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P56178

- DLX5_HUMAN

UniProt

P56178 - DLX5_HUMAN

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Protein

Homeobox protein DLX-5

Gene

DLX5

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli

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
Complete GO annotation...

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
Complete GO annotation...

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.
2440. Split hand-split foot malformation.
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

BgeeiP56178.
CleanExiHS_DLX5.
ExpressionAtlasiP56178. baseline and differential.
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 – 15611Combined sources
Helixi164 – 17310Combined sources
Helixi178 – 19013Combined sources

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.
KOiK18489.
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]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. Align

Isoform 1 (identifier: P56178-1) [UniParc]FASTAAdd to Basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MTGVFDRRVP SIRSGDFQAP FQTSAAMHHP SQESPTLPES SATDSDYYSP
60 70 80 90 100
TGGAPHGYCS PTSASYGKAL NPYQYQYHGV NGSAGSYPAK AYADYSYASS
110 120 130 140 150
YHQYGGAYNR VPSATNQPEK EVTEPEVRMV NGKPKKVRKP RTIYSSFQLA
160 170 180 190 200
ALQRRFQKTQ YLALPERAEL AASLGLTQTQ VKIWFQNKRS KIKKIMKNGE
210 220 230 240 250
MPPEHSPSSS DPMACNSPQS PAVWEPQGSS RSLSHHPHAH PPTSNQSPAS
260 270 280
SYLENSASWY TSAASSINSH LPPPGSLQHP LALASGTLY
Length:289
Mass (Da):31,540
Last modified:January 11, 2001 - v2
Checksum:i5BC9970B12E30554
GO
Isoform 2 (identifier: P56178-2) [UniParc]FASTAAdd to Basket

The sequence of this isoform differs from the canonical sequence as follows:
     182-289: KIWFQNKRSK...PLALASGTLY → NTALPCTRPA

Note: No experimental confirmation available

Show »
Length:191
Mass (Da):20,900
Checksum:i66FAC694851D4A0A
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

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei182 – 289108KIWFQ…SGTLY → NTALPCTRPA in isoform 2. 1 PublicationVSP_056884Add
BLAST

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
AK023493 mRNA. Translation: BAB14587.1.
AK297614 mRNA. Translation: BAH12629.1.
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

Alternative splicing, 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 .
AK297614 mRNA. Translation: BAH12629.1 .
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.
2440. Split hand-split foot malformation.
PharmGKBi PA27373.
GenAtlasi Search...

Phylogenomic databases

eggNOGi NOG263092.
HOGENOMi HOG000231940.
HOVERGENi HBG005493.
InParanoidi P56178.
KOi K18489.
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

Bgeei P56178.
CleanExi HS_DLX5.
ExpressionAtlasi P56178. baseline and differential.
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

« Hide 'large scale' publications
  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] (ISOFORMS 1 AND 2).
    Tissue: Brain and 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] (ISOFORM 1).
    Tissue: Lung.
  4. Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 137-202 (ISOFORM 1).
    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): B7Z4P3, Q9UPL1
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: January 11, 2001
Last modified: October 29, 2014
This is version 131 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