P56178 (DLX5_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Homeobox protein DLX-5

Gene names

Name:

DLX5

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	289 AA.
Sequence status	Complete.
Protein existence	Evidence 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 (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 process	Osteogenesis Transcription Transcription regulation
Cellular component	Nucleus
Coding sequence diversity	Polymorphism
Disease	Deafness Disease mutation
Domain	Homeobox
Ligand	DNA-binding
Molecular function	Activator Developmental protein
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	BMP signaling pathway Inferred from sequence or structural similarity. Source: BHF-UCL anatomical structure formation involved in morphogenesis Inferred from electronic annotation. Source: Compara axon guidance Inferred from electronic annotation. Source: Compara 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: Compara endochondral ossification Inferred from sequence or structural similarity. Source: UniProtKB epithelial cell differentiation Inferred from electronic annotation. Source: Compara face morphogenesis Inferred from electronic annotation. Source: Compara inner ear morphogenesis Inferred from electronic annotation. Source: Compara nervous system development Traceable author statement Ref.4. Source: ProtInc olfactory pit development Inferred from electronic annotation. Source: Compara osteoblast differentiation Inferred from sequence or structural similarity. Source: UniProtKB palate development Inferred from electronic annotation. Source: Compara positive regulation of canonical Wnt receptor signaling pathway Inferred from electronic annotation. Source: Compara positive regulation of epithelial cell proliferation Inferred from electronic annotation. Source: Compara positive regulation of osteoblast differentiation Inferred from electronic annotation. Source: Compara 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
Cellular_component	cytoplasm Inferred from electronic annotation. Source: Compara nuclear chromatin Inferred from sequence or structural similarity. Source: BHF-UCL
Molecular_function	RNA 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
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 289

289

Homeobox protein DLX-5

PRO_0000049031

Regions

DNA binding

137 – 196

60

Homeobox Ref.6

Amino acid modifications

Modified residue

34

1

Phosphoserine; by MAPK14; in vitro By similarity

Modified residue

217

1

Phosphoserine; by MAPK14; in vitro By similarity

Natural variations

Natural variant

178

1

Q → P in SHFM1D. Ref.8

VAR_067413

Natural variant

234

1

S → R.
Corresponds to variant rs35273378 [ dbSNP | Ensembl ].

VAR_033874

Secondary structure

1

.

.

.

.

.

.

.

289

Helix Strand Turn

Details...

Helix

146 – 156

11

Helix

164 – 173

10

Helix

178 – 190

13

Sequences

	Sequence		Length	Mass (Da)
	P56178 [UniParc]. Last modified January 11, 2001. Version 2. Checksum: 5BC9970B12E30554	FASTA	289	31,540
	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

References

	« Hide 'large scale' referencesShow '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. , 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]	"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.

IPI

IPI00008192.

PIR

C53495.

RefSeq

NP_005212.1. NM_005221.5.

UniGene

Hs.99348.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2DJN	NMR	-	A	138-194	[»]

ProteinModelPortal

P56178.

ModBase

Search...

Protein-protein interaction databases

STRING

9606.ENSP00000222598.

PTM databases

PhosphoSite

P56178.

Polymorphism databases

DMDM

12644329.

Proteomic databases

PaxDb

P56178.

PRIDE

P56178.

Protocols and materials databases

DNASU

1749.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000222598; ENSP00000222598; ENSG00000105880.

GeneID

1749.

KEGG

hsa:1749.

UCSC

uc003uon.3. human.

Organism-specific databases

CTD

1749.

GeneCards

GC07M096649.

HGNC

HGNC:2918. DLX5.

HPA

HPA005670.

MIM

220600. phenotype.
600028. gene.

neXtProt

NX_P56178.

Orphanet

71271. Split hand - split foot - deafness.

PharmGKB

PA27373.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG263092.

HOGENOM

HOG000231940.

HOVERGEN

HBG005493.

InParanoid

P56178.

KO

K09315.

OMA

QSPAVWD.

OrthoDB

EOG49PB05.

PhylomeDB

P56178.

Gene expression databases

ArrayExpress

P56178.

Bgee

P56178.

CleanEx

HS_DLX5.

Genevestigator

P56178.

GermOnline

ENSG00000105880. Homo sapiens.

Family and domain databases

Gene3D

1.10.10.60. 1 hit.

InterPro

IPR022135. Distal-less_N.
IPR017970. Homeobox_CS.
IPR020479. Homeobox_metazoa.
IPR001356. Homeodomain.
IPR009057. Homeodomain-like.
IPR000047. HTH_motif.
[Graphical view]

Pfam

PF12413. DLL_N. 1 hit.
PF00046. Homeobox. 1 hit.
[Graphical view]

PRINTS

PR00024. HOMEOBOX.
PR00031. HTHREPRESSR.

SMART

SM00389. HOX. 1 hit.
[Graphical view]

SUPFAM

SSF46689. Homeodomain_like. 1 hit.

PROSITE

PS00027. HOMEOBOX_1. 1 hit.
PS50071. HOMEOBOX_2. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

P56178.

GenomeRNAi

1749.

NextBio

7097.

SOURCE

Search...

Entry information

Entry name

DLX5_HUMAN

Accession

Primary (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:	May 1, 2013
This is version 120 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.