TSEAR_HUMAN
ID TSEAR_HUMAN Reviewed; 669 AA.
AC Q8WU66;
DT 28-NOV-2002, integrated into UniProtKB/Swiss-Prot.
DT 28-NOV-2002, sequence version 2.
DT 03-AUG-2022, entry version 155.
DE RecName: Full=Thrombospondin-type laminin G domain and EAR repeat-containing protein;
DE Short=TSP-EAR;
DE Flags: Precursor;
GN Name=TSPEAR; Synonyms=C21orf29;
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).
RX PubMed=12095917; DOI=10.1093/hmg/11.15.1757;
RA Scheel H., Tomiuk S., Hofmann K.;
RT "A common protein interaction domain links two recently identified epilepsy
RT genes.";
RL Hum. Mol. Genet. 11:1757-1762(2002).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 28-669 (ISOFORM 2).
RC TISSUE=Lung;
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 [3]
RP POSSIBLE FUNCTION, AND INVOLVEMENT IN DFNB98.
RX PubMed=22678063; DOI=10.1093/hmg/dds212;
RA Delmaghani S., Aghaie A., Michalski N., Bonnet C., Weil D., Petit C.;
RT "Defect in the gene encoding the EAR/EPTP domain-containing protein TSPEAR
RT causes DFNB98 profound deafness.";
RL Hum. Mol. Genet. 21:3835-3844(2012).
RN [4]
RP FUNCTION, INVOLVEMENT IN ECTD14, AND VARIANTS ECTD14 PHE-576; ASN-618 AND
RP ASN-639.
RX PubMed=27736875; DOI=10.1371/journal.pgen.1006369;
RA Peled A., Sarig O., Samuelov L., Bertolini M., Ziv L., Weissglas-Volkov D.,
RA Eskin-Schwartz M., Adase C.A., Malchin N., Bochner R., Fainberg G.,
RA Goldberg I., Sugawara K., Baniel A., Tsuruta D., Luxenburg C., Adir N.,
RA Duverger O., Morasso M., Shalev S., Gallo R.L., Shomron N., Paus R.,
RA Sprecher E.;
RT "Mutations in TSPEAR, Encoding a Regulator of Notch Signaling, Affect Tooth
RT and Hair Follicle Morphogenesis.";
RL PLoS Genet. 12:E1006369-E1006369(2016).
RN [5]
RP VARIANT [LARGE SCALE ANALYSIS] THR-166.
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: Plays a critical role in tooth and hair follicle
CC morphogenesis through regulation of the Notch signaling pathway
CC (PubMed:27736875). May play a role in development or function of the
CC auditory system (PubMed:22678063). {ECO:0000269|PubMed:22678063,
CC ECO:0000269|PubMed:27736875}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000250|UniProtKB:J3S6Y1}. Cell
CC surface {ECO:0000250|UniProtKB:J3S6Y1}. Cell projection, stereocilium
CC {ECO:0000250|UniProtKB:J3S6Y1}. Note=Secreted protein which may bind to
CC the cell surface via a membrane receptor.
CC {ECO:0000250|UniProtKB:J3S6Y1}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q8WU66-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8WU66-2; Sequence=VSP_004006, VSP_004007;
CC -!- DISEASE: Deafness, autosomal recessive, 98 (DFNB98) [MIM:614861]: A
CC form of non-syndromic sensorineural hearing loss with prelingual onset.
CC Sensorineural deafness results from damage to the neural receptors of
CC the inner ear, the nerve pathways to the brain, or the area of the
CC brain that receives sound information. {ECO:0000269|PubMed:22678063}.
CC Note=The disease is caused by variants affecting the gene represented
CC in this entry.
CC -!- DISEASE: Ectodermal dysplasia 14, hair/tooth type with or without
CC hypohidrosis (ECTD14) [MIM:618180]: A form of ectodermal dysplasia, a
CC disorder due to abnormal development of two or more ectodermal
CC structures. ECTD14 is an autosomal recessive form characterized by
CC scalp hypotrichosis, hypodontia, and mild facial dysmorphism. Some
CC patients have decreased sweating. {ECO:0000269|PubMed:27736875}.
CC Note=The disease is caused by variants affecting the gene represented
CC in this entry.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH21197.2; Type=Miscellaneous discrepancy; Note=Intron retention.; Evidence={ECO:0000305};
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DR EMBL; AJ487962; CAD32309.1; -; mRNA.
DR EMBL; BC021197; AAH21197.2; ALT_SEQ; mRNA.
DR CCDS; CCDS13712.1; -. [Q8WU66-1]
DR RefSeq; NP_001258966.1; NM_001272037.1.
DR RefSeq; NP_659428.2; NM_144991.2. [Q8WU66-1]
DR AlphaFoldDB; Q8WU66; -.
DR SMR; Q8WU66; -.
DR BioGRID; 119886; 1.
DR IntAct; Q8WU66; 1.
DR STRING; 9606.ENSP00000321987; -.
DR GlyGen; Q8WU66; 5 sites.
DR iPTMnet; Q8WU66; -.
DR PhosphoSitePlus; Q8WU66; -.
DR BioMuta; TSPEAR; -.
DR DMDM; 26006900; -.
DR EPD; Q8WU66; -.
DR MassIVE; Q8WU66; -.
DR PaxDb; Q8WU66; -.
DR PeptideAtlas; Q8WU66; -.
DR PRIDE; Q8WU66; -.
DR Antibodypedia; 53321; 96 antibodies from 14 providers.
DR DNASU; 54084; -.
DR Ensembl; ENST00000323084.9; ENSP00000321987.4; ENSG00000175894.18. [Q8WU66-1]
DR GeneID; 54084; -.
DR KEGG; hsa:54084; -.
DR MANE-Select; ENST00000323084.9; ENSP00000321987.4; NM_144991.3; NP_659428.2.
DR UCSC; uc002zfe.1; human. [Q8WU66-1]
DR CTD; 54084; -.
DR DisGeNET; 54084; -.
DR GeneCards; TSPEAR; -.
DR HGNC; HGNC:1268; TSPEAR.
DR HPA; ENSG00000175894; Tissue enhanced (pituitary gland, skin, testis).
DR MalaCards; TSPEAR; -.
DR MIM; 612920; gene.
DR MIM; 614861; phenotype.
DR MIM; 618180; phenotype.
DR neXtProt; NX_Q8WU66; -.
DR OpenTargets; ENSG00000175894; -.
DR Orphanet; 90636; Autosomal recessive non-syndromic sensorineural deafness type DFNB.
DR PharmGKB; PA25824; -.
DR VEuPathDB; HostDB:ENSG00000175894; -.
DR eggNOG; KOG3544; Eukaryota.
DR GeneTree; ENSGT00510000047718; -.
DR InParanoid; Q8WU66; -.
DR OMA; EIPTCSA; -.
DR OrthoDB; 258208at2759; -.
DR PhylomeDB; Q8WU66; -.
DR TreeFam; TF329841; -.
DR PathwayCommons; Q8WU66; -.
DR SignaLink; Q8WU66; -.
DR BioGRID-ORCS; 54084; 7 hits in 1068 CRISPR screens.
DR ChiTaRS; TSPEAR; human.
DR GenomeRNAi; 54084; -.
DR Pharos; Q8WU66; Tbio.
DR PRO; PR:Q8WU66; -.
DR Proteomes; UP000005640; Chromosome 21.
DR RNAct; Q8WU66; protein.
DR Bgee; ENSG00000175894; Expressed in adenohypophysis and 57 other tissues.
DR ExpressionAtlas; Q8WU66; baseline and differential.
DR Genevisible; Q8WU66; HS.
DR GO; GO:0009986; C:cell surface; ISS:UniProtKB.
DR GO; GO:0060170; C:ciliary membrane; IEA:Ensembl.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0032420; C:stereocilium; ISS:UniProtKB.
DR GO; GO:0022405; P:hair cycle process; IEA:Ensembl.
DR GO; GO:0007219; P:Notch signaling pathway; IEA:Ensembl.
DR GO; GO:0008593; P:regulation of Notch signaling pathway; IMP:UniProtKB.
DR GO; GO:0007605; P:sensory perception of sound; IMP:UniProtKB.
DR GO; GO:0007165; P:signal transduction; IBA:GO_Central.
DR GO; GO:0034505; P:tooth mineralization; IMP:UniProtKB.
DR InterPro; IPR013320; ConA-like_dom_sf.
DR InterPro; IPR009039; EAR.
DR InterPro; IPR005492; EPTP.
DR InterPro; IPR001791; Laminin_G.
DR Pfam; PF03736; EPTP; 5.
DR SMART; SM00210; TSPN; 1.
DR SUPFAM; SSF49899; SSF49899; 1.
DR PROSITE; PS50912; EAR; 7.
PE 1: Evidence at protein level;
KW Alternative splicing; Cell projection; Deafness; Disease variant;
KW Ectodermal dysplasia; Glycoprotein; Hearing; Non-syndromic deafness;
KW Reference proteome; Repeat; Secreted; Signal.
FT SIGNAL 1..19
FT /evidence="ECO:0000255"
FT CHAIN 20..669
FT /note="Thrombospondin-type laminin G domain and EAR repeat-
FT containing protein"
FT /id="PRO_0000022597"
FT DOMAIN 58..277
FT /note="Laminin G-like"
FT REPEAT 313..358
FT /note="EAR 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00075"
FT REPEAT 360..408
FT /note="EAR 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00075"
FT REPEAT 412..460
FT /note="EAR 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00075"
FT REPEAT 464..506
FT /note="EAR 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00075"
FT REPEAT 514..570
FT /note="EAR 5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00075"
FT REPEAT 574..622
FT /note="EAR 6"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00075"
FT REPEAT 625..668
FT /note="EAR 7"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00075"
FT CARBOHYD 320
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 468
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 497
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 556
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 569
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VAR_SEQ 586..598
FT /note="ALDWEFFSVGEDY -> GGRRGLHARRAEG (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_004006"
FT VAR_SEQ 599..669
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_004007"
FT VARIANT 166
FT /note="A -> T (in a colorectal cancer sample; somatic
FT mutation; dbSNP:rs782068174)"
FT /evidence="ECO:0000269|PubMed:16959974"
FT /id="VAR_036271"
FT VARIANT 576
FT /note="V -> F (in ECTD14; unknown pathological
FT significance; dbSNP:rs782543541)"
FT /evidence="ECO:0000269|PubMed:27736875"
FT /id="VAR_081734"
FT VARIANT 618
FT /note="Y -> N (in ECTD14; unknown pathological
FT significance; dbSNP:rs781868760)"
FT /evidence="ECO:0000269|PubMed:27736875"
FT /id="VAR_081735"
FT VARIANT 639
FT /note="D -> N (in ECTD14; unknown pathological
FT significance; dbSNP:rs138480801)"
FT /evidence="ECO:0000269|PubMed:27736875"
FT /id="VAR_081736"
SQ SEQUENCE 669 AA; 74924 MW; E3E880708B63812E CRC64;
MSALLSLCFV LPLAAPGHGT QGWEPCTDLR PLDILAEVVP SDGATSGIRI VQVHGARGLQ
LSVAAPRTMS FPASRIFSQC DLFPEEFSIV VTLRVPNLPP KRNEYLLTVV AEESDLLLLG
LRLSPAQLHF LFLREDTAGA WQTRVSFRSP ALVDGRWHTL VLAVSAGVFS LTTDCGLPVD
IMADVPFPAT LSVKGARFFV GSRRRAKGLF MGLVRQLVLL PGSDATPRLC PSRNAPLAVL
SIPRVLQALT GKPEDNEVLK YPYETNIRVT LGPQPPCTEV EDAQFWFDAS RKGLYLCVGN
EWVSVLAAKE RLDYVEEHQN LSTNSETLGI EVFRIPQVGL FVATANRKAT SAVYKWTEEK
FVSYQNIPTH QAQAWRHFTI GKKIFLAVAN FEPDEKGQEF SVIYKWSHRK LKFTPYQSIA
THSARDWEAF EVDGEHFLAV ANHREGDNHN IDSVIYKWNP ATRLFEANQT IATSGAYDWE
FFSVGPYSFL VVANTFNGTS TKVHSHLYIR LLGSFQLFQS FPTFGAADWE VFQIGERIFL
AVANSHSYDV EMQVQNDSYV INSVIYELNV TAQAFVKFQD ILTCSALDWE FFSVGEDYFL
VVANSFDGRT FSVNSIIYRW QGYEGFVAVH SLPTVGCRDW EAFSTTAGAY LIYSSAKEPL
SRVLRLRTR
