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Protein

Tolloid-like protein 2

Gene

Tll2

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 4 out of 5-Experimental evidence at protein leveli

Functioni

Protease which specifically processes pro-lysyl oxidase. Required for the embryonic development. Predominant protease, which in the development, influences dorsal-ventral patterning and skeletogenesis.

Cofactori

Zn2+By similarityNote: Binds 1 zinc ion per subunit.By similarity

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Metal bindingi239 – 2391Zinc; catalyticPROSITE-ProRule annotation
Active sitei240 – 2401PROSITE-ProRule annotation
Metal bindingi243 – 2431Zinc; catalyticPROSITE-ProRule annotation
Metal bindingi249 – 2491Zinc; catalyticPROSITE-ProRule annotation

GO - Molecular functioni

GO - Biological processi

  • cell differentiation Source: UniProtKB-KW
  • multicellular organism development Source: UniProtKB-KW
  • negative regulation of skeletal muscle tissue growth Source: MGI
Complete GO annotation...

Keywords - Molecular functioni

Developmental protein, Hydrolase, Metalloprotease, Protease

Keywords - Biological processi

Differentiation

Keywords - Ligandi

Calcium, Metal-binding, Zinc

Enzyme and pathway databases

ReactomeiR-MMU-1474228. Degradation of the extracellular matrix.
R-MMU-2214320. Anchoring fibril formation.

Protein family/group databases

MEROPSiM12.018.

Names & Taxonomyi

Protein namesi
Recommended name:
Tolloid-like protein 2 (EC:3.4.24.-)
Gene namesi
Name:Tll2
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 19

Organism-specific databases

MGIiMGI:1346044. Tll2.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Secreted

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2121Sequence analysisAdd
BLAST
Propeptidei22 – 146125By similarityPRO_0000046038Add
BLAST
Chaini147 – 1012866Tolloid-like protein 2PRO_0000046039Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi168 – 1681N-linked (GlcNAc...)Sequence analysis
Disulfide bondi348 ↔ 374By similarity
Glycosylationi358 – 3581N-linked (GlcNAc...)Sequence analysis
Glycosylationi389 – 3891N-linked (GlcNAc...)Sequence analysis
Disulfide bondi401 ↔ 423By similarity
Disulfide bondi461 ↔ 487By similarity
Disulfide bondi514 ↔ 536By similarity
Disulfide bondi577 ↔ 589By similarity
Disulfide bondi585 ↔ 598By similarity
Disulfide bondi600 ↔ 613By similarity
Disulfide bondi617 ↔ 643By similarity
Glycosylationi625 – 6251N-linked (GlcNAc...)Sequence analysis
Disulfide bondi670 ↔ 692By similarity
Disulfide bondi733 ↔ 744By similarity
Disulfide bondi740 ↔ 753By similarity
Disulfide bondi755 ↔ 768By similarity
Disulfide bondi773 ↔ 799By similarity
Glycosylationi802 – 8021N-linked (GlcNAc...)Sequence analysis
Disulfide bondi826 ↔ 848By similarity
Disulfide bondi886 ↔ 916By similarity
Disulfide bondi943 ↔ 965By similarity

Keywords - PTMi

Cleavage on pair of basic residues, Disulfide bond, Glycoprotein, Zymogen

Proteomic databases

MaxQBiQ9WVM6.
PaxDbiQ9WVM6.
PRIDEiQ9WVM6.

PTM databases

iPTMnetiQ9WVM6.
PhosphoSiteiQ9WVM6.

Expressioni

Developmental stagei

Expressed at E7.5, in a limited way, in the posterior portion of the egg cylinder in the nascent mesoderm streaming off the primitive streak. At the distant end of the embryo cylinder, expression ended at the node. Later in the development, expression seems to be limited to developing skeletal muscle and central nervous system.1 Publication

Gene expression databases

BgeeiQ9WVM6.
CleanExiMM_TLL2.
ExpressionAtlasiQ9WVM6. baseline and differential.

Interactioni

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000025986.

Structurei

3D structure databases

ProteinModelPortaliQ9WVM6.
SMRiQ9WVM6. Positions 147-347.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini348 – 460113CUB 1PROSITE-ProRule annotationAdd
BLAST
Domaini461 – 573113CUB 2PROSITE-ProRule annotationAdd
BLAST
Domaini573 – 61442EGF-like 1; calcium-bindingPROSITE-ProRule annotationAdd
BLAST
Domaini617 – 729113CUB 3PROSITE-ProRule annotationAdd
BLAST
Domaini729 – 76941EGF-like 2; calcium-bindingPROSITE-ProRule annotationAdd
BLAST
Domaini773 – 885113CUB 4PROSITE-ProRule annotationAdd
BLAST
Domaini886 – 1002117CUB 5PROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni147 – 347201MetalloproteaseBy similarityAdd
BLAST

Sequence similaritiesi

Belongs to the peptidase M12A family.Curated
Contains 5 CUB domains.PROSITE-ProRule annotation
Contains 2 EGF-like domains.PROSITE-ProRule annotation

Keywords - Domaini

EGF-like domain, Repeat, Signal

Phylogenomic databases

eggNOGiKOG3714. Eukaryota.
ENOG410ZPX7. LUCA.
GeneTreeiENSGT00760000119018.
HOGENOMiHOG000236339.
HOVERGENiHBG004859.
InParanoidiQ9WVM6.
KOiK13047.
OMAiHAGAETF.
OrthoDBiEOG7N8ZTV.
PhylomeDBiQ9WVM6.
TreeFamiTF314351.

Family and domain databases

Gene3Di2.60.120.290. 5 hits.
3.40.390.10. 1 hit.
InterProiIPR015446. BMP_1/tolloid-like.
IPR000859. CUB_dom.
IPR001881. EGF-like_Ca-bd_dom.
IPR013032. EGF-like_CS.
IPR000742. EGF-like_dom.
IPR000152. EGF-type_Asp/Asn_hydroxyl_site.
IPR018097. EGF_Ca-bd_CS.
IPR024079. MetalloPept_cat_dom.
IPR001506. Peptidase_M12A.
IPR006026. Peptidase_Metallo.
[Graphical view]
PfamiPF01400. Astacin. 1 hit.
PF00431. CUB. 5 hits.
PF07645. EGF_CA. 1 hit.
[Graphical view]
PIRSFiPIRSF001199. BMP_1/tolloid-like. 1 hit.
PRINTSiPR00480. ASTACIN.
SMARTiSM00042. CUB. 5 hits.
SM00181. EGF. 2 hits.
SM00179. EGF_CA. 2 hits.
SM00235. ZnMc. 1 hit.
[Graphical view]
SUPFAMiSSF49854. SSF49854. 5 hits.
PROSITEiPS01180. CUB. 5 hits.
PS01186. EGF_2. 2 hits.
PS50026. EGF_3. 2 hits.
PS01187. EGF_CA. 2 hits.
PS00142. ZINC_PROTEASE. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

Q9WVM6-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MPLATTLGTL VLLLLLPLPR GAEVTGDHSN VALDYGALEG EEGTEQQLHY
60 70 80 90 100
HDPCKAAVFW GDIALDEDDL KLFHIDKAED WTKPSIDKPG HDTGGLEETS
110 120 130 140 150
ARWPNDTASN ASIQAPRKDG KDATTFLPNP GTSNTTAKTF SARVRRATTS
160 170 180 190 200
RTERIWPGGV IPYVIGGNFT GTQRAIFKQA MRHWEKHTCV TFVERTDEES
210 220 230 240 250
FIVFSYRTCG CCSYVGRRGG GPQAISIGKN CDKFGIVAHE LGHVVGFWHE
260 270 280 290 300
HTRPDRDQHV TIIRENIQPG QEYNFLKMEA GEVSSLGETY DFDSIMHYAR
310 320 330 340 350
NTFSRGVFLD TILPRRDDNG VRPTIGQRVR LSQGDIAQAR KLYKCPACGE
360 370 380 390 400
TLQDTTGNFS APGFPNGYPS YSHCVWRISV TPGEKIILNF TSMDLFKSRL
410 420 430 440 450
CWYDYVEIRD GYWRKAPLLG RFCGDKIPES LVSSDSRLWV EFRSSSSSLG
460 470 480 490 500
KGFFAVYEAM CGGDITKDAG QIQSPNYPDD YRPSKECVWR ITVPDGFHVG
510 520 530 540 550
LTFQSFEIER HDSCAYDYLE IRDGPTEDST LIGHFCGYEK PEAVKSSANR
560 570 580 590 600
LWVKFVSDGS INKAGFAANF FKEVDECSWP DHGGCEQRCV NTLGSYTCAC
610 620 630 640 650
DPGYELAADK KTCEVACGGF ITKLNGTITS PGWPKEYPTN KNCVWQVVAP
660 670 680 690 700
VQYRISLQFE AFELEGNDVC KYDFVEVRSG LSPDAKLHGK FCGSETPEVI
710 720 730 740 750
TSQSNNMRVE FKSDNTVSKR GFRAHFFSDK DECAKDNGGC QQECVNTFGS
760 770 780 790 800
YLCRCRNGYR LHENGHDCKE AGCAYKISSA EGTLMSPNWP DKYPSRKECT
810 820 830 840 850
WNISSTAGHR VKITFSEFEI EQHQECAYDH LELYDGTDSL APILGRFCGS
860 870 880 890 900
KKPDPVVATG SSLFLRFYSD ASVQRKGFQA VHSTECGGRL KAEVQTKELY
910 920 930 940 950
SHAQFGDNNY PSQARCDWVI VAEDGYGVEL IFRTFEVEEE ADCGYDFMEA
960 970 980 990 1000
YDGYDSSAPR LGRFCGSGPL EEIYSAGDSL MIRFHTDDTI NKKGFHARYT
1010
STKFQDALHM RK
Length:1,012
Mass (Da):113,252
Last modified:November 1, 1999 - v1
Checksum:i72EEE268A4D8C5FE
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF073526 mRNA. Translation: AAD42993.1.
BC132537 mRNA. Translation: AAI32538.1.
CCDSiCCDS37986.1.
RefSeqiNP_036034.1. NM_011904.3.
UniGeneiMm.89983.

Genome annotation databases

EnsembliENSMUST00000025986; ENSMUSP00000025986; ENSMUSG00000025013.
GeneIDi24087.
KEGGimmu:24087.
UCSCiuc008hlr.1. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF073526 mRNA. Translation: AAD42993.1.
BC132537 mRNA. Translation: AAI32538.1.
CCDSiCCDS37986.1.
RefSeqiNP_036034.1. NM_011904.3.
UniGeneiMm.89983.

3D structure databases

ProteinModelPortaliQ9WVM6.
SMRiQ9WVM6. Positions 147-347.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000025986.

Protein family/group databases

MEROPSiM12.018.

PTM databases

iPTMnetiQ9WVM6.
PhosphoSiteiQ9WVM6.

Proteomic databases

MaxQBiQ9WVM6.
PaxDbiQ9WVM6.
PRIDEiQ9WVM6.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000025986; ENSMUSP00000025986; ENSMUSG00000025013.
GeneIDi24087.
KEGGimmu:24087.
UCSCiuc008hlr.1. mouse.

Organism-specific databases

CTDi7093.
MGIiMGI:1346044. Tll2.

Phylogenomic databases

eggNOGiKOG3714. Eukaryota.
ENOG410ZPX7. LUCA.
GeneTreeiENSGT00760000119018.
HOGENOMiHOG000236339.
HOVERGENiHBG004859.
InParanoidiQ9WVM6.
KOiK13047.
OMAiHAGAETF.
OrthoDBiEOG7N8ZTV.
PhylomeDBiQ9WVM6.
TreeFamiTF314351.

Enzyme and pathway databases

ReactomeiR-MMU-1474228. Degradation of the extracellular matrix.
R-MMU-2214320. Anchoring fibril formation.

Miscellaneous databases

PROiQ9WVM6.
SOURCEiSearch...

Gene expression databases

BgeeiQ9WVM6.
CleanExiMM_TLL2.
ExpressionAtlasiQ9WVM6. baseline and differential.

Family and domain databases

Gene3Di2.60.120.290. 5 hits.
3.40.390.10. 1 hit.
InterProiIPR015446. BMP_1/tolloid-like.
IPR000859. CUB_dom.
IPR001881. EGF-like_Ca-bd_dom.
IPR013032. EGF-like_CS.
IPR000742. EGF-like_dom.
IPR000152. EGF-type_Asp/Asn_hydroxyl_site.
IPR018097. EGF_Ca-bd_CS.
IPR024079. MetalloPept_cat_dom.
IPR001506. Peptidase_M12A.
IPR006026. Peptidase_Metallo.
[Graphical view]
PfamiPF01400. Astacin. 1 hit.
PF00431. CUB. 5 hits.
PF07645. EGF_CA. 1 hit.
[Graphical view]
PIRSFiPIRSF001199. BMP_1/tolloid-like. 1 hit.
PRINTSiPR00480. ASTACIN.
SMARTiSM00042. CUB. 5 hits.
SM00181. EGF. 2 hits.
SM00179. EGF_CA. 2 hits.
SM00235. ZnMc. 1 hit.
[Graphical view]
SUPFAMiSSF49854. SSF49854. 5 hits.
PROSITEiPS01180. CUB. 5 hits.
PS01186. EGF_2. 2 hits.
PS50026. EGF_3. 2 hits.
PS01187. EGF_CA. 2 hits.
PS00142. ZINC_PROTEASE. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "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] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], DEVELOPMENTAL STAGE.
  2. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Tissue: Brain.
  3. "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] [Europe PMC] [Abstract]
    Cited for: CHARACTERIZATION.

Entry informationi

Entry nameiTLL2_MOUSE
AccessioniPrimary (citable) accession number: Q9WVM6
Secondary accession number(s): A2RTK3
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 7, 2006
Last sequence update: November 1, 1999
Last modified: June 8, 2016
This is version 113 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. Peptidase families
    Classification of peptidase families and list of entries
  3. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.