NACHO_RAT
ID NACHO_RAT Reviewed; 167 AA.
AC Q6JAM9;
DT 09-JAN-2007, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2004, sequence version 1.
DT 03-AUG-2022, entry version 87.
DE RecName: Full=Novel acetylcholine receptor chaperone {ECO:0000303|PubMed:26875622};
DE AltName: Full=Spinal cord expression protein 4;
DE AltName: Full=TMEM35 gene-derived unknown factor 1;
DE AltName: Full=Transmembrane protein 35A;
GN Name=Tmem35a;
GN Synonyms=Nacho {ECO:0000303|PubMed:26875622}, Tmem35,
GN Tuf1 {ECO:0000303|Ref.1};
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Wang X., Jing N.;
RL Submitted (FEB-2004) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP TISSUE SPECIFICITY, INTERACTION WITH NGFR, MUTAGENESIS OF SER-46,
RP SUBCELLULAR LOCATION, AND INDUCTION.
RX PubMed=20685870; DOI=10.1210/en.2010-0487;
RA Tran P.V., Georgieff M.K., Engeland W.C.;
RT "Sodium depletion increases sympathetic neurite outgrowth and expression of
RT a novel TMEM35 gene-derived protein (TUF1) in the rat adrenal zona
RT glomerulosa.";
RL Endocrinology 151:4852-4860(2010).
RN [3]
RP DEVELOPMENTAL STAGE.
RX PubMed=28131622; DOI=10.1016/j.neuroscience.2017.01.026;
RA Wichern F., Jensen M.M., Christensen D.Z., Mikkelsen J.D.,
RA Gondre-Lewis M.C., Thomsen M.S.;
RT "Perinatal nicotine treatment induces transient increases in NACHO protein
RT levels in the rat frontal cortex.";
RL Neuroscience 346:278-283(2017).
RN [4]
RP FUNCTION, SUBCELLULAR LOCATION, TOPOLOGY, DISRUPTION PHENOTYPE, AND TISSUE
RP SPECIFICITY.
RX PubMed=26875622; DOI=10.1016/j.neuron.2016.01.018;
RA Gu S., Matta J.A., Lord B., Harrington A.W., Sutton S.W., Davini W.B.,
RA Bredt D.S.;
RT "Brain alpha7 Nicotinic Acetylcholine Receptor Assembly Requires NACHO.";
RL Neuron 89:948-955(2016).
CC -!- FUNCTION: Molecular chaperone which mediates the proper assembly and
CC functional expression of the nicotinic acetylcholine receptors (nAChRs)
CC throughout the brain (PubMed:26875622). Essential for the proper
CC folding, assembly, function and surface trafficking of alpha-7
CC (CHRNA7), alpha-4-beta-2, alpha-3-beta-2 and alpha-3-beta-4 receptors
CC (PubMed:26875622). Stably associates with ribophorin-1 (RPN1) and
CC ribophorin-2 (RPN2) (components of the oligosaccharyl transferase (OST)
CC complex) and with calnexin (CANX), both of which are critical for
CC NACHO-mediated effects on CHRNA7 assembly and function (By similarity).
CC Facilitates the proper folding and assembly of alpha-6-beta-2 and
CC alpha-6-beta-2-beta-3 receptors and acts at early stages of the nAChRs
CC subunit assembly (PubMed:26875622). Promotes the expression of the
CC alpha-4(2):beta-2(3) stoichiometric form over the alpha-4(3):beta-2(2)
CC form (By similarity). {ECO:0000250|UniProtKB:Q53FP2,
CC ECO:0000250|UniProtKB:Q9D328, ECO:0000269|PubMed:26875622}.
CC -!- SUBUNIT: May interact with NGFR (PubMed:20685870). Interacts with RPN1,
CC RPN2 and CANX (By similarity). {ECO:0000250|UniProtKB:Q9D328,
CC ECO:0000269|PubMed:20685870}.
CC -!- SUBCELLULAR LOCATION: Peroxisome membrane
CC {ECO:0000250|UniProtKB:Q9D328}; Multi-pass membrane protein
CC {ECO:0000255}. Cytoplasmic vesicle {ECO:0000269|PubMed:20685870}.
CC Endoplasmic reticulum membrane {ECO:0000269|PubMed:26875622}; Multi-
CC pass membrane protein {ECO:0000255}. Note=Shedding may lead to a
CC soluble peptide. {ECO:0000269|PubMed:20685870}.
CC -!- TISSUE SPECIFICITY: Present in adrenal zona glomerusa but not in
CC adrenal medulla (at protein level) (PubMed:20685870). Expressed in the
CC hippocampus (at protein level) (PubMed:26875622).
CC {ECO:0000269|PubMed:20685870, ECO:0000269|PubMed:26875622}.
CC -!- DEVELOPMENTAL STAGE: Levels decrease during early postnatal development
CC after which it remains stable into adulthood and this decrease occurs
CC to a greater degree in the frontal cortex compared to the hippocampus
CC (at protein level). {ECO:0000269|PubMed:28131622}.
CC -!- INDUCTION: By sodium depletion and angiotensin II in adrenal zona
CC glomerusa (at protein level). {ECO:0000269|PubMed:20685870}.
CC -!- DISRUPTION PHENOTYPE: Knockdown in cultured hippocampal neurons shows a
CC complete disruption of the assembly and function of the neuronal
CC acetylcholine receptor subunit alpha-7 (CHRNA7).
CC {ECO:0000269|PubMed:26875622}.
CC -!- SIMILARITY: Belongs to the DoxX family. {ECO:0000305}.
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DR EMBL; AY540309; AAT08467.1; -; mRNA.
DR RefSeq; NP_001001799.1; NM_001001799.1.
DR AlphaFoldDB; Q6JAM9; -.
DR STRING; 10116.ENSRNOP00000002058; -.
DR PhosphoSitePlus; Q6JAM9; -.
DR jPOST; Q6JAM9; -.
DR PaxDb; Q6JAM9; -.
DR PRIDE; Q6JAM9; -.
DR Ensembl; ENSRNOT00000002058; ENSRNOP00000002058; ENSRNOG00000001506.
DR GeneID; 308134; -.
DR KEGG; rno:308134; -.
DR CTD; 59353; -.
DR RGD; 1303093; Tmem35a.
DR eggNOG; ENOG502RXPR; Eukaryota.
DR GeneTree; ENSGT00940000154325; -.
DR HOGENOM; CLU_121618_0_0_1; -.
DR InParanoid; Q6JAM9; -.
DR OMA; ICGIIMT; -.
DR OrthoDB; 1615454at2759; -.
DR PhylomeDB; Q6JAM9; -.
DR TreeFam; TF300206; -.
DR PRO; PR:Q6JAM9; -.
DR Proteomes; UP000002494; Chromosome X.
DR Bgee; ENSRNOG00000001506; Expressed in cerebellum and 13 other tissues.
DR Genevisible; Q6JAM9; RN.
DR GO; GO:0031410; C:cytoplasmic vesicle; IEA:UniProtKB-KW.
DR GO; GO:0005783; C:endoplasmic reticulum; ISO:RGD.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005778; C:peroxisomal membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0030548; F:acetylcholine receptor regulator activity; IMP:UniProtKB.
DR GO; GO:0051131; P:chaperone-mediated protein complex assembly; IMP:UniProtKB.
DR GO; GO:2000010; P:positive regulation of protein localization to cell surface; IMP:UniProtKB.
DR InterPro; IPR029693; TMEM35A.
DR InterPro; IPR040399; TMEM35A/B.
DR PANTHER; PTHR13163; PTHR13163; 1.
DR PANTHER; PTHR13163:SF0; PTHR13163:SF0; 1.
PE 1: Evidence at protein level;
KW Chaperone; Cytoplasmic vesicle; Endoplasmic reticulum; Membrane;
KW Peroxisome; Reference proteome; Transmembrane; Transmembrane helix.
FT CHAIN 1..167
FT /note="Novel acetylcholine receptor chaperone"
FT /id="PRO_0000271610"
FT TOPO_DOM 1..5
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 6..26
FT /note="Helical; Name=1"
FT /evidence="ECO:0000255"
FT TOPO_DOM 27..61
FT /note="Lumenal"
FT /evidence="ECO:0000305|PubMed:26875622"
FT TRANSMEM 62..82
FT /note="Helical; Name=2"
FT /evidence="ECO:0000255"
FT TOPO_DOM 83..88
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305|PubMed:26875622"
FT TRANSMEM 89..109
FT /note="Helical; Name=3"
FT /evidence="ECO:0000255"
FT TOPO_DOM 110..114
FT /note="Lumenal"
FT /evidence="ECO:0000305|PubMed:26875622"
FT TRANSMEM 115..132
FT /note="Helical; Name=4"
FT /evidence="ECO:0000255"
FT TOPO_DOM 133..167
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT REGION 43..54
FT /note="Interaction with NGFR"
FT /evidence="ECO:0000269|PubMed:20685870"
FT REGION 135..167
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MUTAGEN 46
FT /note="S->A: Abolishes interaction with NGFR."
FT /evidence="ECO:0000269|PubMed:20685870"
SQ SEQUENCE 167 AA; 18473 MW; 7F28E4D9E2CDC013 CRC64;
MASPRTITIV ALSVALGLFF VFMGTIKLTP RLSKDAYSEM KRAYKSYVRA LPLLKKMGIN
SILLRKSIGA LEVACGIVMT LVPGRPKDVA NFFLLLLVLA VLFFHQLVGD PLKRYAHALV
FGILLTCRLL IARKPEDRSS EKKALPESAE EQPSLYEKAP QGKVKVS
