LHPL5_MOUSE
ID LHPL5_MOUSE Reviewed; 219 AA.
AC Q4KL25; B2KF30;
DT 01-MAY-2007, integrated into UniProtKB/Swiss-Prot.
DT 02-AUG-2005, sequence version 1.
DT 03-AUG-2022, entry version 104.
DE RecName: Full=LHFPL tetraspan subfamily member 5 protein {ECO:0000250|UniProtKB:Q8TAF8};
DE AltName: Full=Lipoma HMGIC fusion partner-like 5 protein {ECO:0000312|MGI:MGI:1915382};
DE AltName: Full=Tetraspan membrane protein of hair cell stereocilia {ECO:0000303|PubMed:15905332};
GN Name=Lhfpl5 {ECO:0000312|MGI:MGI:1915382};
GN Synonyms=Tmhs {ECO:0000303|PubMed:15905332};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Thyroid;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [3]
RP TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE.
RX PubMed=16459341; DOI=10.1136/jmg.2005.039834;
RA Shabbir M.I., Ahmed Z.M., Khan S.Y., Riazuddin S., Waryah A.M., Khan S.N.,
RA Camps R.D., Ghosh M., Kabra M., Belyantseva I.A., Friedman T.B.,
RA Riazuddin S.;
RT "Mutations of human TMHS cause recessively inherited non-syndromic hearing
RT loss.";
RL J. Med. Genet. 43:634-640(2006).
RN [4]
RP FUNCTION, INTERACTION WITH PCDH15, SUBCELLULAR LOCATION, TISSUE
RP SPECIFICITY, AND DEVELOPMENTAL STAGE.
RX PubMed=23217710; DOI=10.1016/j.cell.2012.10.041;
RA Xiong W., Grillet N., Elledge H.M., Wagner T.F., Zhao B., Johnson K.R.,
RA Kazmierczak P., Muller U.;
RT "TMHS is an integral component of the mechanotransduction machinery of
RT cochlear hair cells.";
RL Cell 151:1283-1295(2012).
RN [5]
RP IDENTIFICATION IN A COMPLEX WITH TMIE AND PCDH15.
RX PubMed=25467981; DOI=10.1016/j.neuron.2014.10.041;
RA Zhao B., Wu Z., Grillet N., Yan L., Xiong W., Harkins-Perry S., Mueller U.;
RT "TMIE is an essential component of the mechanotransduction machinery of
RT cochlear hair cells.";
RL Neuron 84:954-967(2014).
RN [6]
RP TISSUE SPECIFICITY.
RX PubMed=26964900; DOI=10.1038/srep23037;
RA Zhao F., Zhou J., Li R., Dudley E.A., Ye X.;
RT "Novel function of LHFPL2 in female and male distal reproductive tract
RT development.";
RL Sci. Rep. 6:23037-23037(2016).
RN [7]
RP INTERACTION WITH TOMT.
RX PubMed=28504928; DOI=10.7554/elife.24318;
RA Cunningham C.L., Wu Z., Jafari A., Zhao B., Schrode K., Harkins-Perry S.,
RA Lauer A., Mueller U.;
RT "The murine catecholamine methyltransferase mTOMT is essential for
RT mechanotransduction by cochlear hair cells.";
RL Elife 6:0-0(2017).
RN [8]
RP VARIANT HSCY PHE-161, FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=15905332; DOI=10.1073/pnas.0500760102;
RA Longo-Guess C.M., Gagnon L.H., Cook S.A., Wu J., Zheng Q.Y., Johnson K.R.;
RT "A missense mutation in the previously undescribed gene Tmhs underlies
RT deafness in hurry-scurry (hscy) mice.";
RL Proc. Natl. Acad. Sci. U.S.A. 102:7894-7899(2005).
CC -!- FUNCTION: In the inner ear, may be a component of the hair cell's
CC mechanotransduction machinery that functionally couples PCDH15 to the
CC transduction channel. Regulates transducer channel conductance and is
CC required for fast channel adaptation. {ECO:0000269|PubMed:15905332,
CC ECO:0000269|PubMed:23217710}.
CC -!- SUBUNIT: Found in a complex with TMIE and PCDH15 (PubMed:25467981).
CC Interacts with PCDH15; this interaction is required for efficient
CC localization to hair bundles (PubMed:23217710). Interacts with TOMT
CC (PubMed:28504928). {ECO:0000269|PubMed:23217710,
CC ECO:0000269|PubMed:25467981, ECO:0000269|PubMed:28504928}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:23217710};
CC Multi-pass membrane protein {ECO:0000255}. Note=Efficient localization
CC to the plasma membrane requires the presence of PCDH15.
CC {ECO:0000269|PubMed:23217710}.
CC -!- TISSUE SPECIFICITY: Brain, inner ear hair cells and vestibular
CC neuroepithelia of the inner ear (PubMed:16459341, PubMed:23217710,
CC PubMed:15905332). In inner ear, expressed in stereocilia in a punctate
CC pattern and at the tip-link region (at protein level) (PubMed:16459341,
CC PubMed:23217710, PubMed:15905332). Strongly expressed in brain
CC (PubMed:26964900). Weakly expressed in heart, testis and intestine
CC (PubMed:26964900). {ECO:0000269|PubMed:15905332,
CC ECO:0000269|PubMed:16459341, ECO:0000269|PubMed:23217710,
CC ECO:0000269|PubMed:26964900}.
CC -!- DEVELOPMENTAL STAGE: Expressed in inner ear hair cells at 16.5 dpc.
CC Expressed postnatally in inner and outer hair cells of the cochlear, as
CC well as in vestibular hair cells. At the cochlear apex, levels are low
CC at P1 and increased thereafter. After P7, hardly detectable at the
CC protein level, while mRNA levels remains high in adult hair cells.
CC {ECO:0000269|PubMed:16459341, ECO:0000269|PubMed:23217710}.
CC -!- DISEASE: Note=Defects in Lhfpl5 are the cause of the hurry-scurry
CC (hscy) phenotype which is characterized by rapid circling behavior,
CC frequent shaking of head from side to side, deafness and vestibular
CC dysfunction. {ECO:0000269|PubMed:15905332}.
CC -!- SIMILARITY: Belongs to the LHFP family. {ECO:0000305}.
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DR EMBL; CT009661; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC099483; AAH99483.1; -; mRNA.
DR CCDS; CCDS37530.1; -.
DR RefSeq; NP_080847.2; NM_026571.2.
DR PDB; 6C14; EM; 4.50 A; B/D=1-219.
DR PDBsum; 6C14; -.
DR AlphaFoldDB; Q4KL25; -.
DR SMR; Q4KL25; -.
DR IntAct; Q4KL25; 1.
DR STRING; 10090.ENSMUSP00000079598; -.
DR PaxDb; Q4KL25; -.
DR PRIDE; Q4KL25; -.
DR Antibodypedia; 55280; 90 antibodies from 17 providers.
DR DNASU; 328789; -.
DR Ensembl; ENSMUST00000080780; ENSMUSP00000079598; ENSMUSG00000062252.
DR Ensembl; ENSMUST00000232862; ENSMUSP00000156959; ENSMUSG00000062252.
DR Ensembl; ENSMUST00000232974; ENSMUSP00000156557; ENSMUSG00000062252.
DR GeneID; 328789; -.
DR KEGG; mmu:328789; -.
DR UCSC; uc008brg.2; mouse.
DR CTD; 222662; -.
DR MGI; MGI:1915382; Lhfpl5.
DR VEuPathDB; HostDB:ENSMUSG00000062252; -.
DR eggNOG; KOG4026; Eukaryota.
DR GeneTree; ENSGT00990000203541; -.
DR HOGENOM; CLU_084868_1_2_1; -.
DR InParanoid; Q4KL25; -.
DR OMA; RAMGVMW; -.
DR OrthoDB; 1219117at2759; -.
DR PhylomeDB; Q4KL25; -.
DR TreeFam; TF321143; -.
DR BioGRID-ORCS; 328789; 4 hits in 74 CRISPR screens.
DR PRO; PR:Q4KL25; -.
DR Proteomes; UP000000589; Chromosome 17.
DR RNAct; Q4KL25; protein.
DR Bgee; ENSMUSG00000062252; Expressed in otolith organ and 68 other tissues.
DR Genevisible; Q4KL25; MM.
DR GO; GO:0016324; C:apical plasma membrane; IDA:MGI.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0016020; C:membrane; IBA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; IDA:MGI.
DR GO; GO:0032421; C:stereocilium bundle; IDA:MGI.
DR GO; GO:0032426; C:stereocilium tip; IDA:MGI.
DR GO; GO:0060088; P:auditory receptor cell stereocilium organization; IMP:MGI.
DR GO; GO:0050974; P:detection of mechanical stimulus involved in sensory perception; IBA:GO_Central.
DR GO; GO:0050910; P:detection of mechanical stimulus involved in sensory perception of sound; IMP:MGI.
DR GO; GO:0006811; P:ion transport; IEA:UniProtKB-KW.
DR GO; GO:0007605; P:sensory perception of sound; IMP:MGI.
DR InterPro; IPR019372; LHFPL.
DR PANTHER; PTHR12489; PTHR12489; 1.
DR Pfam; PF10242; L_HMGIC_fpl; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cell membrane; Disease variant; Ion transport; Membrane;
KW Reference proteome; Transmembrane; Transmembrane helix; Transport.
FT CHAIN 1..219
FT /note="LHFPL tetraspan subfamily member 5 protein"
FT /id="PRO_0000285923"
FT TOPO_DOM 1..24
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 25..45
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 46..98
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 99..119
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 120..128
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 129..149
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 150..178
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 179..199
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 200..219
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT VARIANT 161
FT /note="C -> F (in hscy)"
FT /evidence="ECO:0000269|PubMed:15905332"
SQ SEQUENCE 219 AA; 24186 MW; 9BFC49260AE9DD02 CRC64;
MVKLLPAQEA AKIYHTNYVR NSRAVGVMWG TLTICFSVLV MALFIQPYWI GDSVSTPQAG
YFGLFSYCVG NVLSSELICK GGPLDFSSIP SRAFKTAMFF VALAMFLIIG SIICFSLFFV
CNTATVYKIC AWMQLAAATG LMIGCLVYPD GWDSSEVRRM CGEQTGKYTL GHCTIRWAFM
LAILSIGDAL ILSFLAFVLG YRQDKLLPDD YKADGNEEV
