ID PIT1_HUMAN Reviewed; 291 AA. AC P28069; O75757; Q15132; Q15133; Q9UD34; Q9UEL3; DT 01-AUG-1992, integrated into UniProtKB/Swiss-Prot. DT 01-AUG-1992, sequence version 1. DT 27-MAR-2024, entry version 223. DE RecName: Full=Pituitary-specific positive transcription factor 1; DE Short=PIT-1; DE AltName: Full=Growth hormone factor 1; DE Short=GHF-1; GN Name=POU1F1; Synonyms=GHF1, PIT1; 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 [MRNA] (ISOFORM B). RC TISSUE=Pituitary anterior lobe; RX PubMed=1956794; DOI=10.1093/nar/19.22.6329; RA Lew A.M., Elsholtz H.P.; RT "Cloning of the human cDNA for transcription factor Pit-1."; RL Nucleic Acids Res. 19:6329-6329(1991). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM B). RX PubMed=1370379; DOI=10.1016/0167-4781(92)90494-k; RA Tatsumi K.I., Notomi T., Amino N., Miyai K.; RT "Nucleotide sequence of the complementary DNA for human Pit-1/GHF-1."; RL Biochim. Biophys. Acta 1129:231-234(1992). RN [3] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM A). RA Tatsumi K., Notomi T., Irie Y., Endo Y., Onogi S., Amino N., Miyai K.; RT "The structure and the chromosomal location of the human PIT1 gene."; RL Submitted (AUG-1992) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-71, AND ALTERNATIVE SPLICING RP (ISOFORM A). RC TISSUE=Placenta; RX PubMed=7721104; DOI=10.1016/0378-1119(94)00757-j; RA Delhase M., Vila V., Hooghe-Peters E.L., Castrillo J.-L.; RT "A novel pituitary transcription factor is produced by alternative splicing RT of the human GHF-1/PIT-1 gene."; RL Gene 155:273-275(1995). RN [5] RP SEQUENCE REVISION. RA Delhase M.; RL Submitted (DEC-2010) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-47. RX PubMed=1487156; DOI=10.1016/0378-1119(92)90234-g; RA Ohta K., Nobukuni Y., Mitsubuchi H., Ohta T., Tohma T., Jinno Y., Endo F., RA Matsuda I.; RT "Characterization of the gene encoding human pituitary-specific RT transcription factor, Pit-1."; RL Gene 122:387-388(1992). RN [7] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 214-273, VARIANT CPHD1 TRP-271, AND RP INVOLVEMENT IN CPHD1. RX PubMed=7852536; DOI=10.1210/jcem.80.2.7852536; RA Cohen L.E., Wondisford F.E., Salvatoni A., Maghnie M., Brucker-Davis F., RA Weintraub B.D., Radovick S.; RT "A 'hot spot' in the Pit-1 gene responsible for combined pituitary hormone RT deficiency: clinical and molecular correlates."; RL J. Clin. Endocrinol. Metab. 80:679-684(1995). RN [8] RP 9AATAD MOTIF. RX PubMed=34342803; DOI=10.1007/s12015-021-10225-8; RA Piskacek M., Otasevic T., Repko M., Knight A.; RT "The 9aaTAD Activation Domains in the Yamanaka Transcription Factors Oct4, RT Sox2, Myc, and Klf4."; RL Stem. Cell. Rev. Rep. 17:1934-1936(2021). RN [9] RP VARIANTS CPHD1 LEU-24; GLN-143 AND TRP-271. RX PubMed=1472057; DOI=10.1016/0006-291x(92)92281-2; RA Ohta K., Nobukuni Y., Mitsubuchi H., Fujimoto S., Matsuo N., Inagaki H., RA Endo F., Matsuda I.; RT "Mutations in the Pit-1 gene in children with combined pituitary hormone RT deficiency."; RL Biochem. Biophys. Res. Commun. 189:851-855(1992). RN [10] RP VARIANT CPHD1 TRP-271. RX PubMed=1509262; DOI=10.1126/science.257.5073.1115; RA Radovick S., Nations M., Du Y., Berg L.A., Weintraub B.D., Wondisford F.E.; RT "A mutation in the POU-homeodomain of Pit-1 responsible for combined RT pituitary hormone deficiency."; RL Science 257:1115-1118(1992). RN [11] RP VARIANT CPHD1 PRO-158. RX PubMed=1509263; DOI=10.1126/science.257.5073.1118; RA Pfaeffle R.W., DiMattia G.E., Parks J.S., Brown M.R., Wit J.M., Jansen M., RA van der Nat H., van den Brande J.L., Rosenfeld M.G., Ingraham H.A.; RT "Mutation of the POU-specific domain of Pit-1 and hypopituitarism without RT pituitary hypoplasia."; RL Science 257:1118-1121(1992). RN [12] RP VARIANTS ARG-4 AND TYR-227. RC TISSUE=Pituitary; RX PubMed=8346040; DOI=10.1093/nar/21.15.3584; RA Pernasetti F.M., Wera S., Belayew A., Martial J.A.; RT "Cloning of a human GHF-1/Pit-1 cDNA variant."; RL Nucleic Acids Res. 21:3584-3584(1993). RN [13] RP VARIANT CPHD1 CYS-135. RX PubMed=8768831; DOI=10.1210/jcem.81.8.8768831; RA Pellegrini-Bouiller I., Belicar P., Barlier A., Gunz G., Charvet J.P., RA Jaquet P., Brue T., Vialettes B., Enjalbert A.; RT "A new mutation of the gene encoding the transcription factor Pit-1 is RT responsible for combined pituitary hormone deficiency."; RL J. Clin. Endocrinol. Metab. 81:2790-2796(1996). RN [14] RP VARIANT CPHD1 GLY-174. RX PubMed=9485179; DOI=10.1159/000023134; RA Brown M.R., Parks J.S., Adess M.E., Rich B.H., Rosenthal I.M., Voss T.C., RA VanderHeyden T.C., Hurley D.L.; RT "Central hypothyroidism reveals compound heterozygous mutations in the Pit- RT 1 gene."; RL Horm. Res. 49:98-102(1998). RN [15] RP VARIANT CPHD1 SER-239. RX PubMed=9626142; DOI=10.1210/jcem.83.6.4901; RA Pernasetti F.M., Milner R.D.G., Al-Ashwal A.A.Z., de Zegher F., RA Chavez V.M., Muller M., Martial J.A.; RT "Pro239Ser: a novel recessive mutation of the Pit-1 gene in seven Middle RT Eastern children with growth hormone, prolactin, and thyrotropin RT deficiency."; RL J. Clin. Endocrinol. Metab. 83:2079-2083(1998). RN [16] RP VARIANT CPHD1 ARG-193. RX PubMed=11297581; DOI=10.1210/jcem.86.4.7371; RA Hendriks-Stegeman B.I., Augustijn K.D., Bakker B., Holthuizen P., RA van der Vliet P.C., Jansen M.; RT "Combined pituitary hormone deficiency caused by compound heterozygosity RT for two novel mutations in the POU domain of the PIT1/POU1F1 gene."; RL J. Clin. Endocrinol. Metab. 86:1545-1550(2001). RN [17] RP VARIANTS CPHD1 GLN-172; LYS-230 AND TRP-271, AND CHARACTERIZATION OF RP VARIANTS CPHD1 GLN-172 AND LYS-230. RX PubMed=15928241; DOI=10.1210/jc.2005-0570; RA Turton J.P.G., Reynaud R., Mehta A., Torpiano J., Saveanu A., Woods K.S., RA Tiulpakov A., Zdravkovic V., Hamilton J., Attard-Montalto S., RA Parascandalo R., Vella C., Clayton P.E., Shalet S., Barton J., Brue T., RA Dattani M.T.; RT "Novel mutations within the POU1F1 gene associated with variable combined RT pituitary hormone deficiency."; RL J. Clin. Endocrinol. Metab. 90:4762-4770(2005). RN [18] RP VARIANT CPHD1 ARG-179, AND CHARACTERIZATION OF VARIANT CPHD1 ARG-179. RX PubMed=16968807; DOI=10.1210/jc.2005-2289; RA Miyata I., Vallette-Kasic S., Saveanu A., Takeuchi M., Yoshikawa H., RA Tajima A., Tojo K., Reynaud R., Gueydan M., Enjalbert A., Tajima N., RA Eto Y., Brue T.; RT "Identification and functional analysis of the novel S179R POU1F1 mutation RT associated with combined pituitary hormone deficiency."; RL J. Clin. Endocrinol. Metab. 91:4981-4987(2006). RN [19] RP VARIANT CPHD1 TRP-265, CHARACTERIZATION OF VARIANT CPHD1 TRP-265, AND RP FUNCTION. RX PubMed=22010633; DOI=10.1111/j.1365-2265.2011.04236.x; RA Turton J.P., Strom M., Langham S., Dattani M.T., Le Tissier P.; RT "Two novel mutations in the POU1F1 gene generate null alleles through RT different mechanisms leading to c ombined pituitary hormone deficiency."; RL Clin. Endocrinol. (Oxf.) 76:387-393(2012). RN [20] RP VARIANT CPHD1 LEU-76, CHARACTERIZATION OF VARIANT CPHD1 LEU-76, FUNCTION, RP INTERACTION WITH ELK1; LHX3 AND PITX1, DNA-BINDING, SUBCELLULAR LOCATION, RP AND MUTAGENESIS OF LEU-74; THR-75; PRO-76; CYS-77 AND LEU-78. RX PubMed=26612202; DOI=10.1093/hmg/ddv486; RA Sobrier M.L., Tsai Y.C., Perez C., Leheup B., Bouceba T., Duquesnoy P., RA Copin B., Sizova D., Penzo A., Stanger B.Z., Cooke N.E., Liebhaber S.A., RA Amselem S.; RT "Functional characterization of a human POU1F1 mutation associated with RT isolated growth hormone deficiency: a novel etiology for IGHD."; RL Hum. Mol. Genet. 25:472-483(2016). CC -!- FUNCTION: Transcription factor involved in the specification of the CC lactotrope, somatotrope, and thyrotrope phenotypes in the developing CC anterior pituitary. Specifically binds to the consensus sequence 5'- CC TAAAT-3'. Activates growth hormone and prolactin genes CC (PubMed:22010633, PubMed:26612202). {ECO:0000269|PubMed:22010633, CC ECO:0000269|PubMed:26612202}. CC -!- SUBUNIT: Interacts with PITX1 (PubMed:26612202). Interacts with LHX3 CC (PubMed:26612202). Interacts with ELK1 (PubMed:26612202). CC {ECO:0000269|PubMed:26612202}. CC -!- INTERACTION: CC P28069; Q03989: ARID5A; NbExp=3; IntAct=EBI-8673859, EBI-948603; CC P28069; P15289: ARSA; NbExp=3; IntAct=EBI-8673859, EBI-2117357; CC P28069; Q96D03: DDIT4L; NbExp=3; IntAct=EBI-8673859, EBI-742054; CC P28069; P60410: KRTAP10-8; NbExp=3; IntAct=EBI-8673859, EBI-10171774; CC P28069; Q3LI76: KRTAP15-1; NbExp=3; IntAct=EBI-8673859, EBI-11992140; CC P28069; Q3LI64: KRTAP6-1; NbExp=3; IntAct=EBI-8673859, EBI-12111050; CC P28069; Q14847-2: LASP1; NbExp=5; IntAct=EBI-8673859, EBI-9088686; CC P28069; Q969G2: LHX4; NbExp=3; IntAct=EBI-8673859, EBI-2865388; CC P28069; P35548: MSX2; NbExp=3; IntAct=EBI-8673859, EBI-6447480; CC P28069; Q9Y4B4: RAD54L2; NbExp=3; IntAct=EBI-8673859, EBI-948156; CC P28069; Q7KZS0: UBE2I; NbExp=3; IntAct=EBI-8673859, EBI-10180829; CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:26612202}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=B; Synonyms=Pit-1B, GHF-1; CC IsoId=P28069-1; Sequence=Displayed; CC Name=A; Synonyms=Pit-1A, GHF-2; CC IsoId=P28069-2; Sequence=VSP_002314; CC -!- DOMAIN: The 9aaTAD motif is a transactivation domain present in a large CC number of yeast and animal transcription factors. CC {ECO:0000269|PubMed:34342803}. CC -!- DISEASE: Pituitary hormone deficiency, combined, 1 (CPHD1) CC [MIM:613038]: Combined pituitary hormone deficiency is defined as the CC impaired production of growth hormone and one or more of the other five CC anterior pituitary hormones. CPHD1 is characterized by pleiotropic CC deficiencies of growth hormone, prolactin and thyroid-stimulating CC hormone, while the production of adrenocorticotropic hormone, CC luteinizing hormone, and follicle-stimulating hormone are preserved. In CC infancy severe growth deficiency from birth as well as distinctive CC facial features with prominent forehead, marked midfacial hypoplasia CC with depressed nasal bridge, deep-set eyes, and a short nose with CC anteverted nostrils and hypoplastic pituitary gland by MRI examination CC can be seen. Some cases present with severe intellectual disability CC along with short stature. {ECO:0000269|PubMed:11297581, CC ECO:0000269|PubMed:1472057, ECO:0000269|PubMed:1509262, CC ECO:0000269|PubMed:1509263, ECO:0000269|PubMed:15928241, CC ECO:0000269|PubMed:16968807, ECO:0000269|PubMed:22010633, CC ECO:0000269|PubMed:26612202, ECO:0000269|PubMed:7852536, CC ECO:0000269|PubMed:8768831, ECO:0000269|PubMed:9485179, CC ECO:0000269|PubMed:9626142}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- MISCELLANEOUS: [Isoform A]: Altered in its ability to trans-activate CC compared to isoform B. {ECO:0000305}. CC -!- SIMILARITY: Belongs to the POU transcription factor family. Class-1 CC subfamily. {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=CAA54440.2; Type=Erroneous gene model prediction; Evidence={ECO:0000305}; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; L18781; AAA60093.1; -; mRNA. DR EMBL; X62429; CAA44295.1; -; mRNA. DR EMBL; D10216; BAA01068.1; -; mRNA. DR EMBL; X72215; CAA51017.1; -; mRNA. DR EMBL; D12892; BAA02291.1; -; Genomic_DNA. DR EMBL; X77223; CAA54440.2; ALT_SEQ; Genomic_DNA. DR EMBL; X77224; CAA54440.2; JOINED; Genomic_DNA. DR EMBL; X77223; CAA54441.1; -; Genomic_DNA. DR EMBL; X77224; CAA54441.1; JOINED; Genomic_DNA. DR EMBL; D11333; BAA34536.1; -; Genomic_DNA. DR CCDS; CCDS2919.1; -. [P28069-1] DR CCDS; CCDS46873.1; -. [P28069-2] DR PIR; S18718; S18718. DR RefSeq; NP_000297.1; NM_000306.3. [P28069-1] DR RefSeq; NP_001116229.1; NM_001122757.2. [P28069-2] DR PDB; 5WC9; X-ray; 3.15 A; A/B/E/F=124-273. DR PDBsum; 5WC9; -. DR AlphaFoldDB; P28069; -. DR SMR; P28069; -. DR BioGRID; 111445; 31. DR IntAct; P28069; 13. DR MINT; P28069; -. DR STRING; 9606.ENSP00000342931; -. DR iPTMnet; P28069; -. DR PhosphoSitePlus; P28069; -. DR BioMuta; POU1F1; -. DR DMDM; 123408; -. DR jPOST; P28069; -. DR MassIVE; P28069; -. DR PaxDb; 9606-ENSP00000342931; -. DR PeptideAtlas; P28069; -. DR ProteomicsDB; 54444; -. [P28069-1] DR ProteomicsDB; 54445; -. [P28069-2] DR Antibodypedia; 15685; 105 antibodies from 20 providers. DR DNASU; 5449; -. DR Ensembl; ENST00000344265.8; ENSP00000342931.3; ENSG00000064835.12. [P28069-2] DR Ensembl; ENST00000350375.7; ENSP00000263781.2; ENSG00000064835.12. [P28069-1] DR GeneID; 5449; -. DR KEGG; hsa:5449; -. DR MANE-Select; ENST00000350375.7; ENSP00000263781.2; NM_000306.4; NP_000297.1. DR UCSC; uc003dqq.2; human. [P28069-1] DR AGR; HGNC:9210; -. DR CTD; 5449; -. DR DisGeNET; 5449; -. DR GeneCards; POU1F1; -. DR HGNC; HGNC:9210; POU1F1. DR HPA; ENSG00000064835; Tissue enriched (pituitary). DR MalaCards; POU1F1; -. DR MIM; 173110; gene. DR MIM; 613038; phenotype. DR neXtProt; NX_P28069; -. DR OpenTargets; ENSG00000064835; -. DR Orphanet; 95494; Combined pituitary hormone deficiencies, genetic forms. DR Orphanet; 226307; Hypothyroidism due to deficient transcription factors involved in pituitary development or function. DR Orphanet; 231679; Isolated growth hormone deficiency type II. DR PharmGKB; PA33534; -. DR VEuPathDB; HostDB:ENSG00000064835; -. DR eggNOG; KOG3802; Eukaryota. DR GeneTree; ENSGT00940000158913; -. DR HOGENOM; CLU_882684_0_0_1; -. DR InParanoid; P28069; -. DR OMA; TSHAHGM; -. DR OrthoDB; 4250502at2759; -. DR PhylomeDB; P28069; -. DR TreeFam; TF316413; -. DR PathwayCommons; P28069; -. DR SignaLink; P28069; -. DR SIGNOR; P28069; -. DR BioGRID-ORCS; 5449; 15 hits in 1169 CRISPR screens. DR GeneWiki; Pituitary-specific_positive_transcription_factor_1; -. DR GenomeRNAi; 5449; -. DR Pharos; P28069; Tbio. DR PRO; PR:P28069; -. DR Proteomes; UP000005640; Chromosome 3. DR RNAct; P28069; Protein. DR Bgee; ENSG00000064835; Expressed in pituitary gland and 48 other cell types or tissues. DR ExpressionAtlas; P28069; baseline and differential. DR GO; GO:0000785; C:chromatin; ISA:NTNU_SB. DR GO; GO:0005829; C:cytosol; IDA:HPA. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; IEA:Ensembl. DR GO; GO:0003700; F:DNA-binding transcription factor activity; IDA:UniProtKB. DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; IDA:UniProtKB. DR GO; GO:0106222; F:lncRNA binding; IEA:Ensembl. DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IBA:GO_Central. DR GO; GO:0061629; F:RNA polymerase II-specific DNA-binding transcription factor binding; IPI:UniProtKB. DR GO; GO:1990837; F:sequence-specific double-stranded DNA binding; IDA:ARUK-UCL. DR GO; GO:0021984; P:adenohypophysis development; IEA:Ensembl. DR GO; GO:0008285; P:negative regulation of cell population proliferation; TAS:ProtInc. DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IEA:Ensembl. DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:UniProtKB. DR GO; GO:0006355; P:regulation of DNA-templated transcription; IDA:UniProtKB. DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central. DR CDD; cd00086; homeodomain; 1. DR Gene3D; 1.10.10.60; Homeodomain-like; 1. DR Gene3D; 1.10.260.40; lambda repressor-like DNA-binding domains; 1. DR InterPro; IPR009057; Homeobox-like_sf. DR InterPro; IPR017970; Homeobox_CS. DR InterPro; IPR001356; Homeobox_dom. DR InterPro; IPR010982; Lambda_DNA-bd_dom_sf. DR InterPro; IPR013847; POU. DR InterPro; IPR000327; POU_dom. DR PANTHER; PTHR11636:SF84; PITUITARY-SPECIFIC POSITIVE TRANSCRIPTION FACTOR 1; 1. DR PANTHER; PTHR11636; POU DOMAIN; 1. DR Pfam; PF00046; Homeodomain; 1. DR Pfam; PF00157; Pou; 1. DR PRINTS; PR00028; POUDOMAIN. DR SMART; SM00389; HOX; 1. DR SMART; SM00352; POU; 1. DR SUPFAM; SSF46689; Homeodomain-like; 1. DR SUPFAM; SSF47413; lambda repressor-like DNA-binding domains; 1. DR PROSITE; PS00027; HOMEOBOX_1; 1. DR PROSITE; PS50071; HOMEOBOX_2; 1. DR PROSITE; PS00035; POU_1; 1. DR PROSITE; PS00465; POU_2; 1. DR PROSITE; PS51179; POU_3; 1. DR Genevisible; P28069; HS. PE 1: Evidence at protein level; KW 3D-structure; Activator; Alternative splicing; Disease variant; KW DNA-binding; Dwarfism; Homeobox; Nucleus; Reference proteome; KW Transcription; Transcription regulation. FT CHAIN 1..291 FT /note="Pituitary-specific positive transcription factor 1" FT /id="PRO_0000100697" FT DOMAIN 124..198 FT /note="POU-specific" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00530" FT DNA_BIND 214..273 FT /note="Homeobox" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00108" FT MOTIF 5..13 FT /note="9aaTAD" FT /evidence="ECO:0000269|PubMed:34342803" FT VAR_SEQ 47 FT /note="T -> TVPSILSLIQTPKCLCTHFSVTTLGNT (in isoform A)" FT /evidence="ECO:0000305" FT /id="VSP_002314" FT VARIANT 4 FT /note="Q -> R (in dbSNP:rs1051612)" FT /evidence="ECO:0000269|PubMed:8346040" FT /id="VAR_003776" FT VARIANT 19 FT /note="A -> V (in dbSNP:rs35182189)" FT /id="VAR_049361" FT VARIANT 24 FT /note="P -> L (in CPHD1; dbSNP:rs104893757)" FT /evidence="ECO:0000269|PubMed:1472057" FT /id="VAR_003777" FT VARIANT 76 FT /note="P -> L (in CPHD1; reduces transactivation capacity FT on the GH1 gene; increases the functional binding on the FT GH1 promoter; increases the interaction with ELK1, LHX3 and FT PITX1)" FT /evidence="ECO:0000269|PubMed:26612202" FT /id="VAR_075530" FT VARIANT 135 FT /note="F -> C (in CPHD1; dbSNP:rs104893761)" FT /evidence="ECO:0000269|PubMed:8768831" FT /id="VAR_010574" FT VARIANT 143 FT /note="R -> Q (in CPHD1; dbSNP:rs104893759)" FT /evidence="ECO:0000269|PubMed:1472057" FT /id="VAR_003778" FT VARIANT 158 FT /note="A -> P (in CPHD1; dbSNP:rs104893756)" FT /evidence="ECO:0000269|PubMed:1509263" FT /id="VAR_003779" FT VARIANT 172 FT /note="R -> Q (in CPHD1; results in severe impairment of FT transactivation; has a greatly reduced DNA-binding affinity FT compared to the wild-type protein; dbSNP:rs104893765)" FT /evidence="ECO:0000269|PubMed:15928241" FT /id="VAR_063425" FT VARIANT 174 FT /note="E -> G (in CPHD1; dbSNP:rs1207179169)" FT /evidence="ECO:0000269|PubMed:9485179" FT /id="VAR_010575" FT VARIANT 179 FT /note="S -> R (in CPHD1; transactivation capacity of this FT mutant is markedly decreased on the GH1; PRL, TSHB and FT POU1F1 genes; abolishes the functional interaction of FT POU1F1 on the PRL promoter with the coactivator CREBBP but FT not with the transcription factor LHX3; displays normal FT nuclear accumulation but a markedly decreased binding to a FT DNA response element; dbSNP:rs104893766)" FT /evidence="ECO:0000269|PubMed:16968807" FT /id="VAR_063426" FT VARIANT 193 FT /note="W -> R (in CPHD1; dbSNP:rs104893758)" FT /evidence="ECO:0000269|PubMed:11297581" FT /id="VAR_015260" FT VARIANT 227 FT /note="D -> Y (in dbSNP:rs1131815)" FT /evidence="ECO:0000269|PubMed:8346040" FT /id="VAR_003780" FT VARIANT 230 FT /note="E -> K (in CPHD1; results in mild impairment of FT transactivation; has a similar DNA-binding affinity as the FT wild-type protein; dbSNP:rs104893764)" FT /evidence="ECO:0000269|PubMed:15928241" FT /id="VAR_063427" FT VARIANT 239 FT /note="P -> S (in CPHD1; loss of function; FT dbSNP:rs104893762)" FT /evidence="ECO:0000269|PubMed:9626142" FT /id="VAR_010576" FT VARIANT 265 FT /note="R -> W (in CPHD1; reduces transactivation capacity FT on the PRL gene; increases instability of the protein; FT dbSNP:rs780359925)" FT /evidence="ECO:0000269|PubMed:22010633" FT /id="VAR_075531" FT VARIANT 271 FT /note="R -> W (in CPHD1; dbSNP:rs104893755)" FT /evidence="ECO:0000269|PubMed:1472057, FT ECO:0000269|PubMed:1509262, ECO:0000269|PubMed:15928241, FT ECO:0000269|PubMed:7852536" FT /id="VAR_003781" FT MUTAGEN 74 FT /note="L->A: No effect on the interaction with ELK1, LHX3 FT and PITX1." FT /evidence="ECO:0000269|PubMed:26612202" FT MUTAGEN 75 FT /note="T->A: Increases the interaction with LHX3. No effect FT on the interaction with ELK1." FT /evidence="ECO:0000269|PubMed:26612202" FT MUTAGEN 76 FT /note="P->A: Increases the interaction with LHX3 and PITX1. FT No effect on the interaction with ELK1." FT /evidence="ECO:0000269|PubMed:26612202" FT MUTAGEN 77 FT /note="C->A: Increases the interaction with LHX3 and PITX1. FT No effect on the interaction with ELK1." FT /evidence="ECO:0000269|PubMed:26612202" FT MUTAGEN 78 FT /note="L->A: Increases the interaction with LHX3 and PITX1. FT No effect on the interaction with ELK1." FT /evidence="ECO:0000269|PubMed:26612202" FT HELIX 127..145 FT /evidence="ECO:0007829|PDB:5WC9" FT HELIX 150..155 FT /evidence="ECO:0007829|PDB:5WC9" FT HELIX 158..161 FT /evidence="ECO:0007829|PDB:5WC9" FT HELIX 167..174 FT /evidence="ECO:0007829|PDB:5WC9" FT HELIX 180..196 FT /evidence="ECO:0007829|PDB:5WC9" FT HELIX 223..235 FT /evidence="ECO:0007829|PDB:5WC9" FT HELIX 241..251 FT /evidence="ECO:0007829|PDB:5WC9" FT HELIX 255..268 FT /evidence="ECO:0007829|PDB:5WC9" SQ SEQUENCE 291 AA; 32912 MW; 0866777E3E425873 CRC64; MSCQAFTSAD TFIPLNSDAS ATLPLIMHHS AAECLPVSNH ATNVMSTATG LHYSVPSCHY GNQPSTYGVM AGSLTPCLYK FPDHTLSHGF PPIHQPLLAE DPTAADFKQE LRRKSKLVEE PIDMDSPEIR ELEKFANEFK VRRIKLGYTQ TNVGEALAAV HGSEFSQTTI CRFENLQLSF KNACKLKAIL SKWLEEAEQV GALYNEKVGA NERKRKRRTT ISIAAKDALE RHFGEQNKPS SQEIMRMAEE LNLEKEVVRV WFCNRRQREK RVKTSLNQSL FSISKEHLEC R //