Q9UBY8 (CLN8_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Protein CLN8

Gene names

Name:	CLN8
Synonyms:	C8orf61

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

General annotation (Comments)

Function	Could play a role in cell proliferation during neuronal differentiation and in protection against cell death. Ref.8
Subcellular location	Endoplasmic reticulum membrane; Multi-pass membrane protein. Endoplasmic reticulum-Golgi intermediate compartment membrane; Multi-pass membrane protein Ref.4.
Post-translational modification	Does not seem to be N-glycosylated.
Involvement in disease	Neuronal ceroid lipofuscinosis 8 (CLN8) [MIM:600143]: A form of neuronal ceroid lipofuscinosis with onset in childhood. 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 8 comprise mixed combinations of granular, curvilinear, and fingerprint profiles. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.1 Ref.5 Ref.6 Ref.7 Ref.8 Ref.9 Neuronal ceroid lipofuscinosis 8, Northern epilepsy variant (CLN8NE) [MIM:610003]: A form of neuronal ceroid lipofuscinosis clinically characterized by epilepsy that presents between 5 and 10 years of age with frequent tonic-clonic seizures followed by progressive mental retardation. Visual loss is not a prominent feature. Intracellular accumulation of autofluorescent material results in curvilinear and granular profiles on ultrastructural analysis. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.1 Ref.9
Sequence similarities	Contains 1 TLC (TRAM/LAG1/CLN8) domain.

Ontologies

Keywords
Cellular component	Endoplasmic reticulum Membrane
Coding sequence diversity	Polymorphism
Disease	Disease mutation Epilepsy Mental retardation Neurodegeneration Neuronal ceroid lipofuscinosis
Domain	Transmembrane Transmembrane helix
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	L-glutamate uptake involved in synaptic transmission Inferred from electronic annotation. Source: Compara adult walking behavior Inferred from electronic annotation. Source: Compara age-dependent response to oxidative stress Inferred from electronic annotation. Source: Compara associative learning Inferred from electronic annotation. Source: Compara cell death Inferred from electronic annotation. Source: UniProtKB-KW cellular protein catabolic process Inferred from electronic annotation. Source: Compara ceramide biosynthetic process Non-traceable author statement PubMed 12151215. Source: UniProtKB cholesterol metabolic process Inferred from mutant phenotype PubMed 16086686. Source: UniProtKB lipid transport Non-traceable author statement PubMed 12151215. Source: UniProtKB lysosome organization Inferred from electronic annotation. Source: Compara mitochondrial membrane organization Inferred from electronic annotation. Source: Compara musculoskeletal movement Inferred from electronic annotation. Source: Compara negative regulation of apoptotic process Inferred from electronic annotation. Source: Compara negative regulation of proteolysis Non-traceable author statement PubMed 12151215. Source: UniProtKB negative regulation of transferase activity Inferred from electronic annotation. Source: Compara nervous system development Inferred from mutant phenotype Ref.1. Source: UniProtKB neurofilament cytoskeleton organization Inferred from electronic annotation. Source: Compara neuromuscular process controlling balance Inferred from electronic annotation. Source: Compara neuromuscular process controlling posture Inferred from electronic annotation. Source: Compara phospholipid metabolic process Inferred from mutant phenotype PubMed 16086686. Source: UniProtKB photoreceptor cell maintenance Inferred from electronic annotation. Source: Compara protein catabolic process Non-traceable author statement PubMed 10740217. Source: UniProtKB regulation of cell size Inferred from electronic annotation. Source: Compara retina development in camera-type eye Inferred from electronic annotation. Source: Compara social behavior Inferred from electronic annotation. Source: Compara somatic motor neuron differentiation Inferred from electronic annotation. Source: Compara
Cellular_component	endoplasmic reticulum Inferred from direct assay Ref.4. Source: UniProtKB endoplasmic reticulum membrane Inferred from electronic annotation. Source: UniProtKB-SubCell endoplasmic reticulum-Golgi intermediate compartment Inferred from direct assay Ref.4. Source: UniProtKB endoplasmic reticulum-Golgi intermediate compartment membrane Inferred from electronic annotation. Source: UniProtKB-SubCell integral to membrane Non-traceable author statement Ref.1Ref.4. Source: UniProtKB mitochondrion Inferred from electronic annotation. Source: Compara
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 286	286	Protein CLN8		PRO_0000185537
Regions
	Transmembrane	21 – 41	21	Helical; Potential
	Transmembrane	62 – 84	23	Helical; Potential
	Transmembrane	103 – 123	21	Helical; Potential
	Transmembrane	131 – 151	21	Helical; Potential
	Transmembrane	226 – 246	21	Helical; Potential
	Domain	62 – 262	201	TLC
	Motif	283 – 286	4	ER-retrieval signal
Natural variations
	Natural variant	16	1	L → M in CLN8; associated with M-170 on the same allele. Ref.5		VAR_026554
	Natural variant	24	1	R → G in CLN8NE. Ref.1 Ref.9		VAR_013174
	Natural variant	30	1	A → P in CLN8. Ref.6		VAR_060573
	Natural variant	61	1	Missing in CLN8. Ref.8		VAR_060574
	Natural variant	70	1	R → H in CLN8. Ref.9		VAR_066920
	Natural variant	76	1	Q → R in CLN8. Ref.9		VAR_066921
	Natural variant	92	1	H → Y. Corresponds to variant rs34030778 [ dbSNP | Ensembl ].		VAR_031704
	Natural variant	107	1	I → S in CLN8. Ref.9		VAR_066922
	Natural variant	125	1	N → S in CLN8. Ref.9		VAR_066923
	Natural variant	139	1	H → Y in CLN8. Ref.9		VAR_066924
	Natural variant	155	1	A → V. Ref.1		VAR_013175
	Natural variant	158	1	Y → C in CLN8. Ref.6 Ref.7		VAR_058438
	Natural variant	170	1	T → M in CLN8; associated with M-16 on the same allele. Ref.5		VAR_026555
	Natural variant	194	1	Q → R in CLN8. Ref.6		VAR_060575
	Natural variant	204	1	R → C in CLN8. Ref.5		VAR_026556
	Natural variant	213	1	Missing in CLN8. Ref.9		VAR_066925
	Natural variant	221	1	G → S in CLN8. Ref.9		VAR_066926
	Natural variant	229	1	P → A in CLN8. Ref.9		VAR_066927
	Natural variant	237	1	G → R in CLN8. Ref.7 Ref.9		VAR_058439
	Natural variant	263	1	W → C in CLN8. Ref.5 Corresponds to variant rs28940569 [ dbSNP | Ensembl ].		VAR_026557
	Natural variant	269	1	E → V in CLN8. Ref.9		VAR_066928
Experimental info
	Mutagenesis	283 – 284	2	KK → RR: Localizes to the Golgi complex. Ref.4
	Sequence conflict	225	1	S → N in AAF13115. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Q9UBY8 [UniParc]. Last modified April 17, 2007. Version 3. Checksum: 1A5995B13E14DCDC	FASTA	286	32,787
	10 20 30 40 50 60 MNPASDGGTS ESIFDLDYAS WGIRSTLMVA GFVFYLGVFV VCHQLSSSLN ATYRSLVARE 70 80 90 100 110 120 KVFWDLAATR AVFGVQSTAA GLWALLGDPV LHADKARGQQ NWCWFHITTA TGFFCFENVA 130 140 150 160 170 180 VHLSNLIFRT FDLFLVIHHL FAFLGFLGCL VNLQAGHYLA MTTLLLEMST PFTCVSWMLL 190 200 210 220 230 240 KAGWSESLFW KLNQWLMIHM FHCRMVLTYH MWWVCFWHWD GLVSSLYLPH LTLFLVGLAL 250 260 270 280 LTLIINPYWT HKKTQQLLNP VDWNFAQPEA KSRPEGNGQL LRKKRP

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"The neuronal ceroid lipofuscinoses in human EPMR and mnd mutant mice are associated with mutations in CLN8." Ranta S., Zhang Y., Ross B., Lonka L., Takkunen E., Messer A., Sharp J., Wheeler R., Kusumi K., Mole S., Liu W., Soares M.B., Bonaldo M.F., Hirvasniemi A., de la Chapelle A., Gilliam T.C., Lehesjoki A.-E. Nat. Genet. 23:233-236(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT CLN8NE GLY-24, VARIANT VAL-155.
[2]	"Cloning of human full-length CDSs in BD Creator(TM) system donor vector." Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A. Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[3]	"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: Uterus.
[4]	"The neuronal ceroid lipofuscinosis CLN8 membrane protein is a resident of the endoplasmic reticulum." Lonka L., Kyttaelae A., Ranta S., Jalanko A., Lehesjoki A.-E. Hum. Mol. Genet. 9:1691-1697(2000) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION, MUTAGENESIS OF 283-LYS-LYS-284.
[5]	"Variant late infantile neuronal ceroid lipofuscinosis in a subset of Turkish patients is allelic to Northern epilepsy." Ranta S., Topcu M., Tegelberg S., Tan H., Uestuebuetuen A., Saatci I., Dufke A., Enders H., Pohl K., Alembik Y., Mitchell W.A., Mole S.E., Lehesjoki A.-E. Hum. Mutat. 23:300-305(2004) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS CLN8 MET-16; MET-170; CYS-204 AND CYS-263.
[6]	"Novel mutations in CLN8 in Italian variant late infantile neuronal ceroid lipofuscinosis: Another genetic hit in the Mediterranean." Cannelli N., Cassandrini D., Bertini E., Striano P., Fusco L., Gaggero R., Specchio N., Biancheri R., Vigevano F., Bruno C., Simonati A., Zara F., Santorelli F.M. Neurogenetics 7:111-117(2006) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS CLN8 PRO-30; CYS-158 AND ARG-194.
[7]	"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 CLN8 CYS-158 AND ARG-237.
[8]	"A novel CLN8 mutation in late-infantile-onset neuronal ceroid lipofuscinosis (LINCL) reveals aspects of CLN8 neurobiological function." Vantaggiato C., Redaelli F., Falcone S., Perrotta C., Tonelli A., Bondioni S., Morbin M., Riva D., Saletti V., Bonaglia M.C., Giorda R., Bresolin N., Clementi E., Bassi M.T. Hum. Mutat. 30:1104-1116(2009) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT CLN8 LYS-61 DEL, FUNCTION.
[9]	"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 CLN8 HIS-70; ARG-76; SER-107; SER-125; TYR-139; TRP-213 DEL; SER-221; ALA-229; ARG-237 AND VAL-269, VARIANT CLN8NE GLY-24.

Web resources

NCL CLN8

Neural Ceroid Lipofuscinoses mutation db

GeneReviews

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF123757 mRNA. Translation: AAF13115.1. AF123758 mRNA. Translation: AAF13116.1. AF123759 mRNA. Translation: AAF13117.1. AF123760 mRNA. Translation: AAF13118.1. AF123761 mRNA. Translation: AAF13119.1. BT007049 mRNA. Translation: AAP35698.1. BC007725 mRNA. Translation: AAH07725.1.
IPI	IPI00003926.
RefSeq	NP_061764.2. NM_018941.3.
UniGene	Hs.127675.
3D structure databases
ProteinModelPortal	Q9UBY8.
ModBase	Search...
Protein-protein interaction databases
STRING	9606.ENSP00000328182.
Polymorphism databases
DMDM	145559455.
Proteomic databases
PaxDb	Q9UBY8.
PRIDE	Q9UBY8.
Protocols and materials databases
DNASU	2055.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000331222; ENSP00000328182; ENSG00000182372.
GeneID	2055.
KEGG	hsa:2055.
UCSC	uc003wpo.4. human.
Organism-specific databases
CTD	2055.
GeneCards	GC08P001699.
HGNC	HGNC:2079. CLN8.
MIM	600143. phenotype. 607837. gene. 610003. phenotype.
neXtProt	NX_Q9UBY8.
Orphanet	228354. CLN8 disease. 1947. Progressive epilepsy - intellectual deficit, Finnish type.
PharmGKB	PA26606.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG239251.
HOGENOM	HOG000111792.
HOVERGEN	HBG028338.
InParanoid	Q9UBY8.
KO	K12360.
OMA	LTYHMWW.
OrthoDB	EOG4V171T.
PhylomeDB	Q9UBY8.
Gene expression databases
Bgee	Q9UBY8.
CleanEx	HS_CLN8.
Genevestigator	Q9UBY8.
GermOnline	ENSG00000182372. Homo sapiens.
Family and domain databases
InterPro	IPR006634. TLC-dom. [Graphical view]
Pfam	PF03798. TRAM_LAG1_CLN8. 1 hit. [Graphical view]
SMART	SM00724. TLC. 1 hit. [Graphical view]
PROSITE	PS50922. TLC. 1 hit. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	CLN8. human.
GenomeRNAi	2055.
NextBio	8357.
SOURCE	Search...

Entry information

Entry name

CLN8_HUMAN

Accession

Primary (citable) accession number: Q9UBY8
Secondary accession number(s): Q86U71, Q96I95

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 2, 2002
Last sequence update:	April 17, 2007
Last modified:	May 1, 2013
This is version 111 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.