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P56178

- DLX5_HUMAN

UniProt

P56178 - DLX5_HUMAN

Protein

Homeobox protein DLX-5

Gene

DLX5

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 130 (01 Oct 2014)
      Sequence version 2 (11 Jan 2001)
      Previous versions | rss
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    Functioni

    Transcriptional factor involved in bone development. Acts as an immediate early BMP-responsive transcriptional activator essential for osteoblast differentiation. Stimulates ALPL promoter activity in a RUNX2-independent manner during osteoblast differentiation. Stimulates SP7 promoter activity during osteoblast differentiation. Promotes cell proliferation by up-regulating MYC promoter activity. Involved as a positive regulator of both chondrogenesis and chondrocyte hypertrophy in the endochondral skeleton. Binds to the homeodomain-response element of the ALPL and SP7 promoter. Binds to the MYC promoter. Requires the 5'-TAATTA-3' consensus sequence for DNA-binding.1 Publication

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    DNA bindingi137 – 19660HomeoboxPROSITE-ProRule annotationAdd
    BLAST

    GO - Molecular functioni

    1. RNA polymerase II core promoter proximal region sequence-specific DNA binding Source: BHF-UCL
    2. RNA polymerase II core promoter proximal region sequence-specific DNA binding transcription factor activity involved in positive regulation of transcription Source: BHF-UCL
    3. transcription regulatory region DNA binding Source: UniProtKB

    GO - Biological processi

    1. anatomical structure formation involved in morphogenesis Source: Ensembl
    2. axon guidance Source: Ensembl
    3. BMP signaling pathway Source: BHF-UCL
    4. cell proliferation Source: UniProtKB
    5. cellular response to BMP stimulus Source: BHF-UCL
    6. embryonic limb morphogenesis Source: Ensembl
    7. endochondral ossification Source: UniProtKB
    8. epithelial cell differentiation Source: Ensembl
    9. face morphogenesis Source: Ensembl
    10. inner ear morphogenesis Source: Ensembl
    11. nervous system development Source: ProtInc
    12. olfactory pit development Source: Ensembl
    13. osteoblast differentiation Source: UniProtKB
    14. palate development Source: Ensembl
    15. positive regulation of canonical Wnt signaling pathway Source: Ensembl
    16. positive regulation of epithelial cell proliferation Source: Ensembl
    17. positive regulation of osteoblast differentiation Source: Ensembl
    18. positive regulation of transcription, DNA-templated Source: UniProtKB
    19. positive regulation of transcription from RNA polymerase II promoter involved in cellular response to chemical stimulus Source: BHF-UCL
    20. skeletal system development Source: ProtInc

    Keywords - Molecular functioni

    Activator, Developmental protein

    Keywords - Biological processi

    Osteogenesis, Transcription, Transcription regulation

    Keywords - Ligandi

    DNA-binding

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Homeobox protein DLX-5
    Gene namesi
    Name:DLX5
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 7

    Organism-specific databases

    HGNCiHGNC:2918. DLX5.

    Subcellular locationi

    Nucleus PROSITE-ProRule annotation

    GO - Cellular componenti

    1. cytoplasm Source: Ensembl
    2. nuclear chromatin Source: BHF-UCL

    Keywords - Cellular componenti

    Nucleus

    Pathology & Biotechi

    Involvement in diseasei

    Split-hand/foot malformation 1 with sensorineural hearing loss, autosomal recessive (SHFM1D) [MIM:220600]: A disease characterized by the association of split-hand/foot malformation with deafness. Split-hand/foot malformation is a limb malformation involving the central rays of the autopod and presenting with syndactyly, median clefts of the hands and feet, and aplasia and/or hypoplasia of the phalanges, metacarpals, and metatarsals. Some patients have been found to have mental retardation, ectodermal and craniofacial findings, and orofacial clefting.1 Publication
    Note: The disease is caused by mutations affecting the gene represented in this entry.
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti178 – 1781Q → P in SHFM1D. 1 Publication
    VAR_067413

    Keywords - Diseasei

    Deafness, Disease mutation

    Organism-specific databases

    MIMi220600. phenotype.
    Orphaneti71271. Split hand - split foot - deafness.
    PharmGKBiPA27373.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 289289Homeobox protein DLX-5PRO_0000049031Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei34 – 341Phosphoserine; by MAPK14; in vitroBy similarity
    Modified residuei217 – 2171Phosphoserine; by MAPK14; in vitroBy similarity

    Post-translational modificationi

    Phosphorylated. Phosphorylation of Ser-34 and Ser-217 by MAPK14 enhances its transcriptional activity. Phosphorylation by CaMK2 increases its protein stability By similarity.By similarity

    Keywords - PTMi

    Phosphoprotein

    Proteomic databases

    PaxDbiP56178.
    PRIDEiP56178.

    PTM databases

    PhosphoSiteiP56178.

    Expressioni

    Developmental stagei

    First expressed in embryos at 8.5-9 days in facial and branchial arch mesenchyme, otic vesicles and frontonasal ectoderm around olfactory placodes, a day later expression is seen in the developing forebrain in primordia of the ganglionic eminence and ventral diencephalic regions. In day 12.5 embryos, expressed in the brain and bones, and also in all skeletal structures of midgestation embryos after the first cartilage formation. Expression remains unaltered in both brain and skeleton in day 15 embryos and slowly decreases in day 17 embryos.

    Gene expression databases

    ArrayExpressiP56178.
    BgeeiP56178.
    CleanExiHS_DLX5.
    GenevestigatoriP56178.

    Organism-specific databases

    HPAiHPA005670.

    Interactioni

    Subunit structurei

    Interacts with XRCC6 (Ku70).1 Publication

    Protein-protein interaction databases

    BioGridi108093. 6 interactions.
    MINTiMINT-4720915.
    STRINGi9606.ENSP00000222598.

    Structurei

    Secondary structure

    1
    289
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Helixi146 – 15611
    Helixi164 – 17310
    Helixi178 – 19013

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    2DJNNMR-A138-194[»]
    ProteinModelPortaliP56178.
    SMRiP56178. Positions 138-194.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiP56178.

    Family & Domainsi

    Sequence similaritiesi

    Belongs to the distal-less homeobox family.Curated
    Contains 1 homeobox DNA-binding domain.PROSITE-ProRule annotation

    Keywords - Domaini

    Homeobox

    Phylogenomic databases

    eggNOGiNOG263092.
    HOGENOMiHOG000231940.
    HOVERGENiHBG005493.
    InParanoidiP56178.
    KOiK09315.
    OMAiQSPAVWD.
    OrthoDBiEOG70W3F8.
    PhylomeDBiP56178.
    TreeFamiTF350606.

    Family and domain databases

    Gene3Di1.10.10.60. 1 hit.
    InterProiIPR022135. Distal-less_N.
    IPR017970. Homeobox_CS.
    IPR001356. Homeobox_dom.
    IPR020479. Homeobox_metazoa.
    IPR009057. Homeodomain-like.
    IPR000047. HTH_motif.
    [Graphical view]
    PfamiPF12413. DLL_N. 1 hit.
    PF00046. Homeobox. 1 hit.
    [Graphical view]
    PRINTSiPR00024. HOMEOBOX.
    PR00031. HTHREPRESSR.
    SMARTiSM00389. HOX. 1 hit.
    [Graphical view]
    SUPFAMiSSF46689. SSF46689. 1 hit.
    PROSITEiPS00027. HOMEOBOX_1. 1 hit.
    PS50071. HOMEOBOX_2. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    P56178-1 [UniParc]FASTAAdd to Basket

    « Hide

    MTGVFDRRVP SIRSGDFQAP FQTSAAMHHP SQESPTLPES SATDSDYYSP    50
    TGGAPHGYCS PTSASYGKAL NPYQYQYHGV NGSAGSYPAK AYADYSYASS 100
    YHQYGGAYNR VPSATNQPEK EVTEPEVRMV NGKPKKVRKP RTIYSSFQLA 150
    ALQRRFQKTQ YLALPERAEL AASLGLTQTQ VKIWFQNKRS KIKKIMKNGE 200
    MPPEHSPSSS DPMACNSPQS PAVWEPQGSS RSLSHHPHAH PPTSNQSPAS 250
    SYLENSASWY TSAASSINSH LPPPGSLQHP LALASGTLY 289
    Length:289
    Mass (Da):31,540
    Last modified:January 11, 2001 - v2
    Checksum:i5BC9970B12E30554
    GO

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti178 – 1781Q → P in SHFM1D. 1 Publication
    VAR_067413
    Natural varianti234 – 2341S → R.
    Corresponds to variant rs35273378 [ dbSNP | Ensembl ].
    VAR_033874

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AK023493 mRNA. Translation: BAB14587.1.
    AC004774 Genomic DNA. Translation: AAC17833.1.
    BC006226 mRNA. Translation: AAH06226.1.
    CCDSiCCDS5647.1.
    PIRiC53495.
    RefSeqiNP_005212.1. NM_005221.5.
    UniGeneiHs.99348.

    Genome annotation databases

    EnsembliENST00000222598; ENSP00000222598; ENSG00000105880.
    GeneIDi1749.
    KEGGihsa:1749.
    UCSCiuc003uon.3. human.

    Polymorphism databases

    DMDMi12644329.

    Keywords - Coding sequence diversityi

    Polymorphism

    Cross-referencesi

    Web resourcesi

    Atlas of Genetics and Cytogenetics in Oncology and Haematology

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AK023493 mRNA. Translation: BAB14587.1 .
    AC004774 Genomic DNA. Translation: AAC17833.1 .
    BC006226 mRNA. Translation: AAH06226.1 .
    CCDSi CCDS5647.1.
    PIRi C53495.
    RefSeqi NP_005212.1. NM_005221.5.
    UniGenei Hs.99348.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    2DJN NMR - A 138-194 [» ]
    ProteinModelPortali P56178.
    SMRi P56178. Positions 138-194.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 108093. 6 interactions.
    MINTi MINT-4720915.
    STRINGi 9606.ENSP00000222598.

    PTM databases

    PhosphoSitei P56178.

    Polymorphism databases

    DMDMi 12644329.

    Proteomic databases

    PaxDbi P56178.
    PRIDEi P56178.

    Protocols and materials databases

    DNASUi 1749.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000222598 ; ENSP00000222598 ; ENSG00000105880 .
    GeneIDi 1749.
    KEGGi hsa:1749.
    UCSCi uc003uon.3. human.

    Organism-specific databases

    CTDi 1749.
    GeneCardsi GC07M096649.
    HGNCi HGNC:2918. DLX5.
    HPAi HPA005670.
    MIMi 220600. phenotype.
    600028. gene.
    neXtProti NX_P56178.
    Orphaneti 71271. Split hand - split foot - deafness.
    PharmGKBi PA27373.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi NOG263092.
    HOGENOMi HOG000231940.
    HOVERGENi HBG005493.
    InParanoidi P56178.
    KOi K09315.
    OMAi QSPAVWD.
    OrthoDBi EOG70W3F8.
    PhylomeDBi P56178.
    TreeFami TF350606.

    Miscellaneous databases

    EvolutionaryTracei P56178.
    GeneWikii DLX5.
    GenomeRNAii 1749.
    NextBioi 7097.
    PROi P56178.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi P56178.
    Bgeei P56178.
    CleanExi HS_DLX5.
    Genevestigatori P56178.

    Family and domain databases

    Gene3Di 1.10.10.60. 1 hit.
    InterProi IPR022135. Distal-less_N.
    IPR017970. Homeobox_CS.
    IPR001356. Homeobox_dom.
    IPR020479. Homeobox_metazoa.
    IPR009057. Homeodomain-like.
    IPR000047. HTH_motif.
    [Graphical view ]
    Pfami PF12413. DLL_N. 1 hit.
    PF00046. Homeobox. 1 hit.
    [Graphical view ]
    PRINTSi PR00024. HOMEOBOX.
    PR00031. HTHREPRESSR.
    SMARTi SM00389. HOX. 1 hit.
    [Graphical view ]
    SUPFAMi SSF46689. SSF46689. 1 hit.
    PROSITEi PS00027. HOMEOBOX_1. 1 hit.
    PS50071. HOMEOBOX_2. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "Complete sequencing and characterization of 21,243 full-length human cDNAs."
      Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.
      , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
      Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
      Tissue: Placenta.
    2. "The DNA sequence of human chromosome 7."
      Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H., Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K., Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A., Delehaunty K.D., Miner T.L.
      , Nash W.E., Cordes M., Du H., Sun H., Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A., Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P., Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M., Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S., Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R., Strowmatt C., Latreille P., Miller N., Johnson D., Murray J., Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W., Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A., Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E., Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E., Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A., Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A., Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R., McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H., Wilson R.K.
      Nature 424:157-164(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    3. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
      The MGC Project Team
      Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
      Tissue: Lung.
    4. Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 137-202.
      Tissue: Embryo.
    5. "Regulation of osteocalcin gene expression by a novel Ku antigen transcription factor complex."
      Willis D.M., Loewy A.P., Charlton-Kachigian N., Shao J.-S., Ornitz D.M., Towler D.A.
      J. Biol. Chem. 277:37280-37291(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH XRCC6.
      Tissue: Osteoblast.
    6. "DLX5 (distal-less homeobox 5) promotes tumor cell proliferation by transcriptionally regulating MYC."
      Xu J., Testa J.R.
      J. Biol. Chem. 284:20593-20601(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, DNA-BINDING.
    7. "The solution structure of the homeobox domain of human homeobox protein DLX-5."
      RIKEN structural genomics initiative (RSGI)
      Submitted (OCT-2006) to the PDB data bank
      Cited for: STRUCTURE BY NMR OF 138-194.
    8. "Identification of a novel DLX5 mutation in a family with autosomal recessive split hand and foot malformation."
      Shamseldin H.E., Faden M.A., Alashram W., Alkuraya F.S.
      J. Med. Genet. 49:16-20(2012) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANT SHFM1D PRO-178.

    Entry informationi

    Entry nameiDLX5_HUMAN
    AccessioniPrimary (citable) accession number: P56178
    Secondary accession number(s): Q9UPL1
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: November 1, 1997
    Last sequence update: January 11, 2001
    Last modified: October 1, 2014
    This is version 130 of the entry and version 2 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program
    DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

    Miscellaneousi

    Keywords - Technical termi

    3D-structure, Complete proteome, Reference proteome

    Documents

    1. Human chromosome 7
      Human chromosome 7: entries, gene names and cross-references to MIM
    2. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    3. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    4. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    5. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    6. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3