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Protein

Gliomedin

Gene

Gldn

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

Functioni

Ligand for NRCAM and NFASC/neurofascin that plays a role in the formation and maintenance of the nodes of Ranvier on myelinated axons. Mediates interaction between Schwann cell microvilli and axons via its interactions with NRCAM and NFASC (PubMed:20188654). Nodes of Ranvier contain clustered sodium channels that are crucial for the saltatory propagation of action potentials along myelinated axons. During development, nodes of Ranvier are formed by the fusion of two heminodes. Required for normal clustering of sodium channels at heminodes; not required for the formation of mature nodes with normal sodium channel clusters (PubMed:20188654). Required, together with NRCAM, for maintaining NFASC and sodium channel clusters at mature nodes of Ranvier (PubMed:24719088).By similarity2 Publications

GO - Molecular functioni

  • protein binding involved in heterotypic cell-cell adhesion Source: MGI

GO - Biological processi

  • clustering of voltage-gated sodium channels Source: MGI
  • heterotypic cell-cell adhesion Source: GOC
  • microvillus organization Source: MGI
Complete GO annotation...

Keywords - Molecular functioni

Developmental protein

Keywords - Biological processi

Differentiation, Neurogenesis

Names & Taxonomyi

Protein namesi
Recommended name:
Gliomedin
Alternative name(s):
Cancer-related gene liver 2 protein
Short name:
CRG-L2
Cleaved into the following chain:
Gene namesi
Name:Gldn
Synonyms:Crgl2
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 9

Organism-specific databases

MGIiMGI:2388361. Gldn.

Subcellular locationi

Gliomedin shedded ectodomain :

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 1717CytoplasmicSequence analysisAdd
BLAST
Transmembranei18 – 3821Helical; Signal-anchor for type II membrane proteinSequence analysisAdd
BLAST
Topological domaini39 – 549511ExtracellularSequence analysisAdd
BLAST

GO - Cellular componenti

  • collagen trimer Source: UniProtKB-KW
  • extracellular space Source: MGI
  • integral component of membrane Source: UniProtKB-KW
  • plasma membrane Source: MGI
  • proteinaceous extracellular matrix Source: UniProtKB-SubCell
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Extracellular matrix, Membrane, Secreted

Pathology & Biotechi

Disruption phenotypei

Mutant mice present no obvious neurological phenotype and have normal nerve conduction. Nerves from their peripheral nervous system have myelin sheets that are indistinguishable from wild-type. In contrast, they present impaired and disorganized attachment of Schwann cell microvilli to the axolemma at nodes of Ranvier. Mature nodes are formed by the fusion of two heminodes. During development, mutant mice present defective clustering of sodium channels at heminodes, but display normal sodium channel clustering at mature nodes (PubMed:20188654). Mice lacking both Gldn and Nrcam are born at the expected Mendelian rate, but are smaller than control littermates and display important neurological impairments, in spite of seemingly normal nerve myelination. Motor abnormalities vary betweeen individuals, ranging from ataxia, uncoordinated movements and premature death to weakness of the hind limbs, hypomotility, strongly impaired ability to hang from a horizontal bar with their forelimbs and a tendency to stumble. The motor defects correlate with decreased velocity of nerve conduction and slower propagation of action potentials. Most mice die within 60 days after birth, and none are fertile. Mutant mice display delayed formation of mature nodes of Ranvier; 15 days after birth about 20% of the nodes lack detectable sodium channel clusters. Sodium channel clustering and nerve conduction appear normal 60 and 75 days after birth, but subsequently a gradual disintegration of the nodal protein complexes is seen. About 70% of the mutant nodes present high-density sodium channel clustering at 120 days after birth, as opposed to nearly 100% for wild-type. Contrary to wild-type, in adult nodes of Ranvier the sodium channels are often clustered near the paranode border with an empty gap in the middle. At nodes of Ranvier, Schwann cell microvilli are sparse or absent and show defects in their orientation, resulting in various structural abnormalities at the node and the paranode border (PubMed:24719088).2 Publications

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi91 – 911R → A: Abolishes furin-mediated cleavage and shedding of ectodomain. 1 Publication
Mutagenesisi278 – 2792DD → AA: Abolishes BMP1-mediated cleavage of ectodomain release of olfactomedin-like domain. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 549549GliomedinPRO_0000246322Add
BLAST
Chaini95 – 451357Gliomedin shedded ectodomain1 PublicationPRO_0000434266Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi130 – 1301N-linked (GlcNAc...)Sequence analysis
Glycosylationi156 – 1561N-linked (GlcNAc...)Sequence analysis
Glycosylationi326 – 3261N-linked (GlcNAc...)Sequence analysis
Glycosylationi354 – 3541N-linked (GlcNAc...)Sequence analysis
Glycosylationi375 – 3751N-linked (GlcNAc...)Sequence analysis
Glycosylationi461 – 4611N-linked (GlcNAc...)Sequence analysis

Post-translational modificationi

N-glycosylated.1 Publication
Proteolytic proccessing by a furin-like protease causes shedding of the ectodomain. Further cleavage by BMP1 releases the olfactomedin-like domain.1 Publication

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sitei94 – 952Cleavage; by furin-like protease1 Publication
Sitei277 – 2782Cleavage; by BMP11 Publication

Keywords - PTMi

Glycoprotein

Proteomic databases

PaxDbiQ8BMF8.
PRIDEiQ8BMF8.

PTM databases

PhosphoSiteiQ8BMF8.

Expressioni

Tissue specificityi

Detected in sciatic nerve (at protein level) (PubMed:17293346, PubMed:20188654, PubMed:24719088). Widely expressed with higher expression in testis and skeletal muscle (PubMed:12642876).4 Publications

Gene expression databases

BgeeiQ8BMF8.
CleanExiMM_GLDN.

Interactioni

Subunit structurei

Homotrimer (via collagen-like domains) (PubMed:17293346). Interacts with NRCAM and NFACS/neurofascin (PubMed:16039564, PubMed:20188654). Interaction with glial NRCAM enhances interaction with axonal NFACS (PubMed:20188654). Interacts with MYOC (PubMed:23897819).4 Publications

GO - Molecular functioni

  • protein binding involved in heterotypic cell-cell adhesion Source: MGI

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000056080.

Structurei

Secondary structure

1
549
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi301 – 3044Combined sources
Beta strandi308 – 3125Combined sources
Beta strandi316 – 3216Combined sources
Beta strandi325 – 3273Combined sources
Beta strandi332 – 34817Combined sources
Helixi349 – 3535Combined sources
Beta strandi358 – 36912Combined sources
Beta strandi375 – 3828Combined sources
Beta strandi385 – 3928Combined sources
Beta strandi399 – 4024Combined sources
Helixi416 – 4183Combined sources
Beta strandi423 – 4275Combined sources
Beta strandi430 – 4378Combined sources
Turni438 – 4403Combined sources
Beta strandi443 – 4508Combined sources
Turni451 – 4544Combined sources
Beta strandi455 – 46511Combined sources
Helixi466 – 4683Combined sources
Beta strandi472 – 4754Combined sources
Beta strandi478 – 4825Combined sources
Beta strandi486 – 4949Combined sources
Turni495 – 4984Combined sources
Beta strandi499 – 5013Combined sources
Beta strandi514 – 5207Combined sources
Turni521 – 5244Combined sources
Beta strandi525 – 5306Combined sources
Beta strandi533 – 5419Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
4XAVX-ray2.05A/B/C/D279-549[»]
ProteinModelPortaliQ8BMF8.
SMRiQ8BMF8. Positions 136-163, 299-542.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini137 – 19559Collagen-like 1Add
BLAST
Domaini196 – 22227Collagen-like 2Add
BLAST
Domaini296 – 543248Olfactomedin-likePROSITE-ProRule annotationAdd
BLAST

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi237 – 26125Pro-richAdd
BLAST

Domaini

The olfactomedin-like domain mediates NFASC/neurofascin and NRCAM binding.1 Publication

Sequence similaritiesi

Contains 2 collagen-like domains.Curated
Contains 1 olfactomedin-like domain.PROSITE-ProRule annotation

Keywords - Domaini

Collagen, Repeat, Signal-anchor, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiENOG410INP7. Eukaryota.
ENOG4110Z7Z. LUCA.
GeneTreeiENSGT00760000119005.
HOGENOMiHOG000112733.
HOVERGENiHBG081557.
InParanoidiQ8BMF8.
KOiK16364.
OMAiERIWLTM.
OrthoDBiEOG7TMZS2.
PhylomeDBiQ8BMF8.
TreeFamiTF315964.

Family and domain databases

InterProiIPR008160. Collagen.
IPR031224. Gliomedin.
IPR003112. Olfac-like_dom.
[Graphical view]
PANTHERiPTHR23192:SF5. PTHR23192:SF5. 1 hit.
PfamiPF01391. Collagen. 1 hit.
PF02191. OLF. 1 hit.
[Graphical view]
SMARTiSM00284. OLF. 1 hit.
[Graphical view]
PROSITEiPS51132. OLF. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

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

Q8BMF8-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MTRAAERGQG ATGWGLRGAL VAIALLSALN AAGTVFVLCQ WRGLSAALRA
60 70 80 90 100
LEAQRGREQR EDSALRAFLA ELSRAPGRVP EPSQDPMSAA RNKRSHNGEP
110 120 130 140 150
ASHIRAESQD MMMMMTYSMV PIRVMIDLCN STQGICLTGP PGPPGPPGAG
160 170 180 190 200
GLPGHNGSDG QPGLQGPKGE KGAIGKRGKM GLPGATGNPG EKGEKGDAGE
210 220 230 240 250
LGLPGNEGPP GQKGDKGDKG DVSNDVLLTG AKGDQGPPGP PGPPGPPGPP
260 270 280 290 300
GSRRSKGPRP PNVFNSQCPG ETCVIPNDDT LVGRADEKAN ERHSPQTESM
310 320 330 340 350
ITSIGNPAQV LKVRETFGTW MRESANKSDD RIWVTEHFSG IMVKEFKDLP
360 370 380 390 400
ALLNSSFTLL HLPHYFHGCG HAVYNNSLYY HKGGSNTIVR FEFGKETPQT
410 420 430 440 450
LKLENALYFD RKYLFANSKT YFNIAVDEKG IWIIYASSVD GSSILVAQLD
460 470 480 490 500
ERTFSVTQHI NTTYPKSKAG NAFIARGILY VTDTKDTRVT FAFDLLGGKQ
510 520 530 540
INANFDFRMS QSVLAMLSYN MRDQHLYSWE DGHLMLYPVQ FLSAASSQR
Length:549
Mass (Da):59,137
Last modified:March 1, 2003 - v1
Checksum:i43F1B89FF9634F1D
GO

Sequence cautioni

The sequence AAO49510.1 differs from that shown. Reason: Erroneous initiation. Curated

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti451 – 4511E → G in AAO49510 (PubMed:12642876).Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK031523 mRNA. Translation: BAC27432.1.
AF548022 mRNA. Translation: AAO49510.1. Different initiation.
CCDSiCCDS23189.1.
RefSeqiNP_796324.1. NM_177350.5.
UniGeneiMm.123549.

Genome annotation databases

EnsembliENSMUST00000056740; ENSMUSP00000056080; ENSMUSG00000046167.
GeneIDi235379.
KEGGimmu:235379.
UCSCiuc009pqx.1. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK031523 mRNA. Translation: BAC27432.1.
AF548022 mRNA. Translation: AAO49510.1. Different initiation.
CCDSiCCDS23189.1.
RefSeqiNP_796324.1. NM_177350.5.
UniGeneiMm.123549.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
4XAVX-ray2.05A/B/C/D279-549[»]
ProteinModelPortaliQ8BMF8.
SMRiQ8BMF8. Positions 136-163, 299-542.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000056080.

PTM databases

PhosphoSiteiQ8BMF8.

Proteomic databases

PaxDbiQ8BMF8.
PRIDEiQ8BMF8.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000056740; ENSMUSP00000056080; ENSMUSG00000046167.
GeneIDi235379.
KEGGimmu:235379.
UCSCiuc009pqx.1. mouse.

Organism-specific databases

CTDi342035.
MGIiMGI:2388361. Gldn.

Phylogenomic databases

eggNOGiENOG410INP7. Eukaryota.
ENOG4110Z7Z. LUCA.
GeneTreeiENSGT00760000119005.
HOGENOMiHOG000112733.
HOVERGENiHBG081557.
InParanoidiQ8BMF8.
KOiK16364.
OMAiERIWLTM.
OrthoDBiEOG7TMZS2.
PhylomeDBiQ8BMF8.
TreeFamiTF315964.

Miscellaneous databases

PROiQ8BMF8.
SOURCEiSearch...

Gene expression databases

BgeeiQ8BMF8.
CleanExiMM_GLDN.

Family and domain databases

InterProiIPR008160. Collagen.
IPR031224. Gliomedin.
IPR003112. Olfac-like_dom.
[Graphical view]
PANTHERiPTHR23192:SF5. PTHR23192:SF5. 1 hit.
PfamiPF01391. Collagen. 1 hit.
PF02191. OLF. 1 hit.
[Graphical view]
SMARTiSM00284. OLF. 1 hit.
[Graphical view]
PROSITEiPS51132. OLF. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "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: Fetal testis.
  2. "Identification and characterization of CRG-L2, a new marker for liver tumor development."
    Graveel C.R., Harkins-Perry S.R., Acevedo L.G., Farnham P.J.
    Oncogene 22:1730-1736(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 103-549, TISSUE SPECIFICITY.
    Strain: C3H/HeJ.
    Tissue: Liver tumor.
  3. "Gliomedin mediates Schwann cell-axon interaction and the molecular assembly of the nodes of Ranvier."
    Eshed Y., Feinberg K., Poliak S., Sabanay H., Sarig-Nadir O., Spiegel I., Bermingham J.R. Jr., Peles E.
    Neuron 47:215-229(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH NRCAM.
  4. "Cleavage and oligomerization of gliomedin, a transmembrane collagen required for node of ranvier formation."
    Maertens B., Hopkins D., Franzke C.W., Keene D.R., Bruckner-Tuderman L., Greenspan D.S., Koch M.
    J. Biol. Chem. 282:10647-10659(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: SUBCELLULAR LOCATION, GLYCOSYLATION, SUBUNIT, PROTEIN SEQUENCE OF 95-99; 122-128 AND 278-289, MUTAGENESIS OF ARG-91 AND 278-ASP-ASP-279.
  5. "A glial signal consisting of gliomedin and NrCAM clusters axonal Na+ channels during the formation of nodes of Ranvier."
    Feinberg K., Eshed-Eisenbach Y., Frechter S., Amor V., Salomon D., Sabanay H., Dupree J.L., Grumet M., Brophy P.J., Shrager P., Peles E.
    Neuron 65:490-502(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: DISRUPTION PHENOTYPE, FUNCTION, INTERACTION WITH NRCAM AND NFACS, DOMAIN, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
  6. "Myocilin mediates myelination in the peripheral nervous system through ErbB2/3 signaling."
    Kwon H.S., Johnson T.V., Joe M.K., Abu-Asab M., Zhang J., Chan C.C., Tomarev S.I.
    J. Biol. Chem. 288:26357-26371(2013) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH MYOC.
  7. "Long-term maintenance of Na+ channels at nodes of Ranvier depends on glial contact mediated by gliomedin and NrCAM."
    Amor V., Feinberg K., Eshed-Eisenbach Y., Vainshtein A., Frechter S., Grumet M., Rosenbluth J., Peles E.
    J. Neurosci. 34:5089-5098(2014) [PubMed] [Europe PMC] [Abstract]
    Cited for: DISRUPTION PHENOTYPE, FUNCTION, TISSUE SPECIFICITY.
  8. "Molecular details of olfactomedin domains provide pathway to structure-function studies."
    Hill S.E., Donegan R.K., Nguyen E., Desai T.M., Lieberman R.L.
    PLoS ONE 10:E0130888-E0130888(2015) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (2.05 ANGSTROMS) OF 279-549.

Entry informationi

Entry nameiGLDN_MOUSE
AccessioniPrimary (citable) accession number: Q8BMF8
Secondary accession number(s): Q80ZC5
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 25, 2006
Last sequence update: March 1, 2003
Last modified: June 8, 2016
This is version 98 of the entry and version 1 of the sequence. [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

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.