[1]	NUCLEOTIDE SEQUENCE [MRNA], AND CHARACTERIZATION. TISSUE=Cartilage; DOI=10.1006/geno.1998.5519; PubMed=9799608 [NCBI, ExPASy, EBI, Israel, Japan] Belluoccio D., Schenker T., Baici A., Trueb B.; "Characterization of human matrilin-3 (MATN3)."; Genomics 53:391-394(1998).
[2]	NUCLEOTIDE SEQUENCE [MRNA] OF 184-486. DOI=10.1016/S0014-5793(97)01126-5; PubMed=9350998 [NCBI, ExPASy, EBI, Israel, Japan] Belluoccio D., Trueb B.; "Matrilin-3 from chicken cartilage."; FEBS Lett. 415:212-216(1997).
[3]	NUCLEOTIDE SEQUENCE [MRNA] OF 177-486. DOI=10.1016/S0014-5793(97)00895-8; PubMed=9287130 [NCBI, ExPASy, EBI, Israel, Japan] Wagener R., Kobbe B., Paulsson M.; "Primary structure of matrilin-3, a new member of a family of extracellular matrix proteins related to cartilage matrix protein (matrilin-1) and von Willebrand factor."; FEBS Lett. 413:129-134(1997).
[4]	PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-295, AND MASS SPECTROMETRY. DOI=10.1038/sj.emboj.7601384; PubMed=17053785 [NCBI, ExPASy, EBI, Israel, Japan] Wang Y., Du D., Fang L., Yang G., Zhang C., Zeng R., Ullrich A., Lottspeich F., Chen Z.; "Tyrosine phosphorylated Par3 regulates epithelial tight junction assembly promoted by EGFR signaling."; EMBO J. 25:5058-5070(2006).
[5]	VARIANTS EDM5 TRP-121 AND ASP-194. DOI=10.1038/ng573; PubMed=11479597 [NCBI, ExPASy, EBI, Israel, Japan] Chapman K.L., Mortier G.R., Chapman K., Loughlin J., Grant M.E., Briggs M.D.; "Mutations in the region encoding the von Willebrand factor A domain of matrilin-3 are associated with multiple epiphyseal dysplasia."; Nat. Genet. 28:393-396(2001).
[6]	VARIANT MET-303, AND ASSOCIATION WITH OS2. DOI=10.1086/375556; PubMed=12736871 [NCBI, ExPASy, EBI, Israel, Japan] Stefansson S.E., Jonsson H., Ingvarsson T., Manolescu I., Jonsson H.H., Olafsdottir G., Palsdottir E., Stefansdottir G., Sveinbjornsdottir G., Frigge M.L., Kong A., Gulcher J.R., Stefansson K.; "Genomewide scan for hand osteoarthritis: a novel mutation in matrilin-3."; Am. J. Hum. Genet. 72:1448-1459(2003).
[7]	VARIANT EDM5 PRO-128. DOI=10.1002/ajmg.a.20034; PubMed=12884427 [NCBI, ExPASy, EBI, Israel, Japan] Mostert A.K., Dijkstra P.F., Jansen B.R.H., van Horn J.R., de Graaf B., Heutink P., Lindhout D.; "Familial multiple epiphyseal dysplasia due to a matrilin-3 mutation: further delineation of the phenotype including 40 years follow-up."; Am. J. Med. Genet. A 120:490-497(2003).
[8]	VARIANTS EDM5 SER-105; MET-120 AND TRP-121, AND VARIANTS SER-11; LYS-252 AND MET-303. DOI=10.1002/humu.9286; PubMed=15459972 [NCBI, ExPASy, EBI, Israel, Japan] Mabuchi A., Haga N., Maeda K., Nakashima E., Manabe N., Hiraoka H., Kitoh H., Kosaki R., Nishimura G., Ohashi H., Ikegawa S.; "Novel and recurrent mutations clustered in the von Willebrand factor A domain of MATN3 in multiple epiphyseal dysplasia."; Hum. Mutat. 24:439-440(2004).
[9]	VARIANTS EDM5 MET-120; TRP-121; LYS-134; ASN-192 AND ASP-219, AND VARIANTS LYS-252 AND MET-303. DOI=10.1136/jmg.2003.011429; PubMed=14729835 [NCBI, ExPASy, EBI, Israel, Japan] Jackson G.C., Barker F.S., Jakkula E., Czarny-Ratajczak M., Maekitie O., Cole W.G., Wright M.J., Smithson S.F., Suri M., Rogala P., Mortier G.R., Baldock C., Wallace A., Elles R., Ala-Kokko L., Briggs M.D.; "Missense mutations in the beta strands of the single A-domain of matrilin-3 result in multiple epiphyseal dysplasia."; J. Med. Genet. 41:52-59(2004).
[10]	VARIANT SEMD BOWED-LEGS TYPE SER-304. DOI=10.1136/jmg.2003.013342; PubMed=15121775 [NCBI, ExPASy, EBI, Israel, Japan] Borochowitz Z.U., Scheffer D., Adir V., Dagoneau N., Munnich A., Cormier-Daire V.; "Spondylo-epi-metaphyseal dysplasia (SEMD) matrilin 3 type: homozygote matrilin 3 mutation in a novel form of SEMD."; J. Med. Genet. 41:366-372(2004).
[11]	VARIANT EDM5 HIS-70. DOI=10.1002/ajmg.a.30832; PubMed=15948199 [NCBI, ExPASy, EBI, Israel, Japan] Maeda K., Nakashima E., Horikoshi T., Mabuchi A., Ikegawa S.; "Mutation in the von Willebrand factor-A domain is not a prerequisite for the MATN3 mutation in multiple epiphyseal dysplasia."; Am. J. Med. Genet. A 136:285-286(2005).
[12]	VARIANTS EDM5 TRP-121; LYS-195 AND ASN-218, VARIANT LYS-252, CHARACTERIZATION OF VARIANTS MET-120; TRP-121; LYS-134; ASN-192; ASP-194 AND ASP-219, AND CHARACTERIZATION OF VARIANT LYS-252. DOI=10.1002/humu.20263; PubMed=16287128 [NCBI, ExPASy, EBI, Israel, Japan] Cotterill S.L., Jackson G.C., Leighton M.P., Wagener R., Maekitie O., Cole W.G., Briggs M.D.; "Multiple epiphyseal dysplasia mutations in MATN3 cause misfolding of the A-domain and prevent secretion of mutant matrilin-3."; Hum. Mutat. 26:557-565(2005).

Comments

FUNCTION: Major component of the extracellular matrix of cartilage and may play a role in the formation of extracellular filamentous networks.
SUBUNIT: Can form homooligomers (monomers, dimers, trimers and tetramers) and heterooligomers with matrilin-1 (By similarity).
SUBCELLULAR LOCATION: Secreted.
TISSUE SPECIFICITY: Expressed only in cartilaginous tissues, such as vertebrae, ribs and shoulders.
DISEASE: Defects in MATN3 are the cause of multiple epiphyseal dysplasia type 5 (EDM5) [MIM:607078]. EDM is a generalized skeletal dysplasia associated with significant morbidity. Joint pain, joint deformity, waddling gait, and short stature are the main clinical signs and symptoms. EDM is broadly categorized into the more severe Fairbank and the milder Ribbing types. EDM5 is relatively mild and clinically variable. It is primarily characterized by delayed and irregular ossification of the epiphyses and early-onset osteoarthritis.
DISEASE: Defects in MATN3 are the cause of spondyloepimetaphyseal dysplasia bowed-legs type (SEMD bowed-legs type) [MIM:608728]; also known as matrilin-3 related SEMD. Affected individuals show disproportionate early-onset dwarfism, bowing of the lower limbs, lumbar lordosis and normal hands. Skeletal abnormalities include short, wide and stocky long bones with severe epiphyseal and metaphyseal changes, hypoplastic iliac bones and flat, ovoid vertebral bodies. SEMD bowed-legs type inheritance is autosomal recessive.
DISEASE: Genetic variations in MATN3 are associated with osteoarthritis susceptibility type 2 (OS2) [MIM:140600]; also called osteoarthritis of distal interphalangeal joints (OADIP) or hand osteoarthritis (HOA). In the hand, osteoarthritis can develop in the distal interphalangeal and the first carpometacarpal (base of thumb) and proximal interphalangeal joints. Patients with osteoarthritis may have one, a few, or all of these sites affected.
SIMILARITY: Contains 4 EGF-like domains.
SIMILARITY: Contains 1 VWFA domain.
WEB RESOURCE: Name=GeneReviews; URL="http://www.genetests.org/query?gene=MATN3";.

Copyright

Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms. Distributed under the Creative Commons Attribution-NoDerivs License.

Cross-references

Sequence databases

EMBL

AJ224741; CAA12110.1; -; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
AJ001047; CAA04501.1; -; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
Y13341; CAA73785.1; -; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]

IPI00005690; -.

NP_002372.1; -.

3D structure databases

HSSP

P00736; 1APQ. [HSSP ENTRY / PDB]

ModBase

O15232.

PTM databases

PhosphoSite

O15232; -.

Organism-specific databases

GC02M020113; -.

HIX0029855; -.

HGNC:6909; MATN3.

140600; phenotype. [NCBI / EBI]
602109; gene. [NCBI / EBI]
607078; phenotype. [NCBI / EBI]
608728; phenotype. [NCBI / EBI]

Orphanet

251; Epiphyseal dysplasia multiple.
93311; Multiple epiphyseal dysplasia, type 5.
252; Spondyloepimetaphyseal dysplasia.
156728; Spondyloepimetaphyseal dysplasia, matrilin-3 type.

PharmGKB

PA30652; -.

Gene expression databases

O15232; -.

O15232; -.

HS_MATN3; -.

ENSG00000132031; Homo sapiens.

Ontologies

GO:0005578;	Cellular component: proteinaceous extracellular matrix (traceable author statement from ProtInc).
GO:0005201;	Molecular function: extracellular matrix structural constituent (traceable author statement from ProtInc).
GO:0001501;	Biological process: skeletal system development (traceable author statement from ProtInc).
QuickGo view.

Family and domain databases

InterPro

IPR006209; EGF.
IPR006210; EGF-like.
IPR013032; EGF-like_reg_CS.
IPR000742; EGF_3.
IPR019466; Matrilin_coiled-coil_trimer.
IPR002035; VWF_A.
Graphical view of domain structure.

Pfam

PF00008; EGF; 4.
PF10393; Matrilin_ccoil; 1.
PF00092; VWA; 1.
Pfam graphical view of domain structure.

SMART

SM00181; EGF; 4.
SM00327; VWA; 1.
SMART graphical view of domain structure.

PROSITE

PS01186; EGF_2; 4.
PS50026; EGF_3; 4.
PS50234; VWFA; 1.
PROSITE graphical view of domain structure (profiles).

Proteomic databases

PRIDE

O15232; -.

Genome annotation databases

Ensembl

ENSG00000132031; Homo sapiens. [Contig view]

GeneID

4148; -.

KEGG

hsa:4148; -.

Phylogenomic databases

HOGENOM

O15232; -.

HOVERGEN

O15232; -.

OMA

O15232; THGCQHI.

Other

16298; -.

O15232; -.

MATN3; Homo sapiens.

View cluster of proteins with at least 50% / 90% / 100% identity.

Keywords

Coiled coil; Disease mutation; Disulfide bond; Dwarfism; EGF-like domain; Phosphoprotein; Polymorphism; Repeat; Secreted; Signal.

Features

Feature table viewer

Feature aligner

`Key`	`From To`	`Length`	`Description`	`FTId`
`SIGNAL`	`1 28`	`28`	`Potential.`
`CHAIN`	`29 486`	`458`	`Matrilin-3.`	`PRO_0000007657`
`DOMAIN`	`83 258`	`176`	`VWFA.`
`DOMAIN`	`264 305`	`42`	`EGF-like 1.`
`DOMAIN`	`306 347`	`42`	`EGF-like 2.`
`DOMAIN`	`348 389`	`42`	`EGF-like 3.`
`DOMAIN`	`390 431`	`42`	`EGF-like 4.`
`COILED`	`456 480`	`25`	`By similarity.`
`MOD_RES`	`295 295`		`Phosphotyrosine.`
`DISULFID`	`268 279`		`By similarity.`
`DISULFID`	`275 289`		`By similarity.`
`DISULFID`	`291 304`		`By similarity.`
`DISULFID`	`310 321`		`By similarity.`
`DISULFID`	`317 331`		`By similarity.`
`DISULFID`	`333 346`		`By similarity.`
`DISULFID`	`352 363`		`By similarity.`
`DISULFID`	`359 373`		`By similarity.`
`DISULFID`	`375 388`		`By similarity.`
`DISULFID`	`394 405`		`By similarity.`
`DISULFID`	`401 415`		`By similarity.`
`DISULFID`	`417 430`		`By similarity.`
`VARIANT`	`11 11`	`1`	`P -> S.`	`VAR_019881`
`VARIANT`	`70 70`	`1`	`R -> H (in EDM5).`	`VAR_054807`
`VARIANT`	`105 105`	`1`	`F -> S (in EDM5).`	`VAR_020844`
`VARIANT`	`120 120`	`1`	`T -> M (in EDM5; retained and accumulates within the cell).`	`VAR_019882`
`VARIANT`	`121 121`	`1`	`R -> W (in EDM5; retained and accumulates within the cell).`	`VAR_013691`
`VARIANT`	`128 128`	`1`	`A -> P (in EDM5; bilateral hereditary microepiphyseal dysplasia).`	`VAR_019883`
`VARIANT`	`134 134`	`1`	`E -> K (in EDM5; retained and accumulates within the cell).`	`VAR_019884`
`VARIANT`	`192 192`	`1`	`I -> N (in EDM5; retained and accumulates within the cell).`	`VAR_019885`
`VARIANT`	`194 194`	`1`	`V -> D (in EDM5; retained and accumulates within the cell).`	`VAR_013692`
`VARIANT`	`195 195`	`1`	`T -> K (in EDM5).`	`VAR_054808`
`VARIANT`	`218 218`	`1`	`Y -> N (in EDM5).`	`VAR_054809`
`VARIANT`	`219 219`	`1`	`A -> D (in EDM5; retained and accumulates within the cell; dbSNP:rs28939677 [NCBI]).`	`VAR_019886`
`VARIANT`	`252 252`	`1`	`E -> K (secreted normally as the wild-type; dbSNP:rs52826764 [NCBI]).`	`VAR_019887`
`VARIANT`	`303 303`	`1`	`T -> M (associated with OS2; may influence the phenotype severity in a multiple epiphyseal dysplasia patient carrying M-120).`	`VAR_015852`
`VARIANT`	`304 304`	`1`	`C -> S (in SEMD bowed-legs type).`	`VAR_019888`

Sequence information

Length: 486 AA [This is the length of the unprocessed precursor]

Molecular weight: 52817 Da [This is the MW of the unprocessed precursor]

CRC64: 688847BCC791B331 [This is a checksum on the sequence]

        10         20         30         40         50         60 
MPRPAPARRL PGLLLLLWPL LLLPSAAPDP VARPGFRRLE TRGPGGSPGR RPSPAAPDGA 

        70         80         90        100        110        120 
PASGTSEPGR ARGAGVCKSR PLDLVFIIDS SRSVRPLEFT KVKTFVSRII DTLDIGPADT 

       130        140        150        160        170        180 
RVAVVNYAST VKIEFQLQAY TDKQSLKQAV GRITPLSTGT MSGLAIQTAM DEAFTVEAGA 

       190        200        210        220        230        240 
REPSSNIPKV AIIVTDGRPQ DQVNEVAARA QASGIELYAV GVDRADMASL KMMASEPLEE 

       250        260        270        280        290        300 
HVFYVETYGV IEKLSSRFQE TFCALDPCVL GTHQCQHVCI SDGEGKHHCE CSQGYTLNAD 

       310        320        330        340        350        360 
KKTCSALDRC ALNTHGCEHI CVNDRSGSYH CECYEGYTLN EDRKTCSAQD KCALGTHGCQ 

       370        380        390        400        410        420 
HICVNDRTGS HHCECYEGYT LNADKKTCSV RDKCALGSHG CQHICVSDGA ASYHCDCYPG 

       430        440        450        460        470        480 
YTLNEDKKTC SATEEARRLV STEDACGCEA TLAFQDKVSS YLQRLNTKLD DILEKLKINE 


YGQIHR

O15232 in FASTA format

View entry in raw text format (no links)
Report form for errors/updates in this UniProtKB/Swiss-Prot entry

	BLAST submission on ExPASy/SIB or at NCBI (USA)		Sequence analysis tools: ProtParam, ProtScale, Compute pI/Mw, PeptideMass, PeptideCutter, Dotlet (Java)
	ScanProsite, MotifScan		Submit a homology modeling request to SWISS-MODEL
	NPSA Sequence analysis tools