UniProtKB - Q8IU68 (TMC8_HUMAN)
Protein
Transmembrane channel-like protein 8
Gene
TMC8
Organism
Homo sapiens (Human)
Status
Functioni
Probable ion channel.By similarity
GO - Molecular functioni
- mechanosensitive ion channel activity Source: GO_Central
- protein sequestering activity Source: UniProtKB
- tumor necrosis factor binding Source: UniProtKB
GO - Biological processi
- negative regulation of protein binding Source: UniProtKB
- negative regulation of protein-containing complex assembly Source: UniProtKB
- regulation of cell growth Source: UniProtKB
- regulation of extrinsic apoptotic signaling pathway via death domain receptors Source: UniProtKB
- zinc ion homeostasis Source: UniProtKB
Keywordsi
Molecular function | Ion channel |
Biological process | Ion transport, Transport |
Enzyme and pathway databases
PathwayCommonsi | Q8IU68 |
Protein family/group databases
TCDBi | 1.A.17.4.11, the calcium-dependent chloride channel (ca-clc) family |
Names & Taxonomyi
Protein namesi | Recommended name: Transmembrane channel-like protein 8Alternative name(s): Epidermodysplasia verruciformis protein 2 |
Gene namesi | Name:TMC8 Synonyms:EVER2, EVIN2 |
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:20474, TMC8 |
MIMi | 605829, gene |
neXtProti | NX_Q8IU68 |
VEuPathDBi | HostDB:ENSG00000167895.14 |
Subcellular locationi
Endoplasmic reticulum
- Endoplasmic reticulum membrane 1 Publication; Multi-pass membrane protein 1 Publication
Endoplasmic reticulum
- endoplasmic reticulum Source: UniProtKB
- endoplasmic reticulum membrane Source: UniProtKB-SubCell
Extracellular region or secreted
- extracellular exosome Source: UniProtKB
- extracellular space Source: UniProtKB
Golgi apparatus
- Golgi apparatus Source: UniProtKB
Nucleus
- nuclear membrane Source: UniProtKB
Plasma Membrane
- integral component of plasma membrane Source: InterPro
Other locations
- cytoplasm Source: UniProtKB
Topology
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Topological domaini | 1 – 114 | CytoplasmicSequence analysisAdd BLAST | 114 | |
Transmembranei | 115 – 135 | HelicalSequence analysisAdd BLAST | 21 | |
Topological domaini | 136 – 200 | LumenalSequence analysisAdd BLAST | 65 | |
Transmembranei | 201 – 221 | HelicalSequence analysisAdd BLAST | 21 | |
Topological domaini | 222 – 299 | CytoplasmicSequence analysisAdd BLAST | 78 | |
Transmembranei | 300 – 320 | HelicalSequence analysisAdd BLAST | 21 | |
Topological domaini | 321 – 338 | LumenalSequence analysisAdd BLAST | 18 | |
Transmembranei | 339 – 359 | HelicalSequence analysisAdd BLAST | 21 | |
Topological domaini | 360 – 426 | CytoplasmicSequence analysisAdd BLAST | 67 | |
Transmembranei | 427 – 447 | HelicalSequence analysisAdd BLAST | 21 | |
Topological domaini | 448 – 488 | LumenalSequence analysisAdd BLAST | 41 | |
Transmembranei | 489 – 509 | HelicalSequence analysisAdd BLAST | 21 | |
Topological domaini | 510 – 531 | CytoplasmicSequence analysisAdd BLAST | 22 | |
Transmembranei | 532 – 552 | HelicalSequence analysisAdd BLAST | 21 | |
Topological domaini | 553 – 594 | LumenalSequence analysisAdd BLAST | 42 | |
Transmembranei | 595 – 615 | HelicalSequence analysisAdd BLAST | 21 | |
Topological domaini | 616 – 726 | CytoplasmicSequence analysisAdd BLAST | 111 |
Keywords - Cellular componenti
Endoplasmic reticulum, MembranePathology & Biotechi
Involvement in diseasei
Epidermodysplasia verruciformis 2 (EV2)2 Publications
The disease is caused by variants affecting the gene represented in this entry.
Disease descriptionA form of epidermodysplasia verruciformis, a rare genodermatosis associated with a high risk of skin carcinoma that results from an abnormal susceptibility to infection by specific human papillomaviruses, including the oncogenic HPV5. Infection leads to the early development of disseminated flat wart-like and pityriasis versicolor-like skin lesions. Cutaneous Bowen's carcinomas in situ and invasive squamous cell carcinomas develop in about half of the patients, mainly on sun-exposed skin areas. EV2 inheritance is autosomal recessive.
Related information in OMIMFeature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_081777 | 362 – 726 | Missing in EV2. 1 PublicationAdd BLAST | 365 |
Keywords - Diseasei
Disease variantOrganism-specific databases
DisGeNETi | 147138 |
MalaCardsi | TMC8 |
MIMi | 618231, phenotype |
OpenTargetsi | ENSG00000167895 |
Orphaneti | 302, Epidermodysplasia verruciformis |
PharmGKBi | PA134892288 |
Miscellaneous databases
Pharosi | Q8IU68, Tbio |
Genetic variation databases
BioMutai | TMC8 |
DMDMi | 74714272 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000185386 | 1 – 726 | Transmembrane channel-like protein 8Add BLAST | 726 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 6 | PhosphoserineBy similarity | 1 | |
Glycosylationi | 148 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Glycosylationi | 567 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Modified residuei | 658 | PhosphoserineCombined sources | 1 | |
Modified residuei | 673 | PhosphoserineBy similarity | 1 |
Keywords - PTMi
Glycoprotein, PhosphoproteinProteomic databases
jPOSTi | Q8IU68 |
MassIVEi | Q8IU68 |
PaxDbi | Q8IU68 |
PeptideAtlasi | Q8IU68 |
PRIDEi | Q8IU68 |
ProteomicsDBi | 70513 [Q8IU68-1] 70514 [Q8IU68-2] |
PTM databases
GlyGeni | Q8IU68, 2 sites |
iPTMneti | Q8IU68 |
PhosphoSitePlusi | Q8IU68 |
SwissPalmi | Q8IU68 |
Expressioni
Tissue specificityi
Expressed in placenta, prostate and testis.1 Publication
Gene expression databases
Bgeei | ENSG00000167895, Expressed in granulocyte and 178 other tissues |
ExpressionAtlasi | Q8IU68, baseline and differential |
Genevisiblei | Q8IU68, HS |
Organism-specific databases
HPAi | ENSG00000167895, Tissue enhanced (bone marrow, intestine, lymphoid tissue) |
Interactioni
Subunit structurei
Interacts with CIB1.
1 PublicationGO - Molecular functioni
- tumor necrosis factor binding Source: UniProtKB
Protein-protein interaction databases
BioGRIDi | 127037, 5 interactors |
IntActi | Q8IU68, 1 interactor |
STRINGi | 9606.ENSP00000325561 |
Miscellaneous databases
RNActi | Q8IU68, protein |
Family & Domainsi
Sequence similaritiesi
Belongs to the TMC family.Curated
Keywords - Domaini
Transmembrane, Transmembrane helixPhylogenomic databases
eggNOGi | ENOG502RKT7, Eukaryota |
GeneTreei | ENSGT00980000198578 |
HOGENOMi | CLU_013958_3_1_1 |
InParanoidi | Q8IU68 |
OMAi | TNTYLFY |
OrthoDBi | 1048914at2759 |
PhylomeDBi | Q8IU68 |
TreeFami | TF313462 |
Family and domain databases
InterProi | View protein in InterPro IPR038900, TMC IPR012496, TMC_dom |
PANTHERi | PTHR23302, PTHR23302, 1 hit |
Pfami | View protein in Pfam PF07810, TMC, 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 1 potential isoform that is computationally mapped.Show allAlign All
Isoform 1 (identifier: Q8IU68-1) [UniParc]FASTAAdd to basket
Also known as: Large EVER2
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
MLLPRSVSSE RAPGVPEPEE LWEAEMERLR GSGTPVRGLP YAMMDKRLIW
60 70 80 90 100
QLREPAGVQT LRWQRWQRRR QTVERRLREA AQRLARGLGL WEGALYEIGG
110 120 130 140 150
LFGTGIRSYF TFLRFLLLLN LLSLLLTASF VLLPLVWLRP PDPGPTLNLT
160 170 180 190 200
LQCPGSRQSP PGVLRFHNQL WHVLTGRAFT NTYLFYGAYR VGPESSSVYS
210 220 230 240 250
IRLAYLLSPL ACLLLCFCGT LRRMVKGLPQ KTLLGQGYQA PLSAKVFSSW
260 270 280 290 300
DFCIRVQEAA TIKKHEISNE FKVELEEGRR FQLMQQQTRA QTACRLLSYL
310 320 330 340 350
RVNVLNGLLV VGAISAIFWA TKYSQDNKEE SLFLLLQYLP PGVIALVNFL
360 370 380 390 400
GPLLFTFLVQ LENYPPNTEV NLTLIWCVVL KLASLGMFSV SLGQTILCIG
410 420 430 440 450
RDKSSCESYG YNVCDYQCWE NSVGEELYKL SIFNFLLTVA FAFLVTLPRR
460 470 480 490 500
LLVDRFSGRF WAWLEREEFL VPKNVLDIVA GQTVTWMGLF YCPLLPLLNS
510 520 530 540 550
VFLFLTFYIK KYTLLKNSRA SSRPFRASSS TFFFQLVLLL GLLLAAVPLG
560 570 580 590 600
YVVSSIHSSW DCGLFTNYSA PWQVVPELVA LGLPPIGQRA LHYLGSHAFS
610 620 630 640 650
FPLLIMLSLV LTVCVSQTQA NARAIHRLRK QLVWQVQEKW HLVEDLSRLL
660 670 680 690 700
PEPGPSDSPG PKYPASQASR PQSFCPGCPC PGSPGHQAPR PGPSVVDAAG
710 720
LRSPCPGQHG APASARRFRF PSGAEL
Computationally mapped potential isoform sequencesi
There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basketK7EJ72 | K7EJ72_HUMAN | Transmembrane channel-like protein ... | TMC8 | 196 | Annotation score: |
Sequence cautioni
The sequence BAC03459 differs from that shown. Reason: Erroneous initiation. Extended N-terminus.Curated
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 5 | R → W in BAC03459 (Ref. 3) Curated | 1 |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_023964 | 306 | N → I2 PublicationsCorresponds to variant dbSNP:rs7208422EnsemblClinVar. | 1 | |
Natural variantiVAR_081777 | 362 – 726 | Missing in EV2. 1 PublicationAdd BLAST | 365 | |
Natural variantiVAR_052337 | 501 | V → I. Corresponds to variant dbSNP:rs11651675EnsemblClinVar. | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_016448 | 1 – 223 | Missing in isoform 2. 1 PublicationAdd BLAST | 223 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AY057380 mRNA Translation: AAL25837.1 AY099358 mRNA Translation: AAM44454.1 AY099359 mRNA Translation: AAM44455.1 AY236500 mRNA Translation: AAP69878.1 AK090478 mRNA Translation: BAC03459.1 Different initiation. AC021593 Genomic DNA No translation available. BC028076 mRNA No translation available. BC110296 mRNA Translation: AAI10297.1 |
CCDSi | CCDS32749.1 [Q8IU68-1] |
RefSeqi | NP_689681.2, NM_152468.4 [Q8IU68-1] |
Genome annotation databases
Ensembli | ENST00000318430; ENSP00000325561; ENSG00000167895 [Q8IU68-1] ENST00000589691; ENSP00000467482; ENSG00000167895 [Q8IU68-2] |
GeneIDi | 147138 |
KEGGi | hsa:147138 |
UCSCi | uc002jup.3, human [Q8IU68-1] |
Keywords - Coding sequence diversityi
Alternative splicingSimilar proteinsi
Cross-referencesi
Web resourcesi
TMC8base TMC8 mutation db |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AY057380 mRNA Translation: AAL25837.1 AY099358 mRNA Translation: AAM44454.1 AY099359 mRNA Translation: AAM44455.1 AY236500 mRNA Translation: AAP69878.1 AK090478 mRNA Translation: BAC03459.1 Different initiation. AC021593 Genomic DNA No translation available. BC028076 mRNA No translation available. BC110296 mRNA Translation: AAI10297.1 |
CCDSi | CCDS32749.1 [Q8IU68-1] |
RefSeqi | NP_689681.2, NM_152468.4 [Q8IU68-1] |
3D structure databases
ModBasei | Search... |
SWISS-MODEL-Workspacei | Submit a new modelling project... |
Protein-protein interaction databases
BioGRIDi | 127037, 5 interactors |
IntActi | Q8IU68, 1 interactor |
STRINGi | 9606.ENSP00000325561 |
Protein family/group databases
TCDBi | 1.A.17.4.11, the calcium-dependent chloride channel (ca-clc) family |
PTM databases
GlyGeni | Q8IU68, 2 sites |
iPTMneti | Q8IU68 |
PhosphoSitePlusi | Q8IU68 |
SwissPalmi | Q8IU68 |
Genetic variation databases
BioMutai | TMC8 |
DMDMi | 74714272 |
Proteomic databases
jPOSTi | Q8IU68 |
MassIVEi | Q8IU68 |
PaxDbi | Q8IU68 |
PeptideAtlasi | Q8IU68 |
PRIDEi | Q8IU68 |
ProteomicsDBi | 70513 [Q8IU68-1] 70514 [Q8IU68-2] |
Protocols and materials databases
Antibodypediai | 32534, 196 antibodies |
Genome annotation databases
Ensembli | ENST00000318430; ENSP00000325561; ENSG00000167895 [Q8IU68-1] ENST00000589691; ENSP00000467482; ENSG00000167895 [Q8IU68-2] |
GeneIDi | 147138 |
KEGGi | hsa:147138 |
UCSCi | uc002jup.3, human [Q8IU68-1] |
Organism-specific databases
CTDi | 147138 |
DisGeNETi | 147138 |
GeneCardsi | TMC8 |
HGNCi | HGNC:20474, TMC8 |
HPAi | ENSG00000167895, Tissue enhanced (bone marrow, intestine, lymphoid tissue) |
MalaCardsi | TMC8 |
MIMi | 605829, gene 618231, phenotype |
neXtProti | NX_Q8IU68 |
OpenTargetsi | ENSG00000167895 |
Orphaneti | 302, Epidermodysplasia verruciformis |
PharmGKBi | PA134892288 |
VEuPathDBi | HostDB:ENSG00000167895.14 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | ENOG502RKT7, Eukaryota |
GeneTreei | ENSGT00980000198578 |
HOGENOMi | CLU_013958_3_1_1 |
InParanoidi | Q8IU68 |
OMAi | TNTYLFY |
OrthoDBi | 1048914at2759 |
PhylomeDBi | Q8IU68 |
TreeFami | TF313462 |
Enzyme and pathway databases
PathwayCommonsi | Q8IU68 |
Miscellaneous databases
BioGRID-ORCSi | 147138, 7 hits in 990 CRISPR screens |
ChiTaRSi | TMC8, human |
GeneWikii | TMC8 |
GenomeRNAii | 147138 |
Pharosi | Q8IU68, Tbio |
PROi | PR:Q8IU68 |
RNActi | Q8IU68, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000167895, Expressed in granulocyte and 178 other tissues |
ExpressionAtlasi | Q8IU68, baseline and differential |
Genevisiblei | Q8IU68, HS |
Family and domain databases
InterProi | View protein in InterPro IPR038900, TMC IPR012496, TMC_dom |
PANTHERi | PTHR23302, PTHR23302, 1 hit |
Pfami | View protein in Pfam PF07810, TMC, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | TMC8_HUMAN | |
Accessioni | Q8IU68Primary (citable) accession number: Q8IU68 Secondary accession number(s): Q2YDC0 Q8NF04 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | December 6, 2005 |
Last sequence update: | March 1, 2003 | |
Last modified: | April 7, 2021 | |
This is version 137 of the entry and version 1 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 17
Human chromosome 17: 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 - SIMILARITY comments
Index of protein domains and families