P58418 (CLRN1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Clarin-1

Alternative name(s):
Usher syndrome type-3 protein

Gene names

Name:	CLRN1
Synonyms:	USH3A

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

General annotation (Comments)

Function	May have a role in the excitatory ribbon synapse junctions between hair cells and cochlear ganglion cells and presumably also in analogous synapses within the retina. Ref.3
Subcellular location	Membrane; Multi-pass membrane protein Potential.
Tissue specificity	Widely expressed. Found in the retina.
Involvement in disease	Usher syndrome 3A (USH3A) [MIM:276902]: USH is a genetically heterogeneous condition characterized by the association of retinitis pigmentosa with sensorineural deafness. Age at onset and differences in auditory and vestibular function distinguish Usher syndrome type 1 (USH1), Usher syndrome type 2 (USH2) and Usher syndrome type 3 (USH3). USH3 is characterized by postlingual, progressive hearing loss, variable vestibular dysfunction, and onset of retinitis pigmentosa symptoms, including nyctalopia, constriction of the visual fields, and loss of central visual acuity, usually by the second decade of life. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.1 Ref.2 Ref.3 Ref.8 Ref.9 Retinitis pigmentosa 61 (RP61) [MIM:614180]: A retinal dystrophy belonging to the group of pigmentary retinopathies. Retinitis pigmentosa is characterized by retinal pigment deposits visible on fundus examination and primary loss of rod photoreceptor cells followed by secondary loss of cone photoreceptors. Patients typically have night vision blindness and loss of midperipheral visual field. As their condition progresses, they lose their far peripheral visual field and eventually central vision as well. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.10
Sequence similarities	Belongs to the clarin family.

Ontologies

Keywords
Biological process	Hearing Sensory transduction Vision
Cellular component	Membrane
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Deafness Disease mutation Retinitis pigmentosa Usher syndrome
Domain	Transmembrane Transmembrane helix
PTM	Glycoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	actin filament organization Inferred from direct assay PubMed 19423712. Source: MGI auditory receptor cell stereocilium organization Inferred from electronic annotation. Source: Compara cell motility Inferred from direct assay PubMed 19423712. Source: MGI equilibrioception Inferred from mutant phenotype Ref.8. Source: HGNC photoreceptor cell maintenance Inferred from mutant phenotype Ref.8. Source: HGNC positive regulation of lamellipodium assembly Inferred from direct assay PubMed 19423712. Source: MGI response to stimulus Inferred from electronic annotation. Source: UniProtKB-KW sensory perception of sound Inferred from mutant phenotype PubMed 15650299. Source: HGNC
Cellular_component	integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW lamellipodium Inferred from direct assay PubMed 19423712. Source: MGI microvillus Inferred from direct assay PubMed 19423712. Source: MGI plasma membrane Inferred from direct assay PubMed 19423712. Source: MGI
Complete GO annotation...

Alternative products

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

Note: Additional isoforms seem to exist.

Isoform 1 (identifier: P58418-3)

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: P58418-1)

Also known as: A;

The sequence of this isoform differs from the canonical sequence as follows:
     1-85: MPSQQKKIIF...LGARPFRFSF → MQALQQQPV
     191-232: VIFFCFFVHFLNGLLIRLAGFQFPFAKSKDAETTNVAADLMY → LTKGHS

Isoform 3 (identifier: P58418-4)

Also known as: 0-2-2b-3;

The sequence of this isoform differs from the canonical sequence as follows:
     144-144: S → SVALWLPATRHQAQ

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 232	232	Clarin-1		PRO_0000065729
Regions
	Transmembrane	8 – 28	21	Helical; Potential
	Transmembrane	101 – 121	21	Helical; Potential
	Transmembrane	135 – 155	21	Helical; Potential
	Transmembrane	186 – 206	21	Helical; Potential
Amino acid modifications
	Glycosylation	48	1	N-linked (GlcNAc...) Potential
Natural variations
	Alternative sequence	1 – 85	85	MPSQQ…FRFSF → MQALQQQPV in isoform 2.		VSP_022868
	Alternative sequence	144	1	S → SVALWLPATRHQAQ in isoform 3.		VSP_043303
	Alternative sequence	191 – 232	42	VIFFC…ADLMY → LTKGHS in isoform 2.		VSP_022869
	Natural variant	7	1	K → I. Corresponds to variant rs3796241 [ dbSNP | Ensembl ].		VAR_053825
	Natural variant	31	1	P → L in RP61; the mutant protein is retained in the endoplasmic reticulum. Ref.10		VAR_066673
	Natural variant	40	1	C → G in USH3A. Ref.8		VAR_054555
	Natural variant	48	1	N → K in USH3A. Ref.2 Ref.3		VAR_030345
	Natural variant	105	1	S → P in USH3A. Ref.9		VAR_054556
	Natural variant	120	1	M → K in USH3A. Ref.1		VAR_012241
	Natural variant	150	1	L → P in USH3A. Ref.2		VAR_030346
	Natural variant	153 – 154	2	IL → M in USH3A.		VAR_012242
	Natural variant	154	1	L → W in RP61; the mutant protein is retained in the endoplasmic reticulum. Ref.10		VAR_066674

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified February 6, 2007. Version 2. Checksum: 2713C621FEBE4281	FASTA	232	25,719
	10 20 30 40 50 60 MPSQQKKIIF CMAGVFSFAC ALGVVTALGT PLWIKATVLC KTGALLVNAS GQELDKFMGE 70 80 90 100 110 120 MQYGLFHGEG VRQCGLGARP FRFSFFPDLL KAIPVSIHVN VILFSAILIV LTMVGTAFFM 130 140 150 160 170 180 YNAFGKPFET LHGPLGLYLL SFISGSCGCL VMILFASEVK IHHLSEKIAN YKEGTYVYKT 190 200 210 220 230 QSEKYTTSFW VIFFCFFVHF LNGLLIRLAG FQFPFAKSKD AETTNVAADL MY
	Isoform 2 (A) [UniParc]. Checksum: 959B081E7665A2D1	FASTA	120	13,421
	10 20 30 40 50 60 MQALQQQPVF PDLLKAIPVS IHVNVILFSA ILIVLTMVGT AFFMYNAFGK PFETLHGPLG 70 80 90 100 110 120 LYLLSFISGS CGCLVMILFA SEVKIHHLSE KIANYKEGTY VYKTQSEKYT TSFWLTKGHS
	Isoform 3 (0-2-2b-3) [UniParc]. Checksum: 024BFE7B5C3788D3	FASTA	245	27,192
	10 20 30 40 50 60 MPSQQKKIIF CMAGVFSFAC ALGVVTALGT PLWIKATVLC KTGALLVNAS GQELDKFMGE 70 80 90 100 110 120 MQYGLFHGEG VRQCGLGARP FRFSFFPDLL KAIPVSIHVN VILFSAILIV LTMVGTAFFM 130 140 150 160 170 180 YNAFGKPFET LHGPLGLYLL SFISVALWLP ATRHQAQGSC GCLVMILFAS EVKIHHLSEK 190 200 210 220 230 240 IANYKEGTYV YKTQSEKYTT SFWVIFFCFF VHFLNGLLIR LAGFQFPFAK SKDAETTNVA ADLMY

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Mutations in a novel gene with transmembrane domains underlie Usher syndrome type 3." Joensuu T., Haemaelaeinen R., Yuan B., Johnson C., Tegelberg S., Gasparini P., Zelante L., Pirvola U., Pakarinen L., Lehesjoki A.-E., de la Chapelle A., Sankila E.-M. Am. J. Hum. Genet. 69:673-684(2001) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), VARIANTS USH3A LYS-120 AND 153-ILE-LEU-154 DELINS MET.
[2]	"Usher syndrome type III: revised genomic structure of the USH3 gene and identification of novel mutations." Fields R.R., Zhou G., Huang D., Davis J.R., Moeller C., Jacobson S.G., Kimberling W.J., Sumegi J. Am. J. Hum. Genet. 71:607-617(2002) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANTS USH3A LYS-48 AND PRO-150.
[3]	"USH3A transcripts encode clarin-1, a four-transmembrane-domain protein with a possible role in sensory synapses." Adato A., Vreugde S., Joensuu T., Avidan N., Hamalainen R., Belenkiy O., Olender T., Bonne-Tamir B., Ben-Asher E., Espinos C., Millan J.M., Lehesjoki A.-E., Flannery J.G., Avraham K.B., Pietrokovski S., Sankila E.-M., Beckmann J.S., Lancet D. Eur. J. Hum. Genet. 10:339-350(2002) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANT USH3A LYS-48, FUNCTION. Tissue: Retina.
[4]	"Alternative splice variants of the USH3A gene Clarin 1 (CLRN1)." Vastinsalo H., Jalkanen R., Dinculescu A., Isosomppi J., Geller S., Flannery J.G., Hauswirth W.W., Sankila E.M. Eur. J. Hum. Genet. 19:30-35(2011) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3), ALTERNATIVE SPLICING. Tissue: Retina.
[5]	"The DNA sequence, annotation and analysis of human chromosome 3." Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R., Buhay C.J., Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J. , Jackson A., Khan Z.M., Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., Morgan M.B., Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D., Wei S., Wheeler D.A., Wright M.W., Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z., Clendenning J., Clerc-Blankenburg K.P., Chen R., Chen Z., Davis C., Delgado O., Dinh H.H., Dong W., Draper H., Ernst S., Fu G., Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J., Hao B., Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W., Jackson L.R., Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B., Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., Palmeiri A., Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B., Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H., Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J., Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J., Zhang X., Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H., Reinhardt R., Naylor S.L., Yang H., Olson M., Weinstock G., Gibbs R.A. Nature 440:1194-1198(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	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 (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]	"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).
[8]	"Mutation screening of USH3 gene (clarin-1) in Spanish patients with Usher syndrome: low prevalence and phenotypic variability." Aller E., Jaijo T., Oltra S., Alio J., Galan F., Najera C., Beneyto M., Millan J.M. Clin. Genet. 66:525-529(2004) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT USH3A GLY-40.
[9]	"Spectrum of USH2A mutations in Scandinavian patients with Usher syndrome type II." Dreyer B., Brox V., Tranebjaerg L., Rosenberg T., Sadeghi A.M., Moeller C., Nilssen O. Hum. Mutat. 29:451-451(2008) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT USH3A PRO-105.
[10]	"CLRN1 mutations cause nonsyndromic retinitis pigmentosa." Khan M.I., Kersten F.F., Azam M., Collin R.W., Hussain A., Shah S.T., Keunen J.E., Kremer H., Cremers F.P., Qamar R., den Hollander A.I. Ophthalmology 118:1444-1448(2011) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS RP61 LEU-31 AND TRP-154, CHARACTERIZATION OF VARIANTS RP61 LEU-31 AND TRP-154.

Web resources

Mutations of the USH3A gene

Retina International's Scientific Newsletter

GeneReviews

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF388366 mRNA. Translation: AAL09581.1. AF482697 mRNA. Translation: AAN07148.1. AF495717 mRNA. Translation: AAM88774.1. HM626132 mRNA. Translation: ADM63096.1. AC020636 Genomic DNA. No translation available. CH471052 Genomic DNA. Translation: EAW78814.1. CH471052 Genomic DNA. Translation: EAW78815.1. BC074970 mRNA. Translation: AAH74970.1. BC074971 mRNA. Translation: AAH74971.1.
IPI	IPI00048232. IPI00166977. IPI00981935.
RefSeq	NP_001182723.1. NM_001195794.1. NP_443721.1. NM_052995.2. NP_777367.1. NM_174878.2.
UniGene	Hs.380222.
3D structure databases
ProteinModelPortal	P58418.
ModBase	Search...
Protein-protein interaction databases
STRING	9606.ENSP00000322280.
PTM databases
PhosphoSite	P58418.
Polymorphism databases
DMDM	125987806.
Proteomic databases
PaxDb	P58418.
PRIDE	P58418.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000295911; ENSP00000295911; ENSG00000163646. ENST00000327047; ENSP00000322280; ENSG00000163646. ENST00000328863; ENSP00000329158; ENSG00000163646.
GeneID	7401.
KEGG	hsa:7401.
UCSC	uc003eyj.3. human. uc003eyk.1. human.
Organism-specific databases
CTD	7401.
GeneCards	GC03M150643.
HGNC	HGNC:12605. CLRN1.
MIM	276902. phenotype. 606397. gene. 614180. phenotype.
neXtProt	NX_P58418.
Orphanet	791. Retinitis pigmentosa. 231183. Usher syndrome type 3.
PharmGKB	PA37231.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG44698.
HOGENOM	HOG000060265.
HOVERGEN	HBG061269.
InParanoid	P58418.
OMA	QCGLGAR.
PhylomeDB	P58418.
Gene expression databases
ArrayExpress	P58418.
Bgee	P58418.
CleanEx	HS_CLRN1.
Genevestigator	P58418.
GermOnline	ENSG00000163646. Homo sapiens.
Family and domain databases
InterPro	IPR026748. Clarin. [Graphical view]
PANTHER	PTHR31548. PTHR31548. 1 hit.
ProtoNet	Search...
Other
GenomeRNAi	7401.
NextBio	28970.
SOURCE	Search...

Entry information

Entry name

CLRN1_HUMAN

Accession

Primary (citable) accession number: P58418
Secondary accession number(s): D3DNJ3, E1ACU9, Q8N6A9

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 5, 2001
Last sequence update:	February 6, 2007
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.