CCN6_HUMAN
ID CCN6_HUMAN Reviewed; 354 AA.
AC O95389; Q3KR29; Q5H8W4; Q6UXH6;
DT 15-AUG-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-1999, sequence version 1.
DT 03-AUG-2022, entry version 169.
DE RecName: Full=Cellular communication network factor 6;
DE AltName: Full=CCN family member 6;
DE AltName: Full=WNT1-inducible-signaling pathway protein 3 {ECO:0000303|PubMed:9843955};
DE Short=WISP-3 {ECO:0000303|PubMed:9843955};
DE Flags: Precursor;
GN Name=CCN6 {ECO:0000312|HGNC:HGNC:12771};
GN Synonyms=WISP3 {ECO:0000312|HGNC:HGNC:12771};
GN ORFNames=UNQ462/PRO790/PRO956;
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] (ISOFORM 1), AND TISSUE SPECIFICITY.
RC TISSUE=Bone marrow, and Fetal kidney;
RX PubMed=9843955; DOI=10.1073/pnas.95.25.14717;
RA Pennica D., Swanson T.A., Welsh J.W., Roy M.A., Lawrence D.A., Lee J.,
RA Brush J., Taneyhill L.A., Deuel B., Lew M., Watanabe C., Cohen R.L.,
RA Melham M.F., Finley G.G., Quirke P., Goddard A.D., Hillan K.J.,
RA Gurney A.L., Botstein D., Levine A.J.;
RT "WISP genes are members of the connective tissue growth factor family that
RT are up-regulated in wnt-1-transformed cells and aberrantly expressed in
RT human colon tumors.";
RL Proc. Natl. Acad. Sci. U.S.A. 95:14717-14722(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=14574404; DOI=10.1038/nature02055;
RA Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L.,
RA Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R.,
RA Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D.,
RA Andrews T.D., Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H.,
RA Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J.,
RA Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V.,
RA Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J.,
RA Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E.,
RA Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J.,
RA French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J.,
RA Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C.,
RA Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A.,
RA Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R.,
RA Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M.,
RA Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K.,
RA Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R.,
RA Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M.,
RA Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A.,
RA Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L.,
RA Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I.,
RA Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y.,
RA Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E.,
RA Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A.,
RA Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W.,
RA Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M.,
RA West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J.,
RA Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M.,
RA Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I.,
RA Rogers J., Beck S.;
RT "The DNA sequence and analysis of human chromosome 6.";
RL Nature 425:805-811(2003).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
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 [6]
RP SUBCELLULAR LOCATION, AND FUNCTION.
RX PubMed=27252383; DOI=10.1242/jcs.186247;
RA Patra M., Mahata S.K., Padhan D.K., Sen M.;
RT "CCN6 regulates mitochondrial function.";
RL J. Cell Sci. 129:2841-2851(2016).
RN [7]
RP INVOLVEMENT IN PPRD, VARIANTS PPRD ARG-78 AND TYR-145, VARIANT HIS-56,
RP TISSUE SPECIFICITY, AND FUNCTION.
RX PubMed=10471507; DOI=10.1038/12699;
RA Hurvitz J.R., Suwairi W.M., Van Hul W., El-Shanti H., Superti-Furga A.,
RA Roudier J., Holderbaum D., Pauli R.M., Herd J.K., Van Hul E.V.,
RA Rezai-Delui H., Legius E., Le Merrer M., Al-Alami J., Bahabri S.A.,
RA Warman M.L.;
RT "Mutations in the CCN gene family member WISP3 cause progressive
RT pseudorheumatoid dysplasia.";
RL Nat. Genet. 23:94-98(1999).
RN [8]
RP VARIANTS PPRD 52-CYS--LEU-354 DEL AND ARG-78, AND VARIANTS HIS-56 AND
RP GLU-83.
RX PubMed=16152649; DOI=10.1002/ajmg.a.30906;
RA Delague V., Chouery E., Corbani S., Ghanem I., Aamar S., Fischer J.,
RA Levy-Lahad E., Urtizberea J.A., Megarbane A.;
RT "Molecular study of WISP3 in nine families originating from the Middle-East
RT and presenting with progressive pseudorheumatoid dysplasia: identification
RT of two novel mutations, and description of a founder effect.";
RL Am. J. Med. Genet. A 138A:118-126(2005).
RN [9]
RP VARIANTS PPRD 46-GLN--LEU-354 DEL AND TYR-114.
RX PubMed=19064006; DOI=10.1016/j.bone.2008.11.005;
RA Yue H., Zhang Z.L., He J.W.;
RT "Identification of novel mutations in WISP3 gene in two unrelated Chinese
RT families with progressive pseudorheumatoid dysplasia.";
RL Bone 44:547-554(2009).
RN [10]
RP VARIANTS PPRD 52-CYS--LEU-354 DEL; TYR-78; ARG-114; 116-TYR--LEU-354 DEL;
RP ARG-145; PRO-228; GLY-268 AND TYR-337, AND VARIANT GLU-83.
RX PubMed=22987568; DOI=10.1002/ajmg.a.35620;
RA Dalal A., Bhavani G.S., Togarrati P.P., Bierhals T., Nandineni M.R.,
RA Danda S., Danda D., Shah H., Vijayan S., Gowrishankar K., Phadke S.R.,
RA Bidchol A.M., Rao A.P., Nampoothiri S., Kutsche K., Girisha K.M.;
RT "Analysis of the WISP3 gene in Indian families with progressive
RT pseudorheumatoid dysplasia.";
RL Am. J. Med. Genet. A 158A:2820-2828(2012).
RN [11]
RP VARIANTS PPRD TRP-114 AND PRO-334.
RX PubMed=22685593; DOI=10.1371/journal.pone.0038643;
RA Sun J., Xia W., He S., Zhao Z., Nie M., Li M., Jiang Y., Xing X., Wang O.,
RA Meng X., Zhou X.;
RT "Novel and recurrent mutations of WISP3 in two Chinese families with
RT progressive pseudorheumatoid dysplasia.";
RL PLoS ONE 7:E38643-E38643(2012).
RN [12]
RP VARIANTS PPRD 52-CYS--LEU-354 DEL; TYR-78; PHE-99; SER-100;
RP 116-TYR--LEU-354 DEL; ARG-145; 177-SER--LEU-354 DEL; VAL-226 AND TYR-337.
RX PubMed=25988854; DOI=10.1002/ajmg.a.37164;
RA Bhavani G.S., Shah H., Dalal A.B., Shukla A., Danda S., Aggarwal S.,
RA Phadke S.R., Gupta N., Kabra M., Gowrishankar K., Gupta A., Bhat M.,
RA Puri R.D., Bijarnia-Mahay S., Nampoothiri S., Mohanasundaram K.M.,
RA Rajeswari S., Kulkarni A.M., Kulkarni M.L., Ranganath P., Ramadevi A.R.,
RA Hariharan S.V., Girisha K.M.;
RT "Novel and recurrent mutations in WISP3 and an atypical phenotype.";
RL Am. J. Med. Genet. A 167A:2481-2484(2015).
RN [13]
RP VARIANTS PPRD GLY-223 AND 252-CYS--LEU-354 DEL.
RX PubMed=25794430; DOI=10.1016/j.gene.2015.03.029;
RA Luo H., Shi C., Mao C., Jiang C., Bao D., Guo J., Du P., Wang Y., Liu Y.,
RA Liu X., Song B., Xu Y.;
RT "A novel compound WISP3 mutation in a Chinese family with progressive
RT pseudorheumatoid dysplasia.";
RL Gene 564:35-38(2015).
RN [14]
RP VARIANTS PPRD 46-GLN--LEU-354 DEL; TRP-114; GLY-223 AND 286-SER--LEU-354
RP DEL.
RX PubMed=25738435; DOI=10.3892/mmr.2015.3430;
RA Yu Y., Hu M., Xing X., Li F., Song Y., Luo Y., Ma H.;
RT "Identification of a mutation in the WISP3 gene in three unrelated families
RT with progressive pseudorheumatoid dysplasia.";
RL Mol. Med. Report. 12:419-425(2015).
RN [15]
RP VARIANTS PPRD 52-CYS--LEU-354 DEL; TYR-78; 116-TYR--LEU-354 DEL; VAL-226
RP AND TYR-337.
RX PubMed=27436824; DOI=10.1302/2046-3758.57.2000520;
RA Madhuri V., Santhanam M., Rajagopal K., Sugumar L.K., Balaji V.;
RT "WISP3 mutational analysis in Indian patients diagnosed with progressive
RT pseudorheumatoid dysplasia and report of a novel mutation at p.Y198.";
RL Bone Joint Res. 5:301-306(2016).
RN [16]
RP VARIANT PPRD 52-CYS--LEU-354 DEL.
RX PubMed=29092958; DOI=10.1101/mcs.a001990;
RA Sailani M.R., Chappell J., Jingga I., Narasimha A., Zia A., Lynch J.L.,
RA Mazrouei S., Bernstein J.A., Aryani O., Snyder M.P.;
RT "WISP3 mutation associated with pseudorheumatoid dysplasia.";
RL Cold Spring Harb. Mol. Case Stud. 4:0-0(2018).
CC -!- FUNCTION: Plays a role in mitochondrial electron transport and
CC mitochondrial respiration (PubMed:27252383). Through its regulation of
CC the mitochondrial function may play a role in normal postnatal skeletal
CC growth and cartilage homeostasis (PubMed:27252383, PubMed:10471507).
CC {ECO:0000269|PubMed:10471507, ECO:0000269|PubMed:27252383}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:27252383}.
CC Mitochondrion {ECO:0000269|PubMed:27252383}. Note=Associated with
CC membranes. {ECO:0000269|PubMed:27252383}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=O95389-1; Sequence=Displayed;
CC Name=2;
CC IsoId=O95389-2; Sequence=VSP_037803;
CC -!- TISSUE SPECIFICITY: Predominant expression in adult kidney and testis
CC and fetal kidney. Weaker expression found in placenta, ovary, prostate
CC and small intestine (PubMed:9843955, PubMed:10471507). Also expressed
CC in skeletally-derived cells such as synoviocytes and articular
CC cartilage chondrocytes (PubMed:10471507). {ECO:0000269|PubMed:10471507,
CC ECO:0000269|PubMed:9843955}.
CC -!- DISEASE: Progressive pseudorheumatoid dysplasia (PPRD) [MIM:208230]: An
CC autosomal recessive disorder characterized by stiffness and swelling of
CC joints, motor weakness and joint contractures. Signs and symptoms of
CC the disease develop typically between three and eight years of age.
CC This progressive disease is a primary disorder of articular cartilage
CC with continued cartilage loss and destructive bone changes with aging.
CC {ECO:0000269|PubMed:10471507, ECO:0000269|PubMed:16152649,
CC ECO:0000269|PubMed:19064006, ECO:0000269|PubMed:22685593,
CC ECO:0000269|PubMed:22987568, ECO:0000269|PubMed:25738435,
CC ECO:0000269|PubMed:25794430, ECO:0000269|PubMed:25988854,
CC ECO:0000269|PubMed:27436824, ECO:0000269|PubMed:29092958}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- SIMILARITY: Belongs to the CCN family. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/WISP3ID469ch6q22.html";
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DR EMBL; AF100781; AAC96323.1; -; mRNA.
DR EMBL; AY358349; AAQ88715.1; -; mRNA.
DR EMBL; AY358350; AAQ88716.1; -; mRNA.
DR EMBL; Z99289; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL512299; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471051; EAW48273.1; -; Genomic_DNA.
DR EMBL; CH471051; EAW48275.1; -; Genomic_DNA.
DR EMBL; BC105941; AAI05942.1; -; mRNA.
DR CCDS; CCDS5097.1; -. [O95389-1]
DR CCDS; CCDS5098.1; -. [O95389-1]
DR RefSeq; NP_003871.1; NM_003880.3. [O95389-1]
DR RefSeq; NP_937882.1; NM_198239.1. [O95389-1]
DR RefSeq; XP_011534522.1; XM_011536220.1. [O95389-1]
DR AlphaFoldDB; O95389; -.
DR SMR; O95389; -.
DR BioGRID; 114365; 19.
DR IntAct; O95389; 4.
DR STRING; 9606.ENSP00000357655; -.
DR GlyGen; O95389; 2 sites.
DR iPTMnet; O95389; -.
DR PhosphoSitePlus; O95389; -.
DR BioMuta; WISP3; -.
DR MassIVE; O95389; -.
DR PaxDb; O95389; -.
DR PeptideAtlas; O95389; -.
DR PRIDE; O95389; -.
DR Antibodypedia; 32438; 192 antibodies from 25 providers.
DR DNASU; 8838; -.
DR Ensembl; ENST00000230529.9; ENSP00000230529.5; ENSG00000112761.22. [O95389-1]
DR Ensembl; ENST00000368666.7; ENSP00000357655.4; ENSG00000112761.22. [O95389-1]
DR Ensembl; ENST00000604763.5; ENSP00000473777.1; ENSG00000112761.22. [O95389-1]
DR GeneID; 8838; -.
DR KEGG; hsa:8838; -.
DR MANE-Select; ENST00000368666.7; ENSP00000357655.4; NM_198239.2; NP_937882.2.
DR UCSC; uc003pvm.4; human. [O95389-1]
DR CTD; 8838; -.
DR DisGeNET; 8838; -.
DR GeneCards; CCN6; -.
DR GeneReviews; CCN6; -.
DR HGNC; HGNC:12771; CCN6.
DR HPA; ENSG00000112761; Tissue enriched (epididymis).
DR MalaCards; CCN6; -.
DR MIM; 208230; phenotype.
DR MIM; 603400; gene.
DR neXtProt; NX_O95389; -.
DR OpenTargets; ENSG00000112761; -.
DR Orphanet; 1159; Progressive pseudorheumatoid arthropathy of childhood.
DR PharmGKB; PA37374; -.
DR VEuPathDB; HostDB:ENSG00000112761; -.
DR eggNOG; ENOG502QW30; Eukaryota.
DR GeneTree; ENSGT00940000160119; -.
DR HOGENOM; CLU_063247_2_0_1; -.
DR InParanoid; O95389; -.
DR OMA; LVQTTPW; -.
DR OrthoDB; 601212at2759; -.
DR PhylomeDB; O95389; -.
DR TreeFam; TF326070; -.
DR PathwayCommons; O95389; -.
DR SignaLink; O95389; -.
DR BioGRID-ORCS; 8838; 7 hits in 1067 CRISPR screens.
DR GeneWiki; WNT1-inducible-signaling_pathway_protein_3; -.
DR GenomeRNAi; 8838; -.
DR Pharos; O95389; Tbio.
DR PRO; PR:O95389; -.
DR Proteomes; UP000005640; Chromosome 6.
DR RNAct; O95389; protein.
DR Bgee; ENSG00000112761; Expressed in tibia and 102 other tissues.
DR ExpressionAtlas; O95389; baseline and differential.
DR Genevisible; O95389; HS.
DR GO; GO:0031012; C:extracellular matrix; IBA:GO_Central.
DR GO; GO:0005615; C:extracellular space; IDA:UniProtKB.
DR GO; GO:0005739; C:mitochondrion; IDA:UniProtKB.
DR GO; GO:0008083; F:growth factor activity; IEA:UniProtKB-KW.
DR GO; GO:0008201; F:heparin binding; IBA:GO_Central.
DR GO; GO:0005178; F:integrin binding; IBA:GO_Central.
DR GO; GO:0007155; P:cell adhesion; IBA:GO_Central.
DR GO; GO:0007267; P:cell-cell signaling; TAS:ProtInc.
DR GO; GO:0016525; P:negative regulation of angiogenesis; IDA:MGI.
DR GO; GO:0060548; P:negative regulation of cell death; IBA:GO_Central.
DR GO; GO:0008285; P:negative regulation of cell population proliferation; IDA:MGI.
DR GO; GO:0051881; P:regulation of mitochondrial membrane potential; IMP:UniProtKB.
DR GO; GO:1903426; P:regulation of reactive oxygen species biosynthetic process; IMP:UniProtKB.
DR GO; GO:0007165; P:signal transduction; IBA:GO_Central.
DR Gene3D; 2.20.100.10; -; 1.
DR InterPro; IPR006207; Cys_knot_C.
DR InterPro; IPR006208; Glyco_hormone_CN.
DR InterPro; IPR009030; Growth_fac_rcpt_cys_sf.
DR InterPro; IPR000867; IGFBP-like.
DR InterPro; IPR012395; IGFBP_CNN.
DR InterPro; IPR017891; Insulin_GF-bd_Cys-rich_CS.
DR InterPro; IPR043973; TSP1_CCN.
DR InterPro; IPR000884; TSP1_rpt.
DR InterPro; IPR036383; TSP1_rpt_sf.
DR Pfam; PF00007; Cys_knot; 1.
DR Pfam; PF00219; IGFBP; 1.
DR Pfam; PF19035; TSP1_CCN; 1.
DR PIRSF; PIRSF036495; IGFBP_rP_CNN; 1.
DR SMART; SM00041; CT; 1.
DR SMART; SM00121; IB; 1.
DR SMART; SM00209; TSP1; 1.
DR SUPFAM; SSF57184; SSF57184; 1.
DR SUPFAM; SSF82895; SSF82895; 1.
DR PROSITE; PS01225; CTCK_2; 1.
DR PROSITE; PS00222; IGFBP_N_1; 1.
DR PROSITE; PS51323; IGFBP_N_2; 1.
DR PROSITE; PS50092; TSP1; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Disease variant; Disulfide bond; Glycoprotein;
KW Growth factor; Mitochondrion; Reference proteome; Secreted; Signal.
FT SIGNAL 1..23
FT /evidence="ECO:0000255"
FT CHAIN 24..354
FT /note="Cellular communication network factor 6"
FT /id="PRO_0000014412"
FT DOMAIN 44..117
FT /note="IGFBP N-terminal"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00653"
FT DOMAIN 208..253
FT /note="TSP type-1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00210"
FT DOMAIN 268..342
FT /note="CTCK"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00039"
FT CARBOHYD 178
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 308
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 268..305
FT /evidence="ECO:0000250"
FT DISULFID 285..319
FT /evidence="ECO:0000250"
FT DISULFID 296..335
FT /evidence="ECO:0000250"
FT DISULFID 299..337
FT /evidence="ECO:0000250"
FT DISULFID 304..341
FT /evidence="ECO:0000250"
FT VAR_SEQ 1
FT /note="M -> MNKRRLLYPSGWLHGPSDM (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:12975309,
FT ECO:0000303|PubMed:15489334"
FT /id="VSP_037803"
FT VARIANT 46..354
FT /note="Missing (in PPRD)"
FT /evidence="ECO:0000269|PubMed:19064006,
FT ECO:0000269|PubMed:25738435"
FT /id="VAR_081483"
FT VARIANT 52..354
FT /note="Missing (in PPRD)"
FT /evidence="ECO:0000269|PubMed:16152649,
FT ECO:0000269|PubMed:22987568, ECO:0000269|PubMed:25988854,
FT ECO:0000269|PubMed:27436824, ECO:0000269|PubMed:29092958"
FT /id="VAR_081484"
FT VARIANT 56
FT /note="Q -> H (in dbSNP:rs1230345)"
FT /evidence="ECO:0000269|PubMed:10471507,
FT ECO:0000269|PubMed:16152649"
FT /id="VAR_016224"
FT VARIANT 60
FT /note="R -> C (in dbSNP:rs17073260)"
FT /id="VAR_049567"
FT VARIANT 78
FT /note="C -> R (in PPRD; dbSNP:rs121908902)"
FT /evidence="ECO:0000269|PubMed:10471507,
FT ECO:0000269|PubMed:16152649"
FT /id="VAR_016225"
FT VARIANT 78
FT /note="C -> Y (in PPRD)"
FT /evidence="ECO:0000269|PubMed:22987568,
FT ECO:0000269|PubMed:25988854, ECO:0000269|PubMed:27436824"
FT /id="VAR_081485"
FT VARIANT 83
FT /note="G -> E (in dbSNP:rs147337485)"
FT /evidence="ECO:0000269|PubMed:16152649,
FT ECO:0000269|PubMed:22987568"
FT /id="VAR_081486"
FT VARIANT 99
FT /note="Y -> F (in PPRD; unknown pathological significance)"
FT /evidence="ECO:0000269|PubMed:25988854"
FT /id="VAR_081652"
FT VARIANT 100
FT /note="C -> S (in PPRD; unknown pathological significance)"
FT /evidence="ECO:0000269|PubMed:25988854"
FT /id="VAR_081653"
FT VARIANT 114
FT /note="C -> R (in PPRD)"
FT /evidence="ECO:0000269|PubMed:22987568"
FT /id="VAR_081487"
FT VARIANT 114
FT /note="C -> W (in PPRD)"
FT /evidence="ECO:0000269|PubMed:22685593,
FT ECO:0000269|PubMed:25738435"
FT /id="VAR_081488"
FT VARIANT 114
FT /note="C -> Y (in PPRD)"
FT /evidence="ECO:0000269|PubMed:19064006"
FT /id="VAR_081654"
FT VARIANT 116..354
FT /note="Missing (in PPRD)"
FT /evidence="ECO:0000269|PubMed:22987568,
FT ECO:0000269|PubMed:25988854, ECO:0000269|PubMed:27436824"
FT /id="VAR_081489"
FT VARIANT 145
FT /note="C -> R (in PPRD; unknown pathological significance)"
FT /evidence="ECO:0000269|PubMed:22987568,
FT ECO:0000269|PubMed:25988854"
FT /id="VAR_081490"
FT VARIANT 145
FT /note="C -> Y (in PPRD; unknown pathological significance;
FT dbSNP:rs121908899)"
FT /evidence="ECO:0000269|PubMed:10471507"
FT /id="VAR_081655"
FT VARIANT 177..354
FT /note="Missing (in PPRD)"
FT /evidence="ECO:0000269|PubMed:25988854"
FT /id="VAR_081656"
FT VARIANT 223
FT /note="C -> G (in PPRD; dbSNP:rs782813346)"
FT /evidence="ECO:0000269|PubMed:25738435,
FT ECO:0000269|PubMed:25794430"
FT /id="VAR_081491"
FT VARIANT 226
FT /note="G -> V (in PPRD)"
FT /evidence="ECO:0000269|PubMed:25988854,
FT ECO:0000269|PubMed:27436824"
FT /id="VAR_081657"
FT VARIANT 228
FT /note="S -> P (in PPRD; unknown pathological significance)"
FT /evidence="ECO:0000269|PubMed:22987568"
FT /id="VAR_081492"
FT VARIANT 252..354
FT /note="Missing (in PPRD)"
FT /evidence="ECO:0000269|PubMed:25794430"
FT /id="VAR_081658"
FT VARIANT 268
FT /note="C -> G (in PPRD; unknown pathological significance)"
FT /evidence="ECO:0000269|PubMed:22987568"
FT /id="VAR_081493"
FT VARIANT 286..354
FT /note="Missing (in PPRD)"
FT /evidence="ECO:0000269|PubMed:25738435"
FT /id="VAR_081494"
FT VARIANT 334
FT /note="S -> P (in PPRD; dbSNP:rs121908903)"
FT /evidence="ECO:0000269|PubMed:22685593"
FT /id="VAR_081659"
FT VARIANT 337
FT /note="C -> Y (in PPRD)"
FT /evidence="ECO:0000269|PubMed:22987568,
FT ECO:0000269|PubMed:25988854, ECO:0000269|PubMed:27436824"
FT /id="VAR_081495"
FT CONFLICT 200
FT /note="N -> D (in Ref. 2; AAQ88715)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 354 AA; 39293 MW; 67F48D0D5C2F5EE3 CRC64;
MQGLLFSTLL LAGLAQFCCR VQGTGPLDTT PEGRPGEVSD APQRKQFCHW PCKCPQQKPR
CPPGVSLVRD GCGCCKICAK QPGEICNEAD LCDPHKGLYC DYSVDRPRYE TGVCAYLVAV
GCEFNQVHYH NGQVFQPNPL FSCLCVSGAI GCTPLFIPKL AGSHCSGAKG GKKSDQSNCS
LEPLLQQLST SYKTMPAYRN LPLIWKKKCL VQATKWTPCS RTCGMGISNR VTNENSNCEM
RKEKRLCYIQ PCDSNILKTI KIPKGKTCQP TFQLSKAEKF VFSGCSSTQS YKPTFCGICL
DKRCCIPNKS KMITIQFDCP NEGSFKWKML WITSCVCQRN CREPGDIFSE LKIL
