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Q3ZAQ7 (VMA21_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 72. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Vacuolar ATPase assembly integral membrane protein VMA21
Alternative name(s):
Myopathy with excessive autophagy protein
Gene names
Name:VMA21
Synonyms:MEAX, XMEA
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length101 AA.
Sequence statusComplete.
Protein existenceEvidence 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 vesicleCOPII-coated vesicle membrane; Multi-pass membrane protein Ref.4.

Involvement in disease

Myopathy, X-linked, with excessive autophagy (MEAX) [MIM:310440]: A muscle disorder characterized by childhood early onset of a slowly progressive proximal limb muscle weakness (especially in legs) and elevation of serum creatine kinase, without evidence of cardiac, respiratory or central nervous system involvement. Histopathological analysis reveals diseased muscle fibers that are not necrotic, but show abnormal autophagic vacuolation as a manifestation of excessive autophagic activity in skeletal muscle cells.
Note: The gene represented in this entry may be involved in disease pathogenesis. VMA21 deficiency results in 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 (Ref.4). 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).

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 keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 101101Vacuolar ATPase assembly integral membrane protein VMA21 HAMAP-Rule MF_03058
PRO_0000331499

Regions

Topological domain1 – 2525Cytoplasmic Potential
Transmembrane26 – 4621Helical; Potential
Topological domain47 – 6519Lumenal Potential
Transmembrane66 – 8621Helical; Potential
Topological domain87 – 10115Cytoplasmic Potential

Natural variations

Alternative sequence1 – 1717MERPD…QPPEF → MLGSPCGPQLSDRDADEDQC SREFRGRRSRRPPRRTMLRG KSRLNVEWLGYSPGLLLEHR PLLAGRTPRSHR in isoform 2.
VSP_041257

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified September 27, 2005. Version 1.
Checksum: 9DE436A7FF533443

FASTA10111,354
        10         20         30         40         50         60 
MERPDKAALN ALQPPEFRNE SSLASTLKTL LFFTALMITV PIGLYFTTKS YIFEGALGMS 

        70         80         90        100 
NRDSYFYAAI VAVVAVHVVL ALFVYVAWNE GSRQWREGKQ D 

« Hide

Isoform 2 [UniParc].

Checksum: 8A3F475CD071D5BC
Show »

FASTA15617,766

References

« Hide '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. expand/collapse author list , 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. expand/collapse author list , 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. expand/collapse author list , 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. expand/collapse author list , 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].
+Additional computationally mapped references.

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.
RefSeqNP_001017980.1. NM_001017980.3.
UniGeneHs.58633.

3D structure databases

ProteinModelPortalQ3ZAQ7.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid128477. 14 interactions.
IntActQ3ZAQ7. 1 interaction.
STRING9606.ENSP00000333255.

Polymorphism databases

DMDM121943063.

Proteomic databases

PaxDbQ3ZAQ7.
PRIDEQ3ZAQ7.

Protocols and materials databases

DNASU203547.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000330374; ENSP00000333255; ENSG00000160131. [Q3ZAQ7-1]
ENST00000370361; ENSP00000359386; ENSG00000160131. [Q3ZAQ7-2]
GeneID203547.
KEGGhsa:203547.
UCSCuc004feu.3. human. [Q3ZAQ7-1]

Organism-specific databases

CTD203547.
GeneCardsGC0XP150564.
HGNCHGNC:22082. VMA21.
HPAHPA010972.
MIM310440. phenotype.
neXtProtNX_Q3ZAQ7.
Orphanet25980. X-linked myopathy with excessive autophagy.
PharmGKBPA164727498.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG287271.
HOGENOMHOG000154822.
OMASSDSYFY.
OrthoDBEOG7XWPR8.
PhylomeDBQ3ZAQ7.
TreeFamTF314021.

Gene expression databases

BgeeQ3ZAQ7.
GenevestigatorQ3ZAQ7.

Family and domain databases

HAMAPMF_03058. VMA21.
InterProIPR019013. VMA21-like_domain.
[Graphical view]
PfamPF09446. VMA21. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GenomeRNAi203547.
NextBio90447.
PROQ3ZAQ7.
SOURCESearch...

Entry information

Entry nameVMA21_HUMAN
AccessionPrimary (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: April 16, 2014
This is version 72 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human chromosome X

Human chromosome X: entries, gene names and cross-references to MIM