ID PAX1_HUMAN Reviewed; 534 AA. AC P15863; B4E0D6; Q642X9; Q6NTC0; Q9Y558; DT 01-APR-1990, integrated into UniProtKB/Swiss-Prot. DT 18-MAY-2010, sequence version 4. DT 27-MAR-2024, entry version 201. DE RecName: Full=Paired box protein Pax-1; DE AltName: Full=HuP48; GN Name=PAX1; Synonyms=HUP48; 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 [LARGE SCALE MRNA] (ISOFORM 2). RC TISSUE=Thymus; 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 [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 3), AND VARIANTS ARG-439; RP LEU-453 AND LEU-504. RG NIEHS SNPs program; RL Submitted (SEP-2004) to the EMBL/GenBank/DDBJ databases. RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=11780052; DOI=10.1038/414865a; RA Deloukas P., Matthews L.H., Ashurst J.L., Burton J., Gilbert J.G.R., RA Jones M., Stavrides G., Almeida J.P., Babbage A.K., Bagguley C.L., RA Bailey J., Barlow K.F., Bates K.N., Beard L.M., Beare D.M., Beasley O.P., RA Bird C.P., Blakey S.E., Bridgeman A.M., Brown A.J., Buck D., Burrill W.D., RA Butler A.P., Carder C., Carter N.P., Chapman J.C., Clamp M., Clark G., RA Clark L.N., Clark S.Y., Clee C.M., Clegg S., Cobley V.E., Collier R.E., RA Connor R.E., Corby N.R., Coulson A., Coville G.J., Deadman R., Dhami P.D., RA Dunn M., Ellington A.G., Frankland J.A., Fraser A., French L., Garner P., RA Grafham D.V., Griffiths C., Griffiths M.N.D., Gwilliam R., Hall R.E., RA Hammond S., Harley J.L., Heath P.D., Ho S., Holden J.L., Howden P.J., RA Huckle E., Hunt A.R., Hunt S.E., Jekosch K., Johnson C.M., Johnson D., RA Kay M.P., Kimberley A.M., King A., Knights A., Laird G.K., Lawlor S., RA Lehvaeslaiho M.H., Leversha M.A., Lloyd C., Lloyd D.M., Lovell J.D., RA Marsh V.L., Martin S.L., McConnachie L.J., McLay K., McMurray A.A., RA Milne S.A., Mistry D., Moore M.J.F., Mullikin J.C., Nickerson T., RA Oliver K., Parker A., Patel R., Pearce T.A.V., Peck A.I., RA Phillimore B.J.C.T., Prathalingam S.R., Plumb R.W., Ramsay H., Rice C.M., RA Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S., Skuce C.D., RA Smith M.L., Soderlund C., Steward C.A., Sulston J.E., Swann R.M., RA Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A., Tracey A., RA Tromans A.C., Vaudin M., Wall M., Wallis J.M., Whitehead S.L., RA Whittaker P., Willey D.L., Williams L., Williams S.A., Wilming L., RA Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S., Rogers J.; RT "The DNA sequence and comparative analysis of human chromosome 20."; RL Nature 414:865-871(2001). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 95-534 (ISOFORM 1). 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 [5] RP PARTIAL NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 2/3). RX PubMed=2501086; DOI=10.1002/j.1460-2075.1989.tb03490.x; RA Burri M., Tromvoukis Y., Bopp D., Frigerio G., Noll M.; RT "Conservation of the paired domain in metazoans and its structure in three RT isolated human genes."; RL EMBO J. 8:1183-1190(1989). RN [6] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21406692; DOI=10.1126/scisignal.2001570; RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.; RT "System-wide temporal characterization of the proteome and phosphoproteome RT of human embryonic stem cell differentiation."; RL Sci. Signal. 4:RS3-RS3(2011). RN [7] RP VARIANT HIS-139. RX PubMed=8863157; DOI=10.1136/jmg.33.8.655; RA Hol F.A., Geurds M.P.A., Chatkupt S., Shugart Y.Y., Balling R., RA Schrander-Stumpel C.T.R.M., Johnson W.G., Hamel B.C.J., Mariman E.C.M.; RT "PAX genes and human neural tube defects: an amino acid substitution in RT PAX1 in a patient with spina bifida."; RL J. Med. Genet. 33:655-660(1996). RN [8] RP VARIANT OTFCS2 VAL-166, AND CHARACTERIZATION OF VARIANT OTFCS2 VAL-166. RX PubMed=23851939; DOI=10.1007/s00439-013-1337-9; RA Pohl E., Aykut A., Beleggia F., Karaca E., Durmaz B., Keupp K., Arslan E., RA Palamar M., Onay M.P., Yigit G., Ozkinay F., Wollnik B.; RT "A hypofunctional PAX1 mutation causes autosomal recessively inherited RT otofaciocervical syndrome."; RL Hum. Genet. 132:1311-1320(2013). CC -!- FUNCTION: This protein is a transcriptional activator. It may play a CC role in the formation of segmented structures of the embryo. May play CC an important role in the normal development of the vertebral column (By CC similarity). {ECO:0000250}. CC -!- SUBCELLULAR LOCATION: Nucleus. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; CC Name=1; CC IsoId=P15863-1; Sequence=Displayed; CC Name=2; CC IsoId=P15863-2; Sequence=VSP_039095, VSP_039096; CC Name=3; CC IsoId=P15863-3; Sequence=VSP_039095; CC -!- DISEASE: Otofaciocervical syndrome 2, with T-cell deficiency (OTFCS2) CC [MIM:615560]: An autosomal recessive disorder characterized by facial CC dysmorphism, cup-shaped low-set ears, preauricular fistulas, hearing CC loss, branchial defects, skeletal anomalies including vertebral CC defects, low-set clavicles, winged scapulae, sloping shoulders, and CC mild intellectual disability. Some patients also exhibit altered thymus CC development with T-cell immunodeficiency. CC {ECO:0000269|PubMed:23851939}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- SEQUENCE CAUTION: CC Sequence=AAH69134.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; CC Sequence=AAU21037.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; CC -!- WEB RESOURCE: Name=NIEHS-SNPs; CC URL="http://egp.gs.washington.edu/data/pax1/"; 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; AK303335; BAG64398.1; -; mRNA. DR EMBL; AY740018; AAU21037.1; ALT_INIT; Genomic_DNA. DR EMBL; AL035562; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC069134; AAH69134.1; ALT_INIT; mRNA. DR EMBL; X15044; CAA33146.1; -; Genomic_DNA. DR CCDS; CCDS13146.2; -. [P15863-1] DR PIR; S06961; S06961. DR RefSeq; NP_006183.2; NM_006192.4. [P15863-1] DR AlphaFoldDB; P15863; -. DR SMR; P15863; -. DR BioGRID; 111109; 3. DR MINT; P15863; -. DR STRING; 9606.ENSP00000381499; -. DR iPTMnet; P15863; -. DR PhosphoSitePlus; P15863; -. DR BioMuta; PAX1; -. DR DMDM; 296439493; -. DR MassIVE; P15863; -. DR PaxDb; 9606-ENSP00000381499; -. DR PeptideAtlas; P15863; -. DR ProteomicsDB; 53230; -. [P15863-1] DR ProteomicsDB; 53231; -. [P15863-2] DR ProteomicsDB; 53232; -. [P15863-3] DR Antibodypedia; 24834; 356 antibodies from 34 providers. DR DNASU; 5075; -. DR Ensembl; ENST00000398485.6; ENSP00000381499.2; ENSG00000125813.15. [P15863-1] DR Ensembl; ENST00000444366.2; ENSP00000410355.2; ENSG00000125813.15. [P15863-2] DR GeneID; 5075; -. DR KEGG; hsa:5075; -. DR UCSC; uc002wsj.4; human. [P15863-1] DR AGR; HGNC:8615; -. DR CTD; 5075; -. DR DisGeNET; 5075; -. DR GeneCards; PAX1; -. DR HGNC; HGNC:8615; PAX1. DR HPA; ENSG00000125813; Tissue enriched (parathyroid). DR MalaCards; PAX1; -. DR MIM; 167411; gene. DR MIM; 615560; phenotype. DR neXtProt; NX_P15863; -. DR OpenTargets; ENSG00000125813; -. DR Orphanet; 2792; Otofaciocervical syndrome. DR PharmGKB; PA32955; -. DR VEuPathDB; HostDB:ENSG00000125813; -. DR eggNOG; KOG3517; Eukaryota. DR GeneTree; ENSGT00940000159137; -. DR HOGENOM; CLU_019281_3_1_1; -. DR InParanoid; P15863; -. DR OMA; MEHTYGE; -. DR OrthoDB; 5393942at2759; -. DR PhylomeDB; P15863; -. DR TreeFam; TF315397; -. DR PathwayCommons; P15863; -. DR SignaLink; P15863; -. DR SIGNOR; P15863; -. DR BioGRID-ORCS; 5075; 8 hits in 1169 CRISPR screens. DR ChiTaRS; PAX1; human. DR GeneWiki; PAX1; -. DR GenomeRNAi; 5075; -. DR Pharos; P15863; Tbio. DR PRO; PR:P15863; -. DR Proteomes; UP000005640; Chromosome 20. DR RNAct; P15863; Protein. DR Bgee; ENSG00000125813; Expressed in thymus and 43 other cell types or tissues. DR ExpressionAtlas; P15863; baseline and differential. DR GO; GO:0000785; C:chromatin; ISA:NTNU_SB. DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell. 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:0048856; P:anatomical structure development; IBA:GO_Central. DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central. DR GO; GO:0001501; P:skeletal system development; TAS:ProtInc. DR GO; GO:0006366; P:transcription by RNA polymerase II; TAS:ProtInc. DR CDD; cd00131; PAX; 1. DR Gene3D; 1.10.10.10; Winged helix-like DNA-binding domain superfamily/Winged helix DNA-binding domain; 2. DR InterPro; IPR009057; Homeobox-like_sf. DR InterPro; IPR043182; PAIRED_DNA-bd_dom. DR InterPro; IPR001523; Paired_dom. DR InterPro; IPR043565; PAX_fam. DR InterPro; IPR036388; WH-like_DNA-bd_sf. DR PANTHER; PTHR45636:SF15; PAIRED BOX PROTEIN PAX-1; 1. DR PANTHER; PTHR45636; PAIRED BOX PROTEIN PAX-6-RELATED-RELATED; 1. DR Pfam; PF00292; PAX; 1. DR PRINTS; PR00027; PAIREDBOX. DR SMART; SM00351; PAX; 1. DR SUPFAM; SSF46689; Homeodomain-like; 1. DR PROSITE; PS00034; PAIRED_1; 1. DR PROSITE; PS51057; PAIRED_2; 1. DR Genevisible; P15863; HS. PE 1: Evidence at protein level; KW Activator; Alternative splicing; Deafness; Developmental protein; KW Disease variant; DNA-binding; Intellectual disability; Nucleus; Paired box; KW Reference proteome; Transcription; Transcription regulation. FT CHAIN 1..534 FT /note="Paired box protein Pax-1" FT /id="PRO_0000050172" FT DNA_BIND 98..224 FT /note="Paired" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00381" FT REGION 101..157 FT /note="PAI subdomain" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00381" FT REGION 176..224 FT /note="RED subdomain" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00381" FT REGION 424..480 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 492..511 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT VAR_SEQ 1..95 FT /note="MKFTLGLGSRAWRVSWEGAAAAAAGPGAGGSALRCRAQRVSSPRLGRRGSRL FT SGALPLCLSRGGGGAQALPDCAGPSPGHPGHPGARQLAGPLAM -> MRRAPLRGSSAP FT LPTPSQTQAVCPWTPSCLGTHRSPLEVRLGAVPRSAWGPLANPPGVFSPSGSLLSGASA FT (in isoform 2 and isoform 3)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_039095" FT VAR_SEQ 428..534 FT /note="GSLPAPAARPRTPSVAYTDCPSRPRPPRGSSPRTRARRERQADPGAQVCAAA FT PAIGTGRIGGLAEEEASAGPRGARPASPQAQPCLWPDPPHFLYWSGFLGFSELGF -> FT VADRKPPSSGSKAPDALSSLHGLPIPASTS (in isoform 2)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_039096" FT VARIANT 139 FT /note="Q -> H (found in a patient with neural tube defects; FT uncertain significance)" FT /evidence="ECO:0000269|PubMed:8863157" FT /id="VAR_003787" FT VARIANT 166 FT /note="G -> V (in OTFCS2; significantly reduced FT transactivation of the regulatory sequence of NKX3-2 in FT cells over-expressing the mutant sequence compared to cells FT over-expressing wild-type sequence; dbSNP:rs540296842)" FT /evidence="ECO:0000269|PubMed:23851939" FT /id="VAR_070922" FT VARIANT 439 FT /note="T -> R (in dbSNP:rs17861058)" FT /evidence="ECO:0000269|Ref.2" FT /id="VAR_055369" FT VARIANT 453 FT /note="P -> L (in dbSNP:rs17861059)" FT /evidence="ECO:0000269|Ref.2" FT /id="VAR_055370" FT VARIANT 504 FT /note="P -> L (in dbSNP:rs17861061)" FT /evidence="ECO:0000269|Ref.2" FT /id="VAR_055371" SQ SEQUENCE 534 AA; 55499 MW; 6B06A2AD302FDEEA CRC64; MKFTLGLGSR AWRVSWEGAA AAAAGPGAGG SALRCRAQRV SSPRLGRRGS RLSGALPLCL SRGGGGAQAL PDCAGPSPGH PGHPGARQLA GPLAMEQTYG EVNQLGGVFV NGRPLPNAIR LRIVELAQLG IRPCDISRQL RVSHGCVSKI LARYNETGSI LPGAIGGSKP RVTTPNVVKH IRDYKQGDPG IFAWEIRDRL LADGVCDKYN VPSVSSISRI LRNKIGSLAQ PGPYEASKQP PSQPTLPYNH IYQYPYPSPV SPTGAKMGSH PGVPGTAGHV SIPRSWPSAH SVSNILGIRT FMEQTGALAG SEGTAYSPKM EDWAGVNRTA FPATPAVNGL EKPALEADIK YTQSASTLSA VGGFLPACAY PASNQHGVYS APGGGYLAPG PPWPPAQGPP LAPPGAGVAV HGGELAAAMT FKHPSREGSL PAPAARPRTP SVAYTDCPSR PRPPRGSSPR TRARRERQAD PGAQVCAAAP AIGTGRIGGL AEEEASAGPR GARPASPQAQ PCLWPDPPHF LYWSGFLGFS ELGF //