CLTRN_RAT
ID CLTRN_RAT Reviewed; 222 AA.
AC Q9ESG3; Q6AYY2;
DT 11-JUL-2006, integrated into UniProtKB/Swiss-Prot.
DT 11-JUL-2006, sequence version 2.
DT 03-AUG-2022, entry version 103.
DE RecName: Full=Collectrin;
DE AltName: Full=Transmembrane protein 27;
DE Flags: Precursor;
GN Name=Cltrn {ECO:0000312|RGD:708489}; Synonyms=Nx17, Tmem27;
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], AND TISSUE SPECIFICITY.
RC STRAIN=Sprague-Dawley;
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 [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC 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 [3]
RP FUNCTION, TISSUE SPECIFICITY, 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).
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 (By
CC similarity). May also play a role in trafficking of amino acid
CC transporters SLC3A1 and SLC7A9 to the renal cortical cell membrane (By
CC similarity). Regulator of SNARE complex function (PubMed:16330323).
CC Stimulator of beta cell replication (By similarity).
CC {ECO:0000250|UniProtKB:Q9ESG4, ECO:0000269|PubMed:16330323}.
CC -!- SUBUNIT: Monomer. Homodimer; dimerization prevents CLTRN cleavage by
CC BACE2 (By similarity). Interacts with SLC6A18; this interaction
CC regulates the trafficking of SLC6A18 to the cell membrane and its amino
CC acid transporter activity. Interacts with SLC6A19; this interaction
CC regulates the trafficking of SLC6A19 to the cell membrane and its amino
CC acid transporter activity (By similarity). Interacts with SNAPIN
CC (PubMed:16330323). {ECO:0000250|UniProtKB:Q9ESG4,
CC ECO:0000250|UniProtKB:Q9HBJ8, ECO:0000269|PubMed:16330323}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:Q9ESG4};
CC Single-pass type I membrane protein {ECO:0000255}. Note=Localizes to
CC the brush border membranes of cells in the proximal tubules of kidney.
CC Colocalized with SLC6A19 in the early proximal S1 tubule.
CC {ECO:0000250|UniProtKB:Q9ESG4}.
CC -!- TISSUE SPECIFICITY: Kidney; collecting ducts. Pancreas; beta cells of
CC islets. {ECO:0000269|PubMed:11278314, ECO:0000269|PubMed:16330323}.
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. This shedding process inactivates CLTRN (By
CC similarity). Three cleavage sites have been identified for BACE2, two
CC clustered sites after Phe-116 and Leu-118 and a more membrane proximal
CC site at Phe-125; the preferred BACE2 cleavage site seems to be between
CC Phe-125 and Leu-126, Phe-116 and Leu-118 act as alternative sites (By
CC similarity). {ECO:0000250|UniProtKB:Q9ESG4,
CC ECO:0000250|UniProtKB:Q9HBJ8}.
CC -!- SIMILARITY: Belongs to the CLTRN family. {ECO:0000305}.
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DR EMBL; AF178086; AAG09307.1; -; mRNA.
DR EMBL; BC078838; AAH78838.1; -; mRNA.
DR RefSeq; NP_066125.1; NM_020976.1.
DR AlphaFoldDB; Q9ESG3; -.
DR SMR; Q9ESG3; -.
DR STRING; 10116.ENSRNOP00000005348; -.
DR GlyGen; Q9ESG3; 2 sites.
DR iPTMnet; Q9ESG3; -.
DR PhosphoSitePlus; Q9ESG3; -.
DR PaxDb; Q9ESG3; -.
DR PRIDE; Q9ESG3; -.
DR GeneID; 57395; -.
DR KEGG; rno:57395; -.
DR UCSC; RGD:708489; rat.
DR CTD; 57393; -.
DR RGD; 708489; Cltrn.
DR VEuPathDB; HostDB:ENSRNOG00000003960; -.
DR eggNOG; ENOG502RWVW; Eukaryota.
DR HOGENOM; CLU_108544_0_0_1; -.
DR InParanoid; Q9ESG3; -.
DR OMA; CKPDAQN; -.
DR OrthoDB; 1212584at2759; -.
DR PhylomeDB; Q9ESG3; -.
DR TreeFam; TF335519; -.
DR PRO; PR:Q9ESG3; -.
DR Proteomes; UP000002494; Chromosome X.
DR Bgee; ENSRNOG00000003960; Expressed in kidney and 16 other tissues.
DR Genevisible; Q9ESG3; RN.
DR GO; GO:0031526; C:brush border membrane; ISO:RGD.
DR GO; GO:0005737; C:cytoplasm; ISO:RGD.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0016020; C:membrane; TAS:RGD.
DR GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
DR GO; GO:0042803; F:protein homodimerization activity; ISO:RGD.
DR GO; GO:0017156; P:calcium-ion regulated exocytosis; ISO:RGD.
DR GO; GO:0035773; P:insulin secretion involved in cellular response to glucose stimulus; ISO:RGD.
DR GO; GO:0051957; P:positive regulation of amino acid transport; ISO:RGD.
DR GO; GO:1905737; P:positive regulation of L-proline import across plasma membrane; ISO:RGD.
DR GO; GO:0022898; P:regulation of transmembrane transporter activity; ISO:RGD.
DR GO; GO:0035493; P:SNARE complex assembly; ISO:RGD.
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_0000245869"
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:0000250|UniProtKB:Q9ESG4"
FT MOD_RES 220
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q9ESG4"
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 96
FT /note="L -> F (in Ref. 1; AAG09307)"
FT /evidence="ECO:0000305"
FT CONFLICT 99
FT /note="A -> V (in Ref. 1; AAG09307)"
FT /evidence="ECO:0000305"
FT CONFLICT 110
FT /note="N -> K (in Ref. 1; AAG09307)"
FT /evidence="ECO:0000305"
FT CONFLICT 205
FT /note="G -> R (in Ref. 1; AAG09307)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 222 AA; 25051 MW; 82716CBF4B6897D8 CRC64;
MLWALFFLVT TIHAELCRPD AENAFKVRLS IKAALGDKAY VWDTDEEYLF RAMVAFSMRK
VPNREGTEIS HVLLCNVTQR VSFWFVVTDP LKNHTLPAAE VQSAIRMNRN RINSAFFLDD
HTLEFLKIPS TLAPPMDPSV PVWIIVFGVI FCIVTVAIAL LVLSGIRQRR RNKKGPPGVE
DAEDKCENII TIENGIPCDP LDMKGGHIND GFLTEDERLT PL
