Q9GZU1 (MCLN1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Mucolipin-1

Alternative name(s):
MG-2
Mucolipidin

Gene names

Name:	MCOLN1
Synonyms:	ML4
ORF Names:	MSTP080

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

General annotation (Comments)

Function	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. Ref.1 Ref.8 Ref.10
Enzyme regulation	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.
Subunit structure	Forms multimeric complexes. Ref.10
Subcellular location	Cell membrane; Multi-pass membrane protein. Late endosome membrane; Multi-pass membrane protein. Lysosome membrane; Multi-pass membrane protein Ref.1 Ref.8 Ref.9 Ref.11.
Tissue specificity	Widely expressed in adult and fetal tissues. Ref.1 Ref.2 Ref.3
Involvement in disease	Mucolipidosis type IV (MLIV) [MIM:252650]: 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. MLIV may be due to a defect in sorting and/or transport along the late endocytic pathway. MLIV is found at relatively high frequency among Ashkenazi Jews. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.2 Ref.9 Ref.10 Ref.13 Ref.14 Ref.15
Sequence similarities	Belongs to the transient receptor (TC 1.A.4) family. Polycystin subfamily. MCOLN1 sub-subfamily. [View classification]
Sequence caution	The sequence AAQ13604.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended. The sequence CAC07813.1 differs from that shown. Reason: Probable cloning artifact. The sequence EAW69031.1 differs from that shown. Reason: Erroneous gene model prediction. The sequence EAW69034.1 differs from that shown. Reason: Erroneous gene model prediction.

Ontologies

Keywords
Biological process	Calcium transport Ion transport Transport
Cellular component	Cell membrane Endosome Lysosome Membrane
Coding sequence diversity	Polymorphism
Disease	Disease mutation Mucolipidosis
Domain	Transmembrane Transmembrane helix
Ligand	Calcium
Molecular function	Ion channel
PTM	Glycoprotein Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	calcium ion transport Inferred from electronic annotation. Source: UniProtKB-KW cellular iron ion homeostasis Traceable author statement. Source: Reactome transferrin transport Traceable author statement. Source: Reactome
Cellular_component	endosome membrane Traceable author statement. Source: Reactome integral to plasma membrane Non-traceable author statement Ref.1. Source: UniProtKB late endosome membrane Inferred from electronic annotation. Source: UniProtKB-SubCell lysosomal membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	cation channel activity Non-traceable author statement Ref.2. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 580	580	Mucolipin-1		PRO_0000215362
Regions
	Transmembrane	66 – 86	21	Helical; Potential
	Transmembrane	297 – 317	21	Helical; Potential
	Transmembrane	350 – 370	21	Helical; Potential
	Transmembrane	388 – 408	21	Helical; Potential
	Transmembrane	428 – 448	21	Helical; Potential
	Transmembrane	497 – 517	21	Helical; Potential
Amino acid modifications
	Modified residue	10	1	Phosphoserine By similarity
	Modified residue	34	1	Phosphothreonine By similarity
	Modified residue	547	1	Phosphoserine By similarity
	Glycosylation	230	1	N-linked (GlcNAc...) Ref.12
Natural variations
	Natural variant	106	1	L → P in MLIV. Ref.14		VAR_019369
	Natural variant	232	1	T → P in MLIV; fails to localize to late endosomes. Ref.9 Ref.13		VAR_019370
	Natural variant	331	1	V → L in a breast cancer sample; somatic mutation. Ref.16		VAR_036453
	Natural variant	362	1	D → Y in MLIV; affects channel activity. Ref.2 Ref.10 Ref.14		VAR_019371
	Natural variant	403	1	R → C in MLIV. Ref.15		VAR_038380
	Natural variant	408	1	Missing in MLIV; mild psychomotor involvement; does not affect channel activity; affects channel inhibition by low pH; still localizes to late endosomes. Ref.2 Ref.9 Ref.10 Ref.13 Ref.14		VAR_019372
	Natural variant	446	1	V → L in MLIV; does not affect channel activity; affects channel inhibition by low pH. Ref.2 Ref.10		VAR_019373
	Natural variant	447	1	L → P in MLIV. Ref.14		VAR_019374
	Natural variant	465	1	F → L in MLIV; still localizes to late endosomes. Ref.9 Ref.13		VAR_019375
Experimental info
	Sequence conflict	164 – 191	28	ALCQR…MVVTD → LSASGTTTEATWTRPTTHLT LIRWWLLVN in AAG42242. Ref.3
	Sequence conflict	203	1	P → S in CAC08215. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Q9GZU1 [UniParc]. Last modified March 1, 2001. Version 1. Checksum: 7E7691F58D01C804	FASTA	580	65,022
	10 20 30 40 50 60 MTAPAGPRGS ETERLLTPNP GYGTQAGPSP APPTPPEEED LRRRLKYFFM SPCDKFRAKG 70 80 90 100 110 120 RKPCKLMLQV VKILVVTVQL ILFGLSNQLA VTFREENTIA FRHLFLLGYS DGADDTFAAY 130 140 150 160 170 180 TREQLYQAIF HAVDQYLALP DVSLGRYAYV RGGGDPWTNG SGLALCQRYY HRGHVDPAND 190 200 210 220 230 240 TFDIDPMVVT DCIQVDPPER PPPPPSDDLT LLESSSSYKN LTLKFHKLVN VTIHFRLKTI 250 260 270 280 290 300 NLQSLINNEI PDCYTFSVLI TFDNKAHSGR IPISLETQAH IQECKHPSVF QHGDNSFRLL 310 320 330 340 350 360 FDVVVILTCS LSFLLCARSL LRGFLLQNEF VGFMWRQRGR VISLWERLEF VNGWYILLVT 370 380 390 400 410 420 SDVLTISGTI MKIGIEAKNL ASYDVCSILL GTSTLLVWVG VIRYLTFFHN YNILIATLRV 430 440 450 460 470 480 ALPSVMRFCC CVAVIYLGYC FCGWIVLGPY HVKFRSLSMV SECLFSLING DDMFVTFAAM 490 500 510 520 530 540 QAQQGRSSLV WLFSQLYLYS FISLFIYMVL SLFIALITGA YDTIKHPGGA GAEESELQAY 550 560 570 580 IAQCQDSPTS GKFRRGSGSA CSLLCCCGRD PSEEHSLLVN

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning of the gene encoding a novel integral membrane protein, mucolipidin, and identification of the two major founder mutations causing mucolipidosis type IV." Bassi M.T., Manzoni M., Monti E., Pizzo M.T., Ballabio A., Borsani G. Am. J. Hum. Genet. 67:1110-1120(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], PROBABLE FUNCTION, TISSUE SPECIFICITY, SUBCELLULAR LOCATION, INVOLVEMENT IN MUCOLIPIDOSIS IV.
[2]	"Mucolipidosis type IV is caused by mutations in a gene encoding a novel transient receptor potential channel." Sun M., Goldin E., Stahl S., Falardeau J.L., Kennedy J.C., Acierno J.S. Jr., Bove C., Kaneski C.R., Nagle J., Bromley M.C., Colman M., Schiffmann R., Slaugenhaupt S.A. Hum. Mol. Genet. 9:2471-2478(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA], TISSUE SPECIFICITY, VARIANTS MLIV TYR-362; PHE-408 DEL AND LEU-446.
[3]	"Identification of the gene causing mucolipidosis type IV." Bargal R., Avidan N., Ben-Asher E., Olender Z., Zeigler M., Frumkin A., Raas-Rothschild A., Glusman G., Lancet D., Bach G. Nat. Genet. 26:118-123(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, INVOLVEMENT IN MUCOLIPIDOSIS IV.
[4]	"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].
[5]	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 (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	"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: Brain.
[7]	Xu H.S., Sheng H., Qin B.M., Liu Y.Q., Zhao B., Liu B., Wang X.Y., Zhang Q., Song L., Gao Y., Zhang C.L., Ye J., Ji X.J., Liu B.H., Lu H., Chen J.Z., Cai M.Q., Zheng W.Y. , Teng C.Y., Liu Q., Yu L.T., Lin J., Gong Q., Zhang A.M., Gao R.L., Hui R.T. Submitted (JUL-1999) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 391-580. Tissue: Aorta.
[8]	"Identification and characterization of the single channel function of human mucolipin-1 implicated in mucolipidosis type IV, a disorder affecting the lysosomal pathway." LaPlante J.M., Falardeau J., Sun M., Kanazirska M., Brown E.M., Slaugenhaupt S.A., Vassilev P.M. FEBS Lett. 532:183-187(2002) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTIONAL CHARACTERIZATION, REGULATION BY CALCIUM, SUBCELLULAR LOCATION.
[9]	"Overexpression of wild-type and mutant mucolipin proteins in mammalian cells: effects on the late endocytic compartment organization." Manzoni M., Monti E., Bresciani R., Bozzato A., Barlati S., Bassi M.T., Borsani G. FEBS Lett. 567:219-224(2004) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION, CHARACTERIZATION OF VARIANTS MLIV PRO-232; PHE-408 DEL AND LEU-465.
[10]	"Molecular pathophysiology of mucolipidosis type IV: pH dysregulation of the mucolipin-1 cation channel." Raychowdhury M.K., Gonzalez-Perrett S., Montalbetti N., Timpanaro G.A., Chasan B., Goldmann W.H., Stahl S., Cooney A., Goldin E., Cantiello H.F. Hum. Mol. Genet. 13:617-627(2004) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTIONAL CHARACTERIZATION, SUBUNIT, CHARACTERIZATION OF VARIANTS MLIV TYR-362; PHE-408 DEL AND LEU-446.
[11]	"Integral and associated lysosomal membrane proteins." Schroeder B., Wrocklage C., Pan C., Jaeger R., Koesters B., Schaefer H., Elsaesser H.-P., Mann M., Hasilik A. Traffic 8:1676-1686(2007) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY. Tissue: Placenta.
[12]	"Glycoproteomics analysis of human liver tissue by combination of multiple enzyme digestion and hydrazide chemistry." Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H. J. Proteome Res. 8:651-661(2009) [PubMed] [Europe PMC] [Abstract] Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-230, MASS SPECTROMETRY. Tissue: Liver.
[13]	"Mucolipidosis type IV: novel MCOLN1 mutations in Jewish and non-Jewish patients and the frequency of the disease in the Ashkenazi Jewish population." Bargal R., Avidan N., Olender Z., Ben-Asher E., Zeigler M., Raas-Rothschild A., Frumkin A., Ben-Yoseph O., Friedlender Y., Lancet D., Bach G. Hum. Mutat. 17:397-402(2001) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS MLIV PRO-232; PHE-408 DEL AND LEU-465.
[14]	"The neurogenetics of mucolipidosis type IV." Altarescu G., Sun M., Moore D.F., Smith J.A., Wiggs E.A., Solomon B.I., Patronas N.J., Frei K.P., Gupta S., Kaneski C.R., Quarrell O.W., Slaugenhaupt S.A., Goldin E., Schiffmann R. Neurology 59:306-313(2002) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS MLIV PRO-106; TYR-362; PHE-408 DEL AND PRO-447.
[15]	"Transfer of a mitochondrial DNA fragment to MCOLN1 causes an inherited case of mucolipidosis IV." Goldin E., Stahl S., Cooney A.M., Kaneski C.R., Gupta S., Brady R.O., Ellis J.R., Schiffmann R. Hum. Mutat. 24:460-465(2004) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT MLIV CYS-403.
[16]	"The consensus coding sequences of human breast and colorectal cancers." Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V. , Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., Velculescu V.E. Science 314:268-274(2006) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT [LARGE SCALE ANALYSIS] LEU-331.
+	Additional computationally mapped references.

Web resources

GeneReviews

Cross-references

Sequence databases
EMBL GenBank DDBJ	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.
IPI	IPI00003750. IPI00452161.
RefSeq	NP_065394.1. NM_020533.2.
UniGene	Hs.631858.
3D structure databases
ProteinModelPortal	Q9GZU1.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q9GZU1. 2 interactions.
MINT	MINT-1409368.
STRING	9606.ENSP00000264079.
Protein family/group databases
TCDB	1.A.5.3.1. polycystin cation channel (PCC) family.
PTM databases
PhosphoSite	Q9GZU1.
Polymorphism databases
DMDM	50401163.
Proteomic databases
PaxDb	Q9GZU1.
PRIDE	Q9GZU1.
Protocols and materials databases
DNASU	57192.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000264079; ENSP00000264079; ENSG00000090674.
GeneID	57192.
KEGG	hsa:57192.
UCSC	uc002mgo.3. human. uc002mgp.3. human.
Organism-specific databases
CTD	57192.
GeneCards	GC19P007493.
H-InvDB	HIX0023287.
HGNC	HGNC:13356. MCOLN1.
HPA	HPA031763.
MIM	252650. phenotype. 605248. gene.
neXtProt	NX_Q9GZU1.
Orphanet	578. Mucolipidosis type 4.
PharmGKB	PA30699.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG149591.
HOGENOM	HOG000232158.
HOVERGEN	HBG052430.
InParanoid	Q9GZU1.
KO	K04992.
OMA	PANDTFN.
OrthoDB	EOG4V9TQN.
PhylomeDB	Q9GZU1.
Enzyme and pathway databases
Reactome	REACT_15518. Transmembrane transport of small molecules.
Gene expression databases
ArrayExpress	Q9GZU1.
Bgee	Q9GZU1.
CleanEx	HS_MCOLN1.
Genevestigator	Q9GZU1.
GermOnline	ENSG00000090674. Homo sapiens.
Family and domain databases
InterPro	IPR013122. PKD1_2_channel. [Graphical view]
Pfam	PF08016. PKD_channel. 1 hit. [Graphical view]
ProtoNet	Search...
Other
GenomeRNAi	57192.
NextBio	63278.
SOURCE	Search...

Entry information

Entry name

MCLN1_HUMAN

Accession

Primary (citable) accession number: Q9GZU1
Secondary accession number(s): D6W647 , Q7Z4F7, Q9H292, Q9H4B3, Q9H4B5

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 19, 2004
Last sequence update:	March 1, 2001
Last modified:	May 1, 2013
This is version 107 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.