P11226 (MBL2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	248 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence 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 process	Complement activation lectin pathway Complement pathway Immunity Innate immunity
Cellular component	Secreted
Coding sequence diversity	Polymorphism
Domain	Collagen Repeat Signal
Ligand	Calcium Lectin Mannose-binding
PTM	Disulfide bond Hydroxylation
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	acute-phase response Traceable author statement PubMed 2477488. Source: BHF-UCL 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 killing by host of symbiont cells Inferred from electronic annotation. Source: Compara 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: Compara response to oxidative stress Non-traceable author statement PubMed 11549596. Source: UniProtKB
Cellular_component	collagen Inferred from electronic annotation. Source: UniProtKB-KW extracellular space Traceable author statement Ref.17. Source: ProtInc
Molecular_function	bacterial cell surface binding Traceable author statement PubMed 2477488. Source: BHF-UCL eukaryotic cell surface binding Traceable author statement PubMed 2477488. Source: BHF-UCL mannose binding Non-traceable author statement PubMed 11549596. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 20

20

Ref.9

Chain

21 – 248

228

Mannose-binding protein C

PRO_0000017401

Regions

Domain

42 – 99

58

Collagen-like

Domain

134 – 245

112

C-type lectin

Compositional bias

21 – 41

21

Cys-rich

Amino acid modifications

Modified residue

47

1

Hydroxyproline Ref.9

Modified residue

73

1

Hydroxyproline Ref.9

Modified residue

79

1

Hydroxyproline Ref.9

Modified residue

82

1

Hydroxyproline Ref.9

Modified residue

88

1

Hydroxyproline Ref.9

Disulfide bond

155 ↔ 244

Disulfide bond

222 ↔ 236

Natural variations

Natural variant

24

1

T → A in Chinese. Ref.6

VAR_013294

Natural variant

52

1

R → C in 0.05% of European and African populations. Ref.5 Ref.20 Ref.21
Corresponds to variant rs5030737 [ dbSNP | Ensembl ].

VAR_008543

Natural variant

54

1

G → 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 variant

57

1

G → 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 variant

214

1

N → Y.
Corresponds to variant rs12260094 [ dbSNP | Ensembl ].

VAR_050119

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

248

Helix Strand Turn

Details...

Helix

110 – 129

20

Beta strand

131 – 134

4

Beta strand

137 – 147

11

Helix

148 – 157

10

Helix

168 – 177

10

Beta strand

182 – 187

6

Beta strand

189 – 191

3

Helix

216 – 218

3

Beta strand

222 – 225

4

Beta strand

231 – 234

4

Beta strand

238 – 247

10

Sequences

	Sequence		Length	Mass (Da)
	P11226 [UniParc]. Last modified April 1, 1990. Version 2. Checksum: C1F2AAED46D0F774	FASTA	248	26,144
	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

References

	« Hide 'large scale' referencesShow '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.

Web resources

GeneReviews

Functional Glycomics Gateway - Glycan Binding

Mannose-binding protein

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

X15422 mRNA. Translation: CAA33462.1.
X15954 , 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.

IPI

IPI00004373.

PIR

LNHUMC. JL0115.

RefSeq

NP_000233.1. NM_000242.2.

UniGene

Hs.499674.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1HUP	X-ray	2.50	A	108-248	[»]

ProteinModelPortal

P11226.

ModBase

Search...

Protein-protein interaction databases

IntAct

P11226. 1 interaction.

STRING

9606.ENSP00000363079.

Polymorphism databases

DMDM

126676.

Proteomic databases

PaxDb

P11226.

PeptideAtlas

P11226.

PRIDE

P11226.

Protocols and materials databases

DNASU

4153.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000373968; ENSP00000363079; ENSG00000165471.

GeneID

4153.

KEGG

hsa:4153.

UCSC

uc001jjt.3. human.

Organism-specific databases

CTD

4153.

GeneCards

GC10M054525.

HGNC

HGNC:6922. MBL2.

HPA

CAB016782.
HPA002027.

MIM

154545. gene.
610424. phenotype.
614372. phenotype.

neXtProt

NX_P11226.

PharmGKB

PA30665.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG265984.

HOVERGEN

HBG108270.

InParanoid

P11226.

KO

K03991.

OMA

DPGKSPD.

OrthoDB

EOG4DJJXF.

PhylomeDB

P11226.

Enzyme and pathway databases

Reactome

REACT_6900. Immune System.

Gene expression databases

ArrayExpress

P11226.

Bgee

P11226.

CleanEx

HS_MBL2.

Genevestigator

P11226.

GermOnline

ENSG00000165471. Homo sapiens.

Family and domain databases

Gene3D

3.10.100.10. 1 hit.

InterPro

IPR001304. C-type_lectin.
IPR016186. C-type_lectin-like.
IPR018378. C-type_lectin_CS.
IPR016187. C-type_lectin_fold.
IPR008160. Collagen.
[Graphical view]

Pfam

PF01391. Collagen. 1 hit.
PF00059. Lectin_C. 1 hit.
[Graphical view]

SMART

SM00034. CLECT. 1 hit.
[Graphical view]

SUPFAM

SSF56436. C-type_lectin_fold. 1 hit.

PROSITE

PS00615. C_TYPE_LECTIN_1. 1 hit.
PS50041. C_TYPE_LECTIN_2. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

ChEMBL

CHEMBL1795113.

EvolutionaryTrace

P11226.

GenomeRNAi

4153.

NextBio

16342.

PMAP-CutDB

P11226.

SOURCE

Search...

Entry information

Entry name

MBL2_HUMAN

Accession

Primary (citable) accession number: P11226
Secondary accession number(s): Q4VB12 , Q4VB13, Q86SI4, Q96KE4, Q96TF7, Q96TF8, Q96TF9

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 1, 1989
Last sequence update:	April 1, 1990
Last modified:	May 1, 2013
This is version 162 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.