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Protein

Myelin-associated glycoprotein

Gene

MAG

Organism
Homo sapiens (Human)
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 (By similarity). Not required for initial myelination, but seems to play a role in the maintenance of normal axon myelination. Protects motoneurons against apoptosis, also after injury; protection against apoptosis is probably mediated via interaction with neuronal RTN4R and RTN4RL2. Required to prevent degeneration of myelinated axons in adults; this probably depends on binding to gangliosides on the axon cell membrane (By similarity). 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. In cerebellar granule cells the inhibition is mediated primarily via binding to neuronal gangliosides. In sensory neurons, inhibition of neurite extension depends only partially on RTN4R, RTN4RL2 and gangliosides. Inhibits axon longitudinal growth (By similarity). Inhibits axon outgrowth by binding to RTN4R (By similarity). Preferentially binds to alpha-2,3-linked sialic acid. Binds ganglioside Gt1b (By similarity).By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei118Ganglioside GT1bBy similarity1

GO - Molecular functioni

GO - Biological processi

Keywordsi

Biological processCell adhesion
LigandLectin, Lipid-binding

Enzyme and pathway databases

ReactomeiR-HSA-193634. Axonal growth inhibition (RHOA activation).
R-HSA-210991. Basigin interactions.
SIGNORiP20916.

Names & Taxonomyi

Protein namesi
Recommended name:
Myelin-associated glycoprotein
Alternative name(s):
Siglec-4a
Gene namesi
Name:MAG
Synonyms:GMA
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 19

Organism-specific databases

HGNCiHGNC:6783. MAG.

Subcellular locationi

Topology

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

GO - Cellular componenti

  • compact myelin Source: UniProtKB
  • cytoplasm Source: Ensembl
  • integral component of plasma membrane Source: UniProtKB
  • membrane raft Source: UniProtKB-SubCell
  • mesaxon Source: Ensembl
  • myelin sheath Source: UniProtKB
  • myelin sheath adaxonal region Source: Ensembl
  • paranode region of axon Source: Ensembl
  • plasma membrane Source: UniProtKB
  • Schmidt-Lanterman incisure Source: Ensembl

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Involvement in diseasei

Spastic paraplegia 75, autosomal recessive (SPG75)3 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA form of spastic paraplegia, a neurodegenerative disorder characterized by a slow, gradual, progressive weakness and spasticity of the lower limbs. Rate of progression and the severity of symptoms are quite variable. Initial symptoms may include difficulty with balance, weakness and stiffness in the legs, muscle spasms, and dragging the toes when walking. In some forms of the disorder, bladder symptoms (such as incontinence) may appear, or the weakness and stiffness may spread to other parts of the body. SPG75 is characterized by onset in early childhood and is associated with mild to moderate cognitive impairment.
See also OMIM:616680
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_077495118R → H in SPG75; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs762045079Ensembl.1
Natural variantiVAR_076224133S → R in SPG75; alters proper folding; impairs N-glycosylation; retained in the endoplasmic reticulum; increased proteasome-dependent degradation. 1 Publication1
Natural variantiVAR_076225430C → G in SPG75; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs587777229Ensembl.1

Keywords - Diseasei

Disease mutation, Hereditary spastic paraplegia, Neurodegeneration

Organism-specific databases

DisGeNETi4099.
MalaCardsiMAG.
MIMi616680. phenotype.
OpenTargetsiENSG00000105695.
PharmGKBiPA30541.

Chemistry databases

ChEMBLiCHEMBL5807.

Polymorphism and mutation databases

BioMutaiMAG.
DMDMi126689.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 19Add BLAST19
ChainiPRO_000001485620 – 626Myelin-associated glycoproteinAdd BLAST607

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi37 ↔ 165PROSITE-ProRule annotation
Disulfide bondi42 ↔ 100PROSITE-ProRule annotation
Glycosylationi99N-linked (GlcNAc...) asparagine1 Publication1
Glycosylationi106N-linked (GlcNAc...) asparagine; partial1 Publication1
Disulfide bondi159 ↔ 217PROSITE-ProRule annotation
Glycosylationi223N-linked (GlcNAc...) asparagine1 Publication1
Glycosylationi246N-linked (GlcNAc...) asparagine1 Publication1
Disulfide bondi261 ↔ 305PROSITE-ProRule annotation
Glycosylationi315N-linked (GlcNAc...) asparagine1 Publication1
Disulfide bondi347 ↔ 392PROSITE-ProRule annotation
Glycosylationi406N-linked (GlcNAc...) asparagine1 Publication1
Disulfide bondi421 ↔ 430PROSITE-ProRule annotation
Disulfide bondi432 ↔ 488PROSITE-ProRule annotation
Glycosylationi450N-linked (GlcNAc...) asparagine1 Publication1
Glycosylationi454N-linked (GlcNAc...) asparagine1 Publication1
Lipidationi531S-palmitoyl cysteineBy similarity1
Modified residuei545PhosphoserineBy similarity1
Modified residuei547PhosphoserineBy similarity1
Modified residuei549PhosphoserineBy similarity1

Post-translational modificationi

N-glycosylated.1 Publication
Phosphorylated on tyrosine residues.By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei332Not glycosylated1 Publication1

Keywords - PTMi

Disulfide bond, Glycoprotein, Lipoprotein, Palmitate, Phosphoprotein

Proteomic databases

PaxDbiP20916.
PeptideAtlasiP20916.
PRIDEiP20916.

PTM databases

iPTMnetiP20916.
PhosphoSitePlusiP20916.

Miscellaneous databases

PMAP-CutDBiP20916.

Expressioni

Tissue specificityi

Both isoform 1 and isoform 2 are detected in myelinated structures in the central and peripheral nervous system, in periaxonal myelin and at Schmidt-Lanterman incisures (PubMed:9495552, PubMed:6200494). Detected in optic nerve, in oligodendroglia and in periaxonal myelin sheaths (PubMed:6200494). Detected in compact myelin (at protein level) (PubMed:6200494). Both isoform 1 and isoform 2 are detected in the central and peripheral nervous system (PubMed:9495552).2 Publications

Gene expression databases

BgeeiENSG00000105695.
CleanExiHS_MAG.
ExpressionAtlasiP20916. baseline and differential.
GenevisibleiP20916. HS.

Organism-specific databases

HPAiCAB009345.
HPA012499.

Interactioni

Subunit structurei

Monomer and homodimer (By similarity). Interacts (via the first three N-terminal Ig-like domains) with RTN4R and RTN4RL2 (By similarity).By similarity

GO - Molecular functioni

Protein-protein interaction databases

BioGridi110273. 11 interactors.
DIPiDIP-58523N.
IntActiP20916. 1 interactor.
MINTiMINT-3009422.
STRINGi9606.ENSP00000376048.

Chemistry databases

BindingDBiP20916.

Structurei

3D structure databases

ProteinModelPortaliP20916.
SMRiP20916.
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 bindingBy similarity3
Regioni124 – 128Ganglioside GT1b bindingBy similarity5
Regioni577 – 626Required for normal axon myelination in the central nervous systemBy similarityAdd BLAST50

Sequence similaritiesi

Keywords - Domaini

Immunoglobulin domain, Repeat, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiENOG410IUGJ. Eukaryota.
ENOG410XQVV. LUCA.
GeneTreeiENSGT00760000119139.
HOGENOMiHOG000113464.
HOVERGENiHBG006317.
InParanoidiP20916.
KOiK06771.
OMAiCQASFPN.
OrthoDBiEOG091G03Q5.
PhylomeDBiP20916.
TreeFamiTF332441.

Family and domain databases

Gene3Di2.60.40.10. 6 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. 5 hits.
PROSITEiView protein in PROSITE
PS50835. IG_LIKE. 3 hits.

Sequences (3)i

Sequence statusi: Complete.

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

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P20916-1) [UniParc]FASTAAdd to basket
Also known as: L-MAG1 Publication

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
MIFLTALPLF WIMISASRGG HWGAWMPSSI SAFEGTCVSI PCRFDFPDEL
60 70 80 90 100
RPAVVHGVWY FNSPYPKNYP PVVFKSRTQV VHESFQGRSR LLGDLGLRNC
110 120 130 140 150
TLLLSNVSPE LGGKYYFRGD LGGYNQYTFS EHSVLDIVNT PNIVVPPEVV
160 170 180 190 200
AGTEVEVSCM VPDNCPELRP ELSWLGHEGL GEPAVLGRLR EDEGTWVQVS
210 220 230 240 250
LLHFVPTREA NGHRLGCQAS FPNTTLQFEG YASMDVKYPP VIVEMNSSVE
260 270 280 290 300
AIEGSHVSLL CGADSNPPPL LTWMRDGTVL REAVAESLLL ELEEVTPAED
310 320 330 340 350
GVYACLAENA YGQDNRTVGL SVMYAPWKPT VNGTMVAVEG ETVSILCSTQ
360 370 380 390 400
SNPDPILTIF KEKQILSTVI YESELQLELP AVSPEDDGEY WCVAENQYGQ
410 420 430 440 450
RATAFNLSVE FAPVLLLESH CAAARDTVQC LCVVKSNPEP SVAFELPSRN
460 470 480 490 500
VTVNESEREF VYSERSGLVL TSILTLRGQA QAPPRVICTA RNLYGAKSLE
510 520 530 540 550
LPFQGAHRLM WAKIGPVGAV VAFAILIAIV CYITQTRRKK NVTESPSFSA
560 570 580 590 600
GDNPPVLFSS DFRISGAPEK YESERRLGSE RRLLGLRGEP PELDLSYSHS
610 620
DLGKRPTKDS YTLTEELAEY AEIRVK
Length:626
Mass (Da):69,069
Last modified:February 1, 1991 - v1
Checksum:iED2D36B24F21CAAA
GO
Isoform 2 (identifier: P20916-2) [UniParc]FASTAAdd to basket
Also known as: S-MAG1 Publication

The sequence of this isoform differs from the canonical sequence as follows:
     574-626: ERRLGSERRLLGLRGEPPELDLSYSHSDLGKRPTKDSYTLTEELAEYAEIRVK → KEVSTLESH

Show »
Length:582
Mass (Da):63,966
Checksum:iA063EDC5681F3638
GO
Isoform 3 (identifier: P20916-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-25: Missing.

Note: No experimental confirmation available.
Show »
Length:601
Mass (Da):66,224
Checksum:iE51F6F12D9B87B35
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti614T → S (PubMed:2479762).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_077495118R → H in SPG75; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs762045079Ensembl.1
Natural variantiVAR_076224133S → R in SPG75; alters proper folding; impairs N-glycosylation; retained in the endoplasmic reticulum; increased proteasome-dependent degradation. 1 Publication1
Natural variantiVAR_059399202L → M1 PublicationCorresponds to variant dbSNP:rs11084810Ensembl.1
Natural variantiVAR_076225430C → G in SPG75; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs587777229Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0458431 – 25Missing in isoform 3. 1 PublicationAdd BLAST25
Alternative sequenceiVSP_042688574 – 626ERRLG…EIRVK → KEVSTLESH in isoform 2. 2 PublicationsAdd BLAST53

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M29273 mRNA. Translation: AAA59545.1.
AK294644 mRNA. Translation: BAH11831.1.
AC002132 Genomic DNA. Translation: AAB58805.1.
AD000684 Genomic DNA. No translation available.
BC053347 mRNA. Translation: AAH53347.1.
BC093045 mRNA. Translation: AAH93045.1.
X98405 mRNA. Translation: CAA67055.1.
CCDSiCCDS12455.1. [P20916-1]
CCDS12456.1. [P20916-2]
CCDS56090.1. [P20916-3]
PIRiA61084.
RefSeqiNP_001186145.1. NM_001199216.1. [P20916-3]
NP_002352.1. NM_002361.3. [P20916-1]
NP_542167.1. NM_080600.2. [P20916-2]
UniGeneiHs.643440.

Genome annotation databases

EnsembliENST00000361922; ENSP00000355234; ENSG00000105695. [P20916-2]
ENST00000392213; ENSP00000376048; ENSG00000105695. [P20916-1]
ENST00000537831; ENSP00000440695; ENSG00000105695. [P20916-3]
GeneIDi4099.
KEGGihsa:4099.
UCSCiuc002nyx.3. human. [P20916-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.

Entry informationi

Entry nameiMAG_HUMAN
AccessioniPrimary (citable) accession number: P20916
Secondary accession number(s): B7Z2E5
, F5GYC0, Q15489, Q567S4
Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 1, 1991
Last sequence update: February 1, 1991
Last modified: May 10, 2017
This is version 174 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 19
    Human chromosome 19: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. SIMILARITY comments
    Index of protein domains and families