Q8NHS3 (MFSD8_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Major facilitator superfamily domain-containing protein 8

Alternative name(s):
Ceroid-lipofuscinosis neuronal protein 7

Gene names

Name:	MFSD8
Synonyms:	CLN7

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

General annotation (Comments)

Function	May be a carrier that transport small solutes by using chemiosmotic ion gradients Potential.
Subcellular location	Lysosome membrane; Multi-pass membrane protein Ref.5 Ref.6.
Tissue specificity	Expressed at very low levels in all tissues tested. Ref.6
Involvement in disease	Neuronal ceroid lipofuscinosis 7 (CLN7) [MIM:610951]: A form of neuronal ceroid lipofuscinosis with onset in early 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 7 comprise mixed combinations of granular, curvilinear, fingerprint, and rectilinear profiles. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.6 Ref.7 Ref.8 Ref.9 Ref.10
Sequence similarities	Belongs to the major facilitator superfamily.

Ontologies

Keywords
Biological process	Transport
Cellular component	Lysosome Membrane
Coding sequence diversity	Polymorphism
Disease	Disease mutation Neurodegeneration Neuronal ceroid lipofuscinosis
Domain	Transmembrane Transmembrane helix
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	cell death Inferred from electronic annotation. Source: UniProtKB-KW transmembrane transport Inferred from electronic annotation. Source: InterPro
Cellular_component	integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW lysosomal membrane Inferred from electronic annotation. Source: UniProtKB-SubCell nucleus Inferred from direct assay. Source: HPA
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 518	518	Major facilitator superfamily domain-containing protein 8		PRO_0000311232
Regions
	Topological domain	1 – 40	40	Cytoplasmic Potential
	Transmembrane	41 – 61	21	Helical; Potential
	Topological domain	62 – 74	13	Extracellular Potential
	Transmembrane	75 – 95	21	Helical; Potential
	Topological domain	96 – 105	10	Cytoplasmic Potential
	Transmembrane	106 – 126	21	Helical; Potential
	Topological domain	127 – 131	5	Extracellular Potential
	Transmembrane	132 – 152	21	Helical; Potential
	Topological domain	153 – 173	21	Cytoplasmic Potential
	Transmembrane	174 – 194	21	Helical; Potential
	Topological domain	195 – 211	17	Extracellular Potential
	Transmembrane	212 – 232	21	Helical; Potential
	Topological domain	233 – 266	34	Cytoplasmic Potential
	Transmembrane	267 – 287	21	Helical; Potential
	Topological domain	288 – 304	17	Extracellular Potential
	Transmembrane	305 – 325	21	Helical; Potential
	Topological domain	326 – 337	12	Cytoplasmic Potential
	Transmembrane	338 – 358	21	Helical; Potential
	Topological domain	359 – 412	54	Extracellular Potential
	Transmembrane	413 – 433	21	Helical; Potential
	Topological domain	434 – 451	18	Cytoplasmic Potential
	Transmembrane	452 – 472	21	Helical; Potential
	Topological domain	473 – 482	10	Extracellular Potential
	Transmembrane	483 – 503	21	Helical; Potential
	Topological domain	504 – 518	15	Cytoplasmic Potential
Natural variations
	Natural variant	52	1	G → R in CLN7. Ref.8		VAR_058427
	Natural variant	109	1	V → G. Corresponds to variant rs11732377 [ dbSNP | Ensembl ].		VAR_037176
	Natural variant	121	1	Y → C in CLN7. Ref.9		VAR_058428
	Natural variant	139	1	R → H in CLN7. Ref.7		VAR_058429
	Natural variant	157	1	A → P in CLN7; due to a deletion-insertion mutation at nucleotide level. Ref.7 Ref.10		VAR_058430
	Natural variant	160	1	T → I in CLN7. Ref.10		VAR_066915
	Natural variant	160	1	T → N in CLN7. Ref.10		VAR_066916
	Natural variant	294	1	T → K in CLN7. Ref.7 Ref.8		VAR_058431
	Natural variant	310	1	G → D in CLN7; lysosomal localization. Ref.6 Ref.7 Ref.8		VAR_037177
	Natural variant	385	1	G → R. Corresponds to variant rs11098943 [ dbSNP | Ensembl ].		VAR_037178
	Natural variant	423	1	A → V. Ref.1 Corresponds to variant rs3733319 [ dbSNP | Ensembl ].		VAR_037179
	Natural variant	429	1	G → D in CLN7; lysosomal localization. Ref.6		VAR_037180
	Natural variant	447	1	P → L in CLN7. Ref.8		VAR_058432
	Natural variant	458	1	T → K in CLN7. Ref.10		VAR_066917
	Natural variant	465	1	R → Q in CLN7. Ref.10		VAR_066918
	Natural variant	465	1	R → W in CLN7. Ref.7		VAR_058433
	Natural variant	470	1	M → V in CLN7. Ref.10		VAR_066919
Experimental info
	Sequence conflict	189	1	C → Y in BAC11062. Ref.1
	Sequence conflict	487	1	L → R in BAC11062. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Q8NHS3 [UniParc]. Last modified October 1, 2002. Version 1. Checksum: 105A5F6A35B2291F	FASTA	518	57,628
	10 20 30 40 50 60 MAGLRNESEQ EPLLGDTPGS REWDILETEE HYKSRWRSIR ILYLTMFLSS VGFSVVMMSI 70 80 90 100 110 120 WPYLQKIDPT ADTSFLGWVI ASYSLGQMVA SPIFGLWSNY RPRKEPLIVS ILISVAANCL 130 140 150 160 170 180 YAYLHIPASH NKYYMLVARG LLGIGAGNVA VVRSYTAGAT SLQERTSSMA NISMCQALGF 190 200 210 220 230 240 ILGPVFQTCF TFLGEKGVTW DVIKLQINMY TTPVLLSAFL GILNIILILA ILREHRVDDS 250 260 270 280 290 300 GRQCKSINFE EASTDEAQVP QGNIDQVAVV AINVLFFVTL FIFALFETII TPLTMDMYAW 310 320 330 340 350 360 TQEQAVLYNG IILAALGVEA VVIFLGVKLL SKKIGERAIL LGGLIVVWVG FFILLPWGNQ 370 380 390 400 410 420 FPKIQWEDLH NNSIPNTTFG EIIIGLWKSP MEDDNERPTG CSIEQAWCLY TPVIHLAQFL 430 440 450 460 470 480 TSAVLIGLGY PVCNLMSYTL YSKILGPKPQ GVYMGWLTAS GSGARILGPM FISQVYAHWG 490 500 510 PRWAFSLVCG IIVLTITLLG VVYKRLIALS VRYGRIQE

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"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], VARIANT VAL-423. Tissue: Embryo and Placenta.
[2]	"Generation and annotation of the DNA sequences of human chromosomes 2 and 4." Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H. , Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., Wilson R.K. Nature 434:724-731(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]	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].
[4]	"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: Testis.
[5]	"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.
[6]	"The novel neuronal ceroid lipofuscinosis gene MFSD8 encodes a putative lysosomal transporter." Siintola E., Topcu M., Aula N., Lohi H., Minassian B.A., Paterson A.D., Liu X.-Q., Wilson C., Lahtinen U., Anttonen A.-K., Lehesjoki A.-E. Am. J. Hum. Genet. 81:136-146(2007) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS CLN7 ASP-310 AND ASP-429, CHARACTERIZATION OF VARIANTS CLN7 ASP-310 AND ASP-429, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
[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 CLN7 HIS-139; PRO-157; LYS-294; ASP-310 AND TRP-465.
[8]	"Mutations in MFSD8/CLN7 are a frequent cause of variant-late infantile neuronal ceroid lipofuscinosis." Aiello C., Terracciano A., Simonati A., Discepoli G., Cannelli N., Claps D., Crow Y.J., Bianchi M., Kitzmuller C., Longo D., Tavoni A., Franzoni E., Tessa A., Veneselli E., Boldrini R., Filocamo M., Williams R.E., Bertini E.S. , Biancheri R., Carrozzo R., Mole S.E., Santorelli F.M. Hum. Mutat. 30:E530-E540(2009) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS CLN7 ARG-52; LYS-294; ASP-310 AND LEU-447.
[9]	"A novel mutation in the MFSD8 gene in late infantile neuronal ceroid lipofuscinosis." Stogmann E., El Tawil S., Wagenstaller J., Gaber A., Edris S., Abdelhady A., Assem-Hilger E., Leutmezer F., Bonelli S., Baumgartner C., Zimprich F., Strom T.M., Zimprich A. Neurogenetics 10:73-77(2009) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT CLN7 CYS-121.
[10]	"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 CLN7 PRO-157; ASN-160; ILE-160; LYS-458; GLN-465 AND VAL-470.
+	Additional computationally mapped references.

Web resources

NCL CLN7/MFSD8

Neural Ceroid Lipofuscinoses mutation db

Cross-references

Sequence databases
EMBL GenBank DDBJ	AK074564 mRNA. Translation: BAC11062.1. AK315596 mRNA. Translation: BAG37968.1. AC099340 Genomic DNA. No translation available. CH471056 Genomic DNA. Translation: EAX05195.1. BC029503 mRNA. Translation: AAH29503.1.
IPI	IPI00296258.
RefSeq	NP_689991.1. NM_152778.2.
UniGene	Hs.480701.
3D structure databases
ProteinModelPortal	Q8NHS3.
ModBase	Search...
Protein-protein interaction databases
STRING	9606.ENSP00000296468.
PTM databases
PhosphoSite	Q8NHS3.
Polymorphism databases
DMDM	74730313.
Proteomic databases
PaxDb	Q8NHS3.
PRIDE	Q8NHS3.
Protocols and materials databases
DNASU	256471.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000296468; ENSP00000296468; ENSG00000164073.
GeneID	256471.
KEGG	hsa:256471.
UCSC	uc003ifp.3. human.
Organism-specific databases
CTD	256471.
GeneCards	GC04M128838.
HGNC	HGNC:28486. MFSD8.
HPA	HPA044802.
MIM	610951. phenotype. 611124. gene.
neXtProt	NX_Q8NHS3.
Orphanet	228366. CLN7 disease.
PharmGKB	PA162395842.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG294425.
HOGENOM	HOG000047970.
HOVERGEN	HBG061584.
InParanoid	Q8NHS3.
KO	K12307.
OMA	FEEASTD.
OrthoDB	EOG40CHH4.
PhylomeDB	Q8NHS3.
Gene expression databases
ArrayExpress	Q8NHS3.
Bgee	Q8NHS3.
CleanEx	HS_MFSD8.
Genevestigator	Q8NHS3.
Family and domain databases
InterPro	IPR011701. MFS. IPR020846. MFS_dom. IPR016196. MFS_dom_general_subst_transpt. [Graphical view]
Pfam	PF07690. MFS_1. 1 hit. [Graphical view]
SUPFAM	SSF103473. MFS_gen_substrate_transporter. 1 hit.
PROSITE	PS50850. MFS. 1 hit. [Graphical view]
ProtoNet	Search...
Other
GenomeRNAi	256471.
NextBio	92817.
SOURCE	Search...

Entry information

Entry name

MFSD8_HUMAN

Accession

Primary (citable) accession number: Q8NHS3
Secondary accession number(s): B2RDM1, Q8N2P3

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 13, 2007
Last sequence update:	October 1, 2002
Last modified:	May 1, 2013
This is version 90 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.