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Q8IU68 (TMC8_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 86. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Transmembrane channel-like protein 8
Alternative name(s):
Epidermodysplasia verruciformis protein 2
Gene names
Name:TMC8
Synonyms:EVER2, EVIN2
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length726 AA.
Sequence statusComplete.
Protein existenceEvidence at transcript level

General annotation (Comments)

Function

Probable ion channel By similarity.

Subcellular location

Endoplasmic reticulum membrane; Multi-pass membrane protein Ref.1.

Tissue specificity

Expressed in placenta, prostate and testis. Ref.2

Involvement in disease

Epidermodysplasia verruciformis (EV) [MIM:226400]: Rare autosomal recessive genodermatosis associated with a high risk of skin carcinoma that results from an abnormal susceptibility to infection by specific human papillomaviruses. Infection leads to persistent wart-like or macular lesions.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.1

Sequence similarities

Belongs to the TMC family.

Sequence caution

The sequence BAC03459.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.

The sequence BC028076 differs from that shown. Reason: Unlikely isoform. Aberrant splice sites.

Ontologies

Keywords
   Biological processIon transport
Transport
   Cellular componentEndoplasmic reticulum
Membrane
   Coding sequence diversityAlternative splicing
Polymorphism
   DomainTransmembrane
Transmembrane helix
   Molecular functionIon channel
   PTMGlycoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_procession transport

Inferred from electronic annotation. Source: UniProtKB-KW

negative regulation of protein binding

Inferred from direct assay PubMed 23429285. Source: UniProt

negative regulation of protein oligomerization

Inferred from direct assay PubMed 23429285. Source: UniProt

regulation of cell growth

Inferred from direct assay PubMed 18158319. Source: UniProt

regulation of extrinsic apoptotic signaling pathway via death domain receptors

Inferred from direct assay PubMed 23429285. Source: UniProt

zinc ion homeostasis

Inferred from direct assay PubMed 18158319. Source: UniProt

   Cellular_componentGolgi apparatus

Inferred from direct assay PubMed 18158319. Source: UniProt

cytoplasm

Inferred from direct assay Ref.1. Source: UniProt

endoplasmic reticulum

Inferred from direct assay Ref.1PubMed 18158319. Source: UniProt

endoplasmic reticulum membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

extracellular space

Inferred from direct assay PubMed 22664934. Source: UniProt

extracellular vesicular exosome

Inferred from direct assay PubMed 20458337. Source: UniProt

integral component of membrane

Inferred from electronic annotation. Source: UniProtKB-KW

nuclear membrane

Inferred from direct assay PubMed 18158319. Source: UniProt

   Molecular_functionprotein binding

Inferred from physical interaction PubMed 18158319. Source: UniProt

receptor binding

Inferred from physical interaction PubMed 23429285. Source: UniProt

Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q8IU68-1)

Also known as: Large EVER2;

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: Q8IU68-2)

Also known as: Small EVER2;

The sequence of this isoform differs from the canonical sequence as follows:
     1-223: Missing.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 726726Transmembrane channel-like protein 8
PRO_0000185386

Regions

Topological domain1 – 114114Cytoplasmic Potential
Transmembrane115 – 13521Helical; Potential
Topological domain136 – 20065Lumenal Potential
Transmembrane201 – 22121Helical; Potential
Topological domain222 – 29978Cytoplasmic Potential
Transmembrane300 – 32021Helical; Potential
Topological domain321 – 33818Lumenal Potential
Transmembrane339 – 35921Helical; Potential
Topological domain360 – 42667Cytoplasmic Potential
Transmembrane427 – 44721Helical; Potential
Topological domain448 – 48841Lumenal Potential
Transmembrane489 – 50921Helical; Potential
Topological domain510 – 53122Cytoplasmic Potential
Transmembrane532 – 55221Helical; Potential
Topological domain553 – 59442Lumenal Potential
Transmembrane595 – 61521Helical; Potential
Topological domain616 – 726111Cytoplasmic Potential

Amino acid modifications

Glycosylation1481N-linked (GlcNAc...) Potential
Glycosylation5671N-linked (GlcNAc...) Potential

Natural variations

Alternative sequence1 – 223223Missing in isoform 2.
VSP_016448
Natural variant3061N → I. Ref.3
Corresponds to variant rs7208422 [ dbSNP | Ensembl ].
VAR_023964
Natural variant5011V → I.
Corresponds to variant rs11651675 [ dbSNP | Ensembl ].
VAR_052337

Experimental info

Sequence conflict51R → W in BAC03459. Ref.3

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 (Large EVER2) [UniParc].

Last modified March 1, 2003. Version 1.
Checksum: AA3F4A01A6C315EF

FASTA72681,641
        10         20         30         40         50         60 
MLLPRSVSSE RAPGVPEPEE LWEAEMERLR GSGTPVRGLP YAMMDKRLIW QLREPAGVQT 

        70         80         90        100        110        120 
LRWQRWQRRR QTVERRLREA AQRLARGLGL WEGALYEIGG LFGTGIRSYF TFLRFLLLLN 

       130        140        150        160        170        180 
LLSLLLTASF VLLPLVWLRP PDPGPTLNLT LQCPGSRQSP PGVLRFHNQL WHVLTGRAFT 

       190        200        210        220        230        240 
NTYLFYGAYR VGPESSSVYS IRLAYLLSPL ACLLLCFCGT LRRMVKGLPQ KTLLGQGYQA 

       250        260        270        280        290        300 
PLSAKVFSSW DFCIRVQEAA TIKKHEISNE FKVELEEGRR FQLMQQQTRA QTACRLLSYL 

       310        320        330        340        350        360 
RVNVLNGLLV VGAISAIFWA TKYSQDNKEE SLFLLLQYLP PGVIALVNFL GPLLFTFLVQ 

       370        380        390        400        410        420 
LENYPPNTEV NLTLIWCVVL KLASLGMFSV SLGQTILCIG RDKSSCESYG YNVCDYQCWE 

       430        440        450        460        470        480 
NSVGEELYKL SIFNFLLTVA FAFLVTLPRR LLVDRFSGRF WAWLEREEFL VPKNVLDIVA 

       490        500        510        520        530        540 
GQTVTWMGLF YCPLLPLLNS VFLFLTFYIK KYTLLKNSRA SSRPFRASSS TFFFQLVLLL 

       550        560        570        580        590        600 
GLLLAAVPLG YVVSSIHSSW DCGLFTNYSA PWQVVPELVA LGLPPIGQRA LHYLGSHAFS 

       610        620        630        640        650        660 
FPLLIMLSLV LTVCVSQTQA NARAIHRLRK QLVWQVQEKW HLVEDLSRLL PEPGPSDSPG 

       670        680        690        700        710        720 
PKYPASQASR PQSFCPGCPC PGSPGHQAPR PGPSVVDAAG LRSPCPGQHG APASARRFRF 


PSGAEL 

« Hide

Isoform 2 (Small EVER2) [UniParc].

Checksum: 9466295B76B989E7
Show »

FASTA50356,132

References

« Hide 'large scale' references
[1]"Mutations in two adjacent novel genes are associated with epidermodysplasia verruciformis."
Ramoz N., Rueda L.-A., Bouadjar B., Montoya L.-S., Orth G., Favre M.
Nat. Genet. 32:579-581(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), SUBCELLULAR LOCATION, INVOLVEMENT IN EV.
[2]"Characterization of the transmembrane channel-like (TMC) gene family: functional clues from hearing loss and epidermodysplasia verruciformis."
Kurima K., Yang Y., Sorber K., Griffith A.J.
Genomics 82:300-308(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY.
[3]"The nucleotide sequence of a long cDNA clone isolated from human spleen."
Jikuya H., Takano J., Kikuno R., Nagase T., Ohara O.
Submitted (JUL-2002) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), VARIANT ILE-306.
Tissue: Spleen.
[4]"DNA sequence of human chromosome 17 and analysis of rearrangement in the human lineage."
Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R., Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A., Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J., Chang J.L. expand/collapse author list , Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J., DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., Gnerre S., Goldstein S., Grafham D.V., Grocock R., Hafez N., Hagopian D.S., Hart E., Norman C.H., Humphray S., Jaffe D.B., Jones M., Kamal M., Khodiyar V.K., LaButti K., Laird G., Lehoczky J., Liu X., Lokyitsang T., Loveland J., Lui A., Macdonald P., Major J.E., Matthews L., Mauceli E., McCarroll S.A., Mihalev A.H., Mudge J., Nguyen C., Nicol R., O'Leary S.B., Osoegawa K., Schwartz D.C., Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D., Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A., Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C.
Nature 440:1045-1049(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]"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] (ISOFORM 1).
Tissue: Blood.
+Additional computationally mapped references.

Web resources

TMC8base

TMC8 mutation db

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
CCDSCCDS32749.1. [Q8IU68-1]
RefSeqNP_689681.2. NM_152468.4. [Q8IU68-1]
XP_006721788.1. XM_006721725.1. [Q8IU68-2]
UniGeneHs.592102.

3D structure databases

ProteinModelPortalQ8IU68.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

STRING9606.ENSP00000325561.

PTM databases

PhosphoSiteQ8IU68.

Polymorphism databases

DMDM74714272.

Proteomic databases

PaxDbQ8IU68.
PRIDEQ8IU68.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000318430; ENSP00000325561; ENSG00000167895. [Q8IU68-1]
ENST00000589691; ENSP00000467482; ENSG00000167895. [Q8IU68-2]
GeneID147138.
KEGGhsa:147138.
UCSCuc002jup.2. human. [Q8IU68-1]

Organism-specific databases

CTD147138.
GeneCardsGC17P076126.
H-InvDBHIX0173689.
HGNCHGNC:20474. TMC8.
HPAHPA054429.
MIM226400. phenotype.
605829. gene.
neXtProtNX_Q8IU68.
Orphanet302. Epidermodysplasia verruciformis.
PharmGKBPA134892288.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG70493.
HOGENOMHOG000038033.
HOVERGENHBG055908.
InParanoidQ8IU68.
OMAWCVVLKL.
OrthoDBEOG73FQM9.
PhylomeDBQ8IU68.
TreeFamTF313462.

Gene expression databases

ArrayExpressQ8IU68.
BgeeQ8IU68.
CleanExHS_TMC8.
GenevestigatorQ8IU68.

Family and domain databases

InterProIPR012496. TMC.
[Graphical view]
PfamPF07810. TMC. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSTMC8. human.
GeneWikiTMC8.
GenomeRNAi147138.
NextBio85549.
PROQ8IU68.
SOURCESearch...

Entry information

Entry nameTMC8_HUMAN
AccessionPrimary (citable) accession number: Q8IU68
Secondary accession number(s): Q2YDC0 expand/collapse secondary AC list , Q8IWU7, Q8N358, Q8NF04
Entry history
Integrated into UniProtKB/Swiss-Prot: December 6, 2005
Last sequence update: March 1, 2003
Last modified: July 9, 2014
This is version 86 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

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 17

Human chromosome 17: entries, gene names and cross-references to MIM