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Protein

Myelin-associated glycoprotein

Gene

MAG

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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

EuPathDBiHostDB:ENSG00000105695.14
HGNCiHGNC:6783 MAG
MIMi159460 gene
neXtProtiNX_P20916

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

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 PublicationCorresponds to variant dbSNP:rs2301600EnsemblClinVar.1
Natural variantiVAR_076225430C → G in SPG75; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs587777229EnsemblClinVar.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
ProteomicsDBi53823
53824 [P20916-2]

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 Expressed in 154 organ(s), highest expression level in C1 segment of cervical spinal cord
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). Interacts with RTN4R (PubMed:19052207).By similarity1 Publication

GO - Molecular functioni

Protein-protein interaction databases

BioGridi110273, 14 interactors
DIPiDIP-58523N
IntActiP20916, 3 interactors
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
OMAiWYFNSPY
OrthoDBiEOG091G03Q5
PhylomeDBiP20916
TreeFamiTF332441

Family and domain databases

Gene3Di2.60.40.10, 4 hits
InterProiView protein in InterPro
IPR013162 CD80_C2-set
IPR007110 Ig-like_dom
IPR036179 Ig-like_dom_sf
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

This entry has 3 described isoforms and 3 potential isoforms that are computationally mapped.Show allAlign All

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

Computationally mapped potential isoform sequencesi

There are 3 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
M0R3I4M0R3I4_HUMAN
Myelin-associated glycoprotein
MAG
58Annotation score:
M0R3B9M0R3B9_HUMAN
Myelin-associated glycoprotein
MAG
158Annotation score:
M0QZU4M0QZU4_HUMAN
Myelin-associated glycoprotein
MAG
131Annotation score:

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 PublicationCorresponds to variant dbSNP:rs2301600EnsemblClinVar.1
Natural variantiVAR_059399202L → M1 PublicationCorresponds to variant dbSNP:rs11084810Ensembl.1
Natural variantiVAR_076225430C → G in SPG75; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs587777229EnsemblClinVar.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

Cross-referencesi

Web resourcesi

Functional Glycomics Gateway - Glycan Binding

Siglec-4

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

3D structure databases

ProteinModelPortaliP20916
SMRiP20916
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi110273, 14 interactors
DIPiDIP-58523N
IntActiP20916, 3 interactors
STRINGi9606.ENSP00000376048

Chemistry databases

BindingDBiP20916
ChEMBLiCHEMBL5807

PTM databases

iPTMnetiP20916
PhosphoSitePlusiP20916

Polymorphism and mutation databases

BioMutaiMAG
DMDMi126689

Proteomic databases

PaxDbiP20916
PeptideAtlasiP20916
PRIDEiP20916
ProteomicsDBi53823
53824 [P20916-2]

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

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]

Organism-specific databases

CTDi4099
DisGeNETi4099
EuPathDBiHostDB:ENSG00000105695.14
GeneCardsiMAG
H-InvDBiHIX0080123
HGNCiHGNC:6783 MAG
HPAiCAB009345
HPA012499
MalaCardsiMAG
MIMi159460 gene
616680 phenotype
neXtProtiNX_P20916
OpenTargetsiENSG00000105695
PharmGKBiPA30541
GenAtlasiSearch...

Phylogenomic databases

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

Enzyme and pathway databases

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

Miscellaneous databases

ChiTaRSiMAG human
GeneWikiiMyelin-associated_glycoprotein
GenomeRNAii4099
PMAP-CutDBiP20916
PROiPR:P20916
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000105695 Expressed in 154 organ(s), highest expression level in C1 segment of cervical spinal cord
CleanExiHS_MAG
ExpressionAtlasiP20916 baseline and differential
GenevisibleiP20916 HS

Family and domain databases

Gene3Di2.60.40.10, 4 hits
InterProiView protein in InterPro
IPR013162 CD80_C2-set
IPR007110 Ig-like_dom
IPR036179 Ig-like_dom_sf
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
ProtoNetiSearch...

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: September 12, 2018
This is version 184 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. SIMILARITY comments
    Index of protein domains and families
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  4. Human chromosome 19
    Human chromosome 19: entries, gene names and cross-references to MIM
  5. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
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