NKX62_HUMAN
ID NKX62_HUMAN Reviewed; 277 AA.
AC Q9C056; Q5JSF3;
DT 11-SEP-2007, integrated into UniProtKB/Swiss-Prot.
DT 11-SEP-2007, sequence version 2.
DT 03-AUG-2022, entry version 149.
DE RecName: Full=Homeobox protein Nkx-6.2;
DE AltName: Full=Homeobox protein NK-6 homolog B;
GN Name=NKX6-2; Synonyms=GTX, NKX6B;
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 [GENOMIC DNA], VARIANT ALA-209, AND TISSUE SPECIFICITY.
RX PubMed=11210186; DOI=10.1007/s003350010247;
RA Lee S.-H., Davison J.A., Vidal S.M., Belouchi A.;
RT "Cloning, expression and chromosomal location of NKX6B to 10q26, a region
RT frequently deleted in brain tumors.";
RL Mamm. Genome 12:157-162(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15164054; DOI=10.1038/nature02462;
RA Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L.,
RA Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K.,
RA Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L.,
RA Taylor A., Battles J., Bird C.P., Ainscough R., Almeida J.P.,
RA Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y.,
RA Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N.,
RA Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A.,
RA Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C.,
RA Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D.,
RA Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C.,
RA Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K.,
RA Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A.,
RA Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S.,
RA McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S.,
RA Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V.,
RA Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A.,
RA Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M.,
RA Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A.,
RA Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P.,
RA Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y.,
RA Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D.,
RA Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 10.";
RL Nature 429:375-381(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANT ALA-209.
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 (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT ALA-209.
RC TISSUE=Brain cortex;
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 INVOLVEMENT IN SPAX8, VARIANTS SPAX8 41-LYS--LEU-277 DEL AND VAL-163, AND
RP CHARACTERIZATION OF VARIANT SPAX8 41-LYS--LEU-277 DEL.
RX PubMed=28575651; DOI=10.1016/j.ajhg.2017.05.009;
RG SYNAPSE Study Group;
RA Chelban V., Patel N., Vandrovcova J., Zanetti M.N., Lynch D.S., Ryten M.,
RA Botia J.A., Bello O., Tribollet E., Efthymiou S., Davagnanam I.,
RA Bashiri F.A., Wood N.W., Rothman J.E., Alkuraya F.S., Houlden H.;
RT "Mutations in NKX6-2 Cause Progressive Spastic Ataxia and
RT Hypomyelination.";
RL Am. J. Hum. Genet. 100:969-977(2017).
CC -!- FUNCTION: Transcription factor with repressor activity involved in the
CC regulation of axon-glial interactions at myelin paranodes in
CC oligodendrocytes. Binds to the consensus DNA sequence 5'-(A/T)TTAATGA-
CC 3'. In oligodendrocytes, binds to MBP and PLP1 promoter regions.
CC {ECO:0000250|UniProtKB:D3Z4R4}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:D3Z4R4}.
CC -!- TISSUE SPECIFICITY: Highest expression in brain.
CC {ECO:0000269|PubMed:11210186}.
CC -!- DISEASE: Spastic ataxia 8, autosomal recessive, with hypomyelinating
CC leukodystrophy (SPAX8) [MIM:617560]: An autosomal recessive
CC neurodegenerative disorder characterized by early-onset hypotonia which
CC progresses to a pyramidal syndrome with ataxia, spasticity,
CC hyperreflexia, weakness and loss of ambulation. Brain imaging shows
CC cerebellar atrophy and hypomyelinating leukodystrophy.
CC {ECO:0000269|PubMed:28575651}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
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DR EMBL; AF184215; AAK13251.1; -; Genomic_DNA.
DR EMBL; AL392043; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471211; EAW61308.1; -; Genomic_DNA.
DR EMBL; BC101635; AAI01636.1; -; mRNA.
DR EMBL; BC104823; AAI04824.1; -; mRNA.
DR CCDS; CCDS7670.1; -.
DR RefSeq; NP_796374.1; NM_177400.2.
DR RefSeq; XP_016872278.1; XM_017016789.1.
DR AlphaFoldDB; Q9C056; -.
DR SMR; Q9C056; -.
DR BioGRID; 124105; 1.
DR STRING; 9606.ENSP00000357581; -.
DR iPTMnet; Q9C056; -.
DR PhosphoSitePlus; Q9C056; -.
DR BioMuta; NKX6-2; -.
DR DMDM; 158564033; -.
DR MassIVE; Q9C056; -.
DR PaxDb; Q9C056; -.
DR PeptideAtlas; Q9C056; -.
DR PRIDE; Q9C056; -.
DR Antibodypedia; 56219; 79 antibodies from 17 providers.
DR DNASU; 84504; -.
DR Ensembl; ENST00000368592.8; ENSP00000357581.5; ENSG00000148826.9.
DR GeneID; 84504; -.
DR KEGG; hsa:84504; -.
DR MANE-Select; ENST00000368592.8; ENSP00000357581.5; NM_177400.3; NP_796374.2.
DR UCSC; uc001llr.3; human.
DR CTD; 84504; -.
DR DisGeNET; 84504; -.
DR GeneCards; NKX6-2; -.
DR GeneReviews; NKX6-2; -.
DR HGNC; HGNC:19321; NKX6-2.
DR HPA; ENSG00000148826; Tissue enriched (brain).
DR MalaCards; NKX6-2; -.
DR MIM; 605955; gene.
DR MIM; 617560; phenotype.
DR neXtProt; NX_Q9C056; -.
DR OpenTargets; ENSG00000148826; -.
DR Orphanet; 527497; NKX6-2-related autosomal recessive hypomyelinating leukodystrophy.
DR PharmGKB; PA134896334; -.
DR VEuPathDB; HostDB:ENSG00000148826; -.
DR eggNOG; KOG0847; Eukaryota.
DR GeneTree; ENSGT00940000161547; -.
DR HOGENOM; CLU_064820_1_1_1; -.
DR InParanoid; Q9C056; -.
DR OMA; MQGAPWR; -.
DR OrthoDB; 1263401at2759; -.
DR PhylomeDB; Q9C056; -.
DR TreeFam; TF327063; -.
DR PathwayCommons; Q9C056; -.
DR BioGRID-ORCS; 84504; 11 hits in 1072 CRISPR screens.
DR ChiTaRS; NKX6-2; human.
DR GeneWiki; NKX6-2; -.
DR GenomeRNAi; 84504; -.
DR Pharos; Q9C056; Tbio.
DR PRO; PR:Q9C056; -.
DR Proteomes; UP000005640; Chromosome 10.
DR RNAct; Q9C056; protein.
DR Bgee; ENSG00000148826; Expressed in C1 segment of cervical spinal cord and 71 other tissues.
DR GO; GO:0000785; C:chromatin; ISA:NTNU_SB.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0003677; F:DNA binding; ISS:UniProtKB.
DR GO; GO:0003700; F:DNA-binding transcription factor activity; NAS:UniProtKB.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; ISA:NTNU_SB.
DR GO; GO:0001227; F:DNA-binding transcription repressor activity, RNA polymerase II-specific; IEA:Ensembl.
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:0030154; P:cell differentiation; IBA:GO_Central.
DR GO; GO:0022010; P:central nervous system myelination; IEA:Ensembl.
DR GO; GO:0010454; P:negative regulation of cell fate commitment; IEA:Ensembl.
DR GO; GO:0048715; P:negative regulation of oligodendrocyte differentiation; IEA:Ensembl.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; ISS:UniProtKB.
DR GO; GO:0050885; P:neuromuscular process controlling balance; IEA:Ensembl.
DR GO; GO:0048663; P:neuron fate commitment; IEA:Ensembl.
DR GO; GO:0003310; P:pancreatic A cell differentiation; IEA:Ensembl.
DR GO; GO:0010455; P:positive regulation of cell fate commitment; IEA:Ensembl.
DR GO; GO:0048714; P:positive regulation of oligodendrocyte differentiation; IEA:Ensembl.
DR GO; GO:0031641; P:regulation of myelination; ISS:UniProtKB.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0006355; P:regulation of transcription, DNA-templated; NAS:UniProtKB.
DR CDD; cd00086; homeodomain; 1.
DR InterPro; IPR009057; Homeobox-like_sf.
DR InterPro; IPR017970; Homeobox_CS.
DR InterPro; IPR001356; Homeobox_dom.
DR InterPro; IPR020479; Homeobox_metazoa.
DR InterPro; IPR000047; HTH_motif.
DR Pfam; PF00046; Homeodomain; 1.
DR PRINTS; PR00024; HOMEOBOX.
DR PRINTS; PR00031; HTHREPRESSR.
DR SMART; SM00389; HOX; 1.
DR SUPFAM; SSF46689; SSF46689; 1.
DR PROSITE; PS00027; HOMEOBOX_1; 1.
DR PROSITE; PS50071; HOMEOBOX_2; 1.
PE 1: Evidence at protein level;
KW Developmental protein; Disease variant; DNA-binding; Homeobox;
KW Leukodystrophy; Neurodegeneration; Nucleus; Reference proteome; Repressor.
FT CHAIN 1..277
FT /note="Homeobox protein Nkx-6.2"
FT /id="PRO_0000300635"
FT DNA_BIND 148..207
FT /note="Homeobox"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00108"
FT REGION 89..142
FT /note="Repressor domain"
FT /evidence="ECO:0000250|UniProtKB:D3Z4R4"
FT REGION 132..155
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 210..250
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 212..235
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VARIANT 41..277
FT /note="Missing (in SPAX8; loss of protein expression)"
FT /evidence="ECO:0000269|PubMed:28575651"
FT /id="VAR_079480"
FT VARIANT 163
FT /note="L -> V (in SPAX8; unknown pathological significance;
FT dbSNP:rs1131692048)"
FT /evidence="ECO:0000269|PubMed:28575651"
FT /id="VAR_079481"
FT VARIANT 209
FT /note="V -> A (in dbSNP:rs2804003)"
FT /evidence="ECO:0000269|PubMed:11210186,
FT ECO:0000269|PubMed:15489334, ECO:0000269|Ref.3"
FT /id="VAR_034878"
SQ SEQUENCE 277 AA; 29263 MW; 4B8EE650EC35D4A9 CRC64;
MDTNRPGAFV LSSAPLAALH NMAEMKTSLF PYALQGPAGF KAPALGGLGA QLPLGTPHGI
SDILGRPVGA AGGGLLGGLP RLNGLASSAG VYFGPAAAVA RGYPKPLAEL PGRPPIFWPG
VVQGAPWRDP RLAGPAPAGG VLDKDGKKKH SRPTFSGQQI FALEKTFEQT KYLAGPERAR
LAYSLGMTES QVKVWFQNRR TKWRKRHAVE MASAKKKQDS DAEKLKVGGS DAEDDDEYNR
PLDPNSDDEK ITRLLKKHKP SNLALVSPCG GGAGDAL
