GPC6_HUMAN
ID GPC6_HUMAN Reviewed; 555 AA.
AC Q9Y625; A8K279; Q96SG5; Q96SG8; Q9H1P4;
DT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1999, sequence version 1.
DT 03-AUG-2022, entry version 169.
DE RecName: Full=Glypican-6;
DE Contains:
DE RecName: Full=Secreted glypican-6;
DE Flags: Precursor;
GN Name=GPC6; ORFNames=UNQ369/PRO705;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=10329016; DOI=10.1006/geno.1999.5793;
RA Paine-Saunders S., Viviano B.L., Saunders S.;
RT "GPC6, a novel member of the glypican gene family, encodes a product
RT structurally related to GPC4 and is colocalized with GPC5 on human
RT chromosome 13.";
RL Genomics 57:455-458(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
RC TISSUE=Fetal brain;
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=12975309; DOI=10.1101/gr.1293003;
RA Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J.,
RA Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P.,
RA Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E., Heldens S., Huang A.,
RA Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D.,
RA Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L.,
RA Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C.,
RA Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J.,
RA Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M.;
RT "The secreted protein discovery initiative (SPDI), a large-scale effort to
RT identify novel human secreted and transmembrane proteins: a bioinformatics
RT assessment.";
RL Genome Res. 13:2265-2270(2003).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT MET-412.
RC TISSUE=Thalamus;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15057823; DOI=10.1038/nature02379;
RA Dunham A., Matthews L.H., Burton J., Ashurst J.L., Howe K.L.,
RA Ashcroft K.J., Beare D.M., Burford D.C., Hunt S.E., Griffiths-Jones S.,
RA Jones M.C., Keenan S.J., Oliver K., Scott C.E., Ainscough R., Almeida J.P.,
RA Ambrose K.D., Andrews D.T., Ashwell R.I.S., Babbage A.K., Bagguley C.L.,
RA Bailey J., Bannerjee R., Barlow K.F., Bates K., Beasley H., Bird C.P.,
RA Bray-Allen S., Brown A.J., Brown J.Y., Burrill W., Carder C., Carter N.P.,
RA Chapman J.C., Clamp M.E., Clark S.Y., Clarke G., Clee C.M., Clegg S.C.,
RA Cobley V., Collins J.E., Corby N., Coville G.J., Deloukas P., Dhami P.,
RA Dunham I., Dunn M., Earthrowl M.E., Ellington A.G., Faulkner L.,
RA Frankish A.G., Frankland J., French L., Garner P., Garnett J.,
RA Gilbert J.G.R., Gilson C.J., Ghori J., Grafham D.V., Gribble S.M.,
RA Griffiths C., Hall R.E., Hammond S., Harley J.L., Hart E.A., Heath P.D.,
RA Howden P.J., Huckle E.J., Hunt P.J., Hunt A.R., Johnson C., Johnson D.,
RA Kay M., Kimberley A.M., King A., Laird G.K., Langford C.J., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Lloyd C., Loveland J.E., Lovell J.,
RA Martin S., Mashreghi-Mohammadi M., McLaren S.J., McMurray A., Milne S.,
RA Moore M.J.F., Nickerson T., Palmer S.A., Pearce A.V., Peck A.I., Pelan S.,
RA Phillimore B., Porter K.M., Rice C.M., Searle S., Sehra H.K., Shownkeen R.,
RA Skuce C.D., Smith M., Steward C.A., Sycamore N., Tester J., Thomas D.W.,
RA Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., West A.P.,
RA Whitehead S.L., Willey D.L., Wilming L., Wray P.W., Wright M.W., Young L.,
RA Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Beck S., Bentley D.R.,
RA Rogers J., Ross M.T.;
RT "The DNA sequence and analysis of human chromosome 13.";
RL Nature 428:522-528(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [7]
RP INVOLVEMENT IN OMOD1.
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).
RN [8]
RP FUNCTION, TISSUE SPECIFICITY, AND INDUCTION.
RX PubMed=21871017; DOI=10.1042/bj20110530;
RA Yiu G.K., Kaunisto A., Chin Y.R., Toker A.;
RT "NFAT promotes carcinoma invasive migration through glypican-6.";
RL Biochem. J. 440:157-166(2011).
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 (By similarity). Enhances
CC migration and invasion of cancer cells through WNT5A signaling.
CC {ECO:0000250, ECO:0000269|PubMed:21871017}.
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: Widely expressed. High expression in fetal kidney
CC and lung and lower expressions in fetal liver and brain. In adult
CC tissues, very abundant in ovary, high levels also observed in liver,
CC kidney, small intestine and colon. Not detected in peripheral blood
CC leukocytes. Detected in breast cancer cells (at protein level).
CC {ECO:0000269|PubMed:10480909, ECO:0000269|PubMed:21871017}.
CC -!- INDUCTION: Expression is induced by NFATC2.
CC {ECO:0000269|PubMed:21871017}.
CC -!- DISEASE: Omodysplasia 1 (OMOD1) [MIM:258315]: A rare autosomal
CC recessive skeletal dysplasia characterized by facial dysmorphism and
CC severe congenital micromelia with shortening and distal tapering of the
CC humeri and femora, to give a club-like appearance. Typical facial
CC features include a prominent forehead, frontal bossing, short nose with
CC a depressed broad bridge, short columella, anteverted nostrils, long
CC philtrum, and small chin. {ECO:0000269|PubMed:19481194}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry. Point mutations leading to protein truncation, as well as larger
CC genomic rearrangements resulting in exon deletions, have been found in
CC family segregating omodysplasia type 1. All mutations identified in
CC individuals affected by omodysplasia could lead to the absence of a
CC functional protein, the mutant RNAs being suspected to be nonsense-
CC mediated mRNA decay (NMD) targets. Even if the mRNA escapes NMD and is
CC translated, all mutations are expected to disrupt the three-dimensional
CC protein structure and often to abolish multiple highly conserved
CC cysteine residues.
CC -!- SIMILARITY: Belongs to the glypican family. {ECO:0000305}.
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DR EMBL; AF111178; AAD31392.1; -; mRNA.
DR EMBL; AF105267; AAD55749.1; -; mRNA.
DR EMBL; AY358462; AAQ88827.1; -; mRNA.
DR EMBL; BC106947; AAI06948.1; -; mRNA.
DR EMBL; AK290144; BAF82833.1; -; mRNA.
DR EMBL; AL139798; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL160036; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL161426; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL162455; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL354811; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL137144; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR CCDS; CCDS9469.1; -.
DR RefSeq; NP_005699.1; NM_005708.4.
DR AlphaFoldDB; Q9Y625; -.
DR SMR; Q9Y625; -.
DR BioGRID; 115391; 28.
DR IntAct; Q9Y625; 14.
DR STRING; 9606.ENSP00000366246; -.
DR iPTMnet; Q9Y625; -.
DR PhosphoSitePlus; Q9Y625; -.
DR BioMuta; GPC6; -.
DR DMDM; 9973298; -.
DR EPD; Q9Y625; -.
DR jPOST; Q9Y625; -.
DR MassIVE; Q9Y625; -.
DR MaxQB; Q9Y625; -.
DR PaxDb; Q9Y625; -.
DR PeptideAtlas; Q9Y625; -.
DR PRIDE; Q9Y625; -.
DR ProteomicsDB; 86591; -.
DR Antibodypedia; 2876; 213 antibodies from 24 providers.
DR DNASU; 10082; -.
DR Ensembl; ENST00000377047.9; ENSP00000366246.3; ENSG00000183098.11.
DR GeneID; 10082; -.
DR KEGG; hsa:10082; -.
DR MANE-Select; ENST00000377047.9; ENSP00000366246.3; NM_005708.5; NP_005699.1.
DR UCSC; uc001vlt.4; human.
DR CTD; 10082; -.
DR DisGeNET; 10082; -.
DR GeneCards; GPC6; -.
DR HGNC; HGNC:4454; GPC6.
DR HPA; ENSG00000183098; Low tissue specificity.
DR MalaCards; GPC6; -.
DR MIM; 258315; phenotype.
DR MIM; 604404; gene.
DR neXtProt; NX_Q9Y625; -.
DR OpenTargets; ENSG00000183098; -.
DR Orphanet; 93329; Autosomal recessive omodysplasia.
DR PharmGKB; PA28835; -.
DR VEuPathDB; HostDB:ENSG00000183098; -.
DR eggNOG; KOG3821; Eukaryota.
DR GeneTree; ENSGT01050000244897; -.
DR HOGENOM; CLU_024658_2_0_1; -.
DR InParanoid; Q9Y625; -.
DR OMA; RSGPMED; -.
DR OrthoDB; 611422at2759; -.
DR PhylomeDB; Q9Y625; -.
DR TreeFam; TF105317; -.
DR PathwayCommons; Q9Y625; -.
DR Reactome; R-HSA-1971475; A tetrasaccharide linker sequence is required for GAG synthesis.
DR Reactome; R-HSA-2022928; HS-GAG biosynthesis.
DR Reactome; R-HSA-2024096; HS-GAG degradation.
DR Reactome; R-HSA-3560783; Defective B4GALT7 causes EDS, progeroid type.
DR Reactome; R-HSA-3560801; Defective B3GAT3 causes JDSSDHD.
DR Reactome; R-HSA-3656237; Defective EXT2 causes exostoses 2.
DR Reactome; R-HSA-3656253; Defective EXT1 causes exostoses 1, TRPS2 and CHDS.
DR Reactome; R-HSA-4420332; Defective B3GALT6 causes EDSP2 and SEMDJL1.
DR Reactome; R-HSA-9694614; Attachment and Entry.
DR Reactome; R-HSA-975634; Retinoid metabolism and transport.
DR SignaLink; Q9Y625; -.
DR SIGNOR; Q9Y625; -.
DR BioGRID-ORCS; 10082; 9 hits in 1070 CRISPR screens.
DR ChiTaRS; GPC6; human.
DR GeneWiki; Glypican_6; -.
DR GenomeRNAi; 10082; -.
DR Pharos; Q9Y625; Tbio.
DR PRO; PR:Q9Y625; -.
DR Proteomes; UP000005640; Chromosome 13.
DR RNAct; Q9Y625; protein.
DR Bgee; ENSG00000183098; Expressed in cartilage tissue and 166 other tissues.
DR ExpressionAtlas; Q9Y625; baseline and differential.
DR Genevisible; Q9Y625; HS.
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:0005796; C:Golgi lumen; TAS:Reactome.
DR GO; GO:0043202; C:lysosomal lumen; TAS:Reactome.
DR GO; GO:0005634; C:nucleus; HDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR GO; GO:0045202; C:synapse; IBA:GO_Central.
DR GO; GO:1904929; F:coreceptor activity involved in Wnt signaling pathway, planar cell polarity pathway; NAS:ParkinsonsUK-UCL.
DR GO; GO:0016477; P:cell migration; IDA:UniProtKB.
DR GO; GO:0098696; P:regulation of neurotransmitter receptor localization to postsynaptic specialization membrane; IBA:GO_Central.
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; Dwarfism; Glycoprotein; GPI-anchor; Heparan sulfate;
KW Lipoprotein; Membrane; Proteoglycan; Reference proteome; Secreted; Signal.
FT SIGNAL 1..23
FT /evidence="ECO:0000255"
FT CHAIN 24..529
FT /note="Glypican-6"
FT /id="PRO_0000012323"
FT CHAIN 24..?
FT /note="Secreted glypican-6"
FT /id="PRO_0000333851"
FT PROPEP 530..555
FT /note="Removed in mature form"
FT /evidence="ECO:0000255"
FT /id="PRO_0000012324"
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 529
FT /note="GPI-anchor amidated serine"
FT /evidence="ECO:0000255"
FT VARIANT 412
FT /note="V -> M (in dbSNP:rs1535692)"
FT /evidence="ECO:0000269|PubMed:14702039"
FT /id="VAR_024229"
FT CONFLICT 15
FT /note="L -> P (in Ref. 4; BAF82833)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 555 AA; 62736 MW; D3D01480FF9C4152 CRC64;
MPSWIGAVIL PLLGLLLSLP AGADVKARSC GEVRQAYGAK 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 SVTAGTSNEE
ECWNGHSKAR YLPEIMNDGL TNQINNPEVD VDITRPDTFI RQQIMALRVM TNKLKNAYNG
NDVNFQDTSD ESSGSGSGSG CMDDVCPTEF EFVTTEAPAV DPDRREVDSS AAQRGHSLLS
WSLTCIVLAL QRLCR
