O60443 (DFNA5_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Non-syndromic hearing impairment protein 5

Alternative name(s):
Inversely correlated with estrogen receptor expression 1
Short name=ICERE-1

Gene names

Name:	DFNA5
Synonyms:	ICERE1

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	496 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Involved in apoptosis and cell survival. Plays a role in the TP53-regulated cellular response to DNA damage probably by cooperating with TP53. Ref.11 Ref.12 Ref.15
Tissue specificity	Expressed in cochlea. Low level of expression in heart, brain, placenta, lung, liver, skeletal muscle, kidney and pancreas, with highest expression in placenta.
Involvement in disease	Deafness, autosomal dominant, 5 (DFNA5) [MIM:600994]: 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. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.1 Is a tumor suppressor gene with an important role in major types of tumors. Could be a valuable molecular marker in cancer.
Sequence similarities	Belongs to the gasdermin family.
Sequence caution	The sequence AAB83938.1 differs from that shown. Reason: Erroneous gene model prediction. The sequence AAC39635.2 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.

Ontologies

Keywords
Biological process	Apoptosis
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Deafness Non-syndromic deafness Tumor suppressor
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	apoptotic process Inferred from direct assay Ref.15. Source: UniProtKB induction of apoptosis Inferred from direct assay Ref.15. Source: UniProtKB inner ear receptor cell differentiation Inferred from electronic annotation. Source: Compara negative regulation of cell proliferation Inferred from direct assay Ref.12. Source: UniProtKB sensory perception of sound Traceable author statement Ref.1. Source: ProtInc
Cellular_component	cytoplasm Inferred from direct assay. Source: HPA
Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: O60443-1)

Also known as: Long;

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: O60443-2)

Also known as: Short;

The sequence of this isoform differs from the canonical sequence as follows:
     1-395: Missing.

Note: No experimental confirmation available.

Isoform 3 (identifier: O60443-3)

The sequence of this isoform differs from the canonical sequence as follows:
     1-164: Missing.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 496	496	Non-syndromic hearing impairment protein 5		PRO_0000148178
Natural variations
	Alternative sequence	1 – 395	395	Missing in isoform 2.		VSP_004190
	Alternative sequence	1 – 164	164	Missing in isoform 3.		VSP_044276
	Natural variant	142	1	P → T. Ref.7 Corresponds to variant rs754554 [ dbSNP | Ensembl ].		VAR_030824
	Natural variant	174	1	M → T. Corresponds to variant rs876306 [ dbSNP | Ensembl ].		VAR_053102
	Natural variant	207	1	V → M. Corresponds to variant rs12540919 [ dbSNP | Ensembl ].		VAR_030825

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (Long) [UniParc]. Last modified August 1, 1999. Version 2. Checksum: A407C9AC31AA716B	FASTA	496	54,555
	10 20 30 40 50 60 MFAKATRNFL REVDADGDLI AVSNLNDSDK LQLLSLVTKK KRFWCWQRPK YQFLSLTLGD 70 80 90 100 110 120 VLIEDQFPSP VVVESDFVKY EGKFANHVSG TLETALGKVK LNLGGSSRVE SQSSFGTLRK 130 140 150 160 170 180 QEVDLQQLIR DSAERTINLR NPVLQQVLEG RNEVLCVLTQ KITTMQKCVI SEHMQVEEKC 190 200 210 220 230 240 GGIVGIQTKT VQVSATEDGN VTKDSNVVLE IPAATTIAYG VIELYVKLDG QFEFCLLRGK 250 260 270 280 290 300 QGGFENKKRI DSVYLDPLVF REFAFIDMPD AAHGISSQDG PLSVLKQATL LLERNFHPFA 310 320 330 340 350 360 ELPEPQQTAL SDIFQAVLFD DELLMVLEPV CDDLVSGLSP TVAVLGELKP RQQQDLVAFL 370 380 390 400 410 420 QLVGCSLQGG CPGPEDAGSK QLFMTAYFLV SALAEMPDSA AALLGTCCKL QIIPTLCHLL 430 440 450 460 470 480 RALSDDGVSD LEDPTLTPLK DTERFGIVQR LFASADISLE RLKSSVKAVI LKDSKVFPLL 490 LCITLNGLCA LGREHS
	Isoform 2 (Short) [UniParc]. Checksum: 31462F171F9DB7B8	FASTA	101	10,906
	10 20 30 40 50 60 MPDSAAALLG TCCKLQIIPT LCHLLRALSD DGVSDLEDPT LTPLKDTERF GIVQRLFASA 70 80 90 100 DISLERLKSS VKAVILKDSK VFPLLLCITL NGLCALGREH S
	Isoform 3 [UniParc]. Checksum: 5F4C0AD8EE2734F6	FASTA	332	36,043
	10 20 30 40 50 60 MQKCVISEHM QVEEKCGGIV GIQTKTVQVS ATEDGNVTKD SNVVLEIPAA TTIAYGVIEL 70 80 90 100 110 120 YVKLDGQFEF CLLRGKQGGF ENKKRIDSVY LDPLVFREFA FIDMPDAAHG ISSQDGPLSV 130 140 150 160 170 180 LKQATLLLER NFHPFAELPE PQQTALSDIF QAVLFDDELL MVLEPVCDDL VSGLSPTVAV 190 200 210 220 230 240 LGELKPRQQQ DLVAFLQLVG CSLQGGCPGP EDAGSKQLFM TAYFLVSALA EMPDSAAALL 250 260 270 280 290 300 GTCCKLQIIP TLCHLLRALS DDGVSDLEDP TLTPLKDTER FGIVQRLFAS ADISLERLKS 310 320 330 SVKAVILKDS KVFPLLLCIT LNGLCALGRE HS

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Nonsyndromic hearing impairment is associated with a mutation in DFNA5." Van Laer L., Huizing E.H., Verstreken M., van Zuijlen D., Wauters J.G., Bossuyt P.J., Van de Heyning P., McGuirt W.T., Smith R.J.H., Willems P.J., Legan P.K., Richardson G.P., Van Camp G. Nat. Genet. 20:194-197(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), INVOLVEMENT IN DFNA5. Tissue: Cochlea.
[2]	Van Laer L., Van Camp G. Submitted (JUN-1998) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
[3]	Mei G., Yu W., Gibbs R.A. Submitted (FEB-1999) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). Tissue: Brain.
[4]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3). Tissue: Amygdala.
[5]	"The DNA sequence of human chromosome 7." Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H., Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K., Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A., Delehaunty K.D., Miner T.L. , Nash W.E., Cordes M., Du H., Sun H., Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A., Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P., Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M., Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S., Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R., Strowmatt C., Latreille P., Miller N., Johnson D., Murray J., Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W., Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A., Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E., Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E., Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A., Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A., Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R., McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H., Wilson R.K. Nature 424:157-164(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	Mural R.J., Istrail S., Sutton 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].
[7]	"Human chromosome 7: DNA sequence and biology." Scherer S.W., Cheung J., MacDonald J.R., Osborne L.R., Nakabayashi K., Herbrick J.-A., Carson A.R., Parker-Katiraee L., Skaug J., Khaja R., Zhang J., Hudek A.K., Li M., Haddad M., Duggan G.E., Fernandez B.A., Kanematsu E., Gentles S. , Christopoulos C.C., Choufani S., Kwasnicka D., Zheng X.H., Lai Z., Nusskern D.R., Zhang Q., Gu Z., Lu F., Zeesman S., Nowaczyk M.J., Teshima I., Chitayat D., Shuman C., Weksberg R., Zackai E.H., Grebe T.A., Cox S.R., Kirkpatrick S.J., Rahman N., Friedman J.M., Heng H.H.Q., Pelicci P.G., Lo-Coco F., Belloni E., Shaffer L.G., Pober B., Morton C.C., Gusella J.F., Bruns G.A.P., Korf B.R., Quade B.J., Ligon A.H., Ferguson H., Higgins A.W., Leach N.T., Herrick S.R., Lemyre E., Farra C.G., Kim H.-G., Summers A.M., Gripp K.W., Roberts W., Szatmari P., Winsor E.J.T., Grzeschik K.-H., Teebi A., Minassian B.A., Kere J., Armengol L., Pujana M.A., Estivill X., Wilson M.D., Koop B.F., Tosi S., Moore G.E., Boright A.P., Zlotorynski E., Kerem B., Kroisel P.M., Petek E., Oscier D.G., Mould S.J., Doehner H., Doehner K., Rommens J.M., Vincent J.B., Venter J.C., Li P.W., Mural R.J., Adams M.D., Tsui L.-C. Science 300:767-772(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], VARIANT THR-142.
[8]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
[9]	"Characterization of a gene that is inversely correlated with estrogen receptor expression (ICERE-1) in breast carcinomas." Thompson D.A., Weigel R.J. Eur. J. Biochem. 252:169-177(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 5-496 (ISOFORM 1). Tissue: Mammary gland.
[10]	Thompson D.A. Submitted (AUG-1999) to the EMBL/GenBank/DDBJ databases Cited for: SEQUENCE REVISION TO C-TERMINUS.
[11]	"The potential role of DFNA5, a hearing impairment gene, in p53-mediated cellular response to DNA damage." Masuda Y., Futamura M., Kamino H., Nakamura Y., Kitamura N., Ohnishi S., Miyamoto Y., Ichikawa H., Ohta T., Ohki M., Kiyono T., Egami H., Baba H., Arakawa H. J. Hum. Genet. 51:652-664(2006) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN TP53-MEDIATED CELLULAR RESPONSE.
[12]	"Aberrant promoter methylation and tumor suppressive activity of the DFNA5 gene in colorectal carcinoma." Kim M.S., Chang X., Yamashita K., Nagpal J.K., Baek J.H., Wu G., Trink B., Ratovitski E.A., Mori M., Sidransky D. Oncogene 27:3624-3634(2008) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN COLORECTAL CARCINOMA.
[13]	"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions." Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K. Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. Tissue: Leukemic T-cell.
[14]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[15]	"The DFNA5 gene, responsible for hearing loss and involved in cancer, encodes a novel apoptosis-inducing protein." Op de Beeck K., Van Camp G., Thys S., Cools N., Callebaut I., Vrijens K., Van Nassauw L., Van Tendeloo V.F., Timmermans J.P., Van Laer L. Eur. J. Hum. Genet. 19:965-973(2011) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN APOPTOSIS.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF073308 mRNA. Translation: AAC69324.1. AF075171 mRNA. Translation: AAC69326.1. AF131765 mRNA. Translation: AAD20039.1. AK094714 mRNA. Translation: BAG52917.1. AK314402 mRNA. Translation: BAG37026.1. AC003093 Genomic DNA. Translation: AAB83938.1. Sequence problems. CH236948 Genomic DNA. Translation: EAL24246.1. CH471073 Genomic DNA. Translation: EAW93813.1. BC125065 mRNA. Translation: AAI25066.1. AF007790 mRNA. Translation: AAC39635.2. Different initiation.
IPI	IPI00029656. IPI00218265.
RefSeq	NP_001120925.1. NM_001127453.1. NP_001120926.1. NM_001127454.1. NP_004394.1. NM_004403.2.
UniGene	Hs.520708.
3D structure databases
ProteinModelPortal	O60443.
ModBase	Search...
Protein-protein interaction databases
IntAct	O60443. 2 interactions.
MINT	MINT-5005878.
STRING	9606.ENSP00000339587.
PTM databases
PhosphoSite	O60443.
Proteomic databases
PaxDb	O60443.
PRIDE	O60443.
Protocols and materials databases
DNASU	1687.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000342947; ENSP00000339587; ENSG00000105928. ENST00000409775; ENSP00000386670; ENSG00000105928. ENST00000409970; ENSP00000387119; ENSG00000105928. ENST00000419307; ENSP00000401332; ENSG00000105928. ENST00000545231; ENSP00000442661; ENSG00000105928.
GeneID	1687.
KEGG	hsa:1687.
UCSC	uc003sxa.1. human.
Organism-specific databases
CTD	1687.
GeneCards	GC07M024704.
HGNC	HGNC:2810. DFNA5.
HPA	CAB019306. HPA011326.
MIM	600994. phenotype. 608798. gene.
neXtProt	NX_O60443.
Orphanet	90635. Autosomal dominant nonsyndromic sensorineural deafness type DFNA.
PharmGKB	PA27281.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG40145.
HOGENOM	HOG000065726.
HOVERGEN	HBG051340.
InParanoid	O60443.
OMA	VVESDFV.
OrthoDB	EOG4BVRTX.
PhylomeDB	O60443.
Gene expression databases
ArrayExpress	O60443.
Bgee	O60443.
CleanEx	HS_DFNA5.
Genevestigator	O60443.
GermOnline	ENSG00000105928. Homo sapiens.
Family and domain databases
InterPro	IPR007677. Gasdermin. [Graphical view]
Pfam	PF04598. Gasdermin. 1 hit. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	DFNA5. human.
GenomeRNAi	1687.
NextBio	6920.
SOURCE	Search...

Entry information

Entry name

DFNA5_HUMAN

Accession

Primary (citable) accession number: O60443
Secondary accession number(s): A4D156 , B2RAX9, B3KT05, O14590, Q08AQ8, Q9UBV3

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 21, 2001
Last sequence update:	August 1, 1999
Last modified:	May 1, 2013
This is version 97 of the entry and version 2 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.