Q96Q45 (TM237_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Transmembrane protein 237

Alternative name(s):
Amyotrophic lateral sclerosis 2 chromosomal region candidate gene 4 protein

Gene names

Name:	TMEM237
Synonyms:	ALS2CR4

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

General annotation (Comments)

Function	Component of the transition zone in primary cilia. Required for ciliogenesis. Ref.6
Subcellular location	Membrane; Multi-pass membrane protein Potential. Cell projection › cilium. Note: Localizes at the proximal region of primary cilia were observed, consistent with localization to the transition zone. Anchored to the transition zone by RPGRIP1L. Ref.6
Involvement in disease	Joubert syndrome 14 (JBTS14) [MIM:614424]: An autosomal recessive disorder characterized by severe mental retardation, hypotonia, breathing abnormalities in infancy, and dysmorphic facial features. 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 renal disease, abnormal eye movements, and postaxial polydactyly. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.6
Sequence similarities	Belongs to the TMEM237 family.
Sequence caution	The sequence AAY14694.1 differs from that shown. Reason: Erroneous gene model prediction. The sequence AAY15056.1 differs from that shown. Reason: Erroneous gene model prediction.

Ontologies

Keywords
Biological process	Cilium biogenesis/degradation
Cellular component	Cell projection Cilium Membrane
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Ciliopathy Joubert syndrome
Domain	Transmembrane Transmembrane helix
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	cilium assembly Inferred from mutant phenotype Ref.6. Source: UniProtKB regulation of Wnt receptor signaling pathway Inferred from mutant phenotype Ref.6. Source: UniProtKB
Cellular_component	ciliary transition zone Inferred from direct assay Ref.6. Source: UniProtKB integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Alternative products

This entry describes 5 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q96Q45-1)

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: Q96Q45-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-14: MRTDSGARLEEGHL → MGKNPV

Isoform 3 (identifier: Q96Q45-3)

The sequence of this isoform differs from the canonical sequence as follows:
     1-14: MRTDSGARLEEGHL → MTHCACARDRAREGWGARCLGARRPPRPAKRRMGKNPV

Isoform 4 (identifier: Q96Q45-4)

The sequence of this isoform differs from the canonical sequence as follows:
     36-130: Missing.

Isoform 5 (identifier: Q96Q45-5)

The sequence of this isoform differs from the canonical sequence as follows:
     132-132: K → KRPYYR

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 408	408	Transmembrane protein 237		PRO_0000076169
Regions
	Transmembrane	227 – 247	21	Helical; Potential
	Transmembrane	268 – 288	21	Helical; Potential
	Transmembrane	303 – 323	21	Helical; Potential
	Transmembrane	358 – 378	21	Helical; Potential
Natural variations
	Alternative sequence	1 – 14	14	MRTDS…EEGHL → MGKNPV in isoform 2.		VSP_016628
	Alternative sequence	1 – 14	14	MRTDS…EEGHL → MTHCACARDRAREGWGARCL GARRPPRPAKRRMGKNPV in isoform 3.		VSP_042381
	Alternative sequence	36 – 130	95	Missing in isoform 4.		VSP_042382
	Alternative sequence	132	1	K → KRPYYR in isoform 5.		VSP_042383
	Natural variant	155	1	D → A Found at heterozygosity in a patient with Bardet-Biedl syndrome also carrying BBS6 mutation A-57 in MKKS; hypomorphic variant. Ref.6		VAR_067019
Experimental info
	Sequence conflict	20	1	L → I in AAH29611. Ref.4
	Sequence conflict	118	1	P → Q in AAH29611. Ref.4
	Sequence conflict	158	1	T → A in BAG64880. Ref.2
	Sequence conflict	215	1	R → I in AAH29611. Ref.4
	Sequence conflict	261	1	L → I in AAH29611. Ref.4

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified February 22, 2012. Version 2. Checksum: 5FF78A331490D190	FASTA	408	45,526
	10 20 30 40 50 60 MRTDSGARLE EGHLRPPRAL PPVPSQDDIP LSRPKKKKPR TKNTPASASL EGLAQTAGRR 70 80 90 100 110 120 PSEGNEPSTK ELKEHPEAPV QRRQKKTRLP LELETSSTQK KSSSSSLLRN ENGIDAEPAE 130 140 150 160 170 180 EAVIQKPRRK TKKTQPAELQ YANELGVEDE DIITDEQTTV EQQSVFTAPT GISQPVGKVF 190 200 210 220 230 240 VEKSRRFQAA DRSELIKTTE NIDVSMDVKP SWTTRDVALT VHRAFRMIGL FSHGFLAGCA 250 260 270 280 290 300 VWNIVVIYVL AGDQLSNLSN LLQQYKTLAY PFQSLLYLLL ALSTISAFDR IDFAKISVAI 310 320 330 340 350 360 RNFLALDPTA LASFLYFTAL ILSLSQQMTS DRIHLYTPSS VNGSLWEAGI EEQILQPWIV 370 380 390 400 VNLVVALLVG LSWLFLSYRP GMDLSEELMF SSEVEEYPDK EKEIKASS
	Isoform 2 [UniParc]. Checksum: B1CFB9BF7823402D	FASTA	400	44,599
	10 20 30 40 50 60 MGKNPVRPPR ALPPVPSQDD IPLSRPKKKK PRTKNTPASA SLEGLAQTAG RRPSEGNEPS 70 80 90 100 110 120 TKELKEHPEA PVQRRQKKTR LPLELETSST QKKSSSSSLL RNENGIDAEP AEEAVIQKPR 130 140 150 160 170 180 RKTKKTQPAE LQYANELGVE DEDIITDEQT TVEQQSVFTA PTGISQPVGK VFVEKSRRFQ 190 200 210 220 230 240 AADRSELIKT TENIDVSMDV KPSWTTRDVA LTVHRAFRMI GLFSHGFLAG CAVWNIVVIY 250 260 270 280 290 300 VLAGDQLSNL SNLLQQYKTL AYPFQSLLYL LLALSTISAF DRIDFAKISV AIRNFLALDP 310 320 330 340 350 360 TALASFLYFT ALILSLSQQM TSDRIHLYTP SSVNGSLWEA GIEEQILQPW IVVNLVVALL 370 380 390 400 VGLSWLFLSY RPGMDLSEEL MFSSEVEEYP DKEKEIKASS
	Isoform 3 [UniParc]. Checksum: 102BEFC17FEF823D	FASTA	432	48,244
	10 20 30 40 50 60 MTHCACARDR AREGWGARCL GARRPPRPAK RRMGKNPVRP PRALPPVPSQ DDIPLSRPKK 70 80 90 100 110 120 KKPRTKNTPA SASLEGLAQT AGRRPSEGNE PSTKELKEHP EAPVQRRQKK TRLPLELETS 130 140 150 160 170 180 STQKKSSSSS LLRNENGIDA EPAEEAVIQK PRRKTKKTQP AELQYANELG VEDEDIITDE 190 200 210 220 230 240 QTTVEQQSVF TAPTGISQPV GKVFVEKSRR FQAADRSELI KTTENIDVSM DVKPSWTTRD 250 260 270 280 290 300 VALTVHRAFR MIGLFSHGFL AGCAVWNIVV IYVLAGDQLS NLSNLLQQYK TLAYPFQSLL 310 320 330 340 350 360 YLLLALSTIS AFDRIDFAKI SVAIRNFLAL DPTALASFLY FTALILSLSQ QMTSDRIHLY 370 380 390 400 410 420 TPSSVNGSLW EAGIEEQILQ PWIVVNLVVA LLVGLSWLFL SYRPGMDLSE ELMFSSEVEE 430 YPDKEKEIKA SS
	Isoform 4 [UniParc]. Checksum: 0A2905B0D4DF85A4	FASTA	313	35,017
	10 20 30 40 50 60 MRTDSGARLE EGHLRPPRAL PPVPSQDDIP LSRPKTKKTQ PAELQYANEL GVEDEDIITD 70 80 90 100 110 120 EQTTVEQQSV FTAPTGISQP VGKVFVEKSR RFQAADRSEL IKTTENIDVS MDVKPSWTTR 130 140 150 160 170 180 DVALTVHRAF RMIGLFSHGF LAGCAVWNIV VIYVLAGDQL SNLSNLLQQY KTLAYPFQSL 190 200 210 220 230 240 LYLLLALSTI SAFDRIDFAK ISVAIRNFLA LDPTALASFL YFTALILSLS QQMTSDRIHL 250 260 270 280 290 300 YTPSSVNGSL WEAGIEEQIL QPWIVVNLVV ALLVGLSWLF LSYRPGMDLS EELMFSSEVE 310 EYPDKEKEIK ASS
	Isoform 5 [UniParc]. Checksum: F99A2856335DC3A9	FASTA	413	46,262
	10 20 30 40 50 60 MRTDSGARLE EGHLRPPRAL PPVPSQDDIP LSRPKKKKPR TKNTPASASL EGLAQTAGRR 70 80 90 100 110 120 PSEGNEPSTK ELKEHPEAPV QRRQKKTRLP LELETSSTQK KSSSSSLLRN ENGIDAEPAE 130 140 150 160 170 180 EAVIQKPRRK TKRPYYRKTQ PAELQYANEL GVEDEDIITD EQTTVEQQSV FTAPTGISQP 190 200 210 220 230 240 VGKVFVEKSR RFQAADRSEL IKTTENIDVS MDVKPSWTTR DVALTVHRAF RMIGLFSHGF 250 260 270 280 290 300 LAGCAVWNIV VIYVLAGDQL SNLSNLLQQY KTLAYPFQSL LYLLLALSTI SAFDRIDFAK 310 320 330 340 350 360 ISVAIRNFLA LDPTALASFL YFTALILSLS QQMTSDRIHL YTPSSVNGSL WEAGIEEQIL 370 380 390 400 410 QPWIVVNLVV ALLVGLSWLF LSYRPGMDLS EELMFSSEVE EYPDKEKEIK ASS

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"A gene encoding a putative GTPase regulator is mutated in familial amyotrophic lateral sclerosis 2." Hadano S., Hand C.K., Osuga H., Yanagisawa Y., Otomo A., Devon R.S., Miyamoto N., Showguchi-Miyata J., Okada Y., Singaraja R., Figlewicz D.A., Kwiatkowski T., Hosler B.A., Sagie T., Skaug J., Nasir J., Brown R.H. Jr., Scherer S.W. , Rouleau G.A., Hayden M.R., Ikeda J.-E. Nat. Genet. 29:166-173(2001) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3).
[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] (ISOFORMS 2; 4 AND 5). Tissue: Trachea.
[3]	"Generation and annotation of the DNA sequences of human chromosomes 2 and 4." Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H. , Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., Wilson R.K. Nature 434:724-731(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	"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 and Ovary.
[5]	"The full-ORF clone resource of the German cDNA consortium." Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., Wiemann S., Schupp I. BMC Genomics 8:399-399(2007) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 272-408. Tissue: Fetal skin.
[6]	"TMEM237 is mutated in individuals with a Joubert syndrome related disorder and expands the role of the TMEM family at the ciliary transition zone." Huang L., Szymanska K., Jensen V.L., Janecke A.R., Innes A.M., Davis E.E., Frosk P., Li C., Willer J.R., Chodirker B.N., Greenberg C.R., McLeod D.R., Bernier F.P., Chudley A.E., Muller T., Shboul M., Logan C.V., Loucks C.M. , Beaulieu C.L., Bowie R.V., Bell S.M., Adkins J., Zuniga F.I., Ross K.D., Wang J., Ban M.R., Becker C., Nurnberg P., Douglas S., Craft C.M., Akimenko M.A., Hegele R.A., Ober C., Utermann G., Bolz H.J., Bulman D.E., Katsanis N., Blacque O.E., Doherty D., Parboosingh J.S., Leroux M.R., Johnson C.A., Boycott K.M. Am. J. Hum. Genet. 89:713-730(2011) [PubMed] [Europe PMC] [Abstract] Cited for: INVOLVEMENT IN JBTS14, SUBCELLULAR LOCATION, FUNCTION, VARIANT ALA-155, CHARACTERIZATION OF VARIANT ALA-155.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AB053301 mRNA. Translation: BAB69011.1. AK090601 mRNA. Translation: BAC03487.1. AK303954 mRNA. Translation: BAG64880.1. AK304395 mRNA. Translation: BAG65230.1. AC007279 Genomic DNA. Translation: AAY15056.1. Sequence problems. AC007282 Genomic DNA. Translation: AAY14694.1. Sequence problems. BC013730 mRNA. Translation: AAH13730.1. BC029611 mRNA. Translation: AAH29611.1. BX538000 mRNA. Translation: CAD97955.1.
IPI	IPI00044683. IPI00658092.
RefSeq	NP_001037850.1. NM_001044385.2. NP_689601.2. NM_152388.3.
UniGene	Hs.12319.
3D structure databases
ProteinModelPortal	Q96Q45.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q96Q45. 1 interaction.
STRING	9606.ENSP00000380113.
PTM databases
PhosphoSite	Q96Q45.
Polymorphism databases
DMDM	74732666.
Proteomic databases
PaxDb	Q96Q45.
PRIDE	Q96Q45.
Protocols and materials databases
DNASU	65062.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000409444; ENSP00000387203; ENSG00000155755. ENST00000409883; ENSP00000386264; ENSG00000155755.
GeneID	65062.
KEGG	hsa:65062.
UCSC	uc021vvd.1. human.
Organism-specific databases
CTD	65062.
GeneCards	GC02M202484.
HGNC	HGNC:14432. TMEM237.
MIM	614423. gene. 614424. phenotype.
neXtProt	NX_Q96Q45.
Orphanet	475. Joubert syndrome. 220493. Joubert syndrome with ocular defect. 2318. Joubert syndrome with oculorenal defect. 220497. Joubert syndrome with renal defect.
PharmGKB	PA24745.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG71278.
HOGENOM	HOG000033887.
HOVERGEN	HBG060391.
InParanoid	Q96Q45.
Gene expression databases
ArrayExpress	Q96Q45.
Bgee	Q96Q45.
CleanEx	HS_ALS2CR4.
Genevestigator	Q96Q45.
GermOnline	ENSG00000155755. Homo sapiens.
Family and domain databases
ProtoNet	Search...
Other
GenomeRNAi	65062.
NextBio	67248.
SOURCE	Search...

Entry information

Entry name

TM237_HUMAN

Accession

Primary (citable) accession number: Q96Q45
Secondary accession number(s): B4E1R8 , B4E2R8, E9PAR8, E9PBF8, E9PG24, E9PGX0, Q53TS9, Q53TT2, Q7Z3B6, Q8IZ18, Q8NBF8, Q96CY1

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 20, 2005
Last sequence update:	February 22, 2012
Last modified:	May 1, 2013
This is version 68 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.