I-type lectins (siglecs) - sequence alignments   - CD33-related siglecs       - Siglecs 1, 2 and 4
	Introduction to I-type lectins (siglecs) Domain organization in siglecs Interpro entry: Immunoglobulin Sequence alignment of human and mouse CD33-related siglecs    The proteins in this subgroup of siglecs exhibit a high level of similarity to human CD33 (siglec 3).  The subgroup has undergone differential expansion in mouse and human.  The mouse proteins are termed siglecs E, F, G and H, while the human proteins, in addition to CD33/siglec 3, are designated siglecs 5-12.  Indicated above the alignment are structural domains, sequence motifs, intron/exon boundaries deduced from the siglec-10 gene (|), and potential N-linked glycosylation sites (+).  Residues that are identical in more than 70% of the aligned sequences are highlighted in green, and residues that are similar in more than 70% of the sequences are highlighted in cyan.  Divergent regions are highlighted in grey.  Cysteine residues are highlighted in yellow.  Three residues involved in sialic acid binding are highlighted in magenta and are shown in the structure of siglec-7: the conserved arginine which makes an electrostatic interaction with sialic acid that is essential for high-affinity binding, plus two hydrophobic aromatic residues.  Note that the essential arginine is missing in siglec 12, as it is in certain other primate siglecs and rat siglec H.  Cytoplasmic tyrosine-based signaling motifs are highlighted in orange.   NB: Siglec-12 is produced with two alternative N-terminal regions.  The longer form, here called siglec-12a, has two V-type immunoglobulin domains whereas the short form, siglec-12b, has the usual single V-type domain.  Residue numbers refer to siglec-12a.  A number of other siglecs are also subject to alternative splicing.  In each case, all the potential domain elements are included in the alignment, but not all are necessarily found within a single siglec isoform.   If alignments appear scrambled please maximize the width of your browser window.
Structure of Siglec-7 CRD Structure adapted from Alphey et al, J Biol Chem 278, 3372

 

 

 

            Leader peptide|                      V-type                                        

Siglec E      1 M-LLLLLLLLLWGIKGVEGQNPQEV--------FTLNVERKVVVQEGLCVLVPCNFSYLKKRLTDWTDSDPVHGFWYREG

Siglec F      1 M-RWAWLLPLLWAGCLATDG-------------YSLSVTGSVTVQEGLCVFVACQVQYP-------NSKGPVFGYWFREG

Siglec G      1 MSLLLFLLSFLLDGPQGQMES------------YFLQVQRIVKAQEGLCIFVPCSFSSPEGK---WLNRSPLYGYWFKGI

Siglec H      1 M-LLSLLLPLLWVLKWASGNCFILPREVIGTYPSLTLELQSVTVQEGLCVLVPCHLIEYPMNR--WSDA--AFGYWFHEG

Siglec-10     1 M–LLPLLLSSLLGGSQAMDGR------------FWIRVQESVMVPEGLCISVPCSFSYPRQD---WTGSTPAYGYWFKAV
Siglec-11     1 MLLLPLLLPVLGAGSLNKDPS------------YSLQVQRQVPVPEGLCVIVSCNLSYPRDG---WDESTAAYGYWFKGR

Siglec-6      1 M--LPLLLPLLWAGALAQERR------------FQLEGPESLTVQEGLCVLVPCRLPTTLPASYYG------YGYWFLEG

Siglec-5      1 M–LPLLLLPLLWGGSLQEKPV------------YELQVQKSVTVQEGLCVLVPCSFSYPWRS---WYSSPPLYVYWFRDG
Siglec-3      1 M–PLLLLLPLLWAGALAMDPN------------FWLQVQESVTVQEGLCVLVPCTFFHPIPY---YDKNSPVHGYWFREG

Siglec-3 M    1 M-LWPLPLFLLCAGSLAQDLE------------FQLVAPESVTVEEGLCVHVPCSVFYPSIK----LTLGPVTGSWLRKG

Siglec-8      1 MLLLLLLLPLLWGTKGMEGDRQYGDG-------YLLQVQELVTVQEGLCVHVPCSFSYPQDG---WTDSDPVHGYWFRAG

Siglec-7      1 M–LLLLLLPLLWGRERVEGQKSNRKD-------YSLTMQSSVTVQEGMCVHVRCSFSYPVDSQ---TDSDPVHGYWFRAG

Siglec-9      1 M-–LLLLLPLLWGRERAEGQTS-----------KLLTMQSSVTVQEGLCVHVPCSFSYPSHG--WIYPGPVVHGYWFREG

Siglec-12a    1 MLLLLLLLPPLLCGRVGAK---EQKD-------YLLTMQKSVTVQEGLCVSVLCSFSYPQNG---WTASDPVHGYWFRAG

Siglec-12b    1 MLLPLL-----WANEERDSGGWADPRFS>

Siglec-12   142                       <VTASQDLLSRYRLEVPESVTVQEGLCVSVPCSVLYPHYN---WTASSPVYGSWFKEG

 

 

                V-TYPE                             +                                              

Siglec E     72 TDRRKDSIVATNNPIRKAVKETRNRFFLLGDPWRNDCSLNIREIRKKDAGLYFFRLERGK-TKYN------YMWDKMTLV

Siglec F     60 ANIFSGSPVATNDPQRSVLKEAQGRFYLMGKENSHNCSLDIRDAQKIDTGTYFFRLD-GS-VKYS------FQKSMLSVL

Siglec G     66 RKPSLSFPVATNNKDKVLEWEARGRFQLLGDISKKNCSLLIKDVQWGDSTNYFFRMERGFER-FS------FKEEF-RLQ

Siglec H     76 ENTHPDSLVATNKPYQLVQKEMQSRFHFSGD-----CSLDIRDAQKGDNGSYFFRLEKGG--KTWN-----FCEERISVH

Siglec-10    65 TETTKGAPVATNHQSREVEMSTRGRFQLTGDPAKGNCSLVIRDAQMQDESQYFFRVERGSYVRYN------FMNDGFFLK
Siglec-11    66 TSPKTGAPVATNNQSREVEMSTRDRFQLTGDPGKGSCSLVIRDAQREDEAWYFFRVERGSRVRHS------FLSNAFFLK
Siglec-6     61 ----ADVPVATNDPDEEVQEETRGRFHLLWDPRRKNCSLSIRDARRRDNAAYFFRL-KSKWMKYG------YTSSKIYVR
Siglec-5     65 EIPYYAEVVATNNPDRRVKPETQGRFRLLGDVQKKNCSLSIGDARMEDTGSYFFRVERGRDVKYS------YQQNKLNLE
Siglec-3     65 AIISGDSPVATNKLDQEVQEETQGRFRLLGDPSRNNCSLSIVDARRRDNGSYFFRMERGST-KYS------YKSPQLSVH
Siglec-3 M   64 VSLHEDSPVATSDPRQLVQKATQGRFQLLGDPQKHDCSLFIRDAQKNDTGMYFFRVVREPFVRYS------YKKSQLSLH

Siglec-8     71 DRPYQDAPVATNNPDREVQAETQGRFQLLGDIWSNDCSLSIRDARKRDKGSYFFRLERGSM-KWSYKSQLNYKTKQLSVF
Siglec-7     70 NDISWKAPVATNNPAWAVQEETRDRFHLLGDPQTKNCTLSIRDARMSDAGRYFFRMEKGNI-KWN------YKYDQLSVN
Siglec-9     66 ANTDQDAPVATNNPARAVWEETRDRFHLLGDPHTKNCTLSIRDARRSDAGRYFFRMEKGSI-KWN------YKHHRLSVN
Siglec-12a   68 DHVSRNIPVATNNPARAVQEETRDRFHLLGDPQNKDCTLSIRDTRESDAGTYVFCVERGN-MKWN------YKYDQLSVN>

Siglec-12   195 ADIPWDIPVATNTPSGKVQEDTHGRFLLLGDPQTNNCSLSIRDARKGDSGKYYFQVERGS-RKWN------YIYDKLSVH

 

 

                  |C-type 1                                                                     
Siglec E    145 VTALTNTPQILLPETLEAGHPSNLTCSVPWD---CGWTAPPIFSWTGTSVSFLST--NTTGSSVLTITPQPQDHGTNLTC

Siglec F    132 VIALTEVPNIQVTSTLVSGNSTKLLCSVPWA---CEQGTPPIFSWMSSALTSLGHR--TTLSSELNLTPRPQDNGTNLTC

Siglec G    138 VEALTQKPDIFIPEVLEPGEPVTVVCLFSWTFNQC---PAPSFSWMGDAVSFQESRPHTSNYSVLSFIPGLQHHDTELTC

Siglec H    144 VTDLTHSPNISIPQTLELGRPTNVMCSVPWA---CERGTPPIFSWMSAALISLG--PTTTLSSVLTLTPRLQDHGTNLTC

Siglec-10   139 VTALTQKPDVYIPETLEPGQPVTVICVFNWAFEEC---PPPSFSWTGAALSSQGTKPTTSHFSVLSFTPRPQDHNTDLTC
Siglec-11   140 VTALTKKPDVYIPETLEPGQPVTVICVFNWAFKKC---PAPSFSWTGAALSPRRTRPSTSHFSVLSFTPSPQDHDTDLTC

Siglec-6    130 VMALTHRPNISIPGPGVW-PSSNLTCSVPWV---CEQGTPPIFSWMSAAPHLLG--PRTTQSSVLTITP-AQDHSTNLTC
Siglec-5    139 VTALIEKPDIHFLEPLESGRPTRLSCSLPGS---CEAGPPLTFSWTGNALSPLD--PETTRSSELTLTPRPEDHGTNLTC
Siglec-3    138 VTDLTHRPKILIPGTLEPGHSKNLTCSVSWA---CEQGTPPIFSWLSAAPTSLG--PRTTHSSVLIITPRPQDHGTNLTC
Siglec-3 M  138 VTSLSRTPDIIIPGTLEAGYPSNLTCSVPWA---CEQGTPPTFSWMSTALTSLS--SRTTDSSVLTFTPQPQDHGTKLTC

Siglec-8    150 VTALTHRPDILILGTLESGHSRNLTCSVPWA---CKQGTPPMISWIGASVSSPG--PTTARSSVLTLTPKPQDHGTSLTC
Siglec-7    143 VTALTHRPNILIPGTLESGCFQNLTCSVPWA---CEQGTPPMISWMGTSVSPLH--PSTTRSSVLTLIPQPQHHGTSLTC
Siglec-9    139 VTALTHRPNILIPGTLESGCPQNLTCSVPWA---CEQGTPPMISWIGTSVSPLD--PSTTRSSVLTLIPQPQDHGTSLTC
Siglec-12   268 VTALTHMPTFSIPGTLESGHPRNLTCSVPWA---CEQGTPPTITWMGASVSSLD--PTITRSSMLSLIPQPQDHGTSLTC

 

 

                C-TYPE 1            |   Linker 1    |C-type 2                                  

Siglec E    220 QVTLPGTNVSTRMTTRLNVSYAPKNLTVTIYQGADSVSTI-LK-NGSSLPISEGQSLRLICSTDSYPPANLSWSWDNLTL

Siglec F    207 QVNLPGTGVTVERTQQLSVIYAPQKMTIRVSWGDDTGTKV-LQ-SGASLQIQEGESLSLVCMADSNPPAVLSWERP--TQ

Siglec G    215 QLDFSRM--STQRTVRLRVAYAPRSLAISIFHDNVSVPD--LHENPSHLEVQQGQSLRLLCTADSQPPATLSWVLEDQVL

Siglec H    219 QVTFPGAGVTVQKTIQLNVTYNSQNSTAHVSGRVGPGKPRPLADVVQVAMGEAAIKFLLLGICFFFLSKRSHTKRVERPA

Siglec-10   216 HVDFSRKGVSVQRTVRLRVAYAPRDLVISISRDNTPALEPQPQGNVPYLEAQKGQFLRLLCAADSQPPATLSWVLQNRVL

Siglec-11   217 HVDFSRKGVSAQRTVRLRVAYAPKDLIISISHDNTSALE--LQGNVIYLEVQKGQFLRLLCAADSQPPATLSWVLQDRVL

Siglec-6    205 QVTFPGAGVTMERTIQLNVS------------------------------------------------------------
Siglec-5    214 QMKRQGAQVTTERTVQLNVS------------------------------------------------------------
Siglec-3    213 QVKFAGAGVTTERTIQLNVT------------------------------------------------------------
Siglec-3 M  213 LVTFSGAGVTVERTIQLNVT

Siglec-8    225 QVTLPGTGVTTTSTVRLDVS------------------------------------------------------------
Siglec-7    218 QVTLPGAGVTTNRTIQLNVS------------------------------------------------------------
Siglec-9    214 QVTFPGASVTTNKTVHLNVS------------------------------------------------------------

Siglec-12   343 QVTLPGAGVTMTRAVRLNIS------------------------------------------------------------

 

 

                C-TYPE 2                                      |   Linker 2 +  |     +   C-TYPE 3    

Siglec E    298 CPSKLSKPGLLELFPVHLKHG--GVYTCQAQHALGSQHISLSLSPQ----------------------------------

Siglec F    283 KPFQLSTPAELQL-------------------------------------------------------------------

Siglec G    291 SWSSPVGSRTLALELPWVKAGDSGHYTCQAENRLGSQQHTLDLSVLYPPQDLRVTVSQANRTVLEILRNAISLPVLEGQS

Siglec H    299 THMDQAHAVMD 309

Siglec-10   296 SSSHPWGPRPLGLELPGVKAGDSGRYTCRAENRLGSQQRALDLSVQYPPENLRVMVSQGNRTVLENLGNGTSLPVLEGQS

Siglec-11   295 SSSHPWGPRTLGLELRGVRAGDSGRYTCRAENRLGSQQQALDLSVQYPPENLRVMVSQANRTVLENLGNGTSLPVLEGQS

Siglec-6    225 ----------------------------------------------YAPQKVAISIFQGNSAAFKILQNSSSLPVLEGQA
Siglec-5    234 ----------------------------------------------YAPQ--TITIF-RNGIALEILQNSSYLPVLEGQA
Siglec-3    233 ----------------------------------------------YVPQNPTTGIFPGDGS------------------
Siglec-3 M  233 --------------------------------------------------------------------------------

Siglec-8    245 ----------------------------------------------YPPWNLTMTVFQGDGTASTALGNGSSLSVLEGQS
Siglec-7    238 ----------------------------------------------YPPQNLTVTVFQGEGTASTALGNSSSLSVLEGQS
Siglec-9    234 ----------------------------------------------YPPQNLTMTVFQGDGTVSTVLGNSSSLSLPEGQS

Siglec-12   363 ----------------------------------------------YPPQNLTMTVFQGDGTASTTLRNGSALSVLEGQS

 

                                         C-TYPE 3                                      |         
Siglec E    341 --------------------------------------------------------------------------------

Siglec F    296 ----------------------------------------PRAELEDQGKYICQAQNSQGAQTASVSLSIRSLLQLLGPS

Siglec G    371 LCLVCVTY---SNPPANVSWAWVTQTLIPIQSSEPGVLELPLVQREHEGEFTCAAQNPLGAQRISLSLSVHYPPQMSSPS

Siglec-10   376 LCLVCVSH---SSPPARLSWTQRGQVLSPSQPSDPGVLELPRVQVEHEGEFTCHARHPLGSQHVSLSLSVHYSPKLLGPS

Siglec-11   375 LRLVCVTH---SSPPARLSWTRWGQTVGPSQPSDPGVLELPPIQMEHEGEFTCHAQHPLGSQHVSLSLSVHYPPQLLGPS

Siglec-6    259 LRLLCDAD---GNPPAHLSWFQGFPALNATPISNTGVLELPQVGSAEEGDFTCRAQHPLGSLQISLSLFVH---------
Siglec-5    265 LRLLCDAP---SNPPAHLSWFQGSPALNATPISNTGILELRRVRSAEKGGFTCRAQHPLGFLQIFLNLSVYSLPQLLGPS
Siglec-3    248 --------------------------------------------------------------------------------
Siglec-3 M      --------------------------------------------------------------------------------

Siglec-8    279 LRLVCAVN---SNPPARLSWTRGSLTLCPSRSSNPGLLELPRVHVRDEGEFTCRAQNAQGSQHISLSLSLQ---------
Siglec-7    272 LRLVCAVD---SNPPARLSWTWRSLTLYPSQPSNPLVLEL-QVHLGDEGEFTCRAQNSLGSQHVSLNLSLQ---------
Siglec-9    268 LHLVCAVDAVDSNPPARLSLSWRGLTLCPSQPSNPGVLELPWVHLRDAAEFTCRAQNPLGSQQVYLNVSLQ---------
Siglec-12   397 LHLVCAVD---SNPPARLSWTWGSLTLSPSQSSNLGVLELPRVHVKDEGEFTCRAQNPLGSQHISLSLSLQ---------

 

 

                C-TYPE 4                         +                 +                                 

Siglec E    341 --------------------------------------------------------------------------------

Siglec F    336 CSFEGQGLHCSCSSRAWPAPSLRWRLGEGVLEGNSSNGSFTVKSSSAGQWANSSLILSMEFSSNHRLSCEAWSDNRVQRA

Siglec G    448 CSWEAKGLHCNCSSRAWPAPSLRWRLGEGLLEGNSSNASFTVTFSSLGPWVNSSLSLLQELGPSLWLSCESWN------T

Siglec-10   453 CSWEAEGLHCSCSSQASPAPSLRWWLGEELLEGNSSQDSFEVTPSSAGPWANSSLSLHGGLSSGLRLRCEAWN------V

Siglec-11   452 CSWEAEGLHCSCSSQASPAPSLRWWLGEELLEGNSSQGSFEVTPSSAGPWANSSLSLHGGLSSGLRLRCKAWN------V

Siglec-6    326 --------------------------------------------------------------------------------

Siglec-5    342 CSWEAEGLHCRC-FRAWPAPSLCWRLEEKPLEGNSSQGSFKVNSSSPGPWANSSLILHGGLNSDLKVSCKAWN------I

Siglec-3    248 --------------------------------------------------------------------------------
Siglec-3 M      --------------------------------------------------------------------------------

Siglec-8    346 --------------------------------------------------------------------------------
Siglec-7    338 --------------------------------------------------------------------------------
Siglec-9    338 --------------------------------------------------------------------------------
Siglec-12   464 --------------------------------------------------------------------------------

 

 

                      |                    Transmembrane   |           Cytoplasmic tail                
Siglec E    342 --------------SSATLSEMMMGTFVGSGVTALLFLSVCILLLAVRSYRRKP--------------------------

Siglec F    416 TILLVSGPKVSQAGKSETSRGTVLGAIWGAGLMALLAVCLCLIFFTVKVLRKKSALKVAATKGNHLAKNPASTINSASIT

Siglec G    528 HGAQTTSVLLLPDKDSA--TAFSKGAVLGFGITALLAL--CLIVVIVKTLQKKGTQEEPSRPKLSRGSTILDYINVVPKT

Siglec-10   527 HGAQSGSILQLPDKKGLISTAFSNGAFLGIGITALLFLCLALIIMKILPKRR--TQTETPRPRFSRHSTILDYInVVPTA
Siglec-11   526 HGAQSGSVFQLLPGKLEHGGGLGLGAALGAGVAALLAFCSCLVVFRVKICRKEARKRAAAEQDVPSTLGPISQGHQHECS

Siglec-6    327 -----------WKPEGRAG-GVL-GAVWGASITTLVFLCVCFIFRV-KTRRKKAAQPVQNTDDVNPVMVSGSRGHQHQFQ
Siglec-5    416 YGSQSGSVL-LLQGRSNLRTGVVPAALGGAGVMALLCICLCLIFFLIVKARRKQAAGRPEK-------------------
Siglec-3    249 -----------GKQETRAG-LVHGAIGG-AGVTALLALCLCLIFFIVKTHRRKA--------------------------
Siglec-3 M      --------------RKSGQMRELVLVAVGEATVKLLILGLCLVFLIVMFCRRKTTKLSVHMGCENPIKGGKPQ

Siglec-8    347 ---------NEGTGTSRPVSQVTLAAVGGAGATALAFLSFCIIFIIVRSCRKKS--------------------------
Siglec-7    273 ---------QEYTGKMRPVSGVLLGAVGGAGATALVFLSFCVIFIVVRSCRKKS--------------------------
Siglec-9    339 ---------------SKATSGVTQGVVGGAGATALVFLSFCVIFVVVRSCRKKS--------------------------
Siglec-12   465 ---------NEYTGKMRPISGVTLGAFGGAGATALVFLYFCIIFVVVRSCRKKS--------------------------

 

 

                   |  Cytoplasmic tail                                                         
Siglec E    382 ----------ARPAV-VAPHP--DALKV--SVSQNPLVESQADDSSEPLPSILEAAPSSTEEEIHYATLSFHEMKPMNLW

Siglec F    496 SSNIALGYPIQGHLNEPGSQTQKEQPPLATV-----------------------PDTQKDEPELHYASLSFQGPMPPKPQ

Siglec G    598 RSLA--RNWKAEPDAPSRSSPLDTHFPKP--KKKQKDPHFTYPGCPDPTSSSQVPVSENNPEELHYAALNFSRLRLQETQ

Siglec-10   605 GPLAQKRNQKATPNSP-RT-PLPPGAPSPESKKNQKKQ-YQLPSFPEPKSSTQAPESQESQEELHYATLNFPGVRPRPEA

Siglec-11   606 AGSSQDHPPPGAATYT---------------------------------------PGKGEEQELHYASLSFQGLRLWEPA

Siglec-6    367 TGIVSDHPAEAG-------------------------------------------PISEDEQELHYAVLHFHKVQPQEPK
Siglec-5    471 ---------------------MDDEDPIMGTITSGSRKKPWPDSPGDQASPPGDAPPLEEQKELHYASLSFSEMKSREPK
Siglec-3    290 ----------ARTAVG-----SNDTHPTTGSASPKHQKNSKLHGPTETSSCSGAAPTVEMDEELHYASLNFHGMNP--SK
Siglec-3 M

Siglec-8    392 ----------ARPAAGVGDTGMEDAKAIRGSASQGPLTESWKDGNPLKKPPPAVAPSSGEEGELHYATLSFHKVKPQDPQ
Siglec-7    384 ----------ARPAADVGDIGMKDANTIRGSASQGNLTESWADDNPRHHG--LAAHSSGEEREIQYAPLSFHKGEPQDLS
Siglec-9    378 ----------ARPAAGVGDTGIEDANAVRGSASQGPLTEPWAEDSPPDQPPPASARSSVGEGELQYASLSFQMVKPWDSR
Siglec-12   510 ----------ARPAVGVGDTGMEDANAVRGSASQGPLIESPADDSPPHHAPPALATPSPEEGEIQYASLSFHKARPQYPQ

 

 

                                                       

Siglec E    447 GQQD-TTTEYSEIKFPQRTAWP                      467

Siglec F    553 NTEAM-KSVYTEIKIHKC                          569

Siglec G    674 DPQD-TYSDYTEVRVH                            688

Siglec-10   682 RMPKGTQADYAEVKFQ                            697

Siglec-11   647 DQEAPSTTEYSEIKIHTGQPLRGPGFGLQLEREMSGMVPK    686

Siglec-6    429 V----TDTEYSEIKIHKD                          442
Siglec-5    535 DQEAPSTTEYSEIKTSK                           551
Siglec-3    352 D----TSTEYSEVRTQ                            364

Siglec-3 M              EYSEI

Siglec-8    462 GQEA-TDSEYSEIKIHKRETAETQACLRNHNPSSKEVRG     499

Siglec-7    452 GQEA-TNNEYSEIKIPK                           467
Siglec-9    448 GQEA-TDTEYSEIKIHR                           463
Siglec-12   580 EQEAI-GYEYSEINIPK                           595       

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This page last updated:	Thursday, 24 August 2006	Animal lectins home
Contact information:	This site is supported by:
Kurt Drickamer Division of Molecular Biosciences Faculty of Natural Sciences Imperial College London   Email: k.drickamer@imperial.ac.uk