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P35453 (HXD13_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 138. 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·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Homeobox protein Hox-D13
Alternative name(s):
Homeobox protein Hox-4I
Gene names
Name:HOXD13
Synonyms:HOX4I
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length343 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Sequence-specific transcription factor which is part of a developmental regulatory system that provides cells with specific positional identities on the anterior-posterior axis.

Subcellular location

Nucleus.

Polymorphism

The poly-Ala region is polymorphic (11 to 15 residues) in the normal population and is expanded to about 22-29 residues in SPD1 and syndactyly type 5 patients.

Involvement in disease

Synpolydactyly 1 (SPD1) [MIM:186000]: Limb malformation that shows a characteristic manifestation in both hands and feet. This condition is inherited as an autosomal dominant trait with reduced penetrance.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.6 Ref.7

Brachydactyly D (BDD) [MIM:113200]: A form of brachydactyly. Brachydactyly defines a group of inherited malformations characterized by shortening of the digits due to abnormal development of the phalanges and/or the metacarpals. Brachydactyly type D is characterized by short and broad terminal phalanges of the thumbs and big toes.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.8

Syndactyly 5 (SDTY5) [MIM:186300]: A form of syndactyly, a congenital anomaly of the hand or foot marked by persistence of the webbing between adjacent digits that are more or less completely attached. The characteristic finding in SDTY5 is the presence of an associated metacarpal and metatarsal fusion. The metacarpals and metatarsals most commonly fused are the 4th and 5th or the 3rd and 4th. Soft tissue syndactyly usually affects the 3rd and 4th fingers and the 2nd and 3rd toes.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.10

Brachydactyly-syndactyly syndrome (BDSD) [MIM:610713]: A disease characterized by generalized shortening of the hands and feet, broad and short distal phalanges of the thumbs, and cutaneous syndactyly of toes 2 and 3. The limb phenotypes observed in this syndrome overlap those of brachydactyly types A4, D, E and syndactyly type 1.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.10

Brachydactyly E1 (BDE1) [MIM:113300]: A form of brachydactyly. Brachydactyly defines a group of inherited malformations characterized by shortening of the digits due to abnormal development of the phalanges and/or the metacarpals. Brachydactyly type E is characterized by shortening of the fingers mainly in the metacarpals and metatarsals. Wide variability in the number of digits affected occurs from person to person, even in the same family. Some individuals are moderately short of stature. Brachydactyly type E1 is characterized by shortening limited to fourth metacarpals and/or metatarsals.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.8

VACTERL association (VACTERL) [MIM:192350]: VACTERL is an acronym for vertebral anomalies, anal atresia, congenital cardiac disease, tracheoesophageal fistula, renal anomalies, radial dysplasia, and other limb defects.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.5

Sequence similarities

Belongs to the Abd-B homeobox family.

Contains 1 homeobox DNA-binding domain.

Caution

It is uncertain whether Met-1 or Met-9 is the initiator.

Sequence caution

The sequence AAC51635.1 differs from that shown. Reason: Erroneous initiation.

The sequence BAA95352.1 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
   Biological processTranscription
Transcription regulation
   Cellular componentNucleus
   Coding sequence diversityPolymorphism
Triplet repeat expansion
   DiseaseDisease mutation
   DomainHomeobox
   LigandDNA-binding
   Molecular functionDevelopmental protein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processanterior/posterior pattern specification

Inferred from electronic annotation. Source: Ensembl

branch elongation of an epithelium

Inferred from electronic annotation. Source: Ensembl

embryonic digit morphogenesis

Inferred from electronic annotation. Source: Ensembl

embryonic hindgut morphogenesis

Inferred from electronic annotation. Source: Ensembl

male genitalia development

Inferred from electronic annotation. Source: Ensembl

morphogenesis of an epithelial fold

Inferred from electronic annotation. Source: Ensembl

multicellular organismal development

Traceable author statement PubMed 9207113. Source: ProtInc

positive regulation of transcription from RNA polymerase II promoter

Inferred from electronic annotation. Source: Ensembl

prostate epithelial cord arborization involved in prostate glandular acinus morphogenesis

Inferred from electronic annotation. Source: Ensembl

regulation of branching involved in prostate gland morphogenesis

Inferred from electronic annotation. Source: Ensembl

regulation of cell proliferation

Inferred from electronic annotation. Source: Ensembl

regulation of transcription, DNA-templated

Traceable author statement PubMed 9207113. Source: ProtInc

skeletal system development

Traceable author statement Ref.1. Source: ProtInc

transcription from RNA polymerase II promoter

Traceable author statement Ref.1. Source: ProtInc

   Cellular_componentnucleus

Inferred from electronic annotation. Source: UniProtKB-SubCell

   Molecular_functionDNA binding

Traceable author statement Ref.1. Source: ProtInc

chromatin binding

Inferred from electronic annotation. Source: Ensembl

sequence-specific DNA binding

Inferred from electronic annotation. Source: InterPro

sequence-specific DNA binding transcription factor activity

Inferred from electronic annotation. Source: Ensembl

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 343343Homeobox protein Hox-D13
PRO_0000200244

Regions

DNA binding276 – 33560Homeobox
Compositional bias25 – 306Poly-Ser
Compositional bias32 – 365Poly-Ala
Compositional bias57 – 7115Poly-Ala
Compositional bias85 – 928Poly-Ser
Compositional bias113 – 1186Poly-Ala

Natural variations

Natural variant57 – 637Missing in BDSD; does not affect capacity to transactivate EPHA7 promoter.
VAR_031649
Natural variant57 – 582Missing.
VAR_031648
Natural variant571A → AAAAAAAAAA in SPD1 and in syndactyly type 5. Ref.6 Ref.9
VAR_003818
Natural variant2521S → A.
Corresponds to variant rs35290213 [ dbSNP | Ensembl ].
VAR_031650
Natural variant3061R → W in SPD1. Ref.7
Corresponds to variant rs28933082 [ dbSNP | Ensembl ].
VAR_031651
Natural variant3161S → C in BDE1 and BDD. Ref.8
Corresponds to variant rs28928892 [ dbSNP | Ensembl ].
VAR_015952
Natural variant3221I → L in BDE1. Ref.8
Corresponds to variant rs28928891 [ dbSNP | Ensembl ].
VAR_015953
Natural variant3251Q → R in SDTY5; impairs capacity to transactivate EPHA7 promoter. Ref.10
VAR_031652

Sequences

Sequence LengthMass (Da)Tools
P35453 [UniParc].

Last modified February 10, 2009. Version 3.
Checksum: CF34D0319021430A

FASTA34336,101
        10         20         30         40         50         60 
MSRAGSWDMD GLRADGGGAG GAPASSSSSS VAAAAASGQC RGFLSAPVFA GTHSGRAAAA 

        70         80         90        100        110        120 
AAAAAAAAAA ASGFAYPGTS ERTGSSSSSS SSAVVAARPE APPAKECPAP TPAAAAAAPP 

       130        140        150        160        170        180 
SAPALGYGYH FGNGYYSCRM SHGVGLQQNA LKSSPHASLG GFPVEKYMDV SGLASSSVPA 

       190        200        210        220        230        240 
NEVPARAKEV SFYQGYTSPY QHVPGYIDMV STFGSGEPRH EAYISMEGYQ SWTLANGWNS 

       250        260        270        280        290        300 
QVYCTKDQPQ GSHFWKSSFP GDVALNQPDM CVYRRGRKKR VPYTKLQLKE LENEYAINKF 

       310        320        330        340 
INKDKRRRIS AATNLSERQV TIWFQNRRVK DKKIVSKLKD TVS 

« Hide

References

« Hide 'large scale' references
[1]"Altered growth and branching patterns in synpolydactyly caused by mutations in HOXD13."
Muragaki Y., Mundlos S., Upton J., Olsen B.R.
Science 272:548-551(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[2]"The t(2:11)(q31:p15) translocation in acute myeloid leukemia fuses NUP98 nucleoporin gene to HOXD13 homeobox gene."
Arai Y., Arai K., Kita K., Miwa H., Kamada N., Ohki M.
Submitted (SEP-1999) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]"Generation and annotation of the DNA sequences of human chromosomes 2 and 4."
Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H. expand/collapse author list , Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., Wilson R.K.
Nature 434:724-731(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]"EVX2, a human homeobox gene homologous to the even-skipped segmentation gene, is localized at the 5' end of HOX4 locus on chromosome 2."
D'Esposito M., Morelli F., Acampora D., Migliaccio E., Simeone A., Boncinelli E.
Genomics 10:43-50(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 276-341.
[5]"Identification of a HOXD13 mutation in a VACTERL patient."
Garcia-Barcelo M.-M., Wong K.K., Lui V.C., Yuan Z.W., So M.T., Ngan E.S., Miao X.P., Chung P.H., Khong P.L., Tam P.K.
Am. J. Med. Genet. A 146:3181-3185(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: INVOLVEMENT IN VACTERL.
[6]"Genomic structure of HOXD13 gene: a nine polyalanine duplication causes synpolydactyly in two unrelated families."
Akarsu A.N., Stoilov I., Yilmaz E., Sayli B.S., Sarfarazi M.
Hum. Mol. Genet. 5:945-952(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT SPD1 ALA-ALA-ALA-ALA-ALA-ALA-ALA-ALA-ALA-57 INS.
[7]"Severe digital abnormalities in a patient heterozygous for both a novel missense mutation in HOXD13 and a polyalanine tract expansion in HOXA13."
Debeer P., Bacchelli C., Scambler P.J., De Smet L., Fryns J.-P., Goodman F.R.
J. Med. Genet. 39:852-856(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT SPD1 TRP-306.
[8]"Missense mutations in the homeodomain of HOXD13 are associated with brachydactyly types D and E."
Johnson D., Kan S.H., Oldridge M., Trembath R.C., Roche P., Esnouf R.M., Giele H., Wilkie A.O.
Am. J. Hum. Genet. 72:984-997(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS BDE1 CYS-316 AND LEU-322, VARIANT BDD CYS-316.
[9]"A 72-year-old Danish puzzle resolved -- comparative analysis of phenotypes in families with different-sized HOXD13 polyalanine expansions."
Kjaer K.W., Hansen L., Eiberg H., Utkus A., Skovgaard L.T., Leicht P., Opitz J.M., Tommerup N.
Am. J. Med. Genet. A 138:328-339(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT ALA-ALA-ALA-ALA-ALA-ALA-ALA-ALA-ALA-57 INS, VARIANT 57-ALA-ALA-58 DEL.
[10]"Mutations in HOXD13 underlie syndactyly type V and a novel brachydactyly-syndactyly syndrome."
Zhao X., Sun M., Zhao J., Leyva J.A., Zhu H., Yang W., Zeng X., Ao Y., Liu Q., Liu G., Lo W.H.Y., Jabs E.W., Amzel L.M., Shan X., Zhang X.
Am. J. Hum. Genet. 80:361-371(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT BDSD 57-ALA--ALA-62 DEL, VARIANT SDTY5 ARG-325, CHARACTERIZATION OF VARIANT BDSD 57-ALA--ALA-62 DEL, CHARACTERIZATION OF VARIANT SDTY5 ARG-325.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF005220, AF005219 Genomic DNA. Translation: AAC51635.1. Different initiation.
AB032481 Genomic DNA. Translation: BAA95352.1. Different initiation.
AC009336 Genomic DNA. No translation available.
CCDSCCDS2264.2.
PIRB39065.
RefSeqNP_000514.2. NM_000523.3.
UniGeneHs.152414.

3D structure databases

ProteinModelPortalP35453.
SMRP35453. Positions 276-341.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid109479. 3 interactions.
STRING9606.ENSP00000376322.

PTM databases

PhosphoSiteP35453.

Polymorphism databases

DMDM223590221.

Proteomic databases

MaxQBP35453.
PaxDbP35453.
PRIDEP35453.

Protocols and materials databases

DNASU3239.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000392539; ENSP00000376322; ENSG00000128714.
GeneID3239.
KEGGhsa:3239.
UCSCuc002ukf.1. human.

Organism-specific databases

CTD3239.
GeneCardsGC02P176921.
HGNCHGNC:5136. HOXD13.
MIM113200. phenotype.
113300. phenotype.
142989. gene.
186000. phenotype.
186300. phenotype.
192350. phenotype.
610713. phenotype.
neXtProtNX_P35453.
Orphanet93385. Brachydactyly type D.
93387. Brachydactyly type E.
93409. Brachydactyly-syndactyly, Zhao type.
93406. Syndactyly type 5.
295195. Synpolydactyly type 1.
887. VACTERL/VATER association.
PharmGKBPA29410.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG251666.
HOGENOMHOG000231176.
HOVERGENHBG106958.
InParanoidP35453.
KOK09298.
OMAAKECPAP.
OrthoDBEOG7SJD53.
PhylomeDBP35453.
TreeFamTF330813.

Gene expression databases

BgeeP35453.
CleanExHS_HOXD13.
GenevestigatorP35453.

Family and domain databases

Gene3D1.10.10.60. 1 hit.
InterProIPR017970. Homeobox_CS.
IPR001356. Homeobox_dom.
IPR009057. Homeodomain-like.
IPR022067. HoxA13_N.
[Graphical view]
PfamPF00046. Homeobox. 1 hit.
PF12284. HoxA13_N. 1 hit.
[Graphical view]
SMARTSM00389. HOX. 1 hit.
[Graphical view]
SUPFAMSSF46689. SSF46689. 1 hit.
PROSITEPS00027. HOMEOBOX_1. 1 hit.
PS50071. HOMEOBOX_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSHOXD13. human.
GeneWikiHOXD13.
GenomeRNAi3239.
NextBio12891.
PROP35453.
SOURCESearch...

Entry information

Entry nameHXD13_HUMAN
AccessionPrimary (citable) accession number: P35453
Entry history
Integrated into UniProtKB/Swiss-Prot: June 1, 1994
Last sequence update: February 10, 2009
Last modified: July 9, 2014
This is version 138 of the entry and version 3 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

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 2

Human chromosome 2: entries, gene names and cross-references to MIM

Vertebrate homeotic Hox proteins

Nomenclature of vertebrate homeotic Hox proteins and list of entries