P19999 (MBL1_RAT) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Mannose-binding protein A
Short name=MBP-A

Alternative name(s):
Mannan-binding protein

Gene names

Name:

Mbl1

Organism

Rattus norvegicus (Rat)

Taxonomic identifier

10116 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus

Protein attributes

Sequence length	238 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 By similarity.
Subunit structure	Oligomeric complex of 3 or more homotrimers. Oligomerization occurs in the endoplasmic reticulum By similarity. Interacts with MASP1 and MASP2. Ref.5 Ref.6
Subcellular location	Secreted. Note: According to Ref.6, long retention times in the endoplasmic reticulum and the Golgi apparatus that have been observed in former studies may reflect the abnormal physiology of the hepatoma cells used. Ref.6
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
Domain	Collagen Repeat Signal
Ligand	Calcium Lectin Mannose-binding
PTM	Disulfide bond Glycoprotein Hydroxylation
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological process	complement activation, classical pathway Inferred from electronic annotation. Source: UniProtKB-KW complement activation, lectin pathway Inferred from direct assay. Source: RGD
Cellular component	collagen Inferred from electronic annotation. Source: UniProtKB-KW extracellular space Inferred from direct assay Ref.6. Source: RGD
Molecular function	calcium ion binding Inferred from direct assay Ref.5. Source: UniProtKB calcium-dependent protein binding Inferred from physical interaction Ref.5. Source: UniProtKB mannose binding Inferred from direct assay. Source: RGD polysaccharide binding Inferred from direct assay. Source: RGD protease binding Inferred from direct assay. Source: RGD protein homodimerization activity Inferred from physical interaction Ref.5. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 17

17

Ref.4

Chain

18 – 238

221

Mannose-binding protein A

PRO_0000017414

Regions

Domain

39 – 88

50

Collagen-like

Domain

143 – 238

96

C-type lectin

Amino acid modifications

Modified residue

43

1

4-hydroxyproline Potential

Modified residue

44

1

5-hydroxylysine

Modified residue

47

1

5-hydroxylysine

Modified residue

61

1

4-hydroxyproline

Modified residue

67

1

4-hydroxyproline

Modified residue

73

1

4-hydroxyproline

Modified residue

78

1

4-hydroxyproline Potential

Modified residue

79

1

5-hydroxylysine Probable

Modified residue

82

1

5-hydroxylysine Probable

Glycosylation

44

1

O-linked (Gal...)

Glycosylation

47

1

O-linked (Gal...)

Disulfide bond

145 ↔ 234

Disulfide bond

212 ↔ 226

Experimental info

Mutagenesis

40

1

R → C: Prevents higher order oligomer assembly. Slight reduction in secretion rate. Ref.6

Mutagenesis

42

1

G → E: Disrupts homotrimer formation. 5-fold reduction in secretion rate. Prevents K-44 hydroxylation and glycosylation. 10-fold decrease in complement activation. Ref.6

Mutagenesis

44

1

K → R: No effect on secretion rate, nor on homooligomer formation. 3-fold reduction in secretion rate; when associated eith R-47. Prevents higher order oligomer assembly; when associated eith R-47. 10-fold decrease in complement activation; when associated eith R-47. Ref.6

Mutagenesis

45

1

G → D: Disrupts homotrimer formation. 5-fold reduction in secretion rate. Prevents K-47 hydroxylation and glycosylation. Ref.6

Mutagenesis

47

1

K → R: No effect on secretion rate, nor on homooligomer formation. 3-fold reduction in secretion rate; when associated eith R-44. Prevents higher order oligomer assembly; when associated eith R-44. 10-fold decrease in complement activation; when associated eith R-44. Ref.6

Sequence conflict

156

1

R → K in AAA98781. Ref.2

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

238

Helix Strand Turn

Details...

Helix

91 – 119

29

Beta strand

128 – 137

10

Helix

138 – 147

10

Helix

158 – 168

11

Beta strand

172 – 181

10

Beta strand

184 – 187

4

Beta strand

190 – 192

3

Beta strand

212 – 215

4

Beta strand

221 – 224

4

Beta strand

228 – 236

9

Sequences

	Sequence		Length	Mass (Da)
	P19999 [UniParc]. Last modified February 1, 1991. Version 1. Checksum: 1A927482B8A8CB3D	FASTA	238	25,308
	10 20 30 40 50 60 MLLLPLLVLL CVVSVSSSGS QTCEETLKTC SVIACGRDGR DGPKGEKGEP GQGLRGLQGP 70 80 90 100 110 120 PGKLGPPGSV GAPGSQGPKG QKGDRGDSRA IEVKLANMEA EINTLKSKLE LTNKLHAFSM 130 140 150 160 170 180 GKKSGKKFFV TNHERMPFSK VKALCSELRG TVAIPRNAEE NKAIQEVAKT SAFLGITDEV 190 200 210 220 230 TEGQFMYVTG GRLTYSNWKK DEPNDHGSGE DCVTIVDNGL WNDISCQASH TAVCEFPA

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Mannose-binding proteins isolated from rat liver contain carbohydrate-recognition domains linked to collagenous tails. Complete primary structures and homology with pulmonary surfactant apoprotein." Drickamer K., Dordal M.S., Reynolds L. J. Biol. Chem. 261:6878-6887(1986) [PubMed: 3009480] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], PARTIAL PROTEIN SEQUENCE. Tissue: Liver.
[2]	"Exon structure of a mannose-binding protein gene reflects its evolutionary relationship to the asialoglycoprotein receptor and nonfibrillar collagens." Drickamer K., McCreary V. J. Biol. Chem. 262:2582-2589(1987) [PubMed: 3029088] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Tissue: Liver.
[3]	"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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Liver.
[4]	"Serum lectin with known structure activates complement through the classical pathway." Ikeda K., Sannoh T., Kawasaki N., Kawasaki T., Yamashina I. J. Biol. Chem. 262:7451-7454(1987) [PubMed: 3584121] [Abstract] Cited for: PROTEIN SEQUENCE OF 18-42.
[5]	"Interaction of mannose-binding protein with associated serine proteases: effects of naturally occuring mutations." Wallis R., Dodd R.B. J. Biol. Chem. 275:30962-30969(2000) [PubMed: 10913141] [Abstract] Cited for: INTERACTION WITH MASP1 AND MASP2. Tissue: Liver.
[6]	"Impaired secretion of rat mannose-binding protein resulting from mutations in the collagen-like domain." Heise C.T., Nicholls J.R., Leamy C.E., Wallis R. J. Immunol. 165:1403-1409(2000) [PubMed: 10903744] [Abstract] Cited for: SUBCELLULAR LOCATION, GLYCOSYLATION, OLIGOMERIZATION, MUTAGENESIS OF ARG-40; GLY-42; LYS-44; GLY-45 AND LYS-47.
[7]	"Structure of the calcium-dependent lectin domain from a rat mannose-binding protein determined by MAD phasing." Weis W.I., Kahn R., Fourme R., Drickamer K., Hendrickson W.A. Science 254:1608-1615(1991) [PubMed: 1721241] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 124-238.
[8]	"Structure of a C-type mannose-binding protein complexed with an oligosaccharide." Weis W.I., Drickamer K., Hendrickson W.A. Nature 360:127-134(1992) [PubMed: 1436090] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) OF 124-238.
[9]	"Trimeric structure of a C-type mannose-binding protein." Weis W.I., Drickamer K. Structure 2:1227-1240(1994) [PubMed: 7704532] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 84-238.
[10]	"Ca2+-dependent structural changes in C-type mannose-binding proteins." Ng K.K.-S., Park-Snyder S., Weis W.I. Biochemistry 37:17965-17976(1998) [PubMed: 9922165] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 90-238.
+	Additional computationally mapped references.

Web resources

Functional Glycomics Gateway - Glycan Binding

Mannose-binding protein A

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

M14105, M14104 Genomic DNA. Translation: AAA98781.1.
BC088159 mRNA. Translation: AAH88159.1.

IPI

IPI00325371.

PIR

LNRTMA. B24791.

RefSeq

NP_036731.2. NM_012599.2.

UniGene

Rn.10273.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1AFA	X-ray	2.00	1/2/3	90-238	[»]
1AFB	X-ray	1.90	1/2/3	90-238	[»]
1AFD	X-ray	2.00	1/2/3	90-238	[»]
1BCH	X-ray	2.00	1/2/3	90-238	[»]
1BCJ	X-ray	2.10	1/2/3	90-238	[»]
1BUU	X-ray	1.90	A	75-238	[»]
1FIF	X-ray	1.95	A/B/C	90-238	[»]
1FIH	X-ray	1.95	A/B/C	90-238	[»]
1KMB	X-ray	2.10	1/2/3	90-238	[»]
1KWT	X-ray	1.95	A/B/C	90-238	[»]
1KWU	X-ray	1.95	A/B/C	90-238	[»]
1KWV	X-ray	2.00	A/B/C	90-238	[»]
1KWW	X-ray	1.90	A/B/C	90-238	[»]
1KWX	X-ray	2.00	A/B/C	90-238	[»]
1KWY	X-ray	2.00	A/B/C	90-238	[»]
1KWZ	X-ray	1.90	A/B/C	90-238	[»]
1KX0	X-ray	2.00	A/B/C	90-238	[»]
1KX1	X-ray	2.80	A/B/C/D/E/F	90-238	[»]
1MSB	X-ray	2.30	A/B	124-238	[»]
1RTM	X-ray	1.80	1/2/3	90-238	[»]
1YTT	X-ray	1.80	A/B	124-238	[»]
2KMB	X-ray	2.00	1/2/3	90-238	[»]
2MSB	X-ray	1.70	A/B	124-238	[»]
3KMB	X-ray	1.95	1/2/3	90-238	[»]
4KMB	X-ray	2.00	1/2/3	90-238	[»]

ProteinModelPortal

P19999.

SMR

P19999. Positions 90-238.

ModBase

Search...

Protein-protein interaction databases

STRING

P19999.

Proteomic databases

PRIDE

P19999.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENSRNOT00000015723; ENSRNOP00000015723; ENSRNOG00000011706.

GeneID

24548.

KEGG

rno:24548.

UCSC

NM_012599. rat.

Organism-specific databases

CTD

17194.

RGD

3055. Mbl1.

Phylogenomic databases

eggNOG

maNOG19819.

GeneTree

ENSGT00550000074259.

HOVERGEN

HBG108270.

InParanoid

P19999.

OMA

NGLWNDI.

OrthoDB

EOG4DJJXF.

PhylomeDB

P19999.

Gene expression databases

ArrayExpress

P19999.

Genevestigator

P19999.

GermOnline

ENSRNOG00000011706. Rattus norvegicus.

Family and domain databases

InterPro

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

Gene3D

G3DSA:3.10.100.10. C-type_lectin-like. 1 hit.

KO

K03991.

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

NextBio

603650.

PMAP-CutDB

P19999.

Entry information

Entry name

MBL1_RAT

Accession

Primary (citable) accession number: P19999

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 1, 1991
Last sequence update:	February 1, 1991
Last modified:	November 16, 2011
This is version 122 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program