ID TLL2_MOUSE Reviewed; 1012 AA.
AC Q9WVM6; A2RTK3;
DT 07-FEB-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1999, sequence version 1.
DT 27-MAR-2024, entry version 156.
DE RecName: Full=Tolloid-like protein 2;
DE EC=3.4.24.-;
DE Flags: Precursor;
GN Name=Tll2;
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], AND DEVELOPMENTAL STAGE.
RX PubMed=10479448; DOI=10.1006/dbio.1999.9383;
RA Scott I.C., Blitz I.L., Pappano W.N., Imamura Y., Clark T.G.,
RA Steiglitz B.M., Thomas C.L., Maas S.A., Takahara K., Cho K.W.,
RA Greenspan D.S.;
RT "Mammalian BMP-1/Tolloid-related metalloproteinases, including novel family
RT member mammalian Tolloid-like 2, have differential enzymatic activities and
RT distributions of expression relevant to patterning and skeletogenesis.";
RL Dev. Biol. 213:283-300(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [3]
RP CHARACTERIZATION.
RX PubMed=11313359; DOI=10.1074/jbc.m102352200;
RA Uzel M.I., Scott I.C., Babakhanlou-Chase H., Palamakumbura A.H.,
RA Pappano W.N., Hong H.-H., Greenspan D.S., Trackman P.C.;
RT "Multiple bone morphogenetic protein 1-related mammalian metalloproteinases
RT process pro-lysyl oxidase at the correct physiological site and control
RT lysyl oxidase activation in mouse embryo fibroblast cultures.";
RL J. Biol. Chem. 276:22537-22543(2001).
RN [4]
RP METHYLATION [LARGE SCALE ANALYSIS] AT ARG-960 AND ARG-963, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Embryo;
RX PubMed=24129315; DOI=10.1074/mcp.o113.027870;
RA Guo A., Gu H., Zhou J., Mulhern D., Wang Y., Lee K.A., Yang V., Aguiar M.,
RA Kornhauser J., Jia X., Ren J., Beausoleil S.A., Silva J.C., Vemulapalli V.,
RA Bedford M.T., Comb M.J.;
RT "Immunoaffinity enrichment and mass spectrometry analysis of protein
RT methylation.";
RL Mol. Cell. Proteomics 13:372-387(2014).
CC -!- FUNCTION: Protease which specifically processes pro-lysyl oxidase.
CC Required for the embryonic development. Predominant protease, which in
CC the development, influences dorsal-ventral patterning and
CC skeletogenesis.
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000255|PROSITE-ProRule:PRU01211};
CC Note=Binds 1 zinc ion per subunit. {ECO:0000255|PROSITE-
CC ProRule:PRU01211};
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000305}.
CC -!- DEVELOPMENTAL STAGE: Expressed at 7.5 dpc, in a limited way, in the
CC posterior portion of the egg cylinder in the nascent mesoderm streaming
CC off the primitive streak. At the distant end of the embryo cylinder,
CC expression ended at the node. Later in the development, expression
CC seems to be limited to developing skeletal muscle and central nervous
CC system. {ECO:0000269|PubMed:10479448}.
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DR EMBL; AF073526; AAD42993.1; -; mRNA.
DR EMBL; BC132537; AAI32538.1; -; mRNA.
DR CCDS; CCDS37986.1; -.
DR RefSeq; NP_036034.1; NM_011904.3.
DR AlphaFoldDB; Q9WVM6; -.
DR SMR; Q9WVM6; -.
DR STRING; 10090.ENSMUSP00000025986; -.
DR MEROPS; M12.018; -.
DR GlyCosmos; Q9WVM6; 5 sites, No reported glycans.
DR GlyGen; Q9WVM6; 5 sites.
DR iPTMnet; Q9WVM6; -.
DR PhosphoSitePlus; Q9WVM6; -.
DR MaxQB; Q9WVM6; -.
DR PaxDb; 10090-ENSMUSP00000025986; -.
DR ProteomicsDB; 259204; -.
DR Antibodypedia; 53639; 56 antibodies from 19 providers.
DR DNASU; 24087; -.
DR Ensembl; ENSMUST00000025986.15; ENSMUSP00000025986.8; ENSMUSG00000025013.16.
DR GeneID; 24087; -.
DR KEGG; mmu:24087; -.
DR UCSC; uc008hlr.1; mouse.
DR AGR; MGI:1346044; -.
DR CTD; 7093; -.
DR MGI; MGI:1346044; Tll2.
DR VEuPathDB; HostDB:ENSMUSG00000025013; -.
DR eggNOG; KOG3714; Eukaryota.
DR GeneTree; ENSGT00940000160572; -.
DR HOGENOM; CLU_005140_0_0_1; -.
DR InParanoid; Q9WVM6; -.
DR OMA; WTKQTVG; -.
DR OrthoDB; 2873870at2759; -.
DR PhylomeDB; Q9WVM6; -.
DR TreeFam; TF314351; -.
DR Reactome; R-MMU-1650814; Collagen biosynthesis and modifying enzymes.
DR Reactome; R-MMU-2214320; Anchoring fibril formation.
DR Reactome; R-MMU-2243919; Crosslinking of collagen fibrils.
DR BioGRID-ORCS; 24087; 4 hits in 81 CRISPR screens.
DR ChiTaRS; Tll2; mouse.
DR PRO; PR:Q9WVM6; -.
DR Proteomes; UP000000589; Chromosome 19.
DR RNAct; Q9WVM6; Protein.
DR Bgee; ENSMUSG00000025013; Expressed in cortical plate and 9 other cell types or tissues.
DR ExpressionAtlas; Q9WVM6; baseline and differential.
DR GO; GO:0005615; C:extracellular space; IBA:GO_Central.
DR GO; GO:0005509; F:calcium ion binding; IEA:InterPro.
DR GO; GO:0004222; F:metalloendopeptidase activity; IBA:GO_Central.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0030154; P:cell differentiation; IEA:UniProtKB-KW.
DR GO; GO:0009953; P:dorsal/ventral pattern formation; IBA:GO_Central.
DR GO; GO:0048632; P:negative regulation of skeletal muscle tissue growth; IMP:MGI.
DR GO; GO:0016485; P:protein processing; IBA:GO_Central.
DR CDD; cd00041; CUB; 5.
DR CDD; cd00054; EGF_CA; 1.
DR CDD; cd04281; ZnMc_BMP1_TLD; 1.
DR Gene3D; 3.40.390.10; Collagenase (Catalytic Domain); 1.
DR Gene3D; 2.10.25.10; Laminin; 2.
DR Gene3D; 2.60.120.290; Spermadhesin, CUB domain; 5.
DR InterPro; IPR015446; BMP_1/tolloid-like.
DR InterPro; IPR000859; CUB_dom.
DR InterPro; IPR001881; EGF-like_Ca-bd_dom.
DR InterPro; IPR000742; EGF-like_dom.
DR InterPro; IPR000152; EGF-type_Asp/Asn_hydroxyl_site.
DR InterPro; IPR018097; EGF_Ca-bd_CS.
DR InterPro; IPR024079; MetalloPept_cat_dom_sf.
DR InterPro; IPR001506; Peptidase_M12A.
DR InterPro; IPR006026; Peptidase_Metallo.
DR InterPro; IPR035914; Sperma_CUB_dom_sf.
DR InterPro; IPR034036; ZnMP_TLD/BMP1.
DR PANTHER; PTHR24251:SF42; BONE MORPHOGENETIC PROTEIN 1; 1.
DR PANTHER; PTHR24251; OVOCHYMASE-RELATED; 1.
DR Pfam; PF01400; Astacin; 1.
DR Pfam; PF00431; CUB; 5.
DR Pfam; PF07645; EGF_CA; 1.
DR Pfam; PF14670; FXa_inhibition; 1.
DR PIRSF; PIRSF001199; BMP_1/tolloid-like; 1.
DR PRINTS; PR00480; ASTACIN.
DR SMART; SM00042; CUB; 5.
DR SMART; SM00181; EGF; 2.
DR SMART; SM00179; EGF_CA; 2.
DR SMART; SM00235; ZnMc; 1.
DR SUPFAM; SSF57196; EGF/Laminin; 2.
DR SUPFAM; SSF55486; Metalloproteases ('zincins'), catalytic domain; 1.
DR SUPFAM; SSF49854; Spermadhesin, CUB domain; 5.
DR PROSITE; PS51864; ASTACIN; 1.
DR PROSITE; PS01180; CUB; 5.
DR PROSITE; PS01186; EGF_2; 2.
DR PROSITE; PS50026; EGF_3; 2.
DR PROSITE; PS01187; EGF_CA; 2.
DR PROSITE; PS00142; ZINC_PROTEASE; 1.
PE 1: Evidence at protein level;
KW Calcium; Cleavage on pair of basic residues; Developmental protein;
KW Differentiation; Disulfide bond; EGF-like domain; Glycoprotein; Hydrolase;
KW Metal-binding; Metalloprotease; Methylation; Protease; Reference proteome;
KW Repeat; Secreted; Signal; Zinc; Zymogen.
FT SIGNAL 1..21
FT /evidence="ECO:0000255"
FT PROPEP 22..146
FT /evidence="ECO:0000250"
FT /id="PRO_0000046038"
FT CHAIN 147..1012
FT /note="Tolloid-like protein 2"
FT /id="PRO_0000046039"
FT DOMAIN 146..346
FT /note="Peptidase M12A"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01211"
FT DOMAIN 348..460
FT /note="CUB 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00059"
FT DOMAIN 461..573
FT /note="CUB 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00059"
FT DOMAIN 573..614
FT /note="EGF-like 1; calcium-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 617..729
FT /note="CUB 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00059"
FT DOMAIN 729..769
FT /note="EGF-like 2; calcium-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 773..885
FT /note="CUB 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00059"
FT DOMAIN 886..1002
FT /note="CUB 5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00059"
FT REGION 83..135
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 100..114
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 240
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01211"
FT BINDING 239
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01211"
FT BINDING 243
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01211"
FT BINDING 249
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01211"
FT MOD_RES 960
FT /note="Omega-N-methylarginine"
FT /evidence="ECO:0007744|PubMed:24129315"
FT MOD_RES 963
FT /note="Omega-N-methylarginine"
FT /evidence="ECO:0007744|PubMed:24129315"
FT CARBOHYD 168
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 358
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 389
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 625
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 802
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 189..345
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01211"
FT DISULFID 209..231
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01211"
FT DISULFID 211..212
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01211"
FT DISULFID 348..374
FT /evidence="ECO:0000250"
FT DISULFID 401..423
FT /evidence="ECO:0000250"
FT DISULFID 461..487
FT /evidence="ECO:0000250"
FT DISULFID 514..536
FT /evidence="ECO:0000250"
FT DISULFID 577..589
FT /evidence="ECO:0000250"
FT DISULFID 585..598
FT /evidence="ECO:0000250"
FT DISULFID 600..613
FT /evidence="ECO:0000250"
FT DISULFID 617..643
FT /evidence="ECO:0000250"
FT DISULFID 670..692
FT /evidence="ECO:0000250"
FT DISULFID 733..744
FT /evidence="ECO:0000250"
FT DISULFID 740..753
FT /evidence="ECO:0000250"
FT DISULFID 755..768
FT /evidence="ECO:0000250"
FT DISULFID 773..799
FT /evidence="ECO:0000250"
FT DISULFID 826..848
FT /evidence="ECO:0000250"
FT DISULFID 886..916
FT /evidence="ECO:0000250"
FT DISULFID 943..965
FT /evidence="ECO:0000250"
SQ SEQUENCE 1012 AA; 113252 MW; 72EEE268A4D8C5FE CRC64;
MPLATTLGTL VLLLLLPLPR GAEVTGDHSN VALDYGALEG EEGTEQQLHY HDPCKAAVFW
GDIALDEDDL KLFHIDKAED WTKPSIDKPG HDTGGLEETS ARWPNDTASN ASIQAPRKDG
KDATTFLPNP GTSNTTAKTF SARVRRATTS RTERIWPGGV IPYVIGGNFT GTQRAIFKQA
MRHWEKHTCV TFVERTDEES FIVFSYRTCG CCSYVGRRGG GPQAISIGKN CDKFGIVAHE
LGHVVGFWHE HTRPDRDQHV TIIRENIQPG QEYNFLKMEA GEVSSLGETY DFDSIMHYAR
NTFSRGVFLD TILPRRDDNG VRPTIGQRVR LSQGDIAQAR KLYKCPACGE TLQDTTGNFS
APGFPNGYPS YSHCVWRISV TPGEKIILNF TSMDLFKSRL CWYDYVEIRD GYWRKAPLLG
RFCGDKIPES LVSSDSRLWV EFRSSSSSLG KGFFAVYEAM CGGDITKDAG QIQSPNYPDD
YRPSKECVWR ITVPDGFHVG LTFQSFEIER HDSCAYDYLE IRDGPTEDST LIGHFCGYEK
PEAVKSSANR LWVKFVSDGS INKAGFAANF FKEVDECSWP DHGGCEQRCV NTLGSYTCAC
DPGYELAADK KTCEVACGGF ITKLNGTITS PGWPKEYPTN KNCVWQVVAP VQYRISLQFE
AFELEGNDVC KYDFVEVRSG LSPDAKLHGK FCGSETPEVI TSQSNNMRVE FKSDNTVSKR
GFRAHFFSDK DECAKDNGGC QQECVNTFGS YLCRCRNGYR LHENGHDCKE AGCAYKISSA
EGTLMSPNWP DKYPSRKECT WNISSTAGHR VKITFSEFEI EQHQECAYDH LELYDGTDSL
APILGRFCGS KKPDPVVATG SSLFLRFYSD ASVQRKGFQA VHSTECGGRL KAEVQTKELY
SHAQFGDNNY PSQARCDWVI VAEDGYGVEL IFRTFEVEEE ADCGYDFMEA YDGYDSSAPR
LGRFCGSGPL EEIYSAGDSL MIRFHTDDTI NKKGFHARYT STKFQDALHM RK
//
