TMEM9_MOUSE
ID TMEM9_MOUSE Reviewed; 183 AA.
AC Q9CR23; Q3U459;
DT 10-MAY-2002, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2001, sequence version 1.
DT 03-AUG-2022, entry version 134.
DE RecName: Full=Proton-transporting V-type ATPase complex assembly regulator TMEM9 {ECO:0000305|PubMed:30374053};
DE Short=v-ATPase assembly regulator TMEM9 {ECO:0000305|PubMed:30374053};
DE AltName: Full=Transmembrane protein 9 {ECO:0000303|PubMed:30374053};
DE Short=Protein TMEM9 {ECO:0000303|PubMed:30374053};
DE Flags: Precursor;
GN Name=Tmem9 {ECO:0000312|MGI:MGI:1913491};
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 MRNA].
RC STRAIN=C57BL/6J, and NOD;
RC TISSUE=Brain, Cerebellum, and Embryonic stem cell;
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 [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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 IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [4]
RP TISSUE SPECIFICITY, AND DISRUPTION PHENOTYPE.
RX PubMed=30374053; DOI=10.1038/s41556-018-0219-8;
RA Jung Y.S., Jun S., Kim M.J., Lee S.H., Suh H.N., Lien E.M., Jung H.Y.,
RA Lee S., Zhang J., Yang J.I., Ji H., Wu J.Y., Wang W., Miller R.K., Chen J.,
RA McCrea P.D., Kopetz S., Park J.I.;
RT "TMEM9 promotes intestinal tumorigenesis through vacuolar-ATPase-activated
RT Wnt/beta-catenin signalling.";
RL Nat. Cell Biol. 20:1421-1433(2018).
RN [5]
RP FUNCTION, TISSUE SPECIFICITY, AND DISRUPTION PHENOTYPE.
RX PubMed=32380568; DOI=10.1002/hep.31305;
RA Jung Y.S., Stratton S.A., Lee S.H., Kim M.J., Jun S., Zhang J., Zheng B.,
RA Cervantes C.L., Cha J.H., Barton M.C., Park J.I.;
RT "TMEM9-v-ATPase Activates Wnt/beta-Catenin Signaling via APC Lysosomal
RT Degradation for Liver Regeneration and Tumorigenesis.";
RL Hepatology 73:776-794(2021).
CC -!- FUNCTION: Transmembrane protein that binds to and facilitates the
CC assembly of lysosomal proton-transporting V-type ATPase (v-ATPase),
CC resulting in enhanced lysosomal acidification and trafficking (By
CC similarity). By bringing the v-ATPase accessory protein ATP6AP2 and the
CC v-ATPase subunit ATP6V0D1 together, allows v-ATPase complex formation
CC and activation (By similarity). TMEM9-controlled vesicular
CC acidification induces hyperactivation of Wnt/beta-catenin signaling,
CC involved in development, tissue homeostasis and tissue regeneration,
CC through lysosomal degradation of adenomatous polyposis coli/APC
CC (PubMed:30374053, PubMed:32380568). In the liver, involved in hepatic
CC regeneration (PubMed:32380568). {ECO:0000250|UniProtKB:Q9P0T7,
CC ECO:0000269|PubMed:30374053, ECO:0000269|PubMed:32380568}.
CC -!- SUBUNIT: Interacts with the v-ATPase accessory protein ATP6AP2 and with
CC the v-ATPase complex subunit ATP6V0D1; these interactions lead to the
CC assembly of the v-ATPase complex. {ECO:0000250|UniProtKB:Q9P0T7}.
CC -!- SUBCELLULAR LOCATION: Lysosome membrane {ECO:0000250|UniProtKB:Q9P0T7};
CC Single-pass type I membrane protein {ECO:0000255}. Late endosome
CC membrane {ECO:0000250|UniProtKB:Q9P0T7}; Single-pass type I membrane
CC protein {ECO:0000255}. Endosome, multivesicular body membrane
CC {ECO:0000250|UniProtKB:Q9P0T7}; Single-pass type I membrane protein
CC {ECO:0000255}.
CC -!- TISSUE SPECIFICITY: Expressed in heart, lung, kidney, liver and
CC intestines (PubMed:30374053). Enriched in the hepatocytes around the
CC central vein (PubMed:32380568). {ECO:0000269|PubMed:30374053,
CC ECO:0000269|PubMed:32380568}.
CC -!- DOMAIN: The transmembrane domain (TMD) is essential for the interaction
CC with ATP6AP2. {ECO:0000250|UniProtKB:Q9P0T7}.
CC -!- PTM: N-glycosylated. {ECO:0000250|UniProtKB:Q9P0T7}.
CC -!- DISRUPTION PHENOTYPE: Knockout mice are viable and exhibit no
CC discernible phenotypes in the overall liver architecture and
CC hepatocytes (PubMed:30374053, PubMed:32380568). However, they display
CC impaired hepatic regeneration with reduced Wnt signaling
CC (PubMed:32380568). Knockout mice also show a suppression of intestinal
CC tumorigenesis (PubMed:30374053). {ECO:0000269|PubMed:30374053,
CC ECO:0000269|PubMed:32380568}.
CC -!- SIMILARITY: Belongs to the TMEM9 family. {ECO:0000305}.
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DR EMBL; AK005248; BAB23903.1; -; mRNA.
DR EMBL; AK021225; BAB32335.1; -; mRNA.
DR EMBL; AK134909; BAE22335.1; -; mRNA.
DR EMBL; AK154423; BAE32575.1; -; mRNA.
DR EMBL; BC016524; AAH16524.1; -; mRNA.
DR CCDS; CCDS15323.1; -.
DR RefSeq; NP_001153617.1; NM_001160145.1.
DR RefSeq; NP_001153618.1; NM_001160146.1.
DR RefSeq; NP_079715.1; NM_025439.3.
DR AlphaFoldDB; Q9CR23; -.
DR STRING; 10090.ENSMUSP00000065409; -.
DR GlyConnect; 2799; 1 N-Linked glycan (1 site).
DR GlyGen; Q9CR23; 3 sites, 1 N-linked glycan (1 site).
DR iPTMnet; Q9CR23; -.
DR PhosphoSitePlus; Q9CR23; -.
DR EPD; Q9CR23; -.
DR jPOST; Q9CR23; -.
DR MaxQB; Q9CR23; -.
DR PaxDb; Q9CR23; -.
DR PeptideAtlas; Q9CR23; -.
DR PRIDE; Q9CR23; -.
DR ProteomicsDB; 259576; -.
DR Antibodypedia; 34497; 62 antibodies from 19 providers.
DR Ensembl; ENSMUST00000063719; ENSMUSP00000065409; ENSMUSG00000026411.
DR Ensembl; ENSMUST00000117950; ENSMUSP00000113416; ENSMUSG00000026411.
DR Ensembl; ENSMUST00000165125; ENSMUSP00000128185; ENSMUSG00000026411.
DR GeneID; 66241; -.
DR KEGG; mmu:66241; -.
DR UCSC; uc007cue.2; mouse.
DR CTD; 252839; -.
DR MGI; MGI:1913491; Tmem9.
DR VEuPathDB; HostDB:ENSMUSG00000026411; -.
DR eggNOG; KOG4007; Eukaryota.
DR GeneTree; ENSGT00390000000819; -.
DR HOGENOM; CLU_093267_2_0_1; -.
DR InParanoid; Q9CR23; -.
DR OMA; YNRNFSQ; -.
DR OrthoDB; 1380345at2759; -.
DR PhylomeDB; Q9CR23; -.
DR TreeFam; TF315146; -.
DR BioGRID-ORCS; 66241; 2 hits in 73 CRISPR screens.
DR ChiTaRS; Tmem9; mouse.
DR PRO; PR:Q9CR23; -.
DR Proteomes; UP000000589; Chromosome 1.
DR RNAct; Q9CR23; protein.
DR Bgee; ENSMUSG00000026411; Expressed in retinal neural layer and 231 other tissues.
DR Genevisible; Q9CR23; MM.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0045171; C:intercellular bridge; ISO:MGI.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; ISO:MGI.
DR GO; GO:0005770; C:late endosome; ISS:UniProtKB.
DR GO; GO:0005765; C:lysosomal membrane; ISS:UniProtKB.
DR GO; GO:0005764; C:lysosome; ISS:UniProtKB.
DR GO; GO:0015630; C:microtubule cytoskeleton; ISO:MGI.
DR GO; GO:0072686; C:mitotic spindle; ISO:MGI.
DR GO; GO:0032585; C:multivesicular body membrane; ISS:UniProtKB.
DR GO; GO:0048388; P:endosomal lumen acidification; ISS:UniProtKB.
DR GO; GO:0007042; P:lysosomal lumen acidification; ISS:UniProtKB.
DR GO; GO:0090263; P:positive regulation of canonical Wnt signaling pathway; IMP:UniProtKB.
DR GO; GO:0015031; P:protein transport; IEA:UniProtKB-KW.
DR GO; GO:0070070; P:proton-transporting V-type ATPase complex assembly; ISS:UniProtKB.
DR GO; GO:0042176; P:regulation of protein catabolic process; IMP:UniProtKB.
DR InterPro; IPR008853; TMEM9/TMEM9B.
DR PANTHER; PTHR13064; PTHR13064; 1.
DR Pfam; PF05434; Tmemb_9; 1.
PE 1: Evidence at protein level;
KW Endosome; Glycoprotein; Lysosome; Membrane; Phosphoprotein;
KW Protein transport; Reference proteome; Signal; Transmembrane;
KW Transmembrane helix; Transport.
FT SIGNAL 1..20
FT /evidence="ECO:0000255"
FT CHAIN 21..183
FT /note="Proton-transporting V-type ATPase complex assembly
FT regulator TMEM9"
FT /id="PRO_0000034375"
FT TOPO_DOM 21..89
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 90..110
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 111..183
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT MOD_RES 144
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9P0T7"
FT CARBOHYD 21
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 38
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 47
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
SQ SEQUENCE 183 AA; 20633 MW; 2F906CC16C15D9A1 CRC64;
MKLLCLVAVV GCLLVPPAQA NKSSEDIRCK CICPPYRNIS GHIYNQNVSQ KDCNCLHVVE
PMPVPGHDVE AYCLLCECRY EERSTTTIKV IIVIYLSVVG ALLLYMAFLM LVDPLIRKPD
AYTEQLHNEE ENEDARTMAT AAASIGGPRA NTVLERVEGA QQRWKLQVQE QRKTVFDRHK
MLS
