Q495M9 (USH1G_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Usher syndrome type-1G protein

Alternative name(s):
Scaffold protein containing ankyrin repeats and SAM domain

Gene names

Name:	USH1G
Synonyms:	SANS

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

General annotation (Comments)

Function	Required for normal development and maintenance of cochlear hair cell bundles. Anchoring/scaffolding protein that is a part of the functional network formed by USH1C, USH1G, CDH23 and MYO7A that mediates mechanotransduction in cochlear hair cells. Required for normal hearing. Ref.4 Ref.7
Subunit structure	Interacts with CDH23 By similarity. Interacts with USH1C (via the first PDZ domain) and with USH1G. Interacts with PDZD7. Interacts with MYO7A. Part of a complex composed of USH1C, USH1G and MYO7A. Ref.3 Ref.4 Ref.5 Ref.6 Ref.7
Subcellular location	Cytoplasm › cytosol. Cytoplasm › cytoskeleton. Cell membrane; Peripheral membrane protein By similarity. Note: Detected at the tip of cochlear hair cell stereocilia. Recruited to the cell membrane via interaction with CDH23 By similarity. Ref.4 Ref.5
Tissue specificity	Expressed in vestibule of the inner ear, eye and small intestine. Ref.7
Involvement in disease	Usher syndrome 1G (USH1G) [MIM:606943]: 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). USH1 is characterized by profound congenital sensorineural deafness, absent vestibular function and prepubertal onset of progressive retinitis pigmentosa leading to blindness. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.4 Ref.5 Ref.7 Ref.8
Sequence similarities	Contains 3 ANK repeats. Contains 1 SAM (sterile alpha motif) domain.

Ontologies

Keywords
Biological process	Hearing
Cellular component	Cell membrane Cytoplasm Cytoskeleton Membrane
Disease	Deafness Disease mutation Retinitis pigmentosa Usher syndrome
Domain	ANK repeat Repeat
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	equilibrioception Inferred from mutant phenotype Ref.7. Source: HGNC inner ear morphogenesis Inferred from electronic annotation. Source: Compara inner ear receptor cell differentiation Inferred from electronic annotation. Source: Compara photoreceptor cell maintenance Inferred from mutant phenotype PubMed 11398101. Source: HGNC sensory perception of sound Inferred from mutant phenotype PubMed 11398101Ref.7. Source: HGNC
Cellular_component	actin cytoskeleton Inferred from sequence or structural similarity Ref.7. Source: HGNC cytosol Inferred from electronic annotation. Source: UniProtKB-SubCell plasma membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 461

461

Usher syndrome type-1G protein

PRO_0000067077

Regions

Repeat

31 – 60

30

ANK 1

Repeat

64 – 93

30

ANK 2

Repeat

97 – 126

30

ANK 3

Domain

385 – 447

63

SAM

Compositional bias

444 – 447

4

Poly-Arg

Natural variations

Natural variant

48

1

L → P in USH1G. Ref.7

VAR_023739

Natural variant

458

1

D → V in USH1G; atypical form with mild retinitis pigmentosa and normal vestibular function; also found in patients with autosomal recessive non-syndromic deafness; strongly reduced affinity for USH1C. Ref.5 Ref.8

VAR_060468

Experimental info

Mutagenesis

307

1

F → E: Reduced affinity for MYO7A. Ref.6

Mutagenesis

317

1

F → E: Reduced affinity for MYO7A. Ref.6

Mutagenesis

374

1

W → Q: Strongly reduced affinity for MYO7A. Ref.6

Sequence conflict

300

1

D → N in BAC03619. Ref.1

Sequence conflict

402

1

E → G in BAC03619. Ref.1

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

461

Helix Strand Turn

Details...

Beta strand

307 – 309

3

Turn

310 – 312

3

Beta strand

313 – 315

3

Beta strand

375 – 377

3

Helix

391 – 397

7

Turn

398 – 400

3

Helix

402 – 404

3

Helix

405 – 410

6

Helix

415 – 418

4

Helix

423 – 428

6

Helix

433 – 451

19

Beta strand

459 – 461

3

Sequences

	Sequence		Length	Mass (Da)
	Q495M9 [UniParc]. Last modified September 13, 2005. Version 1. Checksum: B0ABB9F5711A5095	FASTA	461	51,489
	10 20 30 40 50 60 MNDQYHRAAR DGYLELLKEA TRKELNAPDE DGMTPTLWAA YHGNLESLRL IVSRGGDPDK 70 80 90 100 110 120 CDIWGNTPLH LAASNGHLHC LSFLVSFGAN IWCLDNDYHT PLDMAAMKGH MECVRYLDSI 130 140 150 160 170 180 AAKQSSLNPK LVGKLKDKAF REAERRIREC AKLQRRHHER MERRYRRELA ERSDTLSFSS 190 200 210 220 230 240 LTSSTLSRRL QHLALGSHLP YSQATLHGTA RGKTKMQKKL ERRKQGGEGT FKVSEDGRKS 250 260 270 280 290 300 ARSLSGLQLG SDVMFVRQGT YANPKEWGRA PLRDMFLSDE DSVSRATLAA EPAHSEVSTD 310 320 330 340 350 360 SGHDSLFTRP GLGTMVFRRN YLSSGLHGLG REDGGLDGVG APRGRLQSSP SLDDDSLGSA 370 380 390 400 410 420 NSLQDRSCGE ELPWDELDLG LDEDLEPETS PLETFLASLH MEDFAALLRQ EKIDLEALML 430 440 450 460 CSDLDLRSIS VPLGPRKKIL GAVRRRRQAM ERPPALEDTE L

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"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]. Tissue: Tongue.
[2]	"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].
[3]	"Homozygous disruption of PDZD7 by reciprocal translocation in a consanguineous family: a new member of the Usher syndrome protein interactome causing congenital hearing impairment." Schneider E., Marker T., Daser A., Frey-Mahn G., Beyer V., Farcas R., Schneider-Ratzke B., Kohlschmidt N., Grossmann B., Bauss K., Napiontek U., Keilmann A., Bartsch O., Zechner U., Wolfrum U., Haaf T. Hum. Mol. Genet. 18:655-666(2009) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH PDZD7.
[4]	"Myosin VIIa and sans localization at stereocilia upper tip-link density implicates these Usher syndrome proteins in mechanotransduction." Grati M., Kachar B. Proc. Natl. Acad. Sci. U.S.A. 108:11476-11481(2011) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION, IDENTIFICATION IN A COMPLEX WITH MYO7A; USH1C AND USH1G.
[5]	"The structure of the harmonin/sans complex reveals an unexpected interaction mode of the two Usher syndrome proteins." Yan J., Pan L., Chen X., Wu L., Zhang M. Proc. Natl. Acad. Sci. U.S.A. 107:4040-4045(2010) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 388-461 IN COMPLEX WITH USH1C, INTERACTION WITH USH1C, SUBCELLULAR LOCATION, CHARACTERIZATION OF VARIANT USH1G VAL-458.
[6]	"Structure of MyTH4-FERM domains in myosin VIIa tail bound to cargo." Wu L., Pan L., Wei Z., Zhang M. Science 331:757-760(2011) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 295-390 IN COMPLEX WITH MYO7A, STRUCTURE BY NMR OF 370-380, INTERACTION WITH MYO7A, MUTAGENESIS OF PHE-307; PHE-317 AND TRP-374.
[7]	"Usher syndrome type I G (USH1G) is caused by mutations in the gene encoding SANS, a protein that associates with the USH1C protein, harmonin." Weil D., El-Amraoui A., Masmoudi S., Mustapha M., Kikkawa Y., Laine S., Delmaghani S., Adato A., Nadifi S., Zina Z.B., Hamel C., Gal A., Ayadi H., Yonekawa H., Petit C. Hum. Mol. Genet. 12:463-471(2003) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT USH1G PRO-48, INTERACTION WITH USH1C, TISSUE SPECIFICITY, POSSIBLE FUNCTION.
[8]	"A novel D458V mutation in the SANS PDZ binding motif causes atypical Usher syndrome." Kalay E., de Brouwer A.P.M., Caylan R., Nabuurs S.B., Wollnik B., Karaguzel A., Heister J.G.A.M., Erdol H., Cremers F.P.M., Cremers C.W.R.J., Brunner H.G., Kremer H. J. Mol. Med. 83:1025-1032(2005) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT USH1G VAL-458.
+	Additional computationally mapped references.

Web resources

GeneReviews

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AK091243 mRNA. Translation: BAC03619.1.
BC101096 mRNA. Translation: AAI01097.1.
BC101097 mRNA. Translation: AAI01098.1.
BC101098 mRNA. Translation: AAI01099.1.
BC101099 mRNA. Translation: AAI01100.1.

IPI

IPI00178665.

RefSeq

NP_775748.2. NM_173477.2.

UniGene

Hs.376688.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2L7T	NMR	-	A	370-380	[»]
3K1R	X-ray	2.30	B	388-461	[»]
3PVL	X-ray	2.80	B	295-390	[»]

ProteinModelPortal

Q495M9.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-41617N.

MINT

MINT-257481.

STRING

9606.ENSP00000320076.

PTM databases

PhosphoSite

Q495M9.

Polymorphism databases

DMDM

81175048.

Proteomic databases

PaxDb

Q495M9.

PRIDE

Q495M9.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000319642; ENSP00000320076; ENSG00000182040.

GeneID

124590.

KEGG

hsa:124590.

UCSC

uc002jme.1. human.

Organism-specific databases

CTD

124590.

GeneCards

GC17M072912.

HGNC

HGNC:16356. USH1G.

HPA

HPA024360.

MIM

276900. phenotype.
606943. phenotype.
607696. gene.

neXtProt

NX_Q495M9.

Orphanet

231169. Usher syndrome type 1.

PharmGKB

PA38126.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG0666.

HOGENOM

HOG000007847.

HOVERGEN

HBG051882.

InParanoid

Q495M9.

OMA

LHMEDFA.

OrthoDB

EOG4CG08B.

PhylomeDB

Q495M9.

Gene expression databases

Bgee

Q495M9.

CleanEx

HS_USH1G.

Genevestigator

Q495M9.

GermOnline

ENSG00000182040. Homo sapiens.

Family and domain databases

Gene3D

1.10.150.50. 1 hit.
1.25.40.20. 1 hit.

InterPro

IPR002110. Ankyrin_rpt.
IPR020683. Ankyrin_rpt-contain_dom.
IPR001660. SAM.
IPR013761. SAM/pointed.
IPR021129. SAM_type1.
[Graphical view]

Pfam

PF12796. Ank_2. 1 hit.
PF00536. SAM_1. 1 hit.
[Graphical view]

SMART

SM00248. ANK. 3 hits.
SM00454. SAM. 1 hit.
[Graphical view]

SUPFAM

SSF48403. ANK. 1 hit.
SSF47769. SAM_homology. 1 hit.

PROSITE

PS50297. ANK_REP_REGION. 1 hit.
PS50088. ANK_REPEAT. 2 hits.
PS50105. SAM_DOMAIN. False negative.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

Q495M9.

GenomeRNAi

124590.

NextBio

81331.

SOURCE

Search...

Entry information

Entry name

USH1G_HUMAN

Accession

Primary (citable) accession number: Q495M9
Secondary accession number(s): Q8N251

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 8, 2005
Last sequence update:	September 13, 2005
Last modified:	May 1, 2013
This is version 82 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.