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Espin (Autosomal recessive deafness type 36 protein) (Ectoplasmic specialization protein)

 ESPN_HUMAN              Reviewed;         854 AA.
B1AK53; Q6XYB2; Q9H0A2; Q9Y329;
20-MAY-2008, integrated into UniProtKB/Swiss-Prot.
08-APR-2008, sequence version 1.
05-DEC-2018, entry version 101.
RecName: Full=Espin;
AltName: Full=Autosomal recessive deafness type 36 protein;
AltName: Full=Ectoplasmic specialization protein;
Name=ESPN; Synonyms=DFNB36; ORFNames=LP2654;
Homo sapiens (Human).
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
Catarrhini; Hominidae; Homo.
NCBI_TaxID=9606;
[1]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
PubMed=11230166; DOI=10.1101/gr.GR1547R;
Wiemann S., Weil B., Wellenreuther R., Gassenhuber J., Glassl S.,
Ansorge W., Boecher M., Bloecker H., Bauersachs S., Blum H.,
Lauber J., Duesterhoeft A., Beyer A., Koehrer K., Strack N.,
Mewes H.-W., Ottenwaelder B., Obermaier B., Tampe J., Heubner D.,
Wambutt R., Korn B., Klein M., Poustka A.;
"Towards a catalog of human genes and proteins: sequencing and
analysis of 500 novel complete protein coding human cDNAs.";
Genome Res. 11:422-435(2001).
[2]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
PubMed=15498874; DOI=10.1073/pnas.0404089101;
Wan D., Gong Y., Qin W., Zhang P., Li J., Wei L., Zhou X., Li H.,
Qiu X., Zhong F., He L., Yu J., Yao G., Jiang H., Qian L., Yu Y.,
Shu H., Chen X., Xu H., Guo M., Pan Z., Chen Y., Ge C., Yang S.,
Gu J.;
"Large-scale cDNA transfection screening for genes related to cancer
development and progression.";
Proc. Natl. Acad. Sci. U.S.A. 101:15724-15729(2004).
[3]
NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
PubMed=16710414; DOI=10.1038/nature04727;
Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D.,
Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A.,
Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F.,
McDonald L., Evans R., Phillips K., Atkinson A., Cooper R., Jones C.,
Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P.,
Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K.,
Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G.,
Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D.,
Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G.,
Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J.,
Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R.,
Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D.,
Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G.,
Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M.,
Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J.,
Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M.,
Loveland J., Lovell J., Lush M.J., Lyne R., Martin S.,
Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S.,
Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C.,
Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z.,
Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E.,
Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A.,
Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R.,
Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V.,
Beck S., Rogers J., Bentley D.R.;
"The DNA sequence and biological annotation of human chromosome 1.";
Nature 441:315-321(2006).
[4]
NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
Venter J.C.;
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
[5]
NUCLEOTIDE SEQUENCE [MRNA] OF 663-854.
TISSUE=Testis;
Bartles J.R., Zheng L., Li A., Wang M.;
"Organization and chromosomal location of the espin gene in the
human.";
Submitted (MAR-1999) to the EMBL/GenBank/DDBJ databases.
[6]
INVOLVEMENT IN DFNB36.
PubMed=15286153; DOI=10.1136/jmg.2004.018523;
Naz S., Griffith A.J., Riazuddin S., Hampton L.L., Battey J.F. Jr.,
Khan S.N., Riazuddin S., Wilcox E.R., Friedman T.B.;
"Mutations of ESPN cause autosomal recessive deafness and vestibular
dysfunction.";
J. Med. Genet. 41:591-595(2004).
[7]
VARIANTS DFNB36 ARG-719; ASN-744; GLN-774 AND LYS-848 DEL, AND
CHARACTERIZATION OF VARIANTS DFNB36 ARG-719; ASN-744 AND LYS-848 DEL.
PubMed=15930085; DOI=10.1136/jmg.2005.032086;
Donaudy F., Zheng L., Ficarella R., Ballana E., Carella M.,
Melchionda S., Estivill X., Bartles J.R., Gasparini P.;
"Espin gene (ESPN) mutations associated with autosomal dominant
hearing loss cause defects in microvillar elongation or
organisation.";
J. Med. Genet. 43:157-161(2006).
[8]
VARIANT DFNB36 840-TRP--TYR-854 DEL.
PubMed=28281779; DOI=10.1089/gtmb.2016.0328;
Wang R., Han S., Khan A., Zhang X.;
"Molecular Analysis of Twelve Pakistani Families with Nonsyndromic or
Syndromic Hearing Loss.";
Genet. Test. Mol. Biomarkers 21:316-321(2017).
-!- FUNCTION: Multifunctional actin-bundling protein. Plays a major
role in regulating the organization, dimension, dynamics and
signaling capacities of the actin filament-rich microvilli in the
mechanosensory and chemosensory cells. Required for the assembly
and stabilization of the stereociliary parallel actin bundles.
Plays a crucial role in the formation and maintenance of inner ear
hair cell stereocilia. Involved in the elongation of actin in
stereocilia. In extrastriolar hair cells, required for targeting
MYO3B to stereocilia tips, and for regulation of stereocilia
diameter and staircase formation. {ECO:0000250|UniProtKB:Q9ET47}.
-!- SUBUNIT: Monomer. Binds F-actin in a Ca(2+)-resistant fashion.
Interacts (via N-terminus) with BAIAP2 (via SH3-domain). Interacts
with PFN2. Interacts with MYO3A (via C-terminus). Interacts with
MYO3B (via C-terminus). {ECO:0000250|UniProtKB:Q9ET47}.
-!- SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton
{ECO:0000250|UniProtKB:Q9ET47}. Cell projection, stereocilium
{ECO:0000250|UniProtKB:Q9ET47}. Cell projection, microvillus
{ECO:0000250|UniProtKB:Q9ET47}.
-!- ALTERNATIVE PRODUCTS:
Event=Alternative splicing; Named isoforms=2;
Name=1;
IsoId=B1AK53-1; Sequence=Displayed;
Name=2;
IsoId=B1AK53-2; Sequence=VSP_033728, VSP_033729;
Note=No experimental confirmation available.;
-!- DOMAIN: The WH2-domain binds actin monomer and mediates actin
bundle assembly. {ECO:0000250|UniProtKB:Q9ET47}.
-!- DISEASE: Deafness, autosomal recessive, 36, with or without
vestibular involvement (DFNB36) [MIM:609006]: A form of non-
syndromic sensorineural hearing loss. Sensorineural deafness
results from damage to the neural receptors of the inner ear, the
nerve pathways to the brain, or the area of the brain that
receives sound information. DFNB36 is characterized by prelingual,
profound hearing loss, and vestibular areflexia in some patients.
{ECO:0000269|PubMed:15286153, ECO:0000269|PubMed:15930085,
ECO:0000269|PubMed:28281779}. Note=The disease is caused by
mutations affecting the gene represented in this entry.
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EMBL; AL136880; CAB66814.1; -; mRNA.
EMBL; AY203958; AAP34481.1; -; mRNA.
EMBL; AL031848; -; NOT_ANNOTATED_CDS; Genomic_DNA.
EMBL; AL158217; -; NOT_ANNOTATED_CDS; Genomic_DNA.
EMBL; CH471130; EAW71537.1; -; Genomic_DNA.
EMBL; AF134401; AAD24480.1; -; mRNA.
CCDS; CCDS70.1; -. [B1AK53-1]
RefSeq; NP_113663.2; NM_031475.2. [B1AK53-1]
UniGene; Hs.744222; -.
ProteinModelPortal; B1AK53; -.
SMR; B1AK53; -.
BioGrid; 123738; 1.
STRING; 9606.ENSP00000367059; -.
iPTMnet; B1AK53; -.
PhosphoSitePlus; B1AK53; -.
BioMuta; ESPN; -.
EPD; B1AK53; -.
MaxQB; B1AK53; -.
PaxDb; B1AK53; -.
PRIDE; B1AK53; -.
ProteomicsDB; 3019; -.
ProteomicsDB; 3020; -. [B1AK53-2]
DNASU; 83715; -.
Ensembl; ENST00000377828; ENSP00000367059; ENSG00000187017. [B1AK53-1]
Ensembl; ENST00000461727; ENSP00000465308; ENSG00000187017. [B1AK53-2]
Ensembl; ENST00000645284; ENSP00000496593; ENSG00000187017. [B1AK53-1]
GeneID; 83715; -.
KEGG; hsa:83715; -.
UCSC; uc001amy.3; human. [B1AK53-1]
CTD; 83715; -.
DisGeNET; 83715; -.
EuPathDB; HostDB:ENSG00000187017.14; -.
GeneCards; ESPN; -.
GeneReviews; ESPN; -.
H-InvDB; HIX0000079; -.
H-InvDB; HIX0028654; -.
HGNC; HGNC:13281; ESPN.
HPA; HPA028674; -.
HPA; HPA060220; -.
MalaCards; ESPN; -.
MIM; 606351; gene.
MIM; 609006; phenotype.
neXtProt; NX_B1AK53; -.
OpenTargets; ENSG00000187017; -.
Orphanet; 90636; Autosomal recessive non-syndromic sensorineural deafness type DFNB.
PharmGKB; PA27885; -.
eggNOG; KOG0504; Eukaryota.
eggNOG; COG0666; LUCA.
GeneTree; ENSGT00940000160408; -.
HOGENOM; HOG000049230; -.
HOVERGEN; HBG100662; -.
InParanoid; B1AK53; -.
OrthoDB; EOG091G056N; -.
PhylomeDB; B1AK53; -.
TreeFam; TF326392; -.
ChiTaRS; ESPN; human.
GeneWiki; Espin_(protein); -.
GenomeRNAi; 83715; -.
PRO; PR:B1AK53; -.
Proteomes; UP000005640; Chromosome 1.
Bgee; ENSG00000187017; Expressed in 117 organ(s), highest expression level in right testis.
CleanEx; HS_ESPN; -.
ExpressionAtlas; B1AK53; baseline and differential.
Genevisible; B1AK53; HS.
GO; GO:0005903; C:brush border; ISS:UniProtKB.
GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
GO; GO:0031941; C:filamentous actin; ISS:UniProtKB.
GO; GO:0005902; C:microvillus; IEA:UniProtKB-SubCell.
GO; GO:0032426; C:stereocilium tip; ISS:UniProtKB.
GO; GO:0051015; F:actin filament binding; ISS:UniProtKB.
GO; GO:0017124; F:SH3 domain binding; ISS:UniProtKB.
GO; GO:0051017; P:actin filament bundle assembly; IBA:GO_Central.
GO; GO:0007626; P:locomotory behavior; IEA:Ensembl.
GO; GO:0051494; P:negative regulation of cytoskeleton organization; IEA:Ensembl.
GO; GO:0030046; P:parallel actin filament bundle assembly; IEA:Ensembl.
GO; GO:0051491; P:positive regulation of filopodium assembly; IEA:Ensembl.
GO; GO:0007605; P:sensory perception of sound; IEA:UniProtKB-KW.
CDD; cd00204; ANK; 3.
Gene3D; 1.25.40.20; -; 1.
InterPro; IPR002110; Ankyrin_rpt.
InterPro; IPR020683; Ankyrin_rpt-contain_dom.
InterPro; IPR036770; Ankyrin_rpt-contain_sf.
InterPro; IPR030233; Espn.
InterPro; IPR003124; WH2_dom.
PANTHER; PTHR24153:SF14; PTHR24153:SF14; 1.
Pfam; PF12796; Ank_2; 3.
Pfam; PF02205; WH2; 1.
SMART; SM00248; ANK; 8.
SMART; SM00246; WH2; 1.
SUPFAM; SSF48403; SSF48403; 1.
PROSITE; PS50297; ANK_REP_REGION; 1.
PROSITE; PS50088; ANK_REPEAT; 6.
PROSITE; PS51082; WH2; 1.
1: Evidence at protein level;
Actin-binding; Alternative splicing; ANK repeat; Cell projection;
Coiled coil; Complete proteome; Cytoplasm; Cytoskeleton; Deafness;
Disease mutation; Hearing; Non-syndromic deafness; Phosphoprotein;
Polymorphism; Reference proteome; Repeat.
CHAIN 1 854 Espin.
/FTId=PRO_0000334666.
REPEAT 1 31 ANK 1.
REPEAT 35 64 ANK 2.
REPEAT 69 99 ANK 3.
REPEAT 103 133 ANK 4.
REPEAT 137 167 ANK 5.
REPEAT 171 201 ANK 6.
REPEAT 205 235 ANK 7.
REPEAT 239 268 ANK 8.
REPEAT 271 300 ANK 9.
DOMAIN 651 668 WH2. {ECO:0000255|PROSITE-
ProRule:PRU00406}.
COILED 756 830 {ECO:0000255}.
COMPBIAS 428 730 Pro-rich.
COMPBIAS 768 825 Glu-rich.
MOD_RES 338 338 Phosphoserine.
{ECO:0000250|UniProtKB:Q63618}.
MOD_RES 342 342 Phosphoserine.
{ECO:0000250|UniProtKB:Q9ET47}.
MOD_RES 515 515 Phosphoserine.
{ECO:0000250|UniProtKB:Q63618}.
MOD_RES 647 647 Phosphoserine.
{ECO:0000250|UniProtKB:Q9ET47}.
MOD_RES 690 690 Phosphoserine.
{ECO:0000250|UniProtKB:Q9ET47}.
MOD_RES 696 696 Phosphoserine.
{ECO:0000250|UniProtKB:Q63618}.
VAR_SEQ 1 536 Missing (in isoform 2).
{ECO:0000303|PubMed:15498874}.
/FTId=VSP_033728.
VAR_SEQ 543 572 Missing (in isoform 2).
{ECO:0000303|PubMed:15498874}.
/FTId=VSP_033729.
VARIANT 322 322 R -> H (in dbSNP:rs3817911).
/FTId=VAR_043451.
VARIANT 323 323 Y -> C (in dbSNP:rs3817910).
/FTId=VAR_043452.
VARIANT 719 719 S -> R (in DFNB36; irregular microvillar
organization; dbSNP:rs121908134).
{ECO:0000269|PubMed:15930085}.
/FTId=VAR_043453.
VARIANT 744 744 D -> N (in DFNB36; irregular microvillar
organization; dbSNP:rs121908135).
{ECO:0000269|PubMed:15930085}.
/FTId=VAR_043454.
VARIANT 774 774 R -> Q (in DFNB36; sporadic case with
mild phenotype; unknown pathological
significance; dbSNP:rs121908136).
{ECO:0000269|PubMed:15930085}.
/FTId=VAR_043455.
VARIANT 840 854 Missing (in DFNB36).
{ECO:0000269|PubMed:28281779}.
/FTId=VAR_079505.
VARIANT 848 848 Missing (in DFNB36; severe phenotype;
severe impairment of microvillar
elongation; espin is less efficiently
targeted to the microvilli and
accumulates in the nucleus).
{ECO:0000269|PubMed:15930085}.
/FTId=VAR_043456.
CONFLICT 593 593 R -> G (in Ref. 2; AAP34481).
{ECO:0000305}.
CONFLICT 597 597 P -> L (in Ref. 1; CAB66814).
{ECO:0000305}.
CONFLICT 678 678 F -> L (in Ref. 5; AAD24480).
{ECO:0000305}.
CONFLICT 773 774 RR -> SW (in Ref. 5; AAD24480).
{ECO:0000305}.
SEQUENCE 854 AA; 91733 MW; 34B771071F733B62 CRC64;
MALEQALQAA RQGELDVLRS LHAAGLLGPS LRDPLDALPV HHAARAGKLH CLRFLVEEAA
LPAAARARNG ATPAHDASAT GHLACLQWLL SQGGCRVQDK DNSGATVLHL AARFGHPEVV
NWLLHHGGGD PTAATDMGAL PIHYAAAKGD FPSLRLLVEH YPEGVNAQTK NGATPLYLAC
QEGHLEVTQY LVQECGADPH ARAHDGMTPL HAAAQMGHSP VIVWLVSCTD VSLSEQDKDG
ATAMHFAASR GHTKVLSWLL LHGGEISADL WGGTPLHDAA ENGELECCQI LVVNGAELDV
RDRDGYTAAD LSDFNGHSHC TRYLRTVENL SVEHRVLSRD PSAELEAKQP DSGMSSPNTT
VSVQPLNFDL SSPTSTLSNY DSCSSSHSSI KGQHPPCGLS SARAADIQSY MDMLNPELGL
PRGTIGKPTP PPPPPSFPPP PPPPGTQLPP PPPGYPAPKP PVGPQAADIY MQTKNKLRHV
ETEALKKELS SCDGHDGLRR QDSSRKPRAF SKQPSTGDYY RQLGRCPGET LAARPGMAHS
EEVRARQPAR AGCPRLGPAA RGSLEGPSAP PQAALLPGNH VPNGCAADPK ASRELPPPPP
PPPPPLPEAA SSPPPAPPLP LESAGPGCGQ RRSSSSTGST KSFNMMSPTG DNSELLAEIK
AGKSLKPTPQ SKGLTTVFSG IGQPAFQPDS PLPSVSPALS PVRSPTPPAA GFQPLLNGSL
VPVPPTTPAP GVQLDVEALI PTHDEQGRPI PEWKRQVMVR KMQLKMQEEE EQRRKEEEEE
ARLASMPAWR RDLLRKKLEE EREQKRKEEE RQKQEELRRE KEQSEKLRTL GYDESKLAPW
QRQVILKKGD IAKY


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DFNB57 DFNB55 Gene deafness, autosomal recessive 55
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DFNB56 DFNB51 Gene deafness, autosomal recessive 51
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DFNB82 DFNB74 Gene deafness, autosomal recessive 74
DFNB60 DFNB58 Gene deafness, autosomal recessive 58
DFNB72 DFNB70 Gene deafness, autosomal recessive 70
DFNB71 DFNB69 Gene deafness, autosomal recessive 69
DFNB70 DFNB68 Gene deafness, autosomal recessive 68
DFNB69 DFNB66 Gene deafness, autosomal recessive 66
DFNB68 DFNB65 Gene deafness, autosomal recessive 65
DFNB75 DFNB72 Gene deafness, autosomal recessive 72
DFNB66 DFNB62 Gene deafness, autosomal recessive 62
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