ID   SNX14_DANRE             Reviewed;         934 AA.
AC   Q5PNP1; A1L1U0;
DT   24-JUN-2015, integrated into UniProtKB/Swiss-Prot.
DT   26-JUN-2013, sequence version 3.
DT   03-AUG-2022, entry version 104.
DE   RecName: Full=Sorting nexin-14;
GN   Name=snx14 {ECO:0000312|ZFIN:ZDB-GENE-040724-144};
OS   Danio rerio (Zebrafish) (Brachydanio rerio).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Actinopterygii; Neopterygii; Teleostei; Ostariophysi; Cypriniformes;
OC   Danionidae; Danioninae; Danio.
OX   NCBI_TaxID=7955;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=Tuebingen;
RX   PubMed=23594743; DOI=10.1038/nature12111;
RA   Howe K., Clark M.D., Torroja C.F., Torrance J., Berthelot C., Muffato M.,
RA   Collins J.E., Humphray S., McLaren K., Matthews L., McLaren S., Sealy I.,
RA   Caccamo M., Churcher C., Scott C., Barrett J.C., Koch R., Rauch G.J.,
RA   White S., Chow W., Kilian B., Quintais L.T., Guerra-Assuncao J.A., Zhou Y.,
RA   Gu Y., Yen J., Vogel J.H., Eyre T., Redmond S., Banerjee R., Chi J., Fu B.,
RA   Langley E., Maguire S.F., Laird G.K., Lloyd D., Kenyon E., Donaldson S.,
RA   Sehra H., Almeida-King J., Loveland J., Trevanion S., Jones M., Quail M.,
RA   Willey D., Hunt A., Burton J., Sims S., McLay K., Plumb B., Davis J.,
RA   Clee C., Oliver K., Clark R., Riddle C., Elliot D., Threadgold G.,
RA   Harden G., Ware D., Begum S., Mortimore B., Kerry G., Heath P.,
RA   Phillimore B., Tracey A., Corby N., Dunn M., Johnson C., Wood J., Clark S.,
RA   Pelan S., Griffiths G., Smith M., Glithero R., Howden P., Barker N.,
RA   Lloyd C., Stevens C., Harley J., Holt K., Panagiotidis G., Lovell J.,
RA   Beasley H., Henderson C., Gordon D., Auger K., Wright D., Collins J.,
RA   Raisen C., Dyer L., Leung K., Robertson L., Ambridge K., Leongamornlert D.,
RA   McGuire S., Gilderthorp R., Griffiths C., Manthravadi D., Nichol S.,
RA   Barker G., Whitehead S., Kay M., Brown J., Murnane C., Gray E.,
RA   Humphries M., Sycamore N., Barker D., Saunders D., Wallis J., Babbage A.,
RA   Hammond S., Mashreghi-Mohammadi M., Barr L., Martin S., Wray P.,
RA   Ellington A., Matthews N., Ellwood M., Woodmansey R., Clark G., Cooper J.,
RA   Tromans A., Grafham D., Skuce C., Pandian R., Andrews R., Harrison E.,
RA   Kimberley A., Garnett J., Fosker N., Hall R., Garner P., Kelly D., Bird C.,
RA   Palmer S., Gehring I., Berger A., Dooley C.M., Ersan-Urun Z., Eser C.,
RA   Geiger H., Geisler M., Karotki L., Kirn A., Konantz J., Konantz M.,
RA   Oberlander M., Rudolph-Geiger S., Teucke M., Lanz C., Raddatz G.,
RA   Osoegawa K., Zhu B., Rapp A., Widaa S., Langford C., Yang F.,
RA   Schuster S.C., Carter N.P., Harrow J., Ning Z., Herrero J., Searle S.M.,
RA   Enright A., Geisler R., Plasterk R.H., Lee C., Westerfield M.,
RA   de Jong P.J., Zon L.I., Postlethwait J.H., Nusslein-Volhard C.,
RA   Hubbard T.J., Roest Crollius H., Rogers J., Stemple D.L.;
RT   "The zebrafish reference genome sequence and its relationship to the human
RT   genome.";
RL   Nature 496:498-503(2013).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Embryo {ECO:0000312|EMBL:AAI29211.1};
RG   NIH - Zebrafish Gene Collection (ZGC) project;
RL   Submitted (DEC-2006) to the EMBL/GenBank/DDBJ databases.
RN   [3]
RP   DISRUPTION PHENOTYPE.
RX   PubMed=25848753; DOI=10.1038/ng.3256;
RA   Akizu N., Cantagrel V., Zaki M.S., Al-Gazali L., Wang X., Rosti R.O.,
RA   Dikoglu E., Gelot A.B., Rosti B., Vaux K.K., Scott E.M., Silhavy J.L.,
RA   Schroth J., Copeland B., Schaffer A.E., Gordts P.L., Esko J.D.,
RA   Buschman M.D., Field S.J., Napolitano G., Abdel-Salam G.M., Ozgul R.K.,
RA   Sagiroglu M.S., Azam M., Ismail S., Aglan M., Selim L., Mahmoud I.G.,
RA   Abdel-Hadi S., Badawy A.E., Sadek A.A., Mojahedi F., Kayserili H.,
RA   Masri A., Bastaki L., Temtamy S., Mueller U., Desguerre I., Casanova J.L.,
RA   Dursun A., Gunel M., Gabriel S.B., de Lonlay P., Gleeson J.G.;
RT   "Biallelic mutations in SNX14 cause a syndromic form of cerebellar atrophy
RT   and lysosome-autophagosome dysfunction.";
RL   Nat. Genet. 47:528-534(2015).
CC   -!- FUNCTION: Plays a role in maintaining normal neuronal excitability and
CC       synaptic transmission. May be involved in several stages of
CC       intracellular trafficking (By similarity). Required for autophagosome
CC       clearance, possibly by mediating the fusion of lysosomes with
CC       autophagosomes (PubMed:25848753). Binds phosphatidylinositol 3,5-
CC       bisphosphate (PtdIns(3,5)P2), a key component of late
CC       endosomes/lysosomes. Does not bind phosphatidylinositol 3-phosphate
CC       (PtdIns(3P)) (By similarity). {ECO:0000250|UniProtKB:Q8BHY8,
CC       ECO:0000250|UniProtKB:Q9Y5W7, ECO:0000269|PubMed:25848753}.
CC   -!- SUBCELLULAR LOCATION: Lysosome membrane {ECO:0000250|UniProtKB:Q9Y5W7};
CC       Multi-pass membrane protein {ECO:0000305}. Late endosome membrane
CC       {ECO:0000250|UniProtKB:Q9Y5W7}; Multi-pass membrane protein
CC       {ECO:0000305}. Cell projection, dendrite
CC       {ECO:0000250|UniProtKB:Q8BHY8}.
CC   -!- DISRUPTION PHENOTYPE: Loss of neural tissue volume: neuronal cell death
CC       is associated with impaired autophagic degradation.
CC       {ECO:0000269|PubMed:25848753}.
CC   -!- SIMILARITY: Belongs to the sorting nexin family. {ECO:0000305}.
CC   ---------------------------------------------------------------------------
CC   Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC   Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC   ---------------------------------------------------------------------------
DR   EMBL; BX537259; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; BC129210; AAI29211.1; -; mRNA.
DR   RefSeq; XP_005160373.1; XM_005160316.1.
DR   AlphaFoldDB; Q5PNP1; -.
DR   SMR; Q5PNP1; -.
DR   STRING; 7955.ENSDARP00000095495; -.
DR   PaxDb; Q5PNP1; -.
DR   Ensembl; ENSDART00000142361; ENSDARP00000119620; ENSDARG00000006332.
DR   GeneID; 555970; -.
DR   CTD; 57231; -.
DR   ZFIN; ZDB-GENE-040724-144; snx14.
DR   eggNOG; KOG2101; Eukaryota.
DR   GeneTree; ENSGT00950000182856; -.
DR   HOGENOM; CLU_014115_0_0_1; -.
DR   OMA; HGESEIC; -.
DR   OrthoDB; 257375at2759; -.
DR   PRO; PR:Q5PNP1; -.
DR   Proteomes; UP000000437; Genome assembly.
DR   Proteomes; UP000814640; Chromosome 20.
DR   Bgee; ENSDARG00000006332; Expressed in mature ovarian follicle and 24 other tissues.
DR   ExpressionAtlas; Q5PNP1; baseline and differential.
DR   GO; GO:0030425; C:dendrite; IEA:UniProtKB-SubCell.
DR   GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR   GO; GO:0043231; C:intracellular membrane-bounded organelle; IBA:GO_Central.
DR   GO; GO:0005770; C:late endosome; ISS:UniProtKB.
DR   GO; GO:0031902; C:late endosome membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0005765; C:lysosomal membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0005764; C:lysosome; ISS:UniProtKB.
DR   GO; GO:0035091; F:phosphatidylinositol binding; IBA:GO_Central.
DR   GO; GO:0080025; F:phosphatidylinositol-3,5-bisphosphate binding; ISS:UniProtKB.
DR   GO; GO:0097352; P:autophagosome maturation; IMP:UniProtKB.
DR   GO; GO:0006914; P:autophagy; IMP:ZFIN.
DR   GO; GO:0021680; P:cerebellar Purkinje cell layer development; IMP:ZFIN.
DR   GO; GO:0030902; P:hindbrain development; IMP:ZFIN.
DR   CDD; cd06877; PX_SNX14; 1.
DR   CDD; cd08722; RGS_SNX14; 1.
DR   Gene3D; 1.10.167.10; -; 1.
DR   Gene3D; 3.30.1520.10; -; 1.
DR   InterPro; IPR003114; Phox_assoc.
DR   InterPro; IPR001683; PX_dom.
DR   InterPro; IPR036871; PX_dom_sf.
DR   InterPro; IPR016137; RGS.
DR   InterPro; IPR036305; RGS_sf.
DR   InterPro; IPR044926; RGS_subdomain_2.
DR   InterPro; IPR037436; SNX14_PX.
DR   InterPro; IPR037892; SNX14_RGS.
DR   InterPro; IPR013937; Sorting_nexin_C.
DR   Pfam; PF08628; Nexin_C; 1.
DR   Pfam; PF00787; PX; 1.
DR   Pfam; PF02194; PXA; 1.
DR   Pfam; PF00615; RGS; 1.
DR   SMART; SM00312; PX; 1.
DR   SMART; SM00313; PXA; 1.
DR   SMART; SM00315; RGS; 1.
DR   SUPFAM; SSF48097; SSF48097; 1.
DR   SUPFAM; SSF64268; SSF64268; 1.
DR   PROSITE; PS50195; PX; 1.
DR   PROSITE; PS51207; PXA; 1.
DR   PROSITE; PS50132; RGS; 1.
PE   2: Evidence at transcript level;
KW   Cell projection; Endosome; Lysosome; Membrane; Reference proteome;
KW   Transmembrane; Transmembrane helix.
FT   CHAIN           1..934
FT                   /note="Sorting nexin-14"
FT                   /id="PRO_0000433425"
FT   TRANSMEM        27..47
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        48..68
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   DOMAIN          129..303
FT                   /note="PXA"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00553"
FT   DOMAIN          335..467
FT                   /note="RGS"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00171"
FT   DOMAIN          557..677
FT                   /note="PX"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00147"
FT   CONFLICT        383
FT                   /note="D -> E (in Ref. 2; AAI29211)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   934 AA;  108143 MW;  8B2BE3723596AA83 CRC64;
     MSDPHSFLGC VRRGLRFDMF KDVARQYPVI FCIFTVMISS TIILNQYLHI LMVFWSFLAG
     VITFYCSLSP EYLLPNILIS IKTKRKPQEQ HELFPLGHSC AVCGKNQCKR HRPTLLLENY
     QPWLNLKVPS KVDASISEVL ELVLENFVYP WYRDITDDEA CVDELRQTIR FFAAVLAHRA
     QRVDVPSVVM DKMMKAAMKH IEIIAKAQQK VRNTDGLEQA ALAEYGADLH VALRSRKDEL
     LYLRKLTELL FPYVMPPKAT DCRSLALLIR EVMTGSVFLP IMDFVADPDT VNHMVLIFID
     DSPPEPVTDP PSTLVPFLER FADPRTKKSS VLKLDLKEIR EQQDLLFRFM SFLKEEGAVH
     VLQFCLTVEE FNDRILCPDL SDDEKQRLHE EVKKIYETYC LEESIDKISF DPFIIEEIHS
     IAEGPYTGVV KLQTMRCLFE AYEHVLCLLE KVFTPMFCHS DEYFRHLLCG AESPARNSKL
     NRNTSKRGES FGISRIGSKI KGVFKSSTME GAMLPQYAMI EGEDDTVEEA VMVFEDDSPG
     PMDAVGTPGT LRNLSAWTIS IPYVDFYDDE VKKERIPVFC IDVERNDRKN VGHETESWSV
     YRKYVEFYVL ESKLTEFHGP FQDAQLPSKR IIGPKNYEFL SSKRGEFEEY LQKLLHHPEL
     SNSQLLADFL SPFSMESQFR DKMLPDVNLG KIFKSVPGKL IKEKGQNLEP FIQSFFSSCE
     SPKPKPSRPE LTILSPTAEN NKKLFNELYR NNANLPEGLE KKHNQNYFME LMEVDGAYDY
     MMYIGRVVFR MPDWLHHLLS GVRILLKRTL EAYVGHYFQY KLEQIMEEHR LVSLVTLLRD
     AVFCESTEER SPEDKQRRAK QTFEEMMNYL PDIVGKCIGE EAKYDGVKML FNTIQQPLLN
     KQMTYVLLDI AIQELFPELS KNQKQGLSVS TRWM