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Protein

Homeobox protein DLX-5

Gene

DLX5

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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)DescriptionActionsGraphical viewLength
DNA bindingi137 – 196HomeoboxPROSITE-ProRule annotationAdd BLAST60

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionActivator, Developmental protein, DNA-binding
Biological processOsteogenesis, Transcription, Transcription regulation

Enzyme and pathway databases

ReactomeiR-HSA-8939902 Regulation of RUNX2 expression and activity
SIGNORiP56178

Names & Taxonomyi

Protein namesi
Recommended name:
Homeobox protein DLX-5
Gene namesi
Name:DLX5
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 7

Organism-specific databases

EuPathDBiHostDB:ENSG00000105880.4
HGNCiHGNC:2918 DLX5
MIMi600028 gene
neXtProtiNX_P56178

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Involvement in diseasei

Split-hand/foot malformation 1 with sensorineural hearing loss, autosomal recessive (SHFM1D)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA 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.
See also OMIM:220600
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_067413178Q → P in SHFM1D. 1 PublicationCorresponds to variant dbSNP:rs387906737EnsemblClinVar.1

Keywords - Diseasei

Deafness, Disease mutation

Organism-specific databases

DisGeNETi1749
MalaCardsiDLX5
MIMi220600 phenotype
OpenTargetsiENSG00000105880
Orphaneti71271 Split hand - split foot - deafness
2440 Split hand-split foot malformation
PharmGKBiPA27373

Polymorphism and mutation databases

BioMutaiDLX5
DMDMi12644329

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000490311 – 289Homeobox protein DLX-5Add BLAST289

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei34Phosphoserine; by MAPK14; in vitroBy similarity1
Modified residuei217Phosphoserine; by MAPK14; in vitroBy similarity1

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
PeptideAtlasiP56178
PRIDEiP56178
ProteomicsDBi56892

PTM databases

iPTMnetiP56178
PhosphoSitePlusiP56178

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

BgeeiENSG00000105880
CleanExiHS_DLX5
ExpressionAtlasiP56178 baseline and differential
GenevisibleiP56178 HS

Organism-specific databases

HPAiHPA005670

Interactioni

Subunit structurei

Interacts with XRCC6 (Ku70).1 Publication

GO - Molecular functioni

Protein-protein interaction databases

BioGridi108093, 14 interactors
IntActiP56178, 9 interactors
MINTiP56178
STRINGi9606.ENSP00000222598

Structurei

Secondary structure

1289
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi146 – 158Combined sources13
Helixi164 – 173Combined sources10
Helixi178 – 196Combined sources19

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2DJNNMR-A138-194[»]
4RDUX-ray1.85A/D135-198[»]
ProteinModelPortaliP56178
SMRiP56178
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP56178

Family & Domainsi

Sequence similaritiesi

Belongs to the distal-less homeobox family.Curated

Keywords - Domaini

Homeobox

Phylogenomic databases

eggNOGiKOG0850 Eukaryota
ENOG410ZHZR LUCA
GeneTreeiENSGT00920000148979
HOGENOMiHOG000231940
HOVERGENiHBG005493
InParanoidiP56178
KOiK18489
OMAiNSASWYP
OrthoDBiEOG091G0P17
PhylomeDBiP56178
TreeFamiTF350606

Family and domain databases

CDDicd00086 homeodomain, 1 hit
InterProiView protein in InterPro
IPR022135 Distal-less_N
IPR009057 Homeobox-like_sf
IPR017970 Homeobox_CS
IPR001356 Homeobox_dom
IPR020479 Homeobox_metazoa
IPR000047 HTH_motif
PfamiView protein in Pfam
PF12413 DLL_N, 1 hit
PF00046 Homeobox, 1 hit
PRINTSiPR00024 HOMEOBOX
PR00031 HTHREPRESSR
SMARTiView protein in SMART
SM00389 HOX, 1 hit
SUPFAMiSSF46689 SSF46689, 1 hit
PROSITEiView protein in PROSITE
PS00027 HOMEOBOX_1, 1 hit
PS50071 HOMEOBOX_2, 1 hit

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

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)DescriptionActionsGraphical viewLength
Natural variantiVAR_067413178Q → P in SHFM1D. 1 PublicationCorresponds to variant dbSNP:rs387906737EnsemblClinVar.1
Natural variantiVAR_033874234S → R. Corresponds to variant dbSNP:rs35273378Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_056884182 – 289KIWFQ…SGTLY → NTALPCTRPA in isoform 2. 1 PublicationAdd BLAST108

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
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 [P56178-1]
PIRiC53495
RefSeqiNP_005212.1, NM_005221.5 [P56178-1]
UniGeneiHs.99348

Genome annotation databases

EnsembliENST00000222598; ENSP00000222598; ENSG00000105880 [P56178-1]
ENST00000486603; ENSP00000475008; ENSG00000105880 [P56178-2]
GeneIDi1749
KEGGihsa:1749
UCSCiuc011kim.2 human [P56178-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiDLX5_HUMAN
AccessioniPrimary (citable) accession number: P56178
Secondary accession number(s): B7Z4P3, Q9UPL1
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: January 11, 2001
Last modified: June 20, 2018
This is version 167 of the entry and version 2 of the sequence. See 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

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