SLIK6_MOUSE
ID SLIK6_MOUSE Reviewed; 840 AA.
AC Q8C110; Q8BLL0;
DT 13-APR-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2003, sequence version 1.
DT 03-AUG-2022, entry version 146.
DE RecName: Full=SLIT and NTRK-like protein 6;
DE Flags: Precursor;
GN Name=Slitrk6; Synonyms=Sltk6;
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 {ECO:0000312|EMBL:BAC26368.1};
RN [1] {ECO:0000305}
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND FUNCTION.
RX PubMed=14550773; DOI=10.1016/s1044-7431(03)00129-5;
RA Aruga J., Mikoshiba K.;
RT "Identification and characterization of Slitrk, a novel neuronal
RT transmembrane protein family controlling neurite outgrowth.";
RL Mol. Cell. Neurosci. 24:117-129(2003).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Head;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3] {ECO:0000305}
RP TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE.
RX PubMed=14643680; DOI=10.1016/s1567-133x(03)00141-8;
RA Aruga J.;
RT "Slitrk6 expression profile in the mouse embryo and its relationship to
RT that of Nlrr3.";
RL Gene Expr. Patterns 3:727-733(2003).
RN [4]
RP DISRUPTION PHENOTYPE, AND DEVELOPMENTAL STAGE.
RX PubMed=19936227; DOI=10.1371/journal.pone.0007786;
RA Katayama K., Zine A., Ota M., Matsumoto Y., Inoue T., Fritzsch B.,
RA Aruga J.;
RT "Disorganized innervation and neuronal loss in the inner ear of Slitrk6-
RT deficient mice.";
RL PLoS ONE 4:E7786-E7786(2009).
RN [5]
RP DISRUPTION PHENOTYPE.
RX PubMed=21298075; DOI=10.1371/journal.pone.0016497;
RA Matsumoto Y., Katayama K., Okamoto T., Yamada K., Takashima N., Nagao S.,
RA Aruga J.;
RT "Impaired auditory-vestibular functions and behavioral abnormalities of
RT Slitrk6-deficient mice.";
RL PLoS ONE 6:E16497-E16497(2011).
RN [6]
RP DISRUPTION PHENOTYPE, DEVELOPMENTAL STAGE, AND FUNCTION.
RX PubMed=23543054; DOI=10.1172/jci65853;
RA Tekin M., Chioza B.A., Matsumoto Y., Diaz-Horta O., Cross H.E., Duman D.,
RA Kokotas H., Moore-Barton H.L., Sakoori K., Ota M., Odaka Y.S.,
RA Foster J. II, Cengiz F.B., Tokgoz-Yilmaz S., Tekeli O., Grigoriadou M.,
RA Petersen M.B., Sreekantan-Nair A., Gurtz K., Xia X.J., Pandya A.,
RA Patton M.A., Young J.I., Aruga J., Crosby A.H.;
RT "SLITRK6 mutations cause myopia and deafness in humans and mice.";
RL J. Clin. Invest. 123:2094-2102(2013).
CC -!- FUNCTION: Regulator of neurite outgrowth required for normal hearing
CC and vision. {ECO:0000269|PubMed:14550773, ECO:0000269|PubMed:23543054}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250}; Single-pass type I
CC membrane protein {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: In the embryo, expressed in otic cyst, lateral
CC trunk epidermis and underlying mesodermal tissue, limb bud, maxillary
CC process, cochlea, retina, tongue, tooth primordium, central nervous
CC system, and primordia of visceral organs including lung,
CC gastrointestinal tract and pancreas. In the central nervous system,
CC expressed primarily in dorsal thalamus, cerebellum and medulla.
CC {ECO:0000269|PubMed:14643680}.
CC -!- DEVELOPMENTAL STAGE: During inner ear development, detected early in
CC the otic vesicle, and later in cochlear and vestibular sensory
CC epithelia. Present in the presumptive organ of Corti by 14.5 dpc, and
CC then confined to the supporting cell types at later stages of embryonic
CC development and at the newborn. In the vestibular sensory epithelia,
CC present at the lumenal surface. However, it is detected in the non-hair
CC cell region, presumably in the lumenal processes of the supporting
CC cells. Transiently expressed in the spiral and vestibular ganglion
CC neurons (at protein level) (PubMed:19936227). First expressed at 8.5
CC dpc. In the newborn, broadly detected in neural retina. Later, in P10
CC retina, expression is enhanced in the inner nuclear and outer plexiform
CC layers. Expression in retina decreases as development proceeded, and is
CC detected in the inner nuclear layer and in a subset of cells in the
CC ganglion cell layer of adults (PubMed:23543054).
CC {ECO:0000269|PubMed:14643680, ECO:0000269|PubMed:19936227,
CC ECO:0000269|PubMed:23543054}.
CC -!- DISRUPTION PHENOTYPE: Male and female mice grow without showing any
CC external abnormalities and are fertile but display auditory deficits.
CC In the developing inner ear, mice show pronounced reduction of cochlear
CC innervation, despite normal gross morphology and general organization
CC of the organ of Corti (PubMed:19936227). Adult mice have reduced
CC startle response and impaired auditory brainstem responses consistent
CC with mid-frequency range hearing loss (PubMed:21298075). Retinas in
CC postnatal development display a delay in synaptogenesis
CC (PubMed:23543054). {ECO:0000269|PubMed:19936227,
CC ECO:0000269|PubMed:21298075, ECO:0000269|PubMed:23543054}.
CC -!- SIMILARITY: Belongs to the SLITRK family. {ECO:0000305}.
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DR EMBL; AB097575; BAC67209.1; -; Genomic_DNA.
DR EMBL; AK029275; BAC26368.1; -; mRNA.
DR CCDS; CCDS27326.1; -.
DR RefSeq; NP_780708.1; NM_175499.4.
DR AlphaFoldDB; Q8C110; -.
DR SMR; Q8C110; -.
DR IntAct; Q8C110; 1.
DR STRING; 10090.ENSMUSP00000077492; -.
DR iPTMnet; Q8C110; -.
DR PhosphoSitePlus; Q8C110; -.
DR PaxDb; Q8C110; -.
DR PRIDE; Q8C110; -.
DR ProteomicsDB; 258695; -.
DR Antibodypedia; 24756; 269 antibodies from 31 providers.
DR DNASU; 239250; -.
DR Ensembl; ENSMUST00000078386; ENSMUSP00000077492; ENSMUSG00000045871.
DR GeneID; 239250; -.
DR KEGG; mmu:239250; -.
DR UCSC; uc007uyd.2; mouse.
DR CTD; 84189; -.
DR MGI; MGI:2443198; Slitrk6.
DR VEuPathDB; HostDB:ENSMUSG00000045871; -.
DR eggNOG; ENOG502QZTX; Eukaryota.
DR GeneTree; ENSGT00940000160718; -.
DR HOGENOM; CLU_012706_1_0_1; -.
DR InParanoid; Q8C110; -.
DR OMA; RNPTYCS; -.
DR OrthoDB; 217854at2759; -.
DR PhylomeDB; Q8C110; -.
DR TreeFam; TF326378; -.
DR Reactome; R-MMU-388844; Receptor-type tyrosine-protein phosphatases.
DR BioGRID-ORCS; 239250; 0 hits in 71 CRISPR screens.
DR PRO; PR:Q8C110; -.
DR Proteomes; UP000000589; Chromosome 14.
DR RNAct; Q8C110; protein.
DR Bgee; ENSMUSG00000045871; Expressed in vestibular organ and 145 other tissues.
DR ExpressionAtlas; Q8C110; baseline and differential.
DR Genevisible; Q8C110; MM.
DR GO; GO:0071944; C:cell periphery; IDA:MGI.
DR GO; GO:0009986; C:cell surface; ISO:MGI.
DR GO; GO:0016021; C:integral component of membrane; ISS:MGI.
DR GO; GO:0005887; C:integral component of plasma membrane; ISS:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; ISO:MGI.
DR GO; GO:0008344; P:adult locomotory behavior; IMP:MGI.
DR GO; GO:0031223; P:auditory behavior; IMP:MGI.
DR GO; GO:0002093; P:auditory receptor cell morphogenesis; IMP:MGI.
DR GO; GO:0007409; P:axonogenesis; IDA:MGI.
DR GO; GO:0043010; P:camera-type eye development; IMP:MGI.
DR GO; GO:0090102; P:cochlea development; IMP:MGI.
DR GO; GO:0042472; P:inner ear morphogenesis; IMP:MGI.
DR GO; GO:0060384; P:innervation; IMP:MGI.
DR GO; GO:0002088; P:lens development in camera-type eye; IMP:MGI.
DR GO; GO:0060007; P:linear vestibuloocular reflex; IMP:MGI.
DR GO; GO:0035264; P:multicellular organism growth; IMP:MGI.
DR GO; GO:0048812; P:neuron projection morphogenesis; IMP:MGI.
DR GO; GO:0051965; P:positive regulation of synapse assembly; IDA:MGI.
DR GO; GO:1905606; P:regulation of presynapse assembly; IEA:InterPro.
DR GO; GO:0007605; P:sensory perception of sound; IEA:UniProtKB-KW.
DR GO; GO:0001964; P:startle response; IMP:MGI.
DR GO; GO:0007416; P:synapse assembly; IMP:MGI.
DR GO; GO:0060005; P:vestibular reflex; IMP:MGI.
DR GO; GO:0021562; P:vestibulocochlear nerve development; IMP:MGI.
DR GO; GO:0007601; P:visual perception; IMP:MGI.
DR Gene3D; 3.80.10.10; -; 2.
DR InterPro; IPR000483; Cys-rich_flank_reg_C.
DR InterPro; IPR001611; Leu-rich_rpt.
DR InterPro; IPR003591; Leu-rich_rpt_typical-subtyp.
DR InterPro; IPR032675; LRR_dom_sf.
DR InterPro; IPR043326; Slitrk.
DR PANTHER; PTHR45773; PTHR45773; 1.
DR Pfam; PF13855; LRR_8; 2.
DR SMART; SM00369; LRR_TYP; 9.
DR SMART; SM00082; LRRCT; 2.
DR PROSITE; PS51450; LRR; 10.
PE 1: Evidence at protein level;
KW Cell membrane; Hearing; Leucine-rich repeat; Membrane; Reference proteome;
KW Repeat; Sensory transduction; Signal; Transmembrane; Transmembrane helix;
KW Vision.
FT SIGNAL 1..18
FT /evidence="ECO:0000255"
FT CHAIN 19..840
FT /note="SLIT and NTRK-like protein 6"
FT /evidence="ECO:0000255"
FT /id="PRO_0000032684"
FT TOPO_DOM 23..609
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 610..630
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 631..840
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 22..67
FT /note="LRRNT 1"
FT REPEAT 89..110
FT /note="LRR 1"
FT REPEAT 113..134
FT /note="LRR 2"
FT REPEAT 137..158
FT /note="LRR 3"
FT REPEAT 161..182
FT /note="LRR 4"
FT REPEAT 184..205
FT /note="LRR 5"
FT DOMAIN 218..269
FT /note="LRRCT 1"
FT DOMAIN 319..360
FT /note="LRRNT 2"
FT REPEAT 363..384
FT /note="LRR 6"
FT REPEAT 387..408
FT /note="LRR 7"
FT REPEAT 411..432
FT /note="LRR 8"
FT REPEAT 435..456
FT /note="LRR 9"
FT REPEAT 459..480
FT /note="LRR 10"
FT REPEAT 482..503
FT /note="LRR 11"
FT DOMAIN 516..567
FT /note="LRRCT 2"
FT REGION 717..736
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
SQ SEQUENCE 840 AA; 95056 MW; 9D812FADCFF43097 CRC64;
MKLWTYLLYP SLLACLSLQS QSPMPSVRGS CDTLCNCEEK DGIMIINCEE KGINKLSQIS
VPPSRPFHLS LLNNGLTMLH TNDFSGLTNA LSIHLGFNNI ADIETGAFNG LGLLKQLHIN
HNSLEILKED TFHGLENLEF LQADNNFITI IEPSAFSKLN RLKVLILNDN AIESLPPNIF
RFVPLTHLDL RGNQLQTLPY VGFLEHIGRI LDLQLEDNKW ACNCELLQLK NWLENMPPQS
IIGDVICYSP PPFKGSVLSR LKKESFCPTP PVYEEHEDPS GSLLAITSST SDSRLSSKNT
SILKQPTKAP GLIPYLTKPS TQLPVPYCPI PCNCKVLSPS GLLIHCQERN IESLSDLQPP
PHNPRKLILA GNIIHTLMKS DLTDYFTLEM LHLGNNRIEV LEEGSFMNLT RLQKLYLNGN
HLTKLNKGMF LGLHSLEYLY LEYNAVKEIL PGTFNPMPKL KVLYLNNNLL QVLPAHIFLG
IPLTRVNLKT NQFTHLPVSN ILDDLDFLIQ IDLEDNPWDC SCDLVGLQQW IHKLGKGTMT
DDILCTSPGH LDKKELKALN SDLLCPGLVN NPSMPTQTTY VIVTSPTVAA DTASTLFSSL
TDAVPLSVLI LGLLIVFITI VFCAAGIVVF VLHRRRRYKK KKVEEQLRDN SPVHLQYSMY
GHKTTHHTTE RPSSSLYEQH MVSPMVHVYR SPSFGPKHLE EVEERNDKEG NDAKHLQRSL
LERENHSPLT GSNMKYKTTD QSTDFISFQD ASLLYRNILE KERELQQLGI TEYLRKNLAQ
LQPEVEVNYP GAHEELKLME TLMYSRPRKV LVEQTKNEYF ELKANLHAEP DYLEVLEQQT
