LOCUS       NP_659428                669 aa            linear   PRI 28-APR-2025
DEFINITION  thrombospondin-type laminin G domain and EAR repeat-containing
            protein isoform 1 precursor [Homo sapiens].
ACCESSION   NP_659428
VERSION     NP_659428.2
DBSOURCE    REFSEQ: accession NM_144991.3
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 669)
  AUTHORS   Jackson,A., Lin,S.J., Jones,E.A., Chandler,K.E., Orr,D., Moss,C.,
            Haider,Z., Ryan,G., Holden,S., Harrison,M., Burrows,N., Jones,W.D.,
            Loveless,M., Petree,C., Stewart,H., Low,K., Donnelly,D., Lovell,S.,
            Drosou,K., Varshney,G.K. and Banka,S.
  CONSRTM   Genomics England Research Consortium; Solve-RD consortium
  TITLE     Clinical, genetic, epidemiologic, evolutionary, and functional
            delineation of TSPEAR-related autosomal recessive ectodermal
            dysplasia 14
  JOURNAL   HGG Adv 4 (2), 100186 (2023)
   PUBMED   37009414
  REMARK    GeneRIF: Clinical, genetic, epidemiologic, evolutionary, and
            functional delineation of TSPEAR-related autosomal recessive
            ectodermal dysplasia 14.
            Publication Status: Online-Only
REFERENCE   2  (residues 1 to 669)
  AUTHORS   Rabie,E.A., Sayed,I.S.M., Amr,K., Ahmed,H.A., Mostafa,M.I.,
            Hassib,N.F., El-Sayed,H., Zada,S.K. and El-Kamah,G.
  TITLE     Confirmation of a Phenotypic Entity for TSPEAR Variants in Egyptian
            Ectodermal Dysplasia Patients and Role of Ethnicity
  JOURNAL   Genes (Basel) 13 (6), 1056 (2022)
   PUBMED   35741818
  REMARK    GeneRIF: Confirmation of a Phenotypic Entity for TSPEAR Variants in
            Egyptian Ectodermal Dysplasia Patients and Role of Ethnicity.
            Publication Status: Online-Only
REFERENCE   3  (residues 1 to 669)
  AUTHORS   Bowles,B., Ferrer,A., Nishimura,C.J., Pinto E Vairo,F., Rey,T.,
            Leheup,B., Sullivan,J., Schoch,K., Stong,N., Agolini,E.,
            Cocciadiferro,D., Williams,A., Cummings,A., Loddo,S., Genovese,S.,
            Roadhouse,C., McWalter,K., Wentzensen,I.M., Li,C.,
            Babovic-Vuksanovic,D., Lanpher,B.C., Dentici,M.L., Ankala,A.,
            Hamm,J.A., Dallapiccola,B., Radio,F.C., Shashi,V., Gerard,B.,
            Bloch-Zupan,A., Smith,R.J. and Klee,E.W.
  CONSRTM   Undiagnosed Diseases Network
  TITLE     TSPEAR variants are primarily associated with ectodermal dysplasia
            and tooth agenesis but not hearing loss: A novel cohort study
  JOURNAL   Am J Med Genet A 185 (8), 2417-2433 (2021)
   PUBMED   34042254
  REMARK    GeneRIF: TSPEAR variants are primarily associated with ectodermal
            dysplasia and tooth agenesis but not hearing loss: A novel cohort
            study.
REFERENCE   4  (residues 1 to 669)
  AUTHORS   Song,J.S., Bae,M. and Kim,J.W.
  TITLE     Novel TSPEAR mutations in non-syndromic oligodontia
  JOURNAL   Oral Dis 26 (4), 847-849 (2020)
   PUBMED   32112661
  REMARK    GeneRIF: Novel TSPEAR mutations in non-syndromic oligodontia.
REFERENCE   5  (residues 1 to 669)
  AUTHORS   Du,R., Dinckan,N., Song,X., Coban-Akdemir,Z., Jhangiani,S.N.,
            Guven,Y., Aktoren,O., Kayserili,H., Petty,L.E., Muzny,D.M.,
            Below,J.E., Boerwinkle,E., Wu,N., Gibbs,R.A., Posey,J.E.,
            Lupski,J.R., Letra,A. and Uyguner,Z.O.
  TITLE     Identification of likely pathogenic and known variants in TSPEAR,
            LAMB3, BCOR, and WNT10A in four Turkish families with tooth
            agenesis
  JOURNAL   Hum Genet 137 (9), 689-703 (2018)
   PUBMED   30046887
  REMARK    GeneRIF: TSPEAR mutation is associated with tooth agenesis.
REFERENCE   6  (residues 1 to 669)
  AUTHORS   Wang,Y. and Tatakis,D.N.
  TITLE     Human gingiva transcriptome during wound healing
  JOURNAL   J Clin Periodontol 44 (4), 394-402 (2017)
   PUBMED   28005267
  REMARK    GeneRIF: TSPEAR expression is significantly downregulated in human
            masticatory mucosa during wound healing
REFERENCE   7  (residues 1 to 669)
  AUTHORS   Peled,A., Sarig,O., Samuelov,L., Bertolini,M., Ziv,L.,
            Weissglas-Volkov,D., Eskin-Schwartz,M., Adase,C.A., Malchin,N.,
            Bochner,R., Fainberg,G., Goldberg,I., Sugawara,K., Baniel,A.,
            Tsuruta,D., Luxenburg,C., Adir,N., Duverger,O., Morasso,M.,
            Shalev,S., Gallo,R.L., Shomron,N., Paus,R. and Sprecher,E.
  TITLE     Mutations in TSPEAR, Encoding a Regulator of Notch Signaling,
            Affect Tooth and Hair Follicle Morphogenesis
  JOURNAL   PLoS Genet 12 (10), e1006369 (2016)
   PUBMED   27736875
  REMARK    GeneRIF: using a luciferase-based reporter assay, we showed that
            TSPEAR knock-down is associated with decreased Notch signaling. In
            addition, NOTCH1 protein expression was reduced in patient scalp
            skin. Moreover, TSPEAR silencing in mouse hair follicle organ
            cultures was found to induce apoptosis in follicular epithelial
            cells, resulting in decreased hair bulb diameter
            Publication Status: Online-Only
REFERENCE   8  (residues 1 to 669)
  AUTHORS   Delmaghani,S., Aghaie,A., Michalski,N., Bonnet,C., Weil,D. and
            Petit,C.
  TITLE     Defect in the gene encoding the EAR/EPTP domain-containing protein
            TSPEAR causes DFNB98 profound deafness
  JOURNAL   Hum Mol Genet 21 (17), 3835-3844 (2012)
   PUBMED   22678063
  REMARK    GeneRIF: TSPEAR, cause disorders with auditory features: epilepsy,
            which can include auditory features in humans; audiogenic seizures
            in animals; and/or hearing impairments in humans and mice.
REFERENCE   9  (residues 1 to 669)
  AUTHORS   Scheel,H., Tomiuk,S. and Hofmann,K.
  TITLE     A common protein interaction domain links two recently identified
            epilepsy genes
  JOURNAL   Hum Mol Genet 11 (15), 1757-1762 (2002)
   PUBMED   12095917
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from AJ487962.1.
            This sequence is a reference standard in the RefSeqGene project.
            
            On Jul 29, 2002 this sequence version replaced NP_659428.1.
            
            Summary: This gene encodes a protein that contains a N-terminal
            thrombospondin-type laminin G domain and several tandem arranged
            epilepsy-associated repeats (EARs). A mutation in this gene is the
            cause of autosomal recessive deafness-98. Alternate splicing
            results in multiple transcript variants. [provided by RefSeq, Dec
            2012].
            
            Transcript Variant: This variant (1) encodes the longer isoform
            (1).
            
            ##Evidence-Data-START##
            Transcript exon combination :: AJ487962.1 [ECO:0000332]
            RNAseq introns              :: mixed sample support SAMEA1965299,
                                           SAMEA1966682 [ECO:0006172]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000323084.9/ ENSP00000321987.4
            RefSeq Select criteria :: based on conservation, expression,
                                      longest protein
            ##RefSeq-Attributes-END##
FEATURES             Location/Qualifiers
     source          1..669
                     /organism="Homo sapiens"
                     /db_xref="taxon:9606"
                     /chromosome="21"
                     /map="21q22.3"
     Protein         1..669
                     /product="thrombospondin-type laminin G domain and EAR
                     repeat-containing protein isoform 1 precursor"
                     /note="thrombospondin-type laminin G domain and EAR
                     repeats-containing protein"
                     /calculated_mol_wt=73045
     sig_peptide     1..19
                     /inference="COORDINATES: ab initio prediction:SignalP:6.0"
                     /calculated_mol_wt=1897
     mat_peptide     20..669
                     /product="Thrombospondin-type laminin G domain and EAR
                     repeat-containing protein. /id=PRO_0000022597"
                     /note="propagated from UniProtKB/Swiss-Prot (Q8WU66.2)"
                     /calculated_mol_wt=73045
     Region          <82..222
                     /region_name="LamG"
                     /note="Laminin G domain; Laminin G-like domains are
                     usually Ca++ mediated receptors that can have binding
                     sites for steroids, beta1 integrins, heparin, sulfatides,
                     fibulin-1, and alpha-dystroglycans. Proteins that contain
                     LamG domains serve a variety of...; cl22861"
                     /db_xref="CDD:473984"
     Region          313..358
                     /region_name="EAR 1.
                     /evidence=ECO:0000255|PROSITE-ProRule:PRU00075"
                     /note="propagated from UniProtKB/Swiss-Prot (Q8WU66.2)"
     Site            320
                     /site_type="glycosylation"
                     /note="N-linked (GlcNAc...) asparagine.
                     /evidence=ECO:0000255; propagated from
                     UniProtKB/Swiss-Prot (Q8WU66.2)"
     Region          360..408
                     /region_name="EAR 2.
                     /evidence=ECO:0000255|PROSITE-ProRule:PRU00075"
                     /note="propagated from UniProtKB/Swiss-Prot (Q8WU66.2)"
     Region          360..406
                     /region_name="EPTP"
                     /note="EPTP domain; pfam03736"
                     /db_xref="CDD:461033"
     Region          412..460
                     /region_name="EAR 3.
                     /evidence=ECO:0000255|PROSITE-ProRule:PRU00075"
                     /note="propagated from UniProtKB/Swiss-Prot (Q8WU66.2)"
     Region          412..458
                     /region_name="EPTP"
                     /note="EPTP domain; pfam03736"
                     /db_xref="CDD:461033"
     Region          464..506
                     /region_name="EAR 4.
                     /evidence=ECO:0000255|PROSITE-ProRule:PRU00075"
                     /note="propagated from UniProtKB/Swiss-Prot (Q8WU66.2)"
     Region          465..501
                     /region_name="EPTP"
                     /note="EPTP domain; pfam03736"
                     /db_xref="CDD:461033"
     Site            468
                     /site_type="glycosylation"
                     /note="N-linked (GlcNAc...) asparagine.
                     /evidence=ECO:0000255; propagated from
                     UniProtKB/Swiss-Prot (Q8WU66.2)"
     Site            497
                     /site_type="glycosylation"
                     /note="N-linked (GlcNAc...) asparagine.
                     /evidence=ECO:0000255; propagated from
                     UniProtKB/Swiss-Prot (Q8WU66.2)"
     Region          514..570
                     /region_name="EAR 5.
                     /evidence=ECO:0000255|PROSITE-ProRule:PRU00075"
                     /note="propagated from UniProtKB/Swiss-Prot (Q8WU66.2)"
     Region          515..567
                     /region_name="EPTP"
                     /note="EPTP domain; pfam03736"
                     /db_xref="CDD:461033"
     Site            556
                     /site_type="glycosylation"
                     /note="N-linked (GlcNAc...) asparagine.
                     /evidence=ECO:0000255; propagated from
                     UniProtKB/Swiss-Prot (Q8WU66.2)"
     Site            569
                     /site_type="glycosylation"
                     /note="N-linked (GlcNAc...) asparagine.
                     /evidence=ECO:0000255; propagated from
                     UniProtKB/Swiss-Prot (Q8WU66.2)"
     Region          574..622
                     /region_name="EAR 6.
                     /evidence=ECO:0000255|PROSITE-ProRule:PRU00075"
                     /note="propagated from UniProtKB/Swiss-Prot (Q8WU66.2)"
     Region          575..620
                     /region_name="EPTP"
                     /note="EPTP domain; pfam03736"
                     /db_xref="CDD:461033"
     Region          625..668
                     /region_name="EAR 7.
                     /evidence=ECO:0000255|PROSITE-ProRule:PRU00075"
                     /note="propagated from UniProtKB/Swiss-Prot (Q8WU66.2)"
     CDS             1..669
                     /gene="TSPEAR"
                     /gene_synonym="C21orf29; DFNB98; ECTD14; STHAG10; TSP-EAR"
                     /coded_by="NM_144991.3:59..2068"
                     /note="isoform 1 precursor is encoded by transcript
                     variant 1"
                     /db_xref="CCDS:CCDS13712.1"
                     /db_xref="GeneID:54084"
                     /db_xref="HGNC:HGNC:1268"
                     /db_xref="MIM:612920"
ORIGIN      
        1 msallslcfv lplaapghgt qgwepctdlr pldilaevvp sdgatsgiri vqvhgarglq
       61 lsvaaprtms fpasrifsqc dlfpeefsiv vtlrvpnlpp krneylltvv aeesdllllg
      121 lrlspaqlhf lflredtaga wqtrvsfrsp alvdgrwhtl vlavsagvfs lttdcglpvd
      181 imadvpfpat lsvkgarffv gsrrrakglf mglvrqlvll pgsdatprlc psrnaplavl
      241 siprvlqalt gkpednevlk ypyetnirvt lgpqppctev edaqfwfdas rkglylcvgn
      301 ewvsvlaake rldyveehqn lstnsetlgi evfripqvgl fvatanrkat savykwteek
      361 fvsyqnipth qaqawrhfti gkkiflavan fepdekgqef sviykwshrk lkftpyqsia
      421 thsardweaf evdgehflav anhregdnhn idsviykwnp atrlfeanqt iatsgaydwe
      481 ffsvgpysfl vvantfngts tkvhshlyir llgsfqlfqs fptfgaadwe vfqigerifl
      541 avanshsydv emqvqndsyv insviyelnv taqafvkfqd iltcsaldwe ffsvgedyfl
      601 vvansfdgrt fsvnsiiyrw qgyegfvavh slptvgcrdw eafsttagay liyssakepl
      661 srvlrlrtr
//
