PAX8_HUMAN
ID PAX8_HUMAN Reviewed; 450 AA.
AC Q06710; Q09155; Q16337; Q16338; Q16339; Q4ZG35; Q96J49;
DT 01-JUN-1994, integrated into UniProtKB/Swiss-Prot.
DT 25-NOV-2008, sequence version 2.
DT 03-AUG-2022, entry version 203.
DE RecName: Full=Paired box protein Pax-8;
GN Name=PAX8;
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] (ISOFORMS 1 AND 2), AND VARIANT LEU-329.
RC TISSUE=Kidney;
RX PubMed=1337742; DOI=10.1242/dev.116.3.611;
RA Poleev A., Fickenscher H., Mundlos S., Winterpacht A., Zabel B., Fidler A.,
RA Gruss P., Plachov D.;
RT "PAX8, a human paired box gene: isolation and expression in developing
RT thyroid, kidney and Wilms' tumors.";
RL Development 116:611-623(1992).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND ALTERNATIVE SPLICING.
RC TISSUE=Kidney;
RX PubMed=8413205; DOI=10.1128/mcb.13.10.6024-6035.1993;
RA Kozmik Z., Kurzbauer R., Doerfler P., Busslinger M.;
RT "Alternative splicing of Pax-8 gene transcripts is developmentally
RT regulated and generates isoforms with different transactivation
RT properties.";
RL Mol. Cell. Biol. 13:6024-6035(1993).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 3; 4 AND 5).
RX PubMed=7737192; DOI=10.1111/j.1432-1033.1995.tb20338.x;
RA Poleev A., Wendler F., Fickenscher H., Zannini M.S., Yaginuma K.,
RA Abbott C., Plachov D.;
RT "Distinct functional properties of three human paired-box-protein, PAX8,
RT isoforms generated by alternative splicing in thyroid, kidney and Wilms'
RT tumors.";
RL Eur. J. Biochem. 228:899-911(1995).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Cervix;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT 4.";
RL Nature 434:724-731(2005).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Kidney;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [8]
RP INTERACTION WITH WWTR1.
RX PubMed=19010321; DOI=10.1016/j.yexcr.2008.10.016;
RA Di Palma T., D'Andrea B., Liguori G.L., Liguoro A., de Cristofaro T.,
RA Del Prete D., Pappalardo A., Mascia A., Zannini M.;
RT "TAZ is a coactivator for Pax8 and TTF-1, two transcription factors
RT involved in thyroid differentiation.";
RL Exp. Cell Res. 315:162-175(2009).
RN [9]
RP VARIANTS CHNG2 HIS-31 AND ARG-62.
RX PubMed=9590296; DOI=10.1038/ng0598-83;
RA Macchia P.E., Lapi P., Krude H., Pirro M.T., Missero C., Chiovato L.,
RA Souabni A., Baserga M., Tassi V., Pinchera A., Fenzi G., Gruters A.,
RA Busslinger M., Di Lauro R.;
RT "PAX8 mutations associated with congenital hypothyroidism caused by thyroid
RT dysgenesis.";
RL Nat. Genet. 19:83-86(1998).
RN [10]
RP VARIANT CHNG2 TYR-57.
RX PubMed=11232006; DOI=10.1210/jcem.86.1.7140;
RA Vilain C., Rydlewski C., Duprez L., Heinrichs C., Abramowicz M.,
RA Malvaux P., Renneboog B., Parma J., Costagliola S., Vassart G.;
RT "Autosomal dominant transmission of congenital thyroid hypoplasia due to
RT loss-of-function mutation of PAX8.";
RL J. Clin. Endocrinol. Metab. 86:234-238(2001).
RN [11]
RP VARIANT CHNG2 PRO-40.
RX PubMed=11502839; DOI=10.1210/jcem.86.8.7765;
RA Congdon T., Nguyen L.Q., Nogueira C.R., Habiby R.L., Medeiros-Neto G.,
RA Kopp P.;
RT "A novel mutation (Q40P) in PAX8 associated with congenital hypothyroidism
RT and thyroid hypoplasia: evidence for phenotypic variability in mother and
RT child.";
RL J. Clin. Endocrinol. Metab. 86:3962-3967(2001).
RN [12]
RP STRUCTURE BY NMR OF 1-143.
RX PubMed=18829450; DOI=10.1074/jbc.m805717200;
RA Codutti L., van Ingen H., Vascotto C., Fogolari F., Corazza A., Tell G.,
RA Quadrifoglio F., Viglino P., Boelens R., Esposito G.;
RT "The solution structure of DNA-free Pax-8 paired box domain accounts for
RT redox regulation of transcriptional activity in the pax protein family.";
RL J. Biol. Chem. 283:33321-33328(2008).
CC -!- FUNCTION: Transcription factor for the thyroid-specific expression of
CC the genes exclusively expressed in the thyroid cell type, maintaining
CC the functional differentiation of such cells.
CC -!- SUBUNIT: Interacts with WWTR1. {ECO:0000269|PubMed:19010321}.
CC -!- INTERACTION:
CC Q06710; Q00526: CDK3; NbExp=3; IntAct=EBI-2683132, EBI-1245761;
CC Q06710; Q8TEW6: DOK4; NbExp=3; IntAct=EBI-2683132, EBI-6918542;
CC Q06710; O75603: GCM2; NbExp=3; IntAct=EBI-2683132, EBI-10188645;
CC Q06710; P31273: HOXC8; NbExp=3; IntAct=EBI-2683132, EBI-1752118;
CC Q06710; P31274: HOXC9; NbExp=3; IntAct=EBI-2683132, EBI-1779423;
CC Q06710; Q17RB8: LONRF1; NbExp=3; IntAct=EBI-2683132, EBI-2341787;
CC Q06710; P19338: NCL; NbExp=2; IntAct=EBI-2683132, EBI-346967;
CC Q06710; Q9UBE0: SAE1; NbExp=3; IntAct=EBI-2683132, EBI-743154;
CC Q06710; Q9NRX5: SERINC1; NbExp=2; IntAct=EBI-2683132, EBI-2683145;
CC Q06710; O75177-5: SS18L1; NbExp=3; IntAct=EBI-2683132, EBI-12035119;
CC Q06710; Q08117-2: TLE5; NbExp=3; IntAct=EBI-2683132, EBI-11741437;
CC -!- SUBCELLULAR LOCATION: Nucleus.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=5;
CC Name=1; Synonyms=Pax8a;
CC IsoId=Q06710-1; Sequence=Displayed;
CC Name=2; Synonyms=Pax8b;
CC IsoId=Q06710-2; Sequence=VSP_002372;
CC Name=3; Synonyms=Pax8c;
CC IsoId=Q06710-3; Sequence=VSP_002373;
CC Name=4; Synonyms=Pax8d;
CC IsoId=Q06710-4; Sequence=VSP_002374;
CC Name=5; Synonyms=Pax8e;
CC IsoId=Q06710-5; Sequence=VSP_002375;
CC -!- TISSUE SPECIFICITY: Expressed in the excretory system, thyroid gland
CC and Wilms tumors.
CC -!- DEVELOPMENTAL STAGE: In developing excretory system, during thyroid
CC differentiation and in adult thyroid.
CC -!- DISEASE: Hypothyroidism, congenital, non-goitrous, 2 (CHNG2)
CC [MIM:218700]: A disease characterized by thyroid dysgenesis, the most
CC frequent cause of congenital hypothyroidism, accounting for 85% of
CC case. The thyroid gland can be completely absent (athyreosis),
CC ectopically located and/or severely hypoplastic. Ectopic thyroid gland
CC is the most frequent malformation, with thyroid tissue being found most
CC often at the base of the tongue. {ECO:0000269|PubMed:11232006,
CC ECO:0000269|PubMed:11502839, ECO:0000269|PubMed:9590296}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/PAX8ID382ch2q13.html";
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DR EMBL; X69699; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; L19606; AAA03539.1; -; mRNA.
DR EMBL; S77904; AAB34216.1; -; mRNA.
DR EMBL; S77905; AAB34217.2; -; mRNA.
DR EMBL; S77906; AAB34218.2; -; mRNA.
DR EMBL; AK292191; BAF84880.1; -; mRNA.
DR EMBL; AC016683; AAX88880.1; -; Genomic_DNA.
DR EMBL; CH471217; EAW73629.1; -; Genomic_DNA.
DR EMBL; BC001060; AAH01060.1; -; mRNA.
DR CCDS; CCDS42735.1; -. [Q06710-5]
DR CCDS; CCDS42736.1; -. [Q06710-4]
DR CCDS; CCDS46398.1; -. [Q06710-1]
DR CCDS; CCDS46399.1; -. [Q06710-3]
DR PIR; A54429; A54429.
DR PIR; I53340; I53340.
DR RefSeq; NP_003457.1; NM_003466.3. [Q06710-1]
DR RefSeq; NP_039246.1; NM_013952.3. [Q06710-3]
DR RefSeq; NP_039247.1; NM_013953.3. [Q06710-4]
DR RefSeq; NP_054698.1; NM_013992.3. [Q06710-5]
DR PDB; 2K27; NMR; -; A=1-143.
DR PDBsum; 2K27; -.
DR AlphaFoldDB; Q06710; -.
DR BMRB; Q06710; -.
DR SMR; Q06710; -.
DR BioGRID; 113604; 105.
DR IntAct; Q06710; 102.
DR STRING; 9606.ENSP00000263334; -.
DR ChEMBL; CHEMBL2362980; -.
DR iPTMnet; Q06710; -.
DR PhosphoSitePlus; Q06710; -.
DR BioMuta; PAX8; -.
DR DMDM; 215273928; -.
DR MassIVE; Q06710; -.
DR PaxDb; Q06710; -.
DR PeptideAtlas; Q06710; -.
DR PRIDE; Q06710; -.
DR ProteomicsDB; 58470; -. [Q06710-1]
DR ProteomicsDB; 58471; -. [Q06710-2]
DR ProteomicsDB; 58472; -. [Q06710-3]
DR ProteomicsDB; 58473; -. [Q06710-4]
DR ProteomicsDB; 58474; -. [Q06710-5]
DR Antibodypedia; 9626; 907 antibodies from 48 providers.
DR DNASU; 7849; -.
DR Ensembl; ENST00000263334.9; ENSP00000263334.6; ENSG00000125618.18. [Q06710-1]
DR Ensembl; ENST00000263335.11; ENSP00000263335.7; ENSG00000125618.18. [Q06710-4]
DR Ensembl; ENST00000348715.9; ENSP00000314750.5; ENSG00000125618.18. [Q06710-3]
DR Ensembl; ENST00000397647.7; ENSP00000380768.3; ENSG00000125618.18. [Q06710-5]
DR Ensembl; ENST00000429538.8; ENSP00000395498.3; ENSG00000125618.18. [Q06710-1]
DR GeneID; 7849; -.
DR KEGG; hsa:7849; -.
DR MANE-Select; ENST00000429538.8; ENSP00000395498.3; NM_003466.4; NP_003457.1.
DR UCSC; uc002tjm.4; human. [Q06710-1]
DR CTD; 7849; -.
DR DisGeNET; 7849; -.
DR GeneCards; PAX8; -.
DR HGNC; HGNC:8622; PAX8.
DR HPA; ENSG00000125618; Group enriched (kidney, thyroid gland).
DR MalaCards; PAX8; -.
DR MIM; 167415; gene.
DR MIM; 218700; phenotype.
DR neXtProt; NX_Q06710; -.
DR OpenTargets; ENSG00000125618; -.
DR Orphanet; 95713; Athyreosis.
DR Orphanet; 146; Differentiated thyroid carcinoma.
DR Orphanet; 95712; Thyroid ectopia.
DR Orphanet; 95720; Thyroid hypoplasia.
DR PharmGKB; PA32962; -.
DR VEuPathDB; HostDB:ENSG00000125618; -.
DR eggNOG; KOG3862; Eukaryota.
DR GeneTree; ENSGT00940000161868; -.
DR HOGENOM; CLU_019281_1_3_1; -.
DR InParanoid; Q06710; -.
DR OMA; QLRTEAY; -.
DR PhylomeDB; Q06710; -.
DR TreeFam; TF315397; -.
DR PathwayCommons; Q06710; -.
DR SignaLink; Q06710; -.
DR SIGNOR; Q06710; -.
DR BioGRID-ORCS; 7849; 53 hits in 1094 CRISPR screens.
DR ChiTaRS; PAX8; human.
DR EvolutionaryTrace; Q06710; -.
DR GeneWiki; PAX8; -.
DR GenomeRNAi; 7849; -.
DR Pharos; Q06710; Tchem.
DR PRO; PR:Q06710; -.
DR Proteomes; UP000005640; Chromosome 2.
DR RNAct; Q06710; protein.
DR Bgee; ENSG00000125618; Expressed in right lobe of thyroid gland and 177 other tissues.
DR ExpressionAtlas; Q06710; baseline and differential.
DR Genevisible; Q06710; HS.
DR GO; GO:0000785; C:chromatin; ISA:NTNU_SB.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0003677; F:DNA binding; 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; ISA:NTNU_SB.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IDA:UniProtKB.
DR GO; GO:1990837; F:sequence-specific double-stranded DNA binding; IDA:ARUK-UCL.
DR GO; GO:0004996; F:thyroid-stimulating hormone receptor activity; TAS:ProtInc.
DR GO; GO:0000976; F:transcription cis-regulatory region binding; IDA:UniProtKB.
DR GO; GO:0048856; P:anatomical structure development; IBA:GO_Central.
DR GO; GO:0009653; P:anatomical structure morphogenesis; TAS:ProtInc.
DR GO; GO:0001658; P:branching involved in ureteric bud morphogenesis; IEP:UniProtKB.
DR GO; GO:0071371; P:cellular response to gonadotropin stimulus; IDA:UniProtKB.
DR GO; GO:0007417; P:central nervous system development; IEP:UniProtKB.
DR GO; GO:0042472; P:inner ear morphogenesis; ISS:UniProtKB.
DR GO; GO:0001822; P:kidney development; IEP:UniProtKB.
DR GO; GO:0003337; P:mesenchymal to epithelial transition involved in metanephros morphogenesis; IEP:UniProtKB.
DR GO; GO:0001823; P:mesonephros development; ISS:UniProtKB.
DR GO; GO:0072278; P:metanephric comma-shaped body morphogenesis; IEP:UniProtKB.
DR GO; GO:0072221; P:metanephric distal convoluted tubule development; ISS:UniProtKB.
DR GO; GO:0072207; P:metanephric epithelium development; IEP:UniProtKB.
DR GO; GO:0072289; P:metanephric nephron tubule formation; ISS:UniProtKB.
DR GO; GO:0072284; P:metanephric S-shaped body morphogenesis; IEP:UniProtKB.
DR GO; GO:1900215; P:negative regulation of apoptotic process involved in metanephric collecting duct development; ISS:UniProtKB.
DR GO; GO:1900218; P:negative regulation of apoptotic process involved in metanephric nephron tubule development; ISS:UniProtKB.
DR GO; GO:0010667; P:negative regulation of cardiac muscle cell apoptotic process; IEA:Ensembl.
DR GO; GO:0072305; P:negative regulation of mesenchymal cell apoptotic process involved in metanephric nephron morphogenesis; ISS:UniProtKB.
DR GO; GO:1900212; P:negative regulation of mesenchymal cell apoptotic process involved in metanephros development; ISS:UniProtKB.
DR GO; GO:0071599; P:otic vesicle development; IEP:UniProtKB.
DR GO; GO:0090190; P:positive regulation of branching involved in ureteric bud morphogenesis; ISS:UniProtKB.
DR GO; GO:0072108; P:positive regulation of mesenchymal to epithelial transition involved in metanephros morphogenesis; ISS:UniProtKB.
DR GO; GO:2000594; P:positive regulation of metanephric DCT cell differentiation; ISS:UniProtKB.
DR GO; GO:2000611; P:positive regulation of thyroid hormone generation; IMP:UniProtKB.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:UniProtKB.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IDA:UniProtKB.
DR GO; GO:0039003; P:pronephric field specification; ISS:UniProtKB.
DR GO; GO:0048793; P:pronephros development; ISS:UniProtKB.
DR GO; GO:0042981; P:regulation of apoptotic process; ISS:UniProtKB.
DR GO; GO:0072307; P:regulation of metanephric nephron tubule epithelial cell differentiation; ISS:UniProtKB.
DR GO; GO:2000612; P:regulation of thyroid-stimulating hormone secretion; IMP:UniProtKB.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0006790; P:sulfur compound metabolic process; IEA:Ensembl.
DR GO; GO:0030878; P:thyroid gland development; IMP:UniProtKB.
DR GO; GO:0006351; P:transcription, DNA-templated; IDA:UniProtKB.
DR GO; GO:0001655; P:urogenital system development; ISS:UniProtKB.
DR GO; GO:0003281; P:ventricular septum development; IEA:Ensembl.
DR CDD; cd00131; PAX; 1.
DR DisProt; DP01517; -.
DR Gene3D; 1.10.10.10; -; 2.
DR InterPro; IPR009057; Homeobox-like_sf.
DR InterPro; IPR043182; PAIRED_DNA-bd_dom.
DR InterPro; IPR001523; Paired_dom.
DR InterPro; IPR022130; Pax2_C.
DR InterPro; IPR043565; PAX_fam.
DR InterPro; IPR036388; WH-like_DNA-bd_sf.
DR PANTHER; PTHR45636; PTHR45636; 1.
DR Pfam; PF00292; PAX; 1.
DR Pfam; PF12403; Pax2_C; 1.
DR PRINTS; PR00027; PAIREDBOX.
DR SMART; SM00351; PAX; 1.
DR SUPFAM; SSF46689; SSF46689; 1.
DR PROSITE; PS00034; PAIRED_1; 1.
DR PROSITE; PS51057; PAIRED_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Congenital hypothyroidism;
KW Developmental protein; Differentiation; Disease variant; DNA-binding;
KW Nucleus; Paired box; Phosphoprotein; Reference proteome; Transcription;
KW Transcription regulation.
FT CHAIN 1..450
FT /note="Paired box protein Pax-8"
FT /id="PRO_0000050197"
FT DNA_BIND 9..135
FT /note="Paired"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00381"
FT REGION 12..68
FT /note="PAI subdomain"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00381"
FT REGION 87..135
FT /note="RED subdomain"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00381"
FT REGION 159..222
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 159..186
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 207..222
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 303
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q00288"
FT VAR_SEQ 260..450
FT /note="GLYPLPLLNSTLDDGKATLTPSNTPLGRNLSTHQTYPVVADPHSPFAIKQET
FT PEVSSSSSTPSSLSSSAFLDLQQVGSGVPPFNAFPHAASVYGQFTGQALLSGREMVGPT
FT LPGYPPHIPTSGQGSYASSAIAGMVAGSEYSGNAYGHTPYSSYSEAWRFPNSSLLSSPY
FT YYSSTSRPSAPPTTATAFDHL -> GERWWGPRCPDTHPTSPPADRAAMPPLPSQAWWQ
FT EVNTLAMPMATPPTPPTARPGASPTPAC (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:7737192"
FT /id="VSP_002374"
FT VAR_SEQ 260..450
FT /note="GLYPLPLLNSTLDDGKATLTPSNTPLGRNLSTHQTYPVVADPHSPFAIKQET
FT PEVSSSSSTPSSLSSSAFLDLQQVGSGVPPFNAFPHAASVYGQFTGQALLSGREMVGPT
FT LPGYPPHIPTSGQGSYASSAIAGMVAGSEYSGNAYGHTPYSSYSEAWRFPNSSLLSSPY
FT YYSSTSRPSAPPTTATAFDHL -> EVNTLAMPMATPPTPPTARPGASPTPAC (in
FT isoform 5)"
FT /evidence="ECO:0000303|PubMed:7737192"
FT /id="VSP_002375"
FT VAR_SEQ 300..450
FT /note="DPHSPFAIKQETPEVSSSSSTPSSLSSSAFLDLQQVGSGVPPFNAFPHAASV
FT YGQFTGQALLSGREMVGPTLPGYPPHIPTSGQGSYASSAIAGMVAGSEYSGNAYGHTPY
FT SSYSEAWRFPNSSLLSSPYYYSSTSRPSAPPTTATAFDHL -> APPFWICSKSAPGSR
FT PSMPFPMLPPCTGSSRARPSSQGERWWGPRCPDTHPTSPPADRAAMPPLPSQAWWQEVN
FT TLAMPMATPPTPPTARPGASPTPAC (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:7737192"
FT /id="VSP_002373"
FT VAR_SEQ 300..362
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:1337742"
FT /id="VSP_002372"
FT VARIANT 31
FT /note="R -> H (in CHNG2; loss of activity;
FT dbSNP:rs104893657)"
FT /evidence="ECO:0000269|PubMed:9590296"
FT /id="VAR_012769"
FT VARIANT 40
FT /note="Q -> P (in CHNG2; loss of activity;
FT dbSNP:rs104893656)"
FT /evidence="ECO:0000269|PubMed:11502839"
FT /id="VAR_012770"
FT VARIANT 57
FT /note="C -> Y (in CHNG2; loss of activity;
FT dbSNP:rs104893659)"
FT /evidence="ECO:0000269|PubMed:11232006"
FT /id="VAR_012771"
FT VARIANT 62
FT /note="L -> R (in CHNG2; loss of activity;
FT dbSNP:rs104893658)"
FT /evidence="ECO:0000269|PubMed:9590296"
FT /id="VAR_012772"
FT VARIANT 329
FT /note="F -> L (in dbSNP:rs3188996)"
FT /evidence="ECO:0000269|PubMed:1337742"
FT /id="VAR_012773"
FT CONFLICT 305
FT /note="F -> L (in Ref. 1; X69699)"
FT /evidence="ECO:0000305"
FT CONFLICT 322
FT /note="S -> C (in Ref. 1; X69699)"
FT /evidence="ECO:0000305"
FT CONFLICT 418
FT /note="R -> G (in Ref. 1; X69699)"
FT /evidence="ECO:0000305"
FT STRAND 21..23
FT /evidence="ECO:0007829|PDB:2K27"
FT HELIX 28..40
FT /evidence="ECO:0007829|PDB:2K27"
FT HELIX 44..51
FT /evidence="ECO:0007829|PDB:2K27"
FT HELIX 56..62
FT /evidence="ECO:0007829|PDB:2K27"
FT HELIX 88..98
FT /evidence="ECO:0007829|PDB:2K27"
FT STRAND 100..102
FT /evidence="ECO:0007829|PDB:2K27"
FT HELIX 104..114
FT /evidence="ECO:0007829|PDB:2K27"
FT TURN 119..121
FT /evidence="ECO:0007829|PDB:2K27"
FT HELIX 125..135
FT /evidence="ECO:0007829|PDB:2K27"
SQ SEQUENCE 450 AA; 48218 MW; 7FDAFA8CEAF20A0E CRC64;
MPHNSIRSGH GGLNQLGGAF VNGRPLPEVV RQRIVDLAHQ GVRPCDISRQ LRVSHGCVSK
ILGRYYETGS IRPGVIGGSK PKVATPKVVE KIGDYKRQNP TMFAWEIRDR LLAEGVCDND
TVPSVSSINR IIRTKVQQPF NLPMDSCVAT KSLSPGHTLI PSSAVTPPES PQSDSLGSTY
SINGLLGIAQ PGSDKRKMDD SDQDSCRLSI DSQSSSSGPR KHLRTDAFSQ HHLEPLECPF
ERQHYPEAYA SPSHTKGEQG LYPLPLLNST LDDGKATLTP SNTPLGRNLS THQTYPVVAD
PHSPFAIKQE TPEVSSSSST PSSLSSSAFL DLQQVGSGVP PFNAFPHAAS VYGQFTGQAL
LSGREMVGPT LPGYPPHIPT SGQGSYASSA IAGMVAGSEY SGNAYGHTPY SSYSEAWRFP
NSSLLSSPYY YSSTSRPSAP PTTATAFDHL
