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Protein

Myelin-associated glycoprotein

Gene

Mag

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Adhesion molecule that mediates interactions between myelinating cells and neurons by binding to neuronal sialic acid-containing gangliosides and to the glycoproteins RTN4R and RTN4RL2 (PubMed:7533044, PubMed:12089450, PubMed:27922006). Not required for initial myelination, but seems to play a role in the maintenance of normal axon myelination (PubMed:7516497, PubMed:9262180, PubMed:9482781, PubMed:9482783, PubMed:9469574, PubMed:10625334). Protects motoneurons against apoptosis, also after injury; protection against apoptosis is probably mediated via interaction with neuronal RTN4R and RTN4RL2 (PubMed:26335717). Required to prevent degeneration of myelinated axons in adults; this probably depends on binding to gangliosides on the axon cell membrane (PubMed:15953602, PubMed:19158290). Negative regulator of neurite outgrowth that inhibits axon longitudinal growth (PubMed:19158290, PubMed:27922006, PubMed:12089450). Negative regulator of neurite outgrowth; in dorsal root ganglion neurons the inhibition is mediated primarily via binding to neuronal RTN4R or RTN4RL2 and to a lesser degree via binding to neuronal gangliosides (PubMed:17640868). In cerebellar granule cells the inhibition is mediated via binding to neuronal gangliosides (PubMed:17640868). In sensory neurons, inhibition of neurite extension depends only partially on RTN4R, RTN4RL2 and gangliosides (By similarity). Inhibits axon outgrowth by binding to RTN4R (PubMed:12089450). Preferentially binds to alpha-2,3-linked sialic acid (PubMed:7533044, PubMed:27922006). Binds ganglioside Gt1b (PubMed:27922006).By similarity13 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei118Ganglioside GT1b1 Publication1

GO - Molecular functioni

  • carbohydrate binding Source: UniProtKB-KW
  • ganglioside GT1b binding Source: UniProtKB
  • protein homodimerization activity Source: UniProtKB
  • protein kinase binding Source: Ensembl
  • receptor binding Source: Ensembl
  • sialic acid binding Source: UniProtKB

GO - Biological processi

  • cell adhesion Source: UniProtKB
  • cell-cell adhesion via plasma-membrane adhesion molecules Source: UniProtKB
  • cellular response to mechanical stimulus Source: Ensembl
  • central nervous system myelination Source: UniProtKB
  • negative regulation of axon extension Source: UniProtKB
  • negative regulation of neuron apoptotic process Source: UniProtKB
  • negative regulation of neuron projection development Source: UniProtKB
  • positive regulation of astrocyte differentiation Source: Ensembl
  • positive regulation of myelination Source: CACAO

Keywordsi

Biological processCell adhesion
LigandLectin, Lipid-binding

Enzyme and pathway databases

ReactomeiR-MMU-193634. Axonal growth inhibition (RHOA activation).
R-MMU-210991. Basigin interactions.

Names & Taxonomyi

Protein namesi
Recommended name:
Myelin-associated glycoprotein
Alternative name(s):
Siglec-4a
Gene namesi
Name:Mag
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 7

Organism-specific databases

MGIiMGI:96912. Mag.

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini20 – 516ExtracellularSequence analysisAdd BLAST497
Transmembranei517 – 536HelicalSequence analysisAdd BLAST20
Topological domaini537 – 626CytoplasmicSequence analysisAdd BLAST90

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Disruption phenotypei

Mutant mice appear normal, excepting subtle defects in motor coordination and a slight intention tremor (PubMed:7516497). They have similar numbers of motoneurons as wild-type at birth, but display an important loss of motoneurons during the first week after birth (PubMed:26335717).Five month old mutant mice display a decreased ability to remain on a rotating cylinder (PubMed:15953602). Contrary to wild-type, about 40% of mutant mice have severe episodes of whole-body tremor, both during movement and when resting (PubMed:15953602). The myelination in brain and around peripheral nerves appears grossly normal in young animals, but the periaxonal cytoplasmic collar is often missing in optic nerve (PubMed:7516497, PubMed:9262180, PubMed:9482781, PubMed:9469574). When present, the cytoplasm of the periaxonal collar has generally a disorganized aspect (PubMed:7516497). Mutant mice have an increased percentage of unmyelinated axons in optic nerve (PubMed:9262180, PubMed:9469574). Besides, a small proportion of nerves from mutant mice display redundant myelination, and also rare cases of multiple myelination, where axons are surrounded by two or more compact myelin sheets (PubMed:9469574). Sciatic nerves from over three month old mutant mice show signs of Wallerian degeneration, with redundant myelin, degeneration of myelinated fibers, and an apparent decrease in the diameter of myelinated axons (PubMed:9482781, PubMed:15953602). The distances between neurofilaments in myelinated axons from over 3 month old mice are shorter than normal (PubMed:9482781, PubMed:15953602). With increasing age, mutant mice display progressive axon degeneration in the spinal cord and sciatic nerve, resulting in a decrease of 28% in the number of spinal cord axons after 15 months (PubMed:19158290). Mutant mice display increased motoneuron apoptosis after injury (PubMed:26335717). Likewise, they display strongly increased axon degeneration after treatment with the neurotoxin acrylamide (PubMed:19158290). Mutant mice display much more severe axon loss in response to experimental autoimmune encephalitis (PubMed:19158290).7 Publications

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi25W → Q: Abolishes C-linked mannosylation. 1 Publication1
Mutagenesisi65Y → A: Decreases ganglioside binding. 1 Publication1
Mutagenesisi118 – 120RGD → KGE: Abolishes protection against axon degeneration. 1 Publication3
Mutagenesisi118R → A: Abolishes ganglioside binding. 1 Publication1
Mutagenesisi127Y → A: Abolishes ganglioside binding. 1 Publication1
Mutagenesisi128T → A: Abolishes ganglioside binding. 1 Publication1
Mutagenesisi406N → Q: Increases homodimerization. 1 Publication1
Mutagenesisi473I → E: Abolishes homodimerization. 1 Publication1

Chemistry databases

ChEMBLiCHEMBL1250416.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 19Add BLAST19
ChainiPRO_000001485720 – 626Myelin-associated glycoproteinAdd BLAST607

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi22C-linked (Man) tryptophan1 Publication1
Disulfide bondi37 ↔ 165PROSITE-ProRule annotation1 Publication
Disulfide bondi42 ↔ 100PROSITE-ProRule annotation1 Publication
Glycosylationi99N-linked (GlcNAc...) asparagine1 Publication1
Disulfide bondi159 ↔ 217PROSITE-ProRule annotation1 Publication
Glycosylationi223N-linked (GlcNAc...) asparagine1 Publication1
Glycosylationi246N-linked (GlcNAc...) asparagine1 Publication1
Disulfide bondi261 ↔ 305PROSITE-ProRule annotation1 Publication
Glycosylationi315N-linked (GlcNAc...) asparagine1 Publication1
Glycosylationi332N-linked (GlcNAc...) asparagine1 Publication1
Disulfide bondi347 ↔ 392PROSITE-ProRule annotation1 Publication
Glycosylationi406N-linked (GlcNAc...) asparagine1 Publication1
Disulfide bondi421 ↔ 430PROSITE-ProRule annotation1 Publication
Disulfide bondi432 ↔ 488PROSITE-ProRule annotation1 Publication
Glycosylationi450N-linked (GlcNAc...) asparagine1 Publication1
Glycosylationi454N-linked (GlcNAc...) asparagine1 Publication1
Lipidationi531S-palmitoyl cysteineBy similarity1
Modified residuei545PhosphoserineBy similarity1
Modified residuei547PhosphoserineBy similarity1
Modified residuei549PhosphoserineBy similarity1
Modified residuei590PhosphoserineCombined sources1

Post-translational modificationi

N-glycosylated.2 Publications
Phosphorylated on tyrosine residues.By similarity

Keywords - PTMi

Disulfide bond, Glycoprotein, Lipoprotein, Palmitate, Phosphoprotein

Proteomic databases

MaxQBiP20917.
PaxDbiP20917.
PeptideAtlasiP20917.
PRIDEiP20917.

PTM databases

iPTMnetiP20917.
PhosphoSitePlusiP20917.
SwissPalmiP20917.

Expressioni

Tissue specificityi

Detected in the myelin tract in brain, especially in the corpus callosum and in peripheral nerve (PubMed:7516497, PubMed:9482783). Expressed by myelinating glial cells in the central and peripheral nervous system (PubMed:10625334). Detected in oligodendrocyte processes before formation of compact myelin (PubMed:2474006, PubMed:10625334). Restricted to the periaxonal space after myelination (PubMed:10625334). Isoform S-MAG is the predominant isoform in CNS and PNS of the adult (at protein level) (PubMed:1716323).5 Publications

Developmental stagei

In CNS isoform L-MAG is the major form synthesized early in development, and it persists as a significant proportion of the MAG present in the adult. In the PNS isoform L-MAG is expressed at modest levels during development; it is absent in the adult.1 Publication

Gene expression databases

BgeeiENSMUSG00000036634.
CleanExiMM_MAG.
ExpressionAtlasiP20917. baseline and differential.
GenevisibleiP20917. MM.

Interactioni

Subunit structurei

Monomer and homodimer (PubMed:27922006). Interacts (via the first three N-terminal Ig-like domains) with RTN4R and RTN4RL2 (PubMed:12089450, PubMed:26335717).3 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
Rtn4rQ99PI82EBI-774926,EBI-7766036

GO - Molecular functioni

  • protein homodimerization activity Source: UniProtKB
  • protein kinase binding Source: Ensembl
  • receptor binding Source: Ensembl

Protein-protein interaction databases

BioGridi201285. 1 interactor.
IntActiP20917. 7 interactors.
MINTiMINT-202735.
STRINGi10090.ENSMUSP00000041464.

Chemistry databases

BindingDBiP20917.

Structurei

Secondary structure

1626
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi22 – 25Combined sources4
Beta strandi28 – 33Combined sources6
Beta strandi38 – 40Combined sources3
Beta strandi43 – 45Combined sources3
Helixi48 – 50Combined sources3
Beta strandi56 – 62Combined sources7
Beta strandi72 – 75Combined sources4
Turni76 – 78Combined sources3
Helixi83 – 85Combined sources3
Turni86 – 88Combined sources3
Beta strandi89 – 91Combined sources3
Helixi95 – 97Combined sources3
Beta strandi102 – 104Combined sources3
Helixi109 – 111Combined sources3
Beta strandi113 – 120Combined sources8
Beta strandi126 – 128Combined sources3
Beta strandi133 – 140Combined sources8
Beta strandi142 – 144Combined sources3
Beta strandi155 – 162Combined sources8
Beta strandi171 – 176Combined sources6
Helixi178 – 180Combined sources3
Beta strandi184 – 190Combined sources7
Helixi192 – 194Combined sources3
Beta strandi196 – 204Combined sources9
Helixi208 – 210Combined sources3
Beta strandi214 – 220Combined sources7
Beta strandi227 – 233Combined sources7
Beta strandi236 – 245Combined sources10
Beta strandi248 – 252Combined sources5
Beta strandi257 – 267Combined sources11
Beta strandi270 – 275Combined sources6
Beta strandi278 – 292Combined sources15
Helixi297 – 299Combined sources3
Beta strandi301 – 309Combined sources9
Beta strandi312 – 324Combined sources13

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
5LF5X-ray3.80A20-508[»]
5LFRX-ray2.12A/B20-325[»]
5LFUX-ray4.30A20-508[»]
5LFVX-ray2.30A/B20-325[»]
ProteinModelPortaliP20917.
SMRiP20917.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini22 – 120Ig-like V-typeAdd BLAST99
Domaini139 – 237Ig-like C2-type 1Add BLAST99
Domaini241 – 325Ig-like C2-type 2Add BLAST85
Domaini327 – 412Ig-like C2-type 3Add BLAST86
Domaini413 – 508Ig-like C2-type 4Add BLAST96

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni20 – 325Interaction with RTN4R and RTN4RL2By similarityAdd BLAST306
Regioni65 – 67Ganglioside GT1b binding1 Publication3
Regioni124 – 128Ganglioside GT1b binding1 Publication5
Regioni577 – 626Required for normal axon myelination in the central nervous system1 PublicationAdd BLAST50

Domaini

The C-terminal cytoplasmic region found only in isoform L-MAG is required for normal myelination in the central nervous system (CNS), but is apparently not required for normal myelination in the peripheral nervous system (PNS).1 Publication
The extracellular domain is required to protect against axon degeneration (PubMed:19158290, PubMed:26335717). The first three Ig-like domains mediate interaction with RTN4R and RTN4RL2, but are not sufficient to inhibit neurite outgrowth (By similarity). The two C-terminal extracellular Ig-like C2-type domains are required for inhibition of axon longitudinal growth. Besides, the two C-terminal extracellular Ig-like C2-type domains are required for protection against apoptosis after nerve injury (PubMed:26335717).By similarity2 Publications

Sequence similaritiesi

Keywords - Domaini

Immunoglobulin domain, Repeat, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiENOG410KDW4. Eukaryota.
ENOG410XQVV. LUCA.
GeneTreeiENSGT00760000119139.
HOGENOMiHOG000113464.
HOVERGENiHBG006317.
InParanoidiP20917.
KOiK06771.
PhylomeDBiP20917.
TreeFamiTF332441.

Family and domain databases

Gene3Di2.60.40.10. 5 hits.
InterProiView protein in InterPro
IPR013162. CD80_C2-set.
IPR007110. Ig-like_dom.
IPR013783. Ig-like_fold.
IPR003599. Ig_sub.
IPR003598. Ig_sub2.
PfamiView protein in Pfam
PF08205. C2-set_2. 1 hit.
SMARTiView protein in SMART
SM00409. IG. 4 hits.
SM00408. IGc2. 2 hits.
SUPFAMiSSF48726. SSF48726. 4 hits.
PROSITEiView protein in PROSITE
PS50835. IG_LIKE. 2 hits.

Sequences (2)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform L-MAG (identifier: P20917-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MIFLATLPLF WIMISASRGG HWGAWMPSTI SAFEGTCVSI PCRFDFPDEL
60 70 80 90 100
RPAVVHGVWY FNSPYPKNYP PVVFKSRTQV VHESFQGRSR LLGDLGLRNC
110 120 130 140 150
TLLLSTLSPE LGGKYYFRGD LGGYNQYTFS EHSVLDIVNT PNIVVPPEVV
160 170 180 190 200
AGTEVEVSCM VPDNCPELRP ELSWLGHEGL GEPTVLGRLR EDEGTWVQVS
210 220 230 240 250
LLHFVPTREA NGHRLGCQAA FPNTTLQFEG YASLDVKYPP VIVEMNSSVE
260 270 280 290 300
AIEGSHVSLL CGADSNPPPL LTWMRDGMVL REAVAKSLYL DLEEVTPGED
310 320 330 340 350
GVYACLAENA YGQDNRTVEL SVMYAPWKPT VNGTVVAVEG ETVSILCSTQ
360 370 380 390 400
SNPDPILTIF KEKQILATVI YESQLQLELP AVTPEDDGEY WCVAENQYGQ
410 420 430 440 450
RATAFNLSVE FAPIILLESH CAAARDTVQC LCVVKSNPEP SVAFELPSRN
460 470 480 490 500
VTVNETEREF VYSERSGLLL TSILTIRGQA QAPPRVICTS RNLYGTQSLE
510 520 530 540 550
LPFQGAHRLM WAKIGPVGAV VAFAILIAIV CYITQTRRKK NVTESSSFSG
560 570 580 590 600
GDNPHVLYSP EFRISGAPDK YESEKRLGSE RRLLGLRGES PELDLSYSHS
610 620
DLGKRPTKDS YTLTEELAEY AEIRVK
Length:626
Mass (Da):69,260
Last modified:July 15, 1998 - v2
Checksum:i9C797BD6B52B6057
GO
Isoform S-MAG (identifier: P20917-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     574-582: EKRLGSERR → REVSTRDCH
     583-626: Missing.

Show »
Length:582
Mass (Da):64,268
Checksum:i892DD384D653FCDC
GO

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_002527574 – 582EKRLGSERR → REVSTRDCH in isoform S-MAG. Curated9
Alternative sequenceiVSP_002528583 – 626Missing in isoform S-MAG. CuratedAdd BLAST44

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M31811 mRNA. Translation: AAA39487.1.
M74793
, M74783, M74784, M74785, M74786, M74787, M74788, M74790, M74791 Genomic DNA. Translation: AAA91743.1.
CCDSiCCDS21115.1. [P20917-2]
PIRiB33785.
RefSeqiNP_001333015.1. NM_001346086.1. [P20917-2]
NP_001333016.1. NM_001346087.1. [P20917-2]
NP_001333017.1. NM_001346088.1. [P20917-2]
NP_034888.1. NM_010758.3. [P20917-2]
XP_011248743.1. XM_011250441.2. [P20917-2]
XP_017177497.1. XM_017322008.1. [P20917-2]
UniGeneiMm.241355.

Genome annotation databases

EnsembliENSMUST00000040548; ENSMUSP00000041464; ENSMUSG00000036634. [P20917-2]
ENSMUST00000187137; ENSMUSP00000139564; ENSMUSG00000036634. [P20917-2]
GeneIDi17136.
KEGGimmu:17136.
UCSCiuc009ghb.1. mouse. [P20917-2]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiMAG_MOUSE
AccessioniPrimary (citable) accession number: P20917
Secondary accession number(s): P16880
Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 1, 1991
Last sequence update: July 15, 1998
Last modified: September 27, 2017
This is version 168 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  3. SIMILARITY comments
    Index of protein domains and families