P78411 (IRX5_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Iroquois-class homeodomain protein IRX-5

Alternative name(s):
Homeodomain protein IRX-2A
Homeodomain protein IRXB2
Iroquois homeobox protein 5

Gene names

Name:	IRX5
Synonyms:	IRX2A, IRXB2

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	483 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Establishes the cardiac repolarization gradient by its repressive actions on the KCND2 potassium-channel gene. Required for retinal cone bipolar cell differentiation. May regulate contrast adaptation in the retina and control specific aspects of visual function in circuits of the mammalian retina By similarity. Could be involved in the regulation of both the cell cycle and apoptosis in prostate cancer cells. Involved in craniofacial and gonadal development. Modulates the migration of progenitor cell populations in branchial arches and gonads by repressing CXCL12. Ref.3 Ref.4
Subcellular location	Nucleus Probable.
Induction	Down-regulated by 1,25-dihydroxyvitamin D3 in prostate cancer samples from patients assigned to receive weekly high-dose 1,25-dihydroxyvitamin D3 before radical prostatectomy. Also down-regulated by 1,25-dihydroxyvitamin D3 in the human androgen-sensitive prostate cancer cell line LNCaP and in the estrogen-sensitive breast cancer cell line MCF-7. Ref.3
Involvement in disease	Hamamy syndrome (HMMS) [MIM:611174]: A sydrome characterized by severe hypertelorism, upslanting palpebral fissures, brachycephaly, abnormal ears, sloping shoulders, enamel hypoplasia, and osteopenia with repeated fractures. Additional features include myopia, mild to moderate sensorineural hearing loss, gonadal anomalies and borderline intelligence. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.4
Sequence similarities	Belongs to the TALE/IRO homeobox family. Contains 1 homeobox DNA-binding domain.

Ontologies

Keywords
Biological process	Sensory transduction Transcription Vision
Cellular component	Nucleus
Disease	Disease mutation Mental retardation
Domain	Homeobox
Ligand	DNA-binding Vitamin D
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	embryonic cranial skeleton morphogenesis Inferred from mutant phenotype Ref.4. Source: UniProtKB gonad development Inferred from mutant phenotype Ref.4. Source: UniProtKB neuron maturation Inferred from electronic annotation. Source: Compara regulation of heart rate Inferred from electronic annotation. Source: Compara response to stimulus Inferred from electronic annotation. Source: UniProtKB-KW retinal bipolar neuron differentiation Inferred from electronic annotation. Source: Compara transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW visual perception Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	nucleus Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	sequence-specific DNA binding Inferred from electronic annotation. Source: InterPro sequence-specific DNA binding transcription factor activity Inferred from electronic annotation. Source: InterPro vitamin D binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 483	483	Iroquois-class homeodomain protein IRX-5		PRO_0000049160
Regions
	DNA binding	113 – 175	63	Homeobox; TALE-type
	Compositional bias	72 – 78	7	Poly-Ala
	Compositional bias	186 – 192	7	Poly-Glu
	Compositional bias	320 – 326	7	Poly-Pro
	Compositional bias	350 – 353	4	Poly-Gly
Natural variations
	Natural variant	150	1	A → P in HMMS; hypomorphic mutation. Ref.4		VAR_068483
	Natural variant	166	1	N → K in HMMS; hypomorphic mutation. Ref.4		VAR_068484
Experimental info
	Sequence conflict	67 – 83	17	YGADP…FSSYV → MAVETTVHTHLSASPPQ in AAB50002. Ref.2
	Sequence conflict	211	1	G → A in AAB50007. Ref.2
	Sequence conflict	219	1	Missing in AAQ16550. Ref.1
	Sequence conflict	219	1	Missing in AAQ16551. Ref.1
	Sequence conflict	343	1	S → L in AAB50002. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	P78411 [UniParc]. Last modified April 3, 2007. Version 3. Checksum: 12E9397924EB5E6E	FASTA	483	50,361
	10 20 30 40 50 60 MSYPQGYLYQ PSASLALYSC PAYSTSVISG PRTDELGRSS SGSAFSPYAG STAFTAPSPG 70 80 90 100 110 120 YNSHLQYGAD PAAAAAAAFS SYVGSPYDHT PGMAGSLGYH PYAAPLGSYP YGDPAYRKNA 130 140 150 160 170 180 TRDATATLKA WLNEHRKNPY PTKGEKIMLA IITKMTLTQV STWFANARRR LKKENKMTWT 190 200 210 220 230 240 PRNRSEDEEE EENIDLEKND EDEPQKPEDK GDPEGPEAGG AEQKAASGCE RLQGPPTPAG 250 260 270 280 290 300 KETEGSLSDS DFKEPPSEGR LDALQGPPRT GGPSPAGPAA ARLAEDPAPH YPAGAPAPGP 310 320 330 340 350 360 HPAAGEVPPG PGGPSVIHSP PPPPPPAVLA KPKLWSLAEI ATSSDKVKDG GGGNEGSPCP 370 380 390 400 410 420 PCPGPIAGQA LGGSRASPAP APSRSPSAQC PFPGGTVLSR PLYYTAPFYP GYTNYGSFGH 430 440 450 460 470 480 LHGHPGPGPG PTTGPGSHFN GLNQTVLNRA DALAKDPKML RSQSQLDLCK DSPYELKKGM SDI

References

[1]	"Characterization of the human homeobox two-cluster Iroquois gene family." Hansen L., Wu Q., Tommerup N. Submitted (JUL-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA].
[2]	"Regulated expression patterns of IRX-2, an Iroquois-class homeobox gene, in the human breast." Lewis M.T., Ross S., Strickland P.A., Snyder C.J., Daniel C.W. Cell Tissue Res. 296:549-554(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 67-483.
[3]	"The iroquois homeobox gene 5 is regulated by 1,25-dihydroxyvitamin D3 in human prostate cancer and regulates apoptosis and the cell cycle in LNCaP prostate cancer cells." Myrthue A., Rademacher B.L.S., Pittsenbarger J., Kutyba-Brooks B., Gantner M., Qian D.Z., Beer T.M. Clin. Cancer Res. 14:3562-3570(2008) [PubMed] [Europe PMC] [Abstract] Cited for: DOWN-REGULATION BY 1,25-DIHYDROXYVITAMIN D3, POSSIBLE FUNCTION.
[4]	"Mutations in IRX5 impair craniofacial development and germ cell migration via SDF1." Bonnard C., Strobl A.C., Shboul M., Lee H., Merriman B., Nelson S.F., Ababneh O.H., Uz E., Guran T., Kayserili H., Hamamy H., Reversade B. Nat. Genet. 44:709-713(2012) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, VARIANTS HMMS PRO-150 AND LYS-166, CHARACTERIZATION OF VARIANTS HMMS PRO-150 AND LYS-166.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AY335944 Genomic DNA. Translation: AAQ16550.1. AY335945 mRNA. Translation: AAQ16551.1. U90304 mRNA. Translation: AAB50002.1. U90309 mRNA. Translation: AAB50007.1.
IPI	IPI00456865.
RefSeq	NP_001239126.1. NM_001252197.1. NP_005844.4. NM_005853.5.
UniGene	Hs.435730.
3D structure databases
ProteinModelPortal	P78411.
ModBase	Search...
Protein-protein interaction databases
STRING	9606.ENSP00000378132.
PTM databases
PhosphoSite	P78411.
Polymorphism databases
DMDM	143811406.
Proteomic databases
PaxDb	P78411.
PRIDE	P78411.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000320990; ENSP00000316250; ENSG00000176842. ENST00000394636; ENSP00000378132; ENSG00000176842.
GeneID	10265.
KEGG	hsa:10265.
UCSC	uc002ehv.3. human.
Organism-specific databases
CTD	10265.
GeneCards	GC16P054964.
H-InvDB	HIX0038585.
HGNC	HGNC:14361. IRX5.
HPA	HPA047130.
MIM	606195. gene. 611174. phenotype.
neXtProt	NX_P78411.
PharmGKB	PA29928.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG320023.
HOGENOM	HOG000234546.
HOVERGEN	HBG006180.
InParanoid	P78411.
OMA	KKGMSNI.
OrthoDB	EOG44F69D.
PhylomeDB	P78411.
Gene expression databases
ArrayExpress	P78411.
Bgee	P78411.
CleanEx	HS_IRX5.
Genevestigator	P78411.
GermOnline	ENSG00000176842. Homo sapiens.
Family and domain databases
Gene3D	1.10.10.60. 1 hit.
InterPro	IPR017970. Homeobox_CS. IPR008422. Homeobox_KN_domain. IPR001356. Homeodomain. IPR009057. Homeodomain-like. IPR003893. Iroquois_homeo. [Graphical view]
Pfam	PF05920. Homeobox_KN. 1 hit. [Graphical view]
SMART	SM00389. HOX. 1 hit. SM00548. IRO. 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
GenomeRNAi	10265.
NextBio	38888.
SOURCE	Search...

Entry information

Entry name

IRX5_HUMAN

Accession

Primary (citable) accession number: P78411
Secondary accession number(s): P78416, Q7Z2E1

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 15, 1998
Last sequence update:	April 3, 2007
Last modified:	May 1, 2013
This is version 110 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.