UniProtKB - Q6ZXV5 (TMTC3_HUMAN)
Protein
Protein O-mannosyl-transferase TMTC3
Gene
TMTC3
Organism
Homo sapiens (Human)
Status
Functioni
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.2 Publications
Catalytic activityi
- dolichyl β-D-mannosyl phosphate + L-seryl-[protein] = 3-O-(α-D-mannosyl)-L-seryl-[protein] + dolichyl phosphate + H+1 PublicationEC:2.4.1.1091 PublicationThis reaction proceeds in the forward1 Publication direction.
- dolichyl β-D-mannosyl phosphate + L-threonyl-[protein] = 3-O-(α-D-mannosyl)-L-threonyl-[protein] + dolichyl phosphate + H+1 PublicationEC:2.4.1.1091 PublicationThis reaction proceeds in the forward1 Publication direction.
: protein glycosylation Pathwayi
This protein is involved in the pathway protein glycosylation, which is part of Protein modification.1 PublicationView all proteins of this organism that are known to be involved in the pathway protein glycosylation and in Protein modification.
GO - Molecular functioni
- dolichyl-phosphate-mannose-protein mannosyltransferase activity Source: UniProtKB-EC
- mannosyltransferase activity Source: UniProtKB
GO - Biological processi
- positive regulation of proteasomal protein catabolic process Source: UniProtKB
- protein O-linked mannosylation Source: UniProtKB
- response to endoplasmic reticulum stress Source: UniProtKB
Keywordsi
Molecular function | Transferase |
Enzyme and pathway databases
PathwayCommonsi | Q6ZXV5 |
UniPathwayi | UPA00378 |
Protein family/group databases
TCDBi | 8.A.95.1.1, the transmembrane and tpr repeat-containing protein 3 (tmtc3) family |
Names & Taxonomyi
Protein namesi | Recommended name: Protein O-mannosyl-transferase TMTC3Curated (EC:2.4.1.1091 Publication)Alternative name(s): Protein SMILE1 Publication Transmembrane and TPR repeat-containing protein 3Imported |
Gene namesi | Name:TMTC3Imported |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:26899, TMTC3 |
MIMi | 617218, gene |
neXtProti | NX_Q6ZXV5 |
VEuPathDBi | HostDB:ENSG00000139324.11 |
Subcellular locationi
Endoplasmic reticulum
- Endoplasmic reticulum 1 Publication
Other locations
- Membrane Curated; Multi-pass membrane protein Curated
Note: In odontoblast cultures, it colocalizes with PDIA3 in the endoplasmic reticulum.1 Publication
Endoplasmic reticulum
- endoplasmic reticulum Source: UniProtKB
Other locations
- integral component of membrane Source: UniProtKB-KW
Topology
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Transmembranei | 9 – 29 | HelicalSequence analysisAdd BLAST | 21 | |
Transmembranei | 94 – 114 | HelicalSequence analysisAdd BLAST | 21 | |
Transmembranei | 136 – 158 | HelicalSequence analysisAdd BLAST | 23 | |
Transmembranei | 167 – 187 | HelicalSequence analysisAdd BLAST | 21 | |
Transmembranei | 194 – 214 | HelicalSequence analysisAdd BLAST | 21 | |
Transmembranei | 232 – 252 | HelicalSequence analysisAdd BLAST | 21 | |
Transmembranei | 318 – 338 | HelicalSequence analysisAdd BLAST | 21 | |
Transmembranei | 354 – 374 | HelicalSequence analysisAdd BLAST | 21 | |
Transmembranei | 377 – 397 | HelicalSequence analysisAdd BLAST | 21 |
Keywords - Cellular componenti
Endoplasmic reticulum, MembranePathology & Biotechi
Involvement in diseasei
Lissencephaly 8 (LIS8)1 Publication
The disease is caused by variants affecting the gene represented in this entry.
Disease descriptionA 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.
Related information in OMIMFeature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_077900 | 67 | H → D in LIS8. 1 Publication | 1 | |
Natural variantiVAR_077901 | 384 | G → E in LIS8. 1 Publication | 1 |
Keywords - Diseasei
Disease variant, LissencephalyOrganism-specific databases
DisGeNETi | 160418 |
MalaCardsi | TMTC3 |
MIMi | 617255, phenotype |
OpenTargetsi | ENSG00000139324 |
Orphaneti | 98892, Periventricular nodular heterotopia |
PharmGKBi | PA142670720 |
Miscellaneous databases
Pharosi | Q6ZXV5, Tdark |
Genetic variation databases
BioMutai | TMTC3 |
DMDMi | 134035047 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000280293 | 1 – 915 | Protein O-mannosyl-transferase TMTC3Add BLAST | 915 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Glycosylationi | 117 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Glycosylationi | 494 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Modified residuei | 503 | PhosphotyrosineCombined sources | 1 | |
Glycosylationi | 541 | N-linked (GlcNAc...) asparagineSequence analysis | 1 |
Keywords - PTMi
Glycoprotein, PhosphoproteinProteomic databases
EPDi | Q6ZXV5 |
jPOSTi | Q6ZXV5 |
MassIVEi | Q6ZXV5 |
MaxQBi | Q6ZXV5 |
PaxDbi | Q6ZXV5 |
PeptideAtlasi | Q6ZXV5 |
PRIDEi | Q6ZXV5 |
ProteomicsDBi | 68498 [Q6ZXV5-1] 68499 [Q6ZXV5-2] |
PTM databases
GlyGeni | Q6ZXV5, 4 sites, 2 N-linked glycans (1 site) |
iPTMneti | Q6ZXV5 |
PhosphoSitePlusi | Q6ZXV5 |
SwissPalmi | Q6ZXV5 |
Expressioni
Gene expression databases
Bgeei | ENSG00000139324, Expressed in endothelial cell and 215 other tissues |
ExpressionAtlasi | Q6ZXV5, baseline and differential |
Genevisiblei | Q6ZXV5, HS |
Organism-specific databases
HPAi | ENSG00000139324, Low tissue specificity |
Interactioni
Binary interactionsi
Q6ZXV5
With | #Exp. | IntAct |
---|---|---|
DAB1 [O75553] | 3 | EBI-10188441,EBI-7875264 |
Protein-protein interaction databases
BioGRIDi | 127757, 49 interactors |
IntActi | Q6ZXV5, 17 interactors |
STRINGi | 9606.ENSP00000266712 |
Miscellaneous databases
RNActi | Q6ZXV5, protein |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Repeati | 412 – 445 | TPR 1Add BLAST | 34 | |
Repeati | 446 – 479 | TPR 2Add BLAST | 34 | |
Repeati | 481 – 513 | TPR 3Add BLAST | 33 | |
Repeati | 528 – 562 | TPR 4Add BLAST | 35 | |
Repeati | 563 – 596 | TPR 5Add BLAST | 34 | |
Repeati | 597 – 631 | TPR 6Add BLAST | 35 | |
Repeati | 669 – 702 | TPR 7Add BLAST | 34 | |
Repeati | 704 – 736 | TPR 8Add BLAST | 33 | |
Repeati | 737 – 771 | TPR 9Add BLAST | 35 | |
Repeati | 773 – 805 | TPR 10Add BLAST | 33 |
Sequence similaritiesi
Belongs to the TMTC family.Curated
Keywords - Domaini
Repeat, TPR repeat, Transmembrane, Transmembrane helixPhylogenomic databases
eggNOGi | KOG1124, Eukaryota |
GeneTreei | ENSGT00940000157538 |
HOGENOMi | CLU_011615_1_0_1 |
InParanoidi | Q6ZXV5 |
OMAi | SDYVQAY |
PhylomeDBi | Q6ZXV5 |
TreeFami | TF328339 |
Family and domain databases
Gene3Di | 1.25.40.10, 4 hits |
InterProi | View protein in InterPro IPR013618, DUF1736 IPR013026, TPR-contain_dom IPR011990, TPR-like_helical_dom_sf IPR019734, TPR_repeat |
Pfami | View protein in Pfam PF08409, DUF1736, 1 hit PF13174, TPR_6, 1 hit PF13181, TPR_8, 3 hits |
SMARTi | View protein in SMART SM00028, TPR, 9 hits |
SUPFAMi | SSF48452, SSF48452, 2 hits |
PROSITEi | View protein in PROSITE PS50005, TPR, 9 hits PS50293, TPR_REGION, 1 hit |
s (2+)i Sequence
Sequence statusi: Complete.
This entry describes 2 produced by isoformsialternative splicing. AlignAdd to basketThis entry has 2 described isoforms and 3 potential isoforms that are computationally mapped.Show allAlign All
Isoform 1 (identifier: Q6ZXV5-1) [UniParc]FASTAAdd to basket
This isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
10 20 30 40 50
MANINLKEIT LIVGVVTACY WNSLFCGFVF DDVSAILDNK DLHPSTPLKT
60 70 80 90 100
LFQNDFWGTP MSEERSHKSY RPLTVLTFRL NYLLSELKPM SYHLLNMIFH
110 120 130 140 150
AVVSVIFLKV CKLFLDNKSS VIASLLFAVH PIHTEAVTGV VGRAELLSSI
160 170 180 190 200
FFLAAFLSYT RSKGPDNSII WTPIALTVFL VAVATLCKEQ GITVVGICCV
210 220 230 240 250
YEVFIAQGYT LPLLCTTAGQ FLRGKGSIPF SMLQTLVKLI VLMFSTLLLV
260 270 280 290 300
VIRVQVIQSQ LPVFTRFDNP AAVSPTPTRQ LTFNYLLPVN AWLLLNPSEL
310 320 330 340 350
CCDWTMGTIP LIESLLDIRN LATFTFFCFL GMLGVFSIRY SGDSSKTVLM
360 370 380 390 400
ALCLMALPFI PASNLFFPVG FVVAERVLYV PSMGFCILVA HGWQKISTKS
410 420 430 440 450
VFKKLSWICL SMVILTHSLK TFHRNWDWES EYTLFMSALK VNKNNAKLWN
460 470 480 490 500
NVGHALENEK NFERALKYFL QATHVQPDDI GAHMNVGRTY KNLNRTKEAE
510 520 530 540 550
ESYMMAKSLM PQIIPGKKYA ARIAPNHLNV YINLANLIRA NESRLEEADQ
560 570 580 590 600
LYRQAISMRP DFKQAYISRG ELLLKMNKPL KAKEAYLKAL ELDRNNADLW
610 620 630 640 650
YNLAIVHIEL KEPNEALKKN FNRALELNPK HKLALFNSAI VMQESGEVKL
660 670 680 690 700
RPEARKRLLS YINEEPLDAN GYFNLGMLAM DDKKDNEAEI WMKKAIKLQA
710 720 730 740 750
DFRSALFNLA LLYSQTAKEL KALPILEELL RYYPDHIKGL ILKGDILMNQ
760 770 780 790 800
KKDILGAKKC FERILEMDPS NVQGKHNLCV VYFEEKDLLK AERCLLETLA
810 820 830 840 850
LAPHEEYIQR HLNIVRDKIS SSSFIEPIFP TSKISSVEGK KIPTESVKEI
860 870 880 890 900
RGESRQTQIV KTSDNKSQSK SNKQLGKNGD EETPHKTTKD IKEIEKKRVA
910
ALKRLEEIER ILNGE
Computationally mapped potential isoform sequencesi
There are 3 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketF8VRY4 | F8VRY4_HUMAN | Protein O-mannosyl-transferase TMTC... | TMTC3 | 406 | Annotation score: | ||
F8VR71 | F8VR71_HUMAN | Protein O-mannosyl-transferase TMTC... | TMTC3 | 145 | Annotation score: | ||
F8W044 | F8W044_HUMAN | Protein O-mannosyl-transferase TMTC... | TMTC3 | 148 | Annotation score: |
Sequence cautioni
The sequence BAC11325 differs from that shown. Reason: Erroneous initiation. Truncated N-terminus.Curated
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 120 | S → R in CAH18164 (PubMed:17974005).Curated | 1 | |
Sequence conflicti | 158 | S → P in BAC11325 (PubMed:15489334).Curated | 1 | |
Sequence conflicti | 201 | Y → C in BAC11325 (PubMed:15489334).Curated | 1 | |
Sequence conflicti | 348 | V → G in CAD98046 (PubMed:17974005).Curated | 1 | |
Sequence conflicti | 489 | T → A in CAH18100 (PubMed:17974005).Curated | 1 | |
Sequence conflicti | 538 | I → V in CAI45938 (PubMed:17974005).Curated | 1 | |
Sequence conflicti | 639 | A → V in CAD98046 (PubMed:17974005).Curated | 1 | |
Sequence conflicti | 864 | D → N in CAD98046 (PubMed:17974005).Curated | 1 | |
Sequence conflicti | 883 | T → A in CAD98046 (PubMed:17974005).Curated | 1 |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_077900 | 67 | H → D in LIS8. 1 Publication | 1 | |
Natural variantiVAR_077901 | 384 | G → E in LIS8. 1 Publication | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_023619 | 618 | Missing in isoform 2. 4 Publications | 1 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AJ697717 mRNA Translation: CAG26973.1 BX538169 mRNA Translation: CAD98046.1 CR749244 mRNA Translation: CAH18100.1 CR749309 mRNA Translation: CAH18164.1 CR933632 mRNA Translation: CAI45938.1 CR936640 mRNA Translation: CAI56780.1 BC117175 mRNA Translation: AAI17176.1 BC117177 mRNA Translation: AAI17178.1 AK074973 mRNA Translation: BAC11325.1 Different initiation. |
CCDSi | CCDS9032.1 [Q6ZXV5-2] |
RefSeqi | NP_861448.2, NM_181783.3 [Q6ZXV5-2] |
Genome annotation databases
Ensembli | ENST00000266712; ENSP00000266712; ENSG00000139324 [Q6ZXV5-2] |
GeneIDi | 160418 |
KEGGi | hsa:160418 |
UCSCi | uc001tau.3, human [Q6ZXV5-1] |
Keywords - Coding sequence diversityi
Alternative splicingSimilar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AJ697717 mRNA Translation: CAG26973.1 BX538169 mRNA Translation: CAD98046.1 CR749244 mRNA Translation: CAH18100.1 CR749309 mRNA Translation: CAH18164.1 CR933632 mRNA Translation: CAI45938.1 CR936640 mRNA Translation: CAI56780.1 BC117175 mRNA Translation: AAI17176.1 BC117177 mRNA Translation: AAI17178.1 AK074973 mRNA Translation: BAC11325.1 Different initiation. |
CCDSi | CCDS9032.1 [Q6ZXV5-2] |
RefSeqi | NP_861448.2, NM_181783.3 [Q6ZXV5-2] |
3D structure databases
SMRi | Q6ZXV5 |
ModBasei | Search... |
Protein-protein interaction databases
BioGRIDi | 127757, 49 interactors |
IntActi | Q6ZXV5, 17 interactors |
STRINGi | 9606.ENSP00000266712 |
Protein family/group databases
TCDBi | 8.A.95.1.1, the transmembrane and tpr repeat-containing protein 3 (tmtc3) family |
PTM databases
GlyGeni | Q6ZXV5, 4 sites, 2 N-linked glycans (1 site) |
iPTMneti | Q6ZXV5 |
PhosphoSitePlusi | Q6ZXV5 |
SwissPalmi | Q6ZXV5 |
Genetic variation databases
BioMutai | TMTC3 |
DMDMi | 134035047 |
Proteomic databases
EPDi | Q6ZXV5 |
jPOSTi | Q6ZXV5 |
MassIVEi | Q6ZXV5 |
MaxQBi | Q6ZXV5 |
PaxDbi | Q6ZXV5 |
PeptideAtlasi | Q6ZXV5 |
PRIDEi | Q6ZXV5 |
ProteomicsDBi | 68498 [Q6ZXV5-1] 68499 [Q6ZXV5-2] |
Protocols and materials databases
Antibodypediai | 52318, 21 antibodies |
DNASUi | 160418 |
Genome annotation databases
Ensembli | ENST00000266712; ENSP00000266712; ENSG00000139324 [Q6ZXV5-2] |
GeneIDi | 160418 |
KEGGi | hsa:160418 |
UCSCi | uc001tau.3, human [Q6ZXV5-1] |
Organism-specific databases
CTDi | 160418 |
DisGeNETi | 160418 |
GeneCardsi | TMTC3 |
HGNCi | HGNC:26899, TMTC3 |
HPAi | ENSG00000139324, Low tissue specificity |
MalaCardsi | TMTC3 |
MIMi | 617218, gene 617255, phenotype |
neXtProti | NX_Q6ZXV5 |
OpenTargetsi | ENSG00000139324 |
Orphaneti | 98892, Periventricular nodular heterotopia |
PharmGKBi | PA142670720 |
VEuPathDBi | HostDB:ENSG00000139324.11 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG1124, Eukaryota |
GeneTreei | ENSGT00940000157538 |
HOGENOMi | CLU_011615_1_0_1 |
InParanoidi | Q6ZXV5 |
OMAi | SDYVQAY |
PhylomeDBi | Q6ZXV5 |
TreeFami | TF328339 |
Enzyme and pathway databases
UniPathwayi | UPA00378 |
PathwayCommonsi | Q6ZXV5 |
Miscellaneous databases
BioGRID-ORCSi | 160418, 11 hits in 874 CRISPR screens |
ChiTaRSi | TMTC3, human |
GenomeRNAii | 160418 |
Pharosi | Q6ZXV5, Tdark |
PROi | PR:Q6ZXV5 |
RNActi | Q6ZXV5, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000139324, Expressed in endothelial cell and 215 other tissues |
ExpressionAtlasi | Q6ZXV5, baseline and differential |
Genevisiblei | Q6ZXV5, HS |
Family and domain databases
Gene3Di | 1.25.40.10, 4 hits |
InterProi | View protein in InterPro IPR013618, DUF1736 IPR013026, TPR-contain_dom IPR011990, TPR-like_helical_dom_sf IPR019734, TPR_repeat |
Pfami | View protein in Pfam PF08409, DUF1736, 1 hit PF13174, TPR_6, 1 hit PF13181, TPR_8, 3 hits |
SMARTi | View protein in SMART SM00028, TPR, 9 hits |
SUPFAMi | SSF48452, SSF48452, 2 hits |
PROSITEi | View protein in PROSITE PS50005, TPR, 9 hits PS50293, TPR_REGION, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | TMTC3_HUMAN | |
Accessioni | Q6ZXV5Primary (citable) accession number: Q6ZXV5 Secondary accession number(s): Q5CZ86 Q8NC50 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | March 20, 2007 |
Last sequence update: | March 20, 2007 | |
Last modified: | February 10, 2021 | |
This is version 140 of the entry and version 2 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any 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
Reference proteomeDocuments
- Human chromosome 12
Human chromosome 12: entries, gene names and cross-references to MIM - Human entries with genetic variants
List of human entries with genetic variants - Human variants curated from literature reports
Index of human variants curated from literature reports - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - PATHWAY comments
Index of metabolic and biosynthesis pathways - SIMILARITY comments
Index of protein domains and families