CLTRN_MOUSE
ID CLTRN_MOUSE Reviewed; 222 AA.
AC Q9ESG4; Q3UFF6;
DT 11-JUL-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2001, sequence version 1.
DT 03-AUG-2022, entry version 131.
DE RecName: Full=Collectrin;
DE AltName: Full=Transmembrane protein 27;
DE Flags: Precursor;
GN Name=Cltrn {ECO:0000312|MGI:MGI:1926234};
GN Synonyms=Nx17, Tmem27 {ECO:0000303|PubMed:16330324};
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].
RC STRAIN=ICR;
RX PubMed=10432394; DOI=10.1046/j.1523-1755.1999.00561.x;
RA Zhang H., Wada J., Kanwar Y.S., Tsuchiyama Y., Hiragushi K., Hida K.,
RA Shikata K., Makino H.;
RT "Screening for genes up-regulated in 5/6 nephrectomized mouse kidney.";
RL Kidney Int. 56:549-558(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
RC STRAIN=ICR;
RX PubMed=11278314; DOI=10.1074/jbc.m006723200;
RA Zhang H., Wada J., Hida K., Tsuchiyama Y., Hiragushi K., Shikata K.,
RA Wang H., Lin S., Kanwar Y.S., Makino H.;
RT "Collectrin, a collecting duct-specific transmembrane glycoprotein, is a
RT novel homolog of ACE2 and is developmentally regulated in embryonic
RT kidneys.";
RL J. Biol. Chem. 276:17132-17139(2001).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Kidney, and Pancreas;
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N; TISSUE=Kidney;
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 [5]
RP FUNCTION, TISSUE SPECIFICITY, GLYCOPROTEIN, AND INTERACTION WITH SNAPIN.
RX PubMed=16330323; DOI=10.1016/j.cmet.2005.11.003;
RA Fukui K., Yang Q., Cao Y., Takahashi N., Hatakeyama H., Wang H., Wada J.,
RA Zhang Y., Marselli L., Nammo T., Yoneda K., Onishi M., Higashiyama S.,
RA Matsuzawa Y., Gonzalez F.J., Weir G.C., Kasai H., Shimomura I.,
RA Miyagawa J., Wollheim C.B., Yamagata K.;
RT "The HNF-1 target collectrin controls insulin exocytosis by SNARE complex
RT formation.";
RL Cell Metab. 2:373-384(2005).
RN [6]
RP FUNCTION, TISSUE SPECIFICITY, GLYCOPROTEIN, SUBUNIT, PROTEOLYTIC PROCESSING
RP IN BETA CELLS, AND SUBCELLULAR LOCATION.
RX PubMed=16330324; DOI=10.1016/j.cmet.2005.11.001;
RA Akpinar P., Kuwajima S., Kruetzfeldt J., Stoffel M.;
RT "Tmem27: a cleaved and shed plasma membrane protein that stimulates
RT pancreatic beta cell proliferation.";
RL Cell Metab. 2:385-397(2005).
RN [7]
RP DISRUPTION PHENOTYPE, SUBCELLULAR LOCATION, INTERACTION WITH SLC6A18;
RP SLC6A19 AND SLC6A20B, FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=17167413; DOI=10.1038/nature05475;
RA Danilczyk U., Sarao R., Remy C., Benabbas C., Stange G., Richter A.,
RA Arya S., Pospisilik J.A., Singer D., Camargo S.M., Makrides V., Ramadan T.,
RA Verrey F., Wagner C.A., Penninger J.M.;
RT "Essential role for collectrin in renal amino acid transport.";
RL Nature 444:1088-1091(2006).
RN [8]
RP FUNCTION, TISSUE SPECIFICITY, AND DISRUPTION PHENOTYPE.
RX PubMed=16985211; DOI=10.1152/ajprenal.00325.2006;
RA Malakauskas S.M., Quan H., Fields T.A., McCall S.J., Yu M.J., Kourany W.M.,
RA Frey C.W., Le T.H.;
RT "Aminoaciduria and altered renal expression of luminal amino acid
RT transporters in mice lacking novel gene collectrin.";
RL Am. J. Physiol. 292:F533-F544(2007).
RN [9]
RP INDUCTION.
RX PubMed=19715677; DOI=10.1016/j.bbrc.2009.08.111;
RA Saisho K., Fukuhara A., Yasuda T., Sato Y., Fukui K., Iwahashi H.,
RA Imagawa A., Hatta M., Shimomura I., Yamagata K.;
RT "Glucose enhances collectrin protein expression in insulin-producing MIN6
RT beta cells.";
RL Biochem. Biophys. Res. Commun. 389:133-137(2009).
RN [10]
RP INTERACTION WITH SLC6A18.
RX PubMed=19478081; DOI=10.1074/jbc.m109.011171;
RA Singer D., Camargo S.M., Huggel K., Romeo E., Danilczyk U., Kuba K.,
RA Chesnov S., Caron M.G., Penninger J.M., Verrey F.;
RT "Orphan transporter SLC6A18 is renal neutral amino acid transporter
RT B0AT3.";
RL J. Biol. Chem. 284:19953-19960(2009).
RN [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-214 AND THR-220, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Kidney;
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 [12]
RP SUBCELLULAR LOCATION, AND PROTEOLYTIC PROCESSING.
RX PubMed=21907142; DOI=10.1016/j.cmet.2011.06.018;
RA Esterhazy D., Stuetzer I., Wang H., Rechsteiner M.P., Beauchamp J.,
RA Doebeli H., Hilpert H., Matile H., Prummer M., Schmidt A., Lieske N.,
RA Boehm B., Marselli L., Bosco D., Kerr-Conte J., Aebersold R., Spinas G.A.,
RA Moch H., Migliorini C., Stoffel M.;
RT "Bace2 is a beta cell-enriched protease that regulates pancreatic beta cell
RT function and mass.";
RL Cell Metab. 14:365-377(2011).
CC -!- FUNCTION: Plays an important role in amino acid transport by acting as
CC binding partner of amino acid transporters SLC6A18 and SLC6A19,
CC regulating their trafficking on the cell surface and their activity
CC (PubMed:17167413, PubMed:16985211). May also play a role in trafficking
CC of amino acid transporters SLC3A1 and SLC7A9 to the renal cortical cell
CC membrane (PubMed:16985211). Regulator of SNARE complex function
CC (PubMed:16330323). Stimulator of beta cell replication
CC (PubMed:16330324). {ECO:0000269|PubMed:16330323,
CC ECO:0000269|PubMed:16330324, ECO:0000269|PubMed:16985211,
CC ECO:0000269|PubMed:17167413}.
CC -!- SUBUNIT: Monomer (PubMed:16330324). Homodimer (PubMed:16330324).
CC Homodimer; dimerization prevents CLTRN cleavage by BACE2
CC (PubMed:16330324). Interacts with SNAPIN (PubMed:16330323). Interacts
CC with SLC6A18; this interaction regulates the trafficking of SLC6A18 to
CC the cell membrane and its amino acid transporter activity
CC (PubMed:17167413, PubMed:19478081). Interacts with SLC6A19; this
CC interaction regulates the trafficking of SLC6A19 to the cell membrane
CC and its amino acid transporter activity (PubMed:17167413). Interacts
CC with SLC6A20B (PubMed:17167413). {ECO:0000269|PubMed:16330323,
CC ECO:0000269|PubMed:16330324, ECO:0000269|PubMed:17167413,
CC ECO:0000269|PubMed:19478081}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:16330324,
CC ECO:0000269|PubMed:17167413}; Single-pass type I membrane protein
CC {ECO:0000255}. Note=Localizes to the brush border membranes of cells in
CC the proximal tubules of kidney (PubMed:17167413). Colocalizes with
CC SLC6A19 in the early proximal S1 tubule (PubMed:17167413).
CC {ECO:0000269|PubMed:17167413}.
CC -!- TISSUE SPECIFICITY: Expressed on the apical surface of the proximal
CC tubules in the renal cortex (at protein level) (PubMed:16985211).
CC Kidney; collecting ducts and proximal tubule (PubMed:11278314,
CC PubMed:17167413, PubMed:16985211). Pancreas; beta cells of islets
CC (PubMed:16330323, PubMed:16330324). {ECO:0000269|PubMed:11278314,
CC ECO:0000269|PubMed:16330323, ECO:0000269|PubMed:16330324,
CC ECO:0000269|PubMed:16985211, ECO:0000269|PubMed:17167413}.
CC -!- INDUCTION: Up-regulated by high glucose concentration in beta-cells (at
CC protein level). {ECO:0000269|PubMed:19715677}.
CC -!- DOMAIN: The cleavage site containing the double Phe-Phe motif acts as
CC negative regulator of shedding by BACE2.
CC {ECO:0000250|UniProtKB:Q9HBJ8}.
CC -!- PTM: Glycosylated. Glycosylation is required for plasma membrane
CC localization and for its cleavage by BACE2.
CC {ECO:0000250|UniProtKB:Q9HBJ8}.
CC -!- PTM: Proteolytically processed in pancreatic beta cells by BACE2
CC leading to the generation and extracellular release of soluble CLTRN,
CC and a corresponding cell-associated C-terminal fragment which is later
CC cleaved by gamma-secretase (PubMed:16330324, PubMed:21907142). This
CC shedding process inactivates CLTRN (PubMed:16330324). Three cleavage
CC sites have been identified for BACE2, two clustered sites after Phe-116
CC and Leu-118 and a more membrane proximal site at Phe-125; the preferred
CC BACE2 cleavage site seems to be between Phe-125 and Leu-126, Phe-116
CC and Leu-118 act as alternative sites (By similarity).
CC {ECO:0000250|UniProtKB:Q9HBJ8, ECO:0000269|PubMed:16330324,
CC ECO:0000269|PubMed:21907142}.
CC -!- DISRUPTION PHENOTYPE: Deficient mice are viable and fertile but exhibit
CC a severe defect in renal amino acid uptake due to down-regulation of
CC apical amino acid transporters in the kidney (PubMed:17167413). Greater
CC urine output, more dilute urine, a defect in urinary concentration,
CC higher osmolar clearance and an increase in free water absorption,
CC suggesting an osmotic diuresis (PubMed:16985211). Decreased urine
CC osmolytes sodium and urea, presence of tyrosine and glutamine crystals
CC in the urine, and increased excretion of amino acids in the urine,
CC suggesting an aminoaciduria (PubMed:16985211). Decreased population of
CC amino acid transporters SLC6A19, SLC3A1 and SLC7A9 in the renal
CC cortical cell membrane (PubMed:16985211). Increased intracellular
CC SLC1A1 levels (PubMed:16985211). {ECO:0000269|PubMed:16985211,
CC ECO:0000269|PubMed:17167413}.
CC -!- SIMILARITY: Belongs to the CLTRN 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; AF178085; AAG09306.1; -; mRNA.
DR EMBL; AK002337; BAB22022.1; -; mRNA.
DR EMBL; AK148534; BAE28605.1; -; mRNA.
DR EMBL; BC049912; AAH49912.1; -; mRNA.
DR CCDS; CCDS30517.1; -.
DR RefSeq; NP_001300648.1; NM_001313719.1.
DR RefSeq; NP_065651.1; NM_020626.2.
DR AlphaFoldDB; Q9ESG4; -.
DR SMR; Q9ESG4; -.
DR DIP; DIP-60420N; -.
DR IntAct; Q9ESG4; 3.
DR STRING; 10090.ENSMUSP00000107899; -.
DR GlyGen; Q9ESG4; 2 sites.
DR iPTMnet; Q9ESG4; -.
DR PhosphoSitePlus; Q9ESG4; -.
DR jPOST; Q9ESG4; -.
DR MaxQB; Q9ESG4; -.
DR PaxDb; Q9ESG4; -.
DR PeptideAtlas; Q9ESG4; -.
DR PRIDE; Q9ESG4; -.
DR ProteomicsDB; 259032; -.
DR ABCD; Q9ESG4; 5 sequenced antibodies.
DR DNASU; 57394; -.
DR Ensembl; ENSMUST00000015545; ENSMUSP00000015545; ENSMUSG00000015401.
DR Ensembl; ENSMUST00000112280; ENSMUSP00000107899; ENSMUSG00000015401.
DR GeneID; 57394; -.
DR KEGG; mmu:57394; -.
DR UCSC; uc009uve.1; mouse.
DR CTD; 57393; -.
DR MGI; MGI:1926234; Cltrn.
DR VEuPathDB; HostDB:ENSMUSG00000015401; -.
DR eggNOG; ENOG502RWVW; Eukaryota.
DR GeneTree; ENSGT00940000160862; -.
DR HOGENOM; CLU_108544_0_0_1; -.
DR InParanoid; Q9ESG4; -.
DR OMA; CKPDAQN; -.
DR OrthoDB; 1212584at2759; -.
DR PhylomeDB; Q9ESG4; -.
DR TreeFam; TF335519; -.
DR BioGRID-ORCS; 57394; 1 hit in 74 CRISPR screens.
DR ChiTaRS; Cltrn; mouse.
DR PRO; PR:Q9ESG4; -.
DR Proteomes; UP000000589; Chromosome X.
DR RNAct; Q9ESG4; protein.
DR Bgee; ENSMUSG00000015401; Expressed in right kidney and 102 other tissues.
DR ExpressionAtlas; Q9ESG4; baseline and differential.
DR Genevisible; Q9ESG4; MM.
DR GO; GO:0031526; C:brush border membrane; IDA:MGI.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0042803; F:protein homodimerization activity; IDA:UniProtKB.
DR GO; GO:0017156; P:calcium-ion regulated exocytosis; ISO:MGI.
DR GO; GO:0035773; P:insulin secretion involved in cellular response to glucose stimulus; ISO:MGI.
DR GO; GO:0051957; P:positive regulation of amino acid transport; IDA:MGI.
DR GO; GO:1905737; P:positive regulation of L-proline import across plasma membrane; ISO:MGI.
DR GO; GO:0022898; P:regulation of transmembrane transporter activity; ISO:MGI.
DR GO; GO:0035493; P:SNARE complex assembly; ISO:MGI.
DR InterPro; IPR042944; Collectrin.
DR InterPro; IPR031588; Collectrin_dom.
DR PANTHER; PTHR46884; PTHR46884; 1.
DR Pfam; PF16959; Collectrin; 1.
PE 1: Evidence at protein level;
KW Cell membrane; Glycoprotein; Membrane; Phosphoprotein; Reference proteome;
KW Signal; Transmembrane; Transmembrane helix.
FT SIGNAL 1..14
FT /evidence="ECO:0000255"
FT CHAIN 15..222
FT /note="Collectrin"
FT /id="PRO_0000245868"
FT TOPO_DOM 15..141
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:Q9HBJ8"
FT TRANSMEM 142..162
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 163..222
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:Q9HBJ8"
FT SITE 125..126
FT /note="Cleavage by BACE2"
FT /evidence="ECO:0000250|UniProtKB:Q9HBJ8"
FT MOD_RES 214
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 220
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT CARBOHYD 76
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 93
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CONFLICT 206
FT /note="G -> R (in Ref. 3; BAE28605)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 222 AA; 25070 MW; C07E732CE92935A9 CRC64;
MLWALFFLVT TIHAELCHPD AENAFKVRLS IRAALGDKAY VWDTDQEYLF RAMVAFSMRK
VPNREATEIS HVLLCNITQR VSFWFVVTDP SNNYTLPAAE VQSAIRKNRN RINSAFFLDD
HTLEFLKIPS TLAPPMEPSV PVWIIVFGVI FCIVTVAIAL LVLSGIRQRR RNNKGPPGVE
DAEDKCENII TIENGIPCDP LDMKGGHIND GFLTEDERLT PL
