MMP21_DANRE
ID MMP21_DANRE Reviewed; 599 AA.
AC A0A0N9E2K8;
DT 07-SEP-2016, integrated into UniProtKB/Swiss-Prot.
DT 07-SEP-2016, sequence version 2.
DT 03-AUG-2022, entry version 35.
DE RecName: Full=Matrix metallopeptidase-21 {ECO:0000312|EMBL:ALF36875.1};
DE Short=MMP-21;
DE EC=3.4.24.-;
DE Flags: Precursor;
GN Name=mmp21 {ECO:0000312|EMBL:ALF36875.1,
GN ECO:0000312|ZFIN:ZDB-GENE-100226-2};
OS Danio rerio (Zebrafish) (Brachydanio rerio).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Actinopterygii; Neopterygii; Teleostei; Ostariophysi; Cypriniformes;
OC Danionidae; Danioninae; Danio.
OX NCBI_TaxID=7955;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, DISRUPTION PHENOTYPE, AND
RP DEVELOPMENTAL STAGE.
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 [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Tuebingen;
RX PubMed=23594743; DOI=10.1038/nature12111;
RA Howe K., Clark M.D., Torroja C.F., Torrance J., Berthelot C., Muffato M.,
RA Collins J.E., Humphray S., McLaren K., Matthews L., McLaren S., Sealy I.,
RA Caccamo M., Churcher C., Scott C., Barrett J.C., Koch R., Rauch G.J.,
RA White S., Chow W., Kilian B., Quintais L.T., Guerra-Assuncao J.A., Zhou Y.,
RA Gu Y., Yen J., Vogel J.H., Eyre T., Redmond S., Banerjee R., Chi J., Fu B.,
RA Langley E., Maguire S.F., Laird G.K., Lloyd D., Kenyon E., Donaldson S.,
RA Sehra H., Almeida-King J., Loveland J., Trevanion S., Jones M., Quail M.,
RA Willey D., Hunt A., Burton J., Sims S., McLay K., Plumb B., Davis J.,
RA Clee C., Oliver K., Clark R., Riddle C., Elliot D., Threadgold G.,
RA Harden G., Ware D., Begum S., Mortimore B., Kerry G., Heath P.,
RA Phillimore B., Tracey A., Corby N., Dunn M., Johnson C., Wood J., Clark S.,
RA Pelan S., Griffiths G., Smith M., Glithero R., Howden P., Barker N.,
RA Lloyd C., Stevens C., Harley J., Holt K., Panagiotidis G., Lovell J.,
RA Beasley H., Henderson C., Gordon D., Auger K., Wright D., Collins J.,
RA Raisen C., Dyer L., Leung K., Robertson L., Ambridge K., Leongamornlert D.,
RA McGuire S., Gilderthorp R., Griffiths C., Manthravadi D., Nichol S.,
RA Barker G., Whitehead S., Kay M., Brown J., Murnane C., Gray E.,
RA Humphries M., Sycamore N., Barker D., Saunders D., Wallis J., Babbage A.,
RA Hammond S., Mashreghi-Mohammadi M., Barr L., Martin S., Wray P.,
RA Ellington A., Matthews N., Ellwood M., Woodmansey R., Clark G., Cooper J.,
RA Tromans A., Grafham D., Skuce C., Pandian R., Andrews R., Harrison E.,
RA Kimberley A., Garnett J., Fosker N., Hall R., Garner P., Kelly D., Bird C.,
RA Palmer S., Gehring I., Berger A., Dooley C.M., Ersan-Urun Z., Eser C.,
RA Geiger H., Geisler M., Karotki L., Kirn A., Konantz J., Konantz M.,
RA Oberlander M., Rudolph-Geiger S., Teucke M., Lanz C., Raddatz G.,
RA Osoegawa K., Zhu B., Rapp A., Widaa S., Langford C., Yang F.,
RA Schuster S.C., Carter N.P., Harrow J., Ning Z., Herrero J., Searle S.M.,
RA Enright A., Geisler R., Plasterk R.H., Lee C., Westerfield M.,
RA de Jong P.J., Zon L.I., Postlethwait J.H., Nusslein-Volhard C.,
RA Hubbard T.J., Roest Crollius H., Rogers J., Stemple D.L.;
RT "The zebrafish reference genome sequence and its relationship to the human
RT genome.";
RL Nature 496:498-503(2013).
RN [3]
RP FUNCTION, DISRUPTION PHENOTYPE, AND DEVELOPMENTAL STAGE.
RX PubMed=26429889; DOI=10.1136/jmedgenet-2015-103336;
RA Perles Z., Moon S., Ta-Shma A., Yaacov B., Francescatto L., Edvardson S.,
RA Rein A.J., Elpeleg O., Katsanis N.;
RT "A human laterality disorder caused by a homozygous deleterious mutation in
RT MMP21.";
RL J. Med. Genet. 52:840-847(2015).
CC -!- FUNCTION: Plays a specialized role in the generation of left-right
CC asymmetry during embryogenesis. May act as a negative regulator of the
CC NOTCH-signaling pathway. {ECO:0000269|PubMed:26429889,
CC ECO:0000269|PubMed:26437028}.
CC -!- DEVELOPMENTAL STAGE: At 12 hours post-fertilization, the expression is
CC restricted to Kupffer's vesicle. {ECO:0000269|PubMed:26429889,
CC ECO:0000269|PubMed:26437028}.
CC -!- PTM: The precursor is cleaved by a furin endopeptidase. {ECO:0000250}.
CC -!- DISRUPTION PHENOTYPE: Morpholino knockdown of the protein results in
CC randomnized heart looping at 48 hours post-fertilization.
CC {ECO:0000269|PubMed:26429889, ECO:0000269|PubMed:26437028}.
CC -!- SIMILARITY: Belongs to the peptidase M10A family. {ECO:0000255}.
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DR EMBL; KT207790; ALF36875.1; -; mRNA.
DR EMBL; CABZ01092162; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CABZ01092163; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CABZ01092164; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR RefSeq; NP_001304682.1; NM_001317753.1.
DR AlphaFoldDB; A0A0N9E2K8; -.
DR SMR; A0A0N9E2K8; -.
DR STRING; 7955.ENSDARP00000101806; -.
DR Ensembl; ENSDART00000188582; ENSDARP00000146681; ENSDARG00000112495.
DR GeneID; 100003089; -.
DR KEGG; dre:100003089; -.
DR CTD; 118856; -.
DR ZFIN; ZDB-GENE-100226-2; mmp21.
DR eggNOG; KOG1565; Eukaryota.
DR GeneTree; ENSGT00940000159140; -.
DR OrthoDB; 1075463at2759; -.
DR PRO; PR:A0A0N9E2K8; -.
DR Proteomes; UP000000437; Genome assembly.
DR Proteomes; UP000814640; Chromosome 12.
DR Bgee; ENSDARG00000112495; Expressed in Kupffer's vesicle and 3 other tissues.
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:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0030574; P:collagen catabolic process; IBA:GO_Central.
DR GO; GO:0061371; P:determination of heart left/right asymmetry; IMP:ZFIN.
DR GO; GO:0007368; P:determination of left/right symmetry; IMP:ZFIN.
DR GO; GO:0030198; P:extracellular matrix organization; IBA:GO_Central.
DR GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR CDD; cd04278; ZnMc_MMP; 1.
DR Gene3D; 2.110.10.10; -; 2.
DR Gene3D; 3.40.390.10; -; 1.
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; 2.
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 2: Evidence at transcript level;
KW Calcium; Disulfide bond; Glycoprotein; Hydrolase; Metal-binding;
KW Metalloprotease; Protease; Reference proteome; Repeat; Signal; Zinc.
FT SIGNAL 1..20
FT /evidence="ECO:0000255"
FT PROPEP 21..170
FT /evidence="ECO:0000250"
FT /id="PRO_0000437090"
FT CHAIN 171..599
FT /note="Matrix metallopeptidase-21"
FT /evidence="ECO:0000250|UniProtKB:Q8N119"
FT /id="PRO_0000437091"
FT REPEAT 356..415
FT /note="Hemopexin 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01011"
FT REPEAT 417..473
FT /note="Hemopexin 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01011"
FT REPEAT 474..522
FT /note="Hemopexin 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01011"
FT REPEAT 529..585
FT /note="Hemopexin 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01011"
FT REGION 141..170
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 143..162
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 310
FT /evidence="ECO:0000255|PIRSR:PIRSR001191-1"
FT BINDING 130
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 309
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10095"
FT BINDING 313
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10095"
FT BINDING 319
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10095"
FT CARBOHYD 398
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 355..586
FT /evidence="ECO:0000250"
FT CONFLICT 182
FT /note="S -> K (in Ref. 1; ALF36875)"
FT CONFLICT 190
FT /note="K -> E (in Ref. 1; ALF36875)"
FT CONFLICT 248
FT /note="E -> G (in Ref. 1; ALF36875)"
FT CONFLICT 356
FT /note="T -> M (in Ref. 1; ALF36875)"
FT CONFLICT 461
FT /note="L -> S (in Ref. 1; ALF36875)"
SQ SEQUENCE 599 AA; 68911 MW; B5A706DA9F5796AA CRC64;
MLTVIRRIFI IQTFIFITAE KIFHSRDHSD VLNNIHQAEL ITDTDTAQRF LSKYGFIKAA
GSEESQLSES SGDLDFSLSL DLHEGGTTSG SSSSDLQFVS ALRDFQRLSD LPVTGVFDDA
TKAAMNKPRC GVMDDDQELK DVTGSNSTRN HIRTSTNTSH NHEHQAPVRK KRHLSALLKN
TSLQKRDVSK WTGHMAFSKS VLKWRLIGEG YSSQLSIQEQ KYIFRLAFRM WSEISPLQFI
EDLHSPLENI DIRLGFGTGR HLGCSQRFDG AGREFAHAWF LGDIHFDDDE HFTVPNTGSG
ISLLKVAVHE IGHVLGLPHI YRPGSIMQPS YLPQDAGFEI DWMDRKSIQR LYGVCTGRFS
TVFDWIRKEQ TPYGEVVVRF NTYFMRDGLY WLYENRNNRT RYGDPVAVQV GWHGLPSGGV
DAYVHVWNRK TDAVYFFKGM QYWRYDSEND HVFSHAPDGR LYPRLISEDF PGVSGPLDTA
YYDRRDAHIY FFKGSQVFRF DVRMRRLASS SPQEMTEVFP AIVSGDHPVR SLDAAYFSYT
HNTVFLLKGS LFWRVLSGKE RRRRAFLPMN GLLAHRRVHE QWFDICDVHS SSLRTTRRR
