specific double-stranded DNA binding; IDA:ARUK-UCL.
DR   GO; GO:0008595; P:anterior/posterior axis specification, embryo; NAS:UniProtKB.
DR   GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IEA:Ensembl.
DR   GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:NTNU_SB.
DR   GO; GO:0048705; P:skeletal system morphogenesis; 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   Alternative splicing; Developmental protein; DNA-binding; Homeobox;
KW   Nucleus; Reference proteome; Transcription; Transcription regulation.
FT   CHAIN           1..290
FT                   /note="Homeobox protein Hox-D8"
FT                   /id="PRO_0000200216"
FT   DNA_BIND        197..256
FT                   /note="Homeobox"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00108"
FT   COMPBIAS        15..23
FT                   /note="Poly-Ala"
FT   COMPBIAS        45..50
FT                   /note="Poly-Ala"
FT   COMPBIAS        109..123
FT                   /note="Poly-Pro"
FT   VAR_SEQ         1..184
FT                   /note="Missing (in isoform 3)"
FT                   /evidence="ECO:0000303|Ref.2"
FT                   /id="VSP_045862"
FT   VAR_SEQ         193
FT                   /note="Missing (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:15489334"
FT                   /id="VSP_042856"
FT   VAR_SEQ         252..290
FT                   /note="Missing (in isoform 3)"
FT                   /evidence="ECO:0000303|Ref.2"
FT                   /id="VSP_045863"
FT   CONFLICT        39
FT                   /note="E -> G (in Ref. 4; AAH90853)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        287
FT                   /note="G -> A (in Ref. 5; CAA33529)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   290 AA;  31911 MW;  75FF95A73E2AA85F CRC64;
     MSSYFVNPLY SKYKAAAAAA AAAGEAINPT YYDCHFAPEV GGRHAAAAAA LQLYGNSAAG
     FPHAPPQAHA HPHPSPPPSG TGCGGREGRG QEYFHPGGGS PAAAYQAAPP PPPHPPPPPP
     PPPCGGIACH GEPAKFYGYD NLQRQPIFTT QQEAELVQYP DCKSSSGNIG EDPDHLNQSS
     SPSQMFPWMR PQAAPGRRRG RQTYSRFQTL ELEKEFLFNP YLTRKRRIEV SHALALTERQ
     VKIWFQNRRM KWKKENNKDK FPVSRQEVKD GETKKEAQEL EEDRAEGLTN
//