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O43897 (TLL1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 108. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Tolloid-like protein 1

EC=3.4.24.-
Gene names
Name:TLL1
Synonyms:TLL
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length1013 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence 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. Predominant protease, which in the development, influences dorsal-ventral patterning and skeletogenesis.

Cofactor

Binds 1 zinc ion per subunit By similarity.

Subcellular location

Secreted Probable.

Involvement in disease

Atrial septal defect 6 (ASD6) [MIM:613087]: A congenital heart malformation characterized by incomplete closure of the wall between the atria resulting in blood flow from the left to the right atria.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.10

Sequence similarities

Belongs to the peptidase M12A family.

Contains 5 CUB domains.

Contains 2 EGF-like domains.

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: O43897-1)

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: O43897-2)

The sequence of this isoform differs from the canonical sequence as follows:
     387-392: IVLNFT → VVFSLC
     393-1013: Missing.
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 3030 Potential
Propeptide31 – 147117 Potential
PRO_0000046023
Chain148 – 1013866Tolloid-like protein 1
PRO_0000046024

Regions

Domain349 – 461113CUB 1
Domain462 – 574113CUB 2
Domain574 – 61542EGF-like 1; calcium-binding Potential
Domain618 – 730113CUB 3
Domain730 – 77041EGF-like 2; calcium-binding Potential
Domain774 – 886113CUB 4
Domain887 – 1003117CUB 5
Region148 – 348201Metalloprotease By similarity

Sites

Active site2411 By similarity
Metal binding2401Zinc; catalytic By similarity
Metal binding2441Zinc; catalytic By similarity
Metal binding2501Zinc; catalytic By similarity

Amino acid modifications

Glycosylation1691N-linked (GlcNAc...) Potential
Glycosylation3591N-linked (GlcNAc...) Potential
Glycosylation3901N-linked (GlcNAc...) Potential
Glycosylation6261N-linked (GlcNAc...) Potential
Disulfide bond190 ↔ 346 Ref.8
Disulfide bond210 ↔ 232 By similarity
Disulfide bond212 ↔ 213 By similarity
Disulfide bond349 ↔ 375 By similarity
Disulfide bond402 ↔ 424 By similarity
Disulfide bond462 ↔ 488 By similarity
Disulfide bond515 ↔ 537 By similarity
Disulfide bond578 ↔ 590 By similarity
Disulfide bond586 ↔ 599 By similarity
Disulfide bond601 ↔ 614 By similarity
Disulfide bond618 ↔ 644 By similarity
Disulfide bond671 ↔ 693 By similarity
Disulfide bond734 ↔ 745 By similarity
Disulfide bond741 ↔ 754 By similarity
Disulfide bond756 ↔ 769 By similarity
Disulfide bond774 ↔ 800 By similarity
Disulfide bond827 ↔ 849 By similarity
Disulfide bond887 ↔ 917 By similarity
Disulfide bond944 ↔ 966 By similarity

Natural variations

Alternative sequence387 – 3926IVLNFT → VVFSLC in isoform 2.
VSP_017197
Alternative sequence393 – 1013621Missing in isoform 2.
VSP_017198
Natural variant1821M → L in ASD6. Ref.10
VAR_062519
Natural variant2381V → A in ASD6. Ref.10
VAR_062520
Natural variant6291I → V in ASD6. Ref.10
VAR_062521
Natural variant6881L → V in a breast cancer sample; somatic mutation. Ref.9
VAR_036142
Natural variant9581T → A.
Corresponds to variant rs2291822 [ dbSNP | Ensembl ].
VAR_051585

Experimental info

Sequence conflict1561I → V in AAF86287. Ref.2
Sequence conflict2211N → S in AAF86287. Ref.2
Sequence conflict2841V → A in AAF86287. Ref.2

Secondary structure

................................... 1013
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified June 1, 1998. Version 1.
Checksum: 0FDDB6E8E9032DCC

FASTA1,013114,709
        10         20         30         40         50         60 
MGLGTLSPRM LVWLVASGIV FYGELWVCAG LDYDYTFDGN EEDKTETIDY KDPCKAAVFW 

        70         80         90        100        110        120 
GDIALDDEDL NIFQIDRTID LTQNPFGNLG HTTGGLGDHA MSKKRGALYQ LIDRIRRIGF 

       130        140        150        160        170        180 
GLEQNNTVKG KVPLQFSGQN EKNRVPRAAT SRTERIWPGG VIPYVIGGNF TGSQRAMFKQ 

       190        200        210        220        230        240 
AMRHWEKHTC VTFIERSDEE 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 ETLQESNGNL 

       370        380        390        400        410        420 
SSPGFPNGYP SYTHCIWRVS VTPGEKIVLN FTTMDLYKSS LCWYDYIEVR DGYWRKSPLL 

       430        440        450        460        470        480 
GRFCGDKLPE VLTSTDSRMW IEFRSSSNWV GKGFAAVYEA ICGGEIRKNE GQIQSPNYPD 

       490        500        510        520        530        540 
DYRPMKECVW KITVSESYHV GLTFQSFEIE RHDNCAYDYL EVRDGTSENS PLIGRFCGYD 

       550        560        570        580        590        600 
KPEDIRSTSN TLWMKFVSDG TVNKAGFAAN FFKEEDECAK PDRGGCEQRC LNTLGSYQCA 

       610        620        630        640        650        660 
CEPGYELGPD RRSCEAACGG LLTKLNGTIT TPGWPKEYPP NKNCVWQVVA PTQYRISVKF 

       670        680        690        700        710        720 
EFFELEGNEV CKYDYVEIWS GLSSESKLHG KFCGAEVPEV ITSQFNNMRI EFKSDNTVSK 

       730        740        750        760        770        780 
KGFKAHFFSD KDECSKDNGG CQHECVNTMG SYMCQCRNGF VLHDNKHDCK EAECEQKIHS 

       790        800        810        820        830        840 
PSGLITSPNW PDKYPSRKEC TWEISATPGH RIKLAFSEFE IEQHQECAYD HLEVFDGETE 

       850        860        870        880        890        900 
KSPILGRLCG NKIPDPLVAT GNKMFVRFVS DASVQRKGFQ ATHSTECGGR LKAESKPRDL 

       910        920        930        940        950        960 
YSHAQFGDNN YPGQVDCEWL LVSERGSRLE LSFQTFEVEE EADCGYDYVE LFDGLDSTAV 

       970        980        990       1000       1010 
GLGRFCGSGP PEEIYSIGDS VLIHFHTDDT INKKGFHIRY KSIRYPDTTH TKK 

« Hide

Isoform 2 [UniParc].

Checksum: B240EB78AD353BFE
Show »

FASTA39244,186

References

« Hide 'large scale' references
[1]"Sequence of human mammalian tolloid-like (mTll) and chromosomal localization of the cognate gene TLL."
Greenspan D.S., Takahara K.
Submitted (MAR-1997) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
Tissue: Placenta.
[2]"Human cardiac/brain tolloid-like protein."
Arleth A.J., Elshourbagy N.A., Li X., Willette R.N.
Submitted (JUN-2000) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
Tissue: Heart.
[3]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]"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] (ISOFORMS 1 AND 2).
Tissue: Prostate.
[5]"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: CHARACTERIZATION OF ACTION ON COLLAGENS.
[6]"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] [Europe PMC] [Abstract]
Cited for: CHARACTERIZATION OF ACTION ON PROBIGLYCAN.
[7]"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 OF ACTION ON PRO-LYSYL OXIDASE.
[8]"Structural basis for the substrate specificity of bone morphogenetic protein 1/tolloid-like metalloproteases."
Mac Sweeney A., Gil-Parrado S., Vinzenz D., Bernardi A., Hein A., Bodendorf U., Erbel P., Logel C., Gerhartz B.
J. Mol. Biol. 384:228-239(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.4 ANGSTROMS) OF 148-348, DISULFIDE BONDS.
[9]"The consensus coding sequences of human breast and colorectal cancers."
Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V. expand/collapse author list , Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., Velculescu V.E.
Science 314:268-274(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT [LARGE SCALE ANALYSIS] VAL-688.
[10]"Mutations in mammalian tolloid-like 1 gene detected in adult patients with ASD."
Stanczak P., Witecka J., Szydlo A., Gutmajster E., Lisik M., Augusciak-Duma A., Tarnowski M., Czekaj T., Czekaj H., Sieron A.L.
Eur. J. Hum. Genet. 17:344-351(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS ASD6 LEU-182; ALA-238 AND VAL-629.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
CCDSCCDS3811.1. [O43897-1]
CCDS56342.1. [O43897-2]
RefSeqNP_001191689.1. NM_001204760.1. [O43897-2]
NP_036596.3. NM_012464.4. [O43897-1]
UniGeneHs.106513.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
3EDIX-ray1.40A148-348[»]
ProteinModelPortalO43897.
SMRO43897. Positions 148-1001.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid112947. 2 interactions.
STRING9606.ENSP00000061240.

Protein family/group databases

MEROPSM12.016.

PTM databases

PhosphoSiteO43897.

Proteomic databases

MaxQBO43897.
PaxDbO43897.
PRIDEO43897.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000061240; ENSP00000061240; ENSG00000038295. [O43897-1]
ENST00000513213; ENSP00000422937; ENSG00000038295. [O43897-2]
GeneID7092.
KEGGhsa:7092.
UCSCuc003irh.2. human. [O43897-1]
uc021xud.1. human. [O43897-2]

Organism-specific databases

CTD7092.
GeneCardsGC04P166794.
HGNCHGNC:11843. TLL1.
MIM606742. gene.
613087. phenotype.
neXtProtNX_O43897.
Orphanet99106. Atrial septal defect, ostium primum type.
99103. Atrial septal defect, ostium secundum type.
PharmGKBPA36545.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG70307.
HOGENOMHOG000236339.
HOVERGENHBG004859.
InParanoidO43897.
KOK09608.
OrthoDBEOG7N8ZTV.
PhylomeDBO43897.
TreeFamTF314351.

Enzyme and pathway databases

ReactomeREACT_118779. Extracellular matrix organization.

Gene expression databases

ArrayExpressO43897.
BgeeO43897.
CleanExHS_TLL1.
GenevestigatorO43897.

Family and domain databases

Gene3D2.60.120.290. 5 hits.
3.40.390.10. 1 hit.
InterProIPR015446. BMP_1/tolloid-like.
IPR000859. CUB_dom.
IPR000742. EG-like_dom.
IPR001881. EGF-like_Ca-bd_dom.
IPR013032. EGF-like_CS.
IPR000152. EGF-type_Asp/Asn_hydroxyl_site.
IPR018097. EGF_Ca-bd_CS.
IPR024079. MetalloPept_cat_dom.
IPR001506. Peptidase_M12A.
IPR006026. Peptidase_Metallo.
[Graphical view]
PfamPF01400. Astacin. 1 hit.
PF00431. CUB. 5 hits.
[Graphical view]
PIRSFPIRSF001199. BMP_1/tolloid-like. 1 hit.
PRINTSPR00480. ASTACIN.
SMARTSM00042. CUB. 5 hits.
SM00179. EGF_CA. 2 hits.
SM00235. ZnMc. 1 hit.
[Graphical view]
SUPFAMSSF49854. SSF49854. 5 hits.
PROSITEPS01180. 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]
ProtoNetSearch...

Other

EvolutionaryTraceO43897.
GeneWikiTLL1.
GenomeRNAi7092.
NextBio27743.
PROO43897.
SOURCESearch...

Entry information

Entry nameTLL1_HUMAN
AccessionPrimary (citable) accession number: O43897
Secondary accession number(s): B2RMU2, Q96AN3, Q9NQS4
Entry history
Integrated into UniProtKB/Swiss-Prot: February 7, 2006
Last sequence update: June 1, 1998
Last modified: July 9, 2014
This is version 108 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

Peptidase families

Classification of peptidase families and list of entries

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 4

Human chromosome 4: entries, gene names and cross-references to MIM