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LIM/homeobox protein Lhx4 (LIM homeobox protein 4)

 LHX4_HUMAN              Reviewed;         390 AA.
Q969G2; Q8NHE0; Q8NHM1; Q8TCJ1; Q8WWX2; Q969W2;
23-JAN-2002, integrated into UniProtKB/Swiss-Prot.
14-OCT-2008, sequence version 2.
22-NOV-2017, entry version 162.
RecName: Full=LIM/homeobox protein Lhx4;
Short=LIM homeobox protein 4;
Name=LHX4;
Homo sapiens (Human).
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
Catarrhini; Hominidae; Homo.
NCBI_TaxID=9606;
[1]
NUCLEOTIDE SEQUENCE [MRNA], AND CHROMOSOMAL TRANSLOCATION WITH IGHG1.
PubMed=12118377; DOI=10.1038/sj.onc.1205628;
Kawamata N., Sakajiri S., Sugimoto K.J., Isobe Y., Kobayashi H.,
Oshimi K.;
"A novel chromosomal translocation t(1;14)(q25;q32) in pre-B acute
lymphoblastic leukemia involves the LIM homeodomain protein gene,
Lhx4.";
Oncogene 21:4983-4991(2002).
[2]
NUCLEOTIDE SEQUENCE [MRNA].
Liu Y., Zhou Y., Wang J., Yuan J., Qiang B., Fan M.;
"Isolation and cloning of a novel cDNA encoding human LIM homeobox 4
protein.";
Submitted (AUG-1999) to the EMBL/GenBank/DDBJ databases.
[3]
NUCLEOTIDE SEQUENCE [GENOMIC DNA].
Machinis K., Pantel J., Duquesnoy P., Netchine I., Sobrier M.-L.,
Dastot F., Amselem S.;
"Human LIM homeobox protein 4 (LHX4) gene.";
Submitted (AUG-2001) to the EMBL/GenBank/DDBJ databases.
[4]
NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
PubMed=16710414; DOI=10.1038/nature04727;
Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D.,
Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A.,
Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F.,
McDonald L., Evans R., Phillips K., Atkinson A., Cooper R., Jones C.,
Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P.,
Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K.,
Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G.,
Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D.,
Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G.,
Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J.,
Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R.,
Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D.,
Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G.,
Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M.,
Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J.,
Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M.,
Loveland J., Lovell J., Lush M.J., Lyne R., Martin S.,
Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S.,
Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C.,
Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z.,
Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E.,
Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A.,
Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R.,
Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V.,
Beck S., Rogers J., Bentley D.R.;
"The DNA sequence and biological annotation of human chromosome 1.";
Nature 441:315-321(2006).
[5]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
TISSUE=Muscle;
PubMed=15489334; DOI=10.1101/gr.2596504;
The MGC Project Team;
"The status, quality, and expansion of the NIH full-length cDNA
project: the Mammalian Gene Collection (MGC).";
Genome Res. 14:2121-2127(2004).
[6]
NUCLEOTIDE SEQUENCE [MRNA] OF 23-390.
TISSUE=Placenta;
Muraki T., Nakamura K., Sakai T.;
Submitted (FEB-2001) to the EMBL/GenBank/DDBJ databases.
[7]
NUCLEOTIDE SEQUENCE [MRNA] OF 24-390, NUCLEOTIDE SEQUENCE [GENOMIC
DNA] OF 152-390, AND DISEASE.
PubMed=11567216; DOI=10.1086/323764;
Machinis K., Pantel J., Netchine I., Leger J., Camand O.J.A.,
Sobrier M.-L., Dastot-Le Moal F., Duquesnoy P., Abitbol M.,
Czernichow P., Amselem S.;
"Syndromic short stature in patients with a germline mutation in the
LIM homeobox LHX4.";
Am. J. Hum. Genet. 69:961-968(2001).
[8]
VARIANT CPHD4 THR-389.
PubMed=17527005; DOI=10.1507/endocrj.K06-200;
Tajima T., Hattori T., Nakajima T., Okuhara K., Tsubaki J.,
Fujieda K.;
"A novel missense mutation (P366T) of the LHX4 gene causes severe
combined pituitary hormone deficiency with pituitary hypoplasia,
ectopic posterior lobe and a poorly developed sella turcica.";
Endocr. J. 54:637-641(2007).
[9]
VARIANTS CPHD4 CYS-84; ARG-190 AND PRO-210, AND CHARACTERIZATION OF
VARIANTS CPHD4 CYS-84; ARG-190 AND PRO-210.
PubMed=18073311; DOI=10.1210/jc.2007-1525;
Pfaeffle R.W., Hunter C.S., Savage J.J., Duran-Prado M., Mullen R.D.,
Neeb Z.P., Eiholzer U., Hesse V., Haddad N.G., Stobbe H.M., Blum W.F.,
Weigel J.F.W., Rhodes S.J.;
"Three novel missense mutations within the LHX4 gene are associated
with variable pituitary hormone deficiencies.";
J. Clin. Endocrinol. Metab. 93:1062-1071(2008).
-!- FUNCTION: May play a critical role in the development of
respiratory control mechanisms and in the normal growth and
maturation of the lung. {ECO:0000250}.
-!- INTERACTION:
Q9Y6H1:CHCHD2; NbExp=3; IntAct=EBI-2865388, EBI-2321769;
Q5QP82:DCAF10; NbExp=4; IntAct=EBI-2865388, EBI-723230;
Q6P4F2:FDX2; NbExp=3; IntAct=EBI-2865388, EBI-10252800;
Q17RB8:LONRF1; NbExp=3; IntAct=EBI-2865388, EBI-2341787;
Q9Y5N6:ORC6; NbExp=5; IntAct=EBI-2865388, EBI-374840;
P28069:POU1F1; NbExp=4; IntAct=EBI-2865388, EBI-8673859;
O60880:SH2D1A; NbExp=7; IntAct=EBI-2865388, EBI-6983382;
Q9BV90:SNRNP25; NbExp=5; IntAct=EBI-2865388, EBI-9675976;
Q86UY0:TXNDC5; NbExp=3; IntAct=EBI-2865388, EBI-2825190;
O75604:USP2; NbExp=3; IntAct=EBI-2865388, EBI-743272;
-!- SUBCELLULAR LOCATION: Nucleus {ECO:0000255|PROSITE-
ProRule:PRU00108}.
-!- DISEASE: Pituitary hormone deficiency, combined, 4 (CPHD4)
[MIM:262700]: Combined pituitary hormone deficiency is defined as
the impaired production of growth hormone and one or more of the
other five anterior pituitary hormones. CPHD4 is characterized by
complete or partial deficiencies of growth hormone, thyroid-
stimulating hormone, luteinizing hormone, follicle stimulating
hormone and adrenocorticotropic hormone. Clinical features include
short stature, cerebellar defects, and small sella turcica.
{ECO:0000269|PubMed:17527005, ECO:0000269|PubMed:18073311}.
Note=The disease is caused by mutations affecting the gene
represented in this entry.
-!- DISEASE: Note=A chromosomal aberration involving LHX4 may be a
cause of acute lymphoblastic leukemia. Translocation
t(1;14)(q25;q32) with IGHG1. {ECO:0000269|PubMed:11567216}.
-!- SEQUENCE CAUTION:
Sequence=BAB62817.1; Type=Erroneous initiation; Note=Translation N-terminally extended.; Evidence={ECO:0000305};
-----------------------------------------------------------------------
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-----------------------------------------------------------------------
EMBL; AY053457; AAL07260.1; -; mRNA.
EMBL; AF179849; AAK70923.1; -; mRNA.
EMBL; AF405430; AAM91896.1; -; Genomic_DNA.
EMBL; AF405425; AAM91896.1; JOINED; Genomic_DNA.
EMBL; AF405426; AAM91896.1; JOINED; Genomic_DNA.
EMBL; AF405427; AAM91896.1; JOINED; Genomic_DNA.
EMBL; AF405428; AAM91896.1; JOINED; Genomic_DNA.
EMBL; AF405429; AAM91896.1; JOINED; Genomic_DNA.
EMBL; AL139141; -; NOT_ANNOTATED_CDS; Genomic_DNA.
EMBL; BC011759; AAH11759.1; -; mRNA.
EMBL; AB055703; BAB62817.1; ALT_INIT; mRNA.
EMBL; AB037683; BAC01272.1; -; mRNA.
EMBL; AF282899; AAK69169.1; -; mRNA.
EMBL; AH011598; AAM19349.1; -; Genomic_DNA.
CCDS; CCDS1338.1; -.
RefSeq; NP_203129.1; NM_033343.3.
UniGene; Hs.658487; -.
PDB; 5HOD; X-ray; 2.68 A; A/D=156-216.
PDBsum; 5HOD; -.
ProteinModelPortal; Q969G2; -.
SMR; Q969G2; -.
BioGrid; 124635; 32.
DIP; DIP-29454N; -.
IntAct; Q969G2; 42.
STRING; 9606.ENSP00000263726; -.
iPTMnet; Q969G2; -.
PhosphoSitePlus; Q969G2; -.
BioMuta; LHX4; -.
DMDM; 209572644; -.
PaxDb; Q969G2; -.
PeptideAtlas; Q969G2; -.
PRIDE; Q969G2; -.
DNASU; 89884; -.
Ensembl; ENST00000263726; ENSP00000263726; ENSG00000121454.
GeneID; 89884; -.
KEGG; hsa:89884; -.
UCSC; uc001goe.3; human.
CTD; 89884; -.
DisGeNET; 89884; -.
EuPathDB; HostDB:ENSG00000121454.5; -.
GeneCards; LHX4; -.
HGNC; HGNC:21734; LHX4.
HPA; HPA055705; -.
MalaCards; LHX4; -.
MIM; 262700; phenotype.
MIM; 602146; gene.
neXtProt; NX_Q969G2; -.
OpenTargets; ENSG00000121454; -.
Orphanet; 226307; Hypothyroidism due to deficient transcription factors involved in pituitary development or function.
Orphanet; 95496; Pituitary stalk interruption syndrome.
Orphanet; 85442; Short stature - pituitary and cerebellar defects - small sella turcica.
PharmGKB; PA134962876; -.
eggNOG; KOG4577; Eukaryota.
eggNOG; ENOG410XPDC; LUCA.
GeneTree; ENSGT00760000118921; -.
HOGENOM; HOG000231629; -.
HOVERGEN; HBG006263; -.
InParanoid; Q969G2; -.
KO; K09374; -.
OMA; CSQHILD; -.
OrthoDB; EOG091G0BSD; -.
PhylomeDB; Q969G2; -.
TreeFam; TF315442; -.
Reactome; R-HSA-9010553; Regulation of expression of SLITs and ROBOs.
SIGNOR; Q969G2; -.
GeneWiki; LHX4; -.
GenomeRNAi; 89884; -.
PRO; PR:Q969G2; -.
Proteomes; UP000005640; Chromosome 1.
Bgee; ENSG00000121454; -.
CleanEx; HS_LHX4; -.
ExpressionAtlas; Q969G2; baseline and differential.
Genevisible; Q969G2; HS.
GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
GO; GO:0043565; F:sequence-specific DNA binding; IDA:NTNU_SB.
GO; GO:0001228; F:transcriptional activator activity, RNA polymerase II transcription regulatory region sequence-specific binding; IC:NTNU_SB.
GO; GO:0009887; P:animal organ morphogenesis; IEA:Ensembl.
GO; GO:0021526; P:medial motor column neuron differentiation; IEA:Ensembl.
GO; GO:0008045; P:motor neuron axon guidance; IEA:Ensembl.
GO; GO:0043066; P:negative regulation of apoptotic process; IEA:Ensembl.
GO; GO:0001890; P:placenta development; IEA:Ensembl.
GO; GO:0045944; P:positive regulation of transcription from RNA polymerase II promoter; IDA:NTNU_SB.
CDD; cd00086; homeodomain; 1.
InterPro; IPR009057; Homeobox-like_sf.
InterPro; IPR017970; Homeobox_CS.
InterPro; IPR001356; Homeobox_dom.
InterPro; IPR001781; Znf_LIM.
Pfam; PF00046; Homeobox; 1.
Pfam; PF00412; LIM; 2.
SMART; SM00389; HOX; 1.
SMART; SM00132; LIM; 2.
SUPFAM; SSF46689; SSF46689; 1.
PROSITE; PS00027; HOMEOBOX_1; 1.
PROSITE; PS50071; HOMEOBOX_2; 1.
PROSITE; PS00478; LIM_DOMAIN_1; 2.
PROSITE; PS50023; LIM_DOMAIN_2; 2.
1: Evidence at protein level;
3D-structure; Chromosomal rearrangement; Complete proteome;
Disease mutation; DNA-binding; Dwarfism; Homeobox; LIM domain;
Metal-binding; Nucleus; Phosphoprotein; Polymorphism; Proto-oncogene;
Reference proteome; Repeat; Transcription; Transcription regulation;
Zinc.
CHAIN 1 390 LIM/homeobox protein Lhx4.
/FTId=PRO_0000075787.
DOMAIN 28 87 LIM zinc-binding 1. {ECO:0000255|PROSITE-
ProRule:PRU00125}.
DOMAIN 88 150 LIM zinc-binding 2. {ECO:0000255|PROSITE-
ProRule:PRU00125}.
DNA_BIND 157 216 Homeobox. {ECO:0000255|PROSITE-
ProRule:PRU00108}.
MOD_RES 70 70 Phosphoserine.
{ECO:0000250|UniProtKB:Q9UBR4}.
MOD_RES 234 234 Phosphoserine.
{ECO:0000250|UniProtKB:Q9UBR4}.
MOD_RES 238 238 Phosphoserine.
{ECO:0000250|UniProtKB:Q9UBR4}.
VARIANT 84 84 R -> C (in CPHD4; has impaired activity
on CGA, POU1F1 and TSHB promoters but
exhibits normal DNA binding to the CGA
pituitary glycoprotein basal element
(PGBE) and interaction with the POU1F1
protein; dbSNP:rs121912642).
{ECO:0000269|PubMed:18073311}.
/FTId=VAR_058715.
VARIANT 190 190 L -> R (in CPHD4; the mutant protein is
inactive in DNA binding and pituitary
gene activation assays;
dbSNP:rs121912643).
{ECO:0000269|PubMed:18073311}.
/FTId=VAR_058716.
VARIANT 210 210 A -> P (in CPHD4; the mutant protein is
inactive in DNA binding and pituitary
gene activation assays;
dbSNP:rs121912641).
{ECO:0000269|PubMed:18073311}.
/FTId=VAR_058717.
VARIANT 328 328 N -> S (in dbSNP:rs7536561).
/FTId=VAR_046661.
VARIANT 389 389 P -> T (in CPHD4; dbSNP:rs145433128).
{ECO:0000269|PubMed:17527005}.
/FTId=VAR_063241.
CONFLICT 335 335 D -> G (in Ref. 1; AAL07260).
{ECO:0000305}.
HELIX 165 176 {ECO:0000244|PDB:5HOD}.
HELIX 184 194 {ECO:0000244|PDB:5HOD}.
HELIX 198 214 {ECO:0000244|PDB:5HOD}.
SEQUENCE 390 AA; 43124 MW; 6499F38E78B79FD1 CRC64;
MMQSATVPAE GAVKGLPEML GVPMQQIPQC AGCNQHILDK FILKVLDRHW HSSCLKCADC
QMQLADRCFS RAGSVYCKED FFKRFGTKCT ACQQGIPPTQ VVRKAQDFVY HLHCFACIIC
NRQLATGDEF YLMEDGRLVC KEDYETAKQN DDSEAGAKRP RTTITAKQLE TLKNAYKNSP
KPARHVREQL SSETGLDMRV VQVWFQNRRA KEKRLKKDAG RHRWGQFYKS VKRSRGSSKQ
EKESSAEDCG VSDSELSFRE DQILSELGHT NRIYGNVGDV TGGQLMNGSF SMDGTGQSYQ
DLRDGSPYGI PQSPSSISSL PSHAPLLNGL DYTVDSNLGI IAHAGQGVSQ TLRAMAGGPT
SDISTGSSVG YPDFPTSPGS WLDEMDHPPF


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