P-type lectins sequence alignment

Interpro entries: 1) Mannose 6-phosphate receptor, binding
2) Cation-dependent mannose 6-phosphate receptor
3) Cation-independent mannose 6-phosphate receptor
4) Glucosidase II beta subunit-like (MRH domain)

Regions of secondary structure are indicated above the alignment, and coloured to correspond with the structure of the bovine CD-MPR, left. The N-terminal alpha-helix is denoted H and highlighted in red. Beta-strands are designated S1-S9 and highlighted in yellow. Cysteine residues are highlighted in yellow and the three conserved disulfide pairings are indicated by the numbers 1-3. Residues conserved in the bovine and human CD-MPRs and the two M6P-binding domains of the human CI-MPR are highlighted in green when identical and in cyan when the character of the residue is preserved. Highlighted in dark blue are residues in the bovine CD-MPR, and the conserved equivalents in other proteins, which make direct hydrogen bonds to Man hydroxyl groups in the structure of this receptor with bound M6P. Highlighted in violet are residues in the bovine CD-MPR, and the conserved equivalents in other proteins, which interact with the phosphate group of M6P in the same structure. The dark blue-highlighted Arg residue marked * also interacts with Mn2+, which in turn interacts with the phosphate group of M6P.

In the structure of the third domain of the CI-MPR with bound M6P, the Man ring interacts with the residues highlighted in dark blue in a similar fashion to when bound by the CD-MPR. Two adjacent Ser residues which interact with the phosphate group of M6P in the third domain of the CI-MPR are highlighted in orange. In a different structure of this domain, although M6P was included in the crystallization medium, the ligand in the binding site was an non-phosphorylated N-linked glycan attached to another CI-MPR molecule in the crystal. The glycan has a Man3GlcNAc2 structure in which one of the terminal Man residues occupies the M6P binding site and interacts with the dark blue-highlighted residues. Three additional residues which make direct interactions with other Man residues in the oligosaccharide, and the conserved equivalents in other proteins, are highlighted in grey. The grey-highlighted Tyr marked # interacts with the Man ring of M6P in the M6P-bound structure.

Accession numbers
Abbreviations: HS = human BT = cow DM = Drosophila CE = C elegans SC = Saccharomyces cerevisiae SP = Schizosaccharomyces pombe AT = Arabidopsis thaliana CI = Ciona intestinalis (sea squirt)
ER glucosidase II beta subunit (PRKCSH) HS P14314 CE G5EC87 SC Q04924 AT Q9FM96
GlcNAc phosphotransferase gamma subunit HS Q9UJJ9 CI 14186
OS-9 HS Q13438 CE Q09396 SC Q99220 AT Q8GWH3
Erlectin/XTP3-B HS Q96DZ1 CE Q9NF22
CD-MPR HS P20645 BT P11456 CI 12925 CI-MPR Human P11717
Non-vertebrate MPR-like proteins: Drosophila CG6453 Q9VJD1 LERP Q8IMR0/Q8IMR1; C elegans K09C8.2 O01341; S pombe SPBC530.09c O59745; S cerevisiae Mrl1 Q06815.

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Structure of the bovine CD-MPR with bound M6P and Mn2+

Mannose 6-phosphate is shown in green and Mn2+ in purple. Protein Data Bank structure ID: 1M6P.

H S1 S2

1 # 1

HS Glc II b YSQCYE----------------------------------------------------------LTTNEYVYRLCPFK-

CE Glc II b KDKCFD----------------------------------------------------------RNVQQYTYQFCPFG-

SC Glc II b QSYCLD----------------------------------------------------------DILDNYVYTICFQR-

AT Glc II b HGRCFE----------------------------------------------------------SKQGKYTYKVCAYK-

HS GlcNAcPT SGKCFS----------------------------------------------------------LVESTYKYEFCPFH-

CI GlcNAcPT STDCFV----------------------------------------------------------FKSPGYMYEVCPYH-

HS OS9 DAPCLL----------------------------------------------------------KTKDWWTYEFCYGR-

CE OS9 VDKCVK---------------------------------------------------------LRGNHWWSYILCRGQ-

SC OS9 NERCIF----------------------------------------------------------YQAGFWIYEYCPGI-

AT OS9 SEKCLF----------------------------------------------------------RQEGWWSYEFCHQK-

HS Erl 1 QSSCSY----------------------------------------------------------RIESYWTYEVCHGK-

2 GSYCFR----------------------------------------------------------GGVGWWKYEFCYGK-

CE Erl 1 DKMCSY----------------------------------------------------------LIDVYWTYQVCHGR-

2 GEDCIV----------------------------------------------------------GGTGWWKYEFCYGK-

HS CD-MPR EKTCDL-----VGEKGKESEKELALVKRLKPLFNKSFESTVG--------------------QGSDTYIYIFRVCREAG

BT CD-MPR EKTCDL-----VGEKGKESEKELALLKRLTPLFNKSFESTVG--------------------QSPDMYSYVFRVCREAG

CI CD-MPR KNDCTL---------LKQNQQSQELLKRLDPLKGKIFTYKFK-----------------DEINGGDEYDYTLSICSGVT

HS CI-MPR 9 GDNC------------EVKDPRHGNLYDLKPLGLNDTIVSAG------------------------EYTYYFRVCGKLS

3 SKTCSLS------------GEQQDVSIDLTPLAQSGGSSYIS---------------------DGKEYLFYLNVCGETE

5 GENCTV------------FDSQAGFSFDLSPLTKKNGAYKVE----------------------TKKYDFYINVCGPVS

1 PELCSYTWEAVD---------------------------------------------------TKNNVLYKINICGSVD

2 EVPCYVF-------------DEELRKHDLNPLIKLSGAYLVD--------------------DSDPDTSLFINVCRDID

4 DLLCGA---TDGKKRYDLSALVRHAEPEQNWEAVDGSQTETE------------------------KKHFFINICHRVL

6 PLECVVTDPSTLEQYDLSSLAKSEGGLGGNWYAMDNSGEHVT------------------------WRKYYINVCRPLN

7 DQAC------------SIRDPNSGFVFNLNPLSSQGYNVSGI------------------------GKIFMFNVCGTMP

8 PVDCQVTDLA-------------GNEYDLTGLSTVRKPWTAV-----------------DTSVDGRKRTFYLSVCNPLP

10 LTECSFKD--------GAGNSFDLSSLSRYSDNWEAITGTGD------------------------PEHYLINVCKSLA

11 HDDCQV------------TNPSTGHLFDLSSLSGRAGFTAAY----------------------SEKGLVYMSICGENE

12 ATECSVRNGSSI--------------VDLSPLIHRTGGYEAY--------------DESEDDASDTNPDFYINICQPLN

13 MDGC------------TLTDEQLLYSFNLSSLSTSTFKVTRD------------------------SRTYSVGVCTFAV

14 KLEC--------------KFVQKHKTYDLRLLSSLTGSWSLV----------------------HNGVSYYINLCQKIY

15 QEVQMVNGTITNPINGKSFSL--GDIYFKLFRASGDMRTNGD------------------------NYLYEIQLSSITS

DM CG6453 PPNYDPETQRLIQQANEARNALEEVERSLREIQQEVNEIDDQ------------------NNKGYGLTEEWAVHD----

DM LERP a TTEC---------KLKEPIYGSTFDFSGLHSDLAHVVKSMNI-----------------------GGDQFEFNICGNLS

b SNSC------------RVGDTKSNGTFDLMPLSDSNYHTSNR-----------------------QGAFFVINVCKPVL

c LKPC----------------TAFTSTNELLDLSSLSSKPART--------------------LLKDGKNYTIAVC----

d PIRC--KATTYVDHTNDGLGSSGDELIDLTPLISATDNYEAR-----------VELPASMEHLVPKTTKFFLNVCRPLV

e -HEC---------------TFSADTCDLVHDELGRRFNFKSA-----------PFTKDGKIEIDYNATKMSVNICGAHR

CE K09C8.2 PDAC-----------------DVSLEQYLAAISAFVIIIAFF--KFAQIMCLRALCIFSQDVFQHVDCESFYNRCLTEP

SP BC530.09c EPFC------------ALHHPNTGEYFDLSGLIRDNTSEKGD----------------YSVNGYDFGTNFSINLCHPVV

SC Mrl1 DLFC------------AVTNPVTGSYIDLSQLSSTPNKLREGQKQISGNNKHESSKTKWSVRGWGYDTNFTLGICSSPV

S3 S4 S5

HS Glc II b ------------------------------LVSQKPK-------LGGSPTSLGTWGSWIGPDHDK-----------------------

CE Glc II b ------------------------------QNTQKDT-------GAYSGTSLGSFKEWSGPEGNK-----------------------

SC Glc II b -PMTEGVIYQAEDKVDGKKVLIGRFKTSGFNVDLNMEKYAEHLKATYDEKSDLISNLAAIQDDDGNMQHYVFGNLNELNN--------

AT Glc II b ------------------------------EATQEEG---------YSKTRLGEWDKFENS---------------------------

HS GlcNAcPT ------------------------------HVTQHEQ----TFRWNAYSGILGIWHEWEIANNT------------------------

CI GlcNAcPT ------------------------------NSTQNGK----DSWLIGAGGKLEGNQNEGF----------------------------

HS OS9 ------------------------------HIQQYHME---DSEIKGEVLYLGYYQSAFDWDDETAKASKQHRLKR------------

CE OS9 ------------------------------TIEQVHGE---PGQEGYVKNILGLFDGSLKMPSYQESTDDRLL---------------

SC OS9 ------------------------------EFVQFHGRVNTKTGEIVNRDESLVYRLGKPKANVEEREFELLYDDVGY----------

AT OS9 ------------------------------YVRQLHVEDENKIVQEFF---LGTFDPEATAAFNQTVSDASTDASQR-----------

HS Erl 1 ------------------------------HIRQYHEEKETGQKINIHEYYLGNMLAKNLLFEKEREAEEKEKSNEIPTKNIEGQMTP

2 ------------------------------HVHQYHEDK--DSGKTSVVVGTWNQEEHIEWAKKNTARAYHLQDDGTQTVR-------

CE Erl 1 ------------------------------YVIQYHEDKMLTGQVSRTEFYLGNFDSALTASTNEQVKPATRRIENEDYP--------

2 ------------------------------HVIQFHEDA----NGQRSDILLGVFDEVVHKEWVKLDRHARGAIQGNNQID-------

HS CD-MPR ------------------------------NHTSGAGLVQINKSN-GKETVVGRLNETHIFNGSN-----------------------

BT CD-MPR ------------------------------NHSSGAGLVQINKSN-GKETVVGRFNETQIFNGSN-----------------------

CI CD-MPR ---------------------------ANQFNAPGVGVLQYNKLK-QEYKRVGLINSTVVKGGTD-----------------------

HS CI-MPR 9 ------------------SDVC-----PTSDKSKVVSSCQEKREPQGFHKVAGLLTQKLTYENG------------------------

3 ------------------IQFC---------NKKQAAVCQVKKSDTSQVKAAGRYHNQTLRYSDG-----------------------

5 ------------------VSPC----------QPDSGACQVAKSD-EKTWNLGLSNAKLSYYDG------------------------

1 ------------------IVQC----------GPSSAVCMHDLKT-RTYHSVGDSVLRSATR--------------------------

2 ----------TLRDPGSQLRAC----------PPGTAACLVRGH---QAFDVGQPRDGLKLVRKD-----------------------

4 --------------QEGKARGC----------PEDAAVCAVDKN---GSKNLGKFISSPMKEKG------------------------

6 -----------------PVPGC----------NRYASACQMK-----YEKDQGSFTEVVSISNLGMAKTGPVVEDSG-----------

7 --------------------VC------GTILGKPASGCEAETQTEELKNWKPARPVGIEKSLQLSTEG-------------------

8 -----------------YIPGC---------QGSAVGSCLVSEG---NSWNLGVVQMSPQAAANG-----------------------

10 --------------PQAGTEPC----------PPEAAACLLGGS---KPVNLGRVRDGPQWRDG------------------------

11 --------------------NC----------PPGVGACFGQ-----TRISVGKANKRLRYVDQ------------------------

12 ---------------PMHAVPC----------PAGAAVCKVPID--GPPIDIGRVAGPPILNPIAN----------------------

13 ---------------GPEQGGC-----------KDGGVCLLSGT---KGASFGRLQSMKLDYRHQDE---------------------

14 ----------------KGPLGC----------SERASICRRTTT--GDVQVLGLVHTQKLGVIGD-----------------------

15 ----------------SRNPAC-----------SGANICQVKPNDQHFSRKVGTSDKTKYYLQDG-----------------------

DM CG6453 -------------------GQCYNFEDR----EYVYTLCPFDRA-SQKSRSGGPETTLGRWDWSGEPKQ-------------------

DM LERP a -------------------RTC--------NGESNVAACLKRQG---KEYILGRQHELFYNNG-------------------------

b ---------------YGENSMC----------PAGSSVCLFDSKATNPKERFINFGNVQTHPVVEKG---------------------

c --------------------------------AHAGAPCQENGGACYEQNSTTISLGNSNSQLRFNQTGS------------------

d ---------------PKYQLGC----------AGGSAACMA------KVTAAGAPEEERSMGFPLVSLTQRNRT--------------

e KAMTDYSQALVNIFFTHESPNC---------GREGTMNVQIRLICSDQ...

CE K09C8.2 ---------DRRRRQALRRAQREAQGTTGGEDRETDEEDVVVFERVTGRFPGGSAIKDNSIA--------------------------

SP BC530.09c ---------------------------------SNLTNYTVEGDVSSEDSIGGFFTVEDDDLPYFRGK--------------------

SC Mrl1 ------------------------GEAESQQLSNLTGAFYVDQLNENNLVSIGDFSTRPALVGGSTAK--------------------

S6 S7 S8 S9

2 * 3 2 3

HS Glc II b FSAMKYEQGTG-----CW---------------QGPNRSTTVRLLC-----GKETMV-TSTTEPS--------RCEYLMELMTPAACPE

CE Glc II b YSKMHFGDGQQ-----CW---------------NGPKRSTDITIEC-----GEENEL-VEVTEPA--------KCEYLFTFRTPLACAD

SC Glc II b GLVLEYENGDQ-----CW---------------NGPRRSATVFVRC-----SDKFKI-RSVHEAT--------KCNYIFDVVGPLGCNK

AT Glc II b YQFMSYTNGEK-----CW---------------NGPDRSLKVKLRC-----GLKNEL-MDVDEPS--------RCEYAAILSTPARCLE

HS GlcNAcPT FTGMWMRDGDA-----CR----------------SRSRQSKVELAC-----GKSNRL-AHVSEPS--------TCVYALTFETPLVCHP

CI GlcNAcPT RLVMGNGRGDH-----CP---------------DGKKRTTIITFKC-----GSMDKI-KYVSEKE--------TCIYVVKFDTPAACPP

HS OS9 YHSQTYGNGSK-----CD--------------LNGRPREAEVRFLCDEGAGISGDYI-DRVDEPL--------SCSYVLTIRTPRLCPH

CE OS9 FVEETYTSGTF-----CD------------LEEYREPRMTSVRYECDAQLSTNEVYI-SSVVEVK--------PCQYLMIVKVGTLCRY

SC OS9 YISEIIGSGDI-----CD--------------VTGAERMVEIQYVCGGSNSGPST-I-QWVRETK--------ICVYEAQVTIPELCNL

AT OS9 YHSHVYTNGTT-----CD--------------LTGSPREVEVRFVC----AETRAMV-TSITELS--------TCKYALTVQCPTLCKH

HS Erl 1 YYPVGMGNGTP-----CS-------------LKQNRPRSSTVMYIC---HPESKHEI-LSVAEVT--------TCEYEVVILTPLLCSH

2 MVSHFYGNGDI-----CD--------------ITDKPRQVTVKLKC-KESDSPHAVT-VYMLEPH--------SCQYILGVESPVICKI

CE Erl 1 YYSVSYNHGTS-----CD-------------VTGGKPRTTDVVYIC---VEKVQHKI-LSVTEIS--------SCHYEIVIMTDLLCKH

2 QISQIYAKGDI-----CD---------------ETGAHNVEVRIRCATADHSALSFS-MHLTEPR--------TCQYVLTIDSERFCEP

HS CD-MPR WIMLIYKGGD-EYDNHCG----------------KEQRRAVVMISCNRHTL-ADNFNPVS--EER----GKVQDCFYLFEMDSSLACSP

BT CD-MPR WIMLIYKGGD-EYDNHCG----------------REQRRAVVMISCNRHTL-ADNFNPVS--EER----GKVQDCFYLFEMDSSLACSP

CI CD-MPR WIMLTYKHGD-RYHSHCT-----------SPGSELSRRQAHIMIVCDPNEL-EGQFK-VL-YEH--NDEDTESSCFYMMEISSRAACSH

HS CI-MPR 9 LLKMNFTGGDT-----CH---------------KVYQRSTAIFFYCD-----RGTQRPVFLKE--------TSDCSYLFEWRTQYACPP

3 DLTLIYFGGDE-----CS---------------SGFQRMSVINFECNKTAGNDGKGTPVFTGE----------DCTYFFTWDTEYACVK

5 MIQLNYRGGTP-YNNERH-----------------TPRATLITFLCDRD---AGVGFPEYQEE---------DNSTYNFRWYTSYACPE

1 -SLLEFNTTV-----SCD------------QQGTNHRVQSSIAFLCG-----KTLGTPEFVTA---------TECVHYFEWRTTAACKK

2 RLVLSYVREEAGKLDFCD----------------GHSPAVTITFVCPSER--REGTIPKLTAK---------SNCRYEFEWITEYACHR

4 NIQLSYSDGDD-----CG---------------HGKKIKTNITLVCKPG---DLESAPVLRTS-------GEGGCFYEFEWRTAAACVL

6 SLLLEYVNGSA-----CT-----------TSDGRQTTYTTRIHLVCSRG---RLNSHPIFSLN---------WECVVSFLWNTEAACPI

7 FITLTYKGPLS---------------------AKGTADAFIVRFVCNDD----VYSGPLKFLHQDID--SGQGIRNTYFEFETALACVP

8 SLSIMYVNGDK-----CG----------------NQRFSTRITFECA-----QISGSPAFQLQ---------DGCEYVFIWRTVEACPV

10 IIVLKYVDGDL-----CP--------------DGIRKKSTTIRFTCSES---QVNSRPMFISA--------VEDCEYTFAWPTATACPM

11 VLQLVYKDGSP-----CPSK-------------SGLSYKSVISFVCRPEA--GPTNRPMLISL-------DKQTCTLFFSWHTPLACEQ

12 EIYLNFESSTP-----CLA-------------DKHFNYTSLIAFHCKRG---VSMGTPKLLRT---------SECDFVFEWETPVVCPD

13 AVVLSYVNGDR-----CPPE-------TDDGRHSNSYRTSSIIFKCDED---EDIGRPQVFSE--------VRGCDVTFEWKTKVVCPP

14 KVVVTYSKGYP-----CG---------------GNKTASSVIELTCT-----KTVGRPAFKRF-------DIDSCTYYFSWDSRAACAV

15 DLDVVFASSSK-----CGK-------------DKTKSVSSTIFFHCDPL---VEDGIPEFSHE--------TADCQYLFSWYTSAVCPL

DM CG6453 YSQQKYTNGAA-----CWNG---------------PNRSAIINISCALEPKITAVSEPN--------------RCEYYFEFETPAACDS

DM LERP a NMFLKYKSGAK-----CDNG-----------TADKPNYQLHVMFSCDY----TLDAQPMHVTP------YANEVCSFYISYRTPLACLS

b QLLLRHESPTP-----CAKN-------------SSANYTSVIYFSCDKF---IRNAHPEFAGL-------GADSCTYQFNFATPLACND

c -LYLLYEDGAE-----CSTA--------- --TGMRRWSTKIEFVCANNAT-KDNGASTAGGSDSLK-IIEDSNCQLLIQYQTPLACRE

d FAELAYLKGDP-----CPT-------------DNTSELSTHILFNCNMR---AGRGQPVLRSV---------EDCAYRFEWETNVFCPP

CE K09C8.2 -VDMVFIMA-------CLLNYVSFHVGNDFYAVSVSFVHVGAVFVCI-----VILLSTIYATYGLSV-MNLRKMCTALFIWLGHLACAG

SP BC530.09c KLIMQLDNGSL-----CPKS-------------NHIRMSTLISFTCNR----DPYTAPSVITY-----VGNLNDCAFFFEWKTIHACPT

SC Mrl1 KLTLKYENGSM-----CPNG--------------KDKKATLLNFVCD-----KEIQSKAQISY-----IGNLHNCSYFFEVRSIHACPT

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This page last updated:	Wednesday, 01 January 2014	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