Q8IU68 (TMC8_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Transmembrane channel-like protein 8

Alternative name(s):
Epidermodysplasia verruciformis protein 2

Gene names

Name:	TMC8
Synonyms:	EVER2, EVIN2

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	726 AA.
Sequence status	Complete.
Protein existence	Evidence 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 process	Ion transport Transport
Cellular component	Endoplasmic reticulum Membrane
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Transmembrane Transmembrane helix
Molecular function	Ion channel
PTM	Glycoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	ion transport Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	endoplasmic reticulum membrane Inferred from electronic annotation. Source: UniProtKB-SubCell integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW
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 key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 726	726	Transmembrane channel-like protein 8		PRO_0000185386
Regions
	Topological domain	1 – 114	114	Cytoplasmic Potential
	Transmembrane	115 – 135	21	Helical; Potential
	Topological domain	136 – 200	65	Lumenal Potential
	Transmembrane	201 – 221	21	Helical; Potential
	Topological domain	222 – 299	78	Cytoplasmic Potential
	Transmembrane	300 – 320	21	Helical; Potential
	Topological domain	321 – 338	18	Lumenal Potential
	Transmembrane	339 – 359	21	Helical; Potential
	Topological domain	360 – 426	67	Cytoplasmic Potential
	Transmembrane	427 – 447	21	Helical; Potential
	Topological domain	448 – 488	41	Lumenal Potential
	Transmembrane	489 – 509	21	Helical; Potential
	Topological domain	510 – 531	22	Cytoplasmic Potential
	Transmembrane	532 – 552	21	Helical; Potential
	Topological domain	553 – 594	42	Lumenal Potential
	Transmembrane	595 – 615	21	Helical; Potential
	Topological domain	616 – 726	111	Cytoplasmic Potential
Amino acid modifications
	Glycosylation	148	1	N-linked (GlcNAc...) Potential
	Glycosylation	567	1	N-linked (GlcNAc...) Potential
Natural variations
	Alternative sequence	1 – 223	223	Missing in isoform 2.		VSP_016448
	Natural variant	306	1	N → I. Ref.3 Corresponds to variant rs7208422 [ dbSNP | Ensembl ].		VAR_023964
	Natural variant	501	1	V → I. Corresponds to variant rs11651675 [ dbSNP | Ensembl ].		VAR_052337
Experimental info
	Sequence conflict	5	1	R → W in BAC03459. Ref.3

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (Large EVER2) [UniParc]. Last modified March 1, 2003. Version 1. Checksum: AA3F4A01A6C315EF	FASTA	726	81,641
	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
	Isoform 2 (Small EVER2) [UniParc]. Checksum: 9466295B76B989E7	FASTA	503	56,132
	10 20 30 40 50 60 MVKGLPQKTL LGQGYQAPLS AKVFSSWDFC IRVQEAATIK KHEISNEFKV ELEEGRRFQL 70 80 90 100 110 120 MQQQTRAQTA CRLLSYLRVN VLNGLLVVGA ISAIFWATKY SQDNKEESLF LLLQYLPPGV 130 140 150 160 170 180 IALVNFLGPL LFTFLVQLEN YPPNTEVNLT LIWCVVLKLA SLGMFSVSLG QTILCIGRDK 190 200 210 220 230 240 SSCESYGYNV CDYQCWENSV GEELYKLSIF NFLLTVAFAF LVTLPRRLLV DRFSGRFWAW 250 260 270 280 290 300 LEREEFLVPK NVLDIVAGQT VTWMGLFYCP LLPLLNSVFL FLTFYIKKYT LLKNSRASSR 310 320 330 340 350 360 PFRASSSTFF FQLVLLLGLL LAAVPLGYVV SSIHSSWDCG LFTNYSAPWQ VVPELVALGL 370 380 390 400 410 420 PPIGQRALHY LGSHAFSFPL LIMLSLVLTV CVSQTQANAR AIHRLRKQLV WQVQEKWHLV 430 440 450 460 470 480 EDLSRLLPEP GPSDSPGPKY PASQASRPQS FCPGCPCPGS PGHQAPRPGP SVVDAAGLRS 490 500 PCPGQHGAPA SARRFRFPSG AEL

References

	« Hide 'large scale' referencesShow '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. , 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.
IPI	IPI00182219. IPI00302538. IPI00655718.
RefSeq	NP_689681.2. NM_152468.4.
UniGene	Hs.592102.
3D structure databases
ProteinModelPortal	Q8IU68.
ModBase	Search...
Protein-protein interaction databases
STRING	9606.ENSP00000325561.
PTM databases
PhosphoSite	Q8IU68.
Polymorphism databases
DMDM	74714272.
Proteomic databases
PaxDb	Q8IU68.
PRIDE	Q8IU68.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000318430; ENSP00000325561; ENSG00000167895. ENST00000589691; ENSP00000467482; ENSG00000167895.
GeneID	147138.
KEGG	hsa:147138.
UCSC	uc002jup.2. human.
Organism-specific databases
CTD	147138.
GeneCards	GC17P076126.
H-InvDB	HIX0173689.
HGNC	HGNC:20474. TMC8.
HPA	HPA054429.
MIM	226400. phenotype. 605829. gene.
neXtProt	NX_Q8IU68.
Orphanet	302. Epidermodysplasia verruciformis.
PharmGKB	PA134892288.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG70493.
HOGENOM	HOG000038033.
HOVERGEN	HBG055908.
InParanoid	Q8IU68.
OMA	WEGALYE.
OrthoDB	EOG4FXR75.
Gene expression databases
ArrayExpress	Q8IU68.
Bgee	Q8IU68.
CleanEx	HS_TMC8.
Genevestigator	Q8IU68.
GermOnline	ENSG00000167895. Homo sapiens.
Family and domain databases
InterPro	IPR012496. TMC. [Graphical view]
Pfam	PF07810. TMC. 1 hit. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	TMC8. human.
GenomeRNAi	147138.
NextBio	85549.
SOURCE	Search...

Entry information

Entry name

TMC8_HUMAN

Accession

Primary (citable) accession number: Q8IU68
Secondary accession number(s): Q2YDC0 , Q8IWU7, Q8N358, Q8NF04

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 6, 2005
Last sequence update:	March 1, 2003
Last modified:	May 1, 2013
This is version 76 of the entry and version 1 of the sequence. [Complete history]

Entry status

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.