CALX_CANLF
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 03-AUG-2022, entry version 165.
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).
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).
CC {ECO:0000250|UniProtKB:P27824, ECO:0000250|UniProtKB:P35564,
CC ECO:0000250|UniProtKB:P35565, 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:0000250|UniProtKB:P27824}; Single-pass type I membrane protein
CC {ECO:0000255}. Endoplasmic reticulum {ECO:0000250|UniProtKB:P27824}.
CC Melanosome {ECO:0000250|UniProtKB:P27824}. Note=The palmitoylated form
CC preferentially localizes to the perinuclear rough ER.
CC {ECO:0000250|UniProtKB:P27824}.
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}.
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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; 1.
DR DIP; DIP-29133N; -.
DR IntAct; P24643; 1.
DR STRING; 9612.ENSCAFP00000042695; -.
DR UniLectin; P24643; -.
DR iPTMnet; P24643; -.
DR SwissPalm; P24643; -.
DR PaxDb; P24643; -.
DR PRIDE; P24643; -.
DR GeneID; 403908; -.
DR KEGG; cfa:403908; -.
DR CTD; 821; -.
DR eggNOG; KOG0675; Eukaryota.
DR InParanoid; P24643; -.
DR OrthoDB; 775337at2759; -.
DR EvolutionaryTrace; P24643; -.
DR Proteomes; UP000002254; Unplaced.
DR GO; GO:0005783; C:endoplasmic reticulum; ISS:UniProtKB.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; ISS:AgBase.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0042470; C:melanosome; 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; 2.10.250.10; -; 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; PTHR11073; 1.
DR Pfam; PF00262; Calreticulin; 1.
DR PRINTS; PR00626; CALRETICULIN.
DR SUPFAM; SSF49899; SSF49899; 2.
DR SUPFAM; SSF63887; SSF63887; 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; Palmitate; Phosphoprotein; Reference proteome; Repeat;
KW Signal; Transmembrane; Transmembrane helix; 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 BINDING 118
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT BINDING 165
FT /ligand="an alpha-D-glucoside"
FT /ligand_id="ChEBI:CHEBI:22390"
FT /evidence="ECO:0000250|UniProtKB:P14211,
FT ECO:0000305|PubMed:11583625"
FT BINDING 167
FT /ligand="an alpha-D-glucoside"
FT /ligand_id="ChEBI:CHEBI:22390"
FT /evidence="ECO:0000250|UniProtKB:P14211,
FT ECO:0000305|PubMed:11583625"
FT BINDING 186
FT /ligand="an alpha-D-glucoside"
FT /ligand_id="ChEBI:CHEBI:22390"
FT /evidence="ECO:0000250|UniProtKB:P14211,
FT 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:0000250|UniProtKB:P14211,
FT ECO:0000305|PubMed:11583625"
FT BINDING 437
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
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:0000250"
FT LIPID 504
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000250"
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 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
