GPC6_MOUSE
ID GPC6_MOUSE Reviewed; 555 AA.
AC Q9R087;
DT 24-JAN-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 03-AUG-2022, entry version 152.
DE RecName: Full=Glypican-6;
DE Contains:
DE RecName: Full=Secreted glypican-6;
DE Flags: Precursor;
GN Name=Gpc6;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND DEVELOPMENTAL STAGE.
RC STRAIN=Swiss Webster / NIH; TISSUE=Embryo;
RX PubMed=10480909; DOI=10.1074/jbc.274.38.26968;
RA Veugelers M., De Cat B., Ceulemans H., Bruystens A.-M., Coomans C.,
RA Duerr J., Vermeesch J., Marynen P., David G.;
RT "Glypican-6, a new member of the glypican family of cell surface heparan
RT sulfate proteoglycans.";
RL J. Biol. Chem. 274:26968-26977(1999).
RN [2]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain;
RX PubMed=16452087; DOI=10.1074/mcp.t500041-mcp200;
RA Trinidad J.C., Specht C.G., Thalhammer A., Schoepfer R., Burlingame A.L.;
RT "Comprehensive identification of phosphorylation sites in postsynaptic
RT density preparations.";
RL Mol. Cell. Proteomics 5:914-922(2006).
RN [3]
RP TISSUE SPECIFICITY.
RX PubMed=19481194; DOI=10.1016/j.ajhg.2009.05.002;
RA Campos-Xavier A.B., Martinet D., Bateman J., Belluoccio D., Rowley L.,
RA Tan T.Y., Baxova A., Gustavson K.H., Borochowitz Z.U., Innes A.M.,
RA Unger S., Beckmann J.S., Mittaz L., Ballhausen D., Superti-Furga A.,
RA Savarirayan R., Bonafe L.;
RT "Mutations in the heparan-sulfate proteoglycan glypican 6 (GPC6) impair
RT endochondral ossification and cause recessive omodysplasia.";
RL Am. J. Hum. Genet. 84:760-770(2009).
CC -!- FUNCTION: Cell surface proteoglycan that bears heparan sulfate.
CC Putative cell surface coreceptor for growth factors, extracellular
CC matrix proteins, proteases and anti-proteases. Enhances migration and
CC invasion of cancer cells through WNT5A signaling (By similarity).
CC {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250}; Lipid-anchor, GPI-
CC anchor {ECO:0000250}; Extracellular side {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: [Secreted glypican-6]: Secreted, extracellular
CC space {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: In the cartilage growth-plate, gradient of
CC expression with highest levels from the proliferative and pre-
CC hypertrophic zones to lowest, if any, in the hypertrophic zones (at
CC protein level). {ECO:0000269|PubMed:19481194}.
CC -!- DEVELOPMENTAL STAGE: Detected from 7 to 17 dpc. Overall expression
CC clearly diminishes after 13 dpc. Mostly expressed in mesoderm-derived
CC tissues, but also present in some neurectoderm-derived sites. High
CC expression limited to mesenchymal tissues. In 11.5 and 13.5 dpc lungs,
CC mostly restricted to the peribronchial mesenchymal cells. In the aorta
CC and other major blood vessels, found in the subendothelial smooth
CC muscle cell layers. Also expressed in the outflow tract of the heart
CC ventricle, but not in other parts of the heart. At 13.5 dpc, in the
CC developing kidney, detected in the metanephric cap mesenchyme of the
CC cortical region, in the condensing mesenchyme surrounding the ureteric
CC branches. Not detected in the adrenal glands. At 11.5 and 13.5 dpc,
CC expressed weakly in the liver septae, but not in the parenchyme. Very
CC strong expression in both the stomach and intestine, in the submucosal
CC layers, in the condensing splanchnic mesenchyme. At 13.5 dpc, expressed
CC in the mesenchymal cells of pancreas, gonad, mesonephric tissue and
CC genital eminence. At 13.5 dpc, expressed in the thymus. At 11.5 dpc,
CC strong expression in the mesenchyme of the mandibular process, with
CC highest expression in the mesenchymal cell layer just below the oral
CC epithelium. Not detected in the overlying epithelium. At 13.5 dpc,
CC highly expressed in the dental mesenchyme surrounding the epithelial
CC bud and near the top of the lip furrow, as well as in the tongue. At
CC 13.5 dpc, expressed in the cartilage primordia of the ear and snout.
CC Highly expressed in intervertebral disks, but not detected in the
CC notochord and vertebrae, both at 11.5 and 13.5 dpc. Highly expressed in
CC mesenchymal condensations of both the forelimb and hindlimb. Overall
CC low expression in the nervous system. At 11.5 dpc, low expression in
CC the neuroepithelium of the hindbrain, the telencephalic vesicle and
CC neuro-epithelial cells lining the mesencephalic vesicle. At 13.5 dpc,
CC detected in the roof of the neopallial cortex, which gives rise to the
CC future cerebral cortex. Weak expression also observed in the medulla
CC oblongata, the choroid plexus, and the ventral mantle layer of the
CC spinal cord. Stronger expression in the ganglia of the glossopharyngeal
CC nerve. At 11.5 and 13.5 dpc, expressed in the mesenchyme surrounding
CC the olfactory epithelium, but not in the epithelium itself. Similarly
CC expressed in the mesenchymal tissues lining the dorsal root ganglia
CC (perineurium), but not in the ganglia. Expression also observed in a
CC few epithelial cells (ectodermal origin), including, at 11.5 dpc, the
CC ventromedial wall of the otic vesicle and, at 13.5 dpc, the cochlea of
CC the inner ear. In the eye, expressed not only in the neural retina but
CC also the cells that compose the wall of the lens vesicle.
CC {ECO:0000269|PubMed:10480909}.
CC -!- SIMILARITY: Belongs to the glypican family. {ECO:0000305}.
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DR EMBL; AF105268; AAD55750.1; -; mRNA.
DR CCDS; CCDS27330.1; -.
DR RefSeq; NP_035951.1; NM_011821.3.
DR AlphaFoldDB; Q9R087; -.
DR SMR; Q9R087; -.
DR STRING; 10090.ENSMUSP00000120362; -.
DR PhosphoSitePlus; Q9R087; -.
DR MaxQB; Q9R087; -.
DR PaxDb; Q9R087; -.
DR PRIDE; Q9R087; -.
DR ProteomicsDB; 271036; -.
DR Antibodypedia; 2876; 213 antibodies from 24 providers.
DR DNASU; 23888; -.
DR Ensembl; ENSMUST00000078849; ENSMUSP00000077893; ENSMUSG00000058571.
DR Ensembl; ENSMUST00000088483; ENSMUSP00000085835; ENSMUSG00000058571.
DR GeneID; 23888; -.
DR KEGG; mmu:23888; -.
DR UCSC; uc007uyl.2; mouse.
DR CTD; 10082; -.
DR MGI; MGI:1346322; Gpc6.
DR VEuPathDB; HostDB:ENSMUSG00000058571; -.
DR eggNOG; KOG3821; Eukaryota.
DR GeneTree; ENSGT01050000244897; -.
DR InParanoid; Q9R087; -.
DR OMA; RSGPMED; -.
DR PhylomeDB; Q9R087; -.
DR Reactome; R-MMU-1971475; A tetrasaccharide linker sequence is required for GAG synthesis.
DR Reactome; R-MMU-2022928; HS-GAG biosynthesis.
DR Reactome; R-MMU-2024096; HS-GAG degradation.
DR Reactome; R-MMU-975634; Retinoid metabolism and transport.
DR BioGRID-ORCS; 23888; 2 hits in 72 CRISPR screens.
DR ChiTaRS; Gpc6; mouse.
DR PRO; PR:Q9R087; -.
DR Proteomes; UP000000589; Chromosome 14.
DR RNAct; Q9R087; protein.
DR Bgee; ENSMUSG00000058571; Expressed in ascending aorta and 203 other tissues.
DR ExpressionAtlas; Q9R087; baseline and differential.
DR Genevisible; Q9R087; MM.
DR GO; GO:0046658; C:anchored component of plasma membrane; IEA:InterPro.
DR GO; GO:0009986; C:cell surface; IBA:GO_Central.
DR GO; GO:0062023; C:collagen-containing extracellular matrix; IEA:InterPro.
DR GO; GO:0005615; C:extracellular space; IEA:UniProtKB-SubCell.
DR GO; GO:0098978; C:glutamatergic synapse; ISO:MGI.
DR GO; GO:0005796; C:Golgi lumen; TAS:Reactome.
DR GO; GO:0005887; C:integral component of plasma membrane; ISS:MGI.
DR GO; GO:0045202; C:synapse; IDA:SynGO.
DR GO; GO:0016477; P:cell migration; ISS:UniProtKB.
DR GO; GO:0098696; P:regulation of neurotransmitter receptor localization to postsynaptic specialization membrane; ISO:MGI.
DR GO; GO:1905606; P:regulation of presynapse assembly; IBA:GO_Central.
DR GO; GO:1905475; P:regulation of protein localization to membrane; IBA:GO_Central.
DR GO; GO:0009966; P:regulation of signal transduction; IEA:InterPro.
DR GO; GO:0099560; P:synaptic membrane adhesion; IBA:GO_Central.
DR InterPro; IPR001863; Glypican.
DR InterPro; IPR031183; Glypican-6.
DR InterPro; IPR019803; Glypican_CS.
DR PANTHER; PTHR10822; PTHR10822; 1.
DR PANTHER; PTHR10822:SF31; PTHR10822:SF31; 1.
DR Pfam; PF01153; Glypican; 1.
DR PROSITE; PS01207; GLYPICAN; 1.
PE 1: Evidence at protein level;
KW Cell membrane; Glycoprotein; GPI-anchor; Heparan sulfate; Lipoprotein;
KW Membrane; Proteoglycan; Reference proteome; Secreted; Signal.
FT SIGNAL 1..23
FT /evidence="ECO:0000255"
FT CHAIN 24..530
FT /note="Glypican-6"
FT /id="PRO_0000012325"
FT CHAIN 24..?
FT /note="Secreted glypican-6"
FT /id="PRO_0000333852"
FT PROPEP 531..555
FT /note="Removed in mature form"
FT /evidence="ECO:0000255"
FT /id="PRO_0000012326"
FT REGION 348..376
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 480..501
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 480..499
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT LIPID 530
FT /note="GPI-anchor amidated serine"
FT /evidence="ECO:0000255"
SQ SEQUENCE 555 AA; 63057 MW; 621AFAFF58A839EC CRC64;
MPSWIRAVIL PLSGLLLTLP AAADVKARSC SEVRQAYGAK GFSLADIPYQ EIAGEHLRIC
PQEYTCCTTE MEDKLSQQSK LEFENLVEET SHFVRTTFVS RHKKFDEFFR ELLENAEKSL
NDMFVRTYGM LYMQNSEVFQ DLFTELKRYY TGGNVNLEEM LNDFWARLLE RMFQLINPQY
HFSEDYLECV SKYTDQLKPF GDVPRKLKIQ VTRAFIAART FVQGLTVGRE VANRVSKVSP
TPGCIRALMK MLYCPYCRGL PTVRPCNNYC LNVMKGCLAN QADLDTEWNL FIDAMLLVAE
RLEGPFNIES VMDPIDVKIS EAIMNMQENS MQVSAKVFQG CGQPKPAPAL RSARSAPENF
NTRFRPYNPE ERPTTAAGTS LDRLVTDIKE KLKLSKKVWS ALPYTICKDE RVTAGTSNEE
ECWNGHSKAR YLPEIMNDGL TNQINNPEVE VDITRPDTFI RQQIMALRVM TNKLKNAYNG
NDVNFQDTSD ESSGSGSGSG CMDDVCPTEF EFVTTEAPAV DPDRREEESS ASKFSSSLIS
WSLVCMVLAL QRLYR
