O75503 (CLN5_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Ceroid-lipofuscinosis neuronal protein 5
Short name=Protein CLN5

Gene names

Name:

CLN5

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	358 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Subcellular location	Lysosome Ref.3.
Tissue specificity	Ubiquitous.
Post-translational modification	Glycosylated. Ref.3
Involvement in disease	Defects in CLN5 are the cause of neuronal ceroid lipofuscinosis type 5 (CLN5) [MIM:256731]; also known as Finnish variant late-infantile neuronal ceroid lipofuscinosis (vLINCL). 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 5 comprise mixed combinations of granular, curvilinear, and fingerprint profiles. Ref.1 Ref.4 Ref.5 Ref.6 Ref.7
Sequence similarities	Belongs to the CLN5 family.
Sequence caution	The sequence AAC27614.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.

Ontologies

Keywords
Cellular component	Lysosome
Coding sequence diversity	Polymorphism
Disease	Disease mutation Epilepsy Neurodegeneration Neuronal ceroid lipofuscinosis
Domain	Signal
PTM	Glycoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	brain development Inferred from expression pattern. Source: UniProtKB cell death Inferred from electronic annotation. Source: UniProtKB-KW lysosomal lumen acidification Inferred from mutant phenotype. Source: UniProtKB neuron maturation Non-traceable author statement. Source: UniProtKB protein catabolic process Non-traceable author statement. Source: UniProtKB
Cellular component	Golgi apparatus Inferred from direct assay. Source: UniProtKB endoplasmic reticulum Inferred from direct assay. Source: UniProtKB integral to membrane Inferred from direct assay. Source: UniProtKB lysosomal membrane Inferred from direct assay. Source: UniProtKB perinuclear region of cytoplasm Inferred from direct assay. Source: UniProtKB
Molecular function	protein binding Inferred from physical interaction. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
KRT8	P05787	1	EBI-1043514,EBI-297852

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 46	46	Potential
	Chain	47 – 358	312	Ceroid-lipofuscinosis neuronal protein 5		PRO_0000089860
Amino acid modifications
	Glycosylation	130	1	N-linked (GlcNAc...) Potential
	Glycosylation	143	1	N-linked (GlcNAc...) Potential
	Glycosylation	178	1	N-linked (GlcNAc...) Potential
	Glycosylation	203	1	N-linked (GlcNAc...) Potential
	Glycosylation	255	1	N-linked (GlcNAc...) Potential
	Glycosylation	271	1	N-linked (GlcNAc...) Potential
	Glycosylation	281	1	N-linked (GlcNAc...) Potential
	Glycosylation	352	1	N-linked (GlcNAc...) Potential
Natural variations
	Natural variant	26	1	W → R in CLN5.		VAR_066895
	Natural variant	63	1	R → H in CLN5. Ref.4		VAR_042700
	Natural variant	63	1	R → P in CLN5. Ref.5		VAR_042702
	Natural variant	77	1	C → Y in CLN5.		VAR_066896
	Natural variant	143	1	N → S in CLN5.		VAR_066897
	Natural variant	149	1	L → P in CLN5.		VAR_066898
	Natural variant	156	1	P → S in CLN5.		VAR_066899
	Natural variant	158	1	W → R in CLN5.		VAR_066900
	Natural variant	158	1	W → S in CLN5.		VAR_066901
	Natural variant	193	1	N → K in CLN5.		VAR_066902
	Natural variant	209	1	Y → D in CLN5. Ref.6		VAR_042701
	Natural variant	219	1	E → A. Corresponds to variant rs11842935 [ dbSNP | Ensembl ].		VAR_059031
	Natural variant	230	1	D → N in CLN5. Ref.1 Ref.5		VAR_005137
	Natural variant	319	1	K → R. Ref.1 Corresponds to variant rs1800209 [ dbSNP | Ensembl ].		VAR_005138
	Natural variant	325	1	Y → C in CLN5.		VAR_066903
	Natural variant	330	1	W → C in CLN5; retained in the endoplasmic reticulum rather than reaching the lysosome. Ref.7		VAR_059032

Sequences

	Sequence		Length	Mass (Da)
	O75503 [UniParc]. Last modified April 29, 2008. Version 2. Checksum: 07E49D4913685190	FASTA	358	41,497
	10 20 30 40 50 60 MAQEVDTAQG AEMRRGAGAA RGRASWCWAL ALLWLAVVPG WSRVSGIPSR RHWPVPYKRF 70 80 90 100 110 120 DFRPKPDPYC QAKYTFCPTG SPIPVMEGDD DIEVFRLQAP VWEFKYGDLL GHLKIMHDAI 130 140 150 160 170 180 GFRSTLTGKN YTMEWYELFQ LGNCTFPHLR PEMDAPFWCN QGAACFFEGI DDVHWKENGT 190 200 210 220 230 240 LVQVATISGN MFNQMAKWVK QDNETGIYYE TWNVKASPEK GAETWFDSYD CSKFVLRTFN 250 260 270 280 290 300 KLAEFGAEFK NIETNYTRIF LYSGEPTYLG NETSVFGPTG NKTLGLAIKR FYYPFKPHLP 310 320 330 340 350 TKEFLLSLLQ IFDAVIVHKQ FYLFYNFEYW FLPMKFPFIK ITYEEIPLPI RNKTLSGL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"CLN5, a novel gene encoding a putative transmembrane protein mutated in Finnish variant late infantile neuronal ceroid lipofuscinosis." Savukoski M., Klockars T., Holmberg V., Santavuori P., Lander E.S., Peltonen L. Nat. Genet. 19:286-288(1998) [PubMed: 9662406] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT CLN5 ASN-230, VARIANT ARG-319. Tissue: Fetal brain.
[2]	"The DNA sequence and analysis of human chromosome 13." Dunham A., Matthews L.H., Burton J., Ashurst J.L., Howe K.L., Ashcroft K.J., Beare D.M., Burford D.C., Hunt S.E., Griffiths-Jones S., Jones M.C., Keenan S.J., Oliver K., Scott C.E., Ainscough R., Almeida J.P., Ambrose K.D., Andrews D.T. , Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J., Bannerjee R., Barlow K.F., Bates K., Beasley H., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y., Burrill W., Carder C., Carter N.P., Chapman J.C., Clamp M.E., Clark S.Y., Clarke G., Clee C.M., Clegg S.C., Cobley V., Collins J.E., Corby N., Coville G.J., Deloukas P., Dhami P., Dunham I., Dunn M., Earthrowl M.E., Ellington A.G., Faulkner L., Frankish A.G., Frankland J., French L., Garner P., Garnett J., Gilbert J.G.R., Gilson C.J., Ghori J., Grafham D.V., Gribble S.M., Griffiths C., Hall R.E., Hammond S., Harley J.L., Hart E.A., Heath P.D., Howden P.J., Huckle E.J., Hunt P.J., Hunt A.R., Johnson C., Johnson D., Kay M., Kimberley A.M., King A., Laird G.K., Langford C.J., Lawlor S., Leongamornlert D.A., Lloyd D.M., Lloyd C., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M., McLaren S.J., McMurray A., Milne S., Moore M.J.F., Nickerson T., Palmer S.A., Pearce A.V., Peck A.I., Pelan S., Phillimore B., Porter K.M., Rice C.M., Searle S., Sehra H.K., Shownkeen R., Skuce C.D., Smith M., Steward C.A., Sycamore N., Tester J., Thomas D.W., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., West A.P., Whitehead S.L., Willey D.L., Wilming L., Wray P.W., Wright M.W., Young L., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Beck S., Bentley D.R., Rogers J., Ross M.T. Nature 428:522-528(2004) [PubMed: 15057823] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]	"Lysosomal localization of the neuronal ceroid lipofuscinosis CLN5 protein." Isosomppi J., Vesa J., Jalanko A., Peltonen L. Hum. Mol. Genet. 11:885-891(2002) [PubMed: 11971870] [Abstract] Cited for: SUBCELLULAR LOCATION, GLYCOSYLATION.
[4]	"A CLN5 mutation causing an atypical neuronal ceroid lipofuscinosis of juvenile onset." Pineda-Trujillo N., Cornejo W., Carrizosa J., Wheeler R.B., Munera S., Valencia A., Agudelo-Arango J., Cogollo A., Anderson G., Bedoya G., Mole S.E., Ruiz-Linares A. Neurology 64:740-742(2005) [PubMed: 15728307] [Abstract] Cited for: VARIANT CLN5 HIS-63.
[5]	"Two novel CLN5 mutations in a Portuguese patient with vLINCL: insights into molecular mechanisms of CLN5 deficiency." Bessa C., Teixeira C.A., Mangas M., Dias A., Sa Miranda M.C., Guimaraes A., Ferreira J.C., Canas N., Cabral P., Ribeiro M.G. Mol. Genet. Metab. 89:245-253(2006) [PubMed: 16814585] [Abstract] Cited for: VARIANTS CLN5 PRO-63 AND ASN-230.
[6]	"Revelation of a novel CLN5 mutation in early juvenile neuronal ceroid lipofuscinosis." Cannelli N., Nardocci N., Cassandrini D., Morbin M., Aiello C., Bugiani M., Criscuolo L., Zara F., Striano P., Granata T., Bertini E., Simonati A., Santorelli F.M. Neuropediatrics 38:46-49(2007) [PubMed: 17607606] [Abstract] Cited for: VARIANT CLN5 ASP-209.
[7]	"Retention of lysosomal protein CLN5 in the endoplasmic reticulum causes neuronal ceroid lipofuscinosis in Asian sibship." Lebrun A.-H., Storch S., Rueschendorf F., Schmiedt M.-L., Kyttaelae A., Mole S.E., Kitzmueller C., Saar K., Mewasingh L.D., Boda V., Kohlschuetter A., Ullrich K., Braulke T., Schulz A. Hum. Mutat. 30:E651-E661(2009) [PubMed: 19309691] [Abstract] Cited for: VARIANT CLN5 CYS-330, CHARACTERIZATION OF VARIANT CLN5 CYS-330.
[8]	"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. 0:0-0(2011) [PubMed: 21990111] [Abstract] Cited for: VARIANTS CLN5 ARG-26; HIS-63; TYR-77; SER-143; PRO-149; SER-156; ARG-158; SER-158; LYS-193; ASP-209 AND CYS-325.
+	Additional computationally mapped references.

Web resources

NCL CLN5

Neural Ceroid Lipofuscinoses mutation db

GeneReviews

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF068227 mRNA. Translation: AAC27614.1. Different initiation. AC001226 Genomic DNA. No translation available.
IPI	IPI01012178.
RefSeq	NP_006484.1. NM_006493.2.
UniGene	Hs.30213.
3D structure databases
ModBase	Search...
Protein-protein interaction databases
IntAct	O75503. 2 interactions.
STRING	O75503.
Proteomic databases
PeptideAtlas	O75503.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000377453; ENSP00000366673; ENSG00000102805.
GeneID	1203.
KEGG	hsa:1203.
UCSC	uc001vkc.1. human.
Organism-specific databases
CTD	1203.
GeneCards	GC13P077564.
H-InvDB	HIX0037301.
HGNC	HGNC:2076. CLN5.
HPA	HPA041788.
MIM	256731. phenotype. 608102. gene.
neXtProt	NX_O75503.
Orphanet	228360. CLN5 disease.
PharmGKB	PA26603.
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG17344.
GeneTree	ENSGT00390000010065.
HOGENOM	HBG447053.
HOVERGEN	HBG005345.
InParanoid	O75503.
OrthoDB	EOG4BZN32.
Gene expression databases
ArrayExpress	O75503.
Bgee	O75503.
CleanEx	HS_CLN5.
Genevestigator	O75503.
GermOnline	ENSG00000102805. Homo sapiens.
Family and domain databases
KO	K12390.
ProtoNet	Search...
Other
NextBio	4967.
SOURCE	Search...

Entry information

Entry name

CLN5_HUMAN

Accession

Primary (citable) accession number: O75503

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 15, 1998
Last sequence update:	April 29, 2008
Last modified:	January 25, 2012
This is version 92 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.