TM266_HUMAN
ID TM266_HUMAN Reviewed; 531 AA.
AC Q2M3C6; Q8N993; Q96LL5;
DT 27-JUN-2006, integrated into UniProtKB/Swiss-Prot.
DT 09-JAN-2007, sequence version 2.
DT 03-AUG-2022, entry version 127.
DE RecName: Full=Transmembrane protein 266 {ECO:0000305};
DE Short=hTMEM266 {ECO:0000303|PubMed:30810529};
DE AltName: Full=HV1-related protein 1 {ECO:0000303|PubMed:25165868};
DE Short=HsHVRP1 {ECO:0000303|PubMed:25165868};
GN Name=TMEM266 {ECO:0000312|HGNC:HGNC:26763};
GN Synonyms=C15orf27 {ECO:0000312|HGNC:HGNC:26763},
GN HVRP1 {ECO:0000303|PubMed:25165868};
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16572171; DOI=10.1038/nature04601;
RA Zody M.C., Garber M., Sharpe T., Young S.K., Rowen L., O'Neill K.,
RA Whittaker C.A., Kamal M., Chang J.L., Cuomo C.A., Dewar K.,
RA FitzGerald M.G., Kodira C.D., Madan A., Qin S., Yang X., Abbasi N.,
RA Abouelleil A., Arachchi H.M., Baradarani L., Birditt B., Bloom S.,
RA Bloom T., Borowsky M.L., Burke J., Butler J., Cook A., DeArellano K.,
RA DeCaprio D., Dorris L. III, Dors M., Eichler E.E., Engels R., Fahey J.,
RA Fleetwood P., Friedman C., Gearin G., Hall J.L., Hensley G., Johnson E.,
RA Jones C., Kamat A., Kaur A., Locke D.P., Madan A., Munson G., Jaffe D.B.,
RA Lui A., Macdonald P., Mauceli E., Naylor J.W., Nesbitt R., Nicol R.,
RA O'Leary S.B., Ratcliffe A., Rounsley S., She X., Sneddon K.M.B.,
RA Stewart S., Sougnez C., Stone S.M., Topham K., Vincent D., Wang S.,
RA Zimmer A.R., Birren B.W., Hood L., Lander E.S., Nusbaum C.;
RT "Analysis of the DNA sequence and duplication history of human chromosome
RT 15.";
RL Nature 440:671-675(2006).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), AND VARIANTS HIS-391
RP AND LEU-427.
RC TISSUE=Fetal brain, and Testis;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 174-531.
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP SUBCELLULAR LOCATION.
RX PubMed=22020278; DOI=10.1038/nature10557;
RA Musset B., Smith S.M., Rajan S., Morgan D., Cherny V.V., Decoursey T.E.;
RT "Aspartate 112 is the selectivity filter of the human voltage-gated proton
RT channel.";
RL Nature 480:273-277(2011).
RN [5]
RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND MUTAGENESIS OF
RP 111-VAL--THR-116; 151-SER--THR-153; GLY-175; 184-PRO-MET-185; LYS-213 AND
RP 217-ASP--PRO-222.
RX PubMed=25165868; DOI=10.1371/journal.pone.0105926;
RA Kim I.H., Hevezi P., Varga C., Pathak M.M., Hong L., Ta D., Tran C.T.,
RA Zlotnik A., Soltesz I., Tombola F.;
RT "Evidence for functional diversity between the voltage-gated proton channel
RT Hv1 and its closest related protein HVRP1.";
RL PLoS ONE 9:E105926-E105926(2014).
RN [6]
RP FUNCTION, SUBUNIT, SUBCELLULAR LOCATION, AND DOMAIN.
RX PubMed=30810529; DOI=10.7554/elife.42372;
RA Papp F., Lomash S., Szilagyi O., Babikow E., Smith J., Chang T.H.,
RA Bahamonde M.I., Toombes G.E.S., Swartz K.J.;
RT "TMEM266 is a functional voltage sensor regulated by extracellular Zn2.";
RL Elife 8:0-0(2019).
CC -!- FUNCTION: Voltage-sensor protein present on the post-synaptic side of
CC glutamatergic mossy fibers and granule cells in the cerebellum
CC (PubMed:25165868, PubMed:30810529). Despite the presence of a voltage-
CC sensor segment, does not form a functional ion channel and its precise
CC role remains unclear (PubMed:25165868, PubMed:30810529). Undergoes both
CC rapid and slow structural rearrangements in response to changes in
CC voltage (PubMed:30810529). Contains a zinc-binding site that can
CC regulate the slow conformational transition (PubMed:30810529).
CC {ECO:0000269|PubMed:25165868, ECO:0000269|PubMed:30810529}.
CC -!- SUBUNIT: Homodimer; disulfide-linked. {ECO:0000269|PubMed:30810529}.
CC -!- INTERACTION:
CC Q2M3C6; O60341: KDM1A; NbExp=3; IntAct=EBI-12163061, EBI-710124;
CC Q2M3C6; Q6FHY5: MEOX2; NbExp=3; IntAct=EBI-12163061, EBI-16439278;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:22020278,
CC ECO:0000269|PubMed:25165868}; Multi-pass membrane protein
CC {ECO:0000255}. Cell projection, dendrite {ECO:0000269|PubMed:25165868}.
CC Perikaryon {ECO:0000269|PubMed:25165868}. Note=Present in the dendrites
CC and soma of cerebellar granule neurons, but not in their axon.
CC {ECO:0000269|PubMed:25165868}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q2M3C6-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q2M3C6-2; Sequence=VSP_022108;
CC -!- TISSUE SPECIFICITY: Mainly expressed in the cerebellum
CC (PubMed:25165868). Also expressed in cerebral cortex, skeletal muscle
CC and thyroid, but at much lower levels (PubMed:25165868).
CC {ECO:0000269|PubMed:25165868}.
CC -!- DOMAIN: The transmembrane segment S4 functions as voltage-sensor and is
CC characterized by a series of positively charged amino acids at every
CC third position (PubMed:30810529). Transplantation of the transmembrane
CC segment S4 into HVCN1, generates a functional voltage-activated proton
CC channel (PubMed:30810529). {ECO:0000269|PubMed:30810529}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAI04954.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC Sequence=AAI04956.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC Sequence=BAB71676.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC Sequence=BAC04562.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; AC091100; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AK058126; BAB71676.1; ALT_INIT; mRNA.
DR EMBL; AK095509; BAC04562.1; ALT_FRAME; mRNA.
DR EMBL; BC104953; AAI04954.1; ALT_INIT; mRNA.
DR EMBL; BC104955; AAI04956.1; ALT_INIT; mRNA.
DR CCDS; CCDS10289.2; -. [Q2M3C6-1]
DR RefSeq; NP_689548.2; NM_152335.2. [Q2M3C6-1]
DR RefSeq; XP_005254217.1; XM_005254160.2.
DR RefSeq; XP_016877404.1; XM_017021915.1. [Q2M3C6-1]
DR RefSeq; XP_016877405.1; XM_017021916.1.
DR RefSeq; XP_016877406.1; XM_017021917.1.
DR AlphaFoldDB; Q2M3C6; -.
DR BioGRID; 125826; 15.
DR IntAct; Q2M3C6; 12.
DR STRING; 9606.ENSP00000373594; -.
DR iPTMnet; Q2M3C6; -.
DR PhosphoSitePlus; Q2M3C6; -.
DR BioMuta; TMEM266; -.
DR DMDM; 122065157; -.
DR MassIVE; Q2M3C6; -.
DR PaxDb; Q2M3C6; -.
DR PeptideAtlas; Q2M3C6; -.
DR PRIDE; Q2M3C6; -.
DR TopDownProteomics; Q2M3C6-2; -. [Q2M3C6-2]
DR Antibodypedia; 27411; 106 antibodies from 21 providers.
DR DNASU; 123591; -.
DR Ensembl; ENST00000388942.8; ENSP00000373594.3; ENSG00000169758.13. [Q2M3C6-1]
DR GeneID; 123591; -.
DR KEGG; hsa:123591; -.
DR MANE-Select; ENST00000388942.8; ENSP00000373594.3; NM_152335.3; NP_689548.2.
DR UCSC; uc002bbq.4; human. [Q2M3C6-1]
DR CTD; 123591; -.
DR DisGeNET; 123591; -.
DR GeneCards; TMEM266; -.
DR HGNC; HGNC:26763; TMEM266.
DR HPA; ENSG00000169758; Group enriched (brain, skeletal muscle, tongue).
DR MIM; 618691; gene.
DR neXtProt; NX_Q2M3C6; -.
DR OpenTargets; ENSG00000169758; -.
DR PharmGKB; PA134968419; -.
DR VEuPathDB; HostDB:ENSG00000169758; -.
DR eggNOG; ENOG502QRI0; Eukaryota.
DR GeneTree; ENSGT00940000156738; -.
DR HOGENOM; CLU_039406_0_0_1; -.
DR InParanoid; Q2M3C6; -.
DR OMA; PAREDDM; -.
DR OrthoDB; 826861at2759; -.
DR PhylomeDB; Q2M3C6; -.
DR TreeFam; TF332271; -.
DR PathwayCommons; Q2M3C6; -.
DR SignaLink; Q2M3C6; -.
DR BioGRID-ORCS; 123591; 8 hits in 1051 CRISPR screens.
DR ChiTaRS; TMEM266; human.
DR GenomeRNAi; 123591; -.
DR Pharos; Q2M3C6; Tdark.
DR PRO; PR:Q2M3C6; -.
DR Proteomes; UP000005640; Chromosome 15.
DR RNAct; Q2M3C6; protein.
DR Bgee; ENSG00000169758; Expressed in right hemisphere of cerebellum and 111 other tissues.
DR ExpressionAtlas; Q2M3C6; baseline and differential.
DR Genevisible; Q2M3C6; HS.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0030425; C:dendrite; IDA:UniProtKB.
DR GO; GO:0005887; C:integral component of plasma membrane; IDA:UniProtKB.
DR GO; GO:0043204; C:perikaryon; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; IDA:HPA.
DR GO; GO:0042803; F:protein homodimerization activity; IDA:UniProtKB.
DR Gene3D; 1.20.120.350; -; 1.
DR InterPro; IPR042857; TMEM266.
DR InterPro; IPR027359; Volt_channel_dom_sf.
DR PANTHER; PTHR46842; PTHR46842; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cell membrane; Cell projection; Coiled coil;
KW Disulfide bond; Membrane; Reference proteome; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..531
FT /note="Transmembrane protein 266"
FT /id="PRO_0000244094"
FT TOPO_DOM 1..102
FT /note="Cytoplasmic"
FT /evidence="ECO:0000303|PubMed:30810529"
FT TRANSMEM 103..123
FT /note="Helical; Name=Segment S1"
FT /evidence="ECO:0000255, ECO:0000303|PubMed:30810529"
FT TOPO_DOM 124..129
FT /note="Extracellular"
FT /evidence="ECO:0000303|PubMed:30810529"
FT TRANSMEM 130..150
FT /note="Helical; Name=Segment S2"
FT /evidence="ECO:0000255, ECO:0000303|PubMed:30810529"
FT TOPO_DOM 151..169
FT /note="Cytoplasmic"
FT /evidence="ECO:0000303|PubMed:30810529"
FT TRANSMEM 170..190
FT /note="Helical; Name=Segment S3"
FT /evidence="ECO:0000255, ECO:0000303|PubMed:30810529"
FT TOPO_DOM 191..199
FT /note="Extracellular"
FT /evidence="ECO:0000303|PubMed:30810529"
FT TRANSMEM 200..220
FT /note="Helical; Name=Segment S4"
FT /evidence="ECO:0000303|PubMed:30810529"
FT TOPO_DOM 221..531
FT /note="Cytoplasmic"
FT /evidence="ECO:0000303|PubMed:30810529"
FT REGION 380..477
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 226..278
FT /evidence="ECO:0000255"
FT COMPBIAS 380..419
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 432..452
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VAR_SEQ 93..128
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_022108"
FT VARIANT 391
FT /note="R -> H (in dbSNP:rs937732)"
FT /evidence="ECO:0000269|PubMed:14702039"
FT /id="VAR_026880"
FT VARIANT 427
FT /note="P -> L (in dbSNP:rs937733)"
FT /evidence="ECO:0000269|PubMed:14702039"
FT /id="VAR_026881"
FT MUTAGEN 111..116
FT /note="VVILLT->DVILVL: Despite residues related to HVCN1
FT channel, does not show ion channel activity; when
FT associated with 151-M--I-153, A-175, L-184-D-185, A-213 and
FT 217-N--S-222."
FT /evidence="ECO:0000269|PubMed:25165868"
FT MUTAGEN 151..153
FT /note="SET->MEI: Despite residues related to HVCN1 channel,
FT does not show ion channel activity; when associated with
FT 111-D--L-116, A-175, L-184-D-185, A-213 and 217-N--S-222."
FT /evidence="ECO:0000269|PubMed:25165868"
FT MUTAGEN 175
FT /note="G->A: Despite residues related to HVCN1 channel,
FT does not show ion channel activity; when associated with
FT 111-D--L-116, 151-M--I-153, L-184-D-185, A-213 and 217-N--
FT S-222."
FT /evidence="ECO:0000269|PubMed:25165868"
FT MUTAGEN 184..185
FT /note="PM->LD: Despite residues related to HVCN1 channel,
FT does not show ion channel activity; when associated with
FT 111-D--L-116, 151-M--I-153, A-175, A-213 and 217-N--S-222."
FT /evidence="ECO:0000269|PubMed:25165868"
FT MUTAGEN 213
FT /note="K->A: Despite residues related to HVCN1 channel,
FT does not show ion channel activity; when associated with
FT 111-D--L-116, 151-M--I-153, A-175, L-184-D-185 and 217-N--
FT S-222."
FT /evidence="ECO:0000269|PubMed:25165868"
FT MUTAGEN 217..222
FT /note="DAYVLP->NGYVLS: Despite residues related to HVCN1
FT channel, does not show ion channel activity; when
FT associated with 111-D--L-116, 151-M--I-153, A-175, L-184-D-
FT 185 and A-213."
FT /evidence="ECO:0000269|PubMed:25165868"
SQ SEQUENCE 531 AA; 58444 MW; 4C4151B0B3CD4FB2 CRC64;
MAVAPSFNMT NPQPAIEGGI SEVEIISQQV DEETKSIAPV QLVNFAYRDL PLAAVDLSTA
GSQLLSNLDE DYQREGSNWL KPCCGKRAAV WQVFLLSASL NSFLVACVIL VVILLTLELL
IDIKLLQFSS AFQFAGVIHW ISLVILSVFF SETVLRIVVL GIWDYIENKI EVFDGAVIIL
SLAPMVASTV ANGPRSPWDA ISLIIMLRIW RVKRVIDAYV LPVKLEMEMV IQQYEKAKVI
QDEQLERLTQ ICQEQGFEIR QLRAHLAQQD LDLAAEREAA LQAPHVLSQP RSRFKVLEAG
TWDEETAAES VVEELQPSQE ATMKDDMNSY ISQYYNGPSS DSGVPEPAVC MVTTAAIDIH
QPNISSDLFS LDMPLKLGGN GTSATSESAS RSSVTRAQSD SSQTLGSSMD CSTAREEPSS
EPGPSPPPLP SQQQVEEATV QDLLSSLSED PCPSQKALDP APLARPSPAG SAQTSPELEH
RVSLFNQKNQ EGFTVFQIRP VIHFQPTVPM LEDKFRSLES KEQKLHRVPE A
