P35453 (HXD13_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Homeobox protein Hox-D13

Alternative name(s):
Homeobox protein Hox-4I

Gene names

Name:	HOXD13
Synonyms:	HOX4I

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	343 AA.
Sequence status	Complete.
Protein existence	Evidence 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	Defects in HOXD13 are the cause of synpolydactyly 1 (SPD1) [MIM:186000]; also known as syndactyly type 2 (SDTY2). SPD1 is a limb malformation that shows a characteristic manifestation in both hands and feet. This condition is inherited as an autosomal dominant trait with reduced penetrance. Ref.6 Ref.7 Defects in HOXD13 are the cause of brachydactyly type D (BDD) [MIM:113200]. BDD is characterized by short and broad terminal phalanges of the thumbs and big toes. Inheritance is autosomal dominant. Ref.8 Defects in HOXD13 are the cause of syndactyly type 5 (SDTY5) [MIM:186300]; also known as syndactyly with 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. Inheritance is autosomal dominant. Ref.10 Defects in HOXD13 are the cause of brachydactyly-syndactyly syndrome (BDSD) [MIM:610713]. Most of affected individuals exhibit 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. Ref.10 Defects in HOXD13 are the cause of brachydactyly type E (BDE1) [MIM:113300]. BDE is characterized by shortening of the fingers mainly in the metacarpals and metatarsals. Inheritance is autosomal dominant. Ref.8 Defects in HOXD13 are a cause of VACTERL association (VACTERL) [MIM:192350]; which includes also VATER association. VACTERL is an acronym for vertebral anomalies, anal atresia, congenital cardiac disease, tracheoesophageal fistula, renal anomalies, radial dysplasia, and other limb defects. 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 process	Transcription Transcription regulation
Cellular component	Nucleus
Coding sequence diversity	Polymorphism Triplet repeat expansion
Disease	Disease mutation
Domain	Homeobox
Ligand	DNA-binding
Molecular function	Developmental protein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	skeletal system development Traceable author statement. Source: ProtInc transcription from RNA polymerase II promoter Traceable author statement. Source: ProtInc
Cellular component	nucleus Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	sequence-specific DNA binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 343	343	Homeobox protein Hox-D13		PRO_0000200244
Regions
	DNA binding	276 – 335	60	Homeobox
	Compositional bias	25 – 30	6	Poly-Ser
	Compositional bias	32 – 36	5	Poly-Ala
	Compositional bias	57 – 71	15	Poly-Ala
	Compositional bias	85 – 92	8	Poly-Ser
	Compositional bias	113 – 118	6	Poly-Ala
Natural variations
	Natural variant	57 – 63	7	Missing in BDSD; does not affect capacity to transactivate EPHA7 promoter.		VAR_031649
	Natural variant	57 – 58	2	Missing. Ref.6 Ref.9		VAR_031648
	Natural variant	57	1	A → AAAAAAAAAA in SPD1 and in syndactyly type 5. Ref.6 Ref.9		VAR_003818
	Natural variant	252	1	S → A. Corresponds to variant rs35290213 [ dbSNP | Ensembl ].		VAR_031650
	Natural variant	306	1	R → W in SPD1. Ref.7 Corresponds to variant rs28933082 [ dbSNP | Ensembl ].		VAR_031651
	Natural variant	316	1	S → C in BDE1 and BDD. Ref.8 Corresponds to variant rs28928892 [ dbSNP | Ensembl ].		VAR_015952
	Natural variant	322	1	I → L in BDE1. Ref.8 Corresponds to variant rs28928891 [ dbSNP | Ensembl ].		VAR_015953
	Natural variant	325	1	Q → R in SDTY5; impairs capacity to transactivate EPHA7 promoter. Ref.10		VAR_031652

Sequences

	Sequence		Length	Mass (Da)
	P35453 [UniParc]. Last modified February 10, 2009. Version 3. Checksum: CF34D0319021430A	FASTA	343	36,101
	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

References

	« Hide 'large scale' referencesShow '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: 8614804] [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. , 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: 15815621] [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: 1675198] [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: 19006232] [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: 8817328] [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: 12414828] [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: 12649808] [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: 16222680] [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: 17236141] [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.

Web resources

GeneReviews

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.
IPI	IPI00871270.
PIR	B39065.
RefSeq	NP_000514.2. NM_000523.3.
UniGene	Hs.152414.
3D structure databases
ProteinModelPortal	P35453.
SMR	P35453. Positions 276-341.
ModBase	Search...
Protein-protein interaction databases
STRING	P35453.
Polymorphism databases
DMDM	223590221.
Proteomic databases
PRIDE	P35453.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000392539; ENSP00000376322; ENSG00000128714.
GeneID	3239.
KEGG	hsa:3239.
UCSC	uc002ukf.1. human.
Organism-specific databases
CTD	3239.
GeneCards	GC02P176921.
HGNC	HGNC:5136. HOXD13.
MIM	113200. phenotype. 113300. phenotype. 142989. gene. 186000. phenotype. 186300. phenotype. 192350. phenotype. 610713. phenotype.
neXtProt	NX_P35453.
Orphanet	93385. Brachydactyly type D. 93403. Syndactyly type 2. 93406. Syndactyly type 5. 887. VATER association.
PharmGKB	PA29410.
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG15252.
GeneTree	ENSGT00580000081399.
HOGENOM	HBG716010.
HOVERGEN	HBG106958.
InParanoid	P35453.
OMA	PAKECPA.
OrthoDB	EOG4X3H26.
PhylomeDB	P35453.
Gene expression databases
ArrayExpress	P35453.
Bgee	P35453.
CleanEx	HS_HOXD13.
Genevestigator	P35453.
GermOnline	ENSG00000128714. Homo sapiens.
Family and domain databases
InterPro	IPR001356. Homeobox. IPR017970. Homeobox_CS. IPR009057. Homeodomain-like. IPR012287. Homeodomain-rel. IPR022067. HoxA13_N. [Graphical view]
Gene3D	G3DSA:1.10.10.60. Homeodomain-rel. 1 hit.
KO	K09298.
Pfam	PF00046. Homeobox. 1 hit. PF12284. HoxA13_N. 1 hit. [Graphical view]
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
SOURCE	Search...

Entry information

Entry name

HXD13_HUMAN

Accession

Primary (citable) accession number: P35453

Entry history

Integrated into UniProtKB/Swiss-Prot:	June 1, 1994
Last sequence update:	February 10, 2009
Last modified:	January 25, 2012
This is version 115 of the entry and version 3 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.