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P49257 (LMAN1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 148. 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·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Protein ERGIC-53
Alternative name(s):
ER-Golgi intermediate compartment 53 kDa protein
Gp58
Intracellular mannose-specific lectin MR60
Lectin mannose-binding 1
Gene names
Name:LMAN1
Synonyms:ERGIC53, F5F8D
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length510 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Mannose-specific lectin. May recognize sugar residues of glycoproteins, glycolipids, or glycosylphosphatidyl inositol anchors and may be involved in the sorting or recycling of proteins, lipids, or both. The LMAN1-MCFD2 complex forms a specific cargo receptor for the ER-to-Golgi transport of selected proteins. Ref.8 Ref.9

Subunit structure

Exists both as a covalent disulfide-linked homohexamer, and a complex of three disulfide-linked dimers non-covalently kept together. Interacts with MCFD2. Ref.8 Ref.9 Ref.10 Ref.12 Ref.13

Subcellular location

Endoplasmic reticulum-Golgi intermediate compartment membrane; Single-pass type I membrane protein. Golgi apparatus membrane; Single-pass membrane protein. Endoplasmic reticulum membrane; Single-pass type I membrane protein Ref.8 Ref.10.

Tissue specificity

Ubiquitous. Ref.8

Domain

The FF ER export motif at the C-terminus is not sufficient to support endoplasmic reticulum exit, and needs assistance of Gln-501 for proper recognition of COPII coat components.

Post-translational modification

The N-terminal may be partly blocked.

Involvement in disease

Factor V and factor VIII combined deficiency 1 (F5F8D1) [MIM:227300]: A blood coagulation disorder characterized by bleeding symptoms similar to those in hemophilia or parahemophilia, that are caused by single deficiency of FV or FVIII, respectively. The most common symptoms are epistaxis, menorrhagia, and excessive bleeding during or after trauma. Plasma levels of coagulation factors V and VIII are in the range of 5 to 30% of normal.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.3

Sequence similarities

Contains 1 L-type lectin-like domain.

Mass spectrometry

Molecular mass is 54222.91 Da from positions 31 - 510. Determined by MALDI. Ref.7

Ontologies

Keywords
   Biological processER-Golgi transport
Protein transport
Transport
   Cellular componentEndoplasmic reticulum
Golgi apparatus
Membrane
   Coding sequence diversityPolymorphism
   DomainSignal
Transmembrane
Transmembrane helix
   LigandLectin
Metal-binding
   PTMDisulfide bond
   Technical term3D-structure
Complete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processER to Golgi vesicle-mediated transport

Traceable author statement PubMed 9546392. Source: ProtInc

Golgi organization

Inferred from mutant phenotype PubMed 18287528. Source: UniProtKB

blood coagulation

Traceable author statement PubMed 9546392. Source: ProtInc

cellular protein metabolic process

Traceable author statement. Source: Reactome

endoplasmic reticulum organization

Inferred from electronic annotation. Source: Ensembl

positive regulation of organelle organization

Inferred from mutant phenotype PubMed 18287528. Source: UniProtKB

post-translational protein modification

Traceable author statement. Source: Reactome

protein N-linked glycosylation via asparagine

Traceable author statement. Source: Reactome

protein folding

Traceable author statement PubMed 9546392. Source: ProtInc

protein transport

Inferred from electronic annotation. Source: UniProtKB-KW

   Cellular_componentER to Golgi transport vesicle membrane

Traceable author statement. Source: Reactome

Golgi membrane

Traceable author statement Ref.2. Source: ProtInc

endoplasmic reticulum membrane

Traceable author statement Ref.2. Source: ProtInc

endoplasmic reticulum-Golgi intermediate compartment

Inferred from direct assay PubMed 15308636. Source: UniProtKB

endoplasmic reticulum-Golgi intermediate compartment membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

extracellular vesicular exosome

Inferred from direct assay PubMed 19199708. Source: UniProt

integral component of membrane

Traceable author statement Ref.2. Source: ProtInc

sarcomere

Inferred from electronic annotation. Source: Ensembl

   Molecular_functionmannose binding

Traceable author statement Ref.2. Source: ProtInc

metal ion binding

Inferred from electronic annotation. Source: UniProtKB-KW

protein binding

Inferred from physical interaction PubMed 9774442. Source: UniProtKB

unfolded protein binding

Traceable author statement PubMed 9546392. Source: ProtInc

Complete GO annotation...

Binary interactions

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 3030 Ref.1 Ref.2 Ref.5
Chain31 – 510480Protein ERGIC-53
PRO_0000017660

Regions

Topological domain31 – 477447Lumenal Potential
Transmembrane478 – 49821Helical; Potential
Topological domain499 – 51012Cytoplasmic Potential
Domain44 – 267224L-type lectin-like
Region251 – 2533Carbohydrate binding By similarity
Motif509 – 5102ER export motif

Sites

Metal binding1521Calcium
Metal binding1541Calcium; via carbonyl oxygen
Metal binding1561Calcium
Metal binding1811Calcium
Binding site881Carbohydrate By similarity
Binding site1211Carbohydrate By similarity
Binding site1561Carbohydrate By similarity
Binding site1781Carbohydrate By similarity
Site5011Required for ER export

Amino acid modifications

Disulfide bond190 ↔ 230 Ref.8 Ref.10 Ref.12 Ref.13
Disulfide bond466Interchain Ref.8 Ref.10 Ref.12 Ref.13
Disulfide bond475Interchain Ref.8 Ref.10 Ref.12 Ref.13

Natural variations

Natural variant141R → Q. Ref.3
Corresponds to variant rs1043302 [ dbSNP | Ensembl ].
VAR_013703
Natural variant391V → A. Ref.3
Corresponds to variant rs33926449 [ dbSNP | Ensembl ].
VAR_013704
Natural variant3551I → T.
Corresponds to variant rs3737392 [ dbSNP | Ensembl ].
VAR_049770
Natural variant4101M → L. Ref.3 Ref.4
Corresponds to variant rs2298711 [ dbSNP | Ensembl ].
VAR_013705

Experimental info

Sequence conflict1531S → T in CAA50653. Ref.1

Secondary structure

................................................. 510
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P49257 [UniParc].

Last modified August 13, 2002. Version 2.
Checksum: B87EF117C0CD386C

FASTA51057,549
        10         20         30         40         50         60 
MAGSRQRGLR ARVRPLFCAL LLSLGRFVRG DGVGGDPAVA LPHRRFEYKY SFKGPHLVQS 

        70         80         90        100        110        120 
DGTVPFWAHA GNAIPSSDQI RVAPSLKSQR GSVWTKTKAA FENWEVEVTF RVTGRGRIGA 

       130        140        150        160        170        180 
DGLAIWYAEN QGLEGPVFGS ADLWNGVGIF FDSFDNDGKK NNPAIVIIGN NGQIHYDHQN 

       190        200        210        220        230        240 
DGASQALASC QRDFRNKPYP VRAKITYYQN TLTVMINNGF TPDKNDYEFC AKVENMIIPA 

       250        260        270        280        290        300 
QGHFGISAAT GGLADDHDVL SFLTFQLTEP GKEPPTPDKE ISEKEKEKYQ EEFEHFQQEL 

       310        320        330        340        350        360 
DKKKEEFQKG HPDLQGQPAE EIFESVGDRE LRQVFEGQNR IHLEIKQLNR QLDMILDEQR 

       370        380        390        400        410        420 
RYVSSLTEEI SKRGAGMPGQ HGQITQQELD TVVKTQHEIL RQVNEMKNSM SETVRLVSGM 

       430        440        450        460        470        480 
QHPGSAGGVY ETTQHFIDIK EHLHIVKRDI DNLVQRNMPS NEKPKCPELP PFPSCLSTVH 

       490        500        510 
FIIFVVVQTV LFIGYIMYRS QQEAAAKKFF 

« Hide

References

« Hide 'large scale' references
[1]"ERGIC-53, a membrane protein of the ER-Golgi intermediate compartment, carries an ER retention motif."
Schindler R., Itin C., Zerial M., Lottspeich F., Hauri H.-P.
Eur. J. Cell Biol. 61:1-9(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 31-59 AND 418-432.
Tissue: Liver and Placenta.
[2]"ERGIC-53, a membrane protein of the endoplasmic reticulum-Golgi intermediate compartment, is identical to MR60, an intracellular mannose-specific lectin of myelomonocytic cells."
Arar C., Carpentier V., Le Caer J.-P., Monsigny M., Legrand A., Roche A.-C.
J. Biol. Chem. 270:3551-3553(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 31-41.
Tissue: Peripheral blood.
[3]"ERGIC-53 gene structure and mutation analysis in 19 combined factors V and VIII deficiency families."
Nichols W.C., Terry V.H., Wheatley M.A., Yang A., Zivelin A., Ciavarella N., Stefanile C., Matsushita T., Saito H., de Bosch N.B., Ruiz-Saez A., Torres A., Thompson A.R., Feinstein D.I., White G.C., Negrier C., Vinciguerra C., Aktan M. expand/collapse author list , Kaufman R.J., Ginsburg D., Seligsohn U.
Blood 93:2261-2266(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS GLN-14; ALA-39 AND LEU-410, INVOLVEMENT IN F5F8D1.
[4]"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 LEU-410.
Tissue: Brain.
[5]"Exploring proteomes and analyzing protein processing by mass spectrometric identification of sorted N-terminal peptides."
Gevaert K., Goethals M., Martens L., Van Damme J., Staes A., Thomas G.R., Vandekerckhove J.
Nat. Biotechnol. 21:566-569(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 31-44.
Tissue: Platelet.
[6]"A putative novel class of animal lectins in the secretory pathway homologous to leguminous lectins."
Fiedler K., Simons K.
Cell 77:625-626(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: SIMILARITY TO LEGUMINOUS LECTINS.
[7]"Cluster analysis of an extensive human breast cancer cell line protein expression map database."
Harris R.A., Yang A., Stein R.C., Lucy K., Brusten L., Herath A., Parekh R., Waterfield M.D., O'Hare M.J., Neville M.A., Page M.J., Zvelebil M.J.
Proteomics 2:212-223(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: MASS SPECTROMETRY.
Tissue: Mammary cancer.
[8]"ER export of ERGIC-53 is controlled by cooperation of targeting determinants in all three of its domains."
Nufer O., Kappeler F., Guldbrandsen S., Hauri H.-P.
J. Cell Sci. 116:4429-4440(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, TISSUE SPECIFICITY, SUBCELLULAR LOCATION, MOTIF ER EXPORT, DISULFIDE BOND.
[9]"Bleeding due to disruption of a cargo-specific ER-to-Golgi transport complex."
Zhang B., Cunningham M.A., Nichols W.C., Bernat J.A., Seligsohn U., Pipe S.W., McVey J.H., Schulte-Overberg U., de Bosch N.B., Ruiz-Saez A., White G.C., Tuddenham E.G., Kaufman R.J., Ginsburg D.
Nat. Genet. 34:220-225(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH MCFD2, FUNCTION.
[10]"Oligomerization and intracellular localization of the glycoprotein receptor ERGIC-53 is independent of disulfide bonds."
Neve E.P., Lahtinen U., Pettersson R.F.
J. Mol. Biol. 354:556-568(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION, SUBUNIT, INTERCHAIN DISULFIDE BONDS.
[11]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[12]"Crystal structure of the LMAN1-CRD/MCFD2 transport receptor complex provides insight into combined deficiency of factor V and factor VIII."
Wigren E., Bourhis J.M., Kursula I., Guy J.E., Lindqvist Y.
FEBS Lett. 584:878-882(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.45 ANGSTROMS) OF 32-277 IN COMPLEX WITH MCFD2 AND CALCIUM IONS, SUBUNIT, DISULFIDE BOND.
[13]"Structural basis for the cooperative interplay between the two causative gene products of combined factor V and factor VIII deficiency."
Nishio M., Kamiya Y., Mizushima T., Wakatsuki S., Sasakawa H., Yamamoto K., Uchiyama S., Noda M., McKay A.R., Fukui K., Hauri H.P., Kato K.
Proc. Natl. Acad. Sci. U.S.A. 107:4034-4039(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.84 ANGSTROMS) OF 31-285 IN COMPLEX WITH CALCIUM IONS, SUBUNIT, DISULFIDE BOND.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
X71661 mRNA. Translation: CAA50653.1.
U09716 mRNA. Translation: AAA95960.1.
AF081866, AF081865 Genomic DNA. Translation: AAD32479.1.
AF081867 Genomic DNA. Translation: AAD32480.1.
AF081869, AF081868 Genomic DNA. Translation: AAD32481.1.
AF081871, AF081870 Genomic DNA. Translation: AAD32482.1.
AF081873, AF081872 Genomic DNA. Translation: AAD32483.1.
AF081875, AF081874 Genomic DNA. Translation: AAD32484.1.
AF081877, AF081876 Genomic DNA. Translation: AAD32485.1.
AF081879, AF081878 Genomic DNA. Translation: AAD32486.1.
AF081880 Genomic DNA. Translation: AAD32487.1.
AF081882, AF081881 Genomic DNA. Translation: AAD32488.1.
AF081884, AF081883 Genomic DNA. Translation: AAD32489.1.
AF081885 Genomic DNA. Translation: AAD32490.1.
BC032330 mRNA. Translation: AAH32330.1.
CCDSCCDS11974.1.
PIRS42626.
RefSeqNP_005561.1. NM_005570.3.
UniGeneHs.465295.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
3A4UX-ray1.84A31-285[»]
3LCPX-ray2.45A/B32-277[»]
3WHTX-ray1.80A31-269[»]
3WHUX-ray2.60A31-269[»]
3WNXX-ray2.75A31-269[»]
4GKXX-ray2.70A/B/C/D/E/F31-270[»]
4GKYX-ray2.42A31-270[»]
ProteinModelPortalP49257.
SMRP49257. Positions 41-269.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid110185. 30 interactions.
DIPDIP-42188N.
IntActP49257. 8 interactions.
MINTMINT-4999949.

Chemistry

DrugBankDB00025. Antihemophilic Factor.

PTM databases

PhosphoSiteP49257.

Polymorphism databases

DMDM22261801.

Proteomic databases

MaxQBP49257.
PaxDbP49257.
PeptideAtlasP49257.
PRIDEP49257.

Protocols and materials databases

DNASU3998.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000251047; ENSP00000251047; ENSG00000074695.
GeneID3998.
KEGGhsa:3998.
UCSCuc002lhz.3. human.

Organism-specific databases

CTD3998.
GeneCardsGC18M056969.
HGNCHGNC:6631. LMAN1.
HPACAB037163.
HPA002320.
MIM227300. phenotype.
601567. gene.
neXtProtNX_P49257.
Orphanet35909. Combined deficiency of factor V and factor VIII.
PharmGKBPA30399.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG292314.
HOVERGENHBG052332.
InParanoidP49257.
KOK10080.
OMAGTVPFWA.
OrthoDBEOG7QC7VR.
PhylomeDBP49257.
TreeFamTF313311.

Enzyme and pathway databases

ReactomeREACT_17015. Metabolism of proteins.

Gene expression databases

BgeeP49257.
GenevestigatorP49257.

Family and domain databases

Gene3D2.60.120.200. 1 hit.
InterProIPR008985. ConA-like_lec_gl_sf.
IPR013320. ConA-like_subgrp.
IPR005052. Lectin_leg.
[Graphical view]
PANTHERPTHR12223. PTHR12223. 1 hit.
PfamPF03388. Lectin_leg-like. 1 hit.
[Graphical view]
SUPFAMSSF49899. SSF49899. 1 hit.
PROSITEPS51328. L_LECTIN_LIKE. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceP49257.
GeneWikiLMAN1.
GenomeRNAi3998.
NextBio15688.
PROP49257.
SOURCESearch...

Entry information

Entry nameLMAN1_HUMAN
AccessionPrimary (citable) accession number: P49257
Secondary accession number(s): Q12895 expand/collapse secondary AC list , Q8N5I7, Q9UQG1, Q9UQG2, Q9UQG3, Q9UQG4, Q9UQG5, Q9UQG6, Q9UQG7, Q9UQG8, Q9UQG9, Q9UQH0, Q9UQH1, Q9UQH2
Entry history
Integrated into UniProtKB/Swiss-Prot: February 1, 1996
Last sequence update: August 13, 2002
Last modified: July 9, 2014
This is version 148 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 18

Human chromosome 18: entries, gene names and cross-references to MIM