Q7Z403 (TMC6_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Transmembrane channel-like protein 6

Alternative name(s):
Epidermodysplasia verruciformis protein 1
Protein LAK-4

Gene names

Name:	TMC6
Synonyms:	EVER1, EVIN1

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	805 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, testis, activated T-lymphocytes and lymphokine-activated killer (LAK) lymphocytes. Ref.2 Ref.3
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.
Sequence similarities	Belongs to the TMC family.
Sequence caution	The sequence AAH35648.1 differs from that shown. Reason: Erroneous initiation. The sequence BAA24179.2 differs from that shown. Reason: Erroneous initiation. The sequence BAB84891.1 differs from that shown. Reason: Erroneous initiation.

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 4 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q7Z403-1)

Also known as: Large EVER1;

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: Q7Z403-2)

Also known as: Small EVER1;

The sequence of this isoform differs from the canonical sequence as follows:
     410-760: Missing.

Isoform 3 (identifier: Q7Z403-3)

The sequence of this isoform differs from the canonical sequence as follows:
     1-361: Missing.
     512-571: Missing.

Note: No experimental confirmation available.

Isoform 4 (identifier: Q7Z403-4)

The sequence of this isoform differs from the canonical sequence as follows:
     1-227: Missing.
     513-525: NLILKLAILGTLC → CVAAHENIIWCWS
     526-805: Missing.

Note: No experimental confirmation available.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 805	805	Transmembrane channel-like protein 6		PRO_0000185384
Regions
	Topological domain	1 – 209	209	Lumenal Potential
	Transmembrane	210 – 230	21	Helical; Potential
	Topological domain	231 – 249	19	Cytoplasmic Potential
	Transmembrane	250 – 270	21	Helical; Potential
	Topological domain	271 – 338	68	Lumenal Potential
	Transmembrane	339 – 359	21	Helical; Potential
	Topological domain	360 – 431	72	Cytoplasmic Potential
	Transmembrane	432 – 452	21	Helical; Potential
	Topological domain	453 – 469	17	Lumenal Potential
	Transmembrane	470 – 490	21	Helical; Potential
	Topological domain	491 – 505	15	Cytoplasmic Potential
	Transmembrane	506 – 526	21	Helical; Potential
	Topological domain	527 – 553	27	Lumenal Potential
	Transmembrane	554 – 574	21	Helical; Potential
	Topological domain	575 – 604	30	Cytoplasmic Potential
	Transmembrane	605 – 625	21	Helical; Potential
	Topological domain	626 – 650	25	Lumenal Potential
	Transmembrane	651 – 671	21	Helical; Potential
	Topological domain	672 – 722	51	Cytoplasmic Potential
	Transmembrane	723 – 743	21	Helical; Potential
	Topological domain	744 – 805	62	Lumenal Potential
Amino acid modifications
	Glycosylation	103	1	N-linked (GlcNAc...) Potential
	Glycosylation	312	1	N-linked (GlcNAc...) Potential
Natural variations
	Alternative sequence	1 – 361	361	Missing in isoform 3.		VSP_016437
	Alternative sequence	1 – 227	227	Missing in isoform 4.		VSP_016438
	Alternative sequence	410 – 760	351	Missing in isoform 2.		VSP_016439
	Alternative sequence	512 – 571	60	Missing in isoform 3.		VSP_016440
	Alternative sequence	513 – 525	13	NLILK…LGTLC → CVAAHENIIWCWS in isoform 4.		VSP_016441
	Alternative sequence	526 – 805	280	Missing in isoform 4.		VSP_016442
	Natural variant	125	1	W → R. Ref.1 Corresponds to variant rs2748427 [ dbSNP | Ensembl ].		VAR_023963
	Natural variant	153	1	L → F. Ref.6 Corresponds to variant rs12449858 [ dbSNP | Ensembl ].		VAR_052336
	Natural variant	191	1	G → D. Corresponds to variant rs34712518 [ dbSNP | Ensembl ].		VAR_061851
Experimental info
	Sequence conflict	266	1	L → P in AAP69874. Ref.2
	Sequence conflict	274 – 277	4	QVAF → PRVR in AAH35648. Ref.6
	Sequence conflict	556	1	D → G in AAP69874. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (Large EVER1) [UniParc]. Last modified December 6, 2005. Version 2. Checksum: 9A9A5C43FBA86AD4	FASTA	805	90,045
	10 20 30 40 50 60 MAQPLAFILD VPETPGDQGQ GPSPYDESEV HDSFQQLIQE QSQCTAQEGL ELQQREREVT 70 80 90 100 110 120 GSSQQTLWRP EGTQSTATLR ILASMPSRTI GRSRGAIISQ YYNRTVQLRC RSSRPLLGNF 130 140 150 160 170 180 VRSAWPSLRL YDLELDPTAL EEEEKQSLLV KELQSLAVAQ RDHMLRGMPL SLAEKRSLRE 190 200 210 220 230 240 KSRTPRGKWR GQPGSGGVCS CCGRLRYACV LALHSLGLAL LSALQALMPW RYALKRIGGQ 250 260 270 280 290 300 FGSSVLSYFL FLKTLLAFNA LLLLLLVAFI MGPQVAFPPA LPGPAPVCTG LELLTGAGCF 310 320 330 340 350 360 THTVMYYGHY SNATLNQPCG SPLDGSQCTP RVGGLPYNMP LAYLSTVGVS FFITCITLVY 370 380 390 400 410 420 SMAHSFGESY RVGSTSGIHA ITVFCSWDYK VTQKRASRLQ QDNIRTRLKE LLAEWQLRHS 430 440 450 460 470 480 PRSVCGRLRQ AAVLGLVWLL CLGTALGCAV AVHVFSEFMI QSPEAAGQEA VLLVLPLVVG 490 500 510 520 530 540 LLNLGAPYLC RVLAALEPHD SPVLEVYVAI CRNLILKLAI LGTLCYHWLG RRVGVLQGQC 550 560 570 580 590 600 WEDFVGQELY RFLVMDFVLM LLDTLFGELV WRIISEKKLK RRRKPEFDIA RNVLELIYGQ 610 620 630 640 650 660 TLTWLGVLFS PLLPAVQIIK LLLVFYVKKT SLLANCQAPR RPWLASHMST VFLTLLCFPA 670 680 690 700 710 720 FLGAAVFLCY AVWQVKPSST CGPFRTLDTM YEAGRVWVRH LEAAGPRVSW LPWVHRYLME 730 740 750 760 770 780 NTFFVFLVSA LLLAVIYLNI QVVRGQRKVI CLLKEQISNE GEDKIFLINK LHSIYERKER 790 800 EERSRVGTTE EAAAPPALLT DEQDA
	Isoform 2 (Small EVER1) [UniParc]. Checksum: 0195CCD92CB21D94	FASTA	454	50,259
	10 20 30 40 50 60 MAQPLAFILD VPETPGDQGQ GPSPYDESEV HDSFQQLIQE QSQCTAQEGL ELQQREREVT 70 80 90 100 110 120 GSSQQTLWRP EGTQSTATLR ILASMPSRTI GRSRGAIISQ YYNRTVQLRC RSSRPLLGNF 130 140 150 160 170 180 VRSAWPSLRL YDLELDPTAL EEEEKQSLLV KELQSLAVAQ RDHMLRGMPL SLAEKRSLRE 190 200 210 220 230 240 KSRTPRGKWR GQPGSGGVCS CCGRLRYACV LALHSLGLAL LSALQALMPW RYALKRIGGQ 250 260 270 280 290 300 FGSSVLSYFL FLKTLLAFNA LLLLLLVAFI MGPQVAFPPA LPGPAPVCTG LELLTGAGCF 310 320 330 340 350 360 THTVMYYGHY SNATLNQPCG SPLDGSQCTP RVGGLPYNMP LAYLSTVGVS FFITCITLVY 370 380 390 400 410 420 SMAHSFGESY RVGSTSGIHA ITVFCSWDYK VTQKRASRLQ QDNIRTRLKG EDKIFLINKL 430 440 450 HSIYERKERE ERSRVGTTEE AAAPPALLTD EQDA
	Isoform 3 [UniParc]. Checksum: 845D2E11F8FCDCE2	FASTA	384	43,343
	10 20 30 40 50 60 MAHSFGESYR VGSTSGIHAI TVFCSWDYKV TQKRASRLQQ DNIRTRLKEL LAEWQLRHSP 70 80 90 100 110 120 RSVCGRLRQA AVLGLVWLLC LGTALGCAVA VHVFSEFMIQ SPEAAGQEAV LLVLPLVVGL 130 140 150 160 170 180 LNLGAPYLCR VLAALEPHDS PVLEVYVAIC RIISEKKLKR RRKPEFDIAR NVLELIYGQT 190 200 210 220 230 240 LTWLGVLFSP LLPAVQIIKL LLVFYVKKTS LLANCQAPRR PWLASHMSTV FLTLLCFPAF 250 260 270 280 290 300 LGAAVFLCYA VWQVKPSSTC GPFRTLDTMY EAGRVWVRHL EAAGPRVSWL PWVHRYLMEN 310 320 330 340 350 360 TFFVFLVSAL LLAVIYLNIQ VVRGQRKVIC LLKEQISNEG EDKIFLINKL HSIYERKERE 370 380 ERSRVGTTEE AAAPPALLTD EQDA
	Isoform 4 [UniParc]. Checksum: 249E60460853BA27	FASTA	298	32,485
	10 20 30 40 50 60 MPWRYALKRI GGQFGSSVLS YFLFLKTLLA FNALLLLLLV AFIMGPQVAF PPALPGPAPV 70 80 90 100 110 120 CTGLELLTGA GCFTHTVMYY GHYSNATLNQ PCGSPLDGSQ CTPRVGGLPY NMPLAYLSTV 130 140 150 160 170 180 GVSFFITCIT LVYSMAHSFG ESYRVGSTSG IHAITVFCSW DYKVTQKRAS RLQQDNIRTR 190 200 210 220 230 240 LKELLAEWQL RHSPRSVCGR LRQAAVLGLV WLLCLGTALG CAVAVHVFSE FMIQSPEAAG 250 260 270 280 290 QEAVLLVLPL VVGLLNLGAP YLCRVLAALE PHDSPVLEVY VAICRCVAAH ENIIWCWS

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 EPIDERMODYSPLASIA VERRUCIFORMIS, VARIANT ARG-125.
[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]	Lin L., Nong W., Zhou G., Ke R., Shen C., Zhong G., Zheng Z., Liang M., Wen S., Li H., Yang S. Submitted (JUN-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3), TISSUE SPECIFICITY.
[4]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 4).
[5]	"The nucleotide sequence of a long cDNA clone isolated from human spleen." Jikuya H., Takano J., Nomura N., Kikuno R., Nagase T., Ohara O. Submitted (JAN-2002) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Spleen.
[6]	"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), VARIANT PHE-153. Tissue: B-cell and Brain.
[7]	"LAK-4 clone from the membrane lymphotoxin expressing subtraction library." Abe Y., Takaoka Y. Submitted (MAR-1997) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 345-805. Tissue: Lymphoid tissue.
[8]	"Novel mutations of EVER1/TMC6 gene in a Japanese patient with epidermodysplasia verruciformis." Tate G., Suzuki T., Kishimoto K., Mitsuya T. J. Hum. Genet. 49:223-225(2004) [PubMed] [Europe PMC] [Abstract] Cited for: INVOLVEMENT IN EPIDERMODYSPLASIA VERRUCIFORMIS.
+	Additional computationally mapped references.

Web resources

TMC6base

TMC6 mutation db

Cross-references

Sequence databases
EMBL GenBank DDBJ	AY057379 mRNA. Translation: AAL25836.1. AY099356 mRNA. Translation: AAM44452.1. AY099357 mRNA. Translation: AAM44453.1. AY236496 mRNA. Translation: AAP69874.1. DQ104440 mRNA. Translation: AAZ20186.1. AK021738 mRNA. Translation: BAB13884.1. AK074065 mRNA. Translation: BAB84891.1. Different initiation. BC023597 mRNA. Translation: AAH23597.1. BC035648 mRNA. Translation: AAH35648.1. Different initiation. AB002405 mRNA. Translation: BAA24179.2. Different initiation.
IPI	IPI00165591. IPI00179046. IPI00332386. IPI00647669.
RefSeq	NP_001120670.1. NM_001127198.1. NP_009198.4. NM_007267.6.
UniGene	Hs.632227.
3D structure databases
ProteinModelPortal	Q7Z403.
ModBase	Search...
Protein-protein interaction databases
STRING	9606.ENSP00000313408.
PTM databases
PhosphoSite	Q7Z403.
Polymorphism databases
DMDM	83305925.
Proteomic databases
PaxDb	Q7Z403.
PRIDE	Q7Z403.
Protocols and materials databases
DNASU	11322.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000306591; ENSP00000306405; ENSG00000141524. ENST00000322914; ENSP00000313408; ENSG00000141524. ENST00000322933; ENSP00000313479; ENSG00000141524. ENST00000392467; ENSP00000376260; ENSG00000141524. ENST00000589553; ENSP00000465359; ENSG00000141524. ENST00000590602; ENSP00000465261; ENSG00000141524. ENST00000591436; ENSP00000464853; ENSG00000141524.
GeneID	11322.
KEGG	hsa:11322.
UCSC	uc002jui.1. human. uc002juj.1. human. uc002juo.2. human. uc010dhg.1. human.
Organism-specific databases
CTD	11322.
GeneCards	GC17M076108.
H-InvDB	HIX0200093.
HGNC	HGNC:18021. TMC6.
HPA	HPA051430.
MIM	226400. phenotype. 605828. gene.
neXtProt	NX_Q7Z403.
Orphanet	302. Epidermodysplasia verruciformis.
PharmGKB	PA134949466.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG78295.
HOVERGEN	HBG061579.
InParanoid	Q7Z403.
OMA	VYVAICR.
OrthoDB	EOG4NP73F.
Gene expression databases
ArrayExpress	Q7Z403.
Bgee	Q7Z403.
CleanEx	HS_TMC6.
Genevestigator	Q7Z403.
GermOnline	ENSG00000141524. Homo sapiens.
Family and domain databases
InterPro	IPR012496. TMC. [Graphical view]
Pfam	PF07810. TMC. 1 hit. [Graphical view]
ProtoNet	Search...
Other
GenomeRNAi	11322.
NextBio	43015.
SOURCE	Search...

Entry information

Entry name

TMC6_HUMAN

Accession

Primary (citable) accession number: Q7Z403
Secondary accession number(s): O43284 , Q45VJ2, Q8IU98, Q8IUI7, Q8IWU8, Q8TEQ7, Q9HAG5

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 6, 2005
Last sequence update:	December 6, 2005
Last modified:	May 1, 2013
This is version 81 of the entry and version 2 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.