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Protein

Tolloid-like protein 1

Gene

TLL1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Protease which processes procollagen C-propeptides, such as chordin, pro-biglycan and 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)DescriptionActionsGraphical viewLength
Metal bindingi240Zinc; catalyticPROSITE-ProRule annotation1
Active sitei241PROSITE-ProRule annotation1
Metal bindingi244Zinc; catalyticPROSITE-ProRule annotation1
Metal bindingi250Zinc; catalyticPROSITE-ProRule annotation1

GO - Molecular functioni

GO - Biological processi

  • cell differentiation Source: UniProtKB-KW
  • extracellular matrix disassembly Source: Reactome
  • skeletal system development Source: ProtInc
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

BioCyciZFISH:ENSG00000038295-MONOMER.
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

MEROPSiM12.016.

Names & Taxonomyi

Protein namesi
Recommended name:
Tolloid-like protein 1 (EC:3.4.24.-)
Gene namesi
Name:TLL1
Synonyms:TLL
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 4

Organism-specific databases

HGNCiHGNC:11843. TLL1.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Secreted

Pathology & Biotechi

Involvement in diseasei

Atrial septal defect 6 (ASD6)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA congenital heart malformation characterized by incomplete closure of the wall between the atria resulting in blood flow from the left to the right atria.
See also OMIM:613087
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_062519182M → L in ASD6. 1 PublicationCorresponds to variant rs137852951dbSNPEnsembl.1
Natural variantiVAR_062520238V → A in ASD6. 1 PublicationCorresponds to variant rs137852952dbSNPEnsembl.1
Natural variantiVAR_062521629I → V in ASD6. 1 PublicationCorresponds to variant rs137852953dbSNPEnsembl.1

Keywords - Diseasei

Atrial septal defect, Disease mutation

Organism-specific databases

DisGeNETi7092.
MalaCardsiTLL1.
MIMi613087. phenotype.
OpenTargetsiENSG00000038295.
Orphaneti99106. Atrial septal defect, ostium primum type.
99103. Atrial septal defect, ostium secundum type.
PharmGKBiPA36545.

Polymorphism and mutation databases

BioMutaiTLL1.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 30Sequence analysisAdd BLAST30
PropeptideiPRO_000004602331 – 147Sequence analysisAdd BLAST117
ChainiPRO_0000046024148 – 1013Tolloid-like protein 1Add BLAST866

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi169N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi190 ↔ 3461 Publication
Disulfide bondi210 ↔ 232By similarity
Disulfide bondi212 ↔ 213By similarity
Disulfide bondi349 ↔ 375By similarity
Glycosylationi359N-linked (GlcNAc...)Sequence analysis1
Glycosylationi390N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi402 ↔ 424By similarity
Disulfide bondi462 ↔ 488By similarity
Disulfide bondi515 ↔ 537By similarity
Disulfide bondi578 ↔ 590By similarity
Disulfide bondi586 ↔ 599By similarity
Disulfide bondi601 ↔ 614By similarity
Disulfide bondi618 ↔ 644By similarity
Glycosylationi626N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi671 ↔ 693By similarity
Disulfide bondi734 ↔ 745By similarity
Disulfide bondi741 ↔ 754By similarity
Disulfide bondi756 ↔ 769By similarity
Disulfide bondi774 ↔ 800By similarity
Disulfide bondi827 ↔ 849By similarity
Disulfide bondi887 ↔ 917By similarity
Disulfide bondi944 ↔ 966By similarity

Keywords - PTMi

Disulfide bond, Glycoprotein, Zymogen

Proteomic databases

MaxQBiO43897.
PaxDbiO43897.
PeptideAtlasiO43897.
PRIDEiO43897.

PTM databases

iPTMnetiO43897.
PhosphoSitePlusiO43897.

Expressioni

Gene expression databases

BgeeiENSG00000038295.
CleanExiHS_TLL1.
ExpressionAtlasiO43897. baseline and differential.
GenevisibleiO43897. HS.

Organism-specific databases

HPAiHPA060767.

Interactioni

Protein-protein interaction databases

BioGridi112947. 2 interactors.
STRINGi9606.ENSP00000061240.

Structurei

Secondary structure

11013
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi153 – 155Combined sources3
Helixi158 – 160Combined sources3
Beta strandi161 – 166Combined sources6
Helixi172 – 188Combined sources17
Beta strandi192 – 195Combined sources4
Beta strandi203 – 206Combined sources4
Beta strandi224 – 227Combined sources4
Helixi235 – 246Combined sources12
Helixi251 – 253Combined sources3
Helixi257 – 259Combined sources3
Beta strandi261 – 263Combined sources3
Helixi265 – 267Combined sources3
Helixi273 – 276Combined sources4
Helixi281 – 283Combined sources3
Turni301 – 304Combined sources4
Beta strandi305 – 307Combined sources3
Beta strandi312 – 315Combined sources4
Helixi334 – 343Combined sources10

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3EDIX-ray1.40A148-348[»]
ProteinModelPortaliO43897.
SMRiO43897.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiO43897.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini349 – 461CUB 1PROSITE-ProRule annotationAdd BLAST113
Domaini462 – 574CUB 2PROSITE-ProRule annotationAdd BLAST113
Domaini574 – 615EGF-like 1; calcium-bindingPROSITE-ProRule annotationAdd BLAST42
Domaini618 – 730CUB 3PROSITE-ProRule annotationAdd BLAST113
Domaini730 – 770EGF-like 2; calcium-bindingPROSITE-ProRule annotationAdd BLAST41
Domaini774 – 886CUB 4PROSITE-ProRule annotationAdd BLAST113
Domaini887 – 1003CUB 5PROSITE-ProRule annotationAdd BLAST117

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni148 – 348MetalloproteaseBy similarityAdd BLAST201

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.
InParanoidiO43897.
KOiK09608.
PhylomeDBiO43897.
TreeFamiTF314351.

Family and domain databases

CDDicd00041. CUB. 5 hits.
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]

Sequences (2)i

Sequence statusi: Complete.

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

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: O43897-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MGLGTLSPRM LVWLVASGIV FYGELWVCAG LDYDYTFDGN EEDKTETIDY
60 70 80 90 100
KDPCKAAVFW GDIALDDEDL NIFQIDRTID LTQNPFGNLG HTTGGLGDHA
110 120 130 140 150
MSKKRGALYQ LIDRIRRIGF GLEQNNTVKG KVPLQFSGQN EKNRVPRAAT
160 170 180 190 200
SRTERIWPGG VIPYVIGGNF TGSQRAMFKQ AMRHWEKHTC VTFIERSDEE
210 220 230 240 250
SYIVFTYRPC GCCSYVGRRG NGPQAISIGK NCDKFGIVVH ELGHVIGFWH
260 270 280 290 300
EHTRPDRDNH VTIIRENIQP GQEYNFLKME PGEVNSLGER YDFDSIMHYA
310 320 330 340 350
RNTFSRGMFL DTILPSRDDN GIRPAIGQRT RLSKGDIAQA RKLYRCPACG
360 370 380 390 400
ETLQESNGNL SSPGFPNGYP SYTHCIWRVS VTPGEKIVLN FTTMDLYKSS
410 420 430 440 450
LCWYDYIEVR DGYWRKSPLL GRFCGDKLPE VLTSTDSRMW IEFRSSSNWV
460 470 480 490 500
GKGFAAVYEA ICGGEIRKNE GQIQSPNYPD DYRPMKECVW KITVSESYHV
510 520 530 540 550
GLTFQSFEIE RHDNCAYDYL EVRDGTSENS PLIGRFCGYD KPEDIRSTSN
560 570 580 590 600
TLWMKFVSDG TVNKAGFAAN FFKEEDECAK PDRGGCEQRC LNTLGSYQCA
610 620 630 640 650
CEPGYELGPD RRSCEAACGG LLTKLNGTIT TPGWPKEYPP NKNCVWQVVA
660 670 680 690 700
PTQYRISVKF EFFELEGNEV CKYDYVEIWS GLSSESKLHG KFCGAEVPEV
710 720 730 740 750
ITSQFNNMRI EFKSDNTVSK KGFKAHFFSD KDECSKDNGG CQHECVNTMG
760 770 780 790 800
SYMCQCRNGF VLHDNKHDCK EAECEQKIHS PSGLITSPNW PDKYPSRKEC
810 820 830 840 850
TWEISATPGH RIKLAFSEFE IEQHQECAYD HLEVFDGETE KSPILGRLCG
860 870 880 890 900
NKIPDPLVAT GNKMFVRFVS DASVQRKGFQ ATHSTECGGR LKAESKPRDL
910 920 930 940 950
YSHAQFGDNN YPGQVDCEWL LVSERGSRLE LSFQTFEVEE EADCGYDYVE
960 970 980 990 1000
LFDGLDSTAV GLGRFCGSGP PEEIYSIGDS VLIHFHTDDT INKKGFHIRY
1010
KSIRYPDTTH TKK
Length:1,013
Mass (Da):114,709
Last modified:June 1, 1998 - v1
Checksum:i0FDDB6E8E9032DCC
GO
Isoform 2 (identifier: O43897-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     387-392: IVLNFT → VVFSLC
     393-1013: Missing.

Note: No experimental confirmation available.
Show »
Length:392
Mass (Da):44,186
Checksum:iB240EB78AD353BFE
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti156I → V in AAF86287 (Ref. 2) Curated1
Sequence conflicti221N → S in AAF86287 (Ref. 2) Curated1
Sequence conflicti284V → A in AAF86287 (Ref. 2) Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_062519182M → L in ASD6. 1 PublicationCorresponds to variant rs137852951dbSNPEnsembl.1
Natural variantiVAR_062520238V → A in ASD6. 1 PublicationCorresponds to variant rs137852952dbSNPEnsembl.1
Natural variantiVAR_062521629I → V in ASD6. 1 PublicationCorresponds to variant rs137852953dbSNPEnsembl.1
Natural variantiVAR_036142688L → V in a breast cancer sample; somatic mutation. 1 Publication1
Natural variantiVAR_051585958T → A.Corresponds to variant rs2291822dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_017197387 – 392IVLNFT → VVFSLC in isoform 2. 1 Publication6
Alternative sequenceiVSP_017198393 – 1013Missing in isoform 2. 1 PublicationAdd BLAST621

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U91963 mRNA. Translation: AAB93878.1.
AF282732 mRNA. Translation: AAF86287.1.
CH471056 Genomic DNA. Translation: EAX04813.1.
BC016922 mRNA. Translation: AAH16922.1.
BC136429 mRNA. Translation: AAI36430.1.
BC136430 mRNA. Translation: AAI36431.1.
CCDSiCCDS3811.1. [O43897-1]
CCDS56342.1. [O43897-2]
RefSeqiNP_001191689.1. NM_001204760.1. [O43897-2]
NP_036596.3. NM_012464.4. [O43897-1]
UniGeneiHs.106513.

Genome annotation databases

EnsembliENST00000061240; ENSP00000061240; ENSG00000038295. [O43897-1]
ENST00000513213; ENSP00000422937; ENSG00000038295. [O43897-2]
GeneIDi7092.
KEGGihsa:7092.
UCSCiuc003irh.3. human. [O43897-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U91963 mRNA. Translation: AAB93878.1.
AF282732 mRNA. Translation: AAF86287.1.
CH471056 Genomic DNA. Translation: EAX04813.1.
BC016922 mRNA. Translation: AAH16922.1.
BC136429 mRNA. Translation: AAI36430.1.
BC136430 mRNA. Translation: AAI36431.1.
CCDSiCCDS3811.1. [O43897-1]
CCDS56342.1. [O43897-2]
RefSeqiNP_001191689.1. NM_001204760.1. [O43897-2]
NP_036596.3. NM_012464.4. [O43897-1]
UniGeneiHs.106513.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3EDIX-ray1.40A148-348[»]
ProteinModelPortaliO43897.
SMRiO43897.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi112947. 2 interactors.
STRINGi9606.ENSP00000061240.

Protein family/group databases

MEROPSiM12.016.

PTM databases

iPTMnetiO43897.
PhosphoSitePlusiO43897.

Polymorphism and mutation databases

BioMutaiTLL1.

Proteomic databases

MaxQBiO43897.
PaxDbiO43897.
PeptideAtlasiO43897.
PRIDEiO43897.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000061240; ENSP00000061240; ENSG00000038295. [O43897-1]
ENST00000513213; ENSP00000422937; ENSG00000038295. [O43897-2]
GeneIDi7092.
KEGGihsa:7092.
UCSCiuc003irh.3. human. [O43897-1]

Organism-specific databases

CTDi7092.
DisGeNETi7092.
GeneCardsiTLL1.
HGNCiHGNC:11843. TLL1.
HPAiHPA060767.
MalaCardsiTLL1.
MIMi606742. gene.
613087. phenotype.
neXtProtiNX_O43897.
OpenTargetsiENSG00000038295.
Orphaneti99106. Atrial septal defect, ostium primum type.
99103. Atrial septal defect, ostium secundum type.
PharmGKBiPA36545.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG3714. Eukaryota.
ENOG410ZPX7. LUCA.
GeneTreeiENSGT00760000119018.
HOGENOMiHOG000236339.
HOVERGENiHBG004859.
InParanoidiO43897.
KOiK09608.
PhylomeDBiO43897.
TreeFamiTF314351.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000038295-MONOMER.
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

EvolutionaryTraceiO43897.
GeneWikiiTLL1.
GenomeRNAii7092.
PROiO43897.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000038295.
CleanExiHS_TLL1.
ExpressionAtlasiO43897. baseline and differential.
GenevisibleiO43897. HS.

Family and domain databases

CDDicd00041. CUB. 5 hits.
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...

Entry informationi

Entry nameiTLL1_HUMAN
AccessioniPrimary (citable) accession number: O43897
Secondary accession number(s): B2RMU2, Q96AN3, Q9NQS4
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 7, 2006
Last sequence update: June 1, 1998
Last modified: November 30, 2016
This is version 129 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

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 4
    Human chromosome 4: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. Peptidase families
    Classification of peptidase families and list of entries
  7. 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.