Full text data of CANX
CANX
[Confidence: high (present in two of the MS resources)]
Calnexin (IP90; Major histocompatibility complex class I antigen-binding protein p88; p90; Flags: Precursor)
Calnexin (IP90; Major histocompatibility complex class I antigen-binding protein p88; p90; Flags: Precursor)
hRBCD
IPI00020984
IPI00020984 Calnexin precursor Calnexin precursor membrane n/a 2 3 n/a 3 n/a 2 1 n/a n/a 5 1 3 4 n/a n/a 1 n/a 3 n/a Type I memrbane protein, ER n/a found at its expected molecular weight found at molecular weight
IPI00020984 Calnexin precursor Calnexin precursor membrane n/a 2 3 n/a 3 n/a 2 1 n/a n/a 5 1 3 4 n/a n/a 1 n/a 3 n/a Type I memrbane protein, ER n/a found at its expected molecular weight found at molecular weight
UniProt
P27824
ID CALX_HUMAN Reviewed; 592 AA.
AC P27824; B2R5V8; D3DWQ3;
DT 01-AUG-1992, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-JUN-1994, sequence version 2.
DT 22-JAN-2014, entry version 159.
DE RecName: Full=Calnexin;
DE AltName: Full=IP90;
DE AltName: Full=Major histocompatibility complex class I antigen-binding protein p88;
DE AltName: Full=p90;
DE Flags: Precursor;
GN Name=CANX;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=8486646;
RA David V., Hochstenbach F., Rajagopalan S., Brenner M.B.;
RT "Interaction with newly synthesized and retained proteins in the
RT endoplasmic reticulum suggests a chaperone function for human integral
RT membrane protein IP90 (calnexin).";
RL J. Biol. Chem. 268:9585-9592(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Lymph, and Placenta;
RX PubMed=8136357; DOI=10.1021/bi00177a013;
RA Tjoelker L.W., Seyfried C.E., Eddy R.L. Jr., Shows T.B. Jr.,
RA Calderon J., Schreiber R.B., Gray P.W.;
RT "Human, mouse, and rat calnexin cDNA cloning: identification of
RT potential calcium binding motifs and gene localization to human
RT chromosome 5.";
RL Biochemistry 33:3229-3236(1994).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Keratinocyte;
RX PubMed=8055875; DOI=10.1002/elps.1150150166;
RA Honore B., Rasmussen H.H., Celis A., Leffers H., Madsen P.,
RA Celis J.E.;
RT "The molecular chaperones HSP28, GRP78, endoplasmin, and calnexin
RT exhibit strikingly different levels in quiescent keratinocytes as
RT compared to their proliferating normal and transformed counterparts:
RT cDNA cloning and expression of calnexin.";
RL Electrophoresis 15:482-490(1994).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Fibroblast;
RA Hansen J.J., Jorgensen M.M., Bolund L., Gregersen N.;
RL Submitted (FEB-2000) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Cerebellum;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Placenta;
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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [8]
RP PROTEIN SEQUENCE OF 62-77; 171-193; 200-205; 221-227; 401-415; 517-525
RP AND 574-582, AND MASS SPECTROMETRY.
RC TISSUE=B-cell lymphoma;
RA Bienvenut W.V.;
RL Submitted (MAR-2005) to UniProtKB.
RN [9]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 237-592.
RX PubMed=1326756; DOI=10.1073/pnas.89.18.8452;
RA Galvin K., Krishna S., Ponchel F., Frohlich M., Cummings D.E.,
RA Carlson R., Wands J.R., Isselbacher K.J., Pillai S., Ozturk M.;
RT "The major histocompatibility complex class I antigen-binding protein
RT p88 is the product of the calnexin gene.";
RL Proc. Natl. Acad. Sci. U.S.A. 89:8452-8456(1992).
RN [10]
RP PROTEIN SEQUENCE OF 275-286; 293-313; 383-398 AND 516-523.
RC TISSUE=Keratinocyte;
RX PubMed=1286667; DOI=10.1002/elps.11501301199;
RA Rasmussen H.H., van Damme J., Puype M., Gesser B., Celis J.E.,
RA Vandekerckhove J.;
RT "Microsequences of 145 proteins recorded in the two-dimensional gel
RT protein database of normal human epidermal keratinocytes.";
RL Electrophoresis 13:960-969(1992).
RN [11]
RP SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS], AND MASS SPECTROMETRY.
RC TISSUE=Melanoma;
RX PubMed=12643545; DOI=10.1021/pr025562r;
RA Basrur V., Yang F., Kushimoto T., Higashimoto Y., Yasumoto K.,
RA Valencia J., Muller J., Vieira W.D., Watabe H., Shabanowitz J.,
RA Hearing V.J., Hunt D.F., Appella E.;
RT "Proteomic analysis of early melanosomes: identification of novel
RT melanosomal proteins.";
RL J. Proteome Res. 2:69-79(2003).
RN [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-554 AND SER-583, AND
RP MASS SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P.,
RA Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in
RT signaling networks.";
RL Cell 127:635-648(2006).
RN [13]
RP INTERACTION WITH KCNH2.
RX PubMed=16361248; DOI=10.1074/jbc.M511765200;
RA Gong Q., Jones M.A., Zhou Z.;
RT "Mechanisms of pharmacological rescue of trafficking-defective hERG
RT mutant channels in human long QT syndrome.";
RL J. Biol. Chem. 281:4069-4074(2006).
RN [14]
RP SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS], AND MASS SPECTROMETRY.
RC TISSUE=Melanoma;
RX PubMed=17081065; DOI=10.1021/pr060363j;
RA Chi A., Valencia J.C., Hu Z.-Z., Watabe H., Yamaguchi H.,
RA Mangini N.J., Huang H., Canfield V.A., Cheng K.C., Yang F., Abe R.,
RA Yamagishi S., Shabanowitz J., Hearing V.J., Wu C., Appella E.,
RA Hunt D.F.;
RT "Proteomic and bioinformatic characterization of the biogenesis and
RT function of melanosomes.";
RL J. Proteome Res. 5:3135-3144(2006).
RN [15]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-554 AND SER-583, AND
RP MASS SPECTROMETRY.
RC TISSUE=Platelet;
RX PubMed=18088087; DOI=10.1021/pr0704130;
RA Zahedi R.P., Lewandrowski U., Wiesner J., Wortelkamp S., Moebius J.,
RA Schuetz C., Walter U., Gambaryan S., Sickmann A.;
RT "Phosphoproteome of resting human platelets.";
RL J. Proteome Res. 7:526-534(2008).
RN [16]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-554 AND SER-583, AND
RP MASS SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007;
RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,
RA Greff Z., Keri G., Stemmann O., Mann M.;
RT "Kinase-selective enrichment enables quantitative phosphoproteomics of
RT the kinome across the cell cycle.";
RL Mol. Cell 31:438-448(2008).
RN [17]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-554 AND SER-564, AND
RP MASS SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [18]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-554, AND MASS
RP SPECTROMETRY.
RC TISSUE=Liver;
RX PubMed=18318008; DOI=10.1002/pmic.200700884;
RA Han G., Ye M., Zhou H., Jiang X., Feng S., Jiang X., Tian R., Wan D.,
RA Zou H., Gu J.;
RT "Large-scale phosphoproteome analysis of human liver tissue by
RT enrichment and fractionation of phosphopeptides with strong anion
RT exchange chromatography.";
RL Proteomics 8:1346-1361(2008).
RN [19]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-554, AND MASS
RP SPECTROMETRY.
RX PubMed=19369195; DOI=10.1074/mcp.M800588-MCP200;
RA Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G.,
RA Mann M., Daub H.;
RT "Large-scale proteomics analysis of the human kinome.";
RL Mol. Cell. Proteomics 8:1751-1764(2009).
RN [20]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-564, AND MASS
RP SPECTROMETRY.
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [21]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-137, AND MASS SPECTROMETRY.
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M.,
RA Walther T.C., Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [22]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-554; SER-564 AND
RP SER-583, AND MASS SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [23]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [24]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-554; THR-562; SER-564
RP AND SER-583, AND MASS SPECTROMETRY.
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J.,
RA Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V.,
RA Blagoev B.;
RT "System-wide temporal characterization of the proteome and
RT phosphoproteome of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [25]
RP PALMITOYLATION AT CYS-502 AND CYS-503 BY DHHC6, SUBCELLULAR LOCATION,
RP AND INTERACTION WITH SSR1.
RX PubMed=22314232; DOI=10.1038/emboj.2012.15;
RA Lakkaraju A.K., Abrami L., Lemmin T., Blaskovic S., Kunz B.,
RA Kihara A., Dal Peraro M., van der Goot F.G.;
RT "Palmitoylated calnexin is a key component of the ribosome-translocon
RT complex.";
RL EMBO J. 31:1823-1835(2012).
RN [26]
RP INTERACTION WITH SERPINA2P AND SERPINA1, AND SUBCELLULAR LOCATION.
RX PubMed=23826168; DOI=10.1371/journal.pone.0066889;
RA Marques P.I., Ferreira Z., Martins M., Figueiredo J., Silva D.I.,
RA Castro P., Morales-Hojas R., Simoes-Correia J., Seixas S.;
RT "SERPINA2 is a novel gene with a divergent function from SERPINA1.";
RL PLoS ONE 8:E66889-E66889(2013).
CC -!- FUNCTION: Calcium-binding protein that interacts with newly
CC synthesized glycoproteins in the endoplasmic reticulum. It may act
CC in assisting protein assembly and/or in the retention within the
CC ER of unassembled protein subunits. It seems to play a major role
CC in the quality control apparatus of the ER by the retention of
CC incorrectly folded proteins. Associated with partial T-cell
CC antigen receptor complexes that escape the ER of immature
CC thymocytes, it may function as a signaling complex regulating
CC thymocyte maturation. Additionally it may play a role in receptor-
CC mediated endocytosis at the synapse.
CC -!- SUBUNIT: Interacts with MAPK3/ERK1. Interacts with KCNH2.
CC Associates with ribosomes. Interacts with SGIP1; involved in
CC negative regulation of endocytosis (By similarity). The
CC palmitoylated form interacts with the ribosome-translocon complex
CC component SSR1, promoting efficient folding of glycoproteins.
CC Interacts with SERPINA2P/SERPINA2 and with the S and Z variants of
CC SERPINA1.
CC -!- INTERACTION:
CC P11607:ATP2A2 (xeno); NbExp=2; IntAct=EBI-355947, EBI-8004986;
CC P13569:CFTR; NbExp=3; IntAct=EBI-355947, EBI-349854;
CC Q92597:NDRG1; NbExp=2; IntAct=EBI-355947, EBI-716486;
CC P41143:OPRD1; NbExp=2; IntAct=EBI-355947, EBI-2624456;
CC P30050:RPL12; NbExp=3; IntAct=EBI-355947, EBI-352743;
CC P61619:SEC61A1; NbExp=3; IntAct=EBI-355947, EBI-358919;
CC P43307:SSR1; NbExp=5; IntAct=EBI-355947, EBI-714168;
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane; Single-pass
CC type I membrane protein. Endoplasmic reticulum. Melanosome.
CC Note=Identified by mass spectrometry in melanosome fractions from
CC stage I to stage IV. The palmitoylated form preferentially
CC localizes to the perinuclear rough ER.
CC -!- PTM: Phosphorylated at Ser-564 by MAPK3/ERK1. phosphorylation by
CC MAPK3/ERK1 increases its association with ribosomes (By
CC similarity).
CC -!- PTM: Palmitoylation by DHHC6 leads to the preferential
CC localization to the perinuclear rough ER. It mediates the
CC association of calnexin with the ribosome-translocon complex (RTC)
CC which is required for efficient folding of glycosylated proteins.
CC -!- SIMILARITY: Belongs to the calreticulin family.
CC -!- WEB RESOURCE: Name=Wikipedia; Note=Calnexin entry;
CC URL="http://en.wikipedia.org/wiki/Calnexin";
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DR EMBL; L10284; AAA36125.1; -; mRNA.
DR EMBL; L18887; AAA21013.1; -; mRNA.
DR EMBL; M94859; AAA21749.1; -; mRNA.
DR EMBL; M98452; AAA35696.1; -; mRNA.
DR EMBL; AK312334; BAG35255.1; -; mRNA.
DR EMBL; CH471165; EAW53802.1; -; Genomic_DNA.
DR EMBL; CH471165; EAW53803.1; -; Genomic_DNA.
DR EMBL; CH471165; EAW53805.1; -; Genomic_DNA.
DR EMBL; BC003552; AAH03552.1; -; mRNA.
DR EMBL; BC042843; AAH42843.1; -; mRNA.
DR EMBL; AJ271880; CAB72137.1; -; mRNA.
DR PIR; A46164; A46164.
DR PIR; A46673; A46673.
DR PIR; I53260; I53260.
DR RefSeq; NP_001019820.1; NM_001024649.1.
DR RefSeq; NP_001737.1; NM_001746.3.
DR UniGene; Hs.567968; -.
DR ProteinModelPortal; P27824; -.
DR SMR; P27824; 60-457.
DR DIP; DIP-457N; -.
DR IntAct; P27824; 60.
DR MINT; MINT-5000964; -.
DR STRING; 9606.ENSP00000247461; -.
DR BindingDB; P27824; -.
DR ChEMBL; CHEMBL2719; -.
DR DrugBank; DB00009; Alteplase.
DR DrugBank; DB00029; Anistreplase.
DR DrugBank; DB00025; Antihemophilic Factor.
DR DrugBank; DB00015; Reteplase.
DR DrugBank; DB00031; Tenecteplase.
DR PhosphoSite; P27824; -.
DR DMDM; 543920; -.
DR PaxDb; P27824; -.
DR PeptideAtlas; P27824; -.
DR PRIDE; P27824; -.
DR DNASU; 821; -.
DR Ensembl; ENST00000247461; ENSP00000247461; ENSG00000127022.
DR Ensembl; ENST00000452673; ENSP00000391646; ENSG00000127022.
DR Ensembl; ENST00000504734; ENSP00000424063; ENSG00000127022.
DR GeneID; 821; -.
DR KEGG; hsa:821; -.
DR UCSC; uc003mkk.3; human.
DR CTD; 821; -.
DR GeneCards; GC05P179105; -.
DR HGNC; HGNC:1473; CANX.
DR HPA; CAB004738; -.
DR HPA; HPA009433; -.
DR HPA; HPA009696; -.
DR MIM; 114217; gene.
DR neXtProt; NX_P27824; -.
DR PharmGKB; PA26055; -.
DR eggNOG; NOG305105; -.
DR HOGENOM; HOG000192436; -.
DR HOVERGEN; HBG005407; -.
DR InParanoid; P27824; -.
DR KO; K08054; -.
DR OrthoDB; EOG77126Z; -.
DR PhylomeDB; P27824; -.
DR Reactome; REACT_111102; Signal Transduction.
DR Reactome; REACT_17015; Metabolism of proteins.
DR Reactome; REACT_6900; Immune System.
DR ChiTaRS; CANX; human.
DR GeneWiki; Calnexin; -.
DR GenomeRNAi; 821; -.
DR NextBio; 3360; -.
DR PRO; PR:P27824; -.
DR ArrayExpress; P27824; -.
DR Bgee; P27824; -.
DR CleanEx; HS_CANX; -.
DR Genevestigator; P27824; -.
DR GO; GO:0030424; C:axon; IEA:Ensembl.
DR GO; GO:0032839; C:dendrite cytoplasm; IEA:Ensembl.
DR GO; GO:0043197; C:dendritic spine; IEA:Ensembl.
DR GO; GO:0005788; C:endoplasmic reticulum lumen; TAS:Reactome.
DR GO; GO:0071556; C:integral to lumenal side of endoplasmic reticulum membrane; TAS:Reactome.
DR GO; GO:0042470; C:melanosome; IEA:UniProtKB-SubCell.
DR GO; GO:0043025; C:neuronal cell body; IEA:Ensembl.
DR GO; GO:0005840; C:ribosome; IEA:Ensembl.
DR GO; GO:0005509; F:calcium ion binding; TAS:ProtInc.
DR GO; GO:0051082; F:unfolded protein binding; NAS:UniProtKB.
DR GO; GO:0007568; P:aging; IEA:Ensembl.
DR GO; GO:0019886; P:antigen processing and presentation of exogenous peptide antigen via MHC class II; TAS:Reactome.
DR GO; GO:0002474; P:antigen processing and presentation of peptide antigen via MHC class I; TAS:Reactome.
DR GO; GO:0072583; P:clathrin-mediated endocytosis; ISS:UniProtKB.
DR GO; GO:0043687; P:post-translational protein modification; TAS:Reactome.
DR GO; GO:0006457; P:protein folding; TAS:Reactome.
DR GO; GO:0018279; P:protein N-linked glycosylation via asparagine; TAS:Reactome.
DR GO; GO:0009306; P:protein secretion; TAS:ProtInc.
DR GO; GO:0048488; P:synaptic vesicle endocytosis; ISS:UniProtKB.
DR Gene3D; 2.10.250.10; -; 1.
DR Gene3D; 2.60.120.200; -; 1.
DR InterPro; IPR001580; Calret/calnex.
DR InterPro; IPR018124; Calret/calnex_CS.
DR InterPro; IPR009033; Calreticulin/calnexin_P_dom.
DR InterPro; IPR008985; ConA-like_lec_gl_sf.
DR InterPro; IPR013320; ConA-like_subgrp.
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; Complete proteome;
KW Direct protein sequencing; Disulfide bond; Endoplasmic reticulum;
KW Lectin; Lipoprotein; Membrane; Metal-binding; Palmitate;
KW Phosphoprotein; Reference proteome; Repeat; Signal; Transmembrane;
KW Transmembrane helix.
FT SIGNAL 1 20 Potential.
FT CHAIN 21 592 Calnexin.
FT /FTId=PRO_0000004198.
FT TOPO_DOM 21 481 Lumenal (Potential).
FT TRANSMEM 482 502 Helical; (Potential).
FT TOPO_DOM 503 592 Cytoplasmic (Potential).
FT REPEAT 278 290 1-1.
FT REPEAT 295 307 1-2.
FT REPEAT 314 326 1-3.
FT REPEAT 333 345 1-4.
FT REPEAT 348 358 2-1.
FT REPEAT 367 377 2-2.
FT REPEAT 381 391 2-3.
FT REPEAT 395 405 2-4.
FT REGION 276 409 P domain (Extended arm) (By similarity).
FT REGION 278 345 4 X approximate repeats.
FT REGION 348 405 4 X approximate repeats.
FT REGION 503 592 Sufficient to mediate interaction with
FT SGIP1 (By similarity).
FT METAL 74 74 Calcium; via carbonyl oxygen (By
FT similarity).
FT METAL 117 117 Calcium; via carbonyl oxygen (By
FT similarity).
FT METAL 436 436 Calcium (By similarity).
FT BINDING 164 164 Carbohydrate (By similarity).
FT BINDING 166 166 Carbohydrate (By similarity).
FT BINDING 185 185 Carbohydrate (By similarity).
FT BINDING 216 216 Carbohydrate (By similarity).
FT MOD_RES 137 137 N6-acetyllysine.
FT MOD_RES 554 554 Phosphoserine.
FT MOD_RES 562 562 Phosphothreonine.
FT MOD_RES 564 564 Phosphoserine; by MAPK3.
FT MOD_RES 583 583 Phosphoserine.
FT LIPID 502 502 S-palmitoyl cysteine.
FT LIPID 503 503 S-palmitoyl cysteine.
FT DISULFID 160 194 By similarity.
FT DISULFID 360 366 By similarity.
FT CONFLICT 179 179 F -> L (in Ref. 2; AAA21749).
FT CONFLICT 431 433 SDI -> LTF (in Ref. 9; AAA35696).
FT CONFLICT 480 480 R -> L (in Ref. 9; AAA35696).
SQ SEQUENCE 592 AA; 67568 MW; EDE094D9B82261EE CRC64;
MEGKWLLCML LVLGTAIVEA HDGHDDDVID IEDDLDDVIE EVEDSKPDTT APPSSPKVTY
KAPVPTGEVY FADSFDRGTL SGWILSKAKK DDTDDEIAKY DGKWEVEEMK ESKLPGDKGL
VLMSRAKHHA ISAKLNKPFL FDTKPLIVQY EVNFQNGIEC GGAYVKLLSK TPELNLDQFH
DKTPYTIMFG PDKCGEDYKL HFIFRHKNPK TGIYEEKHAK RPDADLKTYF TDKKTHLYTL
ILNPDNSFEI LVDQSVVNSG NLLNDMTPPV NPSREIEDPE DRKPEDWDER PKIPDPEAVK
PDDWDEDAPA KIPDEEATKP EGWLDDEPEY VPDPDAEKPE DWDEDMDGEW EAPQIANPRC
ESAPGCGVWQ RPVIDNPNYK GKWKPPMIDN PSYQGIWKPR KIPNPDFFED LEPFRMTPFS
AIGLELWSMT SDIFFDNFII CADRRIVDDW ANDGWGLKKA ADGAAEPGVV GQMIEAAEER
PWLWVVYILT VALPVFLVIL FCCSGKKQTS GMEYKKTDAP QPDVKEEEEE KEEEKDKGDE
EEEGEEKLEE KQKSDAEEDG GTVSQEEEDR KPKAEEDEIL NRSPRNRKPR RE
//
ID CALX_HUMAN Reviewed; 592 AA.
AC P27824; B2R5V8; D3DWQ3;
DT 01-AUG-1992, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-JUN-1994, sequence version 2.
DT 22-JAN-2014, entry version 159.
DE RecName: Full=Calnexin;
DE AltName: Full=IP90;
DE AltName: Full=Major histocompatibility complex class I antigen-binding protein p88;
DE AltName: Full=p90;
DE Flags: Precursor;
GN Name=CANX;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=8486646;
RA David V., Hochstenbach F., Rajagopalan S., Brenner M.B.;
RT "Interaction with newly synthesized and retained proteins in the
RT endoplasmic reticulum suggests a chaperone function for human integral
RT membrane protein IP90 (calnexin).";
RL J. Biol. Chem. 268:9585-9592(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Lymph, and Placenta;
RX PubMed=8136357; DOI=10.1021/bi00177a013;
RA Tjoelker L.W., Seyfried C.E., Eddy R.L. Jr., Shows T.B. Jr.,
RA Calderon J., Schreiber R.B., Gray P.W.;
RT "Human, mouse, and rat calnexin cDNA cloning: identification of
RT potential calcium binding motifs and gene localization to human
RT chromosome 5.";
RL Biochemistry 33:3229-3236(1994).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Keratinocyte;
RX PubMed=8055875; DOI=10.1002/elps.1150150166;
RA Honore B., Rasmussen H.H., Celis A., Leffers H., Madsen P.,
RA Celis J.E.;
RT "The molecular chaperones HSP28, GRP78, endoplasmin, and calnexin
RT exhibit strikingly different levels in quiescent keratinocytes as
RT compared to their proliferating normal and transformed counterparts:
RT cDNA cloning and expression of calnexin.";
RL Electrophoresis 15:482-490(1994).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Fibroblast;
RA Hansen J.J., Jorgensen M.M., Bolund L., Gregersen N.;
RL Submitted (FEB-2000) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Cerebellum;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Placenta;
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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [8]
RP PROTEIN SEQUENCE OF 62-77; 171-193; 200-205; 221-227; 401-415; 517-525
RP AND 574-582, AND MASS SPECTROMETRY.
RC TISSUE=B-cell lymphoma;
RA Bienvenut W.V.;
RL Submitted (MAR-2005) to UniProtKB.
RN [9]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 237-592.
RX PubMed=1326756; DOI=10.1073/pnas.89.18.8452;
RA Galvin K., Krishna S., Ponchel F., Frohlich M., Cummings D.E.,
RA Carlson R., Wands J.R., Isselbacher K.J., Pillai S., Ozturk M.;
RT "The major histocompatibility complex class I antigen-binding protein
RT p88 is the product of the calnexin gene.";
RL Proc. Natl. Acad. Sci. U.S.A. 89:8452-8456(1992).
RN [10]
RP PROTEIN SEQUENCE OF 275-286; 293-313; 383-398 AND 516-523.
RC TISSUE=Keratinocyte;
RX PubMed=1286667; DOI=10.1002/elps.11501301199;
RA Rasmussen H.H., van Damme J., Puype M., Gesser B., Celis J.E.,
RA Vandekerckhove J.;
RT "Microsequences of 145 proteins recorded in the two-dimensional gel
RT protein database of normal human epidermal keratinocytes.";
RL Electrophoresis 13:960-969(1992).
RN [11]
RP SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS], AND MASS SPECTROMETRY.
RC TISSUE=Melanoma;
RX PubMed=12643545; DOI=10.1021/pr025562r;
RA Basrur V., Yang F., Kushimoto T., Higashimoto Y., Yasumoto K.,
RA Valencia J., Muller J., Vieira W.D., Watabe H., Shabanowitz J.,
RA Hearing V.J., Hunt D.F., Appella E.;
RT "Proteomic analysis of early melanosomes: identification of novel
RT melanosomal proteins.";
RL J. Proteome Res. 2:69-79(2003).
RN [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-554 AND SER-583, AND
RP MASS SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P.,
RA Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in
RT signaling networks.";
RL Cell 127:635-648(2006).
RN [13]
RP INTERACTION WITH KCNH2.
RX PubMed=16361248; DOI=10.1074/jbc.M511765200;
RA Gong Q., Jones M.A., Zhou Z.;
RT "Mechanisms of pharmacological rescue of trafficking-defective hERG
RT mutant channels in human long QT syndrome.";
RL J. Biol. Chem. 281:4069-4074(2006).
RN [14]
RP SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS], AND MASS SPECTROMETRY.
RC TISSUE=Melanoma;
RX PubMed=17081065; DOI=10.1021/pr060363j;
RA Chi A., Valencia J.C., Hu Z.-Z., Watabe H., Yamaguchi H.,
RA Mangini N.J., Huang H., Canfield V.A., Cheng K.C., Yang F., Abe R.,
RA Yamagishi S., Shabanowitz J., Hearing V.J., Wu C., Appella E.,
RA Hunt D.F.;
RT "Proteomic and bioinformatic characterization of the biogenesis and
RT function of melanosomes.";
RL J. Proteome Res. 5:3135-3144(2006).
RN [15]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-554 AND SER-583, AND
RP MASS SPECTROMETRY.
RC TISSUE=Platelet;
RX PubMed=18088087; DOI=10.1021/pr0704130;
RA Zahedi R.P., Lewandrowski U., Wiesner J., Wortelkamp S., Moebius J.,
RA Schuetz C., Walter U., Gambaryan S., Sickmann A.;
RT "Phosphoproteome of resting human platelets.";
RL J. Proteome Res. 7:526-534(2008).
RN [16]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-554 AND SER-583, AND
RP MASS SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007;
RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,
RA Greff Z., Keri G., Stemmann O., Mann M.;
RT "Kinase-selective enrichment enables quantitative phosphoproteomics of
RT the kinome across the cell cycle.";
RL Mol. Cell 31:438-448(2008).
RN [17]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-554 AND SER-564, AND
RP MASS SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [18]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-554, AND MASS
RP SPECTROMETRY.
RC TISSUE=Liver;
RX PubMed=18318008; DOI=10.1002/pmic.200700884;
RA Han G., Ye M., Zhou H., Jiang X., Feng S., Jiang X., Tian R., Wan D.,
RA Zou H., Gu J.;
RT "Large-scale phosphoproteome analysis of human liver tissue by
RT enrichment and fractionation of phosphopeptides with strong anion
RT exchange chromatography.";
RL Proteomics 8:1346-1361(2008).
RN [19]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-554, AND MASS
RP SPECTROMETRY.
RX PubMed=19369195; DOI=10.1074/mcp.M800588-MCP200;
RA Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G.,
RA Mann M., Daub H.;
RT "Large-scale proteomics analysis of the human kinome.";
RL Mol. Cell. Proteomics 8:1751-1764(2009).
RN [20]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-564, AND MASS
RP SPECTROMETRY.
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [21]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-137, AND MASS SPECTROMETRY.
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M.,
RA Walther T.C., Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [22]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-554; SER-564 AND
RP SER-583, AND MASS SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [23]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [24]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-554; THR-562; SER-564
RP AND SER-583, AND MASS SPECTROMETRY.
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J.,
RA Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V.,
RA Blagoev B.;
RT "System-wide temporal characterization of the proteome and
RT phosphoproteome of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [25]
RP PALMITOYLATION AT CYS-502 AND CYS-503 BY DHHC6, SUBCELLULAR LOCATION,
RP AND INTERACTION WITH SSR1.
RX PubMed=22314232; DOI=10.1038/emboj.2012.15;
RA Lakkaraju A.K., Abrami L., Lemmin T., Blaskovic S., Kunz B.,
RA Kihara A., Dal Peraro M., van der Goot F.G.;
RT "Palmitoylated calnexin is a key component of the ribosome-translocon
RT complex.";
RL EMBO J. 31:1823-1835(2012).
RN [26]
RP INTERACTION WITH SERPINA2P AND SERPINA1, AND SUBCELLULAR LOCATION.
RX PubMed=23826168; DOI=10.1371/journal.pone.0066889;
RA Marques P.I., Ferreira Z., Martins M., Figueiredo J., Silva D.I.,
RA Castro P., Morales-Hojas R., Simoes-Correia J., Seixas S.;
RT "SERPINA2 is a novel gene with a divergent function from SERPINA1.";
RL PLoS ONE 8:E66889-E66889(2013).
CC -!- FUNCTION: Calcium-binding protein that interacts with newly
CC synthesized glycoproteins in the endoplasmic reticulum. It may act
CC in assisting protein assembly and/or in the retention within the
CC ER of unassembled protein subunits. It seems to play a major role
CC in the quality control apparatus of the ER by the retention of
CC incorrectly folded proteins. Associated with partial T-cell
CC antigen receptor complexes that escape the ER of immature
CC thymocytes, it may function as a signaling complex regulating
CC thymocyte maturation. Additionally it may play a role in receptor-
CC mediated endocytosis at the synapse.
CC -!- SUBUNIT: Interacts with MAPK3/ERK1. Interacts with KCNH2.
CC Associates with ribosomes. Interacts with SGIP1; involved in
CC negative regulation of endocytosis (By similarity). The
CC palmitoylated form interacts with the ribosome-translocon complex
CC component SSR1, promoting efficient folding of glycoproteins.
CC Interacts with SERPINA2P/SERPINA2 and with the S and Z variants of
CC SERPINA1.
CC -!- INTERACTION:
CC P11607:ATP2A2 (xeno); NbExp=2; IntAct=EBI-355947, EBI-8004986;
CC P13569:CFTR; NbExp=3; IntAct=EBI-355947, EBI-349854;
CC Q92597:NDRG1; NbExp=2; IntAct=EBI-355947, EBI-716486;
CC P41143:OPRD1; NbExp=2; IntAct=EBI-355947, EBI-2624456;
CC P30050:RPL12; NbExp=3; IntAct=EBI-355947, EBI-352743;
CC P61619:SEC61A1; NbExp=3; IntAct=EBI-355947, EBI-358919;
CC P43307:SSR1; NbExp=5; IntAct=EBI-355947, EBI-714168;
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane; Single-pass
CC type I membrane protein. Endoplasmic reticulum. Melanosome.
CC Note=Identified by mass spectrometry in melanosome fractions from
CC stage I to stage IV. The palmitoylated form preferentially
CC localizes to the perinuclear rough ER.
CC -!- PTM: Phosphorylated at Ser-564 by MAPK3/ERK1. phosphorylation by
CC MAPK3/ERK1 increases its association with ribosomes (By
CC similarity).
CC -!- PTM: Palmitoylation by DHHC6 leads to the preferential
CC localization to the perinuclear rough ER. It mediates the
CC association of calnexin with the ribosome-translocon complex (RTC)
CC which is required for efficient folding of glycosylated proteins.
CC -!- SIMILARITY: Belongs to the calreticulin family.
CC -!- WEB RESOURCE: Name=Wikipedia; Note=Calnexin entry;
CC URL="http://en.wikipedia.org/wiki/Calnexin";
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DR EMBL; L10284; AAA36125.1; -; mRNA.
DR EMBL; L18887; AAA21013.1; -; mRNA.
DR EMBL; M94859; AAA21749.1; -; mRNA.
DR EMBL; M98452; AAA35696.1; -; mRNA.
DR EMBL; AK312334; BAG35255.1; -; mRNA.
DR EMBL; CH471165; EAW53802.1; -; Genomic_DNA.
DR EMBL; CH471165; EAW53803.1; -; Genomic_DNA.
DR EMBL; CH471165; EAW53805.1; -; Genomic_DNA.
DR EMBL; BC003552; AAH03552.1; -; mRNA.
DR EMBL; BC042843; AAH42843.1; -; mRNA.
DR EMBL; AJ271880; CAB72137.1; -; mRNA.
DR PIR; A46164; A46164.
DR PIR; A46673; A46673.
DR PIR; I53260; I53260.
DR RefSeq; NP_001019820.1; NM_001024649.1.
DR RefSeq; NP_001737.1; NM_001746.3.
DR UniGene; Hs.567968; -.
DR ProteinModelPortal; P27824; -.
DR SMR; P27824; 60-457.
DR DIP; DIP-457N; -.
DR IntAct; P27824; 60.
DR MINT; MINT-5000964; -.
DR STRING; 9606.ENSP00000247461; -.
DR BindingDB; P27824; -.
DR ChEMBL; CHEMBL2719; -.
DR DrugBank; DB00009; Alteplase.
DR DrugBank; DB00029; Anistreplase.
DR DrugBank; DB00025; Antihemophilic Factor.
DR DrugBank; DB00015; Reteplase.
DR DrugBank; DB00031; Tenecteplase.
DR PhosphoSite; P27824; -.
DR DMDM; 543920; -.
DR PaxDb; P27824; -.
DR PeptideAtlas; P27824; -.
DR PRIDE; P27824; -.
DR DNASU; 821; -.
DR Ensembl; ENST00000247461; ENSP00000247461; ENSG00000127022.
DR Ensembl; ENST00000452673; ENSP00000391646; ENSG00000127022.
DR Ensembl; ENST00000504734; ENSP00000424063; ENSG00000127022.
DR GeneID; 821; -.
DR KEGG; hsa:821; -.
DR UCSC; uc003mkk.3; human.
DR CTD; 821; -.
DR GeneCards; GC05P179105; -.
DR HGNC; HGNC:1473; CANX.
DR HPA; CAB004738; -.
DR HPA; HPA009433; -.
DR HPA; HPA009696; -.
DR MIM; 114217; gene.
DR neXtProt; NX_P27824; -.
DR PharmGKB; PA26055; -.
DR eggNOG; NOG305105; -.
DR HOGENOM; HOG000192436; -.
DR HOVERGEN; HBG005407; -.
DR InParanoid; P27824; -.
DR KO; K08054; -.
DR OrthoDB; EOG77126Z; -.
DR PhylomeDB; P27824; -.
DR Reactome; REACT_111102; Signal Transduction.
DR Reactome; REACT_17015; Metabolism of proteins.
DR Reactome; REACT_6900; Immune System.
DR ChiTaRS; CANX; human.
DR GeneWiki; Calnexin; -.
DR GenomeRNAi; 821; -.
DR NextBio; 3360; -.
DR PRO; PR:P27824; -.
DR ArrayExpress; P27824; -.
DR Bgee; P27824; -.
DR CleanEx; HS_CANX; -.
DR Genevestigator; P27824; -.
DR GO; GO:0030424; C:axon; IEA:Ensembl.
DR GO; GO:0032839; C:dendrite cytoplasm; IEA:Ensembl.
DR GO; GO:0043197; C:dendritic spine; IEA:Ensembl.
DR GO; GO:0005788; C:endoplasmic reticulum lumen; TAS:Reactome.
DR GO; GO:0071556; C:integral to lumenal side of endoplasmic reticulum membrane; TAS:Reactome.
DR GO; GO:0042470; C:melanosome; IEA:UniProtKB-SubCell.
DR GO; GO:0043025; C:neuronal cell body; IEA:Ensembl.
DR GO; GO:0005840; C:ribosome; IEA:Ensembl.
DR GO; GO:0005509; F:calcium ion binding; TAS:ProtInc.
DR GO; GO:0051082; F:unfolded protein binding; NAS:UniProtKB.
DR GO; GO:0007568; P:aging; IEA:Ensembl.
DR GO; GO:0019886; P:antigen processing and presentation of exogenous peptide antigen via MHC class II; TAS:Reactome.
DR GO; GO:0002474; P:antigen processing and presentation of peptide antigen via MHC class I; TAS:Reactome.
DR GO; GO:0072583; P:clathrin-mediated endocytosis; ISS:UniProtKB.
DR GO; GO:0043687; P:post-translational protein modification; TAS:Reactome.
DR GO; GO:0006457; P:protein folding; TAS:Reactome.
DR GO; GO:0018279; P:protein N-linked glycosylation via asparagine; TAS:Reactome.
DR GO; GO:0009306; P:protein secretion; TAS:ProtInc.
DR GO; GO:0048488; P:synaptic vesicle endocytosis; ISS:UniProtKB.
DR Gene3D; 2.10.250.10; -; 1.
DR Gene3D; 2.60.120.200; -; 1.
DR InterPro; IPR001580; Calret/calnex.
DR InterPro; IPR018124; Calret/calnex_CS.
DR InterPro; IPR009033; Calreticulin/calnexin_P_dom.
DR InterPro; IPR008985; ConA-like_lec_gl_sf.
DR InterPro; IPR013320; ConA-like_subgrp.
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; Complete proteome;
KW Direct protein sequencing; Disulfide bond; Endoplasmic reticulum;
KW Lectin; Lipoprotein; Membrane; Metal-binding; Palmitate;
KW Phosphoprotein; Reference proteome; Repeat; Signal; Transmembrane;
KW Transmembrane helix.
FT SIGNAL 1 20 Potential.
FT CHAIN 21 592 Calnexin.
FT /FTId=PRO_0000004198.
FT TOPO_DOM 21 481 Lumenal (Potential).
FT TRANSMEM 482 502 Helical; (Potential).
FT TOPO_DOM 503 592 Cytoplasmic (Potential).
FT REPEAT 278 290 1-1.
FT REPEAT 295 307 1-2.
FT REPEAT 314 326 1-3.
FT REPEAT 333 345 1-4.
FT REPEAT 348 358 2-1.
FT REPEAT 367 377 2-2.
FT REPEAT 381 391 2-3.
FT REPEAT 395 405 2-4.
FT REGION 276 409 P domain (Extended arm) (By similarity).
FT REGION 278 345 4 X approximate repeats.
FT REGION 348 405 4 X approximate repeats.
FT REGION 503 592 Sufficient to mediate interaction with
FT SGIP1 (By similarity).
FT METAL 74 74 Calcium; via carbonyl oxygen (By
FT similarity).
FT METAL 117 117 Calcium; via carbonyl oxygen (By
FT similarity).
FT METAL 436 436 Calcium (By similarity).
FT BINDING 164 164 Carbohydrate (By similarity).
FT BINDING 166 166 Carbohydrate (By similarity).
FT BINDING 185 185 Carbohydrate (By similarity).
FT BINDING 216 216 Carbohydrate (By similarity).
FT MOD_RES 137 137 N6-acetyllysine.
FT MOD_RES 554 554 Phosphoserine.
FT MOD_RES 562 562 Phosphothreonine.
FT MOD_RES 564 564 Phosphoserine; by MAPK3.
FT MOD_RES 583 583 Phosphoserine.
FT LIPID 502 502 S-palmitoyl cysteine.
FT LIPID 503 503 S-palmitoyl cysteine.
FT DISULFID 160 194 By similarity.
FT DISULFID 360 366 By similarity.
FT CONFLICT 179 179 F -> L (in Ref. 2; AAA21749).
FT CONFLICT 431 433 SDI -> LTF (in Ref. 9; AAA35696).
FT CONFLICT 480 480 R -> L (in Ref. 9; AAA35696).
SQ SEQUENCE 592 AA; 67568 MW; EDE094D9B82261EE CRC64;
MEGKWLLCML LVLGTAIVEA HDGHDDDVID IEDDLDDVIE EVEDSKPDTT APPSSPKVTY
KAPVPTGEVY FADSFDRGTL SGWILSKAKK DDTDDEIAKY DGKWEVEEMK ESKLPGDKGL
VLMSRAKHHA ISAKLNKPFL FDTKPLIVQY EVNFQNGIEC GGAYVKLLSK TPELNLDQFH
DKTPYTIMFG PDKCGEDYKL HFIFRHKNPK TGIYEEKHAK RPDADLKTYF TDKKTHLYTL
ILNPDNSFEI LVDQSVVNSG NLLNDMTPPV NPSREIEDPE DRKPEDWDER PKIPDPEAVK
PDDWDEDAPA KIPDEEATKP EGWLDDEPEY VPDPDAEKPE DWDEDMDGEW EAPQIANPRC
ESAPGCGVWQ RPVIDNPNYK GKWKPPMIDN PSYQGIWKPR KIPNPDFFED LEPFRMTPFS
AIGLELWSMT SDIFFDNFII CADRRIVDDW ANDGWGLKKA ADGAAEPGVV GQMIEAAEER
PWLWVVYILT VALPVFLVIL FCCSGKKQTS GMEYKKTDAP QPDVKEEEEE KEEEKDKGDE
EEEGEEKLEE KQKSDAEEDG GTVSQEEEDR KPKAEEDEIL NRSPRNRKPR RE
//
MIM
114217
*RECORD*
*FIELD* NO
114217
*FIELD* TI
*114217 CALNEXIN; CANX
;;CNX
*FIELD* TX
DESCRIPTION
Calnexin is a ubiquitously expressed molecular lectin-like chaperone.
read moreTogether with calreticulin (CALR; 109091), calnexin promotes folding of
glycosylated proteins in the endoplasmic reticulum (ER) (summary by
Kraus et al., 2010).
CLONING
Calnexin is a 90-kilodalton integral membrane protein of the ER. It
exhibits high affinity for binding calcium ions, which was the means by
which it was first identified. Calcium ions are known to play a central
role in the regulation of cellular metabolism, including signal
transduction events and the transport of proteins through the ER.
Calnexin has been shown to be associated with several cell surface
proteins during translocation through the ER and has been isolated as a
complex with other ER proteins involved in calcium ion-dependent
retention of proteins. Tjoelker et al. (1994) isolated cDNA clones of
the human, mouse, and rat calnexins. Comparisons of the sequences
demonstrated a high level of conservation of sequence identity,
suggesting that calnexin performs important cellular functions.
Schwann cell-derived peripheral myelin protein-22 (PMP22; 601097), when
mutated or overexpressed, causes heritable neuropathies with a
'gain-of-function' endoplasmic reticulum (ER) phenotype. PMP22
associates in a specific and transient manner with CANX in wildtype
sciatic nerves. In the sciatic nerves of the Trembler (TrJ) mouse
carrying the same mutation in the PMP22 gene that causes
Charcot-Marie-Tooth disease (CMT) in the human, Dickson et al. (2002)
found prolonged association of mutant PMP22 with CANX. In cultured cells
expressing the TrJ mutant PMP22, CANX and PMP22 colocalized in large
intracellular structures identified at the electron microscopy level as
myelin-like figures, with CANX localization in the structures dependent
on PMP22 glucosylation. Similar intracellular myelin-like figures were
also present in Schwann cells of sciatic nerves from homozygous TrJ
mice. Sequestration of CANX in intracellular myelin-like figures may be
relevant to the pathogenesis of autosomal dominant CMT-related
neuropathies.
GENE FUNCTION
Using human cell lines, Mueller et al. (2008) identified several
components of a protein complex required for retrotranslocation or
dislocation of misfolded proteins from the ER lumen to the cytosol for
proteasome-dependent degradation. These included SEL1L (602329), HRD1
(SYVN1; 608046), derlin-2 (DERL2; 610304), the ATPase p97 (VCP; 601023),
PDI (P4HB; 176790), BIP (HSPA5; 138120), calnexin, AUP1 (602434), UBXD8
(FAF2), UBC6E (UBE2J1), and OS9 (609677).
BIOCHEMICAL FEATURES
Schrag et al. (2001) determined the 3-dimensional structure of the
luminal domain of calnexin to 2.9-angstrom resolution. The structure
revealed an extended 140-angstrom arm inserted into a beta sandwich
structure characteristic of legume lectins. The arm is composed of
tandem repeats of 2 proline-rich sequence motifs that interact with one
another in a head-to-tail fashion. Identification of the ligand-binding
site established calnexin as a monovalent lectin, providing insight into
the mechanism by which the calnexin family of chaperones interacts with
monoglucosylated glycoproteins.
MAPPING
Gray et al. (1993) hybridized a CANX cDNA probe to Southern blots of a
panel of 31 EcoRI-digested somatic cell human-mouse hybrid DNAs. The
CANX probe segregated concordantly with chromosome 5. In situ
hybridization with a tritium-labeled calnexin cDNA probe regionally
localized the CANX gene to 5q35. Tjoelker et al. (1994) reported the
details of the mapping of the human CANX gene to 5q35 as reported in
abstract by Gray et al. (1993).
ANIMAL MODEL
Denzel et al. (2002) found that Canx-null mice were born at the expected
mendelian ratio and appeared normal, but about half died within the
first 48 hours after birth. After 8 to 10 days, surviving Canx-null mice
were significantly smaller than wildtype littermates. They developed an
unstable gait with marked truncal ataxia and abnormal behavioral
reflexes, and they eventually stopped moving and feeding.
Histopathologic analysis detected decreased numbers of large to medium
myelinated fibers within the sciatic nerve, and loss of large fibers
correlated with the severity of the phenotype.
Kraus et al. (2010) found that Canx -/- mice were indistinguishable from
wildtype mice at birth and had a normal life span and fertility.
However, Caxn -/- mice grew more slowly than wildtype or Caxn +/-
littermates, and they showed neurologic abnormalities, including gait
disturbance with instability, splaying of the hind limbs, ataxia,
tremors, lower limb motor defects, and a rolling walk. Canx -/- brain
and spinal cord appeared normal, with normal number and distribution of
motoneurons, and sympathetic neurons grew normally in culture. Electron
microscopic analysis of spinal cord and sciatic nerve of Caxn -/- mice
revealed defective formation and compaction of myelin sheaths. In Caxn
-/- brain, abnormalities were observed in large white matter tracts.
Electrophysiologic recordings of isolated Caxn -/- neonatal spinal cord
showed reduced conduction velocity. Examination of Caxn -/- retinas
showed increased numbers of nuclei in the outer and inner nuclear
layers, disorganized nuclei, and vacuolization in the retinal pigment
epithelial layer. Histologic examination of other tissues in Canx -/-
mice, including immune tissues, failed to detect gross abnormalities.
*FIELD* RF
1. Denzel, A.; Molinari, M.; Trigueros, C.; Martin, J. E.; Velmurgan,
S.; Brown, S.; Stamp, G.; Owen, M. J.: Early postnatal death and
motor disorders in mice congenitally deficient in calnexin expression. Molec.
Cell. Biol. 22: 7398-7404, 2002.
2. Dickson, K. M.; Bergeron, J. J. M.; Shames, I.; Colby, J.; Nguyen,
D. T.; Chevet, E.; Thomas, D. Y.; Snipes, G. J.: Association of calnexin
with mutant peripheral myelin protein-22 ex vivo: a basis for 'gain-of-function'
ER diseases. Proc. Nat. Acad. Sci. 99: 9852-9857, 2002.
3. Gray, P. W.; Byers, M. G.; Eddy, R. L.; Shows, T. B.: The assignment
of the calnexin gene to the q35 region of chromosome 5. (Abstract) Human
Genome Mapping Workshop 93 9 only, 1993.
4. Kraus, A.; Groenendyk, J.; Bedard, K.; Baldwin, T. A.; Krause,
K.-H.; Dubois-Dauphin, M.; Dyck, J.; Rosenbaum, E. E.; Korngut, L.;
Colley, N. J.; Gosgnach, S.; Zochodne, D.; Todd, K.; Agellon, L. B.;
Michalak, M.: Calnexin deficiency leads to dysmyelination. J. Biol.
Chem. 285: 18928-18938, 2010.
5. Mueller, B.; Klemm, E. J.; Spooner, E.; Claessen, J. H.; Ploegh,
H. L.: SEL1L nucleates a protein complex required for dislocation
of misfolded glycoproteins. Proc. Nat. Acad. Sci. 105: 12325-12330,
2008.
6. Schrag, J. D.; Bergeron, J. J. M.; Li, Y.; Borisova, S.; Hahn,
M.; Thomas, D. Y.; Cygler, M.: The structure of calnexin, an ER chaperone
involved in quality control of protein folding. Molec. Cell 8: 633-644,
2001.
7. Tjoelker, L. W.; Seyfried, C. E.; Eddy, R. L., Jr.; Byers, M. G.;
Shows, T. B.; Calderon, J.; Schreiber, R. B.; Gray, P. W.: Human,
mouse, and rat calnexin cDNA cloning: identification of potential
calcium binding motifs and gene localization to human chromosome 5. Biochemistry 33:
3229-3236, 1994.
*FIELD* CN
Patricia A. Hartz - updated: 12/27/2010
Patricia A. Hartz - updated: 11/10/2009
Patricia A. Hartz - updated: 8/30/2006
Victor A. McKusick - updated: 9/20/2002
Stylianos E. Antonarakis - updated: 11/6/2001
*FIELD* CD
Victor A. McKusick: 12/6/1993
*FIELD* ED
mgross: 01/12/2011
mgross: 1/12/2011
mgross: 1/11/2011
terry: 12/27/2010
mgross: 11/10/2009
wwang: 9/6/2006
terry: 8/30/2006
terry: 7/26/2006
tkritzer: 9/24/2002
carol: 9/20/2002
mgross: 9/20/2002
mgross: 11/6/2001
carol: 5/20/1994
carol: 12/6/1993
*RECORD*
*FIELD* NO
114217
*FIELD* TI
*114217 CALNEXIN; CANX
;;CNX
*FIELD* TX
DESCRIPTION
Calnexin is a ubiquitously expressed molecular lectin-like chaperone.
read moreTogether with calreticulin (CALR; 109091), calnexin promotes folding of
glycosylated proteins in the endoplasmic reticulum (ER) (summary by
Kraus et al., 2010).
CLONING
Calnexin is a 90-kilodalton integral membrane protein of the ER. It
exhibits high affinity for binding calcium ions, which was the means by
which it was first identified. Calcium ions are known to play a central
role in the regulation of cellular metabolism, including signal
transduction events and the transport of proteins through the ER.
Calnexin has been shown to be associated with several cell surface
proteins during translocation through the ER and has been isolated as a
complex with other ER proteins involved in calcium ion-dependent
retention of proteins. Tjoelker et al. (1994) isolated cDNA clones of
the human, mouse, and rat calnexins. Comparisons of the sequences
demonstrated a high level of conservation of sequence identity,
suggesting that calnexin performs important cellular functions.
Schwann cell-derived peripheral myelin protein-22 (PMP22; 601097), when
mutated or overexpressed, causes heritable neuropathies with a
'gain-of-function' endoplasmic reticulum (ER) phenotype. PMP22
associates in a specific and transient manner with CANX in wildtype
sciatic nerves. In the sciatic nerves of the Trembler (TrJ) mouse
carrying the same mutation in the PMP22 gene that causes
Charcot-Marie-Tooth disease (CMT) in the human, Dickson et al. (2002)
found prolonged association of mutant PMP22 with CANX. In cultured cells
expressing the TrJ mutant PMP22, CANX and PMP22 colocalized in large
intracellular structures identified at the electron microscopy level as
myelin-like figures, with CANX localization in the structures dependent
on PMP22 glucosylation. Similar intracellular myelin-like figures were
also present in Schwann cells of sciatic nerves from homozygous TrJ
mice. Sequestration of CANX in intracellular myelin-like figures may be
relevant to the pathogenesis of autosomal dominant CMT-related
neuropathies.
GENE FUNCTION
Using human cell lines, Mueller et al. (2008) identified several
components of a protein complex required for retrotranslocation or
dislocation of misfolded proteins from the ER lumen to the cytosol for
proteasome-dependent degradation. These included SEL1L (602329), HRD1
(SYVN1; 608046), derlin-2 (DERL2; 610304), the ATPase p97 (VCP; 601023),
PDI (P4HB; 176790), BIP (HSPA5; 138120), calnexin, AUP1 (602434), UBXD8
(FAF2), UBC6E (UBE2J1), and OS9 (609677).
BIOCHEMICAL FEATURES
Schrag et al. (2001) determined the 3-dimensional structure of the
luminal domain of calnexin to 2.9-angstrom resolution. The structure
revealed an extended 140-angstrom arm inserted into a beta sandwich
structure characteristic of legume lectins. The arm is composed of
tandem repeats of 2 proline-rich sequence motifs that interact with one
another in a head-to-tail fashion. Identification of the ligand-binding
site established calnexin as a monovalent lectin, providing insight into
the mechanism by which the calnexin family of chaperones interacts with
monoglucosylated glycoproteins.
MAPPING
Gray et al. (1993) hybridized a CANX cDNA probe to Southern blots of a
panel of 31 EcoRI-digested somatic cell human-mouse hybrid DNAs. The
CANX probe segregated concordantly with chromosome 5. In situ
hybridization with a tritium-labeled calnexin cDNA probe regionally
localized the CANX gene to 5q35. Tjoelker et al. (1994) reported the
details of the mapping of the human CANX gene to 5q35 as reported in
abstract by Gray et al. (1993).
ANIMAL MODEL
Denzel et al. (2002) found that Canx-null mice were born at the expected
mendelian ratio and appeared normal, but about half died within the
first 48 hours after birth. After 8 to 10 days, surviving Canx-null mice
were significantly smaller than wildtype littermates. They developed an
unstable gait with marked truncal ataxia and abnormal behavioral
reflexes, and they eventually stopped moving and feeding.
Histopathologic analysis detected decreased numbers of large to medium
myelinated fibers within the sciatic nerve, and loss of large fibers
correlated with the severity of the phenotype.
Kraus et al. (2010) found that Canx -/- mice were indistinguishable from
wildtype mice at birth and had a normal life span and fertility.
However, Caxn -/- mice grew more slowly than wildtype or Caxn +/-
littermates, and they showed neurologic abnormalities, including gait
disturbance with instability, splaying of the hind limbs, ataxia,
tremors, lower limb motor defects, and a rolling walk. Canx -/- brain
and spinal cord appeared normal, with normal number and distribution of
motoneurons, and sympathetic neurons grew normally in culture. Electron
microscopic analysis of spinal cord and sciatic nerve of Caxn -/- mice
revealed defective formation and compaction of myelin sheaths. In Caxn
-/- brain, abnormalities were observed in large white matter tracts.
Electrophysiologic recordings of isolated Caxn -/- neonatal spinal cord
showed reduced conduction velocity. Examination of Caxn -/- retinas
showed increased numbers of nuclei in the outer and inner nuclear
layers, disorganized nuclei, and vacuolization in the retinal pigment
epithelial layer. Histologic examination of other tissues in Canx -/-
mice, including immune tissues, failed to detect gross abnormalities.
*FIELD* RF
1. Denzel, A.; Molinari, M.; Trigueros, C.; Martin, J. E.; Velmurgan,
S.; Brown, S.; Stamp, G.; Owen, M. J.: Early postnatal death and
motor disorders in mice congenitally deficient in calnexin expression. Molec.
Cell. Biol. 22: 7398-7404, 2002.
2. Dickson, K. M.; Bergeron, J. J. M.; Shames, I.; Colby, J.; Nguyen,
D. T.; Chevet, E.; Thomas, D. Y.; Snipes, G. J.: Association of calnexin
with mutant peripheral myelin protein-22 ex vivo: a basis for 'gain-of-function'
ER diseases. Proc. Nat. Acad. Sci. 99: 9852-9857, 2002.
3. Gray, P. W.; Byers, M. G.; Eddy, R. L.; Shows, T. B.: The assignment
of the calnexin gene to the q35 region of chromosome 5. (Abstract) Human
Genome Mapping Workshop 93 9 only, 1993.
4. Kraus, A.; Groenendyk, J.; Bedard, K.; Baldwin, T. A.; Krause,
K.-H.; Dubois-Dauphin, M.; Dyck, J.; Rosenbaum, E. E.; Korngut, L.;
Colley, N. J.; Gosgnach, S.; Zochodne, D.; Todd, K.; Agellon, L. B.;
Michalak, M.: Calnexin deficiency leads to dysmyelination. J. Biol.
Chem. 285: 18928-18938, 2010.
5. Mueller, B.; Klemm, E. J.; Spooner, E.; Claessen, J. H.; Ploegh,
H. L.: SEL1L nucleates a protein complex required for dislocation
of misfolded glycoproteins. Proc. Nat. Acad. Sci. 105: 12325-12330,
2008.
6. Schrag, J. D.; Bergeron, J. J. M.; Li, Y.; Borisova, S.; Hahn,
M.; Thomas, D. Y.; Cygler, M.: The structure of calnexin, an ER chaperone
involved in quality control of protein folding. Molec. Cell 8: 633-644,
2001.
7. Tjoelker, L. W.; Seyfried, C. E.; Eddy, R. L., Jr.; Byers, M. G.;
Shows, T. B.; Calderon, J.; Schreiber, R. B.; Gray, P. W.: Human,
mouse, and rat calnexin cDNA cloning: identification of potential
calcium binding motifs and gene localization to human chromosome 5. Biochemistry 33:
3229-3236, 1994.
*FIELD* CN
Patricia A. Hartz - updated: 12/27/2010
Patricia A. Hartz - updated: 11/10/2009
Patricia A. Hartz - updated: 8/30/2006
Victor A. McKusick - updated: 9/20/2002
Stylianos E. Antonarakis - updated: 11/6/2001
*FIELD* CD
Victor A. McKusick: 12/6/1993
*FIELD* ED
mgross: 01/12/2011
mgross: 1/12/2011
mgross: 1/11/2011
terry: 12/27/2010
mgross: 11/10/2009
wwang: 9/6/2006
terry: 8/30/2006
terry: 7/26/2006
tkritzer: 9/24/2002
carol: 9/20/2002
mgross: 9/20/2002
mgross: 11/6/2001
carol: 5/20/1994
carol: 12/6/1993