Reviewed, UniProtKB/Swiss-Prot P11717 (MPRI_HUMAN)

Names and origin

Protein names

Recommended name:
    Cation-independent mannose-6-phosphate receptor
      Short name=CI Man-6-P receptor
      Short name=CI-MPR
      Short name=M6PR
Alternative name(s):
    Insulin-like growth factor 2 receptor
    Insulin-like growth factor II receptor
      Short name=IGF-II receptor
    M6P/IGF2 receptor
      Short name=M6P/IGF2R
    300 kDa mannose 6-phosphate receptor
    MPR 300
    CD_antigen=CD222

Gene names

Name:	IGF2R
Synonyms:	MPRI

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	2491 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	Transport of phosphorylated lysosomal enzymes from the Golgi complex and the cell surface to lysosomes. Lysosomal enzymes bearing phosphomannosyl residues bind specifically to mannose-6-phosphate receptors in the Golgi apparatus and the resulting receptor-ligand complex is transported to an acidic prelyosomal compartment where the low pH mediates the dissociation of the complex. This receptor also binds IGF2.
Subunit structure	Binds GGA1, GGA2 and GGA3.
Subcellular location	Lysosome membrane; Single-pass type I membrane protein.
Domain	Contains 15 repeating units of approximately 147 AA. The most highly conserved region within the repeat consists of a stretch of 13 AA that contains cysteines at both ends.
Sequence similarities	Belongs to the MRL1/IGF2R family. Contains 1 fibronectin type-II domain.

Ontologies

Keywords
Biological process	Transport
Cellular component	Lysosome Membrane
Coding sequence diversity	Polymorphism
Domain	Repeat Signal Transmembrane
Molecular function	Receptor
PTM	Glycoprotein Phosphoprotein
Technical term	3D-structure Direct protein sequencing
Gene Ontology (GO)
Biological process	receptor-mediated endocytosis Traceable author statement. Source: ProtInc signal transduction Traceable author statement. Source: ProtInc
Cellular component	endosome Inferred from direct assay. Source: MGI integral to plasma membrane Traceable author statement. Source: ProtInc lysosomal membrane Inferred from electronic annotation. Source: UniProtKB-SubCell trans-Golgi network transport vesicle Inferred from direct assay. Source: MGI
Molecular function	insulin-like growth factor receptor activity Traceable author statement. Source: ProtInc transporter activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 40

40

Chain

41 – 2491

2451

Cation-independent mannose-6-phosphate receptor

PRO_0000019229

Regions

Topological domain

41 – 2304

2264

Lumenal Potential

Transmembrane

2305 – 2327

23

Potential

Topological domain

2328 – 2491

164

Cytoplasmic Potential

Repeat

40 – 189

150

1

Repeat

190 – 344

155

2

Repeat

345 – 489

145

3

Repeat

490 – 643

154

4

Repeat

644 – 783

140

5

Repeat

784 – 950

167

6

Repeat

951 – 1099

149

7

Repeat

1100 – 1243

144

8

Repeat

1244 – 1384

141

9

Repeat

1385 – 1532

148

10

Repeat

1533 – 1666

134

11

Repeat

1667 – 1820

154

12

Repeat

1821 – 2008

188

13

Domain

1898 – 1944

47

Fibronectin type-II

Repeat

2009 – 2137

129

14

Repeat

2165 – 2289

125

15

Amino acid modifications

Modified residue

2409

1

Phosphoserine

Modified residue

2479

1

Phosphoserine

Modified residue

2484

1

Phosphoserine

Glycosylation

112

1

N-linked (GlcNAc...)

Glycosylation

400

1

N-linked (GlcNAc...) Potential

Glycosylation

435

1

N-linked (GlcNAc...) Potential

Glycosylation

543

1

N-linked (GlcNAc...) Potential

Glycosylation

581

1

N-linked (GlcNAc...)

Glycosylation

626

1

N-linked (GlcNAc...) Potential

Glycosylation

747

1

N-linked (GlcNAc...)

Glycosylation

871

1

N-linked (GlcNAc...) Potential

Glycosylation

951

1

N-linked (GlcNAc...) Potential

Glycosylation

957

1

N-linked (GlcNAc...) Potential

Glycosylation

1164

1

N-linked (GlcNAc...) Potential

Glycosylation

1246

1

N-linked (GlcNAc...)

Glycosylation

1312

1

N-linked (GlcNAc...) Potential

Glycosylation

1656

1

N-linked (GlcNAc...) Potential

Glycosylation

1757

1

N-linked (GlcNAc...) Potential

Glycosylation

1816

1

N-linked (GlcNAc...) Potential

Glycosylation

2085

1

N-linked (GlcNAc...) Potential

Glycosylation

2136

1

N-linked (GlcNAc...) Potential

Disulfide bond

1903 ↔ 1927

By similarity

Disulfide bond

1917 ↔ 1942

By similarity

Natural variations

Natural variant

91

1

R → H: dbSNP rs8191704.

VAR_021304

Natural variant

203

1

P → L: dbSNP rs8191746.

VAR_020470

Natural variant

231

1

G → D: dbSNP rs8191753.

VAR_021305

Natural variant

252

1

L → V: dbSNP rs8191754.

VAR_020471

Natural variant

273

1

D → G: dbSNP rs8191758.

VAR_021306

Natural variant

512

1

K → Q: dbSNP rs8191776.

VAR_021307

Natural variant

529

1

R → Q: dbSNP rs6413489.

VAR_020472

Natural variant

604

1

G → S: dbSNP rs8191797.

VAR_020473

Natural variant

724

1

A → T: dbSNP rs6413491.

VAR_020474

Natural variant

817

1

L → V: dbSNP rs8191808.

VAR_021308

Natural variant

856

1

G → S: dbSNP rs8191819.

VAR_020475

Natural variant

1107

1

T → M: dbSNP rs8191842.

VAR_020476

Natural variant

1124

1

V → I: dbSNP rs8191843.

VAR_021309

Natural variant

1184

1

T → S: dbSNP rs8191844.

VAR_020477

Natural variant

1315

1

G → E: dbSNP rs8191859.

VAR_021310

Natural variant

1335

1

R → H: dbSNP rs8191860.

VAR_021311

Natural variant

1619

1

G → R: dbSNP rs629849.

VAR_021312

Natural variant

1832

1

R → H: dbSNP rs8191904.

VAR_021313

Natural variant

1860

1

G → D: dbSNP rs8191905.

VAR_021314

Natural variant

1908

1

I → M: dbSNP rs8191908.

VAR_021315

Natural variant

2020

1

N → S: dbSNP rs1805075.

VAR_014722

Natural variant

2459

1

A → V: dbSNP rs8191955.

VAR_021316

Experimental info

Sequence conflict

254

1

L → V in AAA59866. Ref.2

Sequence conflict

510

1

E → K in AAA59866. Ref.2

Sequence conflict

612

1

H → R Ref.1 Ref.3

Sequence conflict

845

1

V → A in AAA59866. Ref.2

Sequence conflict

1489

1

S → N in AAA59866. Ref.2

Sequence conflict

1703

1

G → A Ref.1 Ref.3

Sequence conflict

2026

1

I → M in AAA59866. Ref.2

Sequence conflict

2075

1

T → M in AAA59866. Ref.2

Sequence conflict

2156

1

K → N in AAA59866. Ref.2

Sequence conflict

2160

1

A → E in AAA59866. Ref.2

Sequence conflict

2176

1

Q → L in AAA59866. Ref.2

Sequence conflict

2330

1

E → K in AAA59866. Ref.2

Sequence conflict

2335

1

V → M in AAA59866. Ref.2

Sequence conflict

2341

1

T → S in AAA59866. Ref.2

Sequence conflict

2410

1

E → T in AAA59866. Ref.2

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.