P35564 (CALX_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Calnexin

Gene names

Name:

Canx

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	591 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Calcium-binding protein that interacts with newly synthesized glycoproteins in the endoplasmic reticulum. It may act in assisting protein assembly and/or in the retention within the ER of unassembled protein subunits. It seems to play a major role in the quality control apparatus of the ER by the retention of incorrectly folded proteins. Associated with partial T-cell antigen receptor complexes that escape the ER of immature thymocytes, it may function as a signaling complex regulating thymocyte maturation. Additionally it may play a role in receptor-mediated endocytosis at the synapse. Ref.5 Ref.15
Subunit structure	Interacts with MAPK3/ERK1 By similarity. Interacts with KCNH2 By similarity. Associates with ribosomes. The palmitoylated form interacts with the ribosome-translocon complex component SSR1, promoting efficient folding of glycoproteins By similarity. Interacts with SGIP1; involved in negative regulation of endocytosis. Ref.15
Subcellular location	Endoplasmic reticulum membrane; Single-pass type I membrane protein. Melanosome By similarity. Note: The palmitoylated form preferentially localizes to the perinuclear rough ER By similarity. When bound to CD3 epsilon chains, calnexin's ER retention signal can be masked, permitting it to escape ER retention. Ref.5
Post-translational modification	Phosphorylated at Ser-563 by MAPK3/ERK1. phosphorylation by MAPK3/ERK1 increases its association with ribosomes By similarity. Palmitoylation by DHHC6 leads to the preferential localization to the perinuclear rough ER. It mediates the association of calnexin with the ribosome-translocon complex (RTC) which is required for efficient folding of glycosylated proteins By similarity.
Sequence similarities	Belongs to the calreticulin family.

Ontologies

Keywords
Cellular component	Endoplasmic reticulum Membrane
Domain	Repeat Signal Transmembrane Transmembrane helix
Ligand	Calcium Lectin Metal-binding
Molecular function	Chaperone
PTM	Acetylation Disulfide bond Lipoprotein Palmitate Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	aging Inferred from electronic annotation. Source: Compara clathrin-mediated endocytosis Inferred from mutant phenotype Ref.15. Source: UniProtKB protein folding Inferred from electronic annotation. Source: InterPro synaptic vesicle endocytosis Inferred from mutant phenotype Ref.15. Source: UniProtKB
Cellular_component	axon Inferred from electronic annotation. Source: Compara dendrite cytoplasm Inferred from electronic annotation. Source: Compara dendritic spine Inferred from electronic annotation. Source: Compara integral to lumenal side of endoplasmic reticulum membrane Traceable author statement. Source: Reactome melanosome Inferred from electronic annotation. Source: UniProtKB-SubCell neuronal cell body Inferred from electronic annotation. Source: Compara ribosome Inferred from electronic annotation. Source: Compara
Molecular_function	calcium ion binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
Sgip1	Q8VD37	3	EBI-738422,EBI-776269

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 20	20	Potential
	Chain	21 – 591	571	Calnexin		PRO_0000004199
Regions
	Topological domain	21 – 482	462	Lumenal Potential
	Transmembrane	483 – 503	21	Helical; Potential
	Topological domain	504 – 591	88	Cytoplasmic Potential
	Repeat	279 – 291	13	1-1
	Repeat	296 – 308	13	1-2
	Repeat	315 – 327	13	1-3
	Repeat	334 – 346	13	1-4
	Repeat	349 – 359	11	2-1
	Repeat	368 – 378	11	2-2
	Repeat	382 – 392	11	2-3
	Repeat	396 – 406	11	2-4
	Region	277 – 410	134	P domain (Extended arm) By similarity
	Region	279 – 346	68	4 X approximate repeats
	Region	349 – 406	58	4 X approximate repeats
	Region	504 – 591	88	Sufficient to mediate interaction with SGIP1
Sites
	Metal binding	75	1	Calcium; via carbonyl oxygen By similarity
	Metal binding	118	1	Calcium; via carbonyl oxygen By similarity
	Metal binding	437	1	Calcium By similarity
	Binding site	165	1	Carbohydrate By similarity
	Binding site	167	1	Carbohydrate By similarity
	Binding site	186	1	Carbohydrate By similarity
	Binding site	217	1	Carbohydrate By similarity
Amino acid modifications
	Modified residue	138	1	N6-acetyllysine By similarity
	Modified residue	553	1	Phosphoserine Ref.7 Ref.8 Ref.9 Ref.10 Ref.12 Ref.13
	Modified residue	561	1	Phosphothreonine Ref.8 Ref.9
	Modified residue	563	1	Phosphoserine; by MAPK3 Ref.7 Ref.8 Ref.9 Ref.10 Ref.12
	Modified residue	569	1	Phosphoserine Ref.10
	Modified residue	582	1	Phosphoserine Ref.6 Ref.9 Ref.10 Ref.11 Ref.12 Ref.13 Ref.14
	Lipidation	503	1	S-palmitoyl cysteine By similarity
	Lipidation	504	1	S-palmitoyl cysteine By similarity
	Disulfide bond	161 ↔ 195		By similarity
	Disulfide bond	361 ↔ 367		By similarity
Experimental info
	Sequence conflict	416	1	K → R in AAA62450. Ref.4
	Sequence conflict	468	1	P → L in AAA62450. Ref.4
	Sequence conflict	472	1	L → G in AAA62450. Ref.4
	Sequence conflict	538	1	R → G in AAA62450. Ref.4
	Sequence conflict	560	1	V → G in AAA62450. Ref.4

Sequences

	Sequence		Length	Mass (Da)
	P35564 [UniParc]. Last modified June 1, 1994. Version 1. Checksum: 0D9F8FE03434BADC	FASTA	591	67,278
	10 20 30 40 50 60 MEGKWLLCLL LVLGTAAVEA HDGHDDDAID IEDDLDDVIE EVEDSKSKSD ASTPPSPKVT 70 80 90 100 110 120 YKAPVPTGEV YFADSFDRGS LSGWILSKAK KDDTDDEIAK YDGKWEVDEM KETKLPGDKG 130 140 150 160 170 180 LVLMSRAKHH AISAKLNKPF LFDTKPLIVQ YEVNFQNGIE CGGAYVKLLS KTAELSLDQF 190 200 210 220 230 240 HDKTPYTIMF GPDKCGEDYK LHFIFRHKNP KTGVYEEKHA KRPDADLKTY FTDKKTHLYT 250 260 270 280 290 300 LILNPDNSFE ILVDQSVVNS GNLLNDMTPP VNPSREIEDP EDRKPEDWDE RPKIADPDAV 310 320 330 340 350 360 KPDDWDEDAP SKIPDEEATK PEGWLDDEPE YIPDPDAEKP EDWDEDMDGE WEAPQIANPK 370 380 390 400 410 420 CESAPGCGVW QRPMIDNPNY KGKWKPPMID NPNYQGIWKP RKIPNPDFFE DLEPFKMTPF 430 440 450 460 470 480 SAIGLELWSM TSDIFFDNFI ISGDRRVVDD WANDGWGLKK AADGAAEPGV VLQMLEAAEE 490 500 510 520 530 540 RPWLWVVYIL TVALPVFLVI LFCCSGKKQS NAMEYKKTDA PQPDVKDEEG KEEEKNKRDE 550 560 570 580 590 EEEEEKLEEK QKSDAEEDGV TGSQDEEDSK PKAEEDEILN RSPRNRKPRR E

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Human, mouse, and rat calnexin cDNA cloning: identification of potential calcium binding motifs and gene localization to human chromosome 5." Tjoelker L.W., Seyfried C.E., Eddy R.L. Jr., Shows T.B. Jr., Calderon J., Schreiber R.B., Gray P.W. Biochemistry 33:3229-3236(1994) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Strain: FVB/N. Tissue: Mammary gland.
[3]	"The transcriptional landscape of the mammalian genome." Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y. Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-155. Strain: C57BL/6J. Tissue: Eye.
[4]	"Class II histocompatibility molecules associate with calnexin during assembly in the endoplasmic reticulum." Schreiber K.L., Bell M.P., Huntoon C.J., Rajagopalan S., Brenner M.B., McKean D.J. Int. Immunol. 6:101-111(1994) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 21-591. Strain: BALB/c.
[5]	"The molecular chaperone calnexin is expressed on the surface of immature thymocytes in association with clonotype-independent CD3 complexes." Wiest D.L., Burgess W.H., McKean D., Kearse K.P., Singer A. EMBO J. 14:3425-3433(1995) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN THYMOCYTE MATURATION, SUBCELLULAR LOCATION.
[6]	"Identification of phosphoproteins and their phosphorylation sites in the WEHI-231 B lymphoma cell line." Shu H., Chen S., Bi Q., Mumby M., Brekken D.L. Mol. Cell. Proteomics 3:279-286(2004) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-582, MASS SPECTROMETRY. Tissue: B-cell lymphoma.
[7]	"Proteomic analysis of in vivo phosphorylated synaptic proteins." Collins M.O., Yu L., Coba M.P., Husi H., Campuzano I., Blackstock W.P., Choudhary J.S., Grant S.G. J. Biol. Chem. 280:5972-5982(2005) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-553 AND SER-563, MASS SPECTROMETRY. Tissue: Forebrain.
[8]	"A differential phosphoproteomic analysis of retinoic acid-treated P19 cells." Smith J.C., Duchesne M.A., Tozzi P., Ethier M., Figeys D. J. Proteome Res. 6:3174-3186(2007) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-553; THR-561 AND SER-563, MASS SPECTROMETRY. Tissue: Teratocarcinoma.
[9]	"Qualitative and quantitative analyses of protein phosphorylation in naive and stimulated mouse synaptosomal preparations." Munton R.P., Tweedie-Cullen R., Livingstone-Zatchej M., Weinandy F., Waidelich M., Longo D., Gehrig P., Potthast F., Rutishauser D., Gerrits B., Panse C., Schlapbach R., Mansuy I.M. Mol. Cell. Proteomics 6:283-293(2007) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-553; THR-561; SER-563 AND SER-582, MASS SPECTROMETRY. Tissue: Brain cortex.
[10]	"Mitochondrial phosphoproteome revealed by an improved IMAC method and MS/MS/MS." Lee J., Xu Y., Chen Y., Sprung R., Kim S.C., Xie S., Zhao Y. Mol. Cell. Proteomics 6:669-676(2007) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-553; SER-563; SER-569 AND SER-582, MASS SPECTROMETRY. Tissue: Liver.
[11]	"Specific phosphopeptide enrichment with immobilized titanium ion affinity chromatography adsorbent for phosphoproteome analysis." Zhou H., Ye M., Dong J., Han G., Jiang X., Wu R., Zou H. J. Proteome Res. 7:3957-3967(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-582, MASS SPECTROMETRY. Tissue: Liver.
[12]	"Solid tumor proteome and phosphoproteome analysis by high resolution mass spectrometry." Zanivan S., Gnad F., Wickstroem S.A., Geiger T., Macek B., Cox J., Faessler R., Mann M. J. Proteome Res. 7:5314-5326(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-553; SER-563 AND SER-582, MASS SPECTROMETRY. Tissue: Melanoma.
[13]	"The phagosomal proteome in interferon-gamma-activated macrophages." Trost M., English L., Lemieux S., Courcelles M., Desjardins M., Thibault P. Immunity 30:143-154(2009) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-553 AND SER-582, MASS SPECTROMETRY. Tissue: Macrophage.
[14]	"Large scale localization of protein phosphorylation by use of electron capture dissociation mass spectrometry." Sweet S.M., Bailey C.M., Cunningham D.L., Heath J.K., Cooper H.J. Mol. Cell. Proteomics 8:904-912(2009) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-582, MASS SPECTROMETRY. Tissue: Embryonic fibroblast.
[15]	"Enhanced clathrin-dependent endocytosis in the absence of calnexin." Li H.D., Liu W.X., Michalak M. PLoS ONE 6:E21678-E21678(2011) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH SGIP1.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	L18888 mRNA. Translation: AAA21014.1. BC012408 mRNA. Translation: AAH12408.1. BC040244 mRNA. Translation: AAH40244.1. AK084175 mRNA. Translation: BAC39133.1. L23865 mRNA. Translation: AAA62450.1.
IPI	IPI00119618.
PIR	B54354.
RefSeq	NP_001103969.1. NM_001110499.1. NP_001103970.1. NM_001110500.1. NP_031623.1. NM_007597.3.
UniGene	Mm.248827.
3D structure databases
ProteinModelPortal	P35564.
SMR	P35564. Positions 61-458.
ModBase	Search...
Protein-protein interaction databases
IntAct	P35564. 6 interactions.
MINT	MINT-1862151.
PTM databases
PhosphoSite	P35564.
Proteomic databases
PaxDb	P35564.
PRIDE	P35564.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000020637; ENSMUSP00000020637; ENSMUSG00000020368. ENSMUST00000179865; ENSMUSP00000137440; ENSMUSG00000020368.
GeneID	12330.
KEGG	mmu:12330.
Organism-specific databases
CTD	821.
MGI	MGI:88261. Canx.
Phylogenomic databases
eggNOG	NOG305105.
HOGENOM	HOG000192436.
HOVERGEN	HBG005407.
InParanoid	P35564.
KO	K08054.
OMA	CCSGKKQ.
OrthoDB	EOG4DBTDB.
Enzyme and pathway databases
Reactome	REACT_107772. Immune System.
Gene expression databases
ArrayExpress	P35564.
Bgee	P35564.
CleanEx	MM_CANX.
Genevestigator	P35564.
GermOnline	ENSMUSG00000020368. Mus musculus.
Family and domain databases
Gene3D	2.10.250.10. 1 hit. 2.60.120.200. 1 hit.
InterPro	IPR001580. Calret/calnex. IPR018124. Calret/calnex_CS. IPR009033. Calreticulin/calnexin_P_dom. IPR008985. ConA-like_lec_gl_sf. IPR013320. ConA-like_subgrp. [Graphical view]
PANTHER	PTHR11073. PTHR11073. 1 hit.
Pfam	PF00262. Calreticulin. 1 hit. [Graphical view]
PRINTS	PR00626. CALRETICULIN.
SUPFAM	SSF63887. Calret_calnex_P. 1 hit. SSF49899. ConA_like_lec_gl. 2 hits.
PROSITE	PS00803. CALRETICULIN_1. 1 hit. PS00804. CALRETICULIN_2. 1 hit. PS00805. CALRETICULIN_REPEAT. 3 hits. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	CANX. mouse.
NextBio	280926.
PMAP-CutDB	P35564.
SOURCE	Search...

Entry information

Entry name

CALX_MOUSE

Accession

Primary (citable) accession number: P35564

Entry history

Integrated into UniProtKB/Swiss-Prot:	June 1, 1994
Last sequence update:	June 1, 1994
Last modified:	April 3, 2013
This is version 128 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program