MMP21_MOUSE
ID MMP21_MOUSE Reviewed; 568 AA.
AC Q8K3F2;
DT 19-JUL-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2002, sequence version 1.
DT 03-AUG-2022, entry version 144.
DE RecName: Full=Matrix metalloproteinase-21;
DE Short=MMP-21;
DE EC=3.4.24.-;
DE Flags: Precursor;
GN Name=Mmp21;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=BALB/cJ; TISSUE=Brain;
RX PubMed=12617721; DOI=10.1042/bj20030174;
RA Marchenko G.N., Marchenko N.D., Strongin A.Y.;
RT "The structure and regulation of the human and mouse matrix
RT metalloproteinase-21 gene and protein.";
RL Biochem. J. 372:503-515(2003).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=A/J;
RA Lopez-Otin C., Pendas A.M., Llano E.;
RT "Mouse MMP-21, a novel matrix metalloproteinase.";
RL Submitted (APR-2002) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP FUNCTION, AND MUTAGENESIS OF ILE-225.
RX PubMed=26437028; DOI=10.1038/ng.3376;
RA Guimier A., Gabriel G.C., Bajolle F., Tsang M., Liu H., Noll A.,
RA Schwartz M., El Malti R., Smith L.D., Klena N.T., Jimenez G., Miller N.A.,
RA Oufadem M., Moreau de Bellaing A., Yagi H., Saunders C.J., Baker C.N.,
RA Di Filippo S., Peterson K.A., Thiffault I., Bole-Feysot C., Cooley L.D.,
RA Farrow E.G., Masson C., Schoen P., Deleuze J.F., Nitschke P., Lyonnet S.,
RA de Pontual L., Murray S.A., Bonnet D., Kingsmore S.F., Amiel J.,
RA Bouvagnet P., Lo C.W., Gordon C.T.;
RT "MMP21 is mutated in human heterotaxy and is required for normal left-right
RT asymmetry in vertebrates.";
RL Nat. Genet. 47:1260-1263(2015).
RN [4]
RP FUNCTION, AND MUTAGENESIS OF TRP-177 AND TYR-325.
RX PubMed=26437029; DOI=10.1038/ng.3410;
RG DDD study;
RA Akawi N., McRae J., Ansari M., Balasubramanian M., Blyth M., Brady A.F.,
RA Clayton S., Cole T., Deshpande C., Fitzgerald T.W., Foulds N., Francis R.,
RA Gabriel G., Gerety S.S., Goodship J., Hobson E., Jones W.D., Joss S.,
RA King D., Klena N., Kumar A., Lees M., Lelliott C., Lord J., McMullan D.,
RA O'Regan M., Osio D., Piombo V., Prigmore E., Rajan D., Rosser E.,
RA Sifrim A., Smith A., Swaminathan G.J., Turnpenny P., Whitworth J.,
RA Wright C.F., Firth H.V., Barrett J.C., Lo C.W., FitzPatrick D.R.,
RA Hurles M.E.;
RT "Discovery of four recessive developmental disorders using probabilistic
RT genotype and phenotype matching among 4,125 families.";
RL Nat. Genet. 47:1363-1369(2015).
CC -!- FUNCTION: Plays a specialized role in the generation of left-right
CC asymmetry during embryogenesis (PubMed:26437028). May act as a negative
CC regulator of the NOTCH-signaling pathway. Cleaves alpha-1-antitrypsin
CC (By similarity). {ECO:0000250|UniProtKB:Q8N119,
CC ECO:0000269|PubMed:26437028, ECO:0000269|PubMed:26437029}.
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105; Evidence={ECO:0000250};
CC Note=Binds 1 zinc ion per subunit. {ECO:0000250};
CC -!- COFACTOR:
CC Name=Ca(2+); Xref=ChEBI:CHEBI:29108; Evidence={ECO:0000250};
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000305}.
CC -!- DOMAIN: The conserved cysteine present in the cysteine-switch motif
CC binds the catalytic zinc ion, thus inhibiting the enzyme. The
CC dissociation of the cysteine from the zinc ion upon the activation-
CC peptide release activates the enzyme.
CC -!- PTM: The precursor is cleaved by a furin endopeptidase. {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the peptidase M10A family. {ECO:0000305}.
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DR EMBL; AY124569; AAM94032.1; -; mRNA.
DR EMBL; AF507967; AAN09805.1; -; mRNA.
DR CCDS; CCDS21933.1; -.
DR RefSeq; NP_694423.1; NM_152944.1.
DR AlphaFoldDB; Q8K3F2; -.
DR SMR; Q8K3F2; -.
DR STRING; 10090.ENSMUSP00000033278; -.
DR MEROPS; M10.026; -.
DR GlyGen; Q8K3F2; 1 site.
DR PhosphoSitePlus; Q8K3F2; -.
DR PaxDb; Q8K3F2; -.
DR PRIDE; Q8K3F2; -.
DR ProteomicsDB; 291373; -.
DR Antibodypedia; 19175; 97 antibodies from 25 providers.
DR DNASU; 214766; -.
DR Ensembl; ENSMUST00000033278; ENSMUSP00000033278; ENSMUSG00000030981.
DR GeneID; 214766; -.
DR KEGG; mmu:214766; -.
DR UCSC; uc009kdd.1; mouse.
DR CTD; 118856; -.
DR MGI; MGI:2664387; Mmp21.
DR VEuPathDB; HostDB:ENSMUSG00000030981; -.
DR eggNOG; KOG1565; Eukaryota.
DR GeneTree; ENSGT00940000159140; -.
DR HOGENOM; CLU_015489_9_0_1; -.
DR InParanoid; Q8K3F2; -.
DR OMA; CWLAAPW; -.
DR OrthoDB; 1075463at2759; -.
DR PhylomeDB; Q8K3F2; -.
DR TreeFam; TF315428; -.
DR BioGRID-ORCS; 214766; 0 hits in 72 CRISPR screens.
DR PRO; PR:Q8K3F2; -.
DR Proteomes; UP000000589; Chromosome 7.
DR RNAct; Q8K3F2; protein.
DR Bgee; ENSMUSG00000030981; Expressed in blastocyst and 1 other tissue.
DR ExpressionAtlas; Q8K3F2; baseline and differential.
DR GO; GO:0031012; C:extracellular matrix; IEA:InterPro.
DR GO; GO:0005615; C:extracellular space; IBA:GO_Central.
DR GO; GO:0004222; F:metalloendopeptidase activity; IBA:GO_Central.
DR GO; GO:0008237; F:metallopeptidase activity; ISO:MGI.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0030574; P:collagen catabolic process; IBA:GO_Central.
DR GO; GO:0060976; P:coronary vasculature development; IMP:MGI.
DR GO; GO:0061371; P:determination of heart left/right asymmetry; IMP:UniProtKB.
DR GO; GO:0007368; P:determination of left/right symmetry; IMP:UniProtKB.
DR GO; GO:0030198; P:extracellular matrix organization; IBA:GO_Central.
DR GO; GO:0002244; P:hematopoietic progenitor cell differentiation; IGI:MGI.
DR GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR CDD; cd00094; HX; 1.
DR CDD; cd04278; ZnMc_MMP; 1.
DR Gene3D; 2.110.10.10; -; 2.
DR Gene3D; 3.40.390.10; -; 1.
DR InterPro; IPR000585; Hemopexin-like_dom.
DR InterPro; IPR036375; Hemopexin-like_dom_sf.
DR InterPro; IPR018487; Hemopexin-like_repeat.
DR InterPro; IPR033739; M10A_MMP.
DR InterPro; IPR024079; MetalloPept_cat_dom_sf.
DR InterPro; IPR001818; Pept_M10_metallopeptidase.
DR InterPro; IPR021190; Pept_M10A.
DR InterPro; IPR006026; Peptidase_Metallo.
DR InterPro; IPR002477; Peptidoglycan-bd-like.
DR InterPro; IPR036365; PGBD-like_sf.
DR Pfam; PF00045; Hemopexin; 3.
DR Pfam; PF00413; Peptidase_M10; 1.
DR Pfam; PF01471; PG_binding_1; 1.
DR PIRSF; PIRSF001191; Peptidase_M10A_matrix; 1.
DR PRINTS; PR00138; MATRIXIN.
DR SMART; SM00120; HX; 4.
DR SMART; SM00235; ZnMc; 1.
DR SUPFAM; SSF47090; SSF47090; 1.
DR SUPFAM; SSF50923; SSF50923; 1.
DR PROSITE; PS51642; HEMOPEXIN_2; 4.
DR PROSITE; PS00142; ZINC_PROTEASE; 1.
PE 1: Evidence at protein level;
KW Calcium; Disulfide bond; Glycoprotein; Hydrolase; Metal-binding;
KW Metalloprotease; Protease; Reference proteome; Repeat; Secreted; Signal;
KW Zinc; Zymogen.
FT SIGNAL 1..24
FT /evidence="ECO:0000255"
FT PROPEP 25..143
FT /evidence="ECO:0000250"
FT /id="PRO_0000437089"
FT CHAIN 144..568
FT /note="Matrix metalloproteinase-21"
FT /id="PRO_0000028841"
FT REPEAT 329..388
FT /note="Hemopexin 1"
FT REPEAT 390..446
FT /note="Hemopexin 2"
FT REPEAT 447..495
FT /note="Hemopexin 3"
FT REPEAT 502..558
FT /note="Hemopexin 4"
FT MOTIF 110..117
FT /note="Cysteine switch"
FT /evidence="ECO:0000250"
FT ACT_SITE 283
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10095"
FT BINDING 112
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /note="in inhibited form"
FT /evidence="ECO:0000250"
FT BINDING 282
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10095"
FT BINDING 286
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10095"
FT BINDING 292
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10095"
FT CARBOHYD 371
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 328..559
FT /evidence="ECO:0000250"
FT MUTAGEN 177
FT /note="W->L: Miri mutant, animals exhibit visceral
FT heterotaxy, with heart defects commonly associated with
FT heterotaxy."
FT /evidence="ECO:0000269|PubMed:26437029"
FT MUTAGEN 225
FT /note="I->T: Embryos have congenital heart defects with
FT transposition of the great artery, 61% exhibiting situs
FT inversus or heterotaxy and 39% exhibiting situs solitus.
FT This mutation corresponds to the pathological variant 'T-
FT 226' identified in humans."
FT /evidence="ECO:0000269|PubMed:26437028"
FT MUTAGEN 325
FT /note="Y->N: Koli mutant, animals exhibit visceral
FT heterotaxy, with heart defects commonly associated with
FT heterotaxy."
FT /evidence="ECO:0000269|PubMed:26437029"
SQ SEQUENCE 568 AA; 65454 MW; EDDBDDD9B6E00546 CRC64;
MLAASVLRLT LPLCWLVAPQ PTQPERLFHS RDRSDLEPSP LSQAKPIADL HDAQSFLLKY
GWSEIPSPKE SAGVPVGFTL AQAVRRFQKA NRLPASGELD SPTLAAMNKP RCGVPDTRLP
PRAALPTPPA LLTSLGLRPR ARQKRFLQML FPKPDGQQED ASDTGASRAF SKKTLTWRLV
GDAYSSQLSG DEQRYIFRLA FRMWSEVTPL DFREDRTAPG TMVDIKLGFG RGRHLGCPRV
FDGSGQEFAH AWRLGEIHFD DDEHFTPLSS DTGISLLKVA VHEIGHVLGL PHTYRVGSIM
QPNYIPQEPA FELDWADRKA IQRLYGSCKG SFDTVFDWIR KERNQYGEVR VRFNTYFFRN
SWYWLYENRN NRTRYGDPLQ ILTGWRGIPT QSIDAYVHVW SWGKDERYFF KGSQYWRYDS
ENDQAHTEDE QGRSYPKLIS EGFPGIPSPL DTAFYDRRQQ LIYFFKESLV FAFDVNRNQV
LNSYPKKMSQ VFPAIMPQNH PFRNLDSAYY SYAHNSIFFF KGNSYWKVVS DKDKQQNTRL
PLNGLFPKKP VSEKWFDVCD VHTSTLNM
