PKNX1_HUMAN
ID PKNX1_HUMAN Reviewed; 436 AA.
AC P55347; O00528; Q8IWT7;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 19-SEP-2006, sequence version 3.
DT 03-AUG-2022, entry version 180.
DE RecName: Full=Homeobox protein PKNOX1;
DE AltName: Full=Homeobox protein PREP-1;
DE AltName: Full=PBX/knotted homeobox 1;
GN Name=PKNOX1 {ECO:0000303|PubMed:9479508, ECO:0000312|HGNC:HGNC:9022};
GN Synonyms=PREP1 {ECO:0000303|PubMed:9479508, ECO:0000312|HGNC:HGNC:9022};
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 1), AND TISSUE SPECIFICITY.
RX PubMed=9143494; DOI=10.1006/geno.1997.4632;
RA Chen H., Rossier C., Nakamura Y., Lynn A., Chakravarti A.,
RA Antonarakis S.E.;
RT "Cloning of a novel homeobox-containing gene, PKNOX1, and mapping to human
RT chromosome 21q22.3.";
RL Genomics 41:193-200(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=9479508; DOI=10.1006/geno.1997.5086;
RA Berthelsen J., Viggiano L., Schulz H., Ferretti E., Consalez G.G.,
RA Rocchi M., Blasi F.;
RT "PKNOX1, a gene encoding PREP1, a new regulator of Pbx activity, maps on
RT human chromosome 21q22.3 and murine chromosome 17B/C.";
RL Genomics 47:323-324(1998).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), AND TISSUE SPECIFICITY.
RX PubMed=15468914;
RA Ni B., Li L.Y., Yin Z.C., Zou Y.H., Li H.;
RT "Molecular cloning for an alternatively splicing cDNA of human PKNOX1 gene
RT and it's expression analysis.";
RL Yi Chuan Xue Bao 31:19-25(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=10830953; DOI=10.1038/35012518;
RA Hattori M., Fujiyama A., Taylor T.D., Watanabe H., Yada T., Park H.-S.,
RA Toyoda A., Ishii K., Totoki Y., Choi D.-K., Groner Y., Soeda E., Ohki M.,
RA Takagi T., Sakaki Y., Taudien S., Blechschmidt K., Polley A., Menzel U.,
RA Delabar J., Kumpf K., Lehmann R., Patterson D., Reichwald K., Rump A.,
RA Schillhabel M., Schudy A., Zimmermann W., Rosenthal A., Kudoh J.,
RA Shibuya K., Kawasaki K., Asakawa S., Shintani A., Sasaki T., Nagamine K.,
RA Mitsuyama S., Antonarakis S.E., Minoshima S., Shimizu N., Nordsiek G.,
RA Hornischer K., Brandt P., Scharfe M., Schoen O., Desario A., Reichelt J.,
RA Kauer G., Bloecker H., Ramser J., Beck A., Klages S., Hennig S.,
RA Riesselmann L., Dagand E., Wehrmeyer S., Borzym K., Gardiner K.,
RA Nizetic D., Francis F., Lehrach H., Reinhardt R., Yaspo M.-L.;
RT "The DNA sequence of human chromosome 21.";
RL Nature 405:311-319(2000).
RN [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-41, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [6]
RP INTERACTION WITH MN1.
RX PubMed=31839203; DOI=10.1016/j.ajhg.2019.11.011;
RA Miyake N., Takahashi H., Nakamura K., Isidor B., Hiraki Y., Koshimizu E.,
RA Shiina M., Sasaki K., Suzuki H., Abe R., Kimura Y., Akiyama T.,
RA Tomizawa S.I., Hirose T., Hamanaka K., Miyatake S., Mitsuhashi S.,
RA Mizuguchi T., Takata A., Obo K., Kato M., Ogata K., Matsumoto N.;
RT "Gain-of-function MN1 truncation variants cause a recognizable syndrome
RT with craniofacial and brain abnormalities.";
RL Am. J. Hum. Genet. 106:13-25(2020).
RN [7]
RP STRUCTURE BY NMR OF 258-319.
RG RIKEN structural genomics initiative (RSGI);
RT "Solution structure of the homeobox domain of human homeobox protein
RT PKNOX1.";
RL Submitted (OCT-2005) to the PDB data bank.
RN [8]
RP VARIANT [LARGE SCALE ANALYSIS] ILE-265.
RX PubMed=16959974; DOI=10.1126/science.1133427;
RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D.,
RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P.,
RA Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V.,
RA Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H.,
RA Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W.,
RA Velculescu V.E.;
RT "The consensus coding sequences of human breast and colorectal cancers.";
RL Science 314:268-274(2006).
CC -!- FUNCTION: Activates transcription in the presence of PBX1A and HOXA1.
CC {ECO:0000250|UniProtKB:O70477}.
CC -!- SUBUNIT: Interacts with MN1. {ECO:0000269|PubMed:31839203}.
CC -!- INTERACTION:
CC P55347; Q8TDH9: BLOC1S5; NbExp=3; IntAct=EBI-1373569, EBI-465861;
CC P55347; Q96GS4: BORCS6; NbExp=4; IntAct=EBI-1373569, EBI-10193358;
CC P55347; Q8TC76: FAM110B; NbExp=3; IntAct=EBI-1373569, EBI-2558383;
CC P55347; Q14192: FHL2; NbExp=3; IntAct=EBI-1373569, EBI-701903;
CC P55347; P26583: HMGB2; NbExp=4; IntAct=EBI-1373569, EBI-1057009;
CC P55347; O14901: KLF11; NbExp=3; IntAct=EBI-1373569, EBI-948266;
CC P55347; Q13368: MPP3; NbExp=3; IntAct=EBI-1373569, EBI-716157;
CC P55347; Q9BVL2: NUP58; NbExp=6; IntAct=EBI-1373569, EBI-2811583;
CC P55347; P40424: PBX1; NbExp=10; IntAct=EBI-1373569, EBI-301611;
CC P55347; Q9BYU1: PBX4; NbExp=5; IntAct=EBI-1373569, EBI-10302990;
CC P55347; A5D8V6: VPS37C; NbExp=4; IntAct=EBI-1373569, EBI-2559305;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000305}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P55347-1; Sequence=Displayed;
CC Name=2; Synonyms=PKNOX1B;
CC IsoId=P55347-2; Sequence=VSP_017260;
CC -!- TISSUE SPECIFICITY: Ubiquitous. Isoform 2 is expressed in all examined
CC tissues except in bone marrow. {ECO:0000269|PubMed:15468914,
CC ECO:0000269|PubMed:9143494}.
CC -!- SIMILARITY: Belongs to the TALE/MEIS homeobox family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAC51243.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC Sequence=BAA95533.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; U68727; AAC51243.1; ALT_INIT; mRNA.
DR EMBL; Y13613; CAA73934.1; -; mRNA.
DR EMBL; AY142115; AAN34940.1; -; mRNA.
DR EMBL; AP001748; BAA95533.1; ALT_INIT; Genomic_DNA.
DR CCDS; CCDS13692.1; -. [P55347-1]
DR RefSeq; NP_004562.2; NM_004571.4. [P55347-1]
DR PDB; 1X2N; NMR; -; A=260-319.
DR PDBsum; 1X2N; -.
DR AlphaFoldDB; P55347; -.
DR SASBDB; P55347; -.
DR SMR; P55347; -.
DR BioGRID; 111333; 33.
DR IntAct; P55347; 28.
DR MINT; P55347; -.
DR STRING; 9606.ENSP00000291547; -.
DR BindingDB; P55347; -.
DR GlyGen; P55347; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; P55347; -.
DR PhosphoSitePlus; P55347; -.
DR BioMuta; PKNOX1; -.
DR DMDM; 115311619; -.
DR SWISS-2DPAGE; P55347; -.
DR EPD; P55347; -.
DR jPOST; P55347; -.
DR MassIVE; P55347; -.
DR MaxQB; P55347; -.
DR PaxDb; P55347; -.
DR PeptideAtlas; P55347; -.
DR PRIDE; P55347; -.
DR ProteomicsDB; 56856; -. [P55347-1]
DR ProteomicsDB; 56857; -. [P55347-2]
DR Antibodypedia; 3800; 235 antibodies from 29 providers.
DR DNASU; 5316; -.
DR Ensembl; ENST00000291547.10; ENSP00000291547.4; ENSG00000160199.15. [P55347-1]
DR GeneID; 5316; -.
DR KEGG; hsa:5316; -.
DR MANE-Select; ENST00000291547.10; ENSP00000291547.4; NM_004571.5; NP_004562.2.
DR CTD; 5316; -.
DR DisGeNET; 5316; -.
DR GeneCards; PKNOX1; -.
DR HGNC; HGNC:9022; PKNOX1.
DR HPA; ENSG00000160199; Low tissue specificity.
DR MIM; 602100; gene.
DR neXtProt; NX_P55347; -.
DR OpenTargets; ENSG00000160199; -.
DR PharmGKB; PA33354; -.
DR VEuPathDB; HostDB:ENSG00000160199; -.
DR eggNOG; KOG0773; Eukaryota.
DR GeneTree; ENSGT00940000159505; -.
DR InParanoid; P55347; -.
DR OMA; QHVTMPD; -.
DR PhylomeDB; P55347; -.
DR TreeFam; TF318093; -.
DR PathwayCommons; P55347; -.
DR Reactome; R-HSA-5617472; Activation of anterior HOX genes in hindbrain development during early embryogenesis.
DR SignaLink; P55347; -.
DR SIGNOR; P55347; -.
DR BioGRID-ORCS; 5316; 26 hits in 1108 CRISPR screens.
DR ChiTaRS; PKNOX1; human.
DR EvolutionaryTrace; P55347; -.
DR GeneWiki; PKNOX1; -.
DR GenomeRNAi; 5316; -.
DR Pharos; P55347; Tbio.
DR PRO; PR:P55347; -.
DR Proteomes; UP000005640; Chromosome 21.
DR RNAct; P55347; protein.
DR Bgee; ENSG00000160199; Expressed in right lobe of thyroid gland and 196 other tissues.
DR ExpressionAtlas; P55347; baseline and differential.
DR Genevisible; P55347; HS.
DR GO; GO:0000785; C:chromatin; ISA:NTNU_SB.
DR GO; GO:0005737; C:cytoplasm; IEA:Ensembl.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0005667; C:transcription regulator complex; IEA:Ensembl.
DR GO; GO:0003682; F:chromatin binding; IEA:Ensembl.
DR GO; GO:0003700; F:DNA-binding transcription factor activity; TAS:ProtInc.
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:0001525; P:angiogenesis; IBA:GO_Central.
DR GO; GO:0043010; P:camera-type eye development; IEA:Ensembl.
DR GO; GO:0030218; P:erythrocyte differentiation; IEA:Ensembl.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IEA:Ensembl.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0030217; P:T cell differentiation; IEA:Ensembl.
DR GO; GO:0006366; P:transcription by RNA polymerase II; TAS:ProtInc.
DR CDD; cd00086; homeodomain; 1.
DR InterPro; IPR009057; Homeobox-like_sf.
DR InterPro; IPR001356; Homeobox_dom.
DR InterPro; IPR008422; Homeobox_KN_domain.
DR InterPro; IPR032453; PKNOX/Meis_N.
DR Pfam; PF05920; Homeobox_KN; 1.
DR Pfam; PF16493; Meis_PKNOX_N; 1.
DR SMART; SM00389; HOX; 1.
DR SUPFAM; SSF46689; SSF46689; 1.
DR PROSITE; PS50071; HOMEOBOX_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Activator; Alternative splicing; DNA-binding; Homeobox;
KW Nucleus; Phosphoprotein; Reference proteome; Transcription;
KW Transcription regulation.
FT CHAIN 1..436
FT /note="Homeobox protein PKNOX1"
FT /id="PRO_0000049248"
FT DOMAIN 80..163
FT /note="MEIS N-terminal"
FT /evidence="ECO:0000255"
FT DNA_BIND 259..321
FT /note="Homeobox; TALE-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00108"
FT REGION 1..49
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 401..436
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1..28
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 33
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O70477"
FT MOD_RES 41
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT VAR_SEQ 368..436
FT /note="AVVTITTPVNMNVDSLQSLSSDGATLAVQQVMMAGQSEDESVDSTEEDAGAL
FT APAHISGLVLENSDSLQ -> TGGRPRPDMVDHGVGIMNKRPGSGLLAVSHRARPRMTS
FT (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15468914"
FT /id="VSP_017260"
FT VARIANT 126
FT /note="R -> H (in dbSNP:rs9976017)"
FT /id="VAR_049588"
FT VARIANT 216
FT /note="T -> A (in dbSNP:rs17115709)"
FT /id="VAR_049589"
FT VARIANT 265
FT /note="V -> I (in a colorectal cancer sample; somatic
FT mutation; dbSNP:rs376883451)"
FT /evidence="ECO:0000269|PubMed:16959974"
FT /id="VAR_036440"
FT CONFLICT 153
FT /note="K -> E (in Ref. 2; CAA73934)"
FT /evidence="ECO:0000305"
FT CONFLICT 347
FT /note="P -> A (in Ref. 1; AAC51243)"
FT /evidence="ECO:0000305"
FT CONFLICT 430
FT /note="E -> A (in Ref. 2; CAA73934)"
FT /evidence="ECO:0000305"
FT HELIX 268..280
FT /evidence="ECO:0007829|PDB:1X2N"
FT TURN 281..283
FT /evidence="ECO:0007829|PDB:1X2N"
FT HELIX 289..299
FT /evidence="ECO:0007829|PDB:1X2N"
FT HELIX 303..319
FT /evidence="ECO:0007829|PDB:1X2N"
SQ SEQUENCE 436 AA; 47607 MW; 381E901F435AC5F2 CRC64;
MMATQTLSID SYQDGQQMQV VTELKTEQDP NCSEPDAEGV SPPPVESQTP MDVDKQAIYR
HPLFPLLALL FEKCEQSTQG SEGTTSASFD VDIENFVRKQ EKEGKPFFCE DPETDNLMVK
AIQVLRIHLL ELEKVNELCK DFCSRYIACL KTKMNSETLL SGEPGSPYSP VQSQQIQSAI
TGTISPQGIV VPASALQQGN VAMATVAGGT VYQPVTVVTP QGQVVTQTLS PGTIRIQNSQ
LQLQLNQDLS ILHQDDGSSK NKRGVLPKHA TNVMRSWLFQ HIGHPYPTED EKKQIAAQTN
LTLLQVNNWF INARRRILQP MLDSSCSETP KTKKKTAQNR PVQRFWPDSI ASGVAQPPPS
ELTMSEGAVV TITTPVNMNV DSLQSLSSDG ATLAVQQVMM AGQSEDESVD STEEDAGALA
PAHISGLVLE NSDSLQ
