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Protein

Mucolipin-1

Gene

MCOLN1

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

Functioni

Cation channel probably playing a role in the endocytic pathway and in the control of membrane trafficking of proteins and lipids. Could play a major role in Ca2+ transport regulating lysosomal exocytosis.2 Publications

Enzyme regulationi

Channel function is transiently modulated by changes in Ca2+, and inhibited by a reduction of pH; pH changes modify the aggregation state of unitary channels.

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Ion channel

Keywords - Biological processi

Calcium transport, Ion transport, Transport

Keywords - Ligandi

Calcium

Enzyme and pathway databases

ReactomeiR-HSA-3295583. TRP channels.
R-HSA-917977. Transferrin endocytosis and recycling.
SIGNORiQ9GZU1.

Protein family/group databases

TCDBi1.A.5.3.1. the polycystin cation channel (pcc) family.

Names & Taxonomyi

Protein namesi
Recommended name:
Mucolipin-1
Alternative name(s):
MG-2
Mucolipidin
Gene namesi
Name:MCOLN1
Synonyms:ML4
ORF Names:MSTP080
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 19

Organism-specific databases

HGNCiHGNC:13356. MCOLN1.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Transmembranei66 – 86HelicalSequence analysisAdd BLAST21
Transmembranei297 – 317HelicalSequence analysisAdd BLAST21
Transmembranei350 – 370HelicalSequence analysisAdd BLAST21
Transmembranei388 – 408HelicalSequence analysisAdd BLAST21
Transmembranei428 – 448HelicalSequence analysisAdd BLAST21
Transmembranei497 – 517HelicalSequence analysisAdd BLAST21

GO - Cellular componenti

  • cytoplasm Source: HPA
  • endosome membrane Source: Reactome
  • integral component of membrane Source: UniProtKB
  • integral component of plasma membrane Source: UniProtKB
  • late endosome membrane Source: UniProtKB-SubCell
  • lysosomal membrane Source: UniProtKB
  • plasma membrane Source: HPA
  • receptor complex Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Endosome, Lysosome, Membrane

Pathology & Biotechi

Involvement in diseasei

Mucolipidosis 4 (ML4)4 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionAn autosomal recessive lysosomal storage disorder characterized by severe psychomotor retardation and ophthalmologic abnormalities, including corneal opacity, retinal degeneration and strabismus. Storage bodies of lipids and water-soluble substances are seen by electron microscopy in almost every cell type of the patients. Most patients are unable to speak or walk independently and reach a maximal developmental level of 1-2 years. All patients have constitutive achlorhydia associated with a secondary elevation of serum gastrin levels.
See also OMIM:252650
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_019369106L → P in ML4. 1 Publication1
Natural variantiVAR_019370232T → P in ML4; fails to localize to late endosomes. 2 PublicationsCorresponds to variant rs767122713dbSNPEnsembl.1
Natural variantiVAR_019371362D → Y in ML4; affects channel activity. 3 PublicationsCorresponds to variant rs121908372dbSNPEnsembl.1
Natural variantiVAR_038380403R → C in ML4. 1 PublicationCorresponds to variant rs121908374dbSNPEnsembl.1
Natural variantiVAR_019372408Missing in ML4; mild psychomotor involvement; does not affect channel activity; affects channel inhibition by low pH; still localizes to late endosomes. 5 Publications1
Natural variantiVAR_019373446V → L in ML4; does not affect channel activity; affects channel inhibition by low pH. 2 Publications1
Natural variantiVAR_019374447L → P in ML4. 1 Publication1
Natural variantiVAR_019375465F → L in ML4; still localizes to late endosomes. 2 Publications1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi44 – 46RLK → AAA: Abolishes interaction with PDCD6 and decreases formation of aberrant endosomes upon overexpression. 1 Publication3
Mutagenesisi44R → A: Abolishes interaction with PDCD6. 1 Publication1
Mutagenesisi45L → A: Abolishes interaction with PDCD6. 1 Publication1
Mutagenesisi47 – 49YFF → AAA: Abolishes interaction with PDCD6. 1 Publication3

Keywords - Diseasei

Disease mutation, Mucolipidosis

Organism-specific databases

DisGeNETi57192.
MalaCardsiMCOLN1.
MIMi252650. phenotype.
OpenTargetsiENSG00000090674.
Orphaneti578. Mucolipidosis type 4.
PharmGKBiPA30699.

Chemistry databases

GuidetoPHARMACOLOGYi501.

Polymorphism and mutation databases

BioMutaiMCOLN1.
DMDMi50401163.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002153621 – 580Mucolipin-1Add BLAST580

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei10PhosphoserineBy similarity1
Glycosylationi230N-linked (GlcNAc...)1 Publication1
Modified residuei557PhosphoserineBy similarity1

Keywords - PTMi

Glycoprotein, Phosphoprotein

Proteomic databases

EPDiQ9GZU1.
MaxQBiQ9GZU1.
PaxDbiQ9GZU1.
PeptideAtlasiQ9GZU1.
PRIDEiQ9GZU1.

PTM databases

iPTMnetiQ9GZU1.
PhosphoSitePlusiQ9GZU1.
SwissPalmiQ9GZU1.

Expressioni

Tissue specificityi

Widely expressed in adult and fetal tissues.3 Publications

Gene expression databases

BgeeiENSG00000090674.
CleanExiHS_MCOLN1.
ExpressionAtlasiQ9GZU1. baseline and differential.
GenevisibleiQ9GZU1. HS.

Organism-specific databases

HPAiCAB032637.
HPA031763.

Interactioni

Subunit structurei

Forms multimeric complexes. Interacts with PDCD6.2 Publications

Protein-protein interaction databases

BioGridi121441. 4 interactors.
IntActiQ9GZU1. 3 interactors.
MINTiMINT-1409368.
STRINGi9606.ENSP00000264079.

Structurei

3D structure databases

ProteinModelPortaliQ9GZU1.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG3733. Eukaryota.
ENOG410Z1HH. LUCA.
GeneTreeiENSGT00390000017126.
HOGENOMiHOG000232158.
HOVERGENiHBG052430.
InParanoidiQ9GZU1.
KOiK04992.
OMAiPANDTFN.
OrthoDBiEOG091G026A.
PhylomeDBiQ9GZU1.
TreeFamiTF317783.

Family and domain databases

InterProiIPR013122. PKD1_2_channel.
[Graphical view]
PfamiPF08016. PKD_channel. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Q9GZU1-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MTAPAGPRGS ETERLLTPNP GYGTQAGPSP APPTPPEEED LRRRLKYFFM
60 70 80 90 100
SPCDKFRAKG RKPCKLMLQV VKILVVTVQL ILFGLSNQLA VTFREENTIA
110 120 130 140 150
FRHLFLLGYS DGADDTFAAY TREQLYQAIF HAVDQYLALP DVSLGRYAYV
160 170 180 190 200
RGGGDPWTNG SGLALCQRYY HRGHVDPAND TFDIDPMVVT DCIQVDPPER
210 220 230 240 250
PPPPPSDDLT LLESSSSYKN LTLKFHKLVN VTIHFRLKTI NLQSLINNEI
260 270 280 290 300
PDCYTFSVLI TFDNKAHSGR IPISLETQAH IQECKHPSVF QHGDNSFRLL
310 320 330 340 350
FDVVVILTCS LSFLLCARSL LRGFLLQNEF VGFMWRQRGR VISLWERLEF
360 370 380 390 400
VNGWYILLVT SDVLTISGTI MKIGIEAKNL ASYDVCSILL GTSTLLVWVG
410 420 430 440 450
VIRYLTFFHN YNILIATLRV ALPSVMRFCC CVAVIYLGYC FCGWIVLGPY
460 470 480 490 500
HVKFRSLSMV SECLFSLING DDMFVTFAAM QAQQGRSSLV WLFSQLYLYS
510 520 530 540 550
FISLFIYMVL SLFIALITGA YDTIKHPGGA GAEESELQAY IAQCQDSPTS
560 570 580
GKFRRGSGSA CSLLCCCGRD PSEEHSLLVN
Length:580
Mass (Da):65,022
Last modified:March 1, 2001 - v1
Checksum:i7E7691F58D01C804
GO

Sequence cautioni

The sequence AAQ13604 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated
The sequence CAC07813 differs from that shown. Probable cloning artifact.Curated
The sequence EAW69031 differs from that shown. Reason: Erroneous gene model prediction.Curated
The sequence EAW69034 differs from that shown. Reason: Erroneous gene model prediction.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti164 – 191ALCQR…MVVTD → LSASGTTTEATWTRPTTHLT LIRWWLLVN in AAG42242 (PubMed:10973263).CuratedAdd BLAST28
Sequence conflicti203P → S in CAC08215 (PubMed:11013137).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_019369106L → P in ML4. 1 Publication1
Natural variantiVAR_019370232T → P in ML4; fails to localize to late endosomes. 2 PublicationsCorresponds to variant rs767122713dbSNPEnsembl.1
Natural variantiVAR_036453331V → L in a breast cancer sample; somatic mutation. 1 Publication1
Natural variantiVAR_019371362D → Y in ML4; affects channel activity. 3 PublicationsCorresponds to variant rs121908372dbSNPEnsembl.1
Natural variantiVAR_038380403R → C in ML4. 1 PublicationCorresponds to variant rs121908374dbSNPEnsembl.1
Natural variantiVAR_019372408Missing in ML4; mild psychomotor involvement; does not affect channel activity; affects channel inhibition by low pH; still localizes to late endosomes. 5 Publications1
Natural variantiVAR_019373446V → L in ML4; does not affect channel activity; affects channel inhibition by low pH. 2 Publications1
Natural variantiVAR_019374447L → P in ML4. 1 Publication1
Natural variantiVAR_019375465F → L in ML4; still localizes to late endosomes. 2 Publications1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AJ293659 mRNA. Translation: CAC07813.1. Sequence problems.
AJ293970 mRNA. Translation: CAC08215.1.
AF287269 mRNA. Translation: AAG00797.1.
AF287270 Genomic DNA. Translation: AAG00798.1.
AF249319 mRNA. Translation: AAG10422.1.
AF305579
, AF305572, AF305573, AF305574, AF305575, AF305576, AF305577, AF305578 Genomic DNA. Translation: AAG42242.1.
AK026102 mRNA. Translation: BAB15360.1.
CH471139 Genomic DNA. Translation: EAW69031.1. Sequence problems.
CH471139 Genomic DNA. Translation: EAW69034.1. Sequence problems.
BC005149 mRNA. Translation: AAH05149.1.
AF171088 mRNA. Translation: AAQ13604.1. Different initiation.
CCDSiCCDS12180.1.
RefSeqiNP_065394.1. NM_020533.2.
UniGeneiHs.631858.

Genome annotation databases

EnsembliENST00000264079; ENSP00000264079; ENSG00000090674.
GeneIDi57192.
KEGGihsa:57192.
UCSCiuc002mgo.4. human.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AJ293659 mRNA. Translation: CAC07813.1. Sequence problems.
AJ293970 mRNA. Translation: CAC08215.1.
AF287269 mRNA. Translation: AAG00797.1.
AF287270 Genomic DNA. Translation: AAG00798.1.
AF249319 mRNA. Translation: AAG10422.1.
AF305579
, AF305572, AF305573, AF305574, AF305575, AF305576, AF305577, AF305578 Genomic DNA. Translation: AAG42242.1.
AK026102 mRNA. Translation: BAB15360.1.
CH471139 Genomic DNA. Translation: EAW69031.1. Sequence problems.
CH471139 Genomic DNA. Translation: EAW69034.1. Sequence problems.
BC005149 mRNA. Translation: AAH05149.1.
AF171088 mRNA. Translation: AAQ13604.1. Different initiation.
CCDSiCCDS12180.1.
RefSeqiNP_065394.1. NM_020533.2.
UniGeneiHs.631858.

3D structure databases

ProteinModelPortaliQ9GZU1.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi121441. 4 interactors.
IntActiQ9GZU1. 3 interactors.
MINTiMINT-1409368.
STRINGi9606.ENSP00000264079.

Chemistry databases

GuidetoPHARMACOLOGYi501.

Protein family/group databases

TCDBi1.A.5.3.1. the polycystin cation channel (pcc) family.

PTM databases

iPTMnetiQ9GZU1.
PhosphoSitePlusiQ9GZU1.
SwissPalmiQ9GZU1.

Polymorphism and mutation databases

BioMutaiMCOLN1.
DMDMi50401163.

Proteomic databases

EPDiQ9GZU1.
MaxQBiQ9GZU1.
PaxDbiQ9GZU1.
PeptideAtlasiQ9GZU1.
PRIDEiQ9GZU1.

Protocols and materials databases

DNASUi57192.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000264079; ENSP00000264079; ENSG00000090674.
GeneIDi57192.
KEGGihsa:57192.
UCSCiuc002mgo.4. human.

Organism-specific databases

CTDi57192.
DisGeNETi57192.
GeneCardsiMCOLN1.
GeneReviewsiMCOLN1.
H-InvDBHIX0023287.
HGNCiHGNC:13356. MCOLN1.
HPAiCAB032637.
HPA031763.
MalaCardsiMCOLN1.
MIMi252650. phenotype.
605248. gene.
neXtProtiNX_Q9GZU1.
OpenTargetsiENSG00000090674.
Orphaneti578. Mucolipidosis type 4.
PharmGKBiPA30699.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG3733. Eukaryota.
ENOG410Z1HH. LUCA.
GeneTreeiENSGT00390000017126.
HOGENOMiHOG000232158.
HOVERGENiHBG052430.
InParanoidiQ9GZU1.
KOiK04992.
OMAiPANDTFN.
OrthoDBiEOG091G026A.
PhylomeDBiQ9GZU1.
TreeFamiTF317783.

Enzyme and pathway databases

ReactomeiR-HSA-3295583. TRP channels.
R-HSA-917977. Transferrin endocytosis and recycling.
SIGNORiQ9GZU1.

Miscellaneous databases

ChiTaRSiMCOLN1. human.
GeneWikiiMCOLN1.
GenomeRNAii57192.
PROiQ9GZU1.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000090674.
CleanExiHS_MCOLN1.
ExpressionAtlasiQ9GZU1. baseline and differential.
GenevisibleiQ9GZU1. HS.

Family and domain databases

InterProiIPR013122. PKD1_2_channel.
[Graphical view]
PfamiPF08016. PKD_channel. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiMCLN1_HUMAN
AccessioniPrimary (citable) accession number: Q9GZU1
Secondary accession number(s): D6W647
, Q7Z4F7, Q9H292, Q9H4B3, Q9H4B5
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 19, 2004
Last sequence update: March 1, 2001
Last modified: November 30, 2016
This is version 142 of the entry and version 1 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 19
    Human chromosome 19: 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.