TM216_HUMAN
ID TM216_HUMAN Reviewed; 145 AA.
AC Q9P0N5; A8MZ23; B7Z8N1;
DT 26-FEB-2008, integrated into UniProtKB/Swiss-Prot.
DT 21-MAR-2012, sequence version 3.
DT 03-AUG-2022, entry version 139.
DE RecName: Full=Transmembrane protein 216;
GN Name=TMEM216; ORFNames=HSPC244;
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 MRNA] (ISOFORM 2).
RC TISSUE=Umbilical cord blood;
RX PubMed=11042152; DOI=10.1101/gr.140200;
RA Zhang Q.-H., Ye M., Wu X.-Y., Ren S.-X., Zhao M., Zhao C.-J., Fu G.,
RA Shen Y., Fan H.-Y., Lu G., Zhong M., Xu X.-R., Han Z.-G., Zhang J.-W.,
RA Tao J., Huang Q.-H., Zhou J., Hu G.-X., Gu J., Chen S.-J., Chen Z.;
RT "Cloning and functional analysis of cDNAs with open reading frames for 300
RT previously undefined genes expressed in CD34+ hematopoietic stem/progenitor
RT cells.";
RL Genome Res. 10:1546-1560(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Kidney;
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] (ISOFORM 2).
RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16554811; DOI=10.1038/nature04632;
RA Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K.,
RA Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T.,
RA Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G.,
RA Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C.,
RA Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A.,
RA Hattori M., Rogers J., Lander E.S., Sakaki Y.;
RT "Human chromosome 11 DNA sequence and analysis including novel gene
RT identification.";
RL Nature 440:497-500(2006).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Brain;
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 [6]
RP IDENTIFICATION IN THE TECTONIC-LIKE COMPLEX, AND INTERACTION WITH TMEM107.
RX PubMed=26595381; DOI=10.1038/ncb3273;
RA Lambacher N.J., Bruel A.L., van Dam T.J., Szymanska K., Slaats G.G.,
RA Kuhns S., McManus G.J., Kennedy J.E., Gaff K., Wu K.M., van der Lee R.,
RA Burglen L., Doummar D., Riviere J.B., Faivre L., Attie-Bitach T.,
RA Saunier S., Curd A., Peckham M., Giles R.H., Johnson C.A., Huynen M.A.,
RA Thauvin-Robinet C., Blacque O.E.;
RT "TMEM107 recruits ciliopathy proteins to subdomains of the ciliary
RT transition zone and causes Joubert syndrome.";
RL Nat. Cell Biol. 18:122-131(2016).
RN [7]
RP VARIANT JBTS2 LEU-73.
RX PubMed=20036350; DOI=10.1016/j.ajhg.2009.12.007;
RA Edvardson S., Shaag A., Zenvirt S., Erlich Y., Hannon G.J., Shanske A.L.,
RA Gomori J.M., Ekstein J., Elpeleg O.;
RT "Joubert syndrome 2 (JBTS2) in Ashkenazi Jews is associated with a TMEM216
RT mutation.";
RL Am. J. Hum. Genet. 86:93-97(2010).
RN [8]
RP VARIANTS MKS2 HIS-73; ALA-77 AND ARG-114, AND VARIANTS JBTS2 CYS-73; HIS-73
RP AND LEU-73.
RX PubMed=20512146; DOI=10.1038/ng.594;
RA Valente E.M., Logan C.V., Mougou-Zerelli S., Lee J.H., Silhavy J.L.,
RA Brancati F., Iannicelli M., Travaglini L., Romani S., Illi B., Adams M.,
RA Szymanska K., Mazzotta A., Lee J.E., Tolentino J.C., Swistun D.,
RA Salpietro C.D., Fede C., Gabriel S., Russ C., Cibulskis K., Sougnez C.,
RA Hildebrandt F., Otto E.A., Held S., Diplas B.H., Davis E.E., Mikula M.,
RA Strom C.M., Ben-Zeev B., Lev D., Sagie T.L., Michelson M., Yaron Y.,
RA Krause A., Boltshauser E., Elkhartoufi N., Roume J., Shalev S., Munnich A.,
RA Saunier S., Inglehearn C., Saad A., Alkindy A., Thomas S., Vekemans M.,
RA Dallapiccola B., Katsanis N., Johnson C.A., Attie-Bitach T., Gleeson J.G.;
RT "Mutations in TMEM216 perturb ciliogenesis and cause Joubert, Meckel and
RT related syndromes.";
RL Nat. Genet. 42:619-625(2010).
RN [9]
RP VARIANT JBTS2 PHE-89.
RX PubMed=22425360; DOI=10.1016/j.ajhg.2012.02.011;
RA Srour M., Schwartzentruber J., Hamdan F.F., Ospina L.H., Patry L.,
RA Labuda D., Massicotte C., Dobrzeniecka S., Capo-Chichi J.M.,
RA Papillon-Cavanagh S., Samuels M.E., Boycott K.M., Shevell M.I.,
RA Laframboise R., Desilets V., Maranda B., Rouleau G.A., Majewski J.,
RA Michaud J.L.;
RT "Mutations in C5ORF42 cause Joubert syndrome in the French Canadian
RT population.";
RL Am. J. Hum. Genet. 90:693-700(2012).
RN [10]
RP VARIANTS JBTS2 CYS-73; HIS-73 AND LEU-73, FUNCTION, AND SUBCELLULAR
RP LOCATION.
RX PubMed=22282472; DOI=10.1126/science.1213506;
RA Lee J.H., Silhavy J.L., Lee J.E., Al-Gazali L., Thomas S., Davis E.E.,
RA Bielas S.L., Hill K.J., Iannicelli M., Brancati F., Gabriel S.B., Russ C.,
RA Logan C.V., Sharif S.M., Bennett C.P., Abe M., Hildebrandt F., Diplas B.H.,
RA Attie-Bitach T., Katsanis N., Rajab A., Koul R., Sztriha L., Waters E.R.,
RA Ferro-Novick S., Woods G.C., Johnson C.A., Valente E.M., Zaki M.S.,
RA Gleeson J.G.;
RT "Evolutionarily assembled cis-regulatory module at a human ciliopathy
RT locus.";
RL Science 335:966-969(2012).
CC -!- FUNCTION: Part of the tectonic-like complex which is required for
CC tissue-specific ciliogenesis and may regulate ciliary membrane
CC composition. {ECO:0000269|PubMed:22282472}.
CC -!- SUBUNIT: Part of the tectonic-like complex (also named B9 complex).
CC Interacts with TMEM107. {ECO:0000269|PubMed:26595381}.
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000305}; Multi-pass membrane
CC protein {ECO:0000305}. Cytoplasm, cytoskeleton, cilium basal body
CC {ECO:0000269|PubMed:22282472}. Note=Localizes at the transition zone, a
CC region between the basal body and the ciliary axoneme.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q9P0N5-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9P0N5-2; Sequence=VSP_040295, VSP_040296;
CC Name=3;
CC IsoId=Q9P0N5-3; Sequence=VSP_040296;
CC -!- DISEASE: Joubert syndrome 2 (JBTS2) [MIM:608091]: A disorder presenting
CC with cerebellar ataxia, oculomotor apraxia, hypotonia, neonatal
CC breathing abnormalities and psychomotor delay. Neuroradiologically, it
CC is characterized by cerebellar vermian hypoplasia/aplasia, thickened
CC and reoriented superior cerebellar peduncles, and an abnormally large
CC interpeduncular fossa, giving the appearance of a molar tooth on
CC transaxial slices (molar tooth sign). Additional variable features
CC include retinal dystrophy and renal disease.
CC {ECO:0000269|PubMed:20036350, ECO:0000269|PubMed:20512146,
CC ECO:0000269|PubMed:22282472, ECO:0000269|PubMed:22425360}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- DISEASE: Meckel syndrome 2 (MKS2) [MIM:603194]: A disorder
CC characterized by a combination of renal cysts and variably associated
CC features including developmental anomalies of the central nervous
CC system (typically encephalocele), hepatic ductal dysplasia and cysts,
CC and polydactyly. {ECO:0000269|PubMed:20512146}. Note=The disease is
CC caused by variants affecting the gene represented in this entry.
CC -!- MISCELLANEOUS: TMEM138 and TMEM216 genes are adjacent and are aligned
CC in a head-to-tail configuration. They share some cis regulatory region
CC and display coordinated expression. Genes were joined by chromosomal
CC rearrangement at the amphiboan to reptile evolutionary transition
CC around 340 million years ago (PubMed:22282472).
CC {ECO:0000305|PubMed:22282472}.
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DR EMBL; AF151078; AAF36164.1; -; mRNA.
DR EMBL; AK303687; BAH14017.1; -; mRNA.
DR EMBL; CR457166; CAG33447.1; -; mRNA.
DR EMBL; AP003108; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC011010; AAH11010.1; -; mRNA.
DR CCDS; CCDS53640.1; -. [Q9P0N5-1]
DR CCDS; CCDS86205.1; -. [Q9P0N5-3]
DR RefSeq; NP_001167461.1; NM_001173990.2. [Q9P0N5-1]
DR RefSeq; NP_001167462.1; NM_001173991.2. [Q9P0N5-3]
DR RefSeq; NP_001317214.1; NM_001330285.1.
DR RefSeq; NP_057583.2; NM_016499.5. [Q9P0N5-2]
DR RefSeq; XP_005274096.1; XM_005274039.3. [Q9P0N5-2]
DR AlphaFoldDB; Q9P0N5; -.
DR SMR; Q9P0N5; -.
DR BioGRID; 119415; 244.
DR DIP; DIP-61992N; -.
DR IntAct; Q9P0N5; 243.
DR STRING; 9606.ENSP00000440638; -.
DR BioMuta; TMEM216; -.
DR DMDM; 380865448; -.
DR PaxDb; Q9P0N5; -.
DR PeptideAtlas; Q9P0N5; -.
DR PRIDE; Q9P0N5; -.
DR ProteomicsDB; 83583; -. [Q9P0N5-2]
DR DNASU; 51259; -.
DR Ensembl; ENST00000334888.10; ENSP00000334844.5; ENSG00000187049.11. [Q9P0N5-3]
DR Ensembl; ENST00000515837.7; ENSP00000440638.1; ENSG00000187049.11. [Q9P0N5-1]
DR GeneID; 51259; -.
DR KEGG; hsa:51259; -.
DR MANE-Select; ENST00000515837.7; ENSP00000440638.1; NM_001173990.3; NP_001167461.1.
DR UCSC; uc010rlj.3; human. [Q9P0N5-1]
DR CTD; 51259; -.
DR DisGeNET; 51259; -.
DR GeneCards; TMEM216; -.
DR GeneReviews; TMEM216; -.
DR HGNC; HGNC:25018; TMEM216.
DR HPA; ENSG00000187049; Low tissue specificity.
DR MalaCards; TMEM216; -.
DR MIM; 603194; phenotype.
DR MIM; 608091; phenotype.
DR MIM; 613277; gene.
DR neXtProt; NX_Q9P0N5; -.
DR OpenTargets; ENSG00000187049; -.
DR Orphanet; 2318; Joubert syndrome with oculorenal defect.
DR Orphanet; 564; Meckel syndrome.
DR Orphanet; 2754; Orofaciodigital syndrome type 6.
DR PharmGKB; PA162406553; -.
DR VEuPathDB; HostDB:ENSG00000187049; -.
DR eggNOG; KOG4502; Eukaryota.
DR GeneTree; ENSGT00940000153899; -.
DR HOGENOM; CLU_135948_0_0_1; -.
DR InParanoid; Q9P0N5; -.
DR OMA; QFPWGLK; -.
DR OrthoDB; 1584392at2759; -.
DR TreeFam; TF323824; -.
DR PathwayCommons; Q9P0N5; -.
DR Reactome; R-HSA-5620912; Anchoring of the basal body to the plasma membrane.
DR SignaLink; Q9P0N5; -.
DR BioGRID-ORCS; 51259; 21 hits in 1082 CRISPR screens.
DR ChiTaRS; TMEM216; human.
DR GeneWiki; TMEM216; -.
DR GenomeRNAi; 51259; -.
DR Pharos; Q9P0N5; Tbio.
DR PRO; PR:Q9P0N5; -.
DR Proteomes; UP000005640; Chromosome 11.
DR RNAct; Q9P0N5; protein.
DR Bgee; ENSG00000187049; Expressed in adenohypophysis and 172 other tissues.
DR ExpressionAtlas; Q9P0N5; baseline and differential.
DR Genevisible; Q9P0N5; HS.
DR GO; GO:0035869; C:ciliary transition zone; IBA:GO_Central.
DR GO; GO:0005929; C:cilium; IDA:UniProtKB.
DR GO; GO:0005856; C:cytoskeleton; IEA:UniProtKB-KW.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0036038; C:MKS complex; ISS:UniProtKB.
DR GO; GO:0060271; P:cilium assembly; IMP:UniProtKB.
DR GO; GO:1905515; P:non-motile cilium assembly; IBA:GO_Central.
DR InterPro; IPR019184; Uncharacterised_TM-17.
DR PANTHER; PTHR13531; PTHR13531; 1.
DR Pfam; PF09799; Transmemb_17; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cell projection; Ciliopathy;
KW Cilium biogenesis/degradation; Cytoplasm; Cytoskeleton; Disease variant;
KW Joubert syndrome; Meckel syndrome; Membrane; Reference proteome;
KW Transmembrane; Transmembrane helix.
FT CHAIN 1..145
FT /note="Transmembrane protein 216"
FT /id="PRO_0000318955"
FT TRANSMEM 22..42
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 56..76
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 89..109
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 122..142
FT /note="Helical"
FT /evidence="ECO:0000255"
FT VAR_SEQ 1..61
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:11042152,
FT ECO:0000303|PubMed:15489334, ECO:0000303|Ref.3"
FT /id="VSP_040295"
FT VAR_SEQ 144..145
FT /note="RI -> SMDRI (in isoform 2 and isoform 3)"
FT /evidence="ECO:0000303|PubMed:11042152,
FT ECO:0000303|PubMed:15489334, ECO:0000303|Ref.3"
FT /id="VSP_040296"
FT VARIANT 73
FT /note="R -> C (in JBTS2; dbSNP:rs779526456)"
FT /evidence="ECO:0000269|PubMed:20512146,
FT ECO:0000269|PubMed:22282472"
FT /id="VAR_064028"
FT VARIANT 73
FT /note="R -> H (in JBTS2 and MKS2; dbSNP:rs201108965)"
FT /evidence="ECO:0000269|PubMed:20512146,
FT ECO:0000269|PubMed:22282472"
FT /id="VAR_064029"
FT VARIANT 73
FT /note="R -> L (in JBTS2; dbSNP:rs201108965)"
FT /evidence="ECO:0000269|PubMed:20036350,
FT ECO:0000269|PubMed:20512146, ECO:0000269|PubMed:22282472"
FT /id="VAR_063388"
FT VARIANT 77
FT /note="G -> A (in MKS2; dbSNP:rs386833830)"
FT /evidence="ECO:0000269|PubMed:20512146"
FT /id="VAR_064030"
FT VARIANT 89
FT /note="L -> F (in JBTS2; dbSNP:rs780098806)"
FT /evidence="ECO:0000269|PubMed:22425360"
FT /id="VAR_068170"
FT VARIANT 114
FT /note="L -> R (in MKS2; dbSNP:rs386833831)"
FT /evidence="ECO:0000269|PubMed:20512146"
FT /id="VAR_064031"
FT CONFLICT Q9P0N5-2:86
FT /note="R -> T (in Ref. 1; AAF36164, 3; CAG33447 and 5;
FT AAH11010)"
FT /evidence="ECO:0000305"
FT CONFLICT Q9P0N5-3:147
FT /note="R -> T (in Ref. 1; AAF36164, 3; CAG33447 and 5;
FT AAH11010)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 145 AA; 16487 MW; 0F5024FB2B96D6CB CRC64;
MLPRGLKMAP RGKRLSSTPL EILFFLNGWY NATYFLLELF IFLYKGVLLP YPTANLVLDV
VMLLLYLGIE VIRLFFGTKG NLCQRKMPLS ISVALTFPSA MMASYYLLLQ TYVLRLEAIM
NGILLFFCGS ELLLEVLTLA AFSRI
