CALX_RAT
ID CALX_RAT Reviewed; 591 AA.
AC P35565;
DT 01-JUN-1994, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-1994, sequence version 1.
DT 03-AUG-2022, entry version 187.
DE RecName: Full=Calnexin;
DE Flags: Precursor;
GN Name=Canx;
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].
RC TISSUE=T-cell;
RX PubMed=8136357; DOI=10.1021/bi00177a013;
RA Tjoelker L.W., Seyfried C.E., Eddy R.L. Jr., Shows T.B. Jr., Calderon J.,
RA Schreiber R.B., Gray P.W.;
RT "Human, mouse, and rat calnexin cDNA cloning: identification of potential
RT calcium binding motifs and gene localization to human chromosome 5.";
RL Biochemistry 33:3229-3236(1994).
RN [2]
RP PROTEIN SEQUENCE OF 49-58, AND IDENTIFICATION BY MASS SPECTROMETRY.
RC STRAIN=Sprague-Dawley; TISSUE=Brain;
RA Lubec G., Kang S.U.;
RL Submitted (JUL-2007) to UniProtKB.
RN [3]
RP CHARACTERIZATION.
RX PubMed=8440713; DOI=10.1016/s0021-9258(18)53608-5;
RA Gilchrist J.S., Pierce G.N.;
RT "Identification and purification of a calcium-binding protein in hepatic
RT nuclear membranes.";
RL J. Biol. Chem. 268:4291-4299(1993).
RN [4]
RP PHOSPHORYLATION AT SER-563, INTERACTION WITH MAPK3/ERK1, AND ASSOCIATION
RP WITH RIBOSOMES.
RX PubMed=10393181; DOI=10.1093/emboj/18.13.3655;
RA Chevet E., Wong H.N., Gerber D., Cochet C., Fazel A., Cameron P.H.,
RA Gushue J.N., Thomas D.Y., Bergeron J.J.;
RT "Phosphorylation by CK2 and MAPK enhances calnexin association with
RT ribosomes.";
RL EMBO J. 18:3655-3666(1999).
RN [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-553; SER-563 AND SER-582, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(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.
CC -!- SUBUNIT: Interacts with MAPK3/ERK1 (PubMed:10393181). Interacts with
CC KCNH2 (By similarity). Associates with ribosomes (PubMed:10393181).
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 (By similarity). 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:0000269|PubMed:10393181}.
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-563 by MAPK3/ERK1. phosphorylation by
CC MAPK3/ERK1 increases its association with ribosomes.
CC {ECO:0000269|PubMed:10393181}.
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; L18889; AAA21015.1; -; mRNA.
DR PIR; C54354; C54354.
DR RefSeq; NP_742005.1; NM_172008.2.
DR RefSeq; XP_008765901.1; XM_008767679.2.
DR RefSeq; XP_008765902.1; XM_008767680.2.
DR AlphaFoldDB; P35565; -.
DR SMR; P35565; -.
DR BioGRID; 247827; 6.
DR IntAct; P35565; 12.
DR MINT; P35565; -.
DR STRING; 10116.ENSRNOP00000040859; -.
DR iPTMnet; P35565; -.
DR PhosphoSitePlus; P35565; -.
DR SwissPalm; P35565; -.
DR jPOST; P35565; -.
DR PaxDb; P35565; -.
DR PRIDE; P35565; -.
DR GeneID; 29144; -.
DR KEGG; rno:29144; -.
DR UCSC; RGD:2266; rat.
DR CTD; 821; -.
DR RGD; 2266; Canx.
DR VEuPathDB; HostDB:ENSRNOG00000003343; -.
DR eggNOG; KOG0675; Eukaryota.
DR HOGENOM; CLU_018224_2_0_1; -.
DR InParanoid; P35565; -.
DR OMA; ANPKCEA; -.
DR OrthoDB; 775337at2759; -.
DR PhylomeDB; P35565; -.
DR Reactome; R-RNO-2132295; MHC class II antigen presentation.
DR Reactome; R-RNO-901042; Calnexin/calreticulin cycle.
DR Reactome; R-RNO-983170; Antigen Presentation: Folding, assembly and peptide loading of class I MHC.
DR PRO; PR:P35565; -.
DR Proteomes; UP000002494; Chromosome 10.
DR Bgee; ENSRNOG00000003343; Expressed in lung and 19 other tissues.
DR Genevisible; P35565; RN.
DR GO; GO:0030424; C:axon; IDA:RGD.
DR GO; GO:0005737; C:cytoplasm; IDA:RGD.
DR GO; GO:0032839; C:dendrite cytoplasm; IDA:RGD.
DR GO; GO:0043197; C:dendritic spine; IDA:RGD.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:UniProtKB.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; ISS:AgBase.
DR GO; GO:0044322; C:endoplasmic reticulum quality control compartment; ISO:RGD.
DR GO; GO:0098978; C:glutamatergic synapse; IDA:SynGO.
DR GO; GO:0016021; C:integral component of membrane; ISO:RGD.
DR GO; GO:0099055; C:integral component of postsynaptic membrane; IDA:SynGO.
DR GO; GO:0099059; C:integral component of presynaptic active zone membrane; IDA:SynGO.
DR GO; GO:0042470; C:melanosome; IEA:UniProtKB-SubCell.
DR GO; GO:0016020; C:membrane; ISO:RGD.
DR GO; GO:0044233; C:mitochondria-associated endoplasmic reticulum membrane; ISO:RGD.
DR GO; GO:0043025; C:neuronal cell body; IDA:RGD.
DR GO; GO:0032991; C:protein-containing complex; IDA:RGD.
DR GO; GO:0005840; C:ribosome; IDA:RGD.
DR GO; GO:0005790; C:smooth endoplasmic reticulum; IDA:UniProtKB.
DR GO; GO:0034185; F:apolipoprotein binding; IDA:RGD.
DR GO; GO:0005509; F:calcium ion binding; IBA:GO_Central.
DR GO; GO:0030246; F:carbohydrate binding; IEA:UniProtKB-KW.
DR GO; GO:0035255; F:ionotropic glutamate receptor binding; IDA:RGD.
DR GO; GO:0051082; F:unfolded protein binding; IEA:InterPro.
DR GO; GO:0007568; P:aging; IEP:RGD.
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 Acetylation; Calcium; Chaperone; Direct protein sequencing; Disulfide bond;
KW Endoplasmic reticulum; Lectin; Lipoprotein; Membrane; Metal-binding;
KW Palmitate; Phosphoprotein; Reference proteome; Repeat; Signal;
KW Transmembrane; Transmembrane helix; Ubl conjugation.
FT SIGNAL 1..20
FT /evidence="ECO:0000255"
FT CHAIN 21..591
FT /note="Calnexin"
FT /id="PRO_0000004201"
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..591
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REPEAT 279..291
FT /note="1-1"
FT REPEAT 296..308
FT /note="1-2"
FT REPEAT 315..327
FT /note="1-3"
FT REPEAT 334..346
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..347
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 277..410
FT /note="P domain (Extended arm)"
FT /evidence="ECO:0000250"
FT REGION 279..346
FT /note="4 X approximate repeats"
FT REGION 327..360
FT /note="Interaction with PPIB"
FT /evidence="ECO:0000250"
FT REGION 349..406
FT /note="4 X approximate repeats"
FT REGION 504..591
FT /note="Sufficient to mediate interaction with SGIP1"
FT /evidence="ECO:0000250"
FT REGION 514..591
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..347
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 519..533
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 548..584
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:0000250"
FT BINDING 118
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250"
FT BINDING 165
FT /ligand="an alpha-D-glucoside"
FT /ligand_id="ChEBI:CHEBI:22390"
FT /evidence="ECO:0000250|UniProtKB:P14211"
FT BINDING 167
FT /ligand="an alpha-D-glucoside"
FT /ligand_id="ChEBI:CHEBI:22390"
FT /evidence="ECO:0000250|UniProtKB:P14211"
FT BINDING 186
FT /ligand="an alpha-D-glucoside"
FT /ligand_id="ChEBI:CHEBI:22390"
FT /evidence="ECO:0000250|UniProtKB:P14211"
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 BINDING 437
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250"
FT MOD_RES 138
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P27824"
FT MOD_RES 553
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 561
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P27824"
FT MOD_RES 563
FT /note="Phosphoserine; by MAPK3"
FT /evidence="ECO:0000269|PubMed:10393181,
FT ECO:0007744|PubMed:22673903"
FT MOD_RES 582
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
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:0000250"
FT DISULFID 361..367
FT /evidence="ECO:0000250"
SQ SEQUENCE 591 AA; 67255 MW; DF91D099593C62B2 CRC64;
MEGKWLLCLL LVLGTAAIQA HDGHDDDMID IEDDLDDVIE EVEDSKSKSD TSTPPSPKVT
YKAPVPTGEV YFADSFDRGS LSGWILSKAK KDDTDDEIAK YDGKWEVDEM KETKLPGDKG
LVLMSRAKHH AISAKLNKPF LFDTKPLIVQ YEVNFQNGIE CGGAYVKLLS KTSELNLDQF
HDKTPYTIMF GPDKCGEDYK LHFIFRHKNP KTGVYEEKHA KRPDADLKTY FTDKKTHLYT
LILNPDNSFE ILVDQSVVNS GNLLNDMTPP VNPSREIEDP EDRKPEDWDE RPKIADPDAV
KPDDWDEDAP SKIPDEEATK PEGWLDDEPE YIPDPDAEKP EDWDEDMDGE WEAPQIANPK
CESAPGCGVW QRPMIDNPNY KGKWKPPMID NPNYQGIWKP RKIPNPDFFE DLEPFRMTPF
SAIGLELWSM TSDIFFDNFI ISGDRRVVDD WANDGWGLKK AADGAAEPGV VGQMLEAAEE
RPWLWVVYIL TVALPVFLVI LFCCSGKKQS NAMEYKKTDA PQPDVKDEEG KEEEKNKGDE
EEEEEKLEEK QKSDAEEDGG TGSQDEEDSK PKAEEDEILN RSPRNRKPRR E
