ID   DLX5_HUMAN              Reviewed;         289 AA.
AC   P56178; Q9UPL1;
DT   01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT   11-JAN-2001, sequence version 2.
DT   25-JAN-2012, entry version 107.
DE   RecName: Full=Homeobox protein DLX-5;
GN   Name=DLX5;
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC   Catarrhini; Hominidae; Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Placenta;
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.,
RA   Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA   Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA   Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA   Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA   Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA   Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA   Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA   Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA   Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA   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.,
RA   Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA   Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA   Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA   Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA   Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA   Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA   Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA   Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA   Nakai K., Yada T., Nakamura Y., Ohara O., 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   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   MEDLINE=22737999; 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.,
RA   Wylie K., Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E.,
RA   Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Cordes M., Du H.,
RA   Sun H., Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A.,
RA   Vanbrunt A., Nguyen C., Du F., Lamar B., Courtney L., Kalicki J.,
RA   Ozersky P., Bielicki L., Scott K., Holmes A., Harkins R., Harris A.,
RA   Strong C.M., Hou S., Tomlinson C., Dauphin-Kohlberg S.,
RA   Kozlowicz-Reilly A., Leonard S., Rohlfing T., Rock S.M.,
RA   Tin-Wollam A.-M., Abbott A., Minx P., Maupin R., Strowmatt C.,
RA   Latreille P., Miller N., Johnson D., Murray J., Woessner J.P.,
RA   Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W., Spieth J.,
RA   Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E., Cook L.L.,
RA   Hickenbotham M.T., Eldred J., Williams D., Bedell J.A., Mardis E.R.,
RA   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.,
RA   Simms E., Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S.,
RA   Baertsch R.A., Brent M.R., Keibler E., Flicek P., Bork P., Suyama M.,
RA   Bailey J.A., Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R.,
RA   Eddy S.R., McPherson J.D., Olson M.V., Eichler E.E., Green E.D.,
RA   Waterston R.H., Wilson R.K.;
RT   "The DNA sequence of human chromosome 7.";
RL   Nature 424:157-164(2003).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Lung;
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
RT   project: the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 137-202.
RC   TISSUE=Embryo;
RX   MEDLINE=94181570; PubMed=7907794; DOI=10.1073/pnas.91.6.2250;
RA   Simeone A., Acampora D., Pannese M., D'Esposito M., Stornaiuolo A.,
RA   Gulisano M., Mallamaci A., Kastury K., Druck T., Huebner K.,
RA   Boncinelli E.;
RT   "Cloning and characterization of two members of the vertebrate Dlx
RT   gene family.";
RL   Proc. Natl. Acad. Sci. U.S.A. 91:2250-2254(1994).
RN   [5]
RP   INTERACTION WITH XRCC6.
RC   TISSUE=Osteoblast;
RX   MEDLINE=22241900; PubMed=12145306; DOI=10.1074/jbc.M206482200;
RA   Willis D.M., Loewy A.P., Charlton-Kachigian N., Shao J.-S.,
RA   Ornitz D.M., Towler D.A.;
RT   "Regulation of osteocalcin gene expression by a novel Ku antigen
RT   transcription factor complex.";
RL   J. Biol. Chem. 277:37280-37291(2002).
RN   [6]
RP   FUNCTION, AND DNA-BINDING.
RX   PubMed=19497851; DOI=10.1074/jbc.M109.021477;
RA   Xu J., Testa J.R.;
RT   "DLX5 (distal-less homeobox 5) promotes tumor cell proliferation by
RT   transcriptionally regulating MYC.";
RL   J. Biol. Chem. 284:20593-20601(2009).
RN   [7]
RP   STRUCTURE BY NMR OF 138-194.
RG   RIKEN structural genomics initiative (RSGI);
RT   "The solution structure of the homeobox domain of human homeobox
RT   protein DLX-5.";
RL   Submitted (OCT-2006) to the PDB data bank.
CC   -!- FUNCTION: Transcriptional factor involved in bone development.
CC       Acts as an immediate early BMP-responsive transcriptional
CC       activator essential for osteoblast differentiation. Stimulates
CC       ALPL promoter activity in a RUNX2-independent manner during
CC       osteoblast differentiation. Stimulates SP7 promoter activity
CC       during osteoblast differentiation. Promotes cell proliferation by
CC       up-regulating MYC promoter activity. Involved as a positive
CC       regulator of both chondrogenesis and chondrocyte hypertrophy in
CC       the endochondral skeleton. Binds to the homeodomain-response
CC       element of the ALPL and SP7 promoter. Binds to the MYC promoter.
CC       Requires the 5'-TAATTA-3' consensus sequence for DNA-binding.
CC   -!- SUBUNIT: Interacts with XRCC6 (Ku70).
CC   -!- SUBCELLULAR LOCATION: Nucleus (By similarity).
CC   -!- DEVELOPMENTAL STAGE: First expressed in embryos at 8.5-9 days in
CC       facial and branchial arch mesenchyme, otic vesicles and
CC       frontonasal ectoderm around olfactory placodes, a day later
CC       expression is seen in the developing forebrain in primordia of the
CC       ganglionic eminence and ventral diencephalic regions. In day 12.5
CC       embryos, expressed in the brain and bones, and also in all
CC       skeletal structures of midgestation embryos after the first
CC       cartilage formation. Expression remains unaltered in both brain
CC       and skeleton in day 15 embryos and slowly decreases in day 17
CC       embryos.
CC   -!- PTM: Phosphorylated. Phosphorylation of Ser-34 and Ser-217 by
CC       MAPK14 enhances its transcriptional activity. Phosphorylation by
CC       CaMK2 increases its protein stability (By similarity).
CC   -!- SIMILARITY: Belongs to the distal-less homeobox family.
CC   -!- SIMILARITY: Contains 1 homeobox DNA-binding domain.
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DR   EMBL; AK023493; BAB14587.1; -; mRNA.
DR   EMBL; AC004774; AAC17833.1; -; Genomic_DNA.
DR   EMBL; BC006226; AAH06226.1; -; mRNA.
DR   IPI; IPI00008192; -.
DR   PIR; C53495; C53495.
DR   RefSeq; NP_005212.1; NM_005221.5.
DR   UniGene; Hs.99348; -.
DR   PDB; 2DJN; NMR; -; A=138-194.
DR   PDBsum; 2DJN; -.
DR   ProteinModelPortal; P56178; -.
DR   SMR; P56178; 138-194.
DR   STRING; P56178; -.
DR   PhosphoSite; P56178; -.
DR   DMDM; 12644329; -.
DR   PRIDE; P56178; -.
DR   Ensembl; ENST00000222598; ENSP00000222598; ENSG00000105880.
DR   GeneID; 1749; -.
DR   KEGG; hsa:1749; -.
DR   UCSC; uc003uon.1; human.
DR   CTD; 1749; -.
DR   GeneCards; GC07M096649; -.
DR   H-InvDB; HIX0006872; -.
DR   HGNC; HGNC:2918; DLX5.
DR   HPA; HPA005670; -.
DR   MIM; 600028; gene.
DR   neXtProt; NX_P56178; -.
DR   PharmGKB; PA27373; -.
DR   eggNOG; prNOG08267; -.
DR   HOGENOM; HBG506878; -.
DR   HOVERGEN; HBG005493; -.
DR   InParanoid; P56178; -.
DR   OMA; GELPPEH; -.
DR   OrthoDB; EOG49PB05; -.
DR   PhylomeDB; P56178; -.
DR   NextBio; 7097; -.
DR   ArrayExpress; P56178; -.
DR   Bgee; P56178; -.
DR   CleanEx; HS_DLX5; -.
DR   Genevestigator; P56178; -.
DR   GermOnline; ENSG00000105880; Homo sapiens.
DR   GO; GO:0005634; C:nucleus; IDA:HPA.
DR   GO; GO:0003700; F:sequence-specific DNA binding transcription factor activity; IEA:InterPro.
DR   GO; GO:0000976; F:transcription regulatory region sequence-specific DNA binding; IEA:InterPro.
DR   GO; GO:0008283; P:cell proliferation; IDA:UniProtKB.
DR   GO; GO:0001958; P:endochondral ossification; ISS:UniProtKB.
DR   GO; GO:0001649; P:osteoblast differentiation; ISS:UniProtKB.
DR   GO; GO:0045893; P:positive regulation of transcription, DNA-dependent; IDA:UniProtKB.
DR   GO; GO:0006351; P:transcription, DNA-dependent; IEA:UniProtKB-KW.
DR   InterPro; IPR022135; DLL_N.
DR   InterPro; IPR001356; Homeobox.
DR   InterPro; IPR017970; Homeobox_CS.
DR   InterPro; IPR020479; Homeobox_eu.
DR   InterPro; IPR009057; Homeodomain-like.
DR   InterPro; IPR012287; Homeodomain-rel.
DR   InterPro; IPR000047; HTH_motif.
DR   Gene3D; G3DSA:1.10.10.60; Homeodomain-rel; 1.
DR   KO; K09315; -.
DR   Pfam; PF12413; DLL_N; 1.
DR   Pfam; PF00046; Homeobox; 1.
DR   PRINTS; PR00024; HOMEOBOX.
DR   PRINTS; PR00031; HTHREPRESSR.
DR   SMART; SM00389; HOX; 1.
DR   SUPFAM; SSF46689; Homeodomain_like; 1.
DR   PROSITE; PS00027; HOMEOBOX_1; 1.
DR   PROSITE; PS50071; HOMEOBOX_2; 1.
PE   1: Evidence at protein level;
KW   3D-structure; Activator; Complete proteome; Developmental protein;
KW   DNA-binding; Homeobox; Nucleus; Osteogenesis; Phosphoprotein;
KW   Polymorphism; Reference proteome; Transcription;
KW   Transcription regulation.
FT   CHAIN         1    289       Homeobox protein DLX-5.
FT                                /FTId=PRO_0000049031.
FT   DNA_BIND    137    196       Homeobox.
FT   MOD_RES      34     34       Phosphoserine; by MAPK14; in vitro (By
FT                                similarity).
FT   MOD_RES     217    217       Phosphoserine; by MAPK14; in vitro (By
FT                                similarity).
FT   VARIANT     234    234       S -> R (in dbSNP:rs35273378).
FT                                /FTId=VAR_033874.
FT   HELIX       146    156
FT   HELIX       164    173
FT   HELIX       178    190
SQ   SEQUENCE   289 AA;  31540 MW;  5BC9970B12E30554 CRC64;
     MTGVFDRRVP SIRSGDFQAP FQTSAAMHHP SQESPTLPES SATDSDYYSP TGGAPHGYCS
     PTSASYGKAL NPYQYQYHGV NGSAGSYPAK AYADYSYASS YHQYGGAYNR VPSATNQPEK
     EVTEPEVRMV NGKPKKVRKP RTIYSSFQLA ALQRRFQKTQ YLALPERAEL AASLGLTQTQ
     VKIWFQNKRS KIKKIMKNGE MPPEHSPSSS DPMACNSPQS PAVWEPQGSS RSLSHHPHAH
     PPTSNQSPAS SYLENSASWY TSAASSINSH LPPPGSLQHP LALASGTLY
//