Human Gene TLL2 (uc001kml.2)
  Description: Homo sapiens tolloid-like 2 (TLL2), mRNA.
RefSeq Summary (NM_012465): This gene encodes an astacin-like zinc-dependent metalloprotease and is a subfamily member of the metzincin family. Unlike other family members, a similar protein in mice does not cleave procollagen C-propeptides or chordin. [provided by RefSeq, Jul 2008]. Sequence Note: This RefSeq record was created from transcript and genomic sequence data to make the sequence consistent with the reference genome assembly. The genomic coordinates used for the transcript record were based on transcript alignments.
Transcript (Including UTRs)
   Position: hg19 chr10:98,124,363-98,273,683 Size: 149,321 Total Exon Count: 21 Strand: -
Coding Region
   Position: hg19 chr10:98,127,845-98,273,442 Size: 145,598 Coding Exon Count: 21 

Page IndexSequence and LinksUniProtKB CommentsPrimersGenetic AssociationsMalaCards
CTDGene AllelesRNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein Structure
Other SpeciesGO AnnotationsmRNA DescriptionsPathwaysOther NamesModel Information
Methods
Data last updated at UCSC: 2013-06-14

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr10:98,124,363-98,273,683)mRNA (may differ from genome)Protein (1015 aa)
Gene SorterGenome BrowserOther Species FASTAVisiGeneGene interactionsTable Schema
AlphaFoldBioGPSEnsemblEntrez GeneExonPrimerGeneCards
GeneNetworkH-INVHGNCHPRDLynxMalacards
MGIneXtProtOMIMPubMedReactomeTreefam
UniProtKBWikipediaBioGrid CRISPR DB

-  Comments and Description Text from UniProtKB
  ID: TLL2_HUMAN
DESCRIPTION: RecName: Full=Tolloid-like protein 2; EC=3.4.24.-; Flags: Precursor;
FUNCTION: Protease which specifically processes 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).
SIMILARITY: Belongs to the peptidase M12A family.
SIMILARITY: Contains 5 CUB domains.
SIMILARITY: Contains 2 EGF-like domains.
SEQUENCE CAUTION: Sequence=BAA76776.2; Type=Erroneous initiation;

-  Primer design for this transcript
 

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Click here to load the transcript sequence and exon structure into Primer3Plus

Exonprimer can design one pair of Sanger sequencing primers around every exon, located in non-genic sequence.
Click here to open Exonprimer with this transcript

To design primers for a non-coding sequence, zoom to a region of interest and select from the drop-down menu: View > In External Tools > Primer3


-  Genetic Association Studies of Complex Diseases and Disorders
  Genetic Association Database (archive): TLL2
CDC HuGE Published Literature: TLL2
Positive Disease Associations: ADHD | attention-deficit hyperactivity disorder , Attention Deficit Disorder with Hyperactivity
Related Studies:
  1. ADHD | attention-deficit hyperactivity disorder
    Lesch ,et al. 2008, Molecular genetics of adult ADHD: converging evidence from genome-wide association and extended pedigree linkage studies, Journal of neural transmission (Vienna, Austria : 1996) 2008 115- 11 : 1573-85. [PubMed 18839057]
  2. Attention Deficit Disorder with Hyperactivity
    Klaus-Peter Lesch et al. Journal of neural transmission (Vienna, Austria : 1996) 2008, Molecular genetics of adult ADHD: converging evidence from genome-wide association and extended pedigree linkage studies., Journal of neural transmission (Vienna, Austria : 1996). [PubMed 18839057]

-  MalaCards Disease Associations
  MalaCards Gene Search: TLL2
Diseases sorted by gene-association score: autosomal recessive non-syndromic intellectual disability (1)

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene

+  Common Gene Haplotype Alleles
  Press "+" in the title bar above to open this section.

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 1.50 RPKM in Brain - Spinal cord (cervical c-1)
Total median expression: 15.39 RPKM



View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -97.20241-0.403 Picture PostScript Text
3' UTR -1024.613482-0.294 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR015446 - BMP_1/tolloid-like
IPR000859 - CUB
IPR000742 - EG-like_dom
IPR001881 - EGF-like_Ca-bd
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

Pfam Domains:
PF00431 - CUB domain
PF01400 - Astacin (Peptidase family M12A)
PF07645 - Calcium-binding EGF domain
PF12661 - Human growth factor-like EGF
PF14670 - Coagulation Factor Xa inhibitory site

SCOP Domains:
49854 - Spermadhesin, CUB domain
55486 - Metalloproteases ("zincins"), catalytic domain
57196 - EGF/Laminin

ModBase Predicted Comparative 3D Structure on Q9Y6L7
FrontTopSide
The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.

-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
No orthologNo orthologNo orthologNo orthologNo orthologNo ortholog
Gene Details     
Gene Sorter     
      
      
      

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0004222 metalloendopeptidase activity
GO:0004252 serine-type endopeptidase activity
GO:0005509 calcium ion binding
GO:0008233 peptidase activity
GO:0008237 metallopeptidase activity
GO:0008270 zinc ion binding
GO:0016787 hydrolase activity
GO:0046872 metal ion binding

Biological Process:
GO:0006508 proteolysis
GO:0007275 multicellular organism development
GO:0022617 extracellular matrix disassembly
GO:0030154 cell differentiation
GO:0048632 negative regulation of skeletal muscle tissue growth

Cellular Component:
GO:0005576 extracellular region


-  Descriptions from all associated GenBank mRNAs
  AB023149 - Homo sapiens KIAA0932 mRNA for KIAA0932 protein.
BC112341 - Homo sapiens tolloid-like 2, mRNA (cDNA clone MGC:133312 IMAGE:40038720), complete cds.
BC112366 - Homo sapiens tolloid-like 2, mRNA (cDNA clone MGC:133313 IMAGE:40038726), complete cds.
AF059516 - Homo sapiens tolloid-like 2 protein (TLL2) mRNA, complete cds.
BC113577 - Homo sapiens tolloid-like 2, mRNA (cDNA clone MGC:142137 IMAGE:8322629), complete cds.
BC111599 - Synthetic construct Homo sapiens clone IMAGE:40080557, MGC:133420 TLL2 protein (TLL2) mRNA, encodes complete protein.
AB384048 - Synthetic construct DNA, clone: pF1KSDA0932, Homo sapiens TLL2 gene for tolloid-like protein 2 precursor, complete cds, without stop codon, in Flexi system.
BC013871 - Homo sapiens tolloid-like 2, mRNA (cDNA clone IMAGE:3836889), partial cds.
BC030548 - Homo sapiens cDNA clone IMAGE:5182610, containing frame-shift errors.
AK026106 - Homo sapiens cDNA: FLJ22453 fis, clone HRC09679, highly similar to AF059516 Homo sapiens tolloid-like 2 protein (TLL2) mRNA.
JD053476 - Sequence 34500 from Patent EP1572962.
JD508554 - Sequence 489578 from Patent EP1572962.
JD504169 - Sequence 485193 from Patent EP1572962.
JD504030 - Sequence 485054 from Patent EP1572962.
JD553714 - Sequence 534738 from Patent EP1572962.
JD501334 - Sequence 482358 from Patent EP1572962.
JD062330 - Sequence 43354 from Patent EP1572962.
JD276469 - Sequence 257493 from Patent EP1572962.
JD050002 - Sequence 31026 from Patent EP1572962.
JD350491 - Sequence 331515 from Patent EP1572962.
JD504709 - Sequence 485733 from Patent EP1572962.
JD300902 - Sequence 281926 from Patent EP1572962.
JD166662 - Sequence 147686 from Patent EP1572962.
JD251792 - Sequence 232816 from Patent EP1572962.
JD418362 - Sequence 399386 from Patent EP1572962.
JD339367 - Sequence 320391 from Patent EP1572962.
JD083336 - Sequence 64360 from Patent EP1572962.
JD176613 - Sequence 157637 from Patent EP1572962.
JD424990 - Sequence 406014 from Patent EP1572962.
JD496979 - Sequence 478003 from Patent EP1572962.
JD177431 - Sequence 158455 from Patent EP1572962.
JD501760 - Sequence 482784 from Patent EP1572962.
JD453356 - Sequence 434380 from Patent EP1572962.
JD303471 - Sequence 284495 from Patent EP1572962.
JD436207 - Sequence 417231 from Patent EP1572962.
JD245810 - Sequence 226834 from Patent EP1572962.
JD475533 - Sequence 456557 from Patent EP1572962.
JD424872 - Sequence 405896 from Patent EP1572962.
JD480020 - Sequence 461044 from Patent EP1572962.
JD432325 - Sequence 413349 from Patent EP1572962.
JD483480 - Sequence 464504 from Patent EP1572962.
JD112968 - Sequence 93992 from Patent EP1572962.
JD131174 - Sequence 112198 from Patent EP1572962.
JD273584 - Sequence 254608 from Patent EP1572962.
JD520610 - Sequence 501634 from Patent EP1572962.
JD304188 - Sequence 285212 from Patent EP1572962.
JD188611 - Sequence 169635 from Patent EP1572962.
JD048435 - Sequence 29459 from Patent EP1572962.
JD094606 - Sequence 75630 from Patent EP1572962.
CQ873774 - Sequence 193 from Patent WO2004076622.
DD413611 - Regulation of Mammalian Cells.
JD229442 - Sequence 210466 from Patent EP1572962.
JD461696 - Sequence 442720 from Patent EP1572962.
JD271692 - Sequence 252716 from Patent EP1572962.

-  Biochemical and Signaling Pathways
  Reactome (by CSHL, EBI, and GO)

Protein Q9Y6L7 (Reactome details) participates in the following event(s):

R-HSA-3814820 HSPG2 (perlecan) is cleaved by BMP1, TLL1, TLL2, Cathepsin L1
R-HSA-2214330 Cleavage of collagen VII NC2 region by BMP1
R-HSA-2002440 Removal of fibrillar collagen C-propeptides
R-HSA-2022141 Prolysyl oxidase activation
R-HSA-1474228 Degradation of the extracellular matrix
R-HSA-2214320 Anchoring fibril formation
R-HSA-1650814 Collagen biosynthesis and modifying enzymes
R-HSA-2243919 Crosslinking of collagen fibrils
R-HSA-1474244 Extracellular matrix organization
R-HSA-2022090 Assembly of collagen fibrils and other multimeric structures
R-HSA-1474290 Collagen formation

-  Other Names for This Gene
  Alternate Gene Symbols: A6NDK0, KIAA0932, NM_012465, NP_036597, Q2M1H1, Q6PJN5, Q9UQ00, Q9Y6L7, TLL2_HUMAN
UCSC ID: uc001kml.2
RefSeq Accession: NM_012465
Protein: Q9Y6L7 (aka TLL2_HUMAN)
CCDS: CCDS7449.1

-  Gene Model Information
 
category: coding nonsense-mediated-decay: no RNA accession: NM_012465.3
exon count: 21CDS single in 3' UTR: no RNA size: 6788
ORF size: 3048CDS single in intron: no Alignment % ID: 100.00
txCdsPredict score: 6109.00frame shift in genome: no % Coverage: 99.75
has start codon: yes stop codon in genome: no # of Alignments: 1
has end codon: yes retained intron: no # AT/AC introns 0
selenocysteine: no end bleed into intron: 0# strange splices: 0
Click here for a detailed description of the fields of the table above.

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.