Q9NWW5 (CLN6_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Ceroid-lipofuscinosis neuronal protein 6
Short name=Protein CLN6

Gene names

Name:

CLN6

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

General annotation (Comments)

Subunit structure	Interacts with CRMP2. Ref.8
Subcellular location	Endoplasmic reticulum membrane; Multi-pass membrane protein Ref.5.
Involvement in disease	Neuronal ceroid lipofuscinosis 6 (CLN6) [MIM:601780]: A form of neuronal ceroid lipofuscinosis. Neuronal ceroid lipofuscinoses are progressive neurodegenerative, lysosomal storage diseases characterized by intracellular accumulation of autofluorescent liposomal material, and clinically by seizures, dementia, visual loss, and/or cerebral atrophy. The lipopigment patterns observed most often in neuronal ceroid lipofuscinosis type 6 comprise mixed combinations of granular, curvilinear, and fingerprint profiles. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.2 Ref.14 Ref.15 Ref.16 Ref.17 Ref.18 Ref.20 Neuronal ceroid lipofuscinosis 4A (CLN4A) [MIM:204300]: An adult-onset neuronal ceroid lipofuscinosis. Neuronal ceroid lipofuscinoses are progressive neurodegenerative, lysosomal storage diseases characterized by intracellular accumulation of autofluorescent liposomal material, and clinically by seizures, dementia, visual loss, and/or cerebral atrophy. CLN4A has no visual involvement and is characterized by progressive myoclonic epilepsy. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.19

Ontologies

Keywords
Cellular component	Endoplasmic reticulum Membrane
Coding sequence diversity	Polymorphism
Disease	Disease mutation Neurodegeneration Neuronal ceroid lipofuscinosis
Domain	Transmembrane Transmembrane helix
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	cell death Inferred from electronic annotation. Source: UniProtKB-KW cellular macromolecule catabolic process Inferred from electronic annotation. Source: Compara cholesterol metabolic process Inferred from mutant phenotype PubMed 16857350. Source: UniProtKB ganglioside metabolic process Inferred from mutant phenotype PubMed 16857350. Source: UniProtKB glycosaminoglycan metabolic process Inferred from mutant phenotype PubMed 16857350. Source: UniProtKB locomotion involved in locomotory behavior Inferred from electronic annotation. Source: Compara lysosomal lumen acidification Inferred from mutant phenotype PubMed 11722572. Source: UniProtKB positive regulation of proteolysis Inferred from mutant phenotype PubMed 15010453. Source: UniProtKB protein catabolic process Non-traceable author statement PubMed 10740217. Source: UniProtKB visual perception Inferred from electronic annotation. Source: Compara
Cellular_component	endoplasmic reticulum lumen Inferred from direct assay PubMed 15010453. Source: UniProtKB endoplasmic reticulum membrane Inferred from electronic annotation. Source: UniProtKB-SubCell integral to membrane Non-traceable author statement Ref.15. Source: UniProtKB
Molecular_function	protein homodimerization activity Inferred from direct assay PubMed 15010453. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 311	311	Ceroid-lipofuscinosis neuronal protein 6		PRO_0000089862
Regions
	Transmembrane	56 – 76	21	Helical; Potential
	Transmembrane	81 – 101	21	Helical; Potential
	Transmembrane	111 – 131	21	Helical; Potential
	Transmembrane	179 – 199	21	Helical; Potential
	Transmembrane	204 – 224	21	Helical; Potential
	Transmembrane	225 – 245	21	Helical; Potential
	Transmembrane	260 – 280	21	Helical; Potential
Amino acid modifications
	Modified residue	31	1	Phosphoserine Ref.10 Ref.11 Ref.13
Natural variations
	Natural variant	6	1	R → T in CLN4A. Ref.19		VAR_065834
	Natural variant	12	1	A → T in CLN6. Ref.20		VAR_066904
	Natural variant	17	1	G → S in CLN6. Ref.20		VAR_066905
	Natural variant	34	1	A → T. Ref.19		VAR_065835
	Natural variant	47	1	L → F in CLN4A. Ref.19		VAR_065836
	Natural variant	62	1	R → H in CLN6. Ref.17		VAR_021549
	Natural variant	67	1	L → P in CLN4A. Ref.19		VAR_065837
	Natural variant	72	1	E → Q in CLN6. Ref.17		VAR_021550
	Natural variant	77	1	N → K in CLN4A. Ref.19		VAR_065838
	Natural variant	90	1	N → K in CLN6. Ref.20		VAR_066906
	Natural variant	103	1	R → Q in CLN4A. Ref.19		VAR_065839
	Natural variant	104	1	S → F in CLN6. Ref.20		VAR_066907
	Natural variant	123	1	G → D in CLN6. Ref.15 Corresponds to variant rs28939384 [ dbSNP | Ensembl ].		VAR_015683
	Natural variant	149	1	R → C in CLN6. Ref.20		VAR_066908
	Natural variant	149	1	R → H in CLN4A. Ref.19		VAR_065840
	Natural variant	154	1	Missing in CLN6. Ref.15		VAR_015684
	Natural variant	159	1	P → L in CLN6. Ref.18		VAR_058436
	Natural variant	169	1	L → P in CLN6. Ref.20		VAR_066909
	Natural variant	171	1	Missing in CLN6. Ref.14		VAR_015685
	Natural variant	186	1	F → S in CLN6. Ref.20		VAR_066910
	Natural variant	221	1	Y → C in CLN6. Ref.18		VAR_058437
	Natural variant	221	1	Y → S in CLN6. Ref.17		VAR_021551
	Natural variant	234	1	F → L in CLN6. Ref.2 Ref.20		VAR_066911
	Natural variant	238	1	F → T in CLN4A; requires 2 nucleotide substitutions. Ref.19		VAR_065841
	Natural variant	241	1	M → T in CLN6. Ref.17		VAR_021552
	Natural variant	252	1	R → H in CLN6. Ref.20		VAR_066912
	Natural variant	259	1	G → S in CLN6. Ref.20		VAR_066913
	Natural variant	265	1	Missing in CLN6. Ref.17 Ref.18		VAR_021553
	Natural variant	297	1	P → T in CLN6. Ref.20		VAR_066914
	Natural variant	299	1	P → L in CLN6. Ref.17		VAR_021554
	Natural variant	300	1	W → R in CLN6. Ref.16		VAR_015686
	Natural variant	308	1	S → T. Ref.19		VAR_065842
Experimental info
	Sequence conflict	281	1	W → R in BAB55226. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Q9NWW5 [UniParc]. Last modified October 1, 2000. Version 1. Checksum: C718E6F2DC20CE0F	FASTA	311	35,919
	10 20 30 40 50 60 MEATRRRQHL GATGGPGAQL GASFLQARHG SVSADEAART APFHLDLWFY FTLQNWVLDF 70 80 90 100 110 120 GRPIAMLVFP LEWFPLNKPS VGDYFHMAYN VITPFLLLKL IERSPRTLPR SITYVSIIIF 130 140 150 160 170 180 IMGASIHLVG DSVNHRLLFS GYQHHLSVRE NPIIKNLKPE TLIDSFELLY YYDEYLGHCM 190 200 210 220 230 240 WYIPFFLILF MYFSGCFTAS KAESLIPGPA LLLVAPSGLY YWYLVTEGQI FILFIFTFFA 250 260 270 280 290 300 MLALVLHQKR KRLFLDSNGL FLFSSFALTL LLVALWVAWL WNDPVLRKKY PGVIYVPEPW 310 AFYTLHVSSR H

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"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].
[2]	"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], VARIANT CLN6 LEU-234.
[3]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases 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]. Tissue: Lung and Urinary bladder.
[5]	"CLN6, which is associated with a lysosomal storage disease, is an endoplasmic reticulum protein." Mole S.E., Michaux G., Codlin S., Wheeler R.B., Sharp J.D., Cutler D.F. Exp. Cell Res. 298:399-406(2004) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION.
[6]	"Global, in vivo, and site-specific phosphorylation dynamics in signaling networks." Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M. Cell 127:635-648(2006) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. Tissue: Cervix carcinoma.
[7]	"Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle." Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., Greff Z., Keri G., Stemmann O., Mann M. Mol. Cell 31:438-448(2008) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. Tissue: Cervix carcinoma.
[8]	"Protein product of CLN6 gene responsible for variant late-onset infantile neuronal ceroid lipofuscinosis interacts with CRMP-2." Benedict J.W., Getty A.L., Wishart T.M., Gillingwater T.H., Pearce D.A. J. Neurosci. Res. 87:2157-2166(2009) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH CRMP2.
[9]	"Large-scale proteomics analysis of the human kinome." Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G., Mann M., Daub H. Mol. Cell. Proteomics 8:1751-1764(2009) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[10]	"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions." Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K. Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-31, MASS SPECTROMETRY. Tissue: Leukemic T-cell.
[11]	"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis." Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M. Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-31, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[12]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[13]	"System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation." Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B. Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-31, MASS SPECTROMETRY.
[14]	"Mutations in a novel CLN6-encoded transmembrane protein cause variant neuronal ceroid lipofuscinosis in man and mouse." Gao H., Boustany R.-M.N., Espinola J.A., Cotman S.L., Srinidhi L., Antonellis K.A., Gillis T., Qin X., Liu S., Donahue L.R., Bronson R.T., Faust J.R., Stout D., Haines J.L., Lerner T.J., MacDonald M.E. Am. J. Hum. Genet. 70:324-335(2002) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT CLN6 TYR-171 DEL.
[15]	"The gene mutated in variant late-infantile neuronal ceroid lipofuscinosis (CLN6) and in nclf mutant mice encodes a novel predicted transmembrane protein." Wheeler R.B., Sharp J.D., Schultz R.A., Joslin J.M., Williams R.E., Mole S.E. Am. J. Hum. Genet. 70:537-542(2002) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS CLN6 ASP-123 AND ILE-154 DEL.
[16]	"Novel mutations in the CLN6 gene causing a variant late infantile neuronal ceroid lipofuscinosis." Teixeira C.A., Espinola J., Huo L., Kohlschutter J., Persaud Sawin D.A., Minassian B., Bessa C.J., Guimaraes A., Stephan D.A., Sa Miranda M.C., MacDonald M.E., Ribeiro M.G., Boustany R.-M.N. Hum. Mutat. 21:502-508(2003) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT CLN6 ARG-300.
[17]	"Spectrum of CLN6 mutations in variant late infantile neuronal ceroid lipofuscinosis." Sharp J.D., Wheeler R.B., Parker K.A., Gardiner R.M., Williams R.E., Mole S.E. Hum. Mutat. 22:35-42(2003) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS CLN6 HIS-62; GLN-72; SER-221; THR-241; SER-265 DEL AND LEU-299.
[18]	"Mutations in CLN7/MFSD8 are a common cause of variant late-infantile neuronal ceroid lipofuscinosis." Kousi M., Siintola E., Dvorakova L., Vlaskova H., Turnbull J., Topcu M., Yuksel D., Gokben S., Minassian B.A., Elleder M., Mole S.E., Lehesjoki A.-E. Brain 132:810-819(2009) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS CLN6 LEU-159; CYS-221 AND SER-265 DEL.
[19]	"Kufs disease, the major adult form of neuronal ceroid lipofuscinosis, caused by mutations in CLN6." Arsov T., Smith K.R., Damiano J., Franceschetti S., Canafoglia L., Bromhead C.J., Andermann E., Vears D.F., Cossette P., Rajagopalan S., McDougall A., Sofia V., Farrell M., Aguglia U., Zini A., Meletti S., Morbin M., Mullen S. , Andermann F., Mole S.E., Bahlo M., Berkovic S.F. Am. J. Hum. Genet. 88:566-573(2011) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS CLN4A THR-6; PHE-47; PRO-67; LYS-77; GLN-103; HIS-149 AND THR-238, VARIANTS THR-34 AND THR-308.
[20]	"Update of the mutation spectrum and clinical correlations of over 360 mutations in eight genes that underlie the neuronal ceroid lipofuscinoses." Kousi M., Lehesjoki A.E., Mole S.E. Hum. Mutat. 33:42-63(2012) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS CLN6 THR-12; SER-17; LYS-90; PHE-104; CYS-149; PRO-169; SER-186; LEU-234; HIS-252; SER-259 AND THR-297.
+	Additional computationally mapped references.

Web resources

NCL CLN6

Neural Ceroid Lipofuscinoses mutation db

GeneReviews

Cross-references

Sequence databases
EMBL GenBank DDBJ	AK000568 mRNA. Translation: BAA91260.1. AK027604 mRNA. Translation: BAB55226.1. AK291175 mRNA. Translation: BAF83864.1. CR457244 mRNA. Translation: CAG33525.1. CH471082 Genomic DNA. Translation: EAW77811.1. BC010849 mRNA. Translation: AAH10849.1. BC013130 mRNA. Translation: AAH13130.1.
IPI	IPI00016597.
RefSeq	NP_060352.1. NM_017882.2.
UniGene	Hs.584921.
3D structure databases
ProteinModelPortal	Q9NWW5.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q9NWW5. 3 interactions.
STRING	9606.ENSP00000249806.
PTM databases
PhosphoSite	Q9NWW5.
Polymorphism databases
DMDM	32129457.
Proteomic databases
PaxDb	Q9NWW5.
PRIDE	Q9NWW5.
Protocols and materials databases
DNASU	54982.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000249806; ENSP00000249806; ENSG00000128973.
GeneID	54982.
KEGG	hsa:54982.
UCSC	uc002arf.3. human.
Organism-specific databases
CTD	54982.
GeneCards	GC15M068499.
HGNC	HGNC:2077. CLN6.
MIM	204300. phenotype. 601780. phenotype. 606725. gene.
neXtProt	NX_Q9NWW5.
Orphanet	228340. CLN4A disease. 228363. CLN6 disease.
PharmGKB	PA26604.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG27962.
HOVERGEN	HBG039396.
InParanoid	Q9NWW5.
KO	K12359.
OrthoDB	EOG4229KG.
PhylomeDB	Q9NWW5.
Gene expression databases
ArrayExpress	Q9NWW5.
Bgee	Q9NWW5.
CleanEx	HS_CLN6.
Genevestigator	Q9NWW5.
GermOnline	ENSG00000128973. Homo sapiens.
Family and domain databases
ProtoNet	Search...
Other
ChiTaRS	CLN6. human.
GenomeRNAi	54982.
NextBio	58254.
SOURCE	Search...

Entry information

Entry name

CLN6_HUMAN

Accession

Primary (citable) accession number: Q9NWW5
Secondary accession number(s): A8K560, Q6IAB1, Q96SR0

Entry history

Integrated into UniProtKB/Swiss-Prot:	June 16, 2003
Last sequence update:	October 1, 2000
Last modified:	May 1, 2013
This is version 105 of the entry and version 1 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.