ID CALX_CANLF Reviewed; 593 AA. AC P24643; P79140; DT 01-MAR-1992, integrated into UniProtKB/Swiss-Prot. DT 15-JUL-1998, sequence version 3. DT 27-MAR-2024, entry version 173. DE RecName: Full=Calnexin; DE AltName: Full=pp90; DE Flags: Precursor; GN Name=CANX; OS Canis lupus familiaris (Dog) (Canis familiaris). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Laurasiatheria; Carnivora; Caniformia; Canidae; Canis. OX NCBI_TaxID=9615; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA], AND PARTIAL PROTEIN SEQUENCE. RX PubMed=1918067; DOI=10.1016/s0021-9258(18)55036-5; RA Wada I., Rindress D., Cameron P.H., Ou W.-J., Doherty J.J. II, Louvard D., RA Bell A.W., Dignard D., Thomas D.Y., Bergeron J.J.M.; RT "SSR alpha and associated calnexin are major calcium binding proteins of RT the endoplasmic reticulum membrane."; RL J. Biol. Chem. 266:19599-19610(1991). RN [2] RP SEQUENCE REVISION TO 67. RA Dignard D.; RL Submitted (FEB-1997) to the EMBL/GenBank/DDBJ databases. RN [3] RP INTERACTION WITH PPIB, AND MUTAGENESIS OF ASP-348. RX PubMed=20801878; DOI=10.1074/jbc.m110.160101; RA Kozlov G., Bastos-Aristizabal S., Maattanen P., Rosenauer A., Zheng F., RA Killikelly A., Trempe J.F., Thomas D.Y., Gehring K.; RT "Structural basis of cyclophilin B binding by the calnexin/calreticulin P- RT domain."; RL J. Biol. Chem. 285:35551-35557(2010). RN [4] RP X-RAY CRYSTALLOGRAPHY (2.9 ANGSTROMS) OF 45-468 IN COMPLEX WITH CALCIUM, RP DISULFIDE BONDS, AND PROBABLE CARBOHYDRATE-INTERACTING SITES. RX PubMed=11583625; DOI=10.1016/s1097-2765(01)00318-5; RA Schrag J.D., Bergeron J.J., Li Y., Borisova S., Hahn M., Thomas D.Y., RA Cygler M.; RT "The Structure of calnexin, an ER chaperone involved in quality control of RT protein folding."; RL Mol. Cell 8:633-644(2001). RN [5] RP PALMITOYLATION AT CYS-503 AND CYS-504, SUBCELLULAR LOCATION, AND RP MUTAGENESIS OF 503-CYS--CYS-504. RX PubMed=22045338; DOI=10.1038/emboj.2011.384; RA Lynes E.M., Bui M., Yap M.C., Benson M.D., Schneider B., Ellgaard L., RA Berthiaume L.G., Simmen T.; RT "Palmitoylated TMX and calnexin target to the mitochondria-associated RT membrane."; RL EMBO J. 31:457-470(2012). CC -!- FUNCTION: Calcium-binding protein that interacts with newly synthesized CC monoglucosylated glycoproteins in the endoplasmic reticulum. It may act CC in assisting protein assembly and/or in the retention within the ER of CC unassembled protein subunits. It seems to play a major role in the CC quality control apparatus of the ER by the retention of incorrectly CC folded proteins. Associated with partial T-cell antigen receptor CC complexes that escape the ER of immature thymocytes, it may function as CC a signaling complex regulating thymocyte maturation. Additionally it CC may play a role in receptor-mediated endocytosis at the synapse (By CC similarity). {ECO:0000250}. CC -!- SUBUNIT: Interacts with MAPK3/ERK1 (By similarity). Interacts with CC KCNH2 (By similarity). Associates with ribosomes (By similarity). CC Interacts with SGIP1; involved in negative regulation of endocytosis CC (By similarity). The palmitoylated form interacts with the ribosome- CC translocon complex component SSR1, promoting efficient folding of CC glycoproteins (By similarity). Interacts with SERPINA2P/SERPINA2 and CC with the S and Z variants of SERPINA1 (By similarity). Interacts with CC PPIB (PubMed:20801878). Interacts with ZNRF4 (By similarity). Interacts CC with SMIM22 (By similarity). Interacts with TMX2 (By similarity). CC Interacts with TMEM35A/NACHO and CHRNA7 (By similarity). Interacts with CC reticulophagy regulators RETREG2 and RETREG3 (By similarity). Interacts CC with DNM1L; may form part of a larger protein complex at the ER- CC mitochondrial interface during mitochondrial fission (By similarity). CC Interacts with ADAM7 (By similarity). {ECO:0000250|UniProtKB:P27824, CC ECO:0000250|UniProtKB:P35564, ECO:0000250|UniProtKB:P35565, CC ECO:0000269|PubMed:20801878}. CC -!- INTERACTION: CC P24643; P30101: PDIA3; Xeno; NbExp=3; IntAct=EBI-15596385, EBI-979862; CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane CC {ECO:0000269|PubMed:22045338}; Single-pass type I membrane protein CC {ECO:0000255}. Mitochondrion membrane {ECO:0000269|PubMed:22045338}; CC Single-pass type I membrane protein {ECO:0000255}. Melanosome membrane CC {ECO:0000250|UniProtKB:P27824}; Single-pass type I membrane protein CC {ECO:0000255}. Note=The palmitoylated form preferentially localizes to CC the perinuclear rough ER (By similarity). Localizes to endoplasmic CC reticulum mitochondria-associated membrane (MAMs) that connect the CC endoplasmic reticulum and the mitochondria (PubMed:22045338). CC {ECO:0000250|UniProtKB:P27824, ECO:0000269|PubMed:22045338}. CC -!- PTM: Phosphorylated at Ser-565 by MAPK3/ERK1. Phosphorylation by CC MAPK3/ERK1 increases its association with ribosomes (By similarity). CC {ECO:0000250}. CC -!- PTM: Palmitoylation by DHHC6 leads to the preferential localization to CC the perinuclear rough ER. It mediates the association of calnexin with CC the ribosome-translocon complex (RTC) which is required for efficient CC folding of glycosylated proteins (By similarity). {ECO:0000250}. CC -!- PTM: Ubiquitinated, leading to proteasomal degradation. Probably CC ubiquitinated by ZNRF4. {ECO:0000250|UniProtKB:P27824}. CC -!- SIMILARITY: Belongs to the calreticulin 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; X53616; CAA37678.1; -; mRNA. DR PIR; A37273; A37273. DR RefSeq; NP_001003232.1; NM_001003232.1. DR PDB; 1JHN; X-ray; 2.90 A; A=45-468. DR PDBsum; 1JHN; -. DR AlphaFoldDB; P24643; -. DR SMR; P24643; -. DR BioGRID; 139826; 2. DR DIP; DIP-29133N; -. DR IntAct; P24643; 1. DR STRING; 9615.ENSCAFP00000000498; -. DR UniLectin; P24643; -. DR iPTMnet; P24643; -. DR SwissPalm; P24643; -. DR PaxDb; 9612-ENSCAFP00000042695; -. DR GeneID; 403908; -. DR KEGG; cfa:403908; -. DR CTD; 821; -. DR eggNOG; KOG0675; Eukaryota. DR InParanoid; P24643; -. DR OrthoDB; 5489154at2759; -. DR EvolutionaryTrace; P24643; -. DR Proteomes; UP000002254; Unplaced. DR Proteomes; UP000694429; Unplaced. DR Proteomes; UP000694542; Unplaced. DR Proteomes; UP000805418; Unplaced. DR GO; GO:0005783; C:endoplasmic reticulum; ISS:UniProtKB. DR GO; GO:0005789; C:endoplasmic reticulum membrane; ISS:AgBase. DR GO; GO:0033162; C:melanosome membrane; IEA:UniProtKB-SubCell. DR GO; GO:0031966; C:mitochondrial membrane; IEA:UniProtKB-SubCell. DR GO; GO:0098793; C:presynapse; IEA:GOC. DR GO; GO:0005509; F:calcium ion binding; IBA:GO_Central. DR GO; GO:0030246; F:carbohydrate binding; IEA:UniProtKB-KW. DR GO; GO:0051082; F:unfolded protein binding; IEA:InterPro. DR GO; GO:0072583; P:clathrin-dependent endocytosis; ISS:UniProtKB. DR GO; GO:0006457; P:protein folding; IBA:GO_Central. DR GO; GO:0048488; P:synaptic vesicle endocytosis; ISS:UniProtKB. DR GO; GO:0030433; P:ubiquitin-dependent ERAD pathway; IBA:GO_Central. DR Gene3D; 2.60.120.200; -; 1. DR Gene3D; 2.10.250.10; Calreticulin/calnexin, P domain; 1. DR InterPro; IPR001580; Calret/calnex. DR InterPro; IPR018124; Calret/calnex_CS. DR InterPro; IPR009033; Calreticulin/calnexin_P_dom_sf. DR InterPro; IPR013320; ConA-like_dom_sf. DR PANTHER; PTHR11073:SF11; CALNEXIN; 1. DR PANTHER; PTHR11073; CALRETICULIN AND CALNEXIN; 1. DR Pfam; PF00262; Calreticulin; 1. DR PRINTS; PR00626; CALRETICULIN. DR SUPFAM; SSF49899; Concanavalin A-like lectins/glucanases; 2. DR SUPFAM; SSF63887; P-domain of calnexin/calreticulin; 1. DR PROSITE; PS00803; CALRETICULIN_1; 1. DR PROSITE; PS00804; CALRETICULIN_2; 1. DR PROSITE; PS00805; CALRETICULIN_REPEAT; 3. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Calcium; Chaperone; Direct protein sequencing; KW Disulfide bond; Endoplasmic reticulum; Lectin; Lipoprotein; Membrane; KW Metal-binding; Mitochondrion; Palmitate; Phosphoprotein; KW Reference proteome; Repeat; Signal; Transmembrane; Transmembrane helix; KW Ubl conjugation. FT SIGNAL 1..20 FT CHAIN 21..593 FT /note="Calnexin" FT /id="PRO_0000004197" FT TOPO_DOM 21..482 FT /note="Lumenal" FT /evidence="ECO:0000255" FT TRANSMEM 483..503 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 504..593 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT REPEAT 279..290 FT /note="1-1" FT REPEAT 296..307 FT /note="1-2" FT REPEAT 315..326 FT /note="1-3" FT REPEAT 334..345 FT /note="1-4" FT REPEAT 349..359 FT /note="2-1" FT REPEAT 368..378 FT /note="2-2" FT REPEAT 382..392 FT /note="2-3" FT REPEAT 396..406 FT /note="2-4" FT REGION 261..346 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 277..410 FT /note="P domain (Extended arm)" FT REGION 279..345 FT /note="4 X approximate repeats" FT REGION 327..360 FT /note="Interaction with PPIB" FT /evidence="ECO:0000269|PubMed:20801878" FT REGION 349..406 FT /note="4 X approximate repeats" FT REGION 504..593 FT /note="Sufficient to mediate interaction with SGIP1" FT /evidence="ECO:0000250" FT REGION 511..593 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 275..327 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 328..346 FT /note="Acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 526..547 FT /note="Acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 548..586 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT BINDING 75 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /evidence="ECO:0000269|PubMed:11583625" FT BINDING 118 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /evidence="ECO:0000269|PubMed:11583625" FT BINDING 165 FT /ligand="an alpha-D-glucoside" FT /ligand_id="ChEBI:CHEBI:22390" FT /evidence="ECO:0000305|PubMed:11583625" FT BINDING 167 FT /ligand="an alpha-D-glucoside" FT /ligand_id="ChEBI:CHEBI:22390" FT /evidence="ECO:0000305|PubMed:11583625" FT BINDING 186 FT /ligand="an alpha-D-glucoside" FT /ligand_id="ChEBI:CHEBI:22390" FT /evidence="ECO:0000305|PubMed:11583625" FT BINDING 193 FT /ligand="an alpha-D-glucoside" FT /ligand_id="ChEBI:CHEBI:22390" FT /evidence="ECO:0000250|UniProtKB:P14211" FT BINDING 426 FT /ligand="an alpha-D-glucoside" FT /ligand_id="ChEBI:CHEBI:22390" FT /evidence="ECO:0000305|PubMed:11583625" FT BINDING 437 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /evidence="ECO:0000269|PubMed:11583625" FT MOD_RES 138 FT /note="N6-acetyllysine" FT /evidence="ECO:0000250|UniProtKB:P27824" FT MOD_RES 555 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P27824" FT MOD_RES 563 FT /note="Phosphothreonine" FT /evidence="ECO:0000250|UniProtKB:P27824" FT MOD_RES 565 FT /note="Phosphoserine; by MAPK3" FT /evidence="ECO:0000250|UniProtKB:P27824" FT MOD_RES 584 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P27824" FT LIPID 503 FT /note="S-palmitoyl cysteine" FT /evidence="ECO:0000305|PubMed:22045338" FT LIPID 504 FT /note="S-palmitoyl cysteine" FT /evidence="ECO:0000305|PubMed:22045338" FT DISULFID 161..195 FT /evidence="ECO:0000269|PubMed:11583625" FT DISULFID 361..367 FT /evidence="ECO:0000269|PubMed:11583625" FT MUTAGEN 348 FT /note="D->K: Abolishes interaction with PPIB." FT /evidence="ECO:0000269|PubMed:20801878" FT MUTAGEN 503..504 FT /note="CC->AA: Abolished palmitoylation, leading to FT decreased localization to mitochondria-associated FT endoplasmic reticulum membrane (MAM)." FT /evidence="ECO:0000269|PubMed:22045338" FT STRAND 71..74 FT /evidence="ECO:0007829|PDB:1JHN" FT STRAND 78..80 FT /evidence="ECO:0007829|PDB:1JHN" FT STRAND 104..106 FT /evidence="ECO:0007829|PDB:1JHN" FT STRAND 122..124 FT /evidence="ECO:0007829|PDB:1JHN" FT STRAND 131..140 FT /evidence="ECO:0007829|PDB:1JHN" FT STRAND 142..145 FT /evidence="ECO:0007829|PDB:1JHN" FT STRAND 147..153 FT /evidence="ECO:0007829|PDB:1JHN" FT STRAND 160..163 FT /evidence="ECO:0007829|PDB:1JHN" FT STRAND 166..170 FT /evidence="ECO:0007829|PDB:1JHN" FT HELIX 177..179 FT /evidence="ECO:0007829|PDB:1JHN" FT STRAND 186..197 FT /evidence="ECO:0007829|PDB:1JHN" FT STRAND 200..208 FT /evidence="ECO:0007829|PDB:1JHN" FT TURN 210..212 FT /evidence="ECO:0007829|PDB:1JHN" FT STRAND 215..218 FT /evidence="ECO:0007829|PDB:1JHN" FT HELIX 229..232 FT /evidence="ECO:0007829|PDB:1JHN" FT STRAND 237..244 FT /evidence="ECO:0007829|PDB:1JHN" FT TURN 245..247 FT /evidence="ECO:0007829|PDB:1JHN" FT STRAND 248..253 FT /evidence="ECO:0007829|PDB:1JHN" FT STRAND 256..261 FT /evidence="ECO:0007829|PDB:1JHN" FT STRAND 292..295 FT /evidence="ECO:0007829|PDB:1JHN" FT STRAND 311..314 FT /evidence="ECO:0007829|PDB:1JHN" FT STRAND 325..328 FT /evidence="ECO:0007829|PDB:1JHN" FT TURN 345..347 FT /evidence="ECO:0007829|PDB:1JHN" FT HELIX 359..361 FT /evidence="ECO:0007829|PDB:1JHN" FT STRAND 367..369 FT /evidence="ECO:0007829|PDB:1JHN" FT STRAND 374..376 FT /evidence="ECO:0007829|PDB:1JHN" FT STRAND 388..390 FT /evidence="ECO:0007829|PDB:1JHN" FT STRAND 420..425 FT /evidence="ECO:0007829|PDB:1JHN" FT STRAND 430..432 FT /evidence="ECO:0007829|PDB:1JHN" FT STRAND 437..445 FT /evidence="ECO:0007829|PDB:1JHN" FT HELIX 446..454 FT /evidence="ECO:0007829|PDB:1JHN" FT TURN 455..457 FT /evidence="ECO:0007829|PDB:1JHN" SQ SEQUENCE 593 AA; 67603 MW; A2969701B1EB7B6A CRC64; MEGKWLLCML LVLGTTIVQA HEGHDDDMID IEDDLDDVIE EVEDSKSKPD TSAPTSPKVT YKAPVPTGEV YFADSFDRGT LSGWILSKAK KDDTDDEIAK YDGKWEVDEM KETKLPGDKG LVLMSRAKHH AISAKLNKPF LFDTKPLIVQ YEVNFQNGIE CGGAYVKLLS KTPELNLDQF HDKTPYTIMF GPDKCGEDYK LHFIFRHKNP KTGVYEEKHA KRPDADLKTY FTDKKTHLYT LILNPDNSFE ILVDQSIVNS GNLLNDMTPP VNPSREIEDP EDQKPEDWDE RPKIPDPDAV KPDDWNEDAP AKIPDEEATK PDGWLDDEPE YVPDPDAEKP EDWDEDMDGE WEAPQIANPK CESAPGCGVW QRPMIDNPNY KGKWKPPMID NPNYQGIWKP RKIPNPDFFE DLEPFKMTPF SAIGLELWSM TSDIFFDNFI VCGDRRVVDD WANDGWGLKK AADGAAEPGV VGQMIEAAEE RPWLWVVYVL TVALPVFLVI LFCCSGKKQS SPVEYKKTDA PQPDVKEEEE EKEEEKDKGD EEEEGEEKLE EKQKSDAEED GGTASQEEDD RKPKAEEDEI LNRSPRNRKP RRE //