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Protein

Calnexin

Gene

CANX

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi74Calcium; via carbonyl oxygenBy similarity1
Metal bindingi117Calcium; via carbonyl oxygenBy similarity1
Binding sitei164CarbohydrateBy similarity1
Binding sitei166CarbohydrateBy similarity1
Binding sitei185CarbohydrateBy similarity1
Binding sitei216CarbohydrateBy similarity1
Metal bindingi436CalciumBy similarity1

GO - Molecular functioni

  • calcium ion binding Source: ProtInc
  • carbohydrate binding Source: UniProtKB-KW
  • glycoprotein binding Source: Ensembl
  • poly(A) RNA binding Source: UniProtKB

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Chaperone

Keywords - Ligandi

Calcium, Lectin, Metal-binding

Enzyme and pathway databases

BioCyciZFISH:ENSG00000127022-MONOMER.
ReactomeiR-HSA-168316. Assembly of Viral Components at the Budding Site.
R-HSA-2132295. MHC class II antigen presentation.
R-HSA-901042. Calnexin/calreticulin cycle.
R-HSA-983170. Antigen Presentation: Folding, assembly and peptide loading of class I MHC.

Names & Taxonomyi

Protein namesi
Recommended name:
Calnexin
Alternative name(s):
IP90
Major histocompatibility complex class I antigen-binding protein p88
p90
Gene namesi
Name:CANX
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 5

Organism-specific databases

HGNCiHGNC:1473. CANX.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini21 – 481LumenalSequence analysisAdd BLAST461
Transmembranei482 – 502HelicalSequence analysisAdd BLAST21
Topological domaini503 – 592CytoplasmicSequence analysisAdd BLAST90

GO - Cellular componenti

  • axon Source: Ensembl
  • dendrite cytoplasm Source: Ensembl
  • dendritic spine Source: Ensembl
  • endoplasmic reticulum Source: UniProtKB
  • endoplasmic reticulum lumen Source: Reactome
  • endoplasmic reticulum membrane Source: AgBase
  • ER-mitochondrion membrane contact site Source: MGI
  • extracellular exosome Source: UniProtKB
  • extracellular matrix Source: BHF-UCL
  • integral component of lumenal side of endoplasmic reticulum membrane Source: Reactome
  • melanosome Source: UniProtKB-SubCell
  • membrane Source: UniProtKB
  • myelin sheath Source: Ensembl
  • neuronal cell body Source: Ensembl
  • protein complex Source: Ensembl
  • ribosome Source: Ensembl
  • rough endoplasmic reticulum Source: Ensembl
  • smooth endoplasmic reticulum Source: Ensembl
Complete GO annotation...

Keywords - Cellular componenti

Endoplasmic reticulum, Membrane

Pathology & Biotechi

Organism-specific databases

DisGeNETi821.
OpenTargetsiENSG00000127022.
PharmGKBiPA26055.

Chemistry databases

ChEMBLiCHEMBL2719.
DrugBankiDB00025. Antihemophilic Factor (Recombinant).
DB00031. Tenecteplase.

Polymorphism and mutation databases

BioMutaiCANX.
DMDMi543920.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 20Sequence analysisCombined sourcesAdd BLAST20
ChainiPRO_000000419821 – 592CalnexinAdd BLAST572

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei137N6-acetyllysineCombined sources1
Disulfide bondi160 ↔ 194By similarity
Disulfide bondi360 ↔ 366By similarity
Lipidationi502S-palmitoyl cysteine1 Publication1
Lipidationi503S-palmitoyl cysteine1 Publication1
Modified residuei554PhosphoserineCombined sources1
Modified residuei562PhosphothreonineCombined sources1
Modified residuei564Phosphoserine; by MAPK3Combined sources1
Modified residuei583PhosphoserineCombined sources1

Post-translational modificationi

Phosphorylated at Ser-564 by MAPK3/ERK1. phosphorylation by MAPK3/ERK1 increases its association with ribosomes (By similarity).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.1 Publication
Ubiquitinated, leading to proteasomal degradation. Probably ubiquitinated by ZNRF4.1 Publication

Keywords - PTMi

Acetylation, Disulfide bond, Lipoprotein, Palmitate, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiP27824.
MaxQBiP27824.
PaxDbiP27824.
PeptideAtlasiP27824.
PRIDEiP27824.
TopDownProteomicsiP27824-1. [P27824-1]

PTM databases

iPTMnetiP27824.
PhosphoSitePlusiP27824.
SwissPalmiP27824.

Expressioni

Gene expression databases

BgeeiENSG00000127022.
CleanExiHS_CANX.
ExpressionAtlasiP27824. baseline and differential.
GenevisibleiP27824. HS.

Organism-specific databases

HPAiCAB004738.
HPA009433.
HPA009696.

Interactioni

Subunit structurei

Interacts with MAPK3/ERK1 (By similarity). Interacts with KCNH2 (PubMed:16361248). Associates with ribosomes (By similarity). Interacts with SGIP1; involved in negative regulation of endocytosis (By similarity). The palmitoylated form interacts with the ribosome-translocon complex component SSR1, promoting efficient folding of glycoproteins (PubMed:22314232). Interacts with SERPINA2P/SERPINA2 and with the S and Z variants of SERPINA1 (PubMed:23826168). Part of a complex which includes CANX, DERL1, DERL2, DDOST/OST48, RPN1, RPN2, SELK, STT3A, VCP AND VIMP (PubMed:22016385). Interacts with PPIB (PubMed:20801878). Interacts with ZNRF4 (PubMed:21205830).By similarity6 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
ATP2A2P116072EBI-355947,EBI-8004986From a different organism.
CFTRP135693EBI-355947,EBI-349854
NDRG1Q925972EBI-355947,EBI-716486
OPRD1P411432EBI-355947,EBI-2624456
RPL12P300503EBI-355947,EBI-352743
SEC61A1P616193EBI-355947,EBI-358919
SSR1P433075EBI-355947,EBI-714168

Protein-protein interaction databases

BioGridi107271. 214 interactors.
DIPiDIP-457N.
IntActiP27824. 94 interactors.
MINTiMINT-5000964.
STRINGi9606.ENSP00000247461.

Chemistry databases

BindingDBiP27824.

Structurei

3D structure databases

ProteinModelPortaliP27824.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Repeati278 – 2901-1Add BLAST13
Repeati295 – 3071-2Add BLAST13
Repeati314 – 3261-3Add BLAST13
Repeati333 – 3451-4Add BLAST13
Repeati348 – 3582-1Add BLAST11
Repeati367 – 3772-2Add BLAST11
Repeati381 – 3912-3Add BLAST11
Repeati395 – 4052-4Add BLAST11

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni276 – 409P domain (Extended arm)By similarityAdd BLAST134
Regioni278 – 3454 X approximate repeatsAdd BLAST68
Regioni326 – 359Interaction with PPIBBy similarityAdd BLAST34
Regioni348 – 4054 X approximate repeatsAdd BLAST58
Regioni503 – 592Sufficient to mediate interaction with SGIP1By similarityAdd BLAST90

Sequence similaritiesi

Belongs to the calreticulin family.Curated

Keywords - Domaini

Repeat, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG0675. Eukaryota.
ENOG410XP7T. LUCA.
GeneTreeiENSGT00430000030841.
HOGENOMiHOG000192436.
HOVERGENiHBG005407.
InParanoidiP27824.
KOiK08054.
OMAiLVILFCC.
OrthoDBiEOG091G04SS.
PhylomeDBiP27824.
TreeFamiTF300618.

Family and domain databases

Gene3Di2.10.250.10. 1 hit.
2.60.120.200. 1 hit.
InterProiIPR001580. Calret/calnex.
IPR018124. Calret/calnex_CS.
IPR009033. Calreticulin/calnexin_P_dom.
IPR013320. ConA-like_dom.
[Graphical view]
PANTHERiPTHR11073. PTHR11073. 1 hit.
PfamiPF00262. Calreticulin. 1 hit.
[Graphical view]
PRINTSiPR00626. CALRETICULIN.
SUPFAMiSSF49899. SSF49899. 2 hits.
SSF63887. SSF63887. 1 hit.
PROSITEiPS00803. CALRETICULIN_1. 1 hit.
PS00804. CALRETICULIN_2. 1 hit.
PS00805. CALRETICULIN_REPEAT. 3 hits.
[Graphical view]

Sequences (3)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P27824-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MEGKWLLCML LVLGTAIVEA HDGHDDDVID IEDDLDDVIE EVEDSKPDTT
60 70 80 90 100
APPSSPKVTY KAPVPTGEVY FADSFDRGTL SGWILSKAKK DDTDDEIAKY
110 120 130 140 150
DGKWEVEEMK ESKLPGDKGL VLMSRAKHHA ISAKLNKPFL FDTKPLIVQY
160 170 180 190 200
EVNFQNGIEC GGAYVKLLSK TPELNLDQFH DKTPYTIMFG PDKCGEDYKL
210 220 230 240 250
HFIFRHKNPK TGIYEEKHAK RPDADLKTYF TDKKTHLYTL ILNPDNSFEI
260 270 280 290 300
LVDQSVVNSG NLLNDMTPPV NPSREIEDPE DRKPEDWDER PKIPDPEAVK
310 320 330 340 350
PDDWDEDAPA KIPDEEATKP EGWLDDEPEY VPDPDAEKPE DWDEDMDGEW
360 370 380 390 400
EAPQIANPRC ESAPGCGVWQ RPVIDNPNYK GKWKPPMIDN PSYQGIWKPR
410 420 430 440 450
KIPNPDFFED LEPFRMTPFS AIGLELWSMT SDIFFDNFII CADRRIVDDW
460 470 480 490 500
ANDGWGLKKA ADGAAEPGVV GQMIEAAEER PWLWVVYILT VALPVFLVIL
510 520 530 540 550
FCCSGKKQTS GMEYKKTDAP QPDVKEEEEE KEEEKDKGDE EEEGEEKLEE
560 570 580 590
KQKSDAEEDG GTVSQEEEDR KPKAEEDEIL NRSPRNRKPR RE
Length:592
Mass (Da):67,568
Last modified:June 1, 1994 - v2
Checksum:iEDE094D9B82261EE
GO
Isoform 2 (identifier: P27824-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-1: M → MADRRTPTPFAGCRLPRQRRARDASQVSAPGTRRIM

Note: No experimental confirmation available.
Show »
Length:627
Mass (Da):71,503
Checksum:iE9AD69A866261080
GO
Isoform 3 (identifier: P27824-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-108: Missing.

Note: No experimental confirmation available.
Show »
Length:484
Mass (Da):55,598
Checksum:i61BB56B36E8C7A4C
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti179F → L in AAA21749 (PubMed:8136357).Curated1
Sequence conflicti431 – 433SDI → LTF in AAA35696 (PubMed:1326756).Curated3
Sequence conflicti480R → L in AAA35696 (PubMed:1326756).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0555151 – 108Missing in isoform 3. 1 PublicationAdd BLAST108
Alternative sequenceiVSP_0555161M → MADRRTPTPFAGCRLPRQRR ARDASQVSAPGTRRIM in isoform 2. 1 Publication1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L10284 mRNA. Translation: AAA36125.1.
L18887 mRNA. Translation: AAA21013.1.
M94859 mRNA. Translation: AAA21749.1.
M98452 mRNA. Translation: AAA35696.1.
AK294702 mRNA. Translation: BAG57859.1.
AK304420 mRNA. Translation: BAG65250.1.
AK312334 mRNA. Translation: BAG35255.1.
AC113426 Genomic DNA. No translation available.
AC136604 Genomic DNA. No translation available.
CH471165 Genomic DNA. Translation: EAW53802.1.
CH471165 Genomic DNA. Translation: EAW53803.1.
CH471165 Genomic DNA. Translation: EAW53805.1.
BC003552 mRNA. Translation: AAH03552.1.
BC042843 mRNA. Translation: AAH42843.1.
AJ271880 mRNA. Translation: CAB72137.1.
CCDSiCCDS4447.1. [P27824-1]
PIRiA46164.
A46673.
I53260.
RefSeqiNP_001019820.1. NM_001024649.1. [P27824-1]
NP_001737.1. NM_001746.3. [P27824-1]
XP_011532967.1. XM_011534665.2. [P27824-1]
UniGeneiHs.567968.

Genome annotation databases

EnsembliENST00000247461; ENSP00000247461; ENSG00000127022. [P27824-1]
ENST00000452673; ENSP00000391646; ENSG00000127022. [P27824-1]
ENST00000504734; ENSP00000424063; ENSG00000127022. [P27824-1]
GeneIDi821.
KEGGihsa:821.
UCSCiuc003mkk.4. human. [P27824-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Web resourcesi

Wikipedia

Calnexin entry

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L10284 mRNA. Translation: AAA36125.1.
L18887 mRNA. Translation: AAA21013.1.
M94859 mRNA. Translation: AAA21749.1.
M98452 mRNA. Translation: AAA35696.1.
AK294702 mRNA. Translation: BAG57859.1.
AK304420 mRNA. Translation: BAG65250.1.
AK312334 mRNA. Translation: BAG35255.1.
AC113426 Genomic DNA. No translation available.
AC136604 Genomic DNA. No translation available.
CH471165 Genomic DNA. Translation: EAW53802.1.
CH471165 Genomic DNA. Translation: EAW53803.1.
CH471165 Genomic DNA. Translation: EAW53805.1.
BC003552 mRNA. Translation: AAH03552.1.
BC042843 mRNA. Translation: AAH42843.1.
AJ271880 mRNA. Translation: CAB72137.1.
CCDSiCCDS4447.1. [P27824-1]
PIRiA46164.
A46673.
I53260.
RefSeqiNP_001019820.1. NM_001024649.1. [P27824-1]
NP_001737.1. NM_001746.3. [P27824-1]
XP_011532967.1. XM_011534665.2. [P27824-1]
UniGeneiHs.567968.

3D structure databases

ProteinModelPortaliP27824.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi107271. 214 interactors.
DIPiDIP-457N.
IntActiP27824. 94 interactors.
MINTiMINT-5000964.
STRINGi9606.ENSP00000247461.

Chemistry databases

BindingDBiP27824.
ChEMBLiCHEMBL2719.
DrugBankiDB00025. Antihemophilic Factor (Recombinant).
DB00031. Tenecteplase.

PTM databases

iPTMnetiP27824.
PhosphoSitePlusiP27824.
SwissPalmiP27824.

Polymorphism and mutation databases

BioMutaiCANX.
DMDMi543920.

Proteomic databases

EPDiP27824.
MaxQBiP27824.
PaxDbiP27824.
PeptideAtlasiP27824.
PRIDEiP27824.
TopDownProteomicsiP27824-1. [P27824-1]

Protocols and materials databases

DNASUi821.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000247461; ENSP00000247461; ENSG00000127022. [P27824-1]
ENST00000452673; ENSP00000391646; ENSG00000127022. [P27824-1]
ENST00000504734; ENSP00000424063; ENSG00000127022. [P27824-1]
GeneIDi821.
KEGGihsa:821.
UCSCiuc003mkk.4. human. [P27824-1]

Organism-specific databases

CTDi821.
DisGeNETi821.
GeneCardsiCANX.
HGNCiHGNC:1473. CANX.
HPAiCAB004738.
HPA009433.
HPA009696.
MIMi114217. gene.
neXtProtiNX_P27824.
OpenTargetsiENSG00000127022.
PharmGKBiPA26055.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0675. Eukaryota.
ENOG410XP7T. LUCA.
GeneTreeiENSGT00430000030841.
HOGENOMiHOG000192436.
HOVERGENiHBG005407.
InParanoidiP27824.
KOiK08054.
OMAiLVILFCC.
OrthoDBiEOG091G04SS.
PhylomeDBiP27824.
TreeFamiTF300618.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000127022-MONOMER.
ReactomeiR-HSA-168316. Assembly of Viral Components at the Budding Site.
R-HSA-2132295. MHC class II antigen presentation.
R-HSA-901042. Calnexin/calreticulin cycle.
R-HSA-983170. Antigen Presentation: Folding, assembly and peptide loading of class I MHC.

Miscellaneous databases

ChiTaRSiCANX. human.
GeneWikiiCalnexin.
GenomeRNAii821.
PROiP27824.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000127022.
CleanExiHS_CANX.
ExpressionAtlasiP27824. baseline and differential.
GenevisibleiP27824. HS.

Family and domain databases

Gene3Di2.10.250.10. 1 hit.
2.60.120.200. 1 hit.
InterProiIPR001580. Calret/calnex.
IPR018124. Calret/calnex_CS.
IPR009033. Calreticulin/calnexin_P_dom.
IPR013320. ConA-like_dom.
[Graphical view]
PANTHERiPTHR11073. PTHR11073. 1 hit.
PfamiPF00262. Calreticulin. 1 hit.
[Graphical view]
PRINTSiPR00626. CALRETICULIN.
SUPFAMiSSF49899. SSF49899. 2 hits.
SSF63887. SSF63887. 1 hit.
PROSITEiPS00803. CALRETICULIN_1. 1 hit.
PS00804. CALRETICULIN_2. 1 hit.
PS00805. CALRETICULIN_REPEAT. 3 hits.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiCALX_HUMAN
AccessioniPrimary (citable) accession number: P27824
Secondary accession number(s): B2R5V8
, B4DGP8, B4E2T8, D3DWQ3, D6R9K3
Entry historyi
Integrated into UniProtKB/Swiss-Prot: August 1, 1992
Last sequence update: June 1, 1994
Last modified: November 2, 2016
This is version 190 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 5
    Human chromosome 5: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.