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 24-JAN-2024, entry version 177. 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="https://atlasgeneticsoncology.org/gene/469/WISP3"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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; 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; 20. DR IntAct; O95389; 4. DR STRING; 9606.ENSP00000357655; -. DR GlyCosmos; O95389; 2 sites, No reported glycans. DR GlyGen; O95389; 2 sites. DR iPTMnet; O95389; -. DR PhosphoSitePlus; O95389; -. DR BioMuta; WISP3; -. DR MassIVE; O95389; -. DR PaxDb; 9606-ENSP00000357655; -. DR PeptideAtlas; O95389; -. DR ProteomicsDB; 50840; -. [O95389-1] DR ProteomicsDB; 50841; -. [O95389-2] DR Antibodypedia; 32438; 221 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 AGR; HGNC:12771; -. DR CTD; 8838; -. DR DisGeNET; 8838; -. DR GeneCards; CCN6; -. DR GeneReviews; CCN6; -. DR HGNC; HGNC:12771; CCN6. DR HPA; ENSG00000112761; Tissue enhanced (brain, 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; ERCNERD; -. DR OrthoDB; 2970572at2759; -. DR PhylomeDB; O95389; -. DR TreeFam; TF326070; -. DR PathwayCommons; O95389; -. DR SignaLink; O95389; -. DR BioGRID-ORCS; 8838; 9 hits in 1151 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 104 other cell types or tissues. DR ExpressionAtlas; O95389; baseline and differential. 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:HPA. 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: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; 2.10.70.10; Complement Module, domain 1; 1. DR Gene3D; 2.20.100.10; Thrombospondin type-1 (TSP1) repeat; 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 PANTHER; PTHR11348:SF3; CELLULAR COMMUNICATION NETWORK FACTOR 6; 1. DR PANTHER; PTHR11348; CONNECTIVE TISSUE GROWTH FACTOR-RELATED; 1. 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; SSF57603; FnI-like domain; 1. DR SUPFAM; SSF57184; Growth factor receptor domain; 1. DR SUPFAM; SSF82895; TSP-1 type 1 repeat; 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. DR Genevisible; O95389; HS. 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 48..72 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00653" FT DISULFID 52..74 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00653" FT DISULFID 54..75 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00653" FT DISULFID 61..78 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00653" FT DISULFID 86..100 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00653" FT DISULFID 92..114 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00653" 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; uncertain significance)" FT /evidence="ECO:0000269|PubMed:25988854" FT /id="VAR_081652" FT VARIANT 100 FT /note="C -> S (in PPRD; uncertain 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; uncertain 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; uncertain 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; uncertain 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; uncertain 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 //