Calnexin family - sequence alignment |
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Interpro entry: Calreticulin/Calnexin
Regions of secondary and tertiary structure are indicated above the alignment. The signal sequence is highlighted in yellow, the N- and C-terminal portions of the globular domain in light blue, the arm domain (P domain) in pink and the transmembrane and cytoplasmic regions in light green. Transmembrane domains and ER retention signals are highlighted in red. Within the arm domain, the borders between sequence repeats are indicated (|). Repeats are marked 1, for repeat type 1, and 2, for repeat type 2. Pairs of repeats which interact with one another in the calnexin structure are denoted a-d. Beta strands are highlighted in blue and the alpha helix in red, to correspond with the structure of calnexin, left. Residues which are identical in most proteins of the calnexin/calreticulin family are highlighted in green. Residues which are similar are highlighted in cyan. Cysteine residues involved in disulphide bonding in calnexin, and the conserved equivalents in other proteins, are highlighted in yellow. In calnexin, this disulphide bond is essential for ligand binding.
Two acidic side chains which contribute to Ca2+ coordination in the structure of calnexin, and the conserved equivalents in other proteins, are highlighted in purple. Residues which may contribute backbone oxygen atoms to Ca2+ coordination, and the conserved equivalents in other proteins, are highlighted in violet. Highlighted in magenta are residues in calnexin shown to be essential for glucose binding, and the equivalents (identical and similar) in other calnexins and calmegin. Highlighted in orange are equivalent residues in calreticulin that have been shown to be essential for oligosaccharide binding. Highlighted in pale orange are equivalent residues in calreticulin that are less important for oligosaccharide binding than in calnexin.
Accession numbers Abbreviations: HS = human DM = Drosophila CE = C elegans SC = S cerevisiae SP = S pombe AT = Arabidopsis thaliana Calnexin HS P27824 DM CG11958 O02393 CG9906 Q9VXF6 also CG1924 Q9I7S9 CE P34652 SC P27825 SP P36581 AT 1 P29402 also 2 Q38798 Calmegin HS O14967 Calreticulin: Human P27797 CE P27798 DM P29413 also AT 1 O04151 2 Q38858 3 O04153 Calreticulin 2 HS Q96L12
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Structure of luminal domain of canine
calnexin
The Ca2+ ion is shown in dark blue. The transmembrane region follows the alpha-helix at the bottom of the structure. Protein Data Bank structure ID: 1JHN. |
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Signal sequence N domain
HS calnexin MEGKW-----LLCMLLVLGTAIVEAHDGHDDDVIDIEDDLDDVIEEVEDSKPDTTAPPSSPKVTYKAPVPTG--EVYFADSFDRGTLSG-----WILSKAKKDDTDDEIAKYDGKWEVEE
DM calnexin 1
MAWKMGGNRAATLALLFASSLLLLSSANAADLDTESDD-FED--GYVEDVQEEPAVIGGDEKLAYESPVIDAK-KFHFADHFDDVEESRKR---WVLSQAKKDDIAEEISKYDGIWNWES
DM calnexin 2
MAWKM----------LFAI-LLLLSAAKTGYLAPESE-------NSVEDVQIEPGAIYGDEKFAYKSPVIDAE-KFYFADHFDDVEASRKR---WVLSQAKKNDIADEIAKYDGIWNWES
CE calnexin MVNRKWMY-------IFIQ-FLLVSSIRSDDDVFEDDE---------EEVTKGSDDKEEFVPSLFVAPKLSDKSTPNFFDYFPVGSKIGLT---WIKSLAKKDDVDSDIAKYNGEWSIGA
AT
calnexin MRQRQ----------LFSV-FLLLLAFVSFQKLCYCDDQTVLY------------------------------------ESFDEPFDGR-----WIVSKNSD---------YEGVWKHAK
SC calnexin MKFSAY---------LWWL-FLN-LALVKGTS------------------------------LLSNVTLAEDS----FWEHFQAYTNTKHLNQEWITSEAVN---NEGSKIYGAQWRLSQ
SP
calnexin MKYGK----------VSFL-ALLCSLYVRGSLADPESEQEP---------------------LVFNPTEVKAP----LVEQFQGAWSER-----WIPSHAKRFVNGIEEMSYVGEWTVEE
HS calmegin MHFQA----------FWLC-LGLLFISINAEFMDDDVETEDFEENSEE---IDVNESELSSEIKYKTPQPIG--EVYFAETFDSGRLAG-----WVLSKAKKDDMDEEISIYDGRWEIEE
HS calreticulin MLLSVPLLLGLLGLAVAEPAVYFKEQFLDGDGWTSR---WIESKHKS-DFGKFVLSSGKFYGDEE
CE
calreticulin MKSLC-LLAIVAVVSAE--VYFKEEF-NDASWEKR---WVQSKHKD-DFGAFKLSAGKFFDVES
DM calreticulin MMWCKTVIVLLATVGFISAE--VYLKENF-DNENWEDT---WIYSKHPGKEFGKFVLTPGTFYNDAE
HS calreticulin 2 MARALVQLWAICMLRVALATVYFQEEFLDGEHWRNR---WLQSTNDS-RFGHFRLSSGKFYGHKE
N domain
HS calnexin MKES-KLPGDKGLVLMSRAKHHAISAKLNKPFLFDT-KPLIVQYEVNFQNGIECGGAYVKLLSK-TPELNLDQFHDKTP-YTIMFGPDKCGE-DYKLHFIFRHKNPKTGIYEEKHAK-RP
DM
calnexin
PQRI-VWANDLGLVLKSKAKHAAIAAPLRKPFEFKSDKPLVVQYEVTLQEGQECGGSYLKLLSAGKDTEQLKAFNDKTP-YTIMFGPDKCGN-DVKMHFIFRHVNPINGTITEKHCN-KP
DM
calnexin
PQRI-FWANDLGLVLKSKAKHAAIAAPFRQPFDFKSNKPLVVQYELTLQEGQDCGGSYLKLLSAGKGTEQLNRFNDKTP-YTIMFGPDKCGN-NLKMHFIFRHVNPLNGNITEKHCK-KP
CE calnexin PTKV-SIEGDLGLIVKTKARHHAIAAKLNTPFAFDA-NTFVVQYDIKFEEGQECGGGYLKLLSEG-AEKDLANFQDKTA-YTIMFGPDKCGA-TGKVHLIFRYKNPINGTISEYHAN-QP
AT
calnexin SEG----HEDYGLLVSEKARKYGIVKELDEPLNLKE-GTVVLQYEVRFQEGLECGGAYLKYLRPQEAGWTPQGFDSESP-YSIMFGPDKCGG-TNKVHFILKHKNPKSGEYVEHHLK-FP
SC calnexin
G-RLQGSAWDKGIAVRTGNAAAMIGHLLETPINVSETDTLVVQYEIKLDNSLTCGGAFIKLMSGFMNVEALKHYAPDTEGVELVFGPDYCAPEINGVQFAINKVDKITHESKLRYLQEMP
SP calnexin
SSGPGALKGEAGLVMKDEAAHHAISYEFDEPINEPE-KDLVVQYEVNPEEGLNCGGAYLKLLAEP--THGEMSN--SID-YRIMFGPDKCGV-NDRVHFIFKHKNPLTGEYSEKHLDSRP
HS calmegin LKEN-QVPGDRGLVLKSRAKHHAISAVLAKPFIFAD-KPLIVQYEVNFQDGIDCGGAYIKLLAD-TDDLILENFYDKTS-YIIMFGPDKCGE-DYKLHFIFRHKHPKTGVFEEKHAK-PP
HS calreticulin
--------KDKGLQTSQDARFYALSASFEP-FSNKG-QTLVVQFTVKHEQNIDCGGGYVKLFPN---SLDQTDMHGDSE-YNIMFGPDICGPGTKKVHVIFNYK----G---KNVLI-NK
CE
calreticulin --------RDQGIQTSQDAKFYSRAAKFDKDFSNKG-KTLVIQYTVKHEQGIDCGGGYVKVMRA---DADLGDFHGETP-YNVMFGPDICGP-TRRVHVILNYK----G---ENKLI-KK
DM calreticulin
--------ADKGIQTSQDARFYAASRKFDG-FSNED-KPLVVQFSVKHEQNIDCGGGYVKLFDC---SLDQTDMHGESP-YEIMFGPDICGPGTKKVHVIFSYK----G---KNHLI-SK
HS calreticulin 2 --------KDKGLQTTQNGRFYAISARFKP-FSNKG-KTLVIQYTVKHEQKMDCGGGYIKVFPA---DIDQKNLNGKSQ-YYIMFGPDICGFDIKKVHVILHFK--------NKYHENKK
N domain P domain |1a |1b |1c |1d
HS calnexin DADLKTYFTDKKTHLYTLILNP-DNSFEILVDQSVVNSGNLL-----NDMTPPVNPSREIEDPEDRKPEDWDERPKIPDPEAVKPDDWDEDAPAKIPDEEATKPEGWLDDEPEYVPDPDA
DM
calnexin
KNRLEEPFKDKLPHLYQLVVRP-DNSFEIRVDHKIINEGSLL-----TDFKPPVNPPAEIDDPNDHKPESWDEREKIPDPTAHKPEDWDEDAPPQLPDTDAVMPNGWLEDEPDMIFDPTA
DM
calnexin
NARLGVPFTDKLPHLYQLVVRP-DNSFEIRLDHKIIKEGSLL-----TDFVPPVNPPAEIDDPNDHKPESWDERKKIPDPNAHKPEDWDEDAPPHLPDTDAVMPNGWLEDEPDMIFDPTA
CE calnexin TTIGSTYWDDHNTHLFTLVVKP-TGEYSVSVDGKSLYYGNMM-----SDVTPALTPPKQIFDETDLKPVDWDERENIEDESAVKPDDWDENEPQSVVDEAATKPYDWNEEENELIADPEA
AT calnexin PSVPY----DKLSHVYTAILKP-DNEVRILVDGEEKKKANLLSG---EDFEPALIPAKTIPDPEDKKPEDWDERAKIPDPNAVKPEDWDEDAPMEIEDEEAEKPEGWLDDEPEEVDDPEA
SC
calenexin LSKLT---DTSQSHLYTLIIDESAQSFQILIDGKTVMVREHIEDKKKVNFEPPITPPLMIPDVSVAKPHDWDDRIRIPDPEAVKLSDRDERDPLMIPHPDGTEPPEWNSSIPEYILDPNA
SP calnexin ASLLK----PGITNLYTLIVKP-DQTFEVRINGDVVRQGSLF-----YDFIPPVLPPVEIYDPEDIKPADWVDEPEIPDPNAVKPDDWDEDAPRMIPDPDAVKPEDWLEDEPLYIPDPEA
HS calmegin DVDLKKFFTDRKTHLYTLVMNP-DDTFEVLVDQTVVNKGSLL-----EDVVPPIKPPKEIEDPNDKKPEEWDERAKIPDPSAVKPEDWDESEPAQIEDSSVVKPAGWLDDEPKFIPDPNA
HS calreticulin DIRCK---DDEFTHLYTLIVRP-DNTYEVKIDNSQVESGSLE-----DDWD--FLPPK-----------------KIKDPDASKPEDWDERA--KIDDPTDSKPEDWDKPE--HIPDPDA
CE
calreticulin EITCK---SDELTHLYTLILNS-DNTYEVKIDGESAQTGSLE-----EDWD--LLPAK-----------------KIKDPDAKKPEDWDERE--YIDDAEDAKPEDWEKPE--HIPDPDA
DM calreticulin DIRCK---DDVYTHFYTLIVRP-DNTYEVLIDNEKVESGNLE-----DDWD--FLAPK-----------------KIKDPTATKPEDWDDRA--TIPDPDDKKPEDWDKPE--HIPDPDA
HS calreticulin 2 LIRCK---VDGFTHLYTLILRP-DLSYDVKIDGQSIESGSIE-----YDWN--LTSLK-----------------KETSPAESK--DWEQ--------TKDNKAQDWEK----HFLDAST
1d |2d |2c |2b |2a |C domain
HS calnexin EKPEDWDEDMDGEWEAPQIANPRCESAPGCGVWQRPVIDNPNYKGKWKPPMIDNPSYQGIWKPRKIPNPDFFEDLEPFR-MTPFSAIGLELWSMTSDIFFDNFIICADRRIVDDWANDGW
DM
calnexin
TKPEDWDAEIDGEWEAPLVDNPVCEKAPGCGKWKAPLIPNPNYKGKWRAPMIENPNYQGKWAPRKIPNPDFFEDLKPFQ-MTPISAVGLELWSMSSDILFDNLIITDDVEVARDFAANSF
DM
calnexin
IEPEDWNSEIDGEWEAPLVENPVCKKAPGCGKWKAPLIPNPNYKGKWSAPMIENPNNQGKWAPRKIANPDFFEDLKPFQ-MTPINAVGLELWSMSSDILFDNLIITDDVELARDFAANSF
CE calnexin KKPQDWDEDMDGSWEAPLIDNPACKGLSGCGTWKAPTIKNPKYKGKWIRPKISNPAFKGKWTARLIDNPNYFE-PKPFAGLAPITAVGIEMWTMSENILFDNILITSSEEDSSDVAKQTF
AT
calnexin
TKPEDWDDEEDGMWEAPKIDNPKCEAAPGCGEWKRPMKRNPAYKGKWSSPLIDNPAYKGIWKPRDIPNPDYFELDRPDY--EPIAAIGIEIWTMQDGILFDNILIAKDEKVAETYRQTTW
SC
calnexin QKPSWWKELEHGEWIPPMIKNPLCTAERGCGQQIPGLINNAKYKGPGELNEIINPNYMGEWHPPEIENPLYYEEQHPLRIENVISGVILEFWSGSPNMLISNIYVGKNVTEAQIIGNKTW
SP
calnexin
QKPEDWDDEEDGDWIPSEIINPKCIEGAGCGEWKPPMIRNPNYRGPWSPPMIPNPEFIGEWYPRKIPNPDYFDDDHPSH-FGPLYGVGFELWTMQPNIRFSNIYVGHSIEDAERLGNETF
HS calmegin EKPDDWNEDTDGEWEAPQILNPACR--IGCGEWKPPMIDNPKYKGVWRPPLVDNPNYQGIWSPRKIPNPDYFEDDHPFL-LTSFSALGLELWSMTSDIYFDNFIICSEKEVADHWAADGW
HS calreticulin
KKPEDWDEEMDGEWEPPVIQNPEYK-----GEWKPRQIDNPDYKGTWIHPEIDNPEY--------------SPDPSIYA-YDNFGVLGLDLWQVKSGTIFDNFLITNDEAYAEEFGNETW
CE
calreticulin KKPEDWDDEMDGEWEPPMIDNPEYK-----GEWKPKQIKNPAYKGKWIHPEIENPEY--------------TPDDELYS-YESWGAIGFDLWQVKSGTIFDNIIITDSVEEAEAHAAETF
DM calreticulin TKPEDWDDEMDGEWEPPMIDNPEFK-----GEWQPKQLDNPNYKGAWEHPEIANPEY--------------VPDDKLYL-RKEICTLGFDLWQVKSGTIFDNVLITDDVELAAKAAAEVK
HS calreticulin 2
SKQSDWNGDLDGDWPAPMLQKPPYQ-----DGLKPEGIH----KDVWLHRKMKNTDY--------------LTQYDLSE-FENIGAIGLELWQVRSGTIFDNFLITDDEEYADNFGKATW
C domain Transmembrane Transmembrane
HS calnexin GL------KKAADGAAEPGVVGQMIEAAEERPWLWVVYILTVALPVFLVILFCCS--GKK-----QTSGMEYKKTDAPQPDVK-----EEEEEKEE----EKDKGDEEEEGE---EKLEE
DM
calnexin
DI------KRRYIDRESDSFVNKVVELAKANPSIWGIGLVAIVALVALTIYCRFGTAKSQDSAA-KKAAAEAKKSDDPQPDDE---PEAEEESDER---AAGDTSKESTPLSASPKKNQK
DM
calnexin
DI------KRLYIDRE--SFGNKVVELARANRAIWGIVIVAIAVPVAITIFCKFGLGPSRVAAAKKAAAAAAKKTDDPQPDDD---LGAEEETDER---AAGDTNKESTPLSASPKKNQK
CE calnexin YVKQKEEYRLAAATGNGNGFFQQIIDATNEKPWLWAVYILCVLLPLVAIGVFCFG-KQSK------PTPNFAKKSDAYSADDDRVPNLVDDDEEEIIGDEEDDVNQPGPSGSQSNPEPQD
AT
calnexin KP------KFDVEKEKQ--KAEEEAAGSADGLKSYQKVVFDLLNKVADLSFLS--AYKSK-------ITELIEKAEQ-QPNLTIGVLVAIVVVFFSLFLKLIFGGKKAAAPVEK
SC
calnexin LMR-----DRAFRGSDGP-TERKFMNSRLGNLQTTFHNERESPNPFDRIIDRILEQPLK-------------------------FVLTAA
SP
calnexin LP------KLKAERELLS--KQESMEKQSMHVDEESNQILEKFLDVYDIIKAKLPPNVAE-------KVDYYVETIIETPEIGIAIVAVLGSLTAVILTCYFYFFASSSPASLSTGTTEA
HS calmegin RW------KIMIANANKPGVLKQLMAAAEGHPWLWLIYLVTAGVPIALITSFCWPRKVKK-----KHKDTEYKKTDICIPQTK---GVLEQEEKEEKAALEKPMDLEEEKKQNDGEMLEK
HS calreticulin
GV------TKAAEKQMK--DKQDEEQRL-------------------------------K-------EEEEDKKR----K---------EEEEAEDK---EDDEDKDEDEED----E-ED
CE
calreticulin DK------LKTVEKEKK--EKADEETR--------------------------------K-------AEEEARKK----A---------EEE-KEAK---KDDDEEEKEEE---------
DM calreticulin N-------TQAGEKKMK--EAQDEVQRK-------------------------------K-------DEEEAKKA----S---------DKD-DED----EDDDDEEKDDES----K-QD
HS calreticulin 2 GE------TKGPEREMD--AIQAKEEMK-------------------------------K----------------------------AREEEEEELLSGKI------------------
ER Retention Signal
HS calnexin KQKSDAEEDGG----TVS-QEEEDRKPK-------AEEDEILN------RSPRNRKPRRE
DM calnexin SDLDDNEEESK----AAESREPAQTEES--------------N------TKTRKRQARKE
DM calnexin SYLDNNEDEED----TLKNKEPTPKKRK--------------R------------KALKE
CE calnexin EEENAEQQSANSS--QSSAAEEEDDEHVVPENEPVKPTEEFAKKSPKNTGGAKRRTARRGD
AT
calnexin KKPEVAESSKS--------GDEAEKKEE--------------------TAAPRKRQPRRDN
SP
calnexin EK-EQQEK--------FKQETETEKIDVS------------------YAPETESPTAKNED
HS calmegin EEESEPEEKSEEEIEIIEGQEESNQSNKSGSEDEMKEADESTGSGDGPIKSVRKRRVRKD
HS calreticulin KEEDEEEDVPG-----Q-AKDEL
CE calreticulin ------E-----------GHDEL
DM calreticulin K--DQSE------------HDEL
HS calreticulin 2 NRHEHYFNQFH-------RRNEL
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