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Protein

Tolloid-like protein 1

Gene

TLL1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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+PROSITE-ProRule annotationNote: Binds 1 zinc ion per subunit.PROSITE-ProRule annotation

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi240Zinc; via tele nitrogen; catalyticPROSITE-ProRule annotation1
Active sitei241PROSITE-ProRule annotation1
Metal bindingi244Zinc; via tele nitrogen; catalyticPROSITE-ProRule annotation1
Metal bindingi250Zinc; via tele nitrogen; catalyticPROSITE-ProRule annotation1

GO - Molecular functioni

GO - Biological processi

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

Keywordsi

Molecular functionDevelopmental protein, Hydrolase, Metalloprotease, Protease
Biological processDifferentiation
LigandCalcium, 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

MEROPSiM12.016

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

EuPathDBiHostDB:ENSG00000038295.7
HGNCiHGNC:11843 TLL1
MIMi606742 gene
neXtProtiNX_O43897

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

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 dbSNP:rs137852951EnsemblClinVar.1
Natural variantiVAR_062520238V → A in ASD6. 1 PublicationCorresponds to variant dbSNP:rs137852952EnsemblClinVar.1
Natural variantiVAR_062521629I → V in ASD6. 1 PublicationCorresponds to variant dbSNP:rs137852953EnsemblClinVar.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...) asparagineSequence analysis1
Disulfide bondi190 ↔ 346PROSITE-ProRule annotation1 Publication
Disulfide bondi210 ↔ 232PROSITE-ProRule annotation
Disulfide bondi212 ↔ 213PROSITE-ProRule annotation
Disulfide bondi349 ↔ 375By similarity
Glycosylationi359N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi390N-linked (GlcNAc...) asparagineSequence 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...) asparagineSequence 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
ProteomicsDBi49221
49222 [O43897-2]

PTM databases

iPTMnetiO43897
PhosphoSitePlusiO43897

Expressioni

Gene expression databases

BgeeiENSG00000038295 Expressed in 94 organ(s), highest expression level in secondary oocyte
CleanExiHS_TLL1
ExpressionAtlasiO43897 baseline and differential
GenevisibleiO43897 HS

Organism-specific databases

HPAiHPA060767

Interactioni

Protein-protein interaction databases

BioGridi112947, 3 interactors
STRINGi9606.ENSP00000061240

Structurei

Secondary structure

11013
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliO43897
SMRiO43897
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiO43897

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini148 – 347Peptidase M12APROSITE-ProRule annotationAdd BLAST200
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

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
cd04281 ZnMc_BMP1_TLD, 1 hit
Gene3Di2.60.120.290, 5 hits
3.40.390.10, 1 hit
InterProiView protein in InterPro
IPR015446 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_sf
IPR001506 Peptidase_M12A
IPR006026 Peptidase_Metallo
IPR035914 Sperma_CUB_dom_sf
IPR034036 ZnMP_TLD/BMP1
PfamiView protein in Pfam
PF01400 Astacin, 1 hit
PF00431 CUB, 5 hits
PF07645 EGF_CA, 1 hit
PIRSFiPIRSF001199 BMP_1/tolloid-like, 1 hit
PRINTSiPR00480 ASTACIN
SMARTiView protein in SMART
SM00042 CUB, 5 hits
SM00181 EGF, 2 hits
SM00179 EGF_CA, 2 hits
SM00235 ZnMc, 1 hit
SUPFAMiSSF49854 SSF49854, 5 hits
PROSITEiView protein in PROSITE
PS51864 ASTACIN, 1 hit
PS01180 CUB, 5 hits
PS01186 EGF_2, 2 hits
PS50026 EGF_3, 2 hits
PS01187 EGF_CA, 2 hits
PS00142 ZINC_PROTEASE, 1 hit

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

This entry has 2 described isoforms and 4 potential isoforms that are computationally mapped.iShow all

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

Computationally mapped potential isoform sequencesi

There are 4 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
E9PD25E9PD25_HUMAN
Metalloendopeptidase
TLL1
1,036Annotation score:
D6RAK5D6RAK5_HUMAN
Tolloid-like protein 1
TLL1
57Annotation score:
D6RBI6D6RBI6_HUMAN
Tolloid-like protein 1
TLL1
130Annotation score:
D6RCE0D6RCE0_HUMAN
Tolloid-like protein 1
TLL1
110Annotation score:

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 dbSNP:rs137852951EnsemblClinVar.1
Natural variantiVAR_062520238V → A in ASD6. 1 PublicationCorresponds to variant dbSNP:rs137852952EnsemblClinVar.1
Natural variantiVAR_062521629I → V in ASD6. 1 PublicationCorresponds to variant dbSNP:rs137852953EnsemblClinVar.1
Natural variantiVAR_036142688L → V in a breast cancer sample; somatic mutation. 1 Publication1
Natural variantiVAR_051585958T → A. Corresponds to variant dbSNP:rs2291822Ensembl.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

Similar proteinsi

Entry informationi

Entry nameiTLL1_HUMAN
AccessioniPrimary (citable) accession number: O43897
Secondary accession number(s): B2RMU2, Q96AN3, Q9NQS4
Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 7, 2006
Last sequence update: June 1, 1998
Last modified: September 12, 2018
This is version 140 of the entry and version 1 of the sequence. See 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
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Main funding by: National Institutes of Health

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