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O15232 (MATN3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 140. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Matrilin-3
Gene names
Name:MATN3
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length486 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Major component of the extracellular matrix of cartilage and may play a role in the formation of extracellular filamentous networks.

Subunit structure

Can form homooligomers (monomers, dimers, trimers and tetramers) and heterooligomers with matrilin-1 By similarity. Interacts with COMP. Ref.7

Subcellular location

Secreted.

Tissue specificity

Expressed only in cartilaginous tissues, such as vertebrae, ribs and shoulders.

Involvement in disease

Multiple epiphyseal dysplasia 5 (EDM5) [MIM:607078]: A generalized skeletal dysplasia associated with significant morbidity. Joint pain, joint deformity, waddling gait, and short stature are the main clinical signs and symptoms. Radiological examination of the skeleton shows delayed, irregular mineralization of the epiphyseal ossification centers and of the centers of the carpal and tarsal bones. Multiple epiphyseal dysplasia is broadly categorized into the more severe Fairbank and the milder Ribbing types. The Fairbank type is characterized by shortness of stature, short and stubby fingers, small epiphyses in several joints, including the knee, ankle, hand, and hip. The Ribbing type is confined predominantly to the hip joints and is characterized by hands that are normal and stature that is normal or near-normal. Multiple epiphyseal dysplasia type 5 is relatively mild and clinically variable. It is primarily characterized by delayed and irregular ossification of the epiphyses and early-onset osteoarthritis.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.8 Ref.10 Ref.11 Ref.12 Ref.14 Ref.15 Ref.16

Spondyloepimetaphyseal dysplasia MATN3-related (SEMD-MATN3) [MIM:608728]: A bone disease characterized by 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.
Note: The disease is caused by mutations affecting the gene represented in this entry.

Osteoarthritis 2 (OS2) [MIM:140600]: A degenerative disease of the joints characterized by degradation of the hyaline articular cartilage and remodeling of the subchondral bone with sclerosis. Clinical symptoms include pain and joint stiffness often leading to significant disability and joint replacement. 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.
Note: Disease susceptibility is associated with variations affecting the gene represented in this entry. Ref.9

Sequence similarities

Contains 4 EGF-like domains.

Contains 1 VWFA domain.

Ontologies

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2828 Potential
Chain29 – 486458Matrilin-3
PRO_0000007657

Regions

Domain83 – 258176VWFA
Domain264 – 30542EGF-like 1
Domain306 – 34742EGF-like 2
Domain348 – 38942EGF-like 3
Domain390 – 43142EGF-like 4
Coiled coil456 – 48025 By similarity

Amino acid modifications

Disulfide bond268 ↔ 279 By similarity
Disulfide bond275 ↔ 289 By similarity
Disulfide bond291 ↔ 304 By similarity
Disulfide bond310 ↔ 321 By similarity
Disulfide bond317 ↔ 331 By similarity
Disulfide bond333 ↔ 346 By similarity
Disulfide bond352 ↔ 363 By similarity
Disulfide bond359 ↔ 373 By similarity
Disulfide bond375 ↔ 388 By similarity
Disulfide bond394 ↔ 405 By similarity
Disulfide bond401 ↔ 415 By similarity
Disulfide bond417 ↔ 430 By similarity

Natural variations

Natural variant111P → S. Ref.11
VAR_019881
Natural variant701R → H in EDM5. Ref.14
VAR_054807
Natural variant1051F → S in EDM5. Ref.11
VAR_020844
Natural variant1201T → M in EDM5; retained and accumulates within the cell. Ref.11 Ref.12 Ref.15 Ref.16
VAR_019882
Natural variant1211R → W in EDM5; retained and accumulates within the cell. Ref.8 Ref.11 Ref.12 Ref.15 Ref.16
VAR_013691
Natural variant1281A → P in EDM5; bilateral hereditary microepiphyseal dysplasia. Ref.10
VAR_019883
Natural variant1341E → K in EDM5; retained and accumulates within the cell. Ref.12 Ref.15
VAR_019884
Natural variant171 – 1766Missing in EDM5.
VAR_066830
Natural variant1731A → D in EDM5. Ref.16
VAR_066831
Natural variant1921I → N in EDM5; retained and accumulates within the cell. Ref.12 Ref.15
VAR_019885
Natural variant1941V → D in EDM5; retained and accumulates within the cell. Ref.8 Ref.15
VAR_013692
Natural variant1951T → K in EDM5. Ref.15 Ref.16
VAR_054808
Natural variant2091R → P in EDM5. Ref.16
VAR_066832
Natural variant2181Y → N in EDM5. Ref.15 Ref.16
VAR_054809
Natural variant2191A → D in EDM5; retained and accumulates within the cell. Ref.12 Ref.15 Ref.16
Corresponds to variant rs28939677 [ dbSNP | Ensembl ].
VAR_019886
Natural variant2311K → N in EDM5. Ref.16
VAR_066833
Natural variant2451V → M in EDM5. Ref.16
Corresponds to variant rs182164052 [ dbSNP | Ensembl ].
VAR_066834
Natural variant2521E → K Secreted normally as the wild-type. Ref.11 Ref.12 Ref.15
Corresponds to variant rs52826764 [ dbSNP | Ensembl ].
VAR_019887
Natural variant3031T → M. Ref.9 Ref.11 Ref.12
Corresponds to variant rs28939676 [ dbSNP | Ensembl ].
VAR_015852
Natural variant3041C → S in SEMD-MATN3. Ref.13
VAR_019888

Sequences

Sequence LengthMass (Da)Tools
O15232 [UniParc].

Last modified May 1, 1999. Version 2.
Checksum: 688847BCC791B331

FASTA48652,817
        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 

« Hide

References

« Hide 'large scale' references
[1]"Characterization of human matrilin-3 (MATN3)."
Belluoccio D., Schenker T., Baici A., Trueb B.
Genomics 53:391-394(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], CHARACTERIZATION.
Tissue: Cartilage.
[2]"Generation and annotation of the DNA sequences of human chromosomes 2 and 4."
Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H. expand/collapse author list , Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., Wilson R.K.
Nature 434:724-731(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[5]"Matrilin-3 from chicken cartilage."
Belluoccio D., Trueb B.
FEBS Lett. 415:212-216(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 184-486.
[6]"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."
Wagener R., Kobbe B., Paulsson M.
FEBS Lett. 413:129-134(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 177-486.
[7]"Interactions between the cartilage oligomeric matrix protein and matrilins. Implications for matrix assembly and the pathogenesis of chondrodysplasias."
Mann H.H., Oezbek S., Engel J., Paulsson M., Wagener R.
J. Biol. Chem. 279:25294-25298(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH COMP.
[8]"Mutations in the region encoding the von Willebrand factor A domain of matrilin-3 are associated with multiple epiphyseal dysplasia."
Chapman K.L., Mortier G.R., Chapman K., Loughlin J., Grant M.E., Briggs M.D.
Nat. Genet. 28:393-396(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS EDM5 TRP-121 AND ASP-194.
[9]"Genomewide scan for hand osteoarthritis: a novel mutation in matrilin-3."
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.
Am. J. Hum. Genet. 72:1448-1459(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT MET-303, ASSOCIATION WITH OS2.
[10]"Familial multiple epiphyseal dysplasia due to a matrilin-3 mutation: further delineation of the phenotype including 40 years follow-up."
Mostert A.K., Dijkstra P.F., Jansen B.R.H., van Horn J.R., de Graaf B., Heutink P., Lindhout D.
Am. J. Med. Genet. A 120:490-497(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT EDM5 PRO-128.
[11]"Novel and recurrent mutations clustered in the von Willebrand factor A domain of MATN3 in multiple epiphyseal dysplasia."
Mabuchi A., Haga N., Maeda K., Nakashima E., Manabe N., Hiraoka H., Kitoh H., Kosaki R., Nishimura G., Ohashi H., Ikegawa S.
Hum. Mutat. 24:439-440(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS EDM5 SER-105; MET-120 AND TRP-121, VARIANTS SER-11; LYS-252 AND MET-303.
[12]"Missense mutations in the beta strands of the single A-domain of matrilin-3 result in multiple epiphyseal dysplasia."
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.
J. Med. Genet. 41:52-59(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS EDM5 MET-120; TRP-121; LYS-134; ASN-192 AND ASP-219, VARIANTS LYS-252 AND MET-303.
[13]"Spondylo-epi-metaphyseal dysplasia (SEMD) matrilin 3 type: homozygote matrilin 3 mutation in a novel form of SEMD."
Borochowitz Z.U., Scheffer D., Adir V., Dagoneau N., Munnich A., Cormier-Daire V.
J. Med. Genet. 41:366-372(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT SEMD-MATN3 SER-304.
[14]"Mutation in the von Willebrand factor-A domain is not a prerequisite for the MATN3 mutation in multiple epiphyseal dysplasia."
Maeda K., Nakashima E., Horikoshi T., Mabuchi A., Ikegawa S.
Am. J. Med. Genet. A 136:285-286(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT EDM5 HIS-70.
[15]"Multiple epiphyseal dysplasia mutations in MATN3 cause misfolding of the A-domain and prevent secretion of mutant matrilin-3."
Cotterill S.L., Jackson G.C., Leighton M.P., Wagener R., Maekitie O., Cole W.G., Briggs M.D.
Hum. Mutat. 26:557-565(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: 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, CHARACTERIZATION OF VARIANT LYS-252.
[16]"Pseudoachondroplasia and multiple epiphyseal dysplasia: A 7-year comprehensive analysis of the known disease genes identify novel and recurrent mutations and provides an accurate assessment of their relative contribution."
Jackson G.C., Mittaz-Crettol L., Taylor J.A., Mortier G.R., Spranger J., Zabel B., Le Merrer M., Cormier-Daire V., Hall C.M., Offiah A., Wright M.J., Savarirayan R., Nishimura G., Ramsden S.C., Elles R., Bonafe L., Superti-Furga A., Unger S., Zankl A., Briggs M.D.
Hum. Mutat. 33:144-157(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS EDM5 MET-120; TRP-121; 171-ASP--VAL-176 DEL; ASP-173; LYS-195; PRO-209; ASN-218; ASP-219; ASN-231 AND MET-245.
+Additional computationally mapped references.

Web resources

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AJ224741 mRNA. Translation: CAA12110.1.
AC079145 Genomic DNA. Translation: AAX88937.1.
CH471053 Genomic DNA. Translation: EAX00837.1.
BC139907 mRNA. Translation: AAI39908.1.
AJ001047 mRNA. Translation: CAA04501.1.
Y13341 mRNA. Translation: CAA73785.1.
RefSeqNP_002372.1. NM_002381.4.
UniGeneHs.656199.

3D structure databases

ProteinModelPortalO15232.
SMRO15232. Positions 82-245, 263-470.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid110318. 3 interactions.
IntActO15232. 1 interaction.
STRING9606.ENSP00000383894.

PTM databases

PhosphoSiteO15232.

Proteomic databases

PaxDbO15232.
PRIDEO15232.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000407540; ENSP00000383894; ENSG00000132031.
GeneID4148.
KEGGhsa:4148.
UCSCuc002rdl.3. human.

Organism-specific databases

CTD4148.
GeneCardsGC02M020191.
HGNCHGNC:6909. MATN3.
MIM140600. phenotype.
602109. gene.
607078. phenotype.
608728. phenotype.
neXtProtNX_O15232.
Orphanet93311. Multiple epiphyseal dysplasia type 5.
156728. Spondyloepimetaphyseal dysplasia, matrilin-3 type.
PharmGKBPA30652.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG300624.
HOGENOMHOG000263415.
HOVERGENHBG056906.
InParanoidO15232.
OMARFQETFC.
OrthoDBEOG7X9G6P.
PhylomeDBO15232.
TreeFamTF330078.

Enzyme and pathway databases

ReactomeREACT_118779. Extracellular matrix organization.

Gene expression databases

ArrayExpressO15232.
BgeeO15232.
CleanExHS_MATN3.
GenevestigatorO15232.

Family and domain databases

Gene3D1.20.5.30. 1 hit.
3.40.50.410. 1 hit.
InterProIPR000742. EG-like_dom.
IPR013032. EGF-like_CS.
IPR009030. Growth_fac_rcpt_N_dom.
IPR019466. Matrilin_coiled-coil_trimer.
IPR002035. VWF_A.
[Graphical view]
PfamPF10393. Matrilin_ccoil. 1 hit.
PF00092. VWA. 1 hit.
[Graphical view]
SMARTSM00181. EGF. 4 hits.
SM00327. VWA. 1 hit.
[Graphical view]
SUPFAMSSF53300. SSF53300. 1 hit.
SSF57184. SSF57184. 1 hit.
PROSITEPS01186. EGF_2. 4 hits.
PS50026. EGF_3. 4 hits.
PS50234. VWFA. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiMATN3.
GenomeRNAi4148.
NextBio16298.
PMAP-CutDBO15232.
PROO15232.
SOURCESearch...

Entry information

Entry nameMATN3_HUMAN
AccessionPrimary (citable) accession number: O15232
Secondary accession number(s): Q4ZG02
Entry history
Integrated into UniProtKB/Swiss-Prot: June 20, 2001
Last sequence update: May 1, 1999
Last modified: April 16, 2014
This is version 140 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 2

Human chromosome 2: entries, gene names and cross-references to MIM