B1AK53 (ESPN_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Espin

Alternative name(s):
Autosomal recessive deafness type 36 protein
Ectoplasmic specialization protein

Gene names

Name:	ESPN
Synonyms:	DFNB36
ORF Names:	LP2654

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	854 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Multifunctional actin-bundling protein. Plays a major role in regulating the organization, dimensions, dynamics and signaling capacities of the actin filament-rich, microvillus-type specializations that mediate sensory transduction in variouS mechanosensory and chemosensory cells By similarity.
Subunit structure	Monomer By similarity. Binds F-actin in a Ca2+-resistant fashion By similarity. Interacts (via N-terminal) with BAIAP2 (via SH3-domain) By similarity. Interacts with PFN2 By similarity.
Subcellular location	Cytoplasm › cytoskeleton By similarity. Cell projection › stereocilium By similarity. Cell projection › microvillus By similarity.
Domain	The WH2-domain binds actin monomer and mediates actin bundle assembly By similarity.
Involvement in 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. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.6 Ref.7
Sequence similarities	Contains 9 ANK repeats. Contains 1 WH2 domain.

Ontologies

Keywords
Biological process	Hearing
Cellular component	Cell projection Cytoplasm Cytoskeleton
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Deafness Disease mutation Non-syndromic deafness
Domain	ANK repeat Coiled coil Repeat
Ligand	Actin-binding
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	locomotory behavior Inferred from electronic annotation. Source: Compara negative regulation of cytoskeleton organization Inferred from electronic annotation. Source: Compara parallel actin filament bundle assembly Inferred from electronic annotation. Source: Compara positive regulation of filopodium assembly Inferred from electronic annotation. Source: Compara sensory perception of sound Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	brush border Inferred from sequence or structural similarity PubMed 9763424. Source: UniProtKB cytoplasm Inferred from electronic annotation. Source: UniProtKB-KW filamentous actin Inferred from sequence or structural similarity PubMed 8799813. Source: UniProtKB stereocilium Inferred from electronic annotation. Source: UniProtKB-SubCell stereocilium bundle tip Inferred from electronic annotation. Source: Compara
Molecular_function	SH3 domain binding Inferred from sequence or structural similarity PubMed 12598619. Source: UniProtKB actin filament binding Inferred from sequence or structural similarity PubMed 8799813. Source: UniProtKB
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: B1AK53-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: B1AK53-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-536: Missing.
     543-572: Missing.

Note: No experimental confirmation available.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 854	854	Espin		PRO_0000334666
Regions
	Repeat	1 – 31	31	ANK 1
	Repeat	35 – 64	30	ANK 2
	Repeat	69 – 99	31	ANK 3
	Repeat	103 – 133	31	ANK 4
	Repeat	137 – 167	31	ANK 5
	Repeat	171 – 201	31	ANK 6
	Repeat	205 – 235	31	ANK 7
	Repeat	239 – 268	30	ANK 8
	Repeat	271 – 300	30	ANK 9
	Domain	651 – 668	18	WH2
	Coiled coil	756 – 830	75	Potential
	Compositional bias	428 – 730	303	Pro-rich
	Compositional bias	768 – 825	58	Glu-rich
Natural variations
	Alternative sequence	1 – 536	536	Missing in isoform 2.		VSP_033728
	Alternative sequence	543 – 572	30	Missing in isoform 2.		VSP_033729
	Natural variant	322	1	R → H. Corresponds to variant rs3817911 [ dbSNP | Ensembl ].		VAR_043451
	Natural variant	323	1	Y → C. Corresponds to variant rs3817910 [ dbSNP | Ensembl ].		VAR_043452
	Natural variant	719	1	S → R in DFNB36; irregular microvillar organization. Ref.7		VAR_043453
	Natural variant	744	1	D → N in DFNB36; irregular microvillar organization. Ref.7		VAR_043454
	Natural variant	774	1	R → Q in DFNB36; sporadic case with mild phenotype; could be a rare polymorphism. Ref.7		VAR_043455
	Natural variant	848	1	Missing in DFNB36; severe phenotype; severe impairment of microvillar elongation; espin accumulates in the nucleus. Ref.7		VAR_043456
Experimental info
	Sequence conflict	593	1	R → G in AAP34481. Ref.2
	Sequence conflict	597	1	P → L in CAB66814. Ref.1
	Sequence conflict	678	1	F → L in AAD24480. Ref.5
	Sequence conflict	773 – 774	2	RR → SW in AAD24480. Ref.5

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified April 8, 2008. Version 1. Checksum: 34B771071F733B62	FASTA	854	91,733
	10 20 30 40 50 60 MALEQALQAA RQGELDVLRS LHAAGLLGPS LRDPLDALPV HHAARAGKLH CLRFLVEEAA 70 80 90 100 110 120 LPAAARARNG ATPAHDASAT GHLACLQWLL SQGGCRVQDK DNSGATVLHL AARFGHPEVV 130 140 150 160 170 180 NWLLHHGGGD PTAATDMGAL PIHYAAAKGD FPSLRLLVEH YPEGVNAQTK NGATPLYLAC 190 200 210 220 230 240 QEGHLEVTQY LVQECGADPH ARAHDGMTPL HAAAQMGHSP VIVWLVSCTD VSLSEQDKDG 250 260 270 280 290 300 ATAMHFAASR GHTKVLSWLL LHGGEISADL WGGTPLHDAA ENGELECCQI LVVNGAELDV 310 320 330 340 350 360 RDRDGYTAAD LSDFNGHSHC TRYLRTVENL SVEHRVLSRD PSAELEAKQP DSGMSSPNTT 370 380 390 400 410 420 VSVQPLNFDL SSPTSTLSNY DSCSSSHSSI KGQHPPCGLS SARAADIQSY MDMLNPELGL 430 440 450 460 470 480 PRGTIGKPTP PPPPPSFPPP PPPPGTQLPP PPPGYPAPKP PVGPQAADIY MQTKNKLRHV 490 500 510 520 530 540 ETEALKKELS SCDGHDGLRR QDSSRKPRAF SKQPSTGDYY RQLGRCPGET LAARPGMAHS 550 560 570 580 590 600 EEVRARQPAR AGCPRLGPAA RGSLEGPSAP PQAALLPGNH VPNGCAADPK ASRELPPPPP 610 620 630 640 650 660 PPPPPLPEAA SSPPPAPPLP LESAGPGCGQ RRSSSSTGST KSFNMMSPTG DNSELLAEIK 670 680 690 700 710 720 AGKSLKPTPQ SKGLTTVFSG IGQPAFQPDS PLPSVSPALS PVRSPTPPAA GFQPLLNGSL 730 740 750 760 770 780 VPVPPTTPAP GVQLDVEALI PTHDEQGRPI PEWKRQVMVR KMQLKMQEEE EQRRKEEEEE 790 800 810 820 830 840 ARLASMPAWR RDLLRKKLEE EREQKRKEEE RQKQEELRRE KEQSEKLRTL GYDESKLAPW 850 QRQVILKKGD IAKY
	Isoform 2 [UniParc]. Checksum: 35E402CA6E9C0AB3	FASTA	288	31,636
	10 20 30 40 50 60 MAHSEEAALL PGNHVPNGCA ADPKASRELP PPPPPPPPPL PEAASSPPPA PPLPLESAGP 70 80 90 100 110 120 GCGQRRSSSS TGSTKSFNMM SPTGDNSELL AEIKAGKSLK PTPQSKGLTT VFSGIGQPAF 130 140 150 160 170 180 QPDSPLPSVS PALSPVRSPT PPAAGFQPLL NGSLVPVPPT TPAPGVQLDV EALIPTHDEQ 190 200 210 220 230 240 GRPIPEWKRQ VMVRKMQLKM QEEEEQRRKE EEEEARLASM PAWRRDLLRK KLEEEREQKR 250 260 270 280 KEEERQKQEE LRREKEQSEK LRTLGYDESK LAPWQRQVIL KKGDIAKY

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Towards a catalog of human genes and proteins: sequencing and analysis of 500 novel complete protein coding human cDNAs." 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. Genome Res. 11:422-435(2001) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
[2]	"Large-scale cDNA transfection screening for genes related to cancer development and progression." 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. Proc. Natl. Acad. Sci. U.S.A. 101:15724-15729(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
[3]	"The DNA sequence and biological annotation of human chromosome 1." 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. Nature 441:315-321(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	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 Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	"Organization and chromosomal location of the espin gene in the human." Bartles J.R., Zheng L., Li A., Wang M. Submitted (MAR-1999) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 663-854. Tissue: Testis.
[6]	"Mutations of ESPN cause autosomal recessive deafness and vestibular dysfunction." 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. J. Med. Genet. 41:591-595(2004) [PubMed] [Europe PMC] [Abstract] Cited for: INVOLVEMENT IN DFNB36.
[7]	"Espin gene (ESPN) mutations associated with autosomal dominant hearing loss cause defects in microvillar elongation or organisation." Donaudy F., Zheng L., Ficarella R., Ballana E., Carella M., Melchionda S., Estivill X., Bartles J.R., Gasparini P. J. Med. Genet. 43:157-161(2006) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS DFNB36 ARG-719; ASN-744; GLN-774 AND LYS-848 DEL, CHARACTERIZATION OF VARIANTS DFNB36 ARG-719; ASN-744 AND LYS-848 DEL.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AL136880 mRNA. Translation: CAB66814.1. AY203958 mRNA. Translation: AAP34481.1. AL031848, AL158217 Genomic DNA. Translation: CAI19773.1. AL158217, AL031848 Genomic DNA. Translation: CAI22163.1. CH471130 Genomic DNA. Translation: EAW71537.1. AF134401 mRNA. Translation: AAD24480.1.
IPI	IPI00027820. IPI00642699.
RefSeq	NP_113663.2. NM_031475.2.
UniGene	Hs.744222.
3D structure databases
ProteinModelPortal	B1AK53.
ModBase	Search...
Protein-protein interaction databases
STRING	9606.ENSP00000367059.
PTM databases
PhosphoSite	B1AK53.
Proteomic databases
PaxDb	B1AK53.
PRIDE	B1AK53.
Protocols and materials databases
DNASU	83715.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000377828; ENSP00000367059; ENSG00000187017. ENST00000416731; ENSP00000399239; ENSG00000187017. ENST00000461727; ENSP00000465308; ENSG00000187017.
GeneID	83715.
KEGG	hsa:83715.
UCSC	uc001amy.3. human. uc001amz.3. human.
Organism-specific databases
CTD	83715.
GeneCards	GC01P006484.
H-InvDB	HIX0000079. HIX0028654.
HGNC	HGNC:13281. ESPN.
HPA	HPA028674.
MIM	606351. gene. 609006. phenotype.
neXtProt	NX_B1AK53.
Orphanet	90636. Autosomal recessive nonsyndromic sensorineural deafness type DFNB.
PharmGKB	PA27885.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG0666.
HOGENOM	HOG000049230.
HOVERGEN	HBG100662.
InParanoid	B1AK53.
OMA	AKQPDSG.
OrthoDB	EOG4F1X2P.
PhylomeDB	B1AK53.
Gene expression databases
ArrayExpress	B1AK53.
Bgee	B1AK53.
CleanEx	HS_ESPN.
Genevestigator	B1AK53.
Family and domain databases
Gene3D	1.25.40.20. 1 hit.
InterPro	IPR002110. Ankyrin_rpt. IPR020683. Ankyrin_rpt-contain_dom. IPR003124. WH2_dom. [Graphical view]
Pfam	PF00023. Ank. 1 hit. PF12796. Ank_2. 3 hits. PF02205. WH2. 1 hit. [Graphical view]
SMART	SM00248. ANK. 8 hits. SM00246. WH2. 1 hit. [Graphical view]
SUPFAM	SSF48403. ANK. 2 hits.
PROSITE	PS50297. ANK_REP_REGION. 1 hit. PS50088. ANK_REPEAT. 6 hits. PS51082. WH2. 1 hit. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	ESPN. human.
GenomeRNAi	83715.
NextBio	72707.
SOURCE	Search...

Entry information

Entry name

ESPN_HUMAN

Accession

Primary (citable) accession number: B1AK53
Secondary accession number(s): Q6XYB2, Q9H0A2, Q9Y329

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 20, 2008
Last sequence update:	April 8, 2008
Last modified:	May 29, 2013
This is version 57 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.