TLL1_MOUSE
ID TLL1_MOUSE Reviewed; 1013 AA.
AC Q62381; Q3UTT9; Q8BNP5;
DT 07-FEB-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 03-AUG-2022, entry version 146.
DE RecName: Full=Tolloid-like protein 1;
DE Short=mTll;
DE EC=3.4.24.-;
DE Flags: Precursor;
GN Name=Tll1; Synonyms=Tll;
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] (ISOFORM 1), TISSUE SPECIFICITY, AND
RP DEVELOPMENTAL STAGE.
RX PubMed=8661043; DOI=10.1006/geno.1996.0260;
RA Takahara K., Brevard R., Hoffman G.G., Suzuki N., Greenspan D.S.;
RT "Characterization of a novel gene product (mammalian tolloid-like) with
RT high sequence similarity to mammalian tolloid/bone morphogenetic protein-
RT 1.";
RL Genomics 34:157-165(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), AND NUCLEOTIDE SEQUENCE
RP [LARGE SCALE MRNA] OF 535-1013 (ISOFORM 1).
RC STRAIN=C57BL/6J; TISSUE=Adipose tissue, and Cerebellum;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP CHARACTERIZATION OF ACTION ON CHORDIN.
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 [4]
RP FUNCTION.
RX PubMed=10331975; DOI=10.1242/dev.126.12.2631;
RA Clark T.G., Conway S.J., Scott I.C., Labosky P.A., Winnier G., Bundy J.,
RA Hogan B.L., Greenspan D.S.;
RT "The mammalian Tolloid-like 1 gene, Tll1, is necessary for normal septation
RT and positioning of the heart.";
RL Development 126:2631-2642(1999).
RN [5]
RP CHARACTERIZATION OF ACTION ON PRO-BIGLYCAN.
RX PubMed=10896944; DOI=10.1074/jbc.m004846200;
RA Scott I.C., Imamura Y., Pappano W.N., Troedel J.M., Recklies A.D.,
RA Roughley P.J., Greenspan D.S.;
RT "Bone morphogenetic protein-1 processes probiglycan.";
RL J. Biol. Chem. 275:30504-30511(2000).
RN [6]
RP CHARACTERIZATION OF ACTION ON PRO-LYSYL OXIDASE.
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).
CC -!- FUNCTION: Protease which processes procollagen C-propeptides, such as
CC chordin, pro-biglycan and pro-lysyl oxidase. Required for the embryonic
CC development, especially heart development. Predominant protease, which
CC in the development, influences dorsal-ventral patterning and
CC skeletogenesis. {ECO:0000269|PubMed:10331975}.
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 -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q62381-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q62381-2; Sequence=VSP_017199, VSP_017200;
CC -!- TISSUE SPECIFICITY: Highly expressed in brain and kidney and weakly in
CC lung, skeletal muscle. A perceptible level of expression is observed in
CC heart and testis. {ECO:0000269|PubMed:8661043}.
CC -!- DEVELOPMENTAL STAGE: Expressed at detectable level on 7 dpc, at
CC increased level on 11 dpc, at maximal level on 15 dpc. Then, expression
CC decreases from 17 dpc. Expressed in the developing neural tube.
CC {ECO:0000269|PubMed:8661043}.
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DR EMBL; U34042; AAC52654.1; -; mRNA.
DR EMBL; AK080919; BAC38078.1; -; mRNA.
DR EMBL; AK139103; BAE23891.1; -; mRNA.
DR CCDS; CCDS40352.1; -. [Q62381-1]
DR AlphaFoldDB; Q62381; -.
DR SMR; Q62381; -.
DR BioGRID; 204220; 3.
DR IntAct; Q62381; 3.
DR STRING; 10090.ENSMUSP00000070560; -.
DR MEROPS; M12.016; -.
DR GlyGen; Q62381; 4 sites.
DR iPTMnet; Q62381; -.
DR PhosphoSitePlus; Q62381; -.
DR MaxQB; Q62381; -.
DR PaxDb; Q62381; -.
DR PeptideAtlas; Q62381; -.
DR PRIDE; Q62381; -.
DR ProteomicsDB; 259512; -. [Q62381-1]
DR ProteomicsDB; 259513; -. [Q62381-2]
DR UCSC; uc009luu.1; mouse. [Q62381-2]
DR MGI; MGI:106923; Tll1.
DR eggNOG; KOG3714; Eukaryota.
DR InParanoid; Q62381; -.
DR PhylomeDB; Q62381; -.
DR Reactome; R-MMU-1474228; Degradation of the extracellular matrix.
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; 21892; 2 hits in 73 CRISPR screens.
DR ChiTaRS; Tll1; mouse.
DR PRO; PR:Q62381; -.
DR Proteomes; UP000000589; Unplaced.
DR RNAct; Q62381; protein.
DR GO; GO:0005615; C:extracellular space; IBA:GO_Central.
DR GO; GO:0005509; F:calcium ion binding; IEA:InterPro.
DR GO; GO:0005518; F:collagen binding; IDA:MGI.
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:0016485; P:protein processing; IBA:GO_Central.
DR CDD; cd00041; CUB; 5.
DR CDD; cd04281; ZnMc_BMP1_TLD; 1.
DR Gene3D; 2.60.120.290; -; 5.
DR Gene3D; 3.40.390.10; -; 1.
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 Pfam; PF01400; Astacin; 1.
DR Pfam; PF00431; CUB; 5.
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; SSF49854; SSF49854; 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 Alternative splicing; Calcium; Developmental protein; Differentiation;
KW Disulfide bond; EGF-like domain; Glycoprotein; Hydrolase; Metal-binding;
KW Metalloprotease; Protease; Reference proteome; Repeat; Secreted; Signal;
KW Zinc; Zymogen.
FT SIGNAL 1..30
FT /evidence="ECO:0000255"
FT PROPEP 31..147
FT /evidence="ECO:0000250"
FT /id="PRO_0000046025"
FT CHAIN 148..1013
FT /note="Tolloid-like protein 1"
FT /id="PRO_0000046026"
FT DOMAIN 148..347
FT /note="Peptidase M12A"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01211"
FT DOMAIN 349..461
FT /note="CUB 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00059"
FT DOMAIN 462..574
FT /note="CUB 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00059"
FT DOMAIN 574..615
FT /note="EGF-like 1; calcium-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 618..730
FT /note="CUB 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00059"
FT DOMAIN 730..770
FT /note="EGF-like 2; calcium-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 774..886
FT /note="CUB 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00059"
FT DOMAIN 887..1003
FT /note="CUB 5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00059"
FT REGION 124..150
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 135..149
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 241
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01211"
FT BINDING 240
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01211"
FT BINDING 244
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01211"
FT BINDING 250
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01211"
FT CARBOHYD 169
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 359
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 390
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 626
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 190..346
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01211"
FT DISULFID 210..232
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01211"
FT DISULFID 212..213
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01211"
FT DISULFID 349..375
FT /evidence="ECO:0000250"
FT DISULFID 402..424
FT /evidence="ECO:0000250"
FT DISULFID 462..488
FT /evidence="ECO:0000250"
FT DISULFID 515..537
FT /evidence="ECO:0000250"
FT DISULFID 578..590
FT /evidence="ECO:0000250"
FT DISULFID 586..599
FT /evidence="ECO:0000250"
FT DISULFID 601..614
FT /evidence="ECO:0000250"
FT DISULFID 618..644
FT /evidence="ECO:0000250"
FT DISULFID 671..693
FT /evidence="ECO:0000250"
FT DISULFID 734..745
FT /evidence="ECO:0000250"
FT DISULFID 741..754
FT /evidence="ECO:0000250"
FT DISULFID 756..769
FT /evidence="ECO:0000250"
FT DISULFID 774..800
FT /evidence="ECO:0000250"
FT DISULFID 827..849
FT /evidence="ECO:0000250"
FT DISULFID 887..917
FT /evidence="ECO:0000250"
FT DISULFID 944..966
FT /evidence="ECO:0000250"
FT VAR_SEQ 387..390
FT /note="IVLN -> VVDT (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_017199"
FT VAR_SEQ 391..1013
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_017200"
FT CONFLICT 682
FT /note="P -> L (in Ref. 2; BAE23891)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1013 AA; 114533 MW; B388914642BDD078 CRC64;
MGLQALSPRM LLWLVVSGIV FSRVLWVCAG LDYDYTFDGN EEDKTEPIDY KDPCKAAVFW
GDIALDDEDL NIFQIDRTID LTQSPFGKLG HITGGFGDHG MPKKRGALYQ LIERIRRIGS
GLEQNNTMKG KAPPKLSEQS EKNRVPRAAT SRTERIWPGG VIPYVIGGNF TGSQRAMFKQ
AMRHWEKHTC VTFTERSDEE SYIVFTYRPC GCCSYVGRRG NGPQAISIGK NCDKFGIVVH
ELGHVIGFWH EHTRPDRDNH VTIIRENIQP GQEYNFLKME PGEVNSLGER YDFDSIMHYA
RNTFSRGMFL DTILPSRDDN GIRPAIGQRT RLSKGDIAQA RKLYRCPACG ETLQESSGNL
SSPGFPNGYP SYTHCIWRVS VTPGEKIVLN FTTMDLYKSS LCWYDYIEVR DGYWRKSPLL
GRFCGDKVAG VLTSTDSRMW IEFRSSSNWV GKGFAAVYEA ICGGEIRKNE GQIQSPNYPD
DYRPMKECVW KIMVSEGYHV GLTFQAFEIE RHDSCAYDHL EVRDGASENS PLIGRFCGYD
KPEDIRSTSN TLWMKFVSDG TVNKAGFAAN FFKEEDECAK PDRGGCEQRC LNTLGSYQCA
CEPGYELGPD RRSCEAACGG LLTKLNGTIT TPGWPKEYPP NKNCVWQVIA PSQYRISVKF
EFFELEGNEV CKYDYVEIWS GPSSESKLHG KFCGADIPEV MTSHFNNMRI EFKSDNTVSK
KGFKAHFFSD KDECSKDNGG CQHECVNTMG SYTCQCRNGF VLHENKHDCK EAECEQKIHS
PSGLITSPNW PDKYPSRKEC TWVISAIPGH RITLAFNEFE VEQHQECAYD HLEIFDGETE
KSPILGRLCG SKIPDPLMAT GNEMFIRFIS DASVQRKGFQ ATHSTECGGR LKAESKPRDL
YSHAQFGDNN YPGQLDCEWL LVSERGSRLE LSFQTFEVEE EADCGYDYVE VFDGLSSKAV
GLGRFCGSGP PEEIYSIGDV ALIHFHTDDT INKKGFYIRY KSIRYPETMH AKN
