ID MATN3_HUMAN Reviewed; 486 AA. AC O15232; B2CPU0; Q4ZG02; DT 20-JUN-2001, integrated into UniProtKB/Swiss-Prot. DT 01-MAY-1999, sequence version 2. DT 24-JAN-2024, entry version 210. DE RecName: Full=Matrilin-3; DE Flags: Precursor; GN Name=MATN3; 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 CHARACTERIZATION. RC TISSUE=Cartilage; RX PubMed=9799608; DOI=10.1006/geno.1998.5519; RA Belluoccio D., Schenker T., Baici A., Trueb B.; RT "Characterization of human matrilin-3 (MATN3)."; RL Genomics 53:391-394(1998). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2). RA Vincourt J.-B., Takigawa M.; RT "Matrilin-3 increases not only upon osteoarthritis but also in cartilage- RT forming tumors and down-regulates SOX9 via EGF domain 1-dependent RT signaling."; RL Submitted (MAR-2008) to the EMBL/GenBank/DDBJ databases. RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15815621; DOI=10.1038/nature03466; RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., RA Wilson R.K.; RT "Generation and annotation of the DNA sequences of human chromosomes 2 and RT 4."; RL Nature 434:724-731(2005). 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 (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). 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 NUCLEOTIDE SEQUENCE [MRNA] OF 184-486 (ISOFORM 1). RX PubMed=9350998; DOI=10.1016/s0014-5793(97)01126-5; RA Belluoccio D., Trueb B.; RT "Matrilin-3 from chicken cartilage."; RL FEBS Lett. 415:212-216(1997). RN [7] RP NUCLEOTIDE SEQUENCE [MRNA] OF 177-486 (ISOFORM 1). RX PubMed=9287130; DOI=10.1016/s0014-5793(97)00895-8; RA Wagener R., Kobbe B., Paulsson M.; RT "Primary structure of matrilin-3, a new member of a family of extracellular RT matrix proteins related to cartilage matrix protein (matrilin-1) and von RT Willebrand factor."; RL FEBS Lett. 413:129-134(1997). RN [8] RP INTERACTION WITH COMP. RX PubMed=15075323; DOI=10.1074/jbc.m403778200; RA Mann H.H., Oezbek S., Engel J., Paulsson M., Wagener R.; RT "Interactions between the cartilage oligomeric matrix protein and RT matrilins. Implications for matrix assembly and the pathogenesis of RT chondrodysplasias."; RL J. Biol. Chem. 279:25294-25298(2004). RN [9] RP PHOSPHORYLATION AT SER-441 AND THR-442. RX PubMed=26091039; DOI=10.1016/j.cell.2015.05.028; RA Tagliabracci V.S., Wiley S.E., Guo X., Kinch L.N., Durrant E., Wen J., RA Xiao J., Cui J., Nguyen K.B., Engel J.L., Coon J.J., Grishin N., RA Pinna L.A., Pagliarini D.J., Dixon J.E.; RT "A single kinase generates the majority of the secreted phosphoproteome."; RL Cell 161:1619-1632(2015). RN [10] RP VARIANTS EDM5 TRP-121 AND ASP-194. RX PubMed=11479597; DOI=10.1038/ng573; RA Chapman K.L., Mortier G.R., Chapman K., Loughlin J., Grant M.E., RA Briggs M.D.; RT "Mutations in the region encoding the von Willebrand factor A domain of RT matrilin-3 are associated with multiple epiphyseal dysplasia."; RL Nat. Genet. 28:393-396(2001). RN [11] RP VARIANT MET-303, AND INVOLVEMENT IN OS2. RX PubMed=12736871; DOI=10.1086/375556; RA Stefansson S.E., Jonsson H., Ingvarsson T., Manolescu I., Jonsson H.H., RA Olafsdottir G., Palsdottir E., Stefansdottir G., Sveinbjornsdottir G., RA Frigge M.L., Kong A., Gulcher J.R., Stefansson K.; RT "Genomewide scan for hand osteoarthritis: a novel mutation in matrilin-3."; RL Am. J. Hum. Genet. 72:1448-1459(2003). RN [12] RP VARIANT EDM5 PRO-128. RX PubMed=12884427; DOI=10.1002/ajmg.a.20034; RA Mostert A.K., Dijkstra P.F., Jansen B.R.H., van Horn J.R., de Graaf B., RA Heutink P., Lindhout D.; RT "Familial multiple epiphyseal dysplasia due to a matrilin-3 mutation: RT further delineation of the phenotype including 40 years follow-up."; RL Am. J. Med. Genet. A 120:490-497(2003). RN [13] RP VARIANTS EDM5 SER-105; MET-120 AND TRP-121, AND VARIANTS SER-11; LYS-252 RP AND MET-303. RX PubMed=15459972; DOI=10.1002/humu.9286; RA Mabuchi A., Haga N., Maeda K., Nakashima E., Manabe N., Hiraoka H., RA Kitoh H., Kosaki R., Nishimura G., Ohashi H., Ikegawa S.; RT "Novel and recurrent mutations clustered in the von Willebrand factor A RT domain of MATN3 in multiple epiphyseal dysplasia."; RL Hum. Mutat. 24:439-440(2004). RN [14] RP VARIANTS EDM5 MET-120; TRP-121; LYS-134; ASN-192 AND ASP-219, AND VARIANTS RP LYS-252 AND MET-303. RX PubMed=14729835; DOI=10.1136/jmg.2003.011429; RA Jackson G.C., Barker F.S., Jakkula E., Czarny-Ratajczak M., Maekitie O., RA Cole W.G., Wright M.J., Smithson S.F., Suri M., Rogala P., Mortier G.R., RA Baldock C., Wallace A., Elles R., Ala-Kokko L., Briggs M.D.; RT "Missense mutations in the beta strands of the single A-domain of matrilin- RT 3 result in multiple epiphyseal dysplasia."; RL J. Med. Genet. 41:52-59(2004). RN [15] RP VARIANT SEMDBCD SER-304. RX PubMed=15121775; DOI=10.1136/jmg.2003.013342; RA Borochowitz Z.U., Scheffer D., Adir V., Dagoneau N., Munnich A., RA Cormier-Daire V.; RT "Spondylo-epi-metaphyseal dysplasia (SEMD) matrilin 3 type: homozygote RT matrilin 3 mutation in a novel form of SEMD."; RL J. Med. Genet. 41:366-372(2004). RN [16] RP VARIANT EDM5 HIS-70. RX PubMed=15948199; DOI=10.1002/ajmg.a.30832; RA Maeda K., Nakashima E., Horikoshi T., Mabuchi A., Ikegawa S.; RT "Mutation in the von Willebrand factor-A domain is not a prerequisite for RT the MATN3 mutation in multiple epiphyseal dysplasia."; RL Am. J. Med. Genet. A 136:285-286(2005). RN [17] RP VARIANTS EDM5 TRP-121; LYS-195 AND ASN-218, VARIANT LYS-252, RP CHARACTERIZATION OF VARIANTS MET-120; TRP-121; LYS-134; ASN-192; ASP-194 RP AND ASP-219, AND CHARACTERIZATION OF VARIANT LYS-252. RX PubMed=16287128; DOI=10.1002/humu.20263; RA Cotterill S.L., Jackson G.C., Leighton M.P., Wagener R., Maekitie O., RA Cole W.G., Briggs M.D.; RT "Multiple epiphyseal dysplasia mutations in MATN3 cause misfolding of the RT A-domain and prevent secretion of mutant matrilin-3."; RL Hum. Mutat. 26:557-565(2005). RN [18] RP VARIANTS EDM5 MET-120; TRP-121; 171-ASP--VAL-176 DEL; ASP-173; LYS-195; RP PRO-209; ASN-218; ASP-219; ASN-231 AND MET-245. RX PubMed=21922596; DOI=10.1002/humu.21611; RA Jackson G.C., Mittaz-Crettol L., Taylor J.A., Mortier G.R., Spranger J., RA Zabel B., Le Merrer M., Cormier-Daire V., Hall C.M., Offiah A., RA Wright M.J., Savarirayan R., Nishimura G., Ramsden S.C., Elles R., RA Bonafe L., Superti-Furga A., Unger S., Zankl A., Briggs M.D.; RT "Pseudoachondroplasia and multiple epiphyseal dysplasia: A 7-year RT comprehensive analysis of the known disease genes identify novel and RT recurrent mutations and provides an accurate assessment of their relative RT contribution."; RL Hum. Mutat. 33:144-157(2012). CC -!- FUNCTION: Major component of the extracellular matrix of cartilage and CC may play a role in the formation of extracellular filamentous networks. CC -!- SUBUNIT: Can form homooligomers (monomers, dimers, trimers and CC tetramers) and heterooligomers with matrilin-1 (By similarity). CC Interacts with COMP. Component of a complex containing at least CRELD2, CC MANF, MATN3 and PDIA4 (By similarity). {ECO:0000250, CC ECO:0000250|UniProtKB:O35701, ECO:0000269|PubMed:15075323}. CC -!- INTERACTION: CC O15232; Q0VD86: INCA1; NbExp=3; IntAct=EBI-6262458, EBI-6509505; CC O15232; P60410: KRTAP10-8; NbExp=3; IntAct=EBI-6262458, EBI-10171774; CC O15232; Q7Z3S9: NOTCH2NLA; NbExp=3; IntAct=EBI-6262458, EBI-945833; CC O15232; P13667: PDIA4; NbExp=6; IntAct=EBI-6262458, EBI-1054653; CC O15232; P15884: TCF4; NbExp=3; IntAct=EBI-6262458, EBI-533224; CC O15232; P15884-3: TCF4; NbExp=3; IntAct=EBI-6262458, EBI-13636688; CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000250|UniProtKB:O35701}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=O15232-1; Sequence=Displayed; CC Name=2; CC IsoId=O15232-2; Sequence=VSP_054374; CC -!- TISSUE SPECIFICITY: Expressed only in cartilaginous tissues, such as CC vertebrae, ribs and shoulders. CC -!- DISEASE: Multiple epiphyseal dysplasia 5 (EDM5) [MIM:607078]: A CC generalized skeletal dysplasia associated with significant morbidity. CC Joint pain, joint deformity, waddling gait, and short stature are the CC main clinical signs and symptoms. Radiological examination of the CC skeleton shows delayed, irregular mineralization of the epiphyseal CC ossification centers and of the centers of the carpal and tarsal bones. CC Multiple epiphyseal dysplasia is broadly categorized into the more CC severe Fairbank and the milder Ribbing types. The Fairbank type is CC characterized by shortness of stature, short and stubby fingers, small CC epiphyses in several joints, including the knee, ankle, hand, and hip. CC The Ribbing type is confined predominantly to the hip joints and is CC characterized by hands that are normal and stature that is normal or CC near-normal. Multiple epiphyseal dysplasia type 5 is relatively mild CC and clinically variable. It is primarily characterized by delayed and CC irregular ossification of the epiphyses and early-onset osteoarthritis. CC {ECO:0000269|PubMed:11479597, ECO:0000269|PubMed:12884427, CC ECO:0000269|PubMed:14729835, ECO:0000269|PubMed:15459972, CC ECO:0000269|PubMed:15948199, ECO:0000269|PubMed:16287128, CC ECO:0000269|PubMed:21922596}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- DISEASE: Spondyloepimetaphyseal dysplasia, Borochowitz-Cormier-Daire CC type (SEMDBCD) [MIM:608728]: An autosomal recessive bone disease CC characterized by disproportionate early-onset dwarfism, bowing of the CC lower limbs, lumbar lordosis and normal hands. Skeletal abnormalities CC include short, wide and stocky long bones with severe epiphyseal and CC metaphyseal changes, hypoplastic iliac bones and flat, ovoid vertebral CC bodies. {ECO:0000269|PubMed:15121775}. Note=The disease is caused by CC variants affecting the gene represented in this entry. CC -!- DISEASE: Osteoarthritis 2 (OS2) [MIM:140600]: A degenerative disease of CC the joints characterized by degradation of the hyaline articular CC cartilage and remodeling of the subchondral bone with sclerosis. CC Clinical symptoms include pain and joint stiffness often leading to CC significant disability and joint replacement. In the hand, CC osteoarthritis can develop in the distal interphalangeal and the first CC carpometacarpal (base of thumb) and proximal interphalangeal joints. CC Patients with osteoarthritis may have one, a few, or all of these sites CC affected. {ECO:0000269|PubMed:12736871}. Note=Disease susceptibility is CC associated with variants affecting the gene represented in this entry. 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; AJ224741; CAA12110.1; -; mRNA. DR EMBL; EU541440; ACB29772.1; -; mRNA. DR EMBL; AC079145; AAX88937.1; -; Genomic_DNA. DR EMBL; CH471053; EAX00837.1; -; Genomic_DNA. DR EMBL; BC139907; AAI39908.1; -; mRNA. DR EMBL; AJ001047; CAA04501.1; -; mRNA. DR EMBL; Y13341; CAA73785.1; -; mRNA. DR CCDS; CCDS46226.1; -. [O15232-1] DR RefSeq; NP_002372.1; NM_002381.4. [O15232-1] DR AlphaFoldDB; O15232; -. DR SMR; O15232; -. DR BioGRID; 110318; 12. DR ComplexPortal; CPX-4469; Matrilin-3 complex. DR ComplexPortal; CPX-4503; Matrilin-1 - Matrilin-3 complex. DR IntAct; O15232; 23. DR STRING; 9606.ENSP00000383894; -. DR GlyGen; O15232; 4 sites, 1 O-linked glycan (4 sites). DR iPTMnet; O15232; -. DR PhosphoSitePlus; O15232; -. DR BioMuta; MATN3; -. DR jPOST; O15232; -. DR MassIVE; O15232; -. DR MaxQB; O15232; -. DR PaxDb; 9606-ENSP00000383894; -. DR PeptideAtlas; O15232; -. DR ProteomicsDB; 3408; -. DR ProteomicsDB; 48527; -. [O15232-1] DR Antibodypedia; 27187; 251 antibodies from 27 providers. DR DNASU; 4148; -. DR Ensembl; ENST00000407540.8; ENSP00000383894.3; ENSG00000132031.13. [O15232-1] DR Ensembl; ENST00000421259.2; ENSP00000398753.2; ENSG00000132031.13. [O15232-2] DR GeneID; 4148; -. DR KEGG; hsa:4148; -. DR MANE-Select; ENST00000407540.8; ENSP00000383894.3; NM_002381.5; NP_002372.1. DR UCSC; uc002rdl.4; human. [O15232-1] DR AGR; HGNC:6909; -. DR CTD; 4148; -. DR DisGeNET; 4148; -. DR GeneCards; MATN3; -. DR GeneReviews; MATN3; -. DR HGNC; HGNC:6909; MATN3. DR HPA; ENSG00000132031; Tissue enhanced (lung, placenta). DR MalaCards; MATN3; -. DR MIM; 140600; phenotype. DR MIM; 602109; gene. DR MIM; 607078; phenotype. DR MIM; 608728; phenotype. DR neXtProt; NX_O15232; -. DR OpenTargets; ENSG00000132031; -. DR Orphanet; 93311; Multiple epiphyseal dysplasia type 5. DR Orphanet; 156728; Spondyloepimetaphyseal dysplasia, matrilin-3 type. DR PharmGKB; PA30652; -. DR VEuPathDB; HostDB:ENSG00000132031; -. DR eggNOG; KOG1217; Eukaryota. DR GeneTree; ENSGT00940000157581; -. DR HOGENOM; CLU_008905_6_1_1; -. DR InParanoid; O15232; -. DR OMA; CALGTHQ; -. DR OrthoDB; 1453590at2759; -. DR PhylomeDB; O15232; -. DR TreeFam; TF330078; -. DR PathwayCommons; O15232; -. DR Reactome; R-HSA-3000178; ECM proteoglycans. DR Reactome; R-HSA-381426; Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs). DR Reactome; R-HSA-8957275; Post-translational protein phosphorylation. DR SignaLink; O15232; -. DR BioGRID-ORCS; 4148; 18 hits in 1146 CRISPR screens. DR ChiTaRS; MATN3; human. DR GeneWiki; MATN3; -. DR GenomeRNAi; 4148; -. DR Pharos; O15232; Tbio. DR PRO; PR:O15232; -. DR Proteomes; UP000005640; Chromosome 2. DR RNAct; O15232; Protein. DR Bgee; ENSG00000132031; Expressed in tibia and 101 other cell types or tissues. DR GO; GO:0062023; C:collagen-containing extracellular matrix; ISO:ComplexPortal. DR GO; GO:0005788; C:endoplasmic reticulum lumen; TAS:Reactome. DR GO; GO:0031012; C:extracellular matrix; TAS:ProtInc. DR GO; GO:0005576; C:extracellular region; TAS:Reactome. DR GO; GO:0120216; C:matrilin complex; ISO:ComplexPortal. DR GO; GO:0005509; F:calcium ion binding; IEA:InterPro. DR GO; GO:0005201; F:extracellular matrix structural constituent; TAS:ProtInc. DR GO; GO:0051216; P:cartilage development; IEA:Ensembl. DR GO; GO:0030198; P:extracellular matrix organization; ISO:ComplexPortal. DR GO; GO:0001501; P:skeletal system development; TAS:ProtInc. DR Gene3D; 1.20.5.30; -; 1. DR Gene3D; 2.10.25.10; Laminin; 4. DR Gene3D; 3.40.50.410; von Willebrand factor, type A domain; 1. DR InterPro; IPR026823; cEGF. DR InterPro; IPR001881; EGF-like_Ca-bd_dom. DR InterPro; IPR000742; EGF-like_dom. DR InterPro; IPR009030; Growth_fac_rcpt_cys_sf. DR InterPro; IPR036337; Matrilin_cc_sf. DR InterPro; IPR019466; Matrilin_coiled-coil_trimer. DR InterPro; IPR002035; VWF_A. DR InterPro; IPR036465; vWFA_dom_sf. DR PANTHER; PTHR24020; COLLAGEN ALPHA; 1. DR PANTHER; PTHR24020:SF12; MATRILIN-3; 1. DR Pfam; PF12662; cEGF; 1. DR Pfam; PF07645; EGF_CA; 2. DR Pfam; PF14670; FXa_inhibition; 1. DR Pfam; PF10393; Matrilin_ccoil; 1. DR Pfam; PF00092; VWA; 1. DR PRINTS; PR00453; VWFADOMAIN. DR SMART; SM00181; EGF; 4. DR SMART; SM00179; EGF_CA; 4. DR SMART; SM01279; Matrilin_ccoil; 1. DR SMART; SM00327; VWA; 1. DR SUPFAM; SSF58002; Chicken cartilage matrix protein; 1. DR SUPFAM; SSF57196; EGF/Laminin; 1. DR SUPFAM; SSF57184; Growth factor receptor domain; 1. DR SUPFAM; SSF53300; vWA-like; 1. DR PROSITE; PS01186; EGF_2; 4. DR PROSITE; PS50026; EGF_3; 4. DR PROSITE; PS50234; VWFA; 1. DR Genevisible; O15232; HS. PE 1: Evidence at protein level; KW Alternative splicing; Coiled coil; Disease variant; Disulfide bond; KW Dwarfism; EGF-like domain; Methylation; Phosphoprotein; Reference proteome; KW Repeat; Secreted; Signal. FT SIGNAL 1..28 FT /evidence="ECO:0000255" FT CHAIN 29..486 FT /note="Matrilin-3" FT /id="PRO_0000007657" FT DOMAIN 83..258 FT /note="VWFA" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00219" FT DOMAIN 264..305 FT /note="EGF-like 1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DOMAIN 306..347 FT /note="EGF-like 2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DOMAIN 348..389 FT /note="EGF-like 3" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DOMAIN 390..431 FT /note="EGF-like 4" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT REGION 32..75 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COILED 456..480 FT /evidence="ECO:0000250" FT MOD_RES 198 FT /note="Omega-N-methylarginine" FT /evidence="ECO:0000250|UniProtKB:O35701" FT MOD_RES 441 FT /note="Phosphoserine; by FAM20C" FT /evidence="ECO:0000269|PubMed:26091039" FT MOD_RES 442 FT /note="Phosphothreonine; by FAM20C" FT /evidence="ECO:0000269|PubMed:26091039" FT DISULFID 268..279 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DISULFID 275..289 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DISULFID 291..304 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DISULFID 310..321 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DISULFID 317..331 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DISULFID 333..346 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DISULFID 352..363 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DISULFID 359..373 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DISULFID 375..388 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DISULFID 394..405 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DISULFID 401..415 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DISULFID 417..430 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT VAR_SEQ 266..307 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|Ref.2" FT /id="VSP_054374" FT VARIANT 11 FT /note="P -> S (in dbSNP:rs963330242)" FT /evidence="ECO:0000269|PubMed:15459972" FT /id="VAR_019881" FT VARIANT 70 FT /note="R -> H (in EDM5; dbSNP:rs104893640)" FT /evidence="ECO:0000269|PubMed:15948199" FT /id="VAR_054807" FT VARIANT 105 FT /note="F -> S (in EDM5)" FT /evidence="ECO:0000269|PubMed:15459972" FT /id="VAR_020844" FT VARIANT 120 FT /note="T -> M (in EDM5; retained and accumulates within the FT cell; dbSNP:rs397515546)" FT /evidence="ECO:0000269|PubMed:14729835, FT ECO:0000269|PubMed:15459972, ECO:0000269|PubMed:16287128, FT ECO:0000269|PubMed:21922596" FT /id="VAR_019882" FT VARIANT 121 FT /note="R -> W (in EDM5; retained and accumulates within the FT cell; dbSNP:rs104893637)" FT /evidence="ECO:0000269|PubMed:11479597, FT ECO:0000269|PubMed:14729835, ECO:0000269|PubMed:15459972, FT ECO:0000269|PubMed:16287128, ECO:0000269|PubMed:21922596" FT /id="VAR_013691" FT VARIANT 128 FT /note="A -> P (in EDM5; bilateral hereditary FT microepiphyseal dysplasia; dbSNP:rs104893641)" FT /evidence="ECO:0000269|PubMed:12884427" FT /id="VAR_019883" FT VARIANT 134 FT /note="E -> K (in EDM5; retained and accumulates within the FT cell)" FT /evidence="ECO:0000269|PubMed:14729835, FT ECO:0000269|PubMed:16287128" FT /id="VAR_019884" FT VARIANT 171..176 FT /note="Missing (in EDM5)" FT /evidence="ECO:0000269|PubMed:21922596" FT /id="VAR_066830" FT VARIANT 173 FT /note="A -> D (in EDM5; dbSNP:rs779413744)" FT /evidence="ECO:0000269|PubMed:21922596" FT /id="VAR_066831" FT VARIANT 192 FT /note="I -> N (in EDM5; retained and accumulates within the FT cell)" FT /evidence="ECO:0000269|PubMed:14729835, FT ECO:0000269|PubMed:16287128" FT /id="VAR_019885" FT VARIANT 194 FT /note="V -> D (in EDM5; retained and accumulates within the FT cell; dbSNP:rs104893645)" FT /evidence="ECO:0000269|PubMed:11479597, FT ECO:0000269|PubMed:16287128" FT /id="VAR_013692" FT VARIANT 195 FT /note="T -> K (in EDM5)" FT /evidence="ECO:0000269|PubMed:16287128, FT ECO:0000269|PubMed:21922596" FT /id="VAR_054808" FT VARIANT 209 FT /note="R -> P (in EDM5; dbSNP:rs749845872)" FT /evidence="ECO:0000269|PubMed:21922596" FT /id="VAR_066832" FT VARIANT 218 FT /note="Y -> N (in EDM5)" FT /evidence="ECO:0000269|PubMed:16287128, FT ECO:0000269|PubMed:21922596" FT /id="VAR_054809" FT VARIANT 219 FT /note="A -> D (in EDM5; retained and accumulates within the FT cell; dbSNP:rs28939677)" FT /evidence="ECO:0000269|PubMed:14729835, FT ECO:0000269|PubMed:16287128, ECO:0000269|PubMed:21922596" FT /id="VAR_019886" FT VARIANT 231 FT /note="K -> N (in EDM5; dbSNP:rs773642745)" FT /evidence="ECO:0000269|PubMed:21922596" FT /id="VAR_066833" FT VARIANT 245 FT /note="V -> M (in EDM5; dbSNP:rs182164052)" FT /evidence="ECO:0000269|PubMed:21922596" FT /id="VAR_066834" FT VARIANT 252 FT /note="E -> K (secreted normally as the wild-type; FT dbSNP:rs52826764)" FT /evidence="ECO:0000269|PubMed:14729835, FT ECO:0000269|PubMed:15459972, ECO:0000269|PubMed:16287128" FT /id="VAR_019887" FT VARIANT 303 FT /note="T -> M (in dbSNP:rs77245812)" FT /evidence="ECO:0000269|PubMed:12736871, FT ECO:0000269|PubMed:14729835, ECO:0000269|PubMed:15459972" FT /id="VAR_015852" FT VARIANT 304 FT /note="C -> S (in SEMDBCD; dbSNP:rs104893639)" FT /evidence="ECO:0000269|PubMed:15121775" FT /id="VAR_019888" SQ SEQUENCE 486 AA; 52817 MW; 688847BCC791B331 CRC64; MPRPAPARRL PGLLLLLWPL LLLPSAAPDP VARPGFRRLE TRGPGGSPGR RPSPAAPDGA PASGTSEPGR ARGAGVCKSR PLDLVFIIDS SRSVRPLEFT KVKTFVSRII DTLDIGPADT RVAVVNYAST VKIEFQLQAY TDKQSLKQAV GRITPLSTGT MSGLAIQTAM DEAFTVEAGA REPSSNIPKV AIIVTDGRPQ DQVNEVAARA QASGIELYAV GVDRADMASL KMMASEPLEE HVFYVETYGV IEKLSSRFQE TFCALDPCVL GTHQCQHVCI SDGEGKHHCE CSQGYTLNAD KKTCSALDRC ALNTHGCEHI CVNDRSGSYH CECYEGYTLN EDRKTCSAQD KCALGTHGCQ HICVNDRTGS HHCECYEGYT LNADKKTCSV RDKCALGSHG CQHICVSDGA ASYHCDCYPG YTLNEDKKTC SATEEARRLV STEDACGCEA TLAFQDKVSS YLQRLNTKLD DILEKLKINE YGQIHR //