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Introduction
to
M-type lectins
Interpro entry: Glycoside hydrolase, family 47
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Structure of the
catalytic domain of human ER mannosidase with bound substrate analogue
The thiodisaccharide substrate analogue is shown in green and
the Ca2+ ion in dark blue. Protein Data Bank structure ID:
1X9D. |
Alignment
M-type lectin-like domains from selected mannosidases and M-type lectins. Regions of secondary structure
predicted by the crystal structure of yeast ER mannosidase are indicated above the alignment
and coloured to correspond with the structure of human ER mannosidase, left.
Alpha-helices are designated a1-a15 and highlighted in
red; beta-strands are designated
b1-b19 and highlighted in blue. Residues
highlighted in
green
are conserved in both alpha-mannosidases and M-type lectins. Conserved acidic residues are highlighted
in red.
Cysteine residues conserved in M-type lectins
are highlighted in yellow. Cysteine residues which make essential
disulphide bonds in mannosidase are highlighted in orange; the equivalent residues in M-type lectins are
highlighted in
pale orange.
Accession numbers
Abbreviations: HS = human MM = mouse DM = Drosophila
CE = C elegans SC = S cerevisiae SP = S pombe AT =
Arabidopsis thaliana
SC Mns1
P32906
HS ER mannosidase A1
Q9UKM7
EDEM1: Human
Q92611;
Mouse
Q925U4; C elegans
Q18679;
S pombe
O94726;
S cerevisiae
P38888.
EDEM2: Human
Q9BV94; Mouse
Q91VV3;
Drosophila
O46091; C elegans
P90830.
EDEM3: Human
Q9BZQ6;
Mouse
Q2HXL6;
Drosophila
Q9VK27;
C elegans
Q09641.
Arabidopsis 1
Q9SXC9, 2
Q9FG93.
If alignments appear scrambled please maximize the
width of your browser window.
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a1
b1
b2
a2
SC Man
I
GAGEMRDRIESMFLESWRDYSKHGWGYDVYGPIEHTSHNMP----RGN----------QPLGWIIVDSVDTLMLMYNSST
HS Man
I
HLNYRQKGVIDVFLHAWKGYRKFAWGHDELKPVSRSFSEW-----FG-------------LGLTLIDALDTMWILGLRK-
HS
M1
LRAQMRDLARGMFVFGYDNYMAHAFPQDELNPIHCRGRGP----DRGDPSNLNINDVLGNYSLTLVDALDTLAIMGNSS-
MM
M1
LRAQMRDLARGMFVFGYDNYMAHAFPQDELNPIYCRGRGP----DRGDPSNLNINDVLGNYSLTLVDALDTLAIMGNSS-
CE
M1
DLQYGLAKTREMFQFGWDNYMEHAFPADELDPIHCRGRGH----DHDNPDNINVNDVLGDYSLGLIDTLDSLVVFGDAD-
SP
M1
RMVELRETSRRLFYHGYNNYMQFAFPNDELAPLSCEGLGP----DYENPNNIGVNDVRGDYLLTLVDVLDTLVVLGDRE-
SC M1
ELKAYKQEVKELFYFGFDNYLEHGYPYDEVKPISCVPKKR----NFEDPTDQGTNDILGNFTITLIDSLTTIAILEDRP-
HS
M2
DPAHYRERVKAMFYHAYDSYLENAFPFDELRPLTCDGHD-----TWG------------SFSLTLIDALDTLLILGNVS-
MM
M2
DPAHYRERVKAMFYHAYDSYLENAFPYDELRPLTCDGHD-----TWG------------SFSLTLIDALDTLLILGNTS-
DM
M2
RKLELREDVRRMFQHAYDGYLRHASNYDELRPLTCDGHD-----TWG------------SYSLTLIDALDTLATMGNFT-
CE M2
VIDSYREKVQKMFYHAYNGYLDHAFPLDELKPITCVGQD-----TWG------------SFSLSLIDALDTLLVMGNTT-
HS
M3
EKQKLGNQVLEMFDHAYGNYMEHAYPADELMPLTCRGRVRGQEPSRGD-----VDDALGKFSLTLIDSLDTLVVLNKTK-
MM M3 EKQKLGNQVLEMFDHAYGNYMEHAYPADELMPLTCRGRVRGQEPSRGD-----VDDALGKFSLTLIDSLDTLVVLNKTK
DM
M3
ERAELREEARDMFYHAYNAYMQNAYPADELMPLSCKGRYRGVTPSRGD-----MDDILGNFSMTLVDTLDTLVLLGDFT-
CE
M3
DKKKLQKEAYDMFMHGYNSYMNYAFPADELMPLSCKGRIRGVTPSRGD-----VDDVLGNFSVTLLDSLDTLVVMNELD-
AT M1
KKKQMREKVREMFYHAYDNYMTYAFPHDELKPLT-KSFTDSLS-ELGNLKLEHLPTDYNGSAVTLVESLSSLAILGNST-
AT M2
EAKQLRDEVRGMFYHAFDGYMNNAFPLDELRPLSCQGED-----TLG------------GYALTLIDSLDTLALLGDRE-
a3
b3 * * a4
a5
SC Man
I
LYKSEFEAEIQRSEHWINDVL---DFDIDAEVNVFETTIRMLGGLLSAYHLSDVLEVGN---------KTVYLNKAIDLG
HS Man
I
--------EFEEARKWVSKKL---HFEKDVDVNLFESTIRILGGLLSAYHLSG---------------DSLFLRKAEDFG
HS
M1
--------EFQKAVKLVINTV---SFDKDSTVQVFEATIRVLGSLLSAHRIITD-SKQPFGDMTIKDYDNELLYMAHDLA
MM
M1
--------EFQKAVKLVINTV---SFDKDSTVQVFEATIRVLGSLLSAHRIITD-SKQPFGDMTIEDYDNELLYMAHDLA
CE
M1
--------EFKRAVNLVIKTV---SFEKNTTVQVFESTIRVMGGLLAAHMIAAD-KTNRFGPFYMSDYGGELLTLAHDLA
SP
M1
--------GFQDAVDKVIHHI---NFERDTKVQVFEATIRILGGLLSSHIFASE-EK--YG-FQIPLYKGELLTLATELA
SC M1
--------QFLKAVRLVERTFPDGNFDIDSTIQVFEITIRVIGSLLSSHLYATDPTKAVYLG---DDYDGSLLRLAQNMA
HS
M2
--------EFQRVVEVLQDSV---DFDIDVNASVFETNIRVVGGLLSAHLLS---KKAGVEVEAGWPCSGPLLRMAEEAA
MM
M2
--------EFQRVVEVLQDNV---DFDIDVNASVFETNIRVVGGLLSAHLLS---KKAGVEVEAGWPCSGPLLRMAEEAA
DM
M2
--------EFRRAARLLEEKM---DFDRDINVSVFETNIRIVGGLLSAHLLS---KRAGVELEPGWPCKGPLLRLAEDVA
CE M2
--------EFRRAVSLVLEKA---RDDANVNVSVFETNIRVVGGLISAHMLAGRHKDLVVDWE-GYPCDSPLLKLAVKMA
HS
M3
--------EFEDAVRKVLRDV---NLDNDVVVSVFETNIRVLGGLLGGHSLAIMLKEKGE---YMQWYNDELLQMAKQLG
MM M3
--------EFEDAVRKVLRDV---NLDNDVVVSVFETNIRVLGGLLGGHSLAIMLKEKGE---HMQWYNDELLHMAKQLG
DM
M3
--------EFDHAVKLVIRDV---QFDSDIIVSVFETNIRMVGGLLSAHILAEYLQKHAD---TMHWYKGELLEMSRELG
CE
M3
--------EFEKAIDLVIKHV---RFDSDHVVSVFETNIRVLGGLISAHVLAELVKEKYPN--RLTTYDNQLLKMATEVG
AT M1
--------EFEKGVLWLSENL---TFDIDARVNLFECNIRVLGGLISAHLLAID-PNNRLIQG---SYNNQLLRLAEDLG
AT M2
--------RFTSSVEWIGKNL---QFNINKTVSVFETTIRVLGGLLSAHLIASD-YATGMRIP---SYNNELLVLAENLA
310a
b4
b5
310b
b6
a6
a7a
a7b
SC Man
I
DRLALAFLSTQTGIPYSSINLHSGQAVKNHADG--GASSTAEFTTLQMEFKYLAYLTGNRTYWELVERVYEPLYKNNDLL
HS Man
I
NRLMPAFR-TPSKIPYSDVNIGTGVAHPPRWTS---DSTVAEVTSIQLEFRELSRLTGDKKFQEAVEKVTQHIHG---LS
HS
M1
VRLLPAFENTKTGIPYPRVNLKTGVPPDTNN-----ETCTAGAGSLLVEFGILSRLLGDSTFEWVARRAVKALWN---LR
MM M1
VRLLPAFENTKTGIPYPRVNLKTGVPPDSNN-----ETCTAGAGSLLVEFGILSRLLGDSTFEWVARRAVKALWN---LR
CE
M1
GRLLPAFDGTATGIPYTRINLQKGILPGTTN-----STCTSGAGSLLLEFGVLSKLLGDDTYERLARRVNEKLWN---LR
SP
M1
ERLLPAFR-TPTGIPFARINLMKGVAYREVT-----ENCAAAASSLVLEFSMLTALTGNNKFKASAENAFFSVWK---RR
SC M1
DRLLPAYL-TSTGLPMPRRNIKRKWDVSEFPEFLETENNVAAMASPMFEFTILSYLTGDPKYEKVTRYAFDKTWS---LR
HS
M2
RKLLPAFQ-TPTGMPYGTVNLLHGVNPGETP-----VTCTAGIGTFIVEFATLSSLTGDPVFEDVARVALMRLWE---SR
MM
M2
RKLLPAFQ-TPTGMPYGTVNLLHGVNPGETP-----VTCTAGIGTFIVEFATLSSLTGDPVFEDVARVALMRLWE---SR
DM
M2
RRLLPAFV-TNTGMPYGTVNLRYGVPKGETS-----ITCTAGVGTFLIEFGTLSRLTGKTIYEDVAMKAVHALWA---YR
CE M2
DRLMPAFN-TETGMPYGTVNLKYGVHKDETP-----ITCTAGVGTFLIEFGTLSRLTGDDKYEKVALKALDALWS---TR
HS
M3
YKLLPAFN-TTSGLPYPRINLKFGIRKPEARTGTETDTCTACAGTLILEFAALSRFTGATIFEEYARKALDFLWE---KR
MM M3
YKLLPAFN-TTSGLPYPRINLKFGIRKPEARTGTETDTCTACAGTLILEFAALSRFTGATIFEEYARKALDFLWE---KR
DM
M3
YRLLPAFN-TSTGIPHARVNLRLGMKDPMLKK--SRETCTACAGTILLEFAALSRLTGDPIFEVRAHAAMDALWK---LR
CE M3
NRLLPAFN-TTSGLPFSRINLKHGMQDHLKRQ---KDTCTACGGTMILEFAALTSLTGDPIYEKKARKAMDFLWQ---QR
AT M1
KRFLPAFE-TPTGLPYAWINLKNGVMENETT-----ETSTSGCGSLVLEMGALSRLTGDPRFESAALRALRQLWR---MR
AT M2
RRMLPAFD-TPTGIPFGSVNLMYGVDKHESK-----ITSTAGGGTLSLEFGVLSRLTNDPVFEQVAKNAVRGLWA---RR
a7c
b7
**
a8
a9
b8
SC Man
I
NTYDGLVPIYTFPDTGKFGAS-TIRFGSRGDSFYEYLLKQYLLTHET--LYYDLYRKSMEGMKKHLLAQS---------K
HS Man
I
GKKDGLVPMFINTHSGLFTHLGVFTLGARADSYYEYLLKQWIQGGKQETQLLEDYVEAIEGVRTHLLRHS---------E
HS M1
SNDTGLLGNVVNIQTGHWVGK-QSGLGAGLDSFYEYLLKSYILFGEK--EDLEMFNAAYQSIQNYLRRGREACNEGEGDP
MM M1
SNDTGLLGNVVNIQTGHWVGK-QSGLGAGLDSFYEYLLKSYILFGEK--EDLEMFNAAYQSIQSYLRRGREACNEGEGDP
CE
M1
NEVTGLHGNLIDIQTGEWLGH-LAGLGAGIDSFYEYMLKSYILFGNQ--RDLDMYNESFARITTYMRRGRSRCSSLEGDI
SP
M1
SG-IGLLGNSIDVLSGRWIYP-VSGVGAGIDSFYEYAFKSYIFLGDP--RYLEVWQKSLESLRHYT---------ASLNE
SC M1
TG-LDLLPMSFHPEKLTPYTP-MTGIGASIDSLFEYALKGAILFDDS--ELMEVWNVAYEALKTNCKND-----------
HS
M3
SD-IGLVGNHIDVLTGKWVAQ-DAGIGAGVDSYFEYLVKGAILLQDK--KLMAMFLEYNKAIRNYTRFD-----------
MM
M2
SD-IGLVGNHIDVLTGKWVAQ-DAGIGAGVDSYFEYLVKGAILLQDK--KLMAMFLEYNKAIRNYTHFD-----------
DM
M2
SP-IGLFGNHIDVQSGRWTAL-DSGIGAGVDSLFEYLVKASVLLNRP--ELLELFHEARAAIDKYMRKE-----------
CE M2
SP-IGLVGNHINVQTGQWTAT-DSGIGAGVDSYFEYLAKGAYLFRRP--SLMKQFHEHATSINKHVRKG-----------
HS
M3
QRSSNLVGVTINIHTGDWVRK-DSGVGAGIDSYYEYLLKAYVLLGDD--SFLERFNTHYDAIMRYISQP-----------
MM M3
QRSSNLVGVTINIHTGDWVRK-DSGVGAGIDSYYEYLLKAYVLLGDD--SFLERFNTHYDAIMRYISQP-----------
DM
M3
HRGSDLMGTVLNVHSGDWVRR-DSGVGAGIDSYYEYLFKSYVLLGDD--KYLARFNRHYNAVMKYVSEG-----------
CE M3
HRSSDLMGTVLNVHSGDWTRR-ESGIGAGIDSYYEYTLKAYILLGDE--SYLDRFNKHYEAIKRYINKG-----------
AT M1
SS-LDLLGTTLDVVTGEWIEY-SSSIGAGVDSFYEYLLKAYILFGKE--DYWRMFHSAYLASQKYFRHG-----------
AT M2
SN-LDLVGAHINVFTGEWTQK-DAGIGTSIDSFYEYLLKAYILFGDE--EYLYIFQEAYRSAMQYLHKD-----------
b9
b10
310c
a10
aRL
a11
SC Man
I
PSSLWYIGEREQGLHGQLSPKMDHLVCFMGGLLASGSTEGLSIHEARRRPFFSLSLERKSDWDLAKGITDTCYQMYKQSS
HS Man
I
PSKLTFVGELA---HGRFSAKMDHLVCFLPGTLALGVYH----------------GLPASHMELAQELMETCYQMNRQME
HS
M1
PLYVNVNMFSG---QL-MNTWIDSLQAFFPGLQVL-----------------------IGDVEDAICLHAFYYAI--WKR
MM
M1
PLYVNVNMFSG---QL-MNTWIDSLQAFFPGLQVL-----------------------IGDVEDAICLHAFYYAI--WKR
CE
M1
PIYVNVDSRDG---ST-SNTWIDSLQASFAGVLVL-----------------------AGEVDEAVCHHALYYAI--WKK
SP
M1
YYYQNVYSANG---MV-MSRWVDSLSAYFPGLLVL-----------------------AGELELAKKMHLYYFSI--YLK
SC M1
WFFANVMADTG---HL-FVPWIDSLSAFFSGLQVL-----------------------AGDLDDAIANHLMFLKM--WNT
HS
M2
DWYLWVQMYKG---TV-SMPVFQSLEAYWPGLQSL-----------------------IGDIDNAMRTFLNYYTV--WKQ
MM
M2
DWYLWVQMYKG---TV-SMPVFQSLEAYWPGLQSL-----------------------IGDIDNAMRTFLNYYTV--WKQ
DM
M2
DWYVWVGMNKG---RV-TLPVFQSLEAFWPGILSI-----------------------IGDTEPALRTISRYIGV--WKK
CE M2
EWFMWVSMAKG---SV-SLPIFQSLEAFWPGTLTM-----------------------VGDVQDASRIMLTYSEV--IRK
HS
M3
PLLLDVHIHKP---MLNARTWMDALLAFFPGLQVL-----------------------KGDIRPAIETHEMLYQV--IKK
MM M3
PLLLDVHIHKP---MLNARTWMDALLAFFPGLQVL-----------------------KGDIRPAIETHEMLYQV--IKK
DM
M3
PMLLDVLMHRP---HAKSKNFMDSLLAFWPGLQVL-----------------------SGDLKPAVQTHEMLYQV--MQM
CE
M3
PIFVDVHMHRP---TVATRGFMDSLLAFWPGLQVL-----------------------KGDVKEAIEMHEMLFQV--IQK
AT M1
PWYHEANMWSG---KP-TYWQLTSLQAFWPGLQVL-----------------------VGDIAAANSSHREFFHV--WEK
AT M2
PWYVEVNMDSA---AI-VWPVFNSLQAFWPGLQVL-----------------------AGDVDPAIRTHTAFFSV--WKR
b11
b12
b13
310d
*
C
a12
a13
b14
SC Man
I
SGLAPEIVVFNDGNIKQDG-WWRSSVGDFFVKPLDRHNLQRPETVESIMFMYHLSHDHKYREWGAEIATSFFENTCVDCN
HS Man
I TGLSPEIVHFNLYPQP--------GRRDVEVKPADRHNLLRPETVESLFYLYRVTGDRKYQDWGWEILQSFSRFTRVPSG
HS
M1
YGALPERYNWQLQAP------------------DVLFYPLRPELVESTYLLYQATKNPFYLHVGMDILQSLEKYTKVKCG
MM
M1
YGALPERYNWQLQAP------------------DVLFYPLRPELVESTYLLYQATKNPFYLHVGMDILQSLEKYTKVKCG
CE
M1
YGVLPERFNWQLQAP------------------DVSFYPLRPEFVESTYLLYTATKNPFYQHVGLEILDSLETITRVKCG
SP
M1
FGQLPERYNLYTKSI------------------ELNGYPLRPEFAESTYYLYRATKDVFYLHVGELLLSNIENHLWTPCG
SC M1
FGGIPERWNFSPPEFPPLSPLERSGAVALDNILPLEWYPLRPEFFESTYFLYRATKDPFYLNIGVHLLKDLKQRFKSNCG
HS
M2
FGGLPEFYNIPQGYTV----------------EKREGYPLRPELIESAMYLYRATGDPTLLELGRDAVESIEKISKVECG
MM
M2
FGGLPEFYNIPQGYTV----------------EKREGYPLRPELIESAMYLYRATGDPTLLELGRDAVESIEKISKVECG
DM
M2
YGFLPEFYNIAAGEAS----------------PNREVYPLRPELIESAMYLYRATGNEYLLEFGEHMLETLEFSAKTKCG
CE M2
YGFPPEFYNIHNEEPG----------------EKRAAFPLRPEMVESLMYLYRATKDETWLELGAEMIDAIESSARTKCG
HS
M3
HNFLPEAFTTDFRVH-------------------WAQHPLRPEFAESTYFLYKATGDPYYLEVGKTLIENLNKYARVPCG
MM M3
HNFLPEAFTTDFRVH-------------------WAQHPLRPEFAESTYFLYKATGDPYYLEVGKTLIENLNKYARVPCG
DM
M3
HTFIPEAFTVDFQIH-------------------WGQHPLRPEFIESTYFLYRATGDHHYLQVGKKALKTLQQHAKVSCG
CE
M3
HKFLPEAFTHDFQVH-------------------WAEHPIRPEFVESTYFLYRATKDPHYLHVAKQIMDSINKYVKVPCG
AT M1
FGVLPERYLLDHQIIH----------------PTMKYYPLRPELAESTFYLYQATKDPWYLDVGESMVKSLNLYTKVPGG
AT M2
YGFTPEGFNLATLSVQ----------------YGQKSYPLRPELIESTYWLYKATRDPRYLDAGRDFVASLQYGAKCPCG
b15
b16
b17
*
C
a14
b18
C*
b19
a15
SC Man
I
DPKLRRFTSLSDCITLPTKKS-NNMESFWLAETLKYLYILFL-----DEFDLTK----VVFNTEAHPFPVLDEEILKSQS
HS Man
I
G-----YSSINNVQDPQKPEPRDKMESFFLGETLKYLFLLFS----DDPNLLSLD--AYVFNTEAHPLPIWTPA------
HS
M1
------YATLHHVIDKSTE---DRMESFFLSETCKYLYLLFD----EDNPVHKSG-TRYMFTTEGHIVSVDEHLRELPWK
MM
M1
------YATLHHVIDKSKE---DRMESFFLSETCKYLYLLFD----EENPVHKSG-TRYMFTTEGHIISVDKRLRELPWK
CE
M1
------FATVHDVIDGSLE---DRMESFFLSETLKYLYLLFD----VDHPINKEQQESVLFSTEGHIFPISPLFNLPPTP
SP M1
------FAAVENLEKYTLS---NRMESFFLSETLKYLFLLFD----DDNPIHRSH-HDFIFTTEGHLFPVTNQTRLSTSQ
SC M1
------FAGFQNVITGELQ---DRMETFVLSETLKYLYLLFD----EENELHNSAS-DVIFSTEAHPMWLPQEVRSNYKR
HS
M2
------FATIKDLRDHKLD---NRMESFFLAETVKYLYLLFD----PTNFIHNNGSTFDTVITP-YGECILGAGGYIFNT
MM
M2
------FATIKDLRDHKLD---NRMESFFLAETVKYLYLLFH----PNNFIHNNGSTFDSVMTP-HGECILGAGGYIFNT
DM
M2
------YATIRNVVTHEKE---NRMESFFLAETSKYLYLLFD----EENFLHNDGSGGELLSTE-DDVCVVQAGAYIFNT
CE M2
------YATINNVKEHSIE---DRMESFFLAETTKYLYLLFD----PTNFIHSKGDQARILTSPKNLTCVIYGGGYIFNT
HS
M3
------FAAMKDVRTGSHE---DRMDSFFLAEMFKYLYLLFA---DKEDIIFDIE--DYIFTTEAHLLPLWLSTTNQSIS
MM M3
------FAAMKDVRTGSHE---DRMDSFFLAEMFKYLYLLFA---DKEDIIFDIE--DYIFTTEAHLLPLWLSTTNRSIS
DM
M3
------YAAVNDVRTGKHE---DRMDSFVLSETIKYLFLLFS---DPQDLIINVD--EFVFTTEAHLLPLSIAQLGNATF
CE
M3
------FAALKDIRTMVKE---DQMESFVLSETFKYLYMIFT---DPEDLMFDPD--HYVLTTEAHFLPLSIGHKEKIEN
AT M1
------FASVRDVTTMQLE---DHQHSFFLAETCKYLYLLFD-----DSFVAKR---NYIFTTEGHPIQVVSSWHEKLPE
AT M2
------YCHITDVELHKQE---DHMESFFLAETVKYLWLLFDLAVDSDNLVDNGP-YKYIFSTEGHLLPITPQISLAREH
SC Man
I
LTTGWSL--------
HS Man
I
---------------
HS M1
E--------------
MM M1
E--------------
CE
M1
PSQYDPPLKPLPRTN
SP
M1
RIYDGGEVCVAEDYD
SC M1
NAKFNNSVYSS----
HS
M2
EAHPIDPAA------
MM
M2
EAHPIDPAA------
DM
M2
EAHPMDMSA------
CE M2
EAHPVDPGM------
HS
M3
KKNTTSEYTELDDSN
MM M3
KKNTTSEYTELDDSN...
DM
M3
SFRQTDEHNVLDFMR
CE
M3
KINPRRMILRADEPQ
AT M1
T-YFSG---------
AT M2
CSYFGGY--------
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_________________________________________________________________________________________________________________________________
- This page last updated:
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Wednesday, 01 January 2014
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Animal lectins
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This site is
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- Kurt Drickamer
- Division of Molecular Biosciences
- Faculty of Natural Sciences
- Imperial College London
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- Email:
k.drickamer@imperial.ac.uk
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