Q9P0N5 (TM216_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Transmembrane protein 216

Gene names

Name:	TMEM216
ORF Names:	HSPC244

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	145 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Part of the tectonic-like complex which is required for tissue-specific ciliogenesis and may regulate ciliary membrane composition By similarity. Ref.9
Subunit structure	Part of the tectonic-like complex (also named B9 complex) By similarity.
Subcellular location	Membrane; Multi-pass membrane protein Potential. Cytoplasm › cytoskeleton › cilium basal body By similarity. Note: Localizes at the transition zone, a region between the basal body and the ciliary axoneme By similarity. Ref.9
Involvement in disease	Joubert syndrome 2 (JBTS2) [MIM:608091]: A disorder presenting with cerebellar ataxia, oculomotor apraxia, hypotonia, neonatal breathing abnormalities and psychomotor delay. Neuroradiologically, it is characterized by cerebellar vermian hypoplasia/aplasia, thickened and reoriented superior cerebellar peduncles, and an abnormally large interpeduncular fossa, giving the appearance of a molar tooth on transaxial slices (molar tooth sign). Additional variable features include retinal dystrophy and renal disease. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.6 Ref.7 Ref.8 Ref.9 Meckel syndrome 2 (MKS2) [MIM:603194]: A disorder characterized by a combination of renal cysts and variably associated features including developmental anomalies of the central nervous system (typically encephalocele), hepatic ductal dysplasia and cysts, and polydactyly. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.7
Miscellaneous	TMEM138 and TMEM216 genes are adjacent and are aligned in a head-to-tail configuration. They share some cis regulatory region and display coordinated expression. Genes were joined by chromoaomal rearrangement at the amphiboan to reptile evolutionary transition around 340 million years ago (Ref.9).

Ontologies

Keywords
Biological process	Cilium biogenesis/degradation
Cellular component	Cell projection Cytoplasm Cytoskeleton Membrane
Coding sequence diversity	Alternative splicing
Disease	Ciliopathy Disease mutation Joubert syndrome Meckel syndrome
Domain	Transmembrane Transmembrane helix
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	cilium assembly Inferred from mutant phenotype Ref.9. Source: UniProtKB
Cellular_component	TCTN-B9D complex Inferred from sequence or structural similarity. Source: UniProtKB cytoplasm Inferred from electronic annotation. Source: UniProtKB-KW integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW microtubule basal body Inferred from electronic annotation. Source: UniProtKB-SubCell
Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q9P0N5-1)

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: Q9P0N5-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-61: Missing.
     144-145: RI → SMDRI

Isoform 3 (identifier: Q9P0N5-3)

The sequence of this isoform differs from the canonical sequence as follows:
     144-145: RI → SMDRI

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 145	145	Transmembrane protein 216		PRO_0000318955
Regions
	Transmembrane	22 – 42	21	Helical; Potential
	Transmembrane	56 – 76	21	Helical; Potential
	Transmembrane	89 – 109	21	Helical; Potential
	Transmembrane	122 – 142	21	Helical; Potential
Natural variations
	Alternative sequence	1 – 61	61	Missing in isoform 2.		VSP_040295
	Alternative sequence	144 – 145	2	RI → SMDRI in isoform 2 and isoform 3.		VSP_040296
	Natural variant	73	1	R → C in JBTS2. Ref.7 Ref.9		VAR_064028
	Natural variant	73	1	R → H in JBTS2 and MKS2. Ref.7 Ref.9		VAR_064029
	Natural variant	73	1	R → L in JBTS2. Ref.6 Ref.7 Ref.9		VAR_063388
	Natural variant	77	1	G → A in MKS2. Ref.7		VAR_064030
	Natural variant	89	1	L → F in JBTS2. Ref.8		VAR_068170
	Natural variant	114	1	L → R in MKS2. Ref.7		VAR_064031
Experimental info
Isoform 2:
	Sequence conflict	86	1	R → T in AAF36164. Ref.1
	Sequence conflict	86	1	R → T in CAG33447. Ref.3
	Sequence conflict	86	1	R → T in AAH11010. Ref.5
Isoform 3:
	Sequence conflict	147	1	R → T in AAF36164. Ref.1
	Sequence conflict	147	1	R → T in CAG33447. Ref.3
	Sequence conflict	147	1	R → T in AAH11010. Ref.5

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified March 21, 2012. Version 3. Checksum: 0F5024FB2B96D6CB	FASTA	145	16,487
	10 20 30 40 50 60 MLPRGLKMAP RGKRLSSTPL EILFFLNGWY NATYFLLELF IFLYKGVLLP YPTANLVLDV 70 80 90 100 110 120 VMLLLYLGIE VIRLFFGTKG NLCQRKMPLS ISVALTFPSA MMASYYLLLQ TYVLRLEAIM 130 140 NGILLFFCGS ELLLEVLTLA AFSRI
	Isoform 2 [UniParc]. Checksum: DE574B69C6BBF3C0	FASTA	87	9,803
	10 20 30 40 50 60 MLLLYLGIEV IRLFFGTKGN LCQRKMPLSI SVALTFPSAM MASYYLLLQT YVLRLEAIMN 70 80 GILLFFCGSE LLLEVLTLAA FSSMDRI
	Isoform 3 [UniParc]. Checksum: A64E11999194FB2B	FASTA	148	16,820
	10 20 30 40 50 60 MLPRGLKMAP RGKRLSSTPL EILFFLNGWY NATYFLLELF IFLYKGVLLP YPTANLVLDV 70 80 90 100 110 120 VMLLLYLGIE VIRLFFGTKG NLCQRKMPLS ISVALTFPSA MMASYYLLLQ TYVLRLEAIM 130 140 NGILLFFCGS ELLLEVLTLA AFSSMDRI

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning and functional analysis of cDNAs with open reading frames for 300 previously undefined genes expressed in CD34+ hematopoietic stem/progenitor cells." Zhang Q.-H., Ye M., Wu X.-Y., Ren S.-X., Zhao M., Zhao C.-J., Fu G., Shen Y., Fan H.-Y., Lu G., Zhong M., Xu X.-R., Han Z.-G., Zhang J.-W., Tao J., Huang Q.-H., Zhou J., Hu G.-X. , Gu J., Chen S.-J., Chen Z. Genome Res. 10:1546-1560(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). Tissue: Umbilical cord blood.
[2]	"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 1). Tissue: Kidney.
[3]	"Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)." Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B. Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
[4]	"Human chromosome 11 DNA sequence and analysis including novel gene identification." Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K., Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T., Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G. , Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C., Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A., Hattori M., Rogers J., Lander E.S., Sakaki Y. Nature 440:497-500(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 2). Tissue: Brain.
[6]	"Joubert syndrome 2 (JBTS2) in Ashkenazi Jews is associated with a TMEM216 mutation." Edvardson S., Shaag A., Zenvirt S., Erlich Y., Hannon G.J., Shanske A.L., Gomori J.M., Ekstein J., Elpeleg O. Am. J. Hum. Genet. 86:93-97(2010) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT JBTS2 LEU-73.
[7]	"Mutations in TMEM216 perturb ciliogenesis and cause Joubert, Meckel and related syndromes." Valente E.M., Logan C.V., Mougou-Zerelli S., Lee J.H., Silhavy J.L., Brancati F., Iannicelli M., Travaglini L., Romani S., Illi B., Adams M., Szymanska K., Mazzotta A., Lee J.E., Tolentino J.C., Swistun D., Salpietro C.D., Fede C. , Gabriel S., Russ C., Cibulskis K., Sougnez C., Hildebrandt F., Otto E.A., Held S., Diplas B.H., Davis E.E., Mikula M., Strom C.M., Ben-Zeev B., Lev D., Sagie T.L., Michelson M., Yaron Y., Krause A., Boltshauser E., Elkhartoufi N., Roume J., Shalev S., Munnich A., Saunier S., Inglehearn C., Saad A., Alkindy A., Thomas S., Vekemans M., Dallapiccola B., Katsanis N., Johnson C.A., Attie-Bitach T., Gleeson J.G. Nat. Genet. 42:619-625(2010) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS MKS2 HIS-73; ALA-77 AND ARG-114, VARIANTS JBTS2 CYS-73; HIS-73 AND LEU-73.
[8]	"Mutations in C5ORF42 cause Joubert syndrome in the French Canadian population." Srour M., Schwartzentruber J., Hamdan F.F., Ospina L.H., Patry L., Labuda D., Massicotte C., Dobrzeniecka S., Capo-Chichi J.M., Papillon-Cavanagh S., Samuels M.E., Boycott K.M., Shevell M.I., Laframboise R., Desilets V., Maranda B., Rouleau G.A., Majewski J., Michaud J.L. Am. J. Hum. Genet. 90:693-700(2012) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT JBTS2 PHE-89.
[9]	"Evolutionarily assembled cis-regulatory module at a human ciliopathy locus." Lee J.H., Silhavy J.L., Lee J.E., Al-Gazali L., Thomas S., Davis E.E., Bielas S.L., Hill K.J., Iannicelli M., Brancati F., Gabriel S.B., Russ C., Logan C.V., Sharif S.M., Bennett C.P., Abe M., Hildebrandt F., Diplas B.H. , Attie-Bitach T., Katsanis N., Rajab A., Koul R., Sztriha L., Waters E.R., Ferro-Novick S., Woods G.C., Johnson C.A., Valente E.M., Zaki M.S., Gleeson J.G. Science 335:966-969(2012) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS JBTS2 CYS-73; HIS-73 AND LEU-73, FUNCTION, SUBCELLULAR LOCATION.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF151078 mRNA. Translation: AAF36164.1. AK303687 mRNA. Translation: BAH14017.1. CR457166 mRNA. Translation: CAG33447.1. AP003108 Genomic DNA. No translation available. BC011010 mRNA. Translation: AAH11010.1.
IPI	IPI00009441. IPI00941579.
RefSeq	NP_001167461.1. NM_001173990.2. NP_001167462.1. NM_001173991.2. NP_057583.2. NM_016499.5.
UniGene	Hs.26745.
3D structure databases
ProteinModelPortal	Q9P0N5.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q9P0N5. 1 interaction.
STRING	9606.ENSP00000381950.
Polymorphism databases
DMDM	74734782.
Proteomic databases
PaxDb	Q9P0N5.
PRIDE	Q9P0N5.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000334888; ENSP00000334844; ENSG00000187049. ENST00000515837; ENSP00000440638; ENSG00000187049.
GeneID	51259.
KEGG	hsa:51259.
UCSC	uc001nrn.2. human.
Organism-specific databases
CTD	51259.
GeneCards	GC11P061159.
HGNC	HGNC:25018. TMEM216.
MIM	603194. phenotype. 608091. phenotype. 613277. gene.
neXtProt	NX_Q9P0N5.
Orphanet	2318. Joubert syndrome with oculorenal defect. 2754. Joubert syndrome with orofaciodigital defect. 564. Meckel syndrome.
PharmGKB	PA162406553.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG247493.
HOGENOM	HOG000076881.
HOVERGEN	HBG059533.
InParanoid	Q9P0N5.
OMA	LMFIYKG.
OrthoDB	EOG457584.
Gene expression databases
Bgee	Q9P0N5.
CleanEx	HS_TMEM216.
Genevestigator	Q9P0N5.
Family and domain databases
InterPro	IPR019184. Uncharacterised_TM-17. [Graphical view]
Pfam	PF09799. Transmemb_17. 1 hit. [Graphical view]
ProtoNet	Search...
Other
GenomeRNAi	51259.
NextBio	54428.
SOURCE	Search...

Entry information

Entry name

TM216_HUMAN

Accession

Primary (citable) accession number: Q9P0N5
Secondary accession number(s): A8MZ23, B7Z8N1

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 26, 2008
Last sequence update:	March 21, 2012
Last modified:	May 1, 2013
This is version 77 of the entry and version 3 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.