Q9ERE7 (MESD_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
LDLR chaperone MESD

Alternative name(s):
Mesoderm development candidate 2
Mesoderm development protein

Gene names

Name:	Mesdc2
Synonyms:	Mesd

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	224 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	Chaperone specifically assisting the folding of beta-propeller/EGF modules within the family of low-density lipoprotein receptors (LDLRs). Acts as a modulator of the Wnt pathway through chaperoning the coreceptors of the canonical Wnt pathway, LRP5 and LRP6, to the plasma membrane. Essential for specification of embryonic polarity and mesoderm induction. Ref.4 Ref.7
Subunit structure	Monomer. Interacts with LRP5; the interaction prevents LRP5 from forming aggregates and chaperones LRP6 to the plasma membrane. Interacts with LRP6; the interaction prevents LRP6 from forming aggregates and chaperones LRP6 to the plasma membrane. Ref.4 Ref.5 Ref.8
Subcellular location	Endoplasmic reticulum Ref.4.
Tissue specificity	Expressed in many tissues, but not in skeletal muscles. Ref.1
Domain	The chaperone domain provides a folding template for proper folding of the beta-propeller (BP) domains of LRP5/6. Ref.7 The escort domain ensures LRP5/6 safe-trafficking from the ER to the Golgi by preventing premature ligand-binding. Ref.7
Disruption phenotype	Disruption of embryonic polarity and mesoderm differentiation, likely resulting from a primary defect in Wnt signaling. Ref.4
Sequence similarities	Belongs to the MESD family.
Sequence caution	The sequence AAH14742.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended. The sequence BAC36476.1 differs from that shown. Reason: Frameshift at position 207.

Ontologies

Keywords
Biological process	Wnt signaling pathway
Cellular component	Endoplasmic reticulum
Domain	Signal
Molecular function	Chaperone
PTM	Glycoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	Wnt receptor signaling pathway Inferred from electronic annotation. Source: UniProtKB-KW mesoderm development Non-traceable author statement Ref.1. Source: UniProtKB protein folding Inferred from mutant phenotype Ref.7. Source: UniProtKB protein localization to cell surface Inferred from direct assay PubMed 18505367. Source: MGI
Cellular_component	endoplasmic reticulum Inferred from electronic annotation. Source: UniProtKB-SubCell plasma membrane Inferred from direct assay PubMed 16263759. Source: MGI
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 29

29

Potential

Chain

30 – 224

195

LDLR chaperone MESD

PRO_0000096444

Regions

Region

1 – 155

155

Chaperone domain

Region

156 – 195

40

Escort domain

Motif

221 – 224

4

Prevents secretion from ER

Amino acid modifications

Glycosylation

192

1

N-linked (GlcNAc...) Potential

Experimental info

Sequence conflict

206

1

P → R in BAC36471. Ref.2

Secondary structure

1

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224

Helix Strand Turn

Details...

Turn

43 – 45

3

Helix

47 – 49

3

Helix

51 – 65

15

Beta strand

87 – 90

4

Helix

93 – 99

7

Beta strand

105 – 113

9

Helix

117 – 133

17

Beta strand

138 – 142

5

Beta strand

147 – 153

7

Helix

155 – 157

3

Helix

158 – 166

9

Beta strand

168 – 170

3

Beta strand

171 – 176

6

Beta strand

179 – 181

3

Beta strand

183 – 186

4

Helix

195 – 203

9

Beta strand

208 – 210

3

Helix

211 – 217

7

Sequences

	Sequence		Length	Mass (Da)
	Q9ERE7 [UniParc]. Last modified March 1, 2001. Version 1. Checksum: 6A94D5B315AE1D66	FASTA	224	25,207
	10 20 30 40 50 60 MAASRWLRAV LLFLCASDLL LLPPPNAYAA DTPGEATPPP RKKKDIRDYN DADMARLLEQ 70 80 90 100 110 120 WEKDDDIEEG DLPEHKRPSA PIDFSKLDPG KPESILKMTK KGKTLMMFVT VSGNPTEKET 130 140 150 160 170 180 EEITSLWQGS LFNANYDVQR FIVGSDRAIF MLRDGSYAWE IKDFLVSQDR CAEVTLEGQM 190 200 210 220 YPGKGGGSKE KNKTKPEKAK KKEGDPKPRA SKEDNRAGSR REDL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Identification of mesoderm development (mesd) candidate genes by comparative mapping and genome sequence analysis." Wines M.E., Lee L., Katari M.S., Zhang L., DeRossi C., Shi Y., Perkins S., Feldman M., McCombie W.R., Holdener B.C. Genomics 72:88-98(2001) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], TISSUE SPECIFICITY. Strain: 129/SvJ.
[2]	"The transcriptional landscape of the mammalian genome." Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y. Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Strain: C57BL/6J. Tissue: Medulla oblongata, Stomach and Testis.
[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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Strain: FVB/N. Tissue: Kidney.
[4]	"Mesd encodes an LRP5/6 chaperone essential for specification of mouse embryonic polarity." Hsieh J.-C., Lee L., Zhang L., Wefer S., Brown K., DeRossi C., Wines M.E., Rosenquist T., Holdener B.C. Cell 112:355-367(2003) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH LRP5 AND LRP6, SUBCELLULAR LOCATION, DISRUPTION PHENOTYPE.
[5]	"The solution structure of the core of mesoderm development (MESD), a chaperone for members of the LDLR-family." Kohler C., Andersen O.M., Diehl A., Krause G., Schmieder P., Oschkinat H. J. Struct. Funct. Genomics 7:131-138(2006) [PubMed] [Europe PMC] [Abstract] Cited for: STRUCTURE BY NMR OF 89-184, SUBUNIT.
[6]	"NMR structure note: solution structure of the core domain of MESD that is essential for proper folding of LRP5/6." Chen J., Li Q., Liu C.C., Zhou B., Bu G., Wang J. J. Biomol. NMR 47:283-288(2010) [PubMed] [Europe PMC] [Abstract] Cited for: STRUCTURE BY NMR OF 41-185.
[7]	"Two structural and functional domains of MESD required for proper folding and trafficking of LRP5/6." Chen J., Liu C.C., Li Q., Nowak C., Bu G., Wang J. Structure 19:313-323(2011) [PubMed] [Europe PMC] [Abstract] Cited for: STRUCTURE BY NMR OF 45-184, FUNCTION, DOMAINS CHAPERONE AND ESCORT.
[8]	"Structural characterization of the Boca/Mesd maturation factors for LDL-receptor-type ? propeller domains." Collins M.N., Hendrickson W.A. Structure 19:324-336(2011) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.01 ANGSTROMS) OF 98-183, SUBUNIT.
[9]	"The structure of MESD45-184 brings light into the mechanism of LDLR family folding." Koehler C., Lighthouse J.K., Werther T., Andersen O.M., Diehl A., Schmieder P., Du J., Holdener B.C., Oschkinat H. Structure 19:337-348(2011) [PubMed] [Europe PMC] [Abstract] Cited for: STRUCTURE BY NMR OF 45-184.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AF311213 Genomic DNA. Translation: AAG33621.1.
AK008735 mRNA. Translation: BAB25865.1.
AK031949 mRNA. Translation: BAC27617.1.
AK076760 mRNA. Translation: BAC36471.1.
AK076773 mRNA. Translation: BAC36476.1. Frameshift.
BC014742 mRNA. Translation: AAH14742.1. Different initiation.

IPI

IPI00349285.

RefSeq

NP_075892.3. NM_023403.3.

UniGene

Mm.117365.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2I9S	NMR	-	A	89-184	[»]
2KGL	NMR	-	A	30-224	[»]
2KMI	NMR	-	A	41-185	[»]
2RQK	NMR	-	A	45-184	[»]
2RQM	NMR	-	A	45-184	[»]
3OFH	X-ray	2.01	A/B	98-183	[»]

ProteinModelPortal

Q9ERE7.

SMR

Q9ERE7. Positions 30-224.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-59114N.

STRING

10090.ENSMUSP00000091768.

PTM databases

PhosphoSite

Q9ERE7.

2D gel databases

REPRODUCTION-2DPAGE

IPI00349285.
Q9ERE7.

Proteomic databases

PaxDb

Q9ERE7.

PRIDE

Q9ERE7.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENSMUST00000094215; ENSMUSP00000091768; ENSMUSG00000038503.

GeneID

67943.

KEGG

mmu:67943.

UCSC

uc009idx.2. mouse.

Organism-specific databases

CTD

23184.

MGI

MGI:1891421. Mesdc2.

Phylogenomic databases

eggNOG

NOG286690.

GeneTree

ENSGT00390000000993.

HOGENOM

HOG000230558.

InParanoid

Q91WK8.

OMA

IVGSNRA.

OrthoDB

EOG4QRH59.

Gene expression databases

ArrayExpress

Q9ERE7.

Bgee

Q9ERE7.

CleanEx

MM_MESDC2.

Genevestigator

Q9ERE7.

GermOnline

ENSMUSG00000038503. Mus musculus.

Family and domain databases

InterPro

IPR019330. Mesoderm_development_cand-2.
[Graphical view]

Pfam

PF10185. Mesd. 1 hit.
[Graphical view]

PROSITE

PS00014. ER_TARGET. False negative.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

Q9ERE7.

NextBio

326030.

SOURCE

Search...

Entry information

Entry name

MESD_MOUSE

Accession

Primary (citable) accession number: Q9ERE7
Secondary accession number(s): Q8C611 , Q8CCX7, Q91WK8, Q9CVB9

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 25, 2002
Last sequence update:	March 1, 2001
Last modified:	April 3, 2013
This is version 84 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program