Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Iroquois-class homeodomain protein IRX-5

Gene

IRX5

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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.By similarity1 Publication

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
DNA bindingi113 – 17563Homeobox; TALE-typePROSITE-ProRule annotationAdd
BLAST

GO - Molecular functioni

GO - Biological processi

  • embryonic cranial skeleton morphogenesis Source: UniProtKB
  • gonad development Source: UniProtKB
  • neuron maturation Source: Ensembl
  • regulation of heart rate Source: Ensembl
  • regulation of transcription, DNA-templated Source: InterPro
  • response to stimulus Source: UniProtKB-KW
  • retinal bipolar neuron differentiation Source: Ensembl
  • transcription, DNA-templated Source: UniProtKB-KW
  • visual perception Source: UniProtKB-KW
Complete GO annotation...

Keywords - Biological processi

Sensory transduction, Transcription, Vision

Keywords - Ligandi

DNA-binding, Vitamin D

Names & Taxonomyi

Protein namesi
Recommended name:
Iroquois-class homeodomain protein IRX-5
Alternative name(s):
Homeodomain protein IRX-2A
Homeodomain protein IRXB2
Iroquois homeobox protein 5
Gene namesi
Name:IRX5
Synonyms:IRX2A, IRXB2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 16

Organism-specific databases

HGNCiHGNC:14361. IRX5.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Involvement in diseasei

Hamamy syndrome (HMMS)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA syndrome 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.
See also OMIM:611174
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti150 – 1501A → P in HMMS; hypomorphic mutation. 1 Publication
VAR_068483
Natural varianti166 – 1661N → K in HMMS; hypomorphic mutation. 1 Publication
VAR_068484

Keywords - Diseasei

Disease mutation, Mental retardation

Organism-specific databases

MalaCardsiIRX5.
MIMi611174. phenotype.
Orphaneti314555. Craniofacial dysplasia-osteopenia syndrome.
PharmGKBiPA29928.

Polymorphism and mutation databases

BioMutaiIRX5.
DMDMi143811406.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 483483Iroquois-class homeodomain protein IRX-5PRO_0000049160Add
BLAST

Proteomic databases

EPDiP78411.
MaxQBiP78411.
PaxDbiP78411.
PRIDEiP78411.

PTM databases

iPTMnetiP78411.
PhosphoSiteiP78411.

Expressioni

Inductioni

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.

Gene expression databases

BgeeiP78411.
CleanExiHS_IRX5.
ExpressionAtlasiP78411. baseline and differential.
GenevisibleiP78411. HS.

Organism-specific databases

HPAiHPA047130.

Interactioni

Protein-protein interaction databases

STRINGi9606.ENSP00000378132.

Structurei

3D structure databases

ProteinModelPortaliP78411.
SMRiP78411. Positions 124-171.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi72 – 787Poly-Ala
Compositional biasi186 – 1927Poly-Glu
Compositional biasi320 – 3267Poly-Pro
Compositional biasi350 – 3534Poly-Gly

Sequence similaritiesi

Belongs to the TALE/IRO homeobox family.Curated
Contains 1 homeobox DNA-binding domain.PROSITE-ProRule annotation

Keywords - Domaini

Homeobox

Phylogenomic databases

eggNOGiKOG0773. Eukaryota.
ENOG410XPMQ. LUCA.
GeneTreeiENSGT00750000117365.
HOGENOMiHOG000234546.
HOVERGENiHBG006180.
InParanoidiP78411.
OMAiFGHLHSN.
OrthoDBiEOG7TJ3HS.
PhylomeDBiP78411.
TreeFamiTF319371.

Family and domain databases

Gene3Di1.10.10.60. 1 hit.
InterProiIPR017970. Homeobox_CS.
IPR001356. Homeobox_dom.
IPR008422. Homeobox_KN_domain.
IPR009057. Homeodomain-like.
IPR003893. Iroquois_homeo.
[Graphical view]
PfamiPF05920. Homeobox_KN. 1 hit.
[Graphical view]
SMARTiSM00389. HOX. 1 hit.
SM00548. IRO. 1 hit.
[Graphical view]
SUPFAMiSSF46689. SSF46689. 1 hit.
PROSITEiPS00027. HOMEOBOX_1. 1 hit.
PS50071. HOMEOBOX_2. 1 hit.
[Graphical view]

Sequences (3)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P78411-1) [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
MSYPQGYLYQ PSASLALYSC PAYSTSVISG PRTDELGRSS SGSAFSPYAG
60 70 80 90 100
STAFTAPSPG YNSHLQYGAD PAAAAAAAFS SYVGSPYDHT PGMAGSLGYH
110 120 130 140 150
PYAAPLGSYP YGDPAYRKNA TRDATATLKA WLNEHRKNPY PTKGEKIMLA
160 170 180 190 200
IITKMTLTQV STWFANARRR LKKENKMTWT PRNRSEDEEE EENIDLEKND
210 220 230 240 250
EDEPQKPEDK GDPEGPEAGG AEQKAASGCE RLQGPPTPAG KETEGSLSDS
260 270 280 290 300
DFKEPPSEGR LDALQGPPRT GGPSPAGPAA ARLAEDPAPH YPAGAPAPGP
310 320 330 340 350
HPAAGEVPPG PGGPSVIHSP PPPPPPAVLA KPKLWSLAEI ATSSDKVKDG
360 370 380 390 400
GGGNEGSPCP PCPGPIAGQA LGGSRASPAP APSRSPSAQC PFPGGTVLSR
410 420 430 440 450
PLYYTAPFYP GYTNYGSFGH LHGHPGPGPG PTTGPGSHFN GLNQTVLNRA
460 470 480
DALAKDPKML RSQSQLDLCK DSPYELKKGM SDI
Length:483
Mass (Da):50,361
Last modified:April 3, 2007 - v3
Checksum:i12E9397924EB5E6E
GO
Isoform 2 (identifier: P78411-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     219-219: Missing.

Show »
Length:482
Mass (Da):50,304
Checksum:iDCE0C504C7867851
GO
Isoform 3 (identifier: P78411-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-83: MSYPQGYLYQ...AAAAAFSSYV → MAVETTVHTHLSASPPQ

Show »
Length:417
Mass (Da):43,693
Checksum:i401F3BEA82CAE259
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti211 – 2111G → A in AAB50007 (PubMed:10370142).Curated
Sequence conflicti343 – 3431S → L in AAB50002 (PubMed:10370142).Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti150 – 1501A → P in HMMS; hypomorphic mutation. 1 Publication
VAR_068483
Natural varianti166 – 1661N → K in HMMS; hypomorphic mutation. 1 Publication
VAR_068484

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 8383MSYPQ…FSSYV → MAVETTVHTHLSASPPQ in isoform 3. 1 PublicationVSP_047363Add
BLAST
Alternative sequencei219 – 2191Missing in isoform 2. 1 PublicationVSP_047364

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY335944 Genomic DNA. Translation: AAQ16550.1.
AY335945 mRNA. Translation: AAQ16551.1.
U90304 mRNA. Translation: AAB50002.1.
U90309 mRNA. Translation: AAB50007.1.
AC106738 Genomic DNA. No translation available.
CCDSiCCDS10751.1. [P78411-1]
CCDS58462.1. [P78411-2]
RefSeqiNP_001239126.1. NM_001252197.1. [P78411-2]
NP_005844.4. NM_005853.5. [P78411-1]
UniGeneiHs.435730.

Genome annotation databases

EnsembliENST00000320990; ENSP00000316250; ENSG00000176842. [P78411-2]
ENST00000394636; ENSP00000378132; ENSG00000176842. [P78411-1]
ENST00000558597; ENSP00000453725; ENSG00000176842. [P78411-3]
GeneIDi10265.
KEGGihsa:10265.
UCSCiuc002ehv.4. human. [P78411-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY335944 Genomic DNA. Translation: AAQ16550.1.
AY335945 mRNA. Translation: AAQ16551.1.
U90304 mRNA. Translation: AAB50002.1.
U90309 mRNA. Translation: AAB50007.1.
AC106738 Genomic DNA. No translation available.
CCDSiCCDS10751.1. [P78411-1]
CCDS58462.1. [P78411-2]
RefSeqiNP_001239126.1. NM_001252197.1. [P78411-2]
NP_005844.4. NM_005853.5. [P78411-1]
UniGeneiHs.435730.

3D structure databases

ProteinModelPortaliP78411.
SMRiP78411. Positions 124-171.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi9606.ENSP00000378132.

PTM databases

iPTMnetiP78411.
PhosphoSiteiP78411.

Polymorphism and mutation databases

BioMutaiIRX5.
DMDMi143811406.

Proteomic databases

EPDiP78411.
MaxQBiP78411.
PaxDbiP78411.
PRIDEiP78411.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000320990; ENSP00000316250; ENSG00000176842. [P78411-2]
ENST00000394636; ENSP00000378132; ENSG00000176842. [P78411-1]
ENST00000558597; ENSP00000453725; ENSG00000176842. [P78411-3]
GeneIDi10265.
KEGGihsa:10265.
UCSCiuc002ehv.4. human. [P78411-1]

Organism-specific databases

CTDi10265.
GeneCardsiIRX5.
H-InvDBHIX0038585.
HGNCiHGNC:14361. IRX5.
HPAiHPA047130.
MalaCardsiIRX5.
MIMi606195. gene.
611174. phenotype.
neXtProtiNX_P78411.
Orphaneti314555. Craniofacial dysplasia-osteopenia syndrome.
PharmGKBiPA29928.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0773. Eukaryota.
ENOG410XPMQ. LUCA.
GeneTreeiENSGT00750000117365.
HOGENOMiHOG000234546.
HOVERGENiHBG006180.
InParanoidiP78411.
OMAiFGHLHSN.
OrthoDBiEOG7TJ3HS.
PhylomeDBiP78411.
TreeFamiTF319371.

Miscellaneous databases

GeneWikiiIRX5.
GenomeRNAii10265.
NextBioi35524829.
PROiP78411.
SOURCEiSearch...

Gene expression databases

BgeeiP78411.
CleanExiHS_IRX5.
ExpressionAtlasiP78411. baseline and differential.
GenevisibleiP78411. HS.

Family and domain databases

Gene3Di1.10.10.60. 1 hit.
InterProiIPR017970. Homeobox_CS.
IPR001356. Homeobox_dom.
IPR008422. Homeobox_KN_domain.
IPR009057. Homeodomain-like.
IPR003893. Iroquois_homeo.
[Graphical view]
PfamiPF05920. Homeobox_KN. 1 hit.
[Graphical view]
SMARTiSM00389. HOX. 1 hit.
SM00548. IRO. 1 hit.
[Graphical view]
SUPFAMiSSF46689. SSF46689. 1 hit.
PROSITEiPS00027. HOMEOBOX_1. 1 hit.
PS50071. HOMEOBOX_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  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] (ISOFORM 2).
  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] (ISOFORM 3), NUCLEOTIDE SEQUENCE [MRNA] OF 84-256 (ISOFORM 1/3).
  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. "The sequence and analysis of duplication-rich human chromosome 16."
    Martin J., Han C., Gordon L.A., Terry A., Prabhakar S., She X., Xie G., Hellsten U., Chan Y.M., Altherr M., Couronne O., Aerts A., Bajorek E., Black S., Blumer H., Branscomb E., Brown N.C., Bruno W.J.
    , Buckingham J.M., Callen D.F., Campbell C.S., Campbell M.L., Campbell E.W., Caoile C., Challacombe J.F., Chasteen L.A., Chertkov O., Chi H.C., Christensen M., Clark L.M., Cohn J.D., Denys M., Detter J.C., Dickson M., Dimitrijevic-Bussod M., Escobar J., Fawcett J.J., Flowers D., Fotopulos D., Glavina T., Gomez M., Gonzales E., Goodstein D., Goodwin L.A., Grady D.L., Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Hildebrand C.E., Huang W., Israni S., Jett J., Jewett P.B., Kadner K., Kimball H., Kobayashi A., Krawczyk M.-C., Leyba T., Longmire J.L., Lopez F., Lou Y., Lowry S., Ludeman T., Manohar C.F., Mark G.A., McMurray K.L., Meincke L.J., Morgan J., Moyzis R.K., Mundt M.O., Munk A.C., Nandkeshwar R.D., Pitluck S., Pollard M., Predki P., Parson-Quintana B., Ramirez L., Rash S., Retterer J., Ricke D.O., Robinson D.L., Rodriguez A., Salamov A., Saunders E.H., Scott D., Shough T., Stallings R.L., Stalvey M., Sutherland R.D., Tapia R., Tesmer J.G., Thayer N., Thompson L.S., Tice H., Torney D.C., Tran-Gyamfi M., Tsai M., Ulanovsky L.E., Ustaszewska A., Vo N., White P.S., Williams A.L., Wills P.L., Wu J.-R., Wu K., Yang J., DeJong P., Bruce D., Doggett N.A., Deaven L., Schmutz J., Grimwood J., Richardson P., Rokhsar D.S., Eichler E.E., Gilna P., Lucas S.M., Myers R.M., Rubin E.M., Pennacchio L.A.
    Nature 432:988-994(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  5. "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.

Entry informationi

Entry nameiIRX5_HUMAN
AccessioniPrimary (citable) accession number: P78411
Secondary accession number(s): H0YMS7, P78416, Q7Z2E1
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 15, 1998
Last sequence update: April 3, 2007
Last modified: March 16, 2016
This is version 133 of the entry and version 3 of the sequence. [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

Complete proteome, Reference proteome

Documents

  1. Human chromosome 16
    Human chromosome 16: 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. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.