IRX5_HUMAN
ID IRX5_HUMAN Reviewed; 483 AA.
AC P78411; H0YMS7; P78416; Q7Z2E1;
DT 15-JUL-1998, integrated into UniProtKB/Swiss-Prot.
DT 03-APR-2007, sequence version 3.
DT 03-AUG-2022, entry version 171.
DE RecName: Full=Iroquois-class homeodomain protein IRX-5;
DE AltName: Full=Homeodomain protein IRX-2A;
DE AltName: Full=Homeodomain protein IRXB2;
DE AltName: Full=Iroquois homeobox protein 5;
GN Name=IRX5; Synonyms=IRX2A, IRXB2;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 2).
RA Hansen L., Wu Q., Tommerup N.;
RT "Characterization of the human homeobox two-cluster Iroquois gene family.";
RL Submitted (JUL-2003) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3), AND NUCLEOTIDE SEQUENCE [MRNA] OF
RP 84-256 (ISOFORM 1/3).
RX PubMed=10370142; DOI=10.1007/s004410051316;
RA Lewis M.T., Ross S., Strickland P.A., Snyder C.J., Daniel C.W.;
RT "Regulated expression patterns of IRX-2, an Iroquois-class homeobox gene,
RT in the human breast.";
RL Cell Tissue Res. 296:549-554(1999).
RN [3]
RP DOWN-REGULATION BY 1,25-DIHYDROXYVITAMIN D3, AND POSSIBLE FUNCTION.
RX PubMed=18519790; DOI=10.1158/1078-0432.ccr-07-4649;
RA Myrthue A., Rademacher B.L.S., Pittsenbarger J., Kutyba-Brooks B.,
RA Gantner M., Qian D.Z., Beer T.M.;
RT "The iroquois homeobox gene 5 is regulated by 1,25-dihydroxyvitamin D3 in
RT human prostate cancer and regulates apoptosis and the cell cycle in LNCaP
RT prostate cancer cells.";
RL Clin. Cancer Res. 14:3562-3570(2008).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15616553; DOI=10.1038/nature03187;
RA Martin J., Han C., Gordon L.A., Terry A., Prabhakar S., She X., Xie G.,
RA Hellsten U., Chan Y.M., Altherr M., Couronne O., Aerts A., Bajorek E.,
RA Black S., Blumer H., Branscomb E., Brown N.C., Bruno W.J., Buckingham J.M.,
RA Callen D.F., Campbell C.S., Campbell M.L., Campbell E.W., Caoile C.,
RA Challacombe J.F., Chasteen L.A., Chertkov O., Chi H.C., Christensen M.,
RA Clark L.M., Cohn J.D., Denys M., Detter J.C., Dickson M.,
RA Dimitrijevic-Bussod M., Escobar J., Fawcett J.J., Flowers D., Fotopulos D.,
RA Glavina T., Gomez M., Gonzales E., Goodstein D., Goodwin L.A., Grady D.L.,
RA Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Hildebrand C.E.,
RA Huang W., Israni S., Jett J., Jewett P.B., Kadner K., Kimball H.,
RA Kobayashi A., Krawczyk M.-C., Leyba T., Longmire J.L., Lopez F., Lou Y.,
RA Lowry S., Ludeman T., Manohar C.F., Mark G.A., McMurray K.L., Meincke L.J.,
RA Morgan J., Moyzis R.K., Mundt M.O., Munk A.C., Nandkeshwar R.D.,
RA Pitluck S., Pollard M., Predki P., Parson-Quintana B., Ramirez L., Rash S.,
RA Retterer J., Ricke D.O., Robinson D.L., Rodriguez A., Salamov A.,
RA Saunders E.H., Scott D., Shough T., Stallings R.L., Stalvey M.,
RA Sutherland R.D., Tapia R., Tesmer J.G., Thayer N., Thompson L.S., Tice H.,
RA Torney D.C., Tran-Gyamfi M., Tsai M., Ulanovsky L.E., Ustaszewska A.,
RA Vo N., White P.S., Williams A.L., Wills P.L., Wu J.-R., Wu K., Yang J.,
RA DeJong P., Bruce D., Doggett N.A., Deaven L., Schmutz J., Grimwood J.,
RA Richardson P., Rokhsar D.S., Eichler E.E., Gilna P., Lucas S.M.,
RA Myers R.M., Rubin E.M., Pennacchio L.A.;
RT "The sequence and analysis of duplication-rich human chromosome 16.";
RL Nature 432:988-994(2004).
RN [5]
RP FUNCTION, VARIANTS HMMS PRO-150 AND LYS-166, AND CHARACTERIZATION OF
RP VARIANTS HMMS PRO-150 AND LYS-166.
RX PubMed=22581230; DOI=10.1038/ng.2259;
RA Bonnard C., Strobl A.C., Shboul M., Lee H., Merriman B., Nelson S.F.,
RA Ababneh O.H., Uz E., Guran T., Kayserili H., Hamamy H., Reversade B.;
RT "Mutations in IRX5 impair craniofacial development and germ cell migration
RT via SDF1.";
RL Nat. Genet. 44:709-713(2012).
RN [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-274 AND SER-464, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
CC -!- FUNCTION: Establishes the cardiac repolarization gradient by its
CC repressive actions on the KCND2 potassium-channel gene. Required for
CC retinal cone bipolar cell differentiation. May regulate contrast
CC adaptation in the retina and control specific aspects of visual
CC function in circuits of the mammalian retina (By similarity). Could be
CC involved in the regulation of both the cell cycle and apoptosis in
CC prostate cancer cells. Involved in craniofacial and gonadal
CC development. Modulates the migration of progenitor cell populations in
CC branchial arches and gonads by repressing CXCL12. {ECO:0000250,
CC ECO:0000269|PubMed:22581230}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000305}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=P78411-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P78411-2; Sequence=VSP_047364;
CC Name=3;
CC IsoId=P78411-3; Sequence=VSP_047363;
CC -!- INDUCTION: Down-regulated by 1,25-dihydroxyvitamin D3 in prostate
CC cancer samples from patients assigned to receive weekly high-dose 1,25-
CC dihydroxyvitamin D3 before radical prostatectomy. Also down-regulated
CC by 1,25-dihydroxyvitamin D3 in the human androgen-sensitive prostate
CC cancer cell line LNCaP and in the estrogen-sensitive breast cancer cell
CC line MCF-7.
CC -!- DISEASE: Hamamy syndrome (HMMS) [MIM:611174]: A syndrome characterized
CC by severe hypertelorism, upslanting palpebral fissures, brachycephaly,
CC abnormal ears, sloping shoulders, enamel hypoplasia, and osteopenia
CC with repeated fractures. Additional features include myopia, mild to
CC moderate sensorineural hearing loss, gonadal anomalies and borderline
CC intelligence. {ECO:0000269|PubMed:22581230}. Note=The disease is caused
CC by variants affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the TALE/IRO homeobox family. {ECO:0000305}.
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DR EMBL; AY335944; AAQ16550.1; -; Genomic_DNA.
DR EMBL; AY335945; AAQ16551.1; -; mRNA.
DR EMBL; U90304; AAB50002.1; -; mRNA.
DR EMBL; U90309; AAB50007.1; -; mRNA.
DR EMBL; AC106738; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR CCDS; CCDS10751.1; -. [P78411-1]
DR CCDS; CCDS58462.1; -. [P78411-2]
DR RefSeq; NP_001239126.1; NM_001252197.1. [P78411-2]
DR RefSeq; NP_005844.4; NM_005853.5. [P78411-1]
DR AlphaFoldDB; P78411; -.
DR SMR; P78411; -.
DR BioGRID; 115556; 4.
DR STRING; 9606.ENSP00000378132; -.
DR iPTMnet; P78411; -.
DR PhosphoSitePlus; P78411; -.
DR BioMuta; IRX5; -.
DR DMDM; 143811406; -.
DR EPD; P78411; -.
DR jPOST; P78411; -.
DR MassIVE; P78411; -.
DR MaxQB; P78411; -.
DR PaxDb; P78411; -.
DR PeptideAtlas; P78411; -.
DR PRIDE; P78411; -.
DR ProteomicsDB; 40345; -.
DR ProteomicsDB; 57616; -. [P78411-1]
DR Antibodypedia; 14623; 222 antibodies from 22 providers.
DR DNASU; 10265; -.
DR Ensembl; ENST00000320990.9; ENSP00000316250.5; ENSG00000176842.16. [P78411-2]
DR Ensembl; ENST00000394636.9; ENSP00000378132.4; ENSG00000176842.16. [P78411-1]
DR GeneID; 10265; -.
DR KEGG; hsa:10265; -.
DR MANE-Select; ENST00000394636.9; ENSP00000378132.4; NM_005853.6; NP_005844.4.
DR UCSC; uc002ehv.4; human. [P78411-1]
DR CTD; 10265; -.
DR DisGeNET; 10265; -.
DR GeneCards; IRX5; -.
DR HGNC; HGNC:14361; IRX5.
DR HPA; ENSG00000176842; Tissue enhanced (breast, salivary gland, skin).
DR MalaCards; IRX5; -.
DR MIM; 606195; gene.
DR MIM; 611174; phenotype.
DR neXtProt; NX_P78411; -.
DR OpenTargets; ENSG00000176842; -.
DR Orphanet; 314555; Facial dysmorphism-ocular anomalies-osteopenia-intellectual disability-dental anomalies syndrome.
DR PharmGKB; PA29928; -.
DR VEuPathDB; HostDB:ENSG00000176842; -.
DR eggNOG; KOG0773; Eukaryota.
DR GeneTree; ENSGT00940000159483; -.
DR HOGENOM; CLU_048118_0_0_1; -.
DR InParanoid; P78411; -.
DR OMA; PSEGRHD; -.
DR OrthoDB; 768315at2759; -.
DR PhylomeDB; P78411; -.
DR TreeFam; TF319371; -.
DR PathwayCommons; P78411; -.
DR SignaLink; P78411; -.
DR SIGNOR; P78411; -.
DR BioGRID-ORCS; 10265; 16 hits in 1100 CRISPR screens.
DR ChiTaRS; IRX5; human.
DR GeneWiki; IRX5; -.
DR GenomeRNAi; 10265; -.
DR Pharos; P78411; Tbio.
DR PRO; PR:P78411; -.
DR Proteomes; UP000005640; Chromosome 16.
DR RNAct; P78411; protein.
DR Bgee; ENSG00000176842; Expressed in upper leg skin and 106 other tissues.
DR ExpressionAtlas; P78411; baseline and differential.
DR Genevisible; P78411; HS.
DR GO; GO:0000785; C:chromatin; ISA:NTNU_SB.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; ISA:NTNU_SB.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IBA:GO_Central.
DR GO; GO:1990837; F:sequence-specific double-stranded DNA binding; IDA:ARUK-UCL.
DR GO; GO:0005499; F:vitamin D binding; IEA:UniProtKB-KW.
DR GO; GO:0048468; P:cell development; IBA:GO_Central.
DR GO; GO:0048701; P:embryonic cranial skeleton morphogenesis; IMP:UniProtKB.
DR GO; GO:0008406; P:gonad development; IMP:UniProtKB.
DR GO; GO:0030182; P:neuron differentiation; IBA:GO_Central.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0050896; P:response to stimulus; IEA:UniProtKB-KW.
DR GO; GO:0007601; P:visual perception; IEA:UniProtKB-KW.
DR CDD; cd00086; homeodomain; 1.
DR InterPro; IPR009057; Homeobox-like_sf.
DR InterPro; IPR017970; Homeobox_CS.
DR InterPro; IPR001356; Homeobox_dom.
DR InterPro; IPR008422; Homeobox_KN_domain.
DR InterPro; IPR003893; Iroquois_homeo.
DR Pfam; PF05920; Homeobox_KN; 1.
DR SMART; SM00389; HOX; 1.
DR SMART; SM00548; IRO; 1.
DR SUPFAM; SSF46689; SSF46689; 1.
DR PROSITE; PS00027; HOMEOBOX_1; 1.
DR PROSITE; PS50071; HOMEOBOX_2; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Disease variant; DNA-binding; Homeobox;
KW Intellectual disability; Nucleus; Phosphoprotein; Reference proteome;
KW Sensory transduction; Transcription; Vision; Vitamin D.
FT CHAIN 1..483
FT /note="Iroquois-class homeodomain protein IRX-5"
FT /id="PRO_0000049160"
FT DNA_BIND 113..175
FT /note="Homeobox; TALE-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00108"
FT REGION 177..392
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 423..442
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 199..217
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 291..330
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 274
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 464
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT VAR_SEQ 1..83
FT /note="MSYPQGYLYQPSASLALYSCPAYSTSVISGPRTDELGRSSSGSAFSPYAGST
FT AFTAPSPGYNSHLQYGADPAAAAAAAFSSYV -> MAVETTVHTHLSASPPQ (in
FT isoform 3)"
FT /evidence="ECO:0000303|PubMed:10370142"
FT /id="VSP_047363"
FT VAR_SEQ 219
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|Ref.1"
FT /id="VSP_047364"
FT VARIANT 150
FT /note="A -> P (in HMMS; hypomorphic mutation;
FT dbSNP:rs387907198)"
FT /evidence="ECO:0000269|PubMed:22581230"
FT /id="VAR_068483"
FT VARIANT 166
FT /note="N -> K (in HMMS; hypomorphic mutation;
FT dbSNP:rs786200931)"
FT /evidence="ECO:0000269|PubMed:22581230"
FT /id="VAR_068484"
FT CONFLICT 211
FT /note="G -> A (in Ref. 2; AAB50007)"
FT /evidence="ECO:0000305"
FT CONFLICT 343
FT /note="S -> L (in Ref. 2; AAB50002)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 483 AA; 50361 MW; 12E9397924EB5E6E CRC64;
MSYPQGYLYQ PSASLALYSC PAYSTSVISG PRTDELGRSS SGSAFSPYAG STAFTAPSPG
YNSHLQYGAD PAAAAAAAFS SYVGSPYDHT PGMAGSLGYH PYAAPLGSYP YGDPAYRKNA
TRDATATLKA WLNEHRKNPY PTKGEKIMLA IITKMTLTQV STWFANARRR LKKENKMTWT
PRNRSEDEEE EENIDLEKND EDEPQKPEDK GDPEGPEAGG AEQKAASGCE RLQGPPTPAG
KETEGSLSDS DFKEPPSEGR LDALQGPPRT GGPSPAGPAA ARLAEDPAPH YPAGAPAPGP
HPAAGEVPPG PGGPSVIHSP PPPPPPAVLA KPKLWSLAEI ATSSDKVKDG GGGNEGSPCP
PCPGPIAGQA LGGSRASPAP APSRSPSAQC PFPGGTVLSR PLYYTAPFYP GYTNYGSFGH
LHGHPGPGPG PTTGPGSHFN GLNQTVLNRA DALAKDPKML RSQSQLDLCK DSPYELKKGM
SDI
