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 13-FEB-2019, entry version 183. DE RecName: Full=Matrilin-3; DE Flags: Precursor; GN Name=MATN3; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; 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 RT cartilage-forming tumors and down-regulates SOX9 via EGF domain 1- RT dependent 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., RA Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., RA Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., RA Kremitzki C., Oddy L., Du H., Sun H., Bradshaw-Cordum H., Ali J., RA Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., RA Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., RA Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., RA Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., RA Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., RA 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., RA Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., RA Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., RA Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., RA Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., RA Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., RA Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., RA Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., RA Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., RA 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., RA Waterston R.H., Wilson R.K.; RT "Generation and annotation of the DNA sequences of human chromosomes 2 RT and 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., RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R., RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., RA 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 RT project: 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 RT extracellular matrix proteins related to cartilage matrix protein RT (matrilin-1) and von 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 RT 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 RT of 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., RA Jonsson H.H., Olafsdottir G., Palsdottir E., Stefansdottir G., RA Sveinbjornsdottir G., Frigge M.L., Kong A., Gulcher J.R., RA Stefansson K.; RT "Genomewide scan for hand osteoarthritis: a novel mutation in RT 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., RA de Graaf B., 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; RP LYS-252 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 RT A 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 RP VARIANTS 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., RA Maekitie O., Cole W.G., Wright M.J., Smithson S.F., Suri M., RA Rogala P., Mortier G.R., Baldock C., Wallace A., Elles R., RA Ala-Kokko L., Briggs M.D.; RT "Missense mutations in the beta strands of the single A-domain of RT matrilin-3 result in multiple epiphyseal dysplasia."; RL J. Med. Genet. 41:52-59(2004). RN [15] RP VARIANT SEMD-MATN3 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 RT for 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; RP ASP-194 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 RT the 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; RP LYS-195; 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., RA Spranger J., Zabel B., Le Merrer M., Cormier-Daire V., Hall C.M., RA Offiah A., Wright M.J., Savarirayan R., Nishimura G., Ramsden S.C., RA Elles R., Bonafe L., Superti-Furga A., Unger S., Zankl A., RA 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 RT relative contribution."; RL Hum. Mutat. 33:144-157(2012). CC -!- FUNCTION: Major component of the extracellular matrix of cartilage CC and may play a role in the formation of extracellular filamentous CC networks. CC -!- SUBUNIT: Can form homooligomers (monomers, dimers, trimers and CC tetramers) and heterooligomers with matrilin-1 (By similarity). CC Interacts with COMP. {ECO:0000250, ECO:0000269|PubMed:15075323}. CC -!- INTERACTION: CC P60410:KRTAP10-8; NbExp=3; IntAct=EBI-6262458, EBI-10171774; CC Q7Z3S9:NOTCH2NLA; NbExp=3; IntAct=EBI-6262458, EBI-945833; CC P15884:TCF4; NbExp=3; IntAct=EBI-6262458, EBI-533224; CC -!- SUBCELLULAR LOCATION: Secreted. 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 CC as vertebrae, ribs and shoulders. CC -!- DISEASE: Multiple epiphyseal dysplasia 5 (EDM5) [MIM:607078]: A CC generalized skeletal dysplasia associated with significant CC morbidity. Joint pain, joint deformity, waddling gait, and short CC stature are the main clinical signs and symptoms. Radiological CC examination of the skeleton shows delayed, irregular CC mineralization of the epiphyseal ossification centers and of the CC centers of the carpal and tarsal bones. Multiple epiphyseal CC dysplasia is broadly categorized into the more severe Fairbank and CC the milder Ribbing types. The Fairbank type is characterized by CC shortness of stature, short and stubby fingers, small epiphyses in CC several joints, including the knee, ankle, hand, and hip. The CC Ribbing type is confined predominantly to the hip joints and is CC characterized by hands that are normal and stature that is normal CC or near-normal. Multiple epiphyseal dysplasia type 5 is relatively CC mild and clinically variable. It is primarily characterized by CC delayed and irregular ossification of the epiphyses and early- CC onset osteoarthritis. {ECO:0000269|PubMed:11479597, CC ECO:0000269|PubMed:12884427, ECO:0000269|PubMed:14729835, CC ECO:0000269|PubMed:15459972, ECO:0000269|PubMed:15948199, CC ECO:0000269|PubMed:16287128, ECO:0000269|PubMed:21922596}. CC Note=The disease is caused by mutations affecting the gene CC represented in this entry. CC -!- DISEASE: Spondyloepimetaphyseal dysplasia MATN3-related (SEMD- CC MATN3) [MIM:608728]: A bone disease characterized by CC disproportionate early-onset dwarfism, bowing of the lower limbs, CC lumbar lordosis and normal hands. Skeletal abnormalities include CC short, wide and stocky long bones with severe epiphyseal and CC metaphyseal changes, hypoplastic iliac bones and flat, ovoid CC vertebral bodies. {ECO:0000269|PubMed:15121775}. Note=The disease CC is caused by mutations affecting the gene represented in this CC entry. CC -!- DISEASE: Osteoarthritis 2 (OS2) [MIM:140600]: A degenerative CC disease of the joints characterized by degradation of the hyaline CC articular cartilage and remodeling of the subchondral bone with CC sclerosis. Clinical symptoms include pain and joint stiffness CC often leading to significant disability and joint replacement. In CC the hand, osteoarthritis can develop in the distal interphalangeal CC and the first carpometacarpal (base of thumb) and proximal CC interphalangeal joints. Patients with osteoarthritis may have one, CC a few, or all of these sites affected. CC {ECO:0000269|PubMed:12736871}. Note=Disease susceptibility is CC associated with variations affecting the gene represented in this CC 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 UniGene; Hs.656199; -. DR ProteinModelPortal; O15232; -. DR SMR; O15232; -. DR BioGrid; 110318; 7. DR IntAct; O15232; 5. DR STRING; 9606.ENSP00000383894; -. DR iPTMnet; O15232; -. DR PhosphoSitePlus; O15232; -. DR BioMuta; MATN3; -. DR jPOST; O15232; -. DR MaxQB; O15232; -. DR PaxDb; O15232; -. DR PeptideAtlas; O15232; -. DR PRIDE; O15232; -. DR ProteomicsDB; 48527; -. DR Ensembl; ENST00000407540; ENSP00000383894; ENSG00000132031. [O15232-1] DR Ensembl; ENST00000421259; ENSP00000398753; ENSG00000132031. [O15232-2] DR GeneID; 4148; -. DR KEGG; hsa:4148; -. DR UCSC; uc002rdl.4; human. [O15232-1] DR CTD; 4148; -. DR DisGeNET; 4148; -. DR EuPathDB; HostDB:ENSG00000132031.12; -. DR GeneCards; MATN3; -. DR GeneReviews; MATN3; -. DR HGNC; HGNC:6909; MATN3. DR HPA; HPA051250; -. 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 eggNOG; KOG1217; Eukaryota. DR eggNOG; ENOG4111IJ5; LUCA. DR GeneTree; ENSGT00940000157581; -. DR HOGENOM; HOG000263415; -. DR HOVERGEN; HBG056906; -. DR InParanoid; O15232; -. DR KO; K19467; -. DR OMA; ICVNDGA; -. DR OrthoDB; 1174178at2759; -. DR PhylomeDB; O15232; -. DR TreeFam; TF330078; -. 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 GeneWiki; MATN3; -. DR GenomeRNAi; 4148; -. DR PMAP-CutDB; O15232; -. DR PRO; PR:O15232; -. DR Proteomes; UP000005640; Chromosome 2. DR Bgee; ENSG00000132031; Expressed in 117 organ(s), highest expression level in tibia. DR Genevisible; O15232; HS. DR GO; GO:0005788; C:endoplasmic reticulum lumen; TAS:Reactome. DR GO; GO:0031012; C:extracellular matrix; IBA:GO_Central. DR GO; GO:0005576; C:extracellular region; TAS:Reactome. DR GO; GO:0005615; C:extracellular space; IBA:GO_Central. DR GO; GO:0005509; F:calcium ion binding; IEA:InterPro. DR GO; GO:0005201; F:extracellular matrix structural constituent; TAS:ProtInc. DR GO; GO:0044267; P:cellular protein metabolic process; TAS:Reactome. DR GO; GO:0030198; P:extracellular matrix organization; TAS:Reactome. DR GO; GO:0003429; P:growth plate cartilage chondrocyte morphogenesis; IBA:GO_Central. DR GO; GO:0043687; P:post-translational protein modification; TAS:Reactome. DR GO; GO:0001501; P:skeletal system development; TAS:ProtInc. DR Gene3D; 3.40.50.410; -; 1. DR InterPro; IPR001881; EGF-like_Ca-bd_dom. DR InterPro; IPR013032; EGF-like_CS. DR InterPro; IPR000742; EGF-like_dom. DR InterPro; IPR009030; Growth_fac_rcpt_cys_sf. DR InterPro; IPR030765; Matrilin_3. 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; PTHR45117; PTHR45117; 1. DR Pfam; PF10393; Matrilin_ccoil; 1. DR Pfam; PF00092; VWA; 1. DR SMART; SM00181; EGF; 4. DR SMART; SM00179; EGF_CA; 4. DR SMART; SM01279; Matrilin_ccoil; 1. DR SMART; SM00327; VWA; 1. DR SUPFAM; SSF53300; SSF53300; 1. DR SUPFAM; SSF57184; SSF57184; 1. DR SUPFAM; SSF58002; SSF58002; 1. DR PROSITE; PS01186; EGF_2; 4. DR PROSITE; PS50026; EGF_3; 4. DR PROSITE; PS50234; VWFA; 1. PE 1: Evidence at protein level; KW Alternative splicing; Coiled coil; Complete proteome; KW Disease mutation; Disulfide bond; Dwarfism; EGF-like domain; KW Methylation; Phosphoprotein; Polymorphism; Reference proteome; Repeat; KW Secreted; Signal. FT SIGNAL 1 28 {ECO:0000255}. FT CHAIN 29 486 Matrilin-3. FT /FTId=PRO_0000007657. FT DOMAIN 83 258 VWFA. {ECO:0000255|PROSITE- FT ProRule:PRU00219}. FT DOMAIN 264 305 EGF-like 1. {ECO:0000255|PROSITE- FT ProRule:PRU00076}. FT DOMAIN 306 347 EGF-like 2. {ECO:0000255|PROSITE- FT ProRule:PRU00076}. FT DOMAIN 348 389 EGF-like 3. {ECO:0000255|PROSITE- FT ProRule:PRU00076}. FT DOMAIN 390 431 EGF-like 4. {ECO:0000255|PROSITE- FT ProRule:PRU00076}. FT COILED 456 480 {ECO:0000250}. FT MOD_RES 198 198 Omega-N-methylarginine. FT {ECO:0000250|UniProtKB:O35701}. FT MOD_RES 441 441 Phosphoserine; by FAM20C. FT {ECO:0000269|PubMed:26091039}. FT MOD_RES 442 442 Phosphothreonine; by FAM20C. FT {ECO:0000269|PubMed:26091039}. FT DISULFID 268 279 {ECO:0000255|PROSITE-ProRule:PRU00076}. FT DISULFID 275 289 {ECO:0000255|PROSITE-ProRule:PRU00076}. FT DISULFID 291 304 {ECO:0000255|PROSITE-ProRule:PRU00076}. FT DISULFID 310 321 {ECO:0000255|PROSITE-ProRule:PRU00076}. FT DISULFID 317 331 {ECO:0000255|PROSITE-ProRule:PRU00076}. FT DISULFID 333 346 {ECO:0000255|PROSITE-ProRule:PRU00076}. FT DISULFID 352 363 {ECO:0000255|PROSITE-ProRule:PRU00076}. FT DISULFID 359 373 {ECO:0000255|PROSITE-ProRule:PRU00076}. FT DISULFID 375 388 {ECO:0000255|PROSITE-ProRule:PRU00076}. FT DISULFID 394 405 {ECO:0000255|PROSITE-ProRule:PRU00076}. FT DISULFID 401 415 {ECO:0000255|PROSITE-ProRule:PRU00076}. FT DISULFID 417 430 {ECO:0000255|PROSITE-ProRule:PRU00076}. FT VAR_SEQ 266 307 Missing (in isoform 2). FT {ECO:0000303|Ref.2}. FT /FTId=VSP_054374. FT VARIANT 11 11 P -> S (in dbSNP:rs963330242). FT {ECO:0000269|PubMed:15459972}. FT /FTId=VAR_019881. FT VARIANT 70 70 R -> H (in EDM5; dbSNP:rs104893640). FT {ECO:0000269|PubMed:15948199}. FT /FTId=VAR_054807. FT VARIANT 105 105 F -> S (in EDM5). FT {ECO:0000269|PubMed:15459972}. FT /FTId=VAR_020844. FT VARIANT 120 120 T -> M (in EDM5; retained and accumulates FT within the cell; dbSNP:rs397515546). FT {ECO:0000269|PubMed:14729835, FT ECO:0000269|PubMed:15459972, FT ECO:0000269|PubMed:16287128, FT ECO:0000269|PubMed:21922596}. FT /FTId=VAR_019882. FT VARIANT 121 121 R -> W (in EDM5; retained and accumulates FT within the cell; dbSNP:rs104893637). FT {ECO:0000269|PubMed:11479597, FT ECO:0000269|PubMed:14729835, FT ECO:0000269|PubMed:15459972, FT ECO:0000269|PubMed:16287128, FT ECO:0000269|PubMed:21922596}. FT /FTId=VAR_013691. FT VARIANT 128 128 A -> P (in EDM5; bilateral hereditary FT microepiphyseal dysplasia; FT dbSNP:rs104893641). FT {ECO:0000269|PubMed:12884427}. FT /FTId=VAR_019883. FT VARIANT 134 134 E -> K (in EDM5; retained and accumulates FT within the cell). FT {ECO:0000269|PubMed:14729835, FT ECO:0000269|PubMed:16287128}. FT /FTId=VAR_019884. FT VARIANT 171 176 Missing (in EDM5). FT {ECO:0000269|PubMed:21922596}. FT /FTId=VAR_066830. FT VARIANT 173 173 A -> D (in EDM5; dbSNP:rs779413744). FT {ECO:0000269|PubMed:21922596}. FT /FTId=VAR_066831. FT VARIANT 192 192 I -> N (in EDM5; retained and accumulates FT within the cell). FT {ECO:0000269|PubMed:14729835, FT ECO:0000269|PubMed:16287128}. FT /FTId=VAR_019885. FT VARIANT 194 194 V -> D (in EDM5; retained and accumulates FT within the cell; dbSNP:rs104893645). FT {ECO:0000269|PubMed:11479597, FT ECO:0000269|PubMed:16287128}. FT /FTId=VAR_013692. FT VARIANT 195 195 T -> K (in EDM5). FT {ECO:0000269|PubMed:16287128, FT ECO:0000269|PubMed:21922596}. FT /FTId=VAR_054808. FT VARIANT 209 209 R -> P (in EDM5; dbSNP:rs749845872). FT {ECO:0000269|PubMed:21922596}. FT /FTId=VAR_066832. FT VARIANT 218 218 Y -> N (in EDM5). FT {ECO:0000269|PubMed:16287128, FT ECO:0000269|PubMed:21922596}. FT /FTId=VAR_054809. FT VARIANT 219 219 A -> D (in EDM5; retained and accumulates FT within the cell; dbSNP:rs28939677). FT {ECO:0000269|PubMed:14729835, FT ECO:0000269|PubMed:16287128, FT ECO:0000269|PubMed:21922596}. FT /FTId=VAR_019886. FT VARIANT 231 231 K -> N (in EDM5; dbSNP:rs773642745). FT {ECO:0000269|PubMed:21922596}. FT /FTId=VAR_066833. FT VARIANT 245 245 V -> M (in EDM5; dbSNP:rs182164052). FT {ECO:0000269|PubMed:21922596}. FT /FTId=VAR_066834. FT VARIANT 252 252 E -> K (secreted normally as the wild- FT type; dbSNP:rs52826764). FT {ECO:0000269|PubMed:14729835, FT ECO:0000269|PubMed:15459972, FT ECO:0000269|PubMed:16287128}. FT /FTId=VAR_019887. FT VARIANT 303 303 T -> M (in dbSNP:rs77245812). FT {ECO:0000269|PubMed:12736871, FT ECO:0000269|PubMed:14729835, FT ECO:0000269|PubMed:15459972}. FT /FTId=VAR_015852. FT VARIANT 304 304 C -> S (in SEMD-MATN3; FT dbSNP:rs104893639). FT {ECO:0000269|PubMed:15121775}. FT /FTId=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 //