ID Q6NUX9_DANRE Unreviewed; 217 AA.
AC Q6NUX9; A0A8M1PGR3;
DT 05-JUL-2004, integrated into UniProtKB/TrEMBL.
DT 05-JUL-2004, sequence version 1.
DT 27-MAR-2024, entry version 148.
DE RecName: Full=Metalloproteinase inhibitor 2 {ECO:0000256|ARBA:ARBA00013520};
DE AltName: Full=Tissue inhibitor of metalloproteinases 2 {ECO:0000256|ARBA:ARBA00030102};
GN Name=timp2b {ECO:0000313|EMBL:AAH68388.1,
GN ECO:0000313|Ensembl:ENSDARP00000141124,
GN ECO:0000313|RefSeq:NP_998461.1,
GN ECO:0000313|ZFIN:ZDB-GENE-040426-2655};
GN Synonyms=timp2l {ECO:0000313|RefSeq:NP_998461.1}, zgc:65967
GN {ECO:0000313|RefSeq:NP_998461.1}, zgc:85799
GN {ECO:0000313|RefSeq:NP_998461.1};
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 {ECO:0000313|EMBL:AAH68388.1};
RN [1] {ECO:0000313|EMBL:AAH68388.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Kidney {ECO:0000313|EMBL:AAH68388.1};
RG NIH - Zebrafish Gene Collection (ZGC) project;
RL Submitted (APR-2004) to the EMBL/GenBank/DDBJ databases.
RN [2] {ECO:0000313|RefSeq:NP_998461.1}
RP NUCLEOTIDE SEQUENCE.
RX PubMed=17439641;
RA Huxley-Jones J., Clarke T.K., Beck C., Toubaris G., Robertson D.L.,
RA Boot-Handford R.P.;
RT "The evolution of the vertebrate metzincins; insights from Ciona
RT intestinalis and Danio rerio.";
RL BMC Evol. Biol. 7:63-63(2007).
RN [3] {ECO:0000313|RefSeq:NP_998461.1}
RP NUCLEOTIDE SEQUENCE.
RX PubMed=17637923;
RA Henry T.B., Menn F.M., Fleming J.T., Wilgus J., Compton R.N., Sayler G.S.;
RT "Attributing effects of aqueous C60 nano-aggregates to tetrahydrofuran
RT decomposition products in larval zebrafish by assessment of gene
RT expression.";
RL Environ. Health Perspect. 115:1059-1065(2007).
RN [4] {ECO:0000313|RefSeq:NP_998461.1}
RP NUCLEOTIDE SEQUENCE.
RX PubMed=18423448;
RA Coyle R.C., Latimer A., Jessen J.R.;
RT "Membrane-type 1 matrix metalloproteinase regulates cell migration during
RT zebrafish gastrulation: evidence for an interaction with non-canonical Wnt
RT signaling.";
RL Exp. Cell Res. 314:2150-2162(2008).
RN [5] {ECO:0000313|RefSeq:NP_998461.1}
RP NUCLEOTIDE SEQUENCE.
RX PubMed=19929220;
RA Wyatt R.A., Keow J.Y., Harris N.D., Hache C.A., Li D.H., Crawford B.D.;
RT "The zebrafish embryo: a powerful model system for investigating matrix
RT remodeling.";
RL Zebrafish 6:347-354(2009).
RN [6] {ECO:0000313|RefSeq:NP_998461.1}
RP NUCLEOTIDE SEQUENCE.
RX PubMed=19890097;
RA Kobayashi I., Ono H., Moritomo T., Kano K., Nakanishi T., Suda T.;
RT "Comparative gene expression analysis of zebrafish and mammals identifies
RT common regulators in hematopoietic stem cells.";
RL Blood 115:e1-e9(2010).
RN [7] {ECO:0000313|Ensembl:ENSDARP00000141124, ECO:0000313|Proteomes:UP000000437}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Tuebingen {ECO:0000313|Ensembl:ENSDARP00000141124};
RX PubMed=23594743; DOI=10.1038/nature12111;
RG Genome Reference Consortium Zebrafish;
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., Eliott D.,
RA Threadgold G., Harden G., Ware D., Begum S., Mortimore B., Mortimer B.,
RA Kerry G., Heath P., Phillimore B., Tracey A., Corby N., Dunn M.,
RA Johnson C., Wood J., Clark S., Pelan S., Griffiths G., Smith M.,
RA Glithero R., Howden P., Barker N., Lloyd C., Stevens C., Harley J.,
RA Holt K., Panagiotidis G., Lovell J., Beasley H., Henderson C., Gordon D.,
RA Auger K., Wright D., Collins J., Raisen C., Dyer L., Leung K.,
RA Robertson L., Ambridge K., Leongamornlert D., McGuire S., Gilderthorp R.,
RA Griffiths C., Manthravadi D., Nichol S., Barker G., Whitehead S., Kay M.,
RA Brown J., Murnane C., Gray E., Humphries M., Sycamore N., Barker D.,
RA Saunders D., Wallis J., Babbage A., Hammond S., Mashreghi-Mohammadi M.,
RA Barr L., Martin S., Wray P., Ellington A., Matthews N., Ellwood M.,
RA Woodmansey R., Clark G., Cooper J., Cooper J., Tromans A., Grafham D.,
RA Skuce C., Pandian R., Andrews R., Harrison E., Kimberley A., Garnett J.,
RA Fosker N., Hall R., Garner P., Kelly D., Bird C., Palmer S., Gehring I.,
RA Berger A., Dooley C.M., Ersan-Urun Z., Eser C., Geiger H., Geisler M.,
RA Karotki L., Kirn A., Konantz J., Konantz M., Oberlander M.,
RA Rudolph-Geiger S., Teucke M., Lanz C., Raddatz G., Osoegawa K., Zhu B.,
RA Rapp A., Widaa S., Langford C., Yang F., Schuster S.C., Carter N.P.,
RA Harrow J., Ning Z., Herrero J., Searle S.M., Enright A., Geisler R.,
RA Plasterk R.H., Lee C., Westerfield M., de Jong P.J., Zon L.I.,
RA Postlethwait J.H., Nusslein-Volhard C., Hubbard T.J., Roest Crollius H.,
RA 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 [8] {ECO:0000313|Ensembl:ENSDARP00000141124}
RP IDENTIFICATION.
RC STRAIN=Tuebingen {ECO:0000313|Ensembl:ENSDARP00000141124};
RG Ensembl;
RL Submitted (NOV-2015) to UniProtKB.
RN [9] {ECO:0000313|RefSeq:NP_998461.1}
RP NUCLEOTIDE SEQUENCE.
RX PubMed=28982700; DOI=10.1242/bio.030254;
RA Takada N., Omae M., Sagawa F., Chi N.C., Endo S., Kozawa S., Sato T.N.;
RT "Re-evaluating the functional landscape of the cardiovascular system during
RT development.";
RL Biol. Open 6:1756-1770(2017).
RN [10] {ECO:0000313|RefSeq:NP_998461.1}
RP NUCLEOTIDE SEQUENCE.
RX PubMed=29494911;
RA Li X., Zha X., Wang Y., Jia R., Hu B., Zhao B.;
RT "Toxic effects and foundation of proton radiation on the early-life stage
RT of zebrafish development.";
RL Chemosphere 200:302-312(2018).
RN [11] {ECO:0000313|RefSeq:NP_998461.1}
RP NUCLEOTIDE SEQUENCE.
RX PubMed=30060229;
RA Wu X., Shen W., Zhang B., Meng A.;
RT "The genetic program of oocytes can be modified in vivo in the zebrafish
RT ovary.";
RL J. Mol. Cell Biol. 10:479-493(2018).
RN [12] {ECO:0000313|RefSeq:NP_998461.1}
RP NUCLEOTIDE SEQUENCE.
RX PubMed=30133415;
RA Oh H., Kim C.Y., Ryu B., Kim U., Kim J., Lee J.M., Lee B.H., Moon J.,
RA Jung C.R., Park J.H.;
RT "Respiratory Toxicity of Polyhexamethylene Guanidine Phosphate Exposure in
RT Zebrafish.";
RL Zebrafish 15:460-472(2018).
RN [13] {ECO:0000313|RefSeq:NP_998461.1}
RP NUCLEOTIDE SEQUENCE.
RX PubMed=30924555;
RA Charlton-Perkins M., Almeida A.D., MacDonald R.B., Harris W.A.;
RT "Genetic control of cellular morphogenesis in Muller glia.";
RL Glia 67:1401-1411(2019).
RN [14] {ECO:0000313|RefSeq:NP_998461.1}
RP IDENTIFICATION.
RG RefSeq;
RL Submitted (NOV-2023) to UniProtKB.
CC -!- SIMILARITY: Belongs to the protease inhibitor I35 (TIMP) family.
CC {ECO:0000256|ARBA:ARBA00011027}.
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DR EMBL; CT573423; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CU681857; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC068388; AAH68388.1; -; mRNA.
DR RefSeq; NP_998461.1; NM_213296.1.
DR MEROPS; I35.002; -.
DR Ensembl; ENSDART00000166855.2; ENSDARP00000141124.1; ENSDARG00000075261.4.
DR GeneID; 406650; -.
DR KEGG; dre:406650; -.
DR AGR; ZFIN:ZDB-GENE-040426-2655; -.
DR CTD; 406650; -.
DR ZFIN; ZDB-GENE-040426-2655; timp2b.
DR HOGENOM; CLU_084029_0_0_1; -.
DR OMA; PFGKCET; -.
DR TreeFam; TF317409; -.
DR Reactome; R-DRE-114608; Platelet degranulation.
DR Reactome; R-DRE-1592389; Activation of Matrix Metalloproteinases.
DR Reactome; R-DRE-381426; Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs).
DR Reactome; R-DRE-8957275; Post-translational protein phosphorylation.
DR Proteomes; UP000000437; Chromosome 3.
DR Bgee; ENSDARG00000075261; Expressed in granulocyte and 21 other cell types or tissues.
DR GO; GO:0031012; C:extracellular matrix; IBA:GO_Central.
DR GO; GO:0005615; C:extracellular space; IBA:GO_Central.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0008191; F:metalloendopeptidase inhibitor activity; IBA:GO_Central.
DR GO; GO:0002020; F:protease binding; IBA:GO_Central.
DR GO; GO:0051045; P:negative regulation of membrane protein ectodomain proteolysis; IBA:GO_Central.
DR GO; GO:0034097; P:response to cytokine; IBA:GO_Central.
DR GO; GO:0009725; P:response to hormone; IBA:GO_Central.
DR CDD; cd03585; NTR_TIMP; 1.
DR Gene3D; 2.40.50.120; -; 1.
DR Gene3D; 3.90.370.10; Tissue inhibitor of metalloproteinase-1. Chain B, domain 1; 1.
DR InterPro; IPR001134; Netrin_domain.
DR InterPro; IPR001820; TIMP.
DR InterPro; IPR008993; TIMP-like_OB-fold.
DR InterPro; IPR027465; TIMP_C.
DR PANTHER; PTHR11844; METALLOPROTEASE INHIBITOR; 1.
DR PANTHER; PTHR11844:SF24; METALLOPROTEINASE INHIBITOR 2; 1.
DR Pfam; PF00965; TIMP; 1.
DR SMART; SM00206; NTR; 1.
DR SUPFAM; SSF50242; TIMP-like; 1.
DR PROSITE; PS50189; NTR; 1.
PE 2: Evidence at transcript level;
KW Disulfide bond {ECO:0000256|ARBA:ARBA00023157,
KW ECO:0000256|PIRSR:PIRSR601820-3};
KW Metal-binding {ECO:0000256|PIRSR:PIRSR601820-1};
KW Metalloenzyme inhibitor {ECO:0000256|ARBA:ARBA00023215};
KW Metalloprotease inhibitor {ECO:0000256|ARBA:ARBA00022608};
KW Protease inhibitor {ECO:0000256|ARBA:ARBA00022690};
KW Reference proteome {ECO:0000313|Proteomes:UP000000437};
KW Signal {ECO:0000256|SAM:SignalP, ECO:0000313|RefSeq:NP_998461.1};
KW Zinc {ECO:0000256|PIRSR:PIRSR601820-1}.
FT SIGNAL 1..23
FT /evidence="ECO:0000256|SAM:SignalP"
FT CHAIN 24..217
FT /note="Metalloproteinase inhibitor 2"
FT /evidence="ECO:0000256|SAM:SignalP,
FT ECO:0000313|RefSeq:NP_998461.1"
FT /id="PRO_5035035973"
FT DOMAIN 24..149
FT /note="NTR"
FT /evidence="ECO:0000259|PROSITE:PS50189"
FT BINDING 24
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="ligand shared with metalloproteinase partner"
FT /evidence="ECO:0000256|PIRSR:PIRSR601820-1"
FT SITE 37
FT /note="Involved in metalloproteinase-binding"
FT /evidence="ECO:0000256|PIRSR:PIRSR601820-2"
FT SITE 64
FT /note="Involved in metalloproteinase-binding"
FT /evidence="ECO:0000256|PIRSR:PIRSR601820-2"
FT DISULFID 24..95
FT /evidence="ECO:0000256|PIRSR:PIRSR601820-3"
FT DISULFID 26..124
FT /evidence="ECO:0000256|PIRSR:PIRSR601820-3"
FT DISULFID 36..149
FT /evidence="ECO:0000256|PIRSR:PIRSR601820-3"
FT DISULFID 151..198
FT /evidence="ECO:0000256|PIRSR:PIRSR601820-3"
FT DISULFID 156..161
FT /evidence="ECO:0000256|PIRSR:PIRSR601820-3"
FT DISULFID 169..190
FT /evidence="ECO:0000256|PIRSR:PIRSR601820-3"
SQ SEQUENCE 217 AA; 23968 MW; 02444E3C841107B9 CRC64;
MSMSRSVPLL LLVLCGATDF AGACSCSPEH PQQAYCNADV VIRAKVVGRK EVVTGNDAYG
YPIKMIRYDV KQLKMFKGPN GEIDTIFTGP SSALCGVNLE SNGKQEYLIT GNLNSNGTLR
INLCDYIESW ESLSLTQKKS LGPRYQMGCD CKIVQCPIIP CSISEPVECL WTDWVLEGTV
QGTQAQHYTC VKRSDSSCAW YRGSTPPKKE FMDIEEP
//
