PAX1_HUMAN
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 03-AUG-2022, entry version 192.
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/";
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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 IntAct; P15863; 1.
DR MINT; P15863; -.
DR STRING; 9606.ENSP00000381499; -.
DR iPTMnet; P15863; -.
DR PhosphoSitePlus; P15863; -.
DR BioMuta; PAX1; -.
DR DMDM; 296439493; -.
DR MassIVE; P15863; -.
DR PaxDb; P15863; -.
DR PeptideAtlas; P15863; -.
DR PRIDE; P15863; -.
DR ProteomicsDB; 53230; -. [P15863-1]
DR ProteomicsDB; 53231; -. [P15863-2]
DR ProteomicsDB; 53232; -. [P15863-3]
DR Antibodypedia; 24834; 319 antibodies from 34 providers.
DR DNASU; 5075; -.
DR Ensembl; ENST00000398485.6; ENSP00000381499.2; ENSG00000125813.14. [P15863-1]
DR Ensembl; ENST00000444366.2; ENSP00000410355.2; ENSG00000125813.14. [P15863-2]
DR GeneID; 5075; -.
DR KEGG; hsa:5075; -.
DR UCSC; uc002wsj.4; human. [P15863-1]
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; PWANPPG; -.
DR OrthoDB; 1339212at2759; -.
DR PhylomeDB; P15863; -.
DR TreeFam; TF315397; -.
DR PathwayCommons; P15863; -.
DR SignaLink; P15863; -.
DR SIGNOR; P15863; -.
DR BioGRID-ORCS; 5075; 8 hits in 1091 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 45 other tissues.
DR ExpressionAtlas; P15863; baseline and differential.
DR Genevisible; P15863; HS.
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; -; 2.
DR InterPro; IPR009057; Homeobox-like_sf.
DR InterPro; IPR043182; PAIRED_DNA-bd_dom.
DR InterPro; IPR001523; Paired_dom.
DR InterPro; IPR033206; PAX1.
DR InterPro; IPR043565; PAX_fam.
DR InterPro; IPR036388; WH-like_DNA-bd_sf.
DR PANTHER; PTHR45636; PTHR45636; 1.
DR PANTHER; PTHR45636:SF15; PTHR45636:SF15; 1.
DR Pfam; PF00292; PAX; 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 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 unknown pathological 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
