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Protein

Tolloid-like protein 2

Gene

TLL2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 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 bindingi242 – 2421Zinc; catalyticPROSITE-ProRule annotation
Active sitei243 – 2431PROSITE-ProRule annotation
Metal bindingi246 – 2461Zinc; catalyticPROSITE-ProRule annotation
Metal bindingi252 – 2521Zinc; catalyticPROSITE-ProRule annotation

GO - Molecular functioni

GO - Biological processi

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-HSA-1474228. Degradation of the extracellular matrix.
R-HSA-1650814. Collagen biosynthesis and modifying enzymes.
R-HSA-2214320. Anchoring fibril formation.
R-HSA-2243919. Crosslinking of collagen fibrils.

Protein family/group databases

MEROPSiM12.018.

Names & Taxonomyi

Protein namesi
Recommended name:
Tolloid-like protein 2 (EC:3.4.24.-)
Gene namesi
Name:TLL2
Synonyms:KIAA0932
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 10

Organism-specific databases

HGNCiHGNC:11844. TLL2.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Secreted

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA36546.

Polymorphism and mutation databases

BioMutaiTLL2.
DMDMi74762080.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2525Sequence analysisAdd
BLAST
Propeptidei26 – 1491241 PublicationPRO_0000046036Add
BLAST
Chaini150 – 1015866Tolloid-like protein 2PRO_0000046037Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi171 – 1711N-linked (GlcNAc...)Sequence analysis
Disulfide bondi351 ↔ 377By similarity
Glycosylationi361 – 3611N-linked (GlcNAc...)Sequence analysis
Glycosylationi392 – 3921N-linked (GlcNAc...)Sequence analysis
Disulfide bondi404 ↔ 426By similarity
Disulfide bondi464 ↔ 490By similarity
Disulfide bondi517 ↔ 539By similarity
Disulfide bondi580 ↔ 592By similarity
Disulfide bondi588 ↔ 601By similarity
Disulfide bondi603 ↔ 616By similarity
Disulfide bondi620 ↔ 646By similarity
Glycosylationi628 – 6281N-linked (GlcNAc...)Sequence analysis
Disulfide bondi673 ↔ 695By similarity
Disulfide bondi736 ↔ 747By similarity
Disulfide bondi743 ↔ 756By similarity
Disulfide bondi758 ↔ 771By similarity
Disulfide bondi776 ↔ 802By similarity
Glycosylationi805 – 8051N-linked (GlcNAc...)Sequence analysis
Disulfide bondi829 ↔ 851By similarity
Disulfide bondi889 ↔ 919By similarity
Disulfide bondi946 ↔ 968By similarity

Keywords - PTMi

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

Proteomic databases

MaxQBiQ9Y6L7.
PaxDbiQ9Y6L7.
PeptideAtlasiQ9Y6L7.
PRIDEiQ9Y6L7.

PTM databases

iPTMnetiQ9Y6L7.
PhosphoSiteiQ9Y6L7.

Expressioni

Gene expression databases

BgeeiQ9Y6L7.
CleanExiHS_TLL2.
GenevisibleiQ9Y6L7. HS.

Interactioni

Protein-protein interaction databases

BioGridi112948. 1 interaction.
STRINGi9606.ENSP00000350630.

Structurei

3D structure databases

ProteinModelPortaliQ9Y6L7.
SMRiQ9Y6L7. Positions 150-1003.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini351 – 463113CUB 1PROSITE-ProRule annotationAdd
BLAST
Domaini464 – 576113CUB 2PROSITE-ProRule annotationAdd
BLAST
Domaini576 – 61742EGF-like 1; calcium-bindingPROSITE-ProRule annotationAdd
BLAST
Domaini620 – 732113CUB 3PROSITE-ProRule annotationAdd
BLAST
Domaini732 – 77241EGF-like 2; calcium-bindingPROSITE-ProRule annotationAdd
BLAST
Domaini776 – 888113CUB 4PROSITE-ProRule annotationAdd
BLAST
Domaini889 – 1005117CUB 5PROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni150 – 350201MetalloproteaseBy 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.
InParanoidiQ9Y6L7.
KOiK13047.
OMAiHAGAETF.
OrthoDBiEOG7N8ZTV.
PhylomeDBiQ9Y6L7.
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.

Q9Y6L7-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MPRATALGAL VSLLLLLPLP RGAGGLGERP DATADYSELD GEEGTEQQLE
60 70 80 90 100
HYHDPCKAAV FWGDIALDED DLKLFHIDKA RDWTKQTVGA TGHSTGGLEE
110 120 130 140 150
QASESSPDTT AMDTGTKEAG KDGRENTTLL HSPGTLHAAA KTFSPRVRRA
160 170 180 190 200
TTSRTERIWP GGVIPYVIGG NFTGSQRAIF KQAMRHWEKH TCVTFIERTD
210 220 230 240 250
EESFIVFSYR TCGCCSYVGR RGGGPQAISI GKNCDKFGIV AHELGHVVGF
260 270 280 290 300
WHEHTRPDRD QHVTIIRENI QPGQEYNFLK MEAGEVSSLG ETYDFDSIMH
310 320 330 340 350
YARNTFSRGV FLDTILPRQD DNGVRPTIGQ RVRLSQGDIA QARKLYKCPA
360 370 380 390 400
CGETLQDTTG NFSAPGFPNG YPSYSHCVWR ISVTPGEKIV LNFTSMDLFK
410 420 430 440 450
SRLCWYDYVE VRDGYWRKAP LLGRFCGDKI PEPLVSTDSR LWVEFRSSSN
460 470 480 490 500
ILGKGFFAAY EATCGGDMNK DAGQIQSPNY PDDYRPSKEC VWRITVSEGF
510 520 530 540 550
HVGLTFQAFE IERHDSCAYD YLEVRDGPTE ESALIGHFCG YEKPEDVKSS
560 570 580 590 600
SNRLWMKFVS DGSINKAGFA ANFFKEVDEC SWPDHGGCEH RCVNTLGSYK
610 620 630 640 650
CACDPGYELA ADKKMCEVAC GGFITKLNGT ITSPGWPKEY PTNKNCVWQV
660 670 680 690 700
VAPAQYRISL QFEVFELEGN DVCKYDFVEV RSGLSPDAKL HGRFCGSETP
710 720 730 740 750
EVITSQSNNM RVEFKSDNTV SKRGFRAHFF SDKDECAKDN GGCQHECVNT
760 770 780 790 800
FGSYLCRCRN GYWLHENGHD CKEAGCAHKI SSVEGTLASP NWPDKYPSRR
810 820 830 840 850
ECTWNISSTA GHRVKLTFNE FEIEQHQECA YDHLEMYDGP DSLAPILGRF
860 870 880 890 900
CGSKKPDPTV ASGSSMFLRF YSDASVQRKG FQAVHSTECG GRLKAEVQTK
910 920 930 940 950
ELYSHAQFGD NNYPSEARCD WVIVAEDGYG VELTFRTFEV EEEADCGYDY
960 970 980 990 1000
MEAYDGYDSS APRLGRFCGS GPLEEIYSAG DSLMIRFRTD DTINKKGFHA
1010
RYTSTKFQDA LHMKK
Length:1,015
Mass (Da):113,557
Last modified:November 1, 1999 - v1
Checksum:i25F5B23065861593
GO

Sequence cautioni

The sequence BAA76776.2 differs from that shown. Reason: Erroneous initiation. Curated

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti495 – 4951T → M in BAA76776 (PubMed:10231032).Curated
Sequence conflicti576 – 59318EVDEC…EHRCV → GKKKKKKKKKKKKKKKKK in AAH13871 (PubMed:15489334).CuratedAdd
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF059516 mRNA. Translation: AAD42979.1.
AB023149 mRNA. Translation: BAA76776.2. Different initiation.
AL138765, AL136181, AL391136 Genomic DNA. Translation: CAI13580.1.
AL136181, AL138765, AL391136 Genomic DNA. Translation: CAH72983.1.
AL391136, AL136181, AL138765 Genomic DNA. Translation: CAH72234.1.
BC013871 mRNA. Translation: AAH13871.1.
BC112341 mRNA. Translation: AAI12342.1.
BC112366 mRNA. Translation: AAI12367.1.
BC113577 mRNA. Translation: AAI13578.1.
CCDSiCCDS7449.1.
RefSeqiNP_036597.1. NM_012465.3.
UniGeneiHs.154296.

Genome annotation databases

EnsembliENST00000357947; ENSP00000350630; ENSG00000095587.
GeneIDi7093.
KEGGihsa:7093.
UCSCiuc001kml.3. human.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF059516 mRNA. Translation: AAD42979.1.
AB023149 mRNA. Translation: BAA76776.2. Different initiation.
AL138765, AL136181, AL391136 Genomic DNA. Translation: CAI13580.1.
AL136181, AL138765, AL391136 Genomic DNA. Translation: CAH72983.1.
AL391136, AL136181, AL138765 Genomic DNA. Translation: CAH72234.1.
BC013871 mRNA. Translation: AAH13871.1.
BC112341 mRNA. Translation: AAI12342.1.
BC112366 mRNA. Translation: AAI12367.1.
BC113577 mRNA. Translation: AAI13578.1.
CCDSiCCDS7449.1.
RefSeqiNP_036597.1. NM_012465.3.
UniGeneiHs.154296.

3D structure databases

ProteinModelPortaliQ9Y6L7.
SMRiQ9Y6L7. Positions 150-1003.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi112948. 1 interaction.
STRINGi9606.ENSP00000350630.

Protein family/group databases

MEROPSiM12.018.

PTM databases

iPTMnetiQ9Y6L7.
PhosphoSiteiQ9Y6L7.

Polymorphism and mutation databases

BioMutaiTLL2.
DMDMi74762080.

Proteomic databases

MaxQBiQ9Y6L7.
PaxDbiQ9Y6L7.
PeptideAtlasiQ9Y6L7.
PRIDEiQ9Y6L7.

Protocols and materials databases

DNASUi7093.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000357947; ENSP00000350630; ENSG00000095587.
GeneIDi7093.
KEGGihsa:7093.
UCSCiuc001kml.3. human.

Organism-specific databases

CTDi7093.
GeneCardsiTLL2.
H-InvDBHIX0009074.
HGNCiHGNC:11844. TLL2.
MIMi606743. gene.
neXtProtiNX_Q9Y6L7.
PharmGKBiPA36546.
HUGEiSearch...
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG3714. Eukaryota.
ENOG410ZPX7. LUCA.
GeneTreeiENSGT00760000119018.
HOGENOMiHOG000236339.
HOVERGENiHBG004859.
InParanoidiQ9Y6L7.
KOiK13047.
OMAiHAGAETF.
OrthoDBiEOG7N8ZTV.
PhylomeDBiQ9Y6L7.
TreeFamiTF314351.

Enzyme and pathway databases

ReactomeiR-HSA-1474228. Degradation of the extracellular matrix.
R-HSA-1650814. Collagen biosynthesis and modifying enzymes.
R-HSA-2214320. Anchoring fibril formation.
R-HSA-2243919. Crosslinking of collagen fibrils.

Miscellaneous databases

GeneWikiiTLL2.
GenomeRNAii7093.
PROiQ9Y6L7.
SOURCEiSearch...

Gene expression databases

BgeeiQ9Y6L7.
CleanExiHS_TLL2.
GenevisibleiQ9Y6L7. HS.

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], PROTEIN SEQUENCE OF 150-154.
    Tissue: Placenta.
  2. "Prediction of the coding sequences of unidentified human genes. XIII. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro."
    Nagase T., Ishikawa K., Suyama M., Kikuno R., Hirosawa M., Miyajima N., Tanaka A., Kotani H., Nomura N., Ohara O.
    DNA Res. 6:63-70(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Tissue: Brain.
  3. Ohara O., Nagase T., Kikuno R.
    Submitted (FEB-1999) to the EMBL/GenBank/DDBJ databases
    Cited for: SEQUENCE REVISION.
  4. "The DNA sequence and comparative analysis of human chromosome 10."
    Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L., Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K., Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L., Taylor A., Battles J.
    , Bird C.P., Ainscough R., Almeida J.P., Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P., Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N., Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A., Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C., Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D., Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C., Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K., Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A., Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S., McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S., Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V., Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A., Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M., Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A., Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P., Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y., Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D., Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J.
    Nature 429:375-381(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  5. "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: Ovary.
  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] [Europe PMC] [Abstract]
    Cited for: CHARACTERIZATION.

Entry informationi

Entry nameiTLL2_HUMAN
AccessioniPrimary (citable) accession number: Q9Y6L7
Secondary accession number(s): A6NDK0
, Q2M1H1, Q6PJN5, Q9UQ00
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 7, 2006
Last sequence update: November 1, 1999
Last modified: July 6, 2016
This is version 131 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 10
    Human chromosome 10: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. Peptidase families
    Classification of peptidase families and list of entries
  4. 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.