PDZD7_MOUSE
ID PDZD7_MOUSE Reviewed; 1021 AA.
AC E9Q9W7; E9Q9U9; X4YT42; X4YT46; X4YZM3; X4ZGA7;
DT 05-DEC-2018, integrated into UniProtKB/Swiss-Prot.
DT 03-OCT-2012, sequence version 2.
DT 03-AUG-2022, entry version 83.
DE RecName: Full=PDZ domain-containing protein 7 {ECO:0000305};
GN Name=Pdzd7 {ECO:0000312|MGI:MGI:3608325};
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 [MRNA] (ISOFORMS 2; 3; 4), FUNCTION, DISRUPTION
RP PHENOTYPE, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, ALTERNATIVE SPLICING,
RP AND DEVELOPMENTAL STAGE.
RC STRAIN=C57BL/6J; TISSUE=Retina;
RX PubMed=24334608; DOI=10.1093/hmg/ddt629;
RA Zou J., Zheng T., Ren C., Askew C., Liu X.P., Pan B., Holt J.R., Wang Y.,
RA Yang J.;
RT "Deletion of PDZD7 disrupts the Usher syndrome type 2 protein complex in
RT cochlear hair cells and causes hearing loss in mice.";
RL Hum. Mol. Genet. 23:2374-2390(2014).
RN [2]
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 [3]
RP INTERACTION WITH ADGRV1 AND USH2A.
RX PubMed=23055499; DOI=10.1523/jneurosci.3071-12.2012;
RA Grati M., Shin J.B., Weston M.D., Green J., Bhat M.A., Gillespie P.G.,
RA Kachar B.;
RT "Localization of PDZD7 to the stereocilia ankle-link associates this
RT scaffolding protein with the Usher syndrome protein network.";
RL J. Neurosci. 32:14288-14293(2012).
RN [4]
RP FUNCTION, AND INTERACTION WITH ADGRV1.
RX PubMed=24962568; DOI=10.1074/jbc.m114.549816;
RA Hu Q.X., Dong J.H., Du H.B., Zhang D.L., Ren H.Z., Ma M.L., Cai Y.,
RA Zhao T.C., Yin X.L., Yu X., Xue T., Xu Z.G., Sun J.P.;
RT "Constitutive Galphai coupling activity of very large G protein-coupled
RT receptor 1 (VLGR1) and its regulation by PDZD7 protein.";
RL J. Biol. Chem. 289:24215-24225(2014).
RN [5]
RP IDENTIFICATION IN THE USH2 COMPLEX, SUBUNIT, AND INTERACTION WITH WHRN.
RX PubMed=25406310; DOI=10.1074/jbc.m114.610535;
RA Chen Q., Zou J., Shen Z., Zhang W., Yang J.;
RT "Whirlin and PDZ domain-containing 7 (PDZD7) proteins are both required to
RT form the quaternary protein complex associated with Usher syndrome type
RT 2.";
RL J. Biol. Chem. 289:36070-36088(2014).
RN [6]
RP INTERACTION WITH MYO7A, AND SUBCELLULAR LOCATION.
RX PubMed=27525485; DOI=10.7554/elife.18312;
RA Morgan C.P., Krey J.F., Grati M., Zhao B., Fallen S., Kannan-Sundhari A.,
RA Liu X.Z., Choi D., Mueller U., Barr-Gillespie P.G.;
RT "PDZD7-MYO7A complex identified in enriched stereocilia membranes.";
RL Elife 5:0-0(2016).
CC -!- FUNCTION: In cochlear developing hair cells, essential in organizing
CC the USH2 complex at stereocilia ankle links (PubMed:24334608). Blocks
CC inhibition of adenylate cyclase activity mediated by ADGRV1
CC (PubMed:24962568). {ECO:0000269|PubMed:24334608,
CC ECO:0000269|PubMed:24962568}.
CC -!- SUBUNIT: Homodimerizes (via PDZ2 domain) (PubMed:25406310). Component
CC of USH2 complex, composed of ADGRV1, PDZD7, USH2A and WHRN
CC (PubMed:25406310). Interacts (via PDZ domains) with WHRN; the
CC interaction is direct (PubMed:25406310). Interacts with USH1G (By
CC similarity). Interacts with ADGRV1 (via the cytoplasmic region)
CC (PubMed:24962568, PubMed:23055499). Interacts with USH2A (via the
CC cytoplasmic region) (PubMed:23055499). Interacts with MYO7A (via MyTH4-
CC FERM domains) (PubMed:27525485). {ECO:0000250|UniProtKB:Q9H5P4,
CC ECO:0000269|PubMed:23055499, ECO:0000269|PubMed:24962568,
CC ECO:0000269|PubMed:25406310, ECO:0000269|PubMed:27525485}.
CC -!- SUBCELLULAR LOCATION: Cell projection, cilium
CC {ECO:0000250|UniProtKB:Q9H5P4}. Nucleus {ECO:0000250|UniProtKB:Q9H5P4}.
CC Cell projection, stereocilium {ECO:0000269|PubMed:24334608,
CC ECO:0000269|PubMed:27525485}. Note=Localizes at the ankle region of the
CC stereocilia. {ECO:0000269|PubMed:24334608,
CC ECO:0000269|PubMed:27525485}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=5;
CC Name=1;
CC IsoId=E9Q9W7-1; Sequence=Displayed;
CC Name=2 {ECO:0000303|PubMed:24334608};
CC IsoId=E9Q9W7-2; Sequence=VSP_059957, VSP_059958;
CC Name=3 {ECO:0000303|PubMed:24334608};
CC IsoId=E9Q9W7-3; Sequence=VSP_059955, VSP_059956;
CC Name=4 {ECO:0000303|PubMed:24334608};
CC IsoId=E9Q9W7-4; Sequence=VSP_059952;
CC Name=5 {ECO:0000303|PubMed:24334608};
CC IsoId=E9Q9W7-5; Sequence=VSP_059953, VSP_059954;
CC -!- TISSUE SPECIFICITY: Isoform 1 is expressed in developing and adult
CC cochlea but not retina (PubMed:24334608). Isoform 2 is expressed in
CC developing and adult cochlea and retina (PubMed:24334608). Isoform 3 is
CC expressed in adult cochlea and retina (PubMed:24334608). Isoform 4 is
CC expressed in retina and developing cochlea but not adult cochlea
CC (PubMed:24334608). Isoform 5 is expressed in adult cochlea but not in
CC developing cochlea or retina (PubMed:24334608).
CC {ECO:0000269|PubMed:24334608}.
CC -!- DEVELOPMENTAL STAGE: In cochlea hair cells, only isoforms 1, 2 and 4
CC are expressed at P5. At P24, isoforms 1, 2, 3 and 5 are expressed.
CC {ECO:0000269|PubMed:24334608}.
CC -!- DISRUPTION PHENOTYPE: Mutant mice exhibit congenital profound deafness
CC and normal vestibular function. They show disorganized stereocilia
CC bundles with a reduction in mechanotransduction currents and
CC sensitivity in cochlear outer cells (PubMed:24334608). Knockout mice
CC have normal vision function from rod and cone photoreceptors
CC (PubMed:24334608). {ECO:0000269|PubMed:24334608}.
CC -!- MISCELLANEOUS: [Isoform 1]: Expressed in developing and adult cochlea
CC but not retina. {ECO:0000269|PubMed:24334608}.
CC -!- MISCELLANEOUS: [Isoform 2]: Expressed in developing and adult cochlea
CC and retina. {ECO:0000269|PubMed:24334608}.
CC -!- MISCELLANEOUS: [Isoform 3]: Expressed in adult cochlea and retina.
CC {ECO:0000269|PubMed:24334608}.
CC -!- MISCELLANEOUS: [Isoform 4]: Expressed in retina and developing cochlea
CC but not adult cochlea. {ECO:0000269|PubMed:24334608}.
CC -!- MISCELLANEOUS: [Isoform 5]: Expressed in adult cochlea but not in
CC developing cochlea or retina. {ECO:0000269|PubMed:24334608}.
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DR EMBL; KF041446; AHV90413.1; -; mRNA.
DR EMBL; KF041447; AHV90414.1; -; mRNA.
DR EMBL; KF041449; AHV90416.1; -; mRNA.
DR EMBL; KF041450; AHV90417.1; -; mRNA.
DR EMBL; KF041451; AHV90418.1; -; mRNA.
DR EMBL; AC132957; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR CCDS; CCDS57145.1; -. [E9Q9W7-1]
DR RefSeq; NP_001182194.1; NM_001195265.1. [E9Q9W7-1]
DR RefSeq; XP_006526599.1; XM_006526536.1. [E9Q9W7-1]
DR RefSeq; XP_006526600.1; XM_006526537.3. [E9Q9W7-1]
DR PDB; 7DE7; X-ray; 1.49 A; A/B=546-646.
DR PDBsum; 7DE7; -.
DR AlphaFoldDB; E9Q9W7; -.
DR SMR; E9Q9W7; -.
DR ComplexPortal; CPX-2501; USH2 complex.
DR STRING; 10090.ENSMUSP00000119002; -.
DR iPTMnet; E9Q9W7; -.
DR PhosphoSitePlus; E9Q9W7; -.
DR PaxDb; E9Q9W7; -.
DR PRIDE; E9Q9W7; -.
DR Antibodypedia; 31245; 57 antibodies from 13 providers.
DR Ensembl; ENSMUST00000145391; ENSMUSP00000119002; ENSMUSG00000074818. [E9Q9W7-2]
DR Ensembl; ENSMUST00000169459; ENSMUSP00000133273; ENSMUSG00000074818. [E9Q9W7-1]
DR Ensembl; ENSMUST00000237077; ENSMUSP00000157527; ENSMUSG00000074818. [E9Q9W7-4]
DR Ensembl; ENSMUST00000237227; ENSMUSP00000157966; ENSMUSG00000074818. [E9Q9W7-3]
DR Ensembl; ENSMUST00000237833; ENSMUSP00000157695; ENSMUSG00000074818. [E9Q9W7-5]
DR Ensembl; ENSMUST00000237962; ENSMUSP00000157471; ENSMUSG00000074818. [E9Q9W7-4]
DR GeneID; 100503041; -.
DR KEGG; mmu:100503041; -.
DR UCSC; uc012bmk.1; mouse. [E9Q9W7-1]
DR CTD; 79955; -.
DR MGI; MGI:3608325; Pdzd7.
DR VEuPathDB; HostDB:ENSMUSG00000074818; -.
DR eggNOG; KOG3528; Eukaryota.
DR GeneTree; ENSGT00950000183002; -.
DR HOGENOM; CLU_304541_0_0_1; -.
DR InParanoid; E9Q9W7; -.
DR OMA; REHPPHG; -.
DR OrthoDB; 168224at2759; -.
DR PhylomeDB; E9Q9W7; -.
DR TreeFam; TF325033; -.
DR BioGRID-ORCS; 100503041; 2 hits in 74 CRISPR screens.
DR ChiTaRS; Pdzd7; mouse.
DR PRO; PR:E9Q9W7; -.
DR Proteomes; UP000000589; Chromosome 19.
DR RNAct; E9Q9W7; protein.
DR Bgee; ENSMUSG00000074818; Expressed in quadriceps femoris and 50 other tissues.
DR ExpressionAtlas; E9Q9W7; baseline and differential.
DR GO; GO:0005929; C:cilium; ISO:MGI.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005634; C:nucleus; ISO:MGI.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0002141; C:stereocilia ankle link; IDA:UniProtKB.
DR GO; GO:0002142; C:stereocilia ankle link complex; IDA:UniProtKB.
DR GO; GO:0032420; C:stereocilium; IDA:UniProtKB.
DR GO; GO:0032426; C:stereocilium tip; IBA:GO_Central.
DR GO; GO:1990696; C:USH2 complex; IDA:MGI.
DR GO; GO:0042802; F:identical protein binding; IPI:MGI.
DR GO; GO:0060117; P:auditory receptor cell development; IMP:MGI.
DR GO; GO:0060088; P:auditory receptor cell stereocilium organization; IMP:MGI.
DR GO; GO:0050910; P:detection of mechanical stimulus involved in sensory perception of sound; IMP:MGI.
DR GO; GO:0051649; P:establishment of localization in cell; IMP:MGI.
DR GO; GO:0045184; P:establishment of protein localization; IMP:MGI.
DR GO; GO:0060113; P:inner ear receptor cell differentiation; IC:ComplexPortal.
DR GO; GO:0007605; P:sensory perception of sound; IBA:GO_Central.
DR CDD; cd07358; HN_PDZD7_like; 1.
DR Gene3D; 2.30.42.10; -; 3.
DR InterPro; IPR001478; PDZ.
DR InterPro; IPR036034; PDZ_sf.
DR InterPro; IPR042786; PDZD7_HN-like.
DR Pfam; PF00595; PDZ; 3.
DR SMART; SM00228; PDZ; 3.
DR SUPFAM; SSF50156; SSF50156; 3.
DR PROSITE; PS50106; PDZ; 3.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Cell projection; Cilium; Nucleus;
KW Reference proteome; Repeat.
FT CHAIN 1..1021
FT /note="PDZ domain-containing protein 7"
FT /id="PRO_0000445738"
FT DOMAIN 86..156
FT /note="PDZ 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00143"
FT DOMAIN 210..279
FT /note="PDZ 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00143"
FT DOMAIN 858..930
FT /note="PDZ 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00143"
FT REGION 324..345
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 431..495
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 724..814
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 992..1021
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 324..341
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 438..456
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 479..495
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 728..746
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 751..773
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 774..788
FT /note="Basic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VAR_SEQ 290..1021
FT /note="Missing (in isoform 4)"
FT /id="VSP_059952"
FT VAR_SEQ 386..409
FT /note="VRPTVILRDTAIRSDGPSSTRHLD -> SPPRLLSFWPSADPELPSLDPRAT
FT (in isoform 5)"
FT /id="VSP_059953"
FT VAR_SEQ 410..1021
FT /note="Missing (in isoform 5)"
FT /id="VSP_059954"
FT VAR_SEQ 442..476
FT /note="EEKKQRKKEKSGSSGEKGALQRSKTLMNLFFKGGR -> ALPGAPSYLQRRR
FT NNGRRRSRDLLGRRGPCSAPRR (in isoform 3)"
FT /id="VSP_059955"
FT VAR_SEQ 477..1021
FT /note="Missing (in isoform 3)"
FT /id="VSP_059956"
FT VAR_SEQ 508..553
FT /note="AGSVGPVQKFVTWRLRRDRERGRALLSARSGSPSGQAPTVNEQVQA -> VP
FT RMLVSHGSQPSSLARPLSFHDSSFPLCFLKRGVWGLCRSLSPGD (in isoform
FT 2)"
FT /id="VSP_059957"
FT VAR_SEQ 554..1021
FT /note="Missing (in isoform 2)"
FT /id="VSP_059958"
FT HELIX 548..568
FT /evidence="ECO:0007829|PDB:7DE7"
FT HELIX 571..587
FT /evidence="ECO:0007829|PDB:7DE7"
FT HELIX 590..600
FT /evidence="ECO:0007829|PDB:7DE7"
FT HELIX 605..609
FT /evidence="ECO:0007829|PDB:7DE7"
FT HELIX 610..614
FT /evidence="ECO:0007829|PDB:7DE7"
FT HELIX 619..621
FT /evidence="ECO:0007829|PDB:7DE7"
FT HELIX 622..641
FT /evidence="ECO:0007829|PDB:7DE7"
SQ SEQUENCE 1021 AA; 110694 MW; 325866A1EA64DAF6 CRC64;
MARGFTVGFD PLGLGELSSG SLSSVSSRGH LGSDSGSTAT RYLLRKQQRL LNGPSRGIRA
SSPMGRVILI NSPIEANSDE SDIIHAVRVE KSPSGRLGFS VRGGSEHGLG IFVSKVEEGS
SAERAGLCVG DKITEVNGLS LESTTMGSAV RLLTSSSCLH MMVRRMGRVP GIKFSKEKTT
WVDVVNRRLV VEKCSSTPSD RSSEDGVRRI VHLYTTSDDF CLGFNIRGGK EFGLGIYVSK
VDHGGLAEEN GIKVGDQVLA ANGVRFDDIS HSQAVEVLKG QTHIMLTIKE TGRYPAYKEM
VSEYCWLDRL SNGVLQQLSP ASESSSSVSS YASSAPCSSG SLPSDRMDVC LGPEEPTSHG
PGWGRADTAM QTEPDLDSRV ETWCSVRPTV ILRDTAIRSD GPSSTRHLDS ALSESPKTAL
LLALSRPRTP ITRSQSHLTL WEEKKQRKKE KSGSSGEKGA LQRSKTLMNL FFKGGRQGRP
AGDGHREAWT LDSRSPTKVR PRLDLEKAGS VGPVQKFVTW RLRRDRERGR ALLSARSGSP
SGQAPTVNEQ VQAWESRRPL IQDLARRLLT DDEVLAVTRH CSRYVHEGGV EDLVRPLLAI
LDRPTKLLLL RDIRSVVAPT DLGRFDSMVM PVELEAFEAL KSRAVGPSAL RPTRQDTPPK
RHLITPVPDS RGGFYLLPVN SSEDEDGEIR EKLGVLKVSL GASAPHHKGI PPLQDVPVDA
FSLRRGACAP PPQPPPVAPR PPRPNWLLTE PLSREDTQQN QSQTPAQSCS RSRSRSRSRS
HSRGQGKSPG RRRSPSPAPI ATAATANGRY HRPRKARPLL PRLLDGQVAK VGARQGPLEN
GRIAEEAVGN VSTGALRTIT LSKMKQSLGI SISGGIESKV QPMVKIEKIF PGGAAFLCGD
LQAGFELVAV DGESLEQVTH QRAVDTIRRA YRNKAREPME LVVRVPGPGL LPLASDLRVV
KDQSLAPDCP SALGPVDDAR ILTQLPPPEA RQLQQSLSSA LKVPQSIPKL SPILKDPHDP
S
