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P11226 (MBL2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 172. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Mannose-binding protein C

Short name=MBP-C
Alternative name(s):
Collectin-1
MBP1
Mannan-binding protein
Mannose-binding lectin
Gene names
Name:MBL2
Synonyms:COLEC1, MBL
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length248 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Calcium-dependent lectin involved in innate immune defense. Binds mannose, fucose and N-acetylglucosamine on different microorganisms and activates the lectin complement pathway. Binds to late apoptotic cells, as well as to apoptotic blebs and to necrotic cells, but not to early apoptotic cells, facilitating their uptake by macrophages. May bind DNA. Ref.11

Subunit structure

Oligomeric complex of 3 or more homotrimers. Interacts with MASP1 and MASP2. Interacts with MEP1A and MEP1B and may inhibit their catalytic activity. Ref.10 Ref.13

Subcellular location

Secreted Ref.9.

Tissue specificity

Plasma protein produced mainly in the liver. Ref.14

Polymorphism

Genetic variations in MBL2 influence susceptibility to hepatitis B virus (HBV) infection [MIM:610424].

Genetic variations in MBL2 are responsible for mannose-binding protein deficiency [MIM:614372]. This condition is defined as MBL2 protein level of less than 100 ng/ml, is present in about 5% of people of European descent and in about 10% of sub-Saharan Africans. Most MBL2-deficient adults appear healthy, but low levels of MBL2 are associated with increased risk of infection in toddlers, in cancer patients undergoing chemotherapy, and in organ-transplant patients receiving immunosuppressive drugs, particularly recipients of liver transplants. There is an association between low levels of MBL2 and a defect of opsonization which results in susceptibility to frequent and chronic infections (Ref.16). Functional MBL2 deficiency may be associated with protection against tuberculosis caused by Mycobacterium africanum but not by Mycobacterium tuberculosis, as observed in studies on Ghanaian patients with pulmonary tuberculosis (Ref.22).

Sequence similarities

Contains 1 C-type lectin domain.

Contains 1 collagen-like domain.

Ontologies

Keywords
   Biological processComplement activation lectin pathway
Complement pathway
Immunity
Innate immunity
   Cellular componentSecreted
   Coding sequence diversityPolymorphism
   DomainCollagen
Repeat
Signal
   LigandCalcium
Lectin
Mannose-binding
   PTMDisulfide bond
Hydroxylation
   Technical term3D-structure
Complete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processacute-phase response

Traceable author statement PubMed 2477488. Source: BHF-UCL

complement activation

Traceable author statement. Source: Reactome

complement activation, classical pathway

Inferred from electronic annotation. Source: UniProtKB-KW

complement activation, lectin pathway

Inferred from physical interaction PubMed 11549596. Source: UniProtKB

defense response to Gram-positive bacterium

Inferred from direct assay PubMed 15148336. Source: MGI

defense response to bacterium

Traceable author statement PubMed 2477488. Source: BHF-UCL

innate immune response

Traceable author statement. Source: Reactome

killing by host of symbiont cells

Inferred from electronic annotation. Source: Ensembl

negative regulation of growth of symbiont in host

Inferred from direct assay PubMed 15148336. Source: MGI

opsonization

Traceable author statement PubMed 2477488. Source: BHF-UCL

positive regulation of phagocytosis

Inferred from electronic annotation. Source: Ensembl

response to oxidative stress

Non-traceable author statement PubMed 11549596. Source: UniProtKB

   Cellular_componentcell surface

Traceable author statement PubMed 2477488. Source: BHF-UCL

collagen

Inferred from electronic annotation. Source: UniProtKB-KW

extracellular region

Traceable author statement. Source: Reactome

extracellular space

Traceable author statement Ref.17. Source: ProtInc

   Molecular_functioncalcium-dependent protein binding

Inferred from physical interaction PubMed 12421953PubMed 18596036. Source: UniProtKB

mannose binding

Non-traceable author statement PubMed 11549596. Source: UniProtKB

receptor binding

Inferred from physical interaction PubMed 11549596. Source: UniProtKB

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

LRP1Q079545EBI-5325353,EBI-1046087

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2020 Ref.9
Chain21 – 248228Mannose-binding protein C
PRO_0000017401

Regions

Domain42 – 9958Collagen-like
Domain134 – 245112C-type lectin
Compositional bias21 – 4121Cys-rich

Amino acid modifications

Modified residue471Hydroxyproline Ref.9
Modified residue731Hydroxyproline Ref.9
Modified residue791Hydroxyproline Ref.9
Modified residue821Hydroxyproline Ref.9
Modified residue881Hydroxyproline Ref.9
Disulfide bond155 ↔ 244
Disulfide bond222 ↔ 236

Natural variations

Natural variant241T → A in Chinese. Ref.6
VAR_013294
Natural variant521R → C in 0.05% of European and African populations. Ref.5 Ref.20 Ref.21
Corresponds to variant rs5030737 [ dbSNP | Ensembl ].
VAR_008543
Natural variant541G → D Polymorphism associated with mannose-binding protein deficiency and recurrent infections. Ref.5 Ref.7 Ref.8 Ref.16 Ref.17 Ref.19 Ref.20 Ref.21
Corresponds to variant rs1800450 [ dbSNP | Ensembl ].
VAR_004182
Natural variant571G → E Polymorphism associated with mannose-binding protein deficiency; associated with protection against tuberculosis caused by Mycobacterium africanum. Ref.5 Ref.17 Ref.20 Ref.21 Ref.22
Corresponds to variant rs1800451 [ dbSNP | Ensembl ].
VAR_004183
Natural variant2141N → Y.
Corresponds to variant rs12260094 [ dbSNP | Ensembl ].
VAR_050119

Secondary structure

...................... 248
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P11226 [UniParc].

Last modified April 1, 1990. Version 2.
Checksum: C1F2AAED46D0F774

FASTA24826,144
        10         20         30         40         50         60 
MSLFPSLPLL LLSMVAASYS ETVTCEDAQK TCPAVIACSS PGINGFPGKD GRDGTKGEKG 

        70         80         90        100        110        120 
EPGQGLRGLQ GPPGKLGPPG NPGPSGSPGP KGQKGDPGKS PDGDSSLAAS ERKALQTEMA 

       130        140        150        160        170        180 
RIKKWLTFSL GKQVGNKFFL TNGEIMTFEK VKALCVKFQA SVATPRNAAE NGAIQNLIKE 

       190        200        210        220        230        240 
EAFLGITDEK TEGQFVDLTG NRLTYTNWNE GEPNNAGSDE DCVLLLKNGQ WNDVPCSTSH 


LAVCEFPI 

« Hide

References

« Hide 'large scale' references
[1]"A human mannose-binding protein is an acute-phase reactant that shares sequence homology with other vertebrate lectins."
Ezekowitz R.A.B., Day L.E., Herman G.A.
J. Exp. Med. 167:1034-1046(1988) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]Erratum
Ezekowitz R.A.B., Day L.E., Herman G.A.
J. Exp. Med. 174:753-753(1991)
[3]"The human mannose-binding protein gene. Exon structure reveals its evolutionary relationship to a human pulmonary surfactant gene and localization to chromosome 10."
Sastry K., Herman G.A., Day L.E., Deignan E., Bruns G., Morton C.C., Ezekowitz R.A.B.
J. Exp. Med. 170:1175-1189(1989) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], SEQUENCE REVISION.
Tissue: Liver.
[4]"Structure and evolutionary origin of the gene encoding a human serum mannose-binding protein."
Taylor M.E., Brickell P.M., Craig R.K., Summerfield J.A.
Biochem. J. 262:763-771(1989) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[5]"Different molecular events result in low protein levels of mannan-binding lectin in populations from South-East Africa and South America."
Madsen H.O., Satz M.L., Hogh B., Svejgaard A., Garred P.
J. Immunol. 161:3169-3175(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS CYS-52; ASP-54 AND GLU-57.
[6]"Cloning and sequencing of mannan-binding lectin cDNA of Chinese."
Chen Z., Zhu X., Xie P.
Mian Yi Xue Za Zhi 15:83-86(1999)
Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT ALA-24.
Tissue: Liver.
[7]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT ASP-54.
[8]"Restricted polymorphisms of the mannose-binding lectin gene in a population of Papua New Guinea."
Jueliger S., Kremsner P.G., Alpers M.P., Reeder J.C., Kun J.F.J.
Mutat. Res. 505:87-91(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-59, VARIANT ASP-54.
[9]"Structure and function of mannan-binding proteins isolated from human liver and serum."
Kurata H., Sannoh T., Kozutsumi Y., Yokota Y., Kawasaki T.
J. Biochem. 115:1148-1154(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 21-248, SUBCELLULAR LOCATION, HYDROXYLATION AT PRO-47; PRO-73; PRO-79; PRO-82 AND PRO-88.
Tissue: Liver and Plasma.
[10]"A second serine protease associated with mannan-binding lectin that activates complement."
Thiel S., Vorup-Jensen T., Stover C.M., Schwaeble W.J., Laursen S.B., Poulsen K., Willis A.C., Eggleton P., Hansen S., Holmskov U., Reid K.B.M., Jensenius J.C.
Nature 386:506-510(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH MASP1 AND MASP2.
[11]"Mannose-binding lectin engagement with late apoptotic and necrotic cells."
Nauta A.J., Raaschou-Jensen N., Roos A., Daha M.R., Madsen H.O., Borrias-Essers M.C., Ryder L.P., Koch C., Garred P.
Eur. J. Immunol. 33:2853-2863(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[12]"Nucleic acid is a novel ligand for innate, immune pattern recognition collectins surfactant proteins A and D and mannose-binding lectin."
Palaniyar N., Nadesalingam J., Clark H., Shih M.J., Dodds A.W., Reid K.B.M.
J. Biol. Chem. 279:32728-32736(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: DNA-BINDING.
[13]"Mannan-binding protein blocks the activation of metalloproteases meprin alpha and beta."
Hirano M., Ma B.Y., Kawasaki N., Okimura K., Baba M., Nakagawa T., Miwa K., Kawasaki N., Oka S., Kawasaki T.
J. Immunol. 175:3177-3185(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH MEP1A AND MEP1B.
[14]"Comparative study of the human ficolins reveals unique features of Ficolin-3 (Hakata antigen)."
Hummelshoej T., Fog L.M., Madsen H.O., Sim R.B., Garred P.
Mol. Immunol. 45:1623-1632(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: TISSUE SPECIFICITY.
[15]"Human mannose-binding protein carbohydrate recognition domain trimerizes through a triple alpha-helical coiled-coil."
Sheriff S., Chang C.Y., Ezekowitz R.A.
Nat. Struct. Biol. 1:789-794(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 108-248.
[16]"Molecular basis of opsonic defect in immunodeficient children."
Sumiya M., Super M., Tabona P., Levinsky R.J., Arai T., Turner M.W., Summerfield J.A.
Lancet 337:1569-1570(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT ASP-54, ASSOCIATION WITH MANNOSE-BINDING PROTEIN DEFICIENCY AND SUSCEPTIBILITY TO CHRONIC INFECTIONS.
[17]"High frequencies in African and non-African populations of independent mutations in the mannose binding protein gene."
Lipscombe R.J., Sumiya M., Hill A.V.S., Lau Y.L., Levinsky R.J., Summerfield J.A., Turner M.W.
Hum. Mol. Genet. 1:709-715(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS ASP-54 AND GLU-57, ASSOCIATION WITH MANNOSE-BINDING PROTEIN DEFICIENCY.
[18]Erratum
Lipscombe R.J., Sumiya M., Hill A.V.S., Lau Y.L., Levinsky R.J., Summerfield J.A., Turner M.W.
Hum. Mol. Genet. 2:342-342(1993)
[19]"Distinct and overlapping functions of allelic forms of human mannose binding protein."
Super M., Gillies S.D., Foley S., Sastry K., Schweinle J.E., Silverman V.J., Ezekowitz R.A.
Nat. Genet. 2:50-55(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT ASP-54.
[20]"Genotyping of the three major allelic variants of the human mannose-binding lectin gene by denaturing gradient gel electrophoresis."
Gabolde M., Muralitharan S., Besmond C.
Hum. Mutat. 14:80-83(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS CYS-52; ASP-54 AND GLU-57.
[21]"Mannose binding lectin genotypes influence recovery from hepatitis B virus infection."
Thio C.L., Mosbruger T., Astemborski J., Greer S., Kirk G.D., O'Brien S.J., Thomas D.L.
J. Virol. 79:9192-9196(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: INVOLVEMENT IN SUSCEPTIBILITY TO HBV INFECTION, VARIANTS CYS-52; ASP-54 AND GLU-57.
[22]"Variant G57E of mannose binding lectin associated with protection against tuberculosis caused by Mycobacterium africanum but not by M. tuberculosis."
Thye T., Niemann S., Walter K., Homolka S., Intemann C.D., Chinbuah M.A., Enimil A., Gyapong J., Osei I., Owusu-Dabo E., Rusch-Gerdes S., Horstmann R.D., Ehlers S., Meyer C.G.
PLoS ONE 6:E20908-E20908(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT GLU-57, ASSOCIATION WITH PROTECTION AGAINST TUBERCULOSIS.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
X15422 mRNA. Translation: CAA33462.1.
X15954 expand/collapse EMBL AC list , X15955, X15956, X15957 Genomic DNA. Translation: CAA34079.1.
AF080510, AF080508, AF080509 Genomic DNA. Translation: AAC31937.1.
Y16576 Genomic DNA. Translation: CAB56044.1.
Y16577 Genomic DNA. Translation: CAB56120.1.
Y16578 Genomic DNA. Translation: CAB56045.1.
Y16579 Genomic DNA. Translation: CAB56121.1.
Y16580 Genomic DNA. Translation: CAB56122.1.
Y16581 Genomic DNA. Translation: CAB56123.1.
Y16582 Genomic DNA. Translation: CAB56124.1.
AF360991 mRNA. Translation: AAK52907.1.
BC069338 mRNA. Translation: AAH69338.1.
BC096181 mRNA. Translation: AAH96181.3.
BC096182 mRNA. Translation: AAH96182.3.
AF482699 Genomic DNA. Translation: AAN39274.1.
AF482700 Genomic DNA. Translation: AAN39275.1.
PIRLNHUMC. JL0115.
RefSeqNP_000233.1. NM_000242.2.
UniGeneHs.499674.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1HUPX-ray2.50A108-248[»]
ProteinModelPortalP11226.
SMRP11226. Positions 41-102, 108-248.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid110323. 4 interactions.
IntActP11226. 3 interactions.
MINTMINT-6630459.
STRING9606.ENSP00000363079.

Chemistry

ChEMBLCHEMBL1795113.

Polymorphism databases

DMDM126676.

Proteomic databases

PaxDbP11226.
PeptideAtlasP11226.
PRIDEP11226.

Protocols and materials databases

DNASU4153.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000373968; ENSP00000363079; ENSG00000165471.
GeneID4153.
KEGGhsa:4153.
UCSCuc001jjt.3. human.

Organism-specific databases

CTD4153.
GeneCardsGC10M054525.
HGNCHGNC:6922. MBL2.
HPACAB016782.
HPA002027.
MIM154545. gene.
610424. phenotype.
614372. phenotype.
neXtProtNX_P11226.
PharmGKBPA30665.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG265984.
HOVERGENHBG108270.
InParanoidP11226.
KOK03991.
OMALCAQFQG.
OrthoDBEOG7VTDPW.
PhylomeDBP11226.
TreeFamTF330481.

Enzyme and pathway databases

ReactomeREACT_6900. Immune System.

Gene expression databases

ArrayExpressP11226.
BgeeP11226.
CleanExHS_MBL2.
GenevestigatorP11226.

Family and domain databases

Gene3D3.10.100.10. 1 hit.
InterProIPR001304. C-type_lectin.
IPR016186. C-type_lectin-like.
IPR018378. C-type_lectin_CS.
IPR016187. C-type_lectin_fold.
IPR008160. Collagen.
[Graphical view]
PfamPF01391. Collagen. 1 hit.
PF00059. Lectin_C. 1 hit.
[Graphical view]
SMARTSM00034. CLECT. 1 hit.
[Graphical view]
SUPFAMSSF56436. SSF56436. 1 hit.
PROSITEPS00615. C_TYPE_LECTIN_1. 1 hit.
PS50041. C_TYPE_LECTIN_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceP11226.
GeneWikiMannan-binding_lectin.
GenomeRNAi4153.
NextBio16342.
PMAP-CutDBP11226.
PROP11226.
SOURCESearch...

Entry information

Entry nameMBL2_HUMAN
AccessionPrimary (citable) accession number: P11226
Secondary accession number(s): Q4VB12 expand/collapse secondary AC list , Q4VB13, Q86SI4, Q96KE4, Q96TF7, Q96TF8, Q96TF9
Entry history
Integrated into UniProtKB/Swiss-Prot: July 1, 1989
Last sequence update: April 1, 1990
Last modified: April 16, 2014
This is version 172 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 10

Human chromosome 10: entries, gene names and cross-references to MIM