P49257 (LMAN1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

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	510 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	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 process	ER-Golgi transport Protein transport Transport
Cellular component	Endoplasmic reticulum Golgi apparatus Membrane
Coding sequence diversity	Polymorphism
Domain	Signal Transmembrane Transmembrane helix
Ligand	Lectin Metal-binding
PTM	Disulfide bond
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	ER 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 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_component	ER 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 integral to membrane Traceable author statement Ref.2. Source: ProtInc sarcomere Inferred from electronic annotation. Source: Compara
Molecular_function	mannose binding Traceable author statement Ref.2. Source: ProtInc metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW unfolded protein binding Traceable author statement PubMed 9546392. Source: ProtInc
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
SURF4	O15260	3	EBI-1057738,EBI-1044848

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 30

30

Ref.1 Ref.2 Ref.5

Chain

31 – 510

480

Protein ERGIC-53

PRO_0000017660

Regions

Topological domain

31 – 477

447

Lumenal Potential

Transmembrane

478 – 498

21

Helical; Potential

Topological domain

499 – 510

12

Cytoplasmic Potential

Domain

44 – 267

224

L-type lectin-like

Region

251 – 253

3

Carbohydrate binding By similarity

Motif

509 – 510

2

ER export motif

Sites

Metal binding

152

1

Calcium

Metal binding

154

1

Calcium; via carbonyl oxygen

Metal binding

156

1

Calcium

Metal binding

181

1

Calcium

Binding site

88

1

Carbohydrate By similarity

Binding site

121

1

Carbohydrate By similarity

Binding site

156

1

Carbohydrate By similarity

Binding site

178

1

Carbohydrate By similarity

Site

501

1

Required for ER export

Amino acid modifications

Disulfide bond

190 ↔ 230

Ref.8 Ref.10 Ref.12 Ref.13

Disulfide bond

466

Interchain Ref.8 Ref.10 Ref.12 Ref.13

Disulfide bond

475

Interchain Ref.8 Ref.10 Ref.12 Ref.13

Natural variations

Natural variant

14

1

R → Q. Ref.3
Corresponds to variant rs1043302 [ dbSNP | Ensembl ].

VAR_013703

Natural variant

39

1

V → A. Ref.3
Corresponds to variant rs33926449 [ dbSNP | Ensembl ].

VAR_013704

Natural variant

355

1

I → T.
Corresponds to variant rs3737392 [ dbSNP | Ensembl ].

VAR_049770

Natural variant

410

1

M → L. Ref.3 Ref.4
Corresponds to variant rs2298711 [ dbSNP | Ensembl ].

VAR_013705

Experimental info

Sequence conflict

153

1

S → T in CAA50653. Ref.1

Secondary structure

1

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510

Helix Strand Turn

Details...

Beta strand

43 – 46

4

Helix

48 – 50

3

Beta strand

52 – 56

5

Beta strand

67 – 71

5

Beta strand

80 – 83

4

Beta strand

90 – 97

8

Beta strand

102 – 113

12

Beta strand

115 – 118

4

Beta strand

122 – 130

9

Beta strand

134 – 137

4

Beta strand

145 – 152

8

Beta strand

163 – 172

10

Helix

178 – 180

3

Helix

183 – 185

3

Beta strand

187 – 191

5

Beta strand

201 – 208

8

Beta strand

211 – 217

7

Beta strand

219 – 222

4

Beta strand

228 – 235

8

Beta strand

240 – 249

10

Beta strand

256 – 268

13

Sequences

	Sequence		Length	Mass (Da)
	P49257 [UniParc]. Last modified August 13, 2002. Version 2. Checksum: B87EF117C0CD386C	FASTA	510	57,549
	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

References

	« Hide 'large scale' referencesShow '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. , 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.

IPI

IPI00026530.

PIR

S42626.

RefSeq

NP_005561.1. NM_005570.3.

UniGene

Hs.465295.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
3A4U	X-ray	1.84	A	31-285	[»]
3LCP	X-ray	2.45	A/B	32-277	[»]

ProteinModelPortal

P49257.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-42188N.

IntAct

P49257. 5 interactions.

MINT

MINT-4999949.

PTM databases

PhosphoSite

P49257.

Polymorphism databases

DMDM

22261801.

Proteomic databases

PaxDb

P49257.

PeptideAtlas

P49257.

PRIDE

P49257.

Protocols and materials databases

DNASU

3998.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000251047; ENSP00000251047; ENSG00000074695.

GeneID

3998.

KEGG

hsa:3998.

UCSC

uc002lhz.3. human.

Organism-specific databases

CTD

3998.

GeneCards

GC18M056969.

HGNC

HGNC:6631. LMAN1.

HPA

HPA002320.

MIM

227300. phenotype.
601567. gene.

neXtProt

NX_P49257.

Orphanet

35909. Combined deficiency of factor V and factor VIII.

PharmGKB

PA30399.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG292314.

HOVERGEN

HBG052332.

InParanoid

P49257.

KO

K10080.

OMA

GTVPFWA.

OrthoDB

EOG4NCMCM.

PhylomeDB

P49257.

Enzyme and pathway databases

Reactome

REACT_17015. Metabolism of proteins.

Gene expression databases

Bgee

P49257.

Genevestigator

P49257.

GermOnline

ENSG00000074695. Homo sapiens.

Family and domain databases

Gene3D

2.60.120.200. 1 hit.

InterPro

IPR008985. ConA-like_lec_gl_sf.
IPR013320. ConA-like_subgrp.
IPR005052. Lectin_leg.
[Graphical view]

PANTHER

PTHR12223. PTHR12223. 1 hit.

Pfam

PF03388. Lectin_leg-like. 1 hit.
[Graphical view]

SUPFAM

SSF49899. ConA_like_lec_gl. 1 hit.

PROSITE

PS51328. L_LECTIN_LIKE. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

DrugBank

DB00025. Antihemophilic Factor.

EvolutionaryTrace

P49257.

GenomeRNAi

3998.

NextBio

15688.

SOURCE

Search...

Entry information

Entry name

LMAN1_HUMAN

Accession

Primary (citable) accession number: P49257
Secondary accession number(s): Q12895 , 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:	May 1, 2013
This is version 136 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.