Reviewed, UniProtKB/Swiss-Prot Q62381 (TLL1_MOUSE)

Names and origin

Protein names

Recommended name:
    Tolloid-like protein 1
      Short name=mTll
    EC=3.4.24.-

Gene names

Name:	Tll1
Synonyms:	Tll

Organism

Mus musculus (Mouse)

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus

Protein attributes

Sequence length	1013 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Protease which processes procollagen C-propeptides, such as chordin, pro-biglycan and pro-lysyl oxidase. Required for the embryonic development, especially heart development. Predominant protease, which in the development, influences dorsal-ventral patterning and skeletogenesis. Ref.4
Cofactor	Binds 1 zinc ion per subunit By similarity.
Subcellular location	Secreted Probable.
Tissue specificity	Highly expressed in brain and kidney and weakly in lung, skeletal muscle. A perceptible level of expression is observed in heart and testis. Ref.1
Developmental stage	Expressed at detectable level on E7, at increased level on E11, at maximal level on E15. Then, expression decreases from E17. Expressed in the developing neural tube. Ref.1
Sequence similarities	Belongs to the peptidase M12A family. Contains 5 CUB domains. Contains 2 EGF-like domains.

Ontologies

Keywords
Biological process	Differentiation
Cellular component	Secreted
Coding sequence diversity	Alternative splicing
Domain	EGF-like domain Repeat Signal
Ligand	Calcium Metal-binding Zinc
Molecular function	Developmental protein Hydrolase Metalloprotease Protease
PTM	Disulfide bond Glycoprotein Zymogen
Gene Ontology (GO)
Biological process	cell differentiation Inferred from electronic annotation. Source: UniProtKB-KW multicellular organismal development Inferred from electronic annotation. Source: UniProtKB-KW proteolysis Inferred from electronic annotation. Source: InterPro
Cellular component	extracellular region Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	calcium ion binding Inferred from electronic annotation. Source: UniProtKB-KW metalloendopeptidase activity Inferred from electronic annotation. Source: InterPro zinc ion binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q62381-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: Q62381-2)

The sequence of this isoform differs from the canonical sequence as follows:
     387-390: IVLN → VVDT
     391-1013: Missing.

Note: No experimental confirmation available.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 30	30	Potential
	Propeptide	31 – 147	117	By similarity		PRO_0000046025
	Chain	148 – 1013	866	Tolloid-like protein 1		PRO_0000046026
Regions
	Domain	349 – 461	113	CUB 1
	Domain	462 – 574	113	CUB 2
	Domain	574 – 615	42	EGF-like 1; calcium-binding Potential
	Domain	618 – 730	113	CUB 3
	Domain	730 – 770	41	EGF-like 2; calcium-binding Potential
	Domain	774 – 886	113	CUB 4
	Domain	887 – 1003	117	CUB 5
	Region	148 – 348	201	Metalloprotease By similarity
Sites
	Active site	241	1	By similarity
	Metal binding	240	1	Zinc; catalytic By similarity
	Metal binding	244	1	Zinc; catalytic By similarity
	Metal binding	250	1	Zinc; catalytic By similarity
Amino acid modifications
	Glycosylation	169	1	N-linked (GlcNAc...) Potential
	Glycosylation	359	1	N-linked (GlcNAc...) Potential
	Glycosylation	390	1	N-linked (GlcNAc...) Potential
	Glycosylation	626	1	N-linked (GlcNAc...) Potential
	Disulfide bond	349 ↔ 375		By similarity
	Disulfide bond	402 ↔ 424		By similarity
	Disulfide bond	462 ↔ 488		By similarity
	Disulfide bond	515 ↔ 537		By similarity
	Disulfide bond	578 ↔ 590		By similarity
	Disulfide bond	586 ↔ 599		By similarity
	Disulfide bond	601 ↔ 614		By similarity
	Disulfide bond	618 ↔ 644		By similarity
	Disulfide bond	671 ↔ 693		By similarity
	Disulfide bond	734 ↔ 745		By similarity
	Disulfide bond	741 ↔ 754		By similarity
	Disulfide bond	756 ↔ 769		By similarity
	Disulfide bond	774 ↔ 800		By similarity
	Disulfide bond	827 ↔ 849		By similarity
	Disulfide bond	887 ↔ 917		By similarity
	Disulfide bond	944 ↔ 966		By similarity
Natural variations
	Alternative sequence	387 – 390	4	IVLN → VVDT in isoform 2.		VSP_017199
	Alternative sequence	391 – 1013	623	Missing in isoform 2.		VSP_017200
Experimental info
	Sequence conflict	682	1	P → L in BAE23891. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified November 1, 1996. Version 1. Checksum: B388914642BDD078	FASTA	1,013	114,533
	10 20 30 40 50 60 MGLQALSPRM LLWLVVSGIV FSRVLWVCAG LDYDYTFDGN EEDKTEPIDY KDPCKAAVFW 70 80 90 100 110 120 GDIALDDEDL NIFQIDRTID LTQSPFGKLG HITGGFGDHG MPKKRGALYQ LIERIRRIGS 130 140 150 160 170 180 GLEQNNTMKG KAPPKLSEQS EKNRVPRAAT SRTERIWPGG VIPYVIGGNF TGSQRAMFKQ 190 200 210 220 230 240 AMRHWEKHTC VTFTERSDEE SYIVFTYRPC GCCSYVGRRG NGPQAISIGK NCDKFGIVVH 250 260 270 280 290 300 ELGHVIGFWH EHTRPDRDNH VTIIRENIQP GQEYNFLKME PGEVNSLGER YDFDSIMHYA 310 320 330 340 350 360 RNTFSRGMFL DTILPSRDDN GIRPAIGQRT RLSKGDIAQA RKLYRCPACG ETLQESSGNL 370 380 390 400 410 420 SSPGFPNGYP SYTHCIWRVS VTPGEKIVLN FTTMDLYKSS LCWYDYIEVR DGYWRKSPLL 430 440 450 460 470 480 GRFCGDKVAG VLTSTDSRMW IEFRSSSNWV GKGFAAVYEA ICGGEIRKNE GQIQSPNYPD 490 500 510 520 530 540 DYRPMKECVW KIMVSEGYHV GLTFQAFEIE RHDSCAYDHL EVRDGASENS PLIGRFCGYD 550 560 570 580 590 600 KPEDIRSTSN TLWMKFVSDG TVNKAGFAAN FFKEEDECAK PDRGGCEQRC LNTLGSYQCA 610 620 630 640 650 660 CEPGYELGPD RRSCEAACGG LLTKLNGTIT TPGWPKEYPP NKNCVWQVIA PSQYRISVKF 670 680 690 700 710 720 EFFELEGNEV CKYDYVEIWS GPSSESKLHG KFCGADIPEV MTSHFNNMRI EFKSDNTVSK 730 740 750 760 770 780 KGFKAHFFSD KDECSKDNGG CQHECVNTMG SYTCQCRNGF VLHENKHDCK EAECEQKIHS 790 800 810 820 830 840 PSGLITSPNW PDKYPSRKEC TWVISAIPGH RITLAFNEFE VEQHQECAYD HLEIFDGETE 850 860 870 880 890 900 KSPILGRLCG SKIPDPLMAT GNEMFIRFIS DASVQRKGFQ ATHSTECGGR LKAESKPRDL 910 920 930 940 950 960 YSHAQFGDNN YPGQLDCEWL LVSERGSRLE LSFQTFEVEE EADCGYDYVE VFDGLSSKAV 970 980 990 1000 1010 GLGRFCGSGP PEEIYSIGDV ALIHFHTDDT INKKGFYIRY KSIRYPETMH AKN
	Isoform 2. Checksum: 31193DE9826893E8	FASTA	390	43,967
	10 20 30 40 50 60 MGLQALSPRM LLWLVVSGIV FSRVLWVCAG LDYDYTFDGN EEDKTEPIDY KDPCKAAVFW 70 80 90 100 110 120 GDIALDDEDL NIFQIDRTID LTQSPFGKLG HITGGFGDHG MPKKRGALYQ LIERIRRIGS 130 140 150 160 170 180 GLEQNNTMKG KAPPKLSEQS EKNRVPRAAT SRTERIWPGG VIPYVIGGNF TGSQRAMFKQ 190 200 210 220 230 240 AMRHWEKHTC VTFTERSDEE SYIVFTYRPC GCCSYVGRRG NGPQAISIGK NCDKFGIVVH 250 260 270 280 290 300 ELGHVIGFWH EHTRPDRDNH VTIIRENIQP GQEYNFLKME PGEVNSLGER YDFDSIMHYA 310 320 330 340 350 360 RNTFSRGMFL DTILPSRDDN GIRPAIGQRT RLSKGDIAQA RKLYRCPACG ETLQESSGNL 370 380 390 SSPGFPNGYP SYTHCIWRVS VTPGEKVVDT

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Characterization of a novel gene product (mammalian tolloid-like) with high sequence similarity to mammalian tolloid/bone morphogenetic protein-1." Takahara K., Brevard R., Hoffman G.G., Suzuki N., Greenspan D.S. Genomics 34:157-165(1996) [PubMed: 8661043] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY, DEVELOPMENTAL STAGE.
[2]	"The transcriptional landscape of the mammalian genome." Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y. Science 309:1559-1563(2005) [PubMed: 16141072] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 535-1013 (ISOFORM 1). Strain: C57BL/6J. Tissue: Adipose tissue and Cerebellum.
[3]	"Mammalian BMP-1/Tolloid-related metalloproteinases, including novel family member mammalian Tolloid-like 2, have differential enzymatic activities and distributions of expression relevant to patterning and skeletogenesis." Scott I.C., Blitz I.L., Pappano W.N., Imamura Y., Clark T.G., Steiglitz B.M., Thomas C.L., Maas S.A., Takahara K., Cho K.W., Greenspan D.S. Dev. Biol. 213:283-300(1999) [PubMed: 10479448] [Abstract] Cited for: CHARACTERIZATION OF ACTION ON CHORDIN.
[4]	"The mammalian Tolloid-like 1 gene, Tll1, is necessary for normal septation and positioning of the heart." Clark T.G., Conway S.J., Scott I.C., Labosky P.A., Winnier G., Bundy J., Hogan B.L., Greenspan D.S. Development 126:2631-2642(1999) [PubMed: 10331975] [Abstract] Cited for: FUNCTION.
[5]	"Bone morphogenetic protein-1 processes probiglycan." Scott I.C., Imamura Y., Pappano W.N., Troedel J.M., Recklies A.D., Roughley P.J., Greenspan D.S. J. Biol. Chem. 275:30504-30511(2000) [PubMed: 10896944] [Abstract] Cited for: CHARACTERIZATION OF ACTION ON PRO-BIGLYCAN.
[6]	"Multiple bone morphogenetic protein 1-related mammalian metalloproteinases process pro-lysyl oxidase at the correct physiological site and control lysyl oxidase activation in mouse embryo fibroblast cultures." Uzel M.I., Scott I.C., Babakhanlou-Chase H., Palamakumbura A.H., Pappano W.N., Hong H.-H., Greenspan D.S., Trackman P.C. J. Biol. Chem. 276:22537-22543(2001) [PubMed: 11313359] [Abstract] Cited for: CHARACTERIZATION OF ACTION ON PRO-LYSYL OXIDASE.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBLGenBankDDBJ	U34042 mRNA. Translation: AAC52654.1. AK080919 mRNA. Translation: BAC38078.1. AK139103 mRNA. Translation: BAE23891.1.
IPI	IPI00124795. IPI00720182.
RefSeq	NP_033416.2.
UniGene	Mm.418367 Mm.438712 Mm.458015
3D structure databases
HSSP	HSSP built from PDB template 1APQ based on UniProtKB P00736.
ModBase	Search...
Protein family/group databases
MEROPS	M12.016.
Genome annotation databases
Ensembl	ENSMUSG00000053626. Mus musculus. [Contig view]
GeneID	21892.
KEGG	mmu:21892.
Organism-specific databases
MGI	MGI:106923. Tll1.
Phylogenomic databases
HOGENOM	Q62381.
HOVERGEN	Q62381.
Gene expression databases
ArrayExpress	Q62381.
Bgee	Q62381.
CleanEx	MM_TLL1.
GermOnline	ENSMUSG00000053626. Mus musculus.
Family and domain databases
InterPro	IPR015446. BMP_1/tolloid-like. IPR000859. CUB. IPR006209. EGF. IPR013032. EGF-like_reg_CS. IPR000742. EGF_3. IPR001881. EGF_Ca_bd. IPR013091. EGF_Ca_bd_2. IPR018097. EGF_Ca_bd_CS. IPR006025. Pept_M_Zn_BS. IPR006026. Peptidase_M. IPR001506. Peptidase_M12A. [Graphical view]
Gene3D	G3DSA:2.60.120.290. CUB. 5 hits.
PANTHER	PTHR10127:SF71. BMP_1. 1 hit.
Pfam	PF01400. Astacin. 1 hit. PF00431. CUB. 5 hits. PF00008. EGF. 1 hit. PF07645. EGF_CA. 1 hit. [Graphical view]
PIRSF	PIRSF001199. BMP_1/tolloid-like. 1 hit.
PRINTS	PR00480. ASTACIN.
SMART	SM00042. CUB. 5 hits. SM00179. EGF_CA. 2 hits. SM00235. ZnMc. 1 hit. [Graphical view]
PROSITE	PS01180. CUB. 5 hits. PS00022. EGF_1. False negative. PS01186. EGF_2. 2 hits. PS50026. EGF_3. 2 hits. PS01187. EGF_CA. 2 hits. PS00142. ZINC_PROTEASE. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	301420.
SOURCE	Search...

Entry information

Entry name

TLL1_MOUSE

Accession

Primary (citable) accession number: Q62381
Secondary accession number(s): Q3UTT9, Q8BNP5

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 7, 2006
Last sequence update:	November 1, 1996
Last modified:	June 16, 2009
This is version 65 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)