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Protein

Ceroid-lipofuscinosis neuronal protein 5

Gene

CLN5

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Plays a role in influencing the retrograde trafficking of lysosomal sorting receptors SORT1 and IGF2R from the endosomes to the trans-Golgi network by controlling the recruitment of retromer complex to the endosomal membrane. Regulates the localization and activation of RAB7A which is required to recruit the retromer complex to the endosomal membrane (PubMed:22431521).1 Publication

GO - Molecular functioni

  • mannose binding Source: UniProtKB

GO - Biological processi

  • brain development Source: UniProtKB
  • glycosylation Source: UniProtKB
  • lysosomal lumen acidification Source: UniProtKB
  • neurogenesis Source: UniProtKB
  • neuron maturation Source: UniProtKB
  • positive regulation of GTP binding Source: UniProtKB
  • protein catabolic process Source: UniProtKB
  • retrograde transport, endosome to Golgi Source: UniProtKB
  • signal peptide processing Source: UniProtKB
Complete GO annotation...

Enzyme and pathway databases

BioCyciZFISH:ENSG00000102805-MONOMER.

Names & Taxonomyi

Protein namesi
Recommended name:
Ceroid-lipofuscinosis neuronal protein 5
Short name:
Protein CLN5
Cleaved into the following chain:
Gene namesi
Name:CLN5
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 13

Organism-specific databases

HGNCiHGNC:2076. CLN5.

Subcellular locationi

Ceroid-lipofuscinosis neuronal protein 5, secreted form :
Ceroid-lipofuscinosis neuronal protein 5 :
  • Membrane 1 Publication; Single-pass type II membrane protein 1 Publication

  • Note: An amphipathic anchor region facilitates its association with the membrane.1 Publication

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 23Cytoplasmic1 PublicationAdd BLAST23
Transmembranei24 – 41Helical; Signal-anchor for type II membrane proteinSequence analysisAdd BLAST18
Topological domaini42 – 358Lumenal1 PublicationAdd BLAST317

GO - Cellular componenti

  • cytosol Source: GOC
  • endoplasmic reticulum Source: UniProtKB
  • extracellular exosome Source: UniProtKB
  • Golgi apparatus Source: UniProtKB
  • integral component of membrane Source: UniProtKB
  • lysosomal membrane Source: UniProtKB
  • lysosome Source: UniProtKB
  • perinuclear region of cytoplasm Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Lysosome, Membrane

Pathology & Biotechi

Involvement in diseasei

Ceroid lipofuscinosis, neuronal, 5 (CLN5)10 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA 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.
See also OMIM:256731
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_06689526W → R in CLN5. 1 PublicationCorresponds to variant rs199727787dbSNPEnsembl.1
Natural variantiVAR_04270063R → H in CLN5; retained in the endoplasmic reticulum rather than reaching the lysosome. 3 PublicationsCorresponds to variant rs104894386dbSNPEnsembl.1
Natural variantiVAR_04270263R → P in CLN5; Retained in the endoplasmic reticulum rather than reaching the lysosome. 2 PublicationsCorresponds to variant rs104894386dbSNPEnsembl.1
Natural variantiVAR_06689677C → Y in CLN5. 1 PublicationCorresponds to variant rs267606738dbSNPEnsembl.1
Natural variantiVAR_066897143N → S in CLN5; loss of glycosylation; effectively transported to the lysosome. 2 PublicationsCorresponds to variant rs386833975dbSNPEnsembl.1
Natural variantiVAR_066898149L → P in CLN5. 1 PublicationCorresponds to variant rs386833976dbSNPEnsembl.1
Natural variantiVAR_066899156P → S in CLN5. 1 PublicationCorresponds to variant rs386833977dbSNPEnsembl.1
Natural variantiVAR_066900158W → R in CLN5. 1 PublicationCorresponds to variant rs147065248dbSNPEnsembl.1
Natural variantiVAR_066901158W → S in CLN5. 1 PublicationCorresponds to variant rs386833978dbSNPEnsembl.1
Natural variantiVAR_066902193N → K in CLN5. 1 PublicationCorresponds to variant rs138611001dbSNPEnsembl.1
Natural variantiVAR_042701209Y → D in CLN5. 2 PublicationsCorresponds to variant rs386833981dbSNPEnsembl.1
Natural variantiVAR_005137230D → N in CLN5; creates a new N-glycosylation site; retained in the endoplasmic reticulum rather than reaching the lysosome. 6 PublicationsCorresponds to variant rs28940280dbSNPEnsembl.1
Natural variantiVAR_066903325Y → C in CLN5. 1 PublicationCorresponds to variant rs148862100dbSNPEnsembl.1
Natural variantiVAR_059032330W → C in CLN5; retained in the endoplasmic reticulum rather than reaching the lysosome. 1 PublicationCorresponds to variant rs386833968dbSNPEnsembl.1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi130N → Q: Loss of glycosylation. Retained in the endoplasmic reticulum rather than reaching the lysosome. 1 Publication1
Mutagenesisi143N → Q: Loss of glycosylation. Effectively transported to the lysosome. 1 Publication1
Mutagenesisi178N → Q: Loss of glycosylation. Effectively transported to the lysosome. 1 Publication1
Mutagenesisi203N → Q: Loss of glycosylation. Retained in the endoplasmic reticulum rather than reaching the lysosome. 1 Publication1
Mutagenesisi255N → Q: Loss of glycosylation. Retained in the endoplasmic reticulum rather than reaching the lysosome. 1 Publication1
Mutagenesisi271N → Q: Loss of glycosylation. Retained in the endoplasmic reticulum rather than reaching the lysosome. 1 Publication1
Mutagenesisi281N → Q: Loss of glycosylation. Partially retained in the endoplasmic reticulum. 1 Publication1
Mutagenesisi352N → Q: Loss of glycosylation. Retained in the Golgi apparatus rather than reaching the lysosome. 1 Publication1

Keywords - Diseasei

Disease mutation, Epilepsy, Neurodegeneration, Neuronal ceroid lipofuscinosis

Organism-specific databases

DisGeNETi1203.
MalaCardsiCLN5.
MIMi256731. phenotype.
OpenTargetsiENSG00000102805.
Orphaneti228360. CLN5 disease.
PharmGKBiPA26603.

Polymorphism and mutation databases

BioMutaiCLN5.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_0000438009? – 358Ceroid-lipofuscinosis neuronal protein 5, secreted form
ChainiPRO_00000898601 – 358Ceroid-lipofuscinosis neuronal protein 5Add BLAST358

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi130N-linked (GlcNAc...)1 Publication1
Glycosylationi143N-linked (GlcNAc...)1 Publication1
Glycosylationi178N-linked (GlcNAc...)1 Publication1
Glycosylationi203N-linked (GlcNAc...)1 Publication1
Glycosylationi255N-linked (GlcNAc...)1 Publication1
Glycosylationi271N-linked (GlcNAc...)1 Publication1
Glycosylationi281N-linked (GlcNAc...)1 Publication1
Glycosylationi352N-linked (GlcNAc...)1 Publication1

Post-translational modificationi

N-glycosylated with both high mannose and complex type sugars. Glycosylation is important for proper folding and trafficking to the lysosomes.4 Publications
Ceroid-lipofuscinosis neuronal protein 5: The type II membrane signal anchor is proteolytically cleaved to produce a mature form that is transported to the lysosomes (Ceroid-lipofuscinosis neuronal protein 5, secreted form) (PubMed:24038957, PubMed:20052765).2 Publications
Can undergo proteolytic cleavage at the C-terminus, probably by a cysteine protease and may involve the removal of approximately 10-15 residues from the C-terminal end (PubMed:26342652).1 Publication

Keywords - PTMi

Glycoprotein

Proteomic databases

EPDiO75503.
MaxQBiO75503.
PaxDbiO75503.
PeptideAtlasiO75503.
PRIDEiO75503.

PTM databases

iPTMnetiO75503.
PhosphoSitePlusiO75503.

Expressioni

Tissue specificityi

Ubiquitous.

Gene expression databases

BgeeiENSG00000102805.
CleanExiHS_CLN5.
ExpressionAtlasiO75503. baseline and differential.
GenevisibleiO75503. HS.

Organism-specific databases

HPAiHPA041788.

Interactioni

Subunit structurei

Interacts with SORT1, RAB5A and RAB7A (PubMed:22431521). Interacts with PPT1, TPP1, CLN3, CLN6, CLN8, ATP5A1 and ATP5B (By similarity).By similarity1 Publication

Protein-protein interaction databases

BioGridi107614. 43 interactors.
IntActiO75503. 3 interactors.
MINTiMINT-4656296.
STRINGi9606.ENSP00000366673.

Structurei

3D structure databases

ProteinModelPortaliO75503.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni304 – 343Membrane-anchoring1 PublicationAdd BLAST40

Sequence similaritiesi

Belongs to the CLN5 family.Curated

Keywords - Domaini

Signal-anchor, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiENOG410IJEH. Eukaryota.
ENOG4110RH0. LUCA.
GeneTreeiENSGT00390000010065.
HOGENOMiHOG000060233.
HOVERGENiHBG005345.
InParanoidiO75503.
KOiK12390.
PhylomeDBiO75503.
TreeFamiTF330864.

Family and domain databases

InterProiIPR026138. CLN5.
[Graphical view]
PANTHERiPTHR15380. PTHR15380. 1 hit.
PfamiPF15014. CLN5. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

O75503-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MAQEVDTAQG AEMRRGAGAA RGRASWCWAL ALLWLAVVPG WSRVSGIPSR
60 70 80 90 100
RHWPVPYKRF DFRPKPDPYC QAKYTFCPTG SPIPVMEGDD DIEVFRLQAP
110 120 130 140 150
VWEFKYGDLL GHLKIMHDAI GFRSTLTGKN YTMEWYELFQ LGNCTFPHLR
160 170 180 190 200
PEMDAPFWCN QGAACFFEGI DDVHWKENGT LVQVATISGN MFNQMAKWVK
210 220 230 240 250
QDNETGIYYE TWNVKASPEK GAETWFDSYD CSKFVLRTFN KLAEFGAEFK
260 270 280 290 300
NIETNYTRIF LYSGEPTYLG NETSVFGPTG NKTLGLAIKR FYYPFKPHLP
310 320 330 340 350
TKEFLLSLLQ IFDAVIVHKQ FYLFYNFEYW FLPMKFPFIK ITYEEIPLPI

RNKTLSGL
Length:358
Mass (Da):41,497
Last modified:April 29, 2008 - v2
Checksum:i07E49D4913685190
GO

Sequence cautioni

The sequence AAC27614 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti57Y → C in BAG52069 (PubMed:14702039).Curated1
Sequence conflicti92I → T in BAG52069 (PubMed:14702039).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_06689526W → R in CLN5. 1 PublicationCorresponds to variant rs199727787dbSNPEnsembl.1
Natural variantiVAR_04270063R → H in CLN5; retained in the endoplasmic reticulum rather than reaching the lysosome. 3 PublicationsCorresponds to variant rs104894386dbSNPEnsembl.1
Natural variantiVAR_04270263R → P in CLN5; Retained in the endoplasmic reticulum rather than reaching the lysosome. 2 PublicationsCorresponds to variant rs104894386dbSNPEnsembl.1
Natural variantiVAR_06689677C → Y in CLN5. 1 PublicationCorresponds to variant rs267606738dbSNPEnsembl.1
Natural variantiVAR_066897143N → S in CLN5; loss of glycosylation; effectively transported to the lysosome. 2 PublicationsCorresponds to variant rs386833975dbSNPEnsembl.1
Natural variantiVAR_066898149L → P in CLN5. 1 PublicationCorresponds to variant rs386833976dbSNPEnsembl.1
Natural variantiVAR_066899156P → S in CLN5. 1 PublicationCorresponds to variant rs386833977dbSNPEnsembl.1
Natural variantiVAR_066900158W → R in CLN5. 1 PublicationCorresponds to variant rs147065248dbSNPEnsembl.1
Natural variantiVAR_066901158W → S in CLN5. 1 PublicationCorresponds to variant rs386833978dbSNPEnsembl.1
Natural variantiVAR_066902193N → K in CLN5. 1 PublicationCorresponds to variant rs138611001dbSNPEnsembl.1
Natural variantiVAR_042701209Y → D in CLN5. 2 PublicationsCorresponds to variant rs386833981dbSNPEnsembl.1
Natural variantiVAR_059031219E → A.Corresponds to variant rs11842935dbSNPEnsembl.1
Natural variantiVAR_005137230D → N in CLN5; creates a new N-glycosylation site; retained in the endoplasmic reticulum rather than reaching the lysosome. 6 PublicationsCorresponds to variant rs28940280dbSNPEnsembl.1
Natural variantiVAR_005138319K → R.1 PublicationCorresponds to variant rs1800209dbSNPEnsembl.1
Natural variantiVAR_066903325Y → C in CLN5. 1 PublicationCorresponds to variant rs148862100dbSNPEnsembl.1
Natural variantiVAR_059032330W → C in CLN5; retained in the endoplasmic reticulum rather than reaching the lysosome. 1 PublicationCorresponds to variant rs386833968dbSNPEnsembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF068227 mRNA. Translation: AAC27614.1. Different initiation.
AK075109 mRNA. Translation: BAG52069.1.
AC001226 Genomic DNA. No translation available.
RefSeqiNP_006484.1. NM_006493.2.
UniGeneiHs.30213.

Genome annotation databases

EnsembliENST00000377453; ENSP00000366673; ENSG00000102805.
GeneIDi1203.
KEGGihsa:1203.
UCSCiuc058xoc.1. human.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Web resourcesi

NCL CLN5

Neural Ceroid Lipofuscinoses mutation db

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF068227 mRNA. Translation: AAC27614.1. Different initiation.
AK075109 mRNA. Translation: BAG52069.1.
AC001226 Genomic DNA. No translation available.
RefSeqiNP_006484.1. NM_006493.2.
UniGeneiHs.30213.

3D structure databases

ProteinModelPortaliO75503.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi107614. 43 interactors.
IntActiO75503. 3 interactors.
MINTiMINT-4656296.
STRINGi9606.ENSP00000366673.

PTM databases

iPTMnetiO75503.
PhosphoSitePlusiO75503.

Polymorphism and mutation databases

BioMutaiCLN5.

Proteomic databases

EPDiO75503.
MaxQBiO75503.
PaxDbiO75503.
PeptideAtlasiO75503.
PRIDEiO75503.

Protocols and materials databases

DNASUi1203.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000377453; ENSP00000366673; ENSG00000102805.
GeneIDi1203.
KEGGihsa:1203.
UCSCiuc058xoc.1. human.

Organism-specific databases

CTDi1203.
DisGeNETi1203.
GeneCardsiCLN5.
GeneReviewsiCLN5.
HGNCiHGNC:2076. CLN5.
HPAiHPA041788.
MalaCardsiCLN5.
MIMi256731. phenotype.
608102. gene.
neXtProtiNX_O75503.
OpenTargetsiENSG00000102805.
Orphaneti228360. CLN5 disease.
PharmGKBiPA26603.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IJEH. Eukaryota.
ENOG4110RH0. LUCA.
GeneTreeiENSGT00390000010065.
HOGENOMiHOG000060233.
HOVERGENiHBG005345.
InParanoidiO75503.
KOiK12390.
PhylomeDBiO75503.
TreeFamiTF330864.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000102805-MONOMER.

Miscellaneous databases

ChiTaRSiCLN5. human.
GeneWikiiCLN5.
GenomeRNAii1203.
PROiO75503.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000102805.
CleanExiHS_CLN5.
ExpressionAtlasiO75503. baseline and differential.
GenevisibleiO75503. HS.

Family and domain databases

InterProiIPR026138. CLN5.
[Graphical view]
PANTHERiPTHR15380. PTHR15380. 1 hit.
PfamiPF15014. CLN5. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiCLN5_HUMAN
AccessioniPrimary (citable) accession number: O75503
Secondary accession number(s): B3KQK7
Entry historyi
Integrated into UniProtKB/Swiss-Prot: December 15, 1998
Last sequence update: April 29, 2008
Last modified: November 2, 2016
This is version 138 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 13
    Human chromosome 13: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.