Q3ZAQ7 (VMA21_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Vacuolar ATPase assembly integral membrane protein VMA21

Alternative name(s):
Myopathy with excessive autophagy protein

Gene names

Name:	VMA21
Synonyms:	MEAX, XMEA

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

General annotation (Comments)

Function	Required for the assembly of the V0 complex of the vacuolar ATPase (V-ATPase) in the endoplasmic reticulum. Ref.4
Subunit structure	Associates with the V0 complex of the vacuolar ATPase (V-ATPase).
Subcellular location	Endoplasmic reticulum membrane; Multi-pass membrane protein. Endoplasmic reticulum-Golgi intermediate compartment membrane; Multi-pass membrane protein. Cytoplasmic vesicle › COPII-coated vesicle membrane; Multi-pass membrane protein Ref.4.
Involvement in disease	X-linked myopathy with excessive autophagy (MEAX) [MIM:310440]: Childhood-onset disease characterized by progressive vacuolation and atrophy of skeletal muscle. It is inherited in recessive fashion, affecting boys and sparing carrier females. Onset is in childhood, and patients exhibit weakness of the proximal muscles of the lower extremities, progressing slowly to involve other skeletal muscle groups over time. Other organs including the heart and brain are clinically unaffected. Phenotype is due to an increase of lysosomal pH from 4.7 to 5.2, which reduces lysosomal degradative ability and blocks autophagy. This reduces cellular free amino acids, which upregulates the mTOR pathway and mTOR-dependent macroautophagy, resulting in proliferation of large and ineffective autolysosomes that engulf sections of cytoplasm, merge together, and vacuolate the cell. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.4
Sequence similarities	Belongs to the VMA21 family.
Caution	Protein characterization data are from Ref.4. Due to a number of errors in the figure panels, the article has been retracted but the authors stand by the validity of the main results and conclusions (Ref.5).

Ontologies

Keywords
Cellular component	Cytoplasmic vesicle Endoplasmic reticulum Membrane
Coding sequence diversity	Alternative splicing
Domain	Transmembrane Transmembrane helix
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	vacuolar proton-transporting V-type ATPase complex assembly Inferred from direct assay Ref.4. Source: UniProtKB
Cellular_component	COPII vesicle coat Inferred from direct assay Ref.4. Source: UniProtKB endoplasmic reticulum membrane Inferred from direct assay Ref.4. Source: UniProtKB endoplasmic reticulum-Golgi intermediate compartment membrane Inferred from electronic annotation. Source: UniProtKB-SubCell integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW lysosome Inferred from direct assay. Source: LIFEdb
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q3ZAQ7-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: Q3ZAQ7-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-17: MERPDKAALNALQPPEF → MLGSPCGPQL...LAGRTPRSHR

Note: No experimental confirmation available.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 101	101	Vacuolar ATPase assembly integral membrane protein VMA21		PRO_0000331499
Regions
	Transmembrane	26 – 46	21	Helical; Potential
	Transmembrane	66 – 86	21	Helical; Potential
Natural variations
	Alternative sequence	1 – 17	17	MERPD…QPPEF → MLGSPCGPQLSDRDADEDQC SREFRGRRSRRPPRRTMLRG KSRLNVEWLGYSPGLLLEHR PLLAGRTPRSHR in isoform 2.		VSP_041257

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified September 27, 2005. Version 1. Checksum: 9DE436A7FF533443	FASTA	101	11,354
	10 20 30 40 50 60 MERPDKAALN ALQPPEFRNE SSLASTLKTL LFFTALMITV PIGLYFTTKS YIFEGALGMS 70 80 90 100 NRDSYFYAAI VAVVAVHVVL ALFVYVAWNE GSRQWREGKQ D
	Isoform 2 [UniParc]. Checksum: 8A3F475CD071D5BC	FASTA	156	17,766
	10 20 30 40 50 60 MLGSPCGPQL SDRDADEDQC SREFRGRRSR RPPRRTMLRG KSRLNVEWLG YSPGLLLEHR 70 80 90 100 110 120 PLLAGRTPRS HRRNESSLAS TLKTLLFFTA LMITVPIGLY FTTKSYIFEG ALGMSNRDSY 130 140 150 FYAAIVAVVA VHVVLALFVY VAWNEGSRQW REGKQD

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] (ISOFORM 1).
[2]	"The DNA sequence of the human X chromosome." Ross M.T., Grafham D.V., Coffey A.J., Scherer S., McLay K., Muzny D., Platzer M., Howell G.R., Burrows C., Bird C.P., Frankish A., Lovell F.L., Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G., Jones M.C. , Hurles M.E., Andrews T.D., Scott C.E., Searle S., Ramser J., Whittaker A., Deadman R., Carter N.P., Hunt S.E., Chen R., Cree A., Gunaratne P., Havlak P., Hodgson A., Metzker M.L., Richards S., Scott G., Steffen D., Sodergren E., Wheeler D.A., Worley K.C., Ainscough R., Ambrose K.D., Ansari-Lari M.A., Aradhya S., Ashwell R.I., Babbage A.K., Bagguley C.L., Ballabio A., Banerjee R., Barker G.E., Barlow K.F., Barrett I.P., Bates K.N., Beare D.M., Beasley H., Beasley O., Beck A., Bethel G., Blechschmidt K., Brady N., Bray-Allen S., Bridgeman A.M., Brown A.J., Brown M.J., Bonnin D., Bruford E.A., Buhay C., Burch P., Burford D., Burgess J., Burrill W., Burton J., Bye J.M., Carder C., Carrel L., Chako J., Chapman J.C., Chavez D., Chen E., Chen G., Chen Y., Chen Z., Chinault C., Ciccodicola A., Clark S.Y., Clarke G., Clee C.M., Clegg S., Clerc-Blankenburg K., Clifford K., Cobley V., Cole C.G., Conquer J.S., Corby N., Connor R.E., David R., Davies J., Davis C., Davis J., Delgado O., Deshazo D., Dhami P., Ding Y., Dinh H., Dodsworth S., Draper H., Dugan-Rocha S., Dunham A., Dunn M., Durbin K.J., Dutta I., Eades T., Ellwood M., Emery-Cohen A., Errington H., Evans K.L., Faulkner L., Francis F., Frankland J., Fraser A.E., Galgoczy P., Gilbert J., Gill R., Gloeckner G., Gregory S.G., Gribble S., Griffiths C., Grocock R., Gu Y., Gwilliam R., Hamilton C., Hart E.A., Hawes A., Heath P.D., Heitmann K., Hennig S., Hernandez J., Hinzmann B., Ho S., Hoffs M., Howden P.J., Huckle E.J., Hume J., Hunt P.J., Hunt A.R., Isherwood J., Jacob L., Johnson D., Jones S., de Jong P.J., Joseph S.S., Keenan S., Kelly S., Kershaw J.K., Khan Z., Kioschis P., Klages S., Knights A.J., Kosiura A., Kovar-Smith C., Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L., Liu W., Lloyd C., Lloyd D.M., Loulseged H., Loveland J.E., Lovell J.D., Lozado R., Lu J., Lyne R., Ma J., Maheshwari M., Matthews L.H., McDowall J., McLaren S., McMurray A., Meidl P., Meitinger T., Milne S., Miner G., Mistry S.L., Morgan M., Morris S., Mueller I., Mullikin J.C., Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N., Okwuonu G., Palmer S., Pandian R., Parker D., Parrish J., Pasternak S., Patel D., Pearce A.V., Pearson D.M., Pelan S.E., Perez L., Porter K.M., Ramsey Y., Reichwald K., Rhodes S., Ridler K.A., Schlessinger D., Schueler M.G., Sehra H.K., Shaw-Smith C., Shen H., Sheridan E.M., Shownkeen R., Skuce C.D., Smith M.L., Sotheran E.C., Steingruber H.E., Steward C.A., Storey R., Swann R.M., Swarbreck D., Tabor P.E., Taudien S., Taylor T., Teague B., Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S., Tromans A.C., d'Urso M., Verduzco D., Villasana D., Waldron L., Wall M., Wang Q., Warren J., Warry G.L., Wei X., West A., Whitehead S.L., Whiteley M.N., Wilkinson J.E., Willey D.L., Williams G., Williams L., Williamson A., Williamson H., Wilming L., Woodmansey R.L., Wray P.W., Yen J., Zhang J., Zhou J., Zoghbi H., Zorilla S., Buck D., Reinhardt R., Poustka A., Rosenthal A., Lehrach H., Meindl A., Minx P.J., Hillier L.W., Willard H.F., Wilson R.K., Waterston R.H., Rice C.M., Vaudin M., Coulson A., Nelson D.L., Weinstock G., Sulston J.E., Durbin R.M., Hubbard T., Gibbs R.A., Beck S., Rogers J., Bentley D.R. Nature 434:325-337(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]	"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] (ISOFORM 1). Tissue: Testis carcinoma.
[4]	"VMA21 deficiency causes an autophagic myopathy by compromising V-ATPase activity and lysosomal acidification." Ramachandran N., Munteanu I., Wang P., Aubourg P., Rilstone J.J., Israelian N., Naranian T., Paroutis P., Guo R., Ren Z.-P., Nishino I., Chabrol B., Pellissier J.-F., Minetti C., Udd B., Fardeau M., Tailor C.S., Mahuran D.J. , Kissel J.T., Kalimo H., Levy N., Manolson M.F., Ackerley C.A., Minassian B.A. Cell 137:235-246(2009) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION, INVOLVEMENT IN MEAX.
[5]	Erratum Ramachandran N., Munteanu I., Wang P., Aubourg P., Rilstone J.J., Israelian N., Naranian T., Paroutis P., Guo R., Ren Z.-P., Nishino I., Chabrol B., Pellissier J.-F., Minetti C., Udd B., Fardeau M., Tailor C.S., Mahuran D.J. , Kissel J.T., Kalimo H., Levy N., Manolson M.F., Ackerley C.A., Minassian B.A. Cell 142:984-984(2010) [PubMed] [Europe PMC] [Abstract] Cited for: RETRACTION.
[6]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].

Cross-references

Sequence databases
EMBL GenBank DDBJ	AK096835 mRNA. Translation: BAG53371.1. AF003627 Genomic DNA. No translation available. BC103701 mRNA. Translation: AAI03702.1. BC103702 mRNA. Translation: AAI03703.1. BC105693 mRNA. Translation: AAI05694.1. BC105694 mRNA. Translation: AAI05695.1. BC110800 mRNA. Translation: AAI10801.1.
IPI	IPI00146447. IPI00334343.
RefSeq	NP_001017980.1. NM_001017980.3.
UniGene	Hs.58633.
3D structure databases
ProteinModelPortal	Q3ZAQ7.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q3ZAQ7. 1 interaction.
STRING	9606.ENSP00000333255.
Polymorphism databases
DMDM	121943063.
Proteomic databases
PaxDb	Q3ZAQ7.
PRIDE	Q3ZAQ7.
Protocols and materials databases
DNASU	203547.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000330374; ENSP00000333255; ENSG00000160131. ENST00000370361; ENSP00000359386; ENSG00000160131.
GeneID	203547.
KEGG	hsa:203547.
UCSC	uc004feu.3. human.
Organism-specific databases
CTD	203547.
GeneCards	GC0XP150564.
HGNC	HGNC:22082. VMA21.
HPA	HPA010972.
MIM	310440. phenotype.
neXtProt	NX_Q3ZAQ7.
Orphanet	25980. X-linked myopathy with excessive autophagy.
PharmGKB	PA164727498.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG287271.
HOGENOM	HOG000154822.
OMA	SKAYIFE.
OrthoDB	EOG4DNF5W.
Gene expression databases
Bgee	Q3ZAQ7.
Genevestigator	Q3ZAQ7.
Family and domain databases
InterPro	IPR019013. VMA21-like_domain. [Graphical view]
Pfam	PF09446. VMA21. 1 hit. [Graphical view]
ProtoNet	Search...
Other
GenomeRNAi	203547.
NextBio	90447.
SOURCE	Search...

Entry information

Entry name

VMA21_HUMAN

Accession

Primary (citable) accession number: Q3ZAQ7
Secondary accession number(s): A6NKV7, B3KUA9

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 29, 2008
Last sequence update:	September 27, 2005
Last modified:	May 1, 2013
This is version 65 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.