This gene encodes a protein that belongs to the transmembrane and tetratricopeptide repeat-containing protein family. [provided by RefSeq, May 2010] See more...

Aliases for TMTC3 Gene

Aliases for TMTC3 Gene

  • Transmembrane O-Mannosyltransferase Targeting Cadherins 3 2 3
  • Transmembrane And Tetratricopeptide Repeat Containing 3 2 3 5
  • Transmembrane And TPR Repeat-Containing Protein 3 3 4
  • Protein O-Mannosyl-Transferase TMTC3 3 4
  • Protein SMILE 4
  • EC 2.4.1.109 4
  • SMILE 3
  • LIS8 3

External Ids for TMTC3 Gene

Previous GeneCards Identifiers for TMTC3 Gene

  • GC12P087042
  • GC12P088536
  • GC12P085603

Summaries for TMTC3 Gene

Entrez Gene Summary for TMTC3 Gene

  • This gene encodes a protein that belongs to the transmembrane and tetratricopeptide repeat-containing protein family. [provided by RefSeq, May 2010]

GeneCards Summary for TMTC3 Gene

TMTC3 (Transmembrane O-Mannosyltransferase Targeting Cadherins 3) is a Protein Coding gene. Diseases associated with TMTC3 include Lissencephaly 8 and Periventricular Nodular Heterotopia. An important paralog of this gene is TMTC4.

UniProtKB/Swiss-Prot Summary for TMTC3 Gene

  • Transfers mannosyl residues to the hydroxyl group of serine or threonine residues. The 4 members of the TMTC family are O-mannosyl-transferases dedicated primarily to the cadherin superfamily, each member seems to have a distinct role in decorating the cadherin domains with O-linked mannose glycans at specific regions. Also acts as O-mannosyl-transferase on other proteins such as PDIA3 (PubMed:28973932). Involved in the positive regulation of proteasomal protein degradation in the endoplasmic reticulum (ER), and the control of ER stress response.

Additional gene information for TMTC3 Gene

No data available for CIViC Summary , Tocris Summary , Gene Wiki entry , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for TMTC3 Gene

Genomics for TMTC3 Gene

GeneHancer (GH) Regulatory Elements for TMTC3 Gene

Promoters and enhancers for TMTC3 Gene
GeneHancer (GH) Identifier GH Type GH
Score
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH12J088142 Promoter/Enhancer 2 EPDnew Ensembl ENCODE CraniofacialAtlas 750.6 +0.2 205 3 SIN3A ZNF24 ZBTB40 SIX5 ZBTB6 FOXA1 MLX RBPJ POLR2A ATF1 CEP290 TMTC3 piR-61803
GH12J088577 Promoter/Enhancer 2.1 EPDnew Ensembl ENCODE CraniofacialAtlas dbSUPER 10.6 +436.0 436004 6.6 CTCF POLR2A RAD21 ZNF121 MNT MTA3 BCL6B SP1 ZNF384 MAFK KITLG TMTC3 ENSG00000281333 HSALNG0092900
GH12J088034 Promoter/Enhancer 2 EPDnew Ensembl ENCODE CraniofacialAtlas 9.1 -106.0 -105995 3 SIN3A ZBTB40 SIX5 MLX POLR2A USF2 CREB1 HCFC1 MIXL1 ZNF362 C12orf29 C12orf50 HSALNG0092879 CEP290 TMTC3 RNA5SP364
GH12J088297 Enhancer 1.4 FANTOM5 Ensembl ENCODE dbSUPER 9.3 +157.5 157486 4 ZNF24 SP1 POLR2A USF2 HCFC1 JUND ETV6 RELA L3MBTL2 RAD21 lnc-TMTC3-18 TMTC3 C12orf29 RF00017-1199
GH12J088942 Enhancer 1 Ensembl ENCODE dbSUPER 11.2 +803.3 803281 5.2 CTCF ZNF133 MAX MAFK FOSL2 IKZF1 PKNOX1 NFE2L2 JUN SOX13 ENSG00000258302 CEP290 TMTC3 piR-48965-032 HSALNG0092925
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around TMTC3 on UCSC Golden Path with GeneCards custom track

Top Transcription factor binding sites by QIAGEN in the TMTC3 gene promoter:
  • ATF-2
  • Bach1
  • CUTL1
  • GATA-1
  • HFH-1
  • Ik-3
  • Pbx1a
  • POU2F1
  • POU2F1a
  • POU3F1

Genomic Locations for TMTC3 Gene

Genomic Locations for TMTC3 Gene
chr12:88,142,296-88,199,887
(GRCh38/hg38)
Size:
57,592 bases
Orientation:
Plus strand
chr12:88,536,073-88,593,664
(GRCh37/hg19)
Size:
57,592 bases
Orientation:
Plus strand

Genomic View for TMTC3 Gene

Genes around TMTC3 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
TMTC3 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for TMTC3 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for TMTC3 Gene

Proteins for TMTC3 Gene

  • Protein details for TMTC3 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q6ZXV5-TMTC3_HUMAN
    Recommended name:
    Protein O-mannosyl-transferase TMTC3
    Protein Accession:
    Q6ZXV5
    Secondary Accessions:
    • Q5CZ86
    • Q5H9T6
    • Q68DQ6
    • Q68DX0
    • Q7Z332
    • Q8NC50

    Protein attributes for TMTC3 Gene

    Size:
    915 amino acids
    Molecular mass:
    104009 Da
    Quaternary structure:
    No Data Available
    SequenceCaution:
    • Sequence=BAC11325.1; Type=Erroneous initiation; Note=Translation N-terminally extended.; Evidence={ECO:0000305};

    Alternative splice isoforms for TMTC3 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for TMTC3 Gene

Post-translational modifications for TMTC3 Gene

  • Glycosylation at Asn117, Asn494, Asn541, and Thr844
  • Ubiquitination at Lys460 and Lys738
  • Modification sites at PhosphoSitePlus

Other Protein References for TMTC3 Gene

No data available for DME Specific Peptides for TMTC3 Gene

Domains & Families for TMTC3 Gene

Gene Families for TMTC3 Gene

Protein Domains for TMTC3 Gene

Suggested Antigen Peptide Sequences for TMTC3 Gene

GenScript: Design optimal peptide antigens:
  • Protein SMILE (TMTC3_HUMAN)

Graphical View of Domain Structure for InterPro Entry

Q6ZXV5

UniProtKB/Swiss-Prot:

TMTC3_HUMAN :
  • Belongs to the TMTC family.
Family:
  • Belongs to the TMTC family.
genes like me logo Genes that share domains with TMTC3: view

Function for TMTC3 Gene

Molecular function for TMTC3 Gene

UniProtKB/Swiss-Prot Function:
Transfers mannosyl residues to the hydroxyl group of serine or threonine residues. The 4 members of the TMTC family are O-mannosyl-transferases dedicated primarily to the cadherin superfamily, each member seems to have a distinct role in decorating the cadherin domains with O-linked mannose glycans at specific regions. Also acts as O-mannosyl-transferase on other proteins such as PDIA3 (PubMed:28973932). Involved in the positive regulation of proteasomal protein degradation in the endoplasmic reticulum (ER), and the control of ER stress response.
UniProtKB/Swiss-Prot CatalyticActivity:
Reaction=dolichyl beta-D-mannosyl phosphate + L-seryl-[protein] = 3-O-(alpha-D-mannosyl)-L-seryl-[protein] + dolichyl phosphate + H(+); Xref=Rhea:RHEA:17377, Rhea:RHEA-COMP:9517, Rhea:RHEA-COMP:9527, Rhea:RHEA-COMP:9863, Rhea:RHEA-COMP:13546, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:57683, ChEBI:CHEBI:58211, ChEBI:CHEBI:137321; EC=2.4.1.109; Evidence=. ; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:17378; Evidence=. ;.
UniProtKB/Swiss-Prot CatalyticActivity:
Reaction=dolichyl beta-D-mannosyl phosphate + L-threonyl-[protein] = 3-O-(alpha-D-mannosyl)-L-threonyl-[protein] + dolichyl phosphate + H(+); Xref=Rhea:RHEA:53396, Rhea:RHEA-COMP:9517, Rhea:RHEA-COMP:9527, Rhea:RHEA-COMP:11060, Rhea:RHEA-COMP:13547, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013, ChEBI:CHEBI:57683, ChEBI:CHEBI:58211, ChEBI:CHEBI:137323; EC=2.4.1.109; Evidence=. ; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:53397; Evidence=. ;.

Enzyme Numbers (IUBMB) for TMTC3 Gene

Phenotypes From GWAS Catalog for TMTC3 Gene

Gene Ontology (GO) - Molecular Function for TMTC3 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000030 mannosyltransferase activity IMP 28973932
GO:0004169 dolichyl-phosphate-mannose-protein mannosyltransferase activity IEA --
GO:0005515 protein binding IPI 25416956
GO:0016740 transferase activity IEA --
genes like me logo Genes that share ontologies with TMTC3: view
genes like me logo Genes that share phenotypes with TMTC3: view

Human Phenotype Ontology for TMTC3 Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Models for TMTC3 Gene

MGI Knock Outs for TMTC3:
  • Tmtc3 Tmtc3<tm1b(EUCOMM)Wtsi>

Animal Model Products

CRISPR Products

miRNA for TMTC3 Gene

miRTarBase miRNAs that target TMTC3

Clone Products

  • Addgene plasmids for TMTC3

No data available for Transcription Factor Targets and HOMER Transcription for TMTC3 Gene

Localization for TMTC3 Gene

Subcellular locations from UniProtKB/Swiss-Prot for TMTC3 Gene

Membrane; Multi-pass membrane protein. Endoplasmic reticulum. Note=In odontoblast cultures, it colocalizes with PDIA3 in the endoplasmic reticulum. {ECO:0000269 PubMed:21603654}.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for TMTC3 gene
Compartment Confidence
endoplasmic reticulum 5
cytoskeleton 2
plasma membrane 0

Gene Ontology (GO) - Cellular Components for TMTC3 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005783 endoplasmic reticulum IEA,IDA 21603654
GO:0016020 membrane IEA --
GO:0016021 integral component of membrane IEA --
genes like me logo Genes that share ontologies with TMTC3: view

No data available for Subcellular locations from the Human Protein Atlas (HPA) for TMTC3 Gene

Pathways & Interactions for TMTC3 Gene

PathCards logo

SuperPathways for TMTC3 Gene

No Data Available

UniProtKB/Swiss-Prot Q6ZXV5-TMTC3_HUMAN

  • Pathway: Protein modification; protein glycosylation.

Gene Ontology (GO) - Biological Process for TMTC3 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006486 protein glycosylation IEA --
GO:0034976 response to endoplasmic reticulum stress IMP 21603654
GO:0035269 protein O-linked mannosylation IMP 28973932
GO:1901800 positive regulation of proteasomal protein catabolic process IMP 21603654
genes like me logo Genes that share ontologies with TMTC3: view

No data available for Pathways by source and SIGNOR curated interactions for TMTC3 Gene

Drugs & Compounds for TMTC3 Gene

No Compound Related Data Available

Transcripts for TMTC3 Gene

CRISPR Products

Clone Products

  • Addgene plasmids for TMTC3

Alternative Splicing Database (ASD) splice patterns (SP) for TMTC3 Gene

No ASD Table

Relevant External Links for TMTC3 Gene

GeneLoc Exon Structure for
TMTC3
ECgene alternative splicing isoforms for
TMTC3

Expression for TMTC3 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and CGAP SAGE for TMTC3 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

Protein differential expression in normal tissues from HIPED for TMTC3 Gene

This gene is overexpressed in Nasal epithelium (26.5), Breast (17.2), and Cervix (8.7).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for TMTC3 Gene



NURSA nuclear receptor signaling pathways regulating expression of TMTC3 Gene:

TMTC3

SOURCE GeneReport for Unigene cluster for TMTC3 Gene:

Hs.331268

Evidence on tissue expression from TISSUES for TMTC3 Gene

  • Nervous system(4.3)
  • Intestine(4.2)
genes like me logo Genes that share expression patterns with TMTC3: view

No data available for mRNA differential expression in normal tissues , Protein tissue co-expression partners , mRNA Expression by UniProt/SwissProt and Phenotype-based relationships between genes and organs from Gene ORGANizer for TMTC3 Gene

Orthologs for TMTC3 Gene

This gene was present in the common ancestor of animals.

Orthologs for TMTC3 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia TMTC3 33 32
  • 99.78 (n)
OneToOne
dog
(Canis familiaris)
Mammalia TMTC3 33 32
  • 93.29 (n)
OneToOne
cow
(Bos Taurus)
Mammalia TMTC3 33 32
  • 92.38 (n)
OneToOne
rat
(Rattus norvegicus)
Mammalia Tmtc3 32
  • 86.67 (n)
oppossum
(Monodelphis domestica)
Mammalia TMTC3 33
  • 86 (a)
OneToOne
mouse
(Mus musculus)
Mammalia Tmtc3 17 33 32
  • 85.54 (n)
platypus
(Ornithorhynchus anatinus)
Mammalia TMTC3 33
  • 83 (a)
OneToOne
chicken
(Gallus gallus)
Aves TMTC3 33 32
  • 78.44 (n)
OneToOne
lizard
(Anolis carolinensis)
Reptilia TMTC3 33
  • 84 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia Str.10499 32
zebrafish
(Danio rerio)
Actinopterygii tmtc3 33 32
  • 66.45 (n)
OneToOne
African malaria mosquito
(Anopheles gambiae)
Insecta AgaP_AGAP010599 32
  • 56.36 (n)
fruit fly
(Drosophila melanogaster)
Insecta CG4050 33 32
  • 53.84 (n)
OneToOne
sea squirt
(Ciona savignyi)
Ascidiacea -- 33
  • 42 (a)
OneToOne
Species where no ortholog for TMTC3 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)
  • worm (Caenorhabditis elegans)

Evolution for TMTC3 Gene

ENSEMBL:
Gene Tree for TMTC3 (if available)
TreeFam:
Gene Tree for TMTC3 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for TMTC3: view image

Paralogs for TMTC3 Gene

(3) SIMAP similar genes for TMTC3 Gene using alignment to 5 proteins:

  • TMTC3_HUMAN
  • F8VR71_HUMAN
  • F8VRY4_HUMAN
  • F8W044_HUMAN
  • L8ECP4_HUMAN
genes like me logo Genes that share paralogs with TMTC3: view

Variants for TMTC3 Gene

Sequence variations from dbSNP and Humsavar for TMTC3 Gene

SNP ID Clin Chr 12 pos Variation AA Info Type
rs1057517696 pathogenic, Lissencephaly 8 88,188,871(+) AA/A coding_sequence_variant, frameshift, non_coding_transcript_variant
rs1057517697 pathogenic, Lissencephaly 8 88,195,521(+) C/T coding_sequence_variant, non_coding_transcript_variant, stop_gained
rs1057517698 pathogenic, Lissencephaly 8 88,148,318(+) G/A initiator_codon_variant, intron_variant, missense_variant, non_coding_transcript_variant
rs1057519417 pathogenic, Lissencephaly 8 88,194,863(+) T/TTT coding_sequence_variant, frameshift, non_coding_transcript_variant
rs1264332374 uncertain-significance, Joubert syndrome, Meckel-Gruber syndrome, Nephronophthisis 88,140,985(+) G/A/T upstream_transcript_variant

Structural Variations from Database of Genomic Variants (DGV) for TMTC3 Gene

Variant ID Type Subtype PubMed ID
nsv1132853 CNV insertion 24896259
nsv483111 CNV loss 15286789
nsv807 CNV deletion 18451855
nsv826471 CNV loss 20364138
nsv826472 CNV gain 20364138

Variation tolerance for TMTC3 Gene

Residual Variation Intolerance Score: 11.1% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 5.91; 74.35% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for TMTC3 Gene

Human Gene Mutation Database (HGMD)
TMTC3
SNPedia medical, phenotypic, and genealogical associations of SNPs for
TMTC3

SNP Genotyping and Copy Number Assay Products

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for TMTC3 Gene

Disorders for TMTC3 Gene

MalaCards: The human disease database

(10) MalaCards diseases for TMTC3 Gene - From: HGMD, OMIM, ClinVar, GTR, Orphanet, DISEASES, and GeneCards

Disorder Aliases PubMed IDs
lissencephaly 8
  • lis8
periventricular nodular heterotopia
  • periventricular heterotopia
lissencephaly
joubert syndrome 5
  • jbts5
meckel syndrome, type 4
  • mks4
- elite association - COSMIC cancer census association via MalaCards
Search TMTC3 in MalaCards View complete list of genes associated with diseases

UniProtKB/Swiss-Prot

TMTC3_HUMAN
  • Lissencephaly 8 (LIS8) [MIM:617255]: A form of lissencephaly, a disorder of cortical development characterized by agyria or pachygyria and disorganization of the clear neuronal lamination of normal six-layered cortex. LIS8 patients manifest delayed psychomotor development, intellectual disability with poor or absent speech, early-onset refractory seizures, hypotonia, cortical gyral abnormalities, and hypoplasia of the corpus callosum, brainstem and cerebellum. LIS8 inheritance is autosomal recessive. {ECO:0000269 PubMed:27773428}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Additional Disease Information for TMTC3

genes like me logo Genes that share disorders with TMTC3: view

No data available for Genatlas for TMTC3 Gene

Publications for TMTC3 Gene

  1. Discovery of an O-mannosylation pathway selectively serving cadherins and protocadherins. (PMID: 28973932) Larsen ISB … Halim A (Proceedings of the National Academy of Sciences of the United States of America 2017) 3 4 56
  2. The involvement of SMILE/TMTC3 in endoplasmic reticulum stress response. (PMID: 21603654) Racapé M … Brouard S (PloS one 2011) 3 4 56
  3. Complete sequencing and characterization of 21,243 full-length human cDNAs. (PMID: 14702039) Ota T … Sugano S (Nature genetics 2004) 3 4 56
  4. The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). (PMID: 15489334) Gerhard DS … MGC Project Team (Genome research 2004) 3 4 56
  5. VIRMA mediates preferential m6A mRNA methylation in 3'UTR and near stop codon and associates with alternative polyadenylation. (PMID: 29507755) Yue Y … Liu J (Cell discovery 2018) 3 56

Products for TMTC3 Gene

Sources for TMTC3 Gene