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P56178 (DLX5_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 128. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Homeobox protein DLX-5
Gene names
Name:DLX5
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length289 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.6

Subunit structure

Interacts with XRCC6 (Ku70). Ref.5

Subcellular location

Nucleus By similarity.

Developmental stage

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.

Post-translational modification

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

Involvement in disease

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.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.8

Sequence similarities

Belongs to the distal-less homeobox family.

Contains 1 homeobox DNA-binding domain.

Ontologies

Keywords
   Biological processOsteogenesis
Transcription
Transcription regulation
   Cellular componentNucleus
   Coding sequence diversityPolymorphism
   DiseaseDeafness
Disease mutation
   DomainHomeobox
   LigandDNA-binding
   Molecular functionActivator
Developmental protein
   PTMPhosphoprotein
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processBMP signaling pathway

Inferred from sequence or structural similarity. Source: BHF-UCL

anatomical structure formation involved in morphogenesis

Inferred from electronic annotation. Source: Ensembl

axon guidance

Inferred from electronic annotation. Source: Ensembl

cell proliferation

Inferred from direct assay Ref.6. Source: UniProtKB

cellular response to BMP stimulus

Inferred from sequence or structural similarity. Source: BHF-UCL

embryonic limb morphogenesis

Inferred from electronic annotation. Source: Ensembl

endochondral ossification

Inferred from sequence or structural similarity. Source: UniProtKB

epithelial cell differentiation

Inferred from electronic annotation. Source: Ensembl

face morphogenesis

Inferred from electronic annotation. Source: Ensembl

inner ear morphogenesis

Inferred from electronic annotation. Source: Ensembl

nervous system development

Traceable author statement Ref.4. Source: ProtInc

olfactory pit development

Inferred from electronic annotation. Source: Ensembl

osteoblast differentiation

Inferred from sequence or structural similarity. Source: UniProtKB

palate development

Inferred from electronic annotation. Source: Ensembl

positive regulation of canonical Wnt signaling pathway

Inferred from electronic annotation. Source: Ensembl

positive regulation of epithelial cell proliferation

Inferred from electronic annotation. Source: Ensembl

positive regulation of osteoblast differentiation

Inferred from electronic annotation. Source: Ensembl

positive regulation of transcription from RNA polymerase II promoter involved in cellular response to chemical stimulus

Inferred from sequence or structural similarity. Source: BHF-UCL

positive regulation of transcription, DNA-templated

Inferred from direct assay Ref.6. Source: UniProtKB

skeletal system development

Traceable author statement Ref.4. Source: ProtInc

   Cellular_componentcytoplasm

Inferred from electronic annotation. Source: Ensembl

nuclear chromatin

Inferred from sequence or structural similarity. Source: BHF-UCL

   Molecular_functionRNA polymerase II core promoter proximal region sequence-specific DNA binding

Inferred from sequence or structural similarity. Source: BHF-UCL

RNA polymerase II core promoter proximal region sequence-specific DNA binding transcription factor activity involved in positive regulation of transcription

Inferred from sequence or structural similarity. Source: BHF-UCL

transcription regulatory region DNA binding

Inferred from direct assay Ref.6. Source: UniProtKB

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 289289Homeobox protein DLX-5
PRO_0000049031

Regions

DNA binding137 – 19660Homeobox Ref.6

Amino acid modifications

Modified residue341Phosphoserine; by MAPK14; in vitro By similarity
Modified residue2171Phosphoserine; by MAPK14; in vitro By similarity

Natural variations

Natural variant1781Q → P in SHFM1D. Ref.8
VAR_067413
Natural variant2341S → R.
Corresponds to variant rs35273378 [ dbSNP | Ensembl ].
VAR_033874

Secondary structure

....... 289
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P56178 [UniParc].

Last modified January 11, 2001. Version 2.
Checksum: 5BC9970B12E30554

FASTA28931,540
        10         20         30         40         50         60 
MTGVFDRRVP SIRSGDFQAP FQTSAAMHHP SQESPTLPES SATDSDYYSP TGGAPHGYCS 

        70         80         90        100        110        120 
PTSASYGKAL NPYQYQYHGV NGSAGSYPAK AYADYSYASS YHQYGGAYNR VPSATNQPEK 

       130        140        150        160        170        180 
EVTEPEVRMV NGKPKKVRKP RTIYSSFQLA ALQRRFQKTQ YLALPERAEL AASLGLTQTQ 

       190        200        210        220        230        240 
VKIWFQNKRS KIKKIMKNGE MPPEHSPSSS DPMACNSPQS PAVWEPQGSS RSLSHHPHAH 

       250        260        270        280 
PPTSNQSPAS SYLENSASWY TSAASSINSH LPPPGSLQHP LALASGTLY 

« Hide

References

« Hide 'large scale' references
[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. expand/collapse author list , 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. expand/collapse author list , 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]"Cloning and characterization of two members of the vertebrate Dlx gene family."
Simeone A., Acampora D., Pannese M., D'Esposito M., Stornaiuolo A., Gulisano M., Mallamaci A., Kastury K., Druck T., Huebner K., Boncinelli E.
Proc. Natl. Acad. Sci. U.S.A. 91:2250-2254(1994) [PubMed] [Europe PMC] [Abstract]
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.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AK023493 mRNA. Translation: BAB14587.1.
AC004774 Genomic DNA. Translation: AAC17833.1.
BC006226 mRNA. Translation: AAH06226.1.
PIRC53495.
RefSeqNP_005212.1. NM_005221.5.
UniGeneHs.99348.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2DJNNMR-A138-194[»]
ProteinModelPortalP56178.
SMRP56178. Positions 138-194.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid108093. 6 interactions.
MINTMINT-4720915.
STRING9606.ENSP00000222598.

PTM databases

PhosphoSiteP56178.

Polymorphism databases

DMDM12644329.

Proteomic databases

PaxDbP56178.
PRIDEP56178.

Protocols and materials databases

DNASU1749.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000222598; ENSP00000222598; ENSG00000105880.
GeneID1749.
KEGGhsa:1749.
UCSCuc003uon.3. human.

Organism-specific databases

CTD1749.
GeneCardsGC07M096649.
HGNCHGNC:2918. DLX5.
HPAHPA005670.
MIM220600. phenotype.
600028. gene.
neXtProtNX_P56178.
Orphanet71271. Split hand - split foot - deafness.
PharmGKBPA27373.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG263092.
HOGENOMHOG000231940.
HOVERGENHBG005493.
InParanoidP56178.
KOK09315.
OMAQSPAVWD.
OrthoDBEOG70W3F8.
PhylomeDBP56178.
TreeFamTF350606.

Gene expression databases

ArrayExpressP56178.
BgeeP56178.
CleanExHS_DLX5.
GenevestigatorP56178.

Family and domain databases

Gene3D1.10.10.60. 1 hit.
InterProIPR022135. Distal-less_N.
IPR017970. Homeobox_CS.
IPR001356. Homeobox_dom.
IPR020479. Homeobox_metazoa.
IPR009057. Homeodomain-like.
IPR000047. HTH_motif.
[Graphical view]
PfamPF12413. DLL_N. 1 hit.
PF00046. Homeobox. 1 hit.
[Graphical view]
PRINTSPR00024. HOMEOBOX.
PR00031. HTHREPRESSR.
SMARTSM00389. HOX. 1 hit.
[Graphical view]
SUPFAMSSF46689. SSF46689. 1 hit.
PROSITEPS00027. HOMEOBOX_1. 1 hit.
PS50071. HOMEOBOX_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceP56178.
GeneWikiDLX5.
GenomeRNAi1749.
NextBio7097.
PROP56178.
SOURCESearch...

Entry information

Entry nameDLX5_HUMAN
AccessionPrimary (citable) accession number: P56178
Secondary accession number(s): Q9UPL1
Entry history
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: January 11, 2001
Last modified: April 16, 2014
This is version 128 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 7

Human chromosome 7: entries, gene names and cross-references to MIM