LOCUS       NP_055306                715 aa            linear   PRI 28-APR-2025
DEFINITION  forkhead box protein P2 isoform I [Homo sapiens].
ACCESSION   NP_055306
VERSION     NP_055306.1
DBSOURCE    REFSEQ: accession NM_014491.4
KEYWORDS    RefSeq; MANE Select.
SOURCE      Homo sapiens (human)
  ORGANISM  Homo sapiens
            Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
            Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
            Catarrhini; Hominidae; Homo.
REFERENCE   1  (residues 1 to 715)
  AUTHORS   Che,F., Li,C., Zhang,L., Qian,C., Mo,L., Li,B., Wu,H., Wang,L. and
            Yang,Y.
  TITLE     Novel FOXP2 variant associated with speech and language dysfunction
            in a Chinese family and literature review
  JOURNAL   J Appl Genet 65 (2), 367-373 (2024)
   PUBMED   38418803
  REMARK    GeneRIF: Novel FOXP2 variant associated with speech and language
            dysfunction in a Chinese family and literature review.
            Review article
            Erratum:[J Appl Genet. 2024 May;65(2):417. doi:
            10.1007/s13353-024-00851-6. PMID: 38523169]
REFERENCE   2  (residues 1 to 715)
  AUTHORS   Yan,L., Sun,H., Chen,Y., Yu,X., Zhang,J. and Li,P.
  TITLE     FOXP2 suppresses the proliferation, invasion, and aerobic
            glycolysis of hepatocellular carcinoma cells by regulating the
            KDM5A/FBP1 axis
  JOURNAL   Environ Toxicol 39 (1), 341-356 (2024)
   PUBMED   37713600
  REMARK    GeneRIF: FOXP2 suppresses the proliferation, invasion, and aerobic
            glycolysis of hepatocellular carcinoma cells by regulating the
            KDM5A/FBP1 axis.
REFERENCE   3  (residues 1 to 715)
  AUTHORS   Stroud,J.C., Wu,Y., Bates,D.L., Han,A., Nowick,K., Paabo,S.,
            Tong,H. and Chen,L.
  TITLE     Structure of the forkhead domain of FOXP2 bound to DNA
  JOURNAL   Structure 14 (1), 159-166 (2006)
   PUBMED   16407075
  REMARK    GeneRIF: Disease-causing mutations in FOXP2 map either to the DNA
            binding surface or the domain-swapping dimer interface,
            functionally corroborating the crystal structure.
REFERENCE   4  (residues 1 to 715)
  AUTHORS   Gauthier,J., Joober,R., Mottron,L., Laurent,S., Fuchs,M., De
            Kimpe,V. and Rouleau,G.A.
  TITLE     Mutation screening of FOXP2 in individuals diagnosed with autistic
            disorder
  JOURNAL   Am J Med Genet A 118A (2), 172-175 (2003)
   PUBMED   12655497
  REMARK    GeneRIF: Observational study of gene-disease association. (HuGE
            Navigator)
REFERENCE   5  (residues 1 to 715)
  AUTHORS   Enard,W., Przeworski,M., Fisher,S.E., Lai,C.S., Wiebe,V.,
            Kitano,T., Monaco,A.P. and Paabo,S.
  TITLE     Molecular evolution of FOXP2, a gene involved in speech and
            language
  JOURNAL   Nature 418 (6900), 869-872 (2002)
   PUBMED   12192408
  REMARK    GeneRIF: Human FOXP2 contains changes in amino-acid coding and a
            pattern of nucleotide polymorphism, which strongly suggest that
            this gene has been the target of selection during recent human
            evolution.
REFERENCE   6  (residues 1 to 715)
  AUTHORS   Bruce,H.A. and Margolis,R.L.
  TITLE     FOXP2: novel exons, splice variants, and CAG repeat length
            stability
  JOURNAL   Hum Genet 111 (2), 136-144 (2002)
   PUBMED   12189486
REFERENCE   7  (residues 1 to 715)
  AUTHORS   Lai,C.S., Fisher,S.E., Hurst,J.A., Vargha-Khadem,F. and Monaco,A.P.
  TITLE     A forkhead-domain gene is mutated in a severe speech and language
            disorder
  JOURNAL   Nature 413 (6855), 519-523 (2001)
   PUBMED   11586359
  REMARK    GeneRIF: FOXP2 is disrupted by a translocation in CS, a child with
            severe speech/language disorder. Moreover, a point mutation,
            altering a critical residue of the forkhead domain, segregates with
            speech/language deficits in all 15 affected members of family KE.
REFERENCE   8  (residues 1 to 715)
  AUTHORS   Margolis,R.L., Abraham,M.R., Gatchell,S.B., Li,S.H., Kidwai,A.S.,
            Breschel,T.S., Stine,O.C., Callahan,C., McInnis,M.G. and Ross,C.A.
  TITLE     cDNAs with long CAG trinucleotide repeats from human brain
  JOURNAL   Hum Genet 100 (1), 114-122 (1997)
   PUBMED   9225980
REFERENCE   9  (residues 1 to 715)
  AUTHORS   Morgan,A., Fisher,S.E., Scheffer,I. and Hildebrand,M.
  TITLE     FOXP2-Related Speech and Language Disorder
  JOURNAL   (in) Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE and
            Amemiya A (Eds.);
            GENEREVIEWS(R);
            (1993)
   PUBMED   27336128
REFERENCE   10 (residues 1 to 715)
  AUTHORS   Hurst,J.A., Baraitser,M., Auger,E., Graham,F. and Norell,S.
  TITLE     An extended family with a dominantly inherited speech disorder
  JOURNAL   Dev Med Child Neurol 32 (4), 352-355 (1990)
   PUBMED   2332125
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from AC073626.7, BC018016.1,
            AF337817.1, AC020606.7 and AI369947.1.
            This sequence is a reference standard in the RefSeqGene project.
            
            Summary: This gene encodes a member of the forkhead/winged-helix
            (FOX) family of transcription factors. It is expressed in fetal and
            adult brain as well as in several other organs such as the lung and
            gut. The protein product contains a FOX DNA-binding domain and a
            large polyglutamine tract and is an evolutionarily conserved
            transcription factor, which may bind directly to approximately 300
            to 400 gene promoters in the human genome to regulate the
            expression of a variety of genes. This gene is required for proper
            development of speech and language regions of the brain during
            embryogenesis, and may be involved in a variety of biological
            pathways and cascades that may ultimately influence language
            development. Mutations in this gene cause speech-language disorder
            1 (SPCH1), also known as autosomal dominant speech and language
            disorder with orofacial dyspraxia. Multiple alternative transcripts
            encoding different isoforms have been identified in this
            gene.[provided by RefSeq, Feb 2010].
            
            Transcript Variant: This variant (1) lacks an in-frame exon in the
            5' coding region, as compared to variant 2. The resulting isoform
            (I) is shorter than isoform II.
            
            Sequence Note: This RefSeq record was created from transcript and
            genomic sequence data to make the sequence consistent with the
            reference genome assembly. The genomic coordinates used for the
            transcript record were based on transcript alignments.
            
            Publication Note:  This RefSeq record includes a subset of the
            publications that are available for this gene. Please see the Gene
            record to access additional publications.
            
            ##Evidence-Data-START##
            Transcript exon combination :: AF337817.1, SRR14038191.839039.1
                                           [ECO:0000332]
            RNAseq introns              :: single sample supports all introns
                                           SAMN03267753 [ECO:0000348]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000350908.9/ ENSP00000265436.7
            RefSeq Select criteria :: based on conservation, expression
            ##RefSeq-Attributes-END##
FEATURES             Location/Qualifiers
     source          1..715
                     /organism="Homo sapiens"
                     /db_xref="taxon:9606"
                     /chromosome="7"
                     /map="7q31.1"
     Protein         1..715
                     /product="forkhead box protein P2 isoform I"
                     /note="trinucleotide repeat containing 10;
                     forkhead/winged-helix transcription factor; CAG repeat
                     protein 44; forkhead box protein P2; trinucleotide
                     repeat-containing gene 10 protein"
                     /calculated_mol_wt=79788
     Region          1..46
                     /region_name="Disordered.
                     /evidence=ECO:0000256|SAM:MobiDB-lite"
                     /note="propagated from UniProtKB/Swiss-Prot (O15409.2)"
     Region          281..339
                     /region_name="Disordered.
                     /evidence=ECO:0000256|SAM:MobiDB-lite"
                     /note="propagated from UniProtKB/Swiss-Prot (O15409.2)"
     Region          342..409
                     /region_name="FOXP-CC"
                     /note="FOXP coiled-coil domain; pfam16159"
                     /db_xref="CDD:465036"
     Region          388..409
                     /region_name="Leucine-zipper"
                     /note="propagated from UniProtKB/Swiss-Prot (O15409.2)"
     Region          422..426
                     /region_name="CTBP1-binding. /evidence=ECO:0000250"
                     /note="propagated from UniProtKB/Swiss-Prot (O15409.2)"
     Region          438..465
                     /region_name="Disordered.
                     /evidence=ECO:0000256|SAM:MobiDB-lite"
                     /note="propagated from UniProtKB/Swiss-Prot (O15409.2)"
     Region          477..>708
                     /region_name="COG5025"
                     /note="Transcription factor of the Forkhead/HNF3 family
                     [Transcription]"
                     /db_xref="CDD:227358"
     Region          503..584
                     /region_name="FH_FOXP2"
                     /note="Forkhead (FH) domain found in Forkhead box protein
                     P2 (FOXP2); cd20065"
                     /db_xref="CDD:410839"
     Site            order(508..515,517,519,523..527,531,533..535,537..538,
                     540..541,543,548..549,551..553,555..556,562,565,571..575,
                     577,580)
                     /site_type="other"
                     /note="dimer interface [polypeptide binding]"
                     /db_xref="CDD:410839"
     Site            order(540,543,547,550,553..554,557,582..583)
                     /site_type="DNA binding"
                     /note="DNA binding site [nucleotide binding]"
                     /db_xref="CDD:410839"
     Region          649..668
                     /region_name="Disordered.
                     /evidence=ECO:0000256|SAM:MobiDB-lite"
                     /note="propagated from UniProtKB/Swiss-Prot (O15409.2)"
     Region          678..715
                     /region_name="Disordered.
                     /evidence=ECO:0000256|SAM:MobiDB-lite"
                     /note="propagated from UniProtKB/Swiss-Prot (O15409.2)"
     CDS             1..715
                     /gene="FOXP2"
                     /gene_synonym="CAGH44; SPCH1; TNRC10"
                     /coded_by="NM_014491.4:557..2704"
                     /note="isoform I is encoded by transcript variant 1"
                     /db_xref="CCDS:CCDS5760.1"
                     /db_xref="GeneID:93986"
                     /db_xref="HGNC:HGNC:13875"
                     /db_xref="MIM:605317"
ORIGIN      
        1 mmqesateti snssmnqngm stlssqldag srdgrssgdt ssevstvell hlqqqqalqa
       61 arqlllqqqt sglkspkssd kqrplqvpvs vammtpqvit pqqmqqilqq qvlspqqlqa
      121 llqqqqavml qqqqlqefyk kqqeqlhlql lqqqqqqqqq qqqqqqqqqq qqqqqqqqqq
      181 qqqqqqqqqq qhpgkqakeq qqqqqqqqql aaqqlvfqqq llqmqqlqqq qhllslqrqg
      241 lisippgqaa lpvqslpqag lspaeiqqlw kevtgvhsme dngikhggld lttnnssstt
      301 ssntskaspp ithhsivngq ssvlsarrds ssheetgash tlyghgvckw pgcesicedf
      361 gqflkhlnne halddrstaq crvqmqvvqq leiqlskere rlqammthlh mrpsepkpsp
      421 kplnlvssvt msknmletsp qslpqtpttp tapvtpitqg psvitpasvp nvgairrrhs
      481 dkynipmsse iapnyefykn advrppftya tlirqaimes sdrqltlnei yswftrtfay
      541 frrnaatwkn avrhnlslhk cfvrvenvkg avwtvdevey qkrrsqkitg sptlvknipt
      601 slgygaalna slqaalaess lpllsnpgli nnassgllqa vhedlngsld hidsngnssp
      661 gcspqphihs ihvkeepvia ededcpmslv ttanhspele ddreieeepl sedle
//
