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Q9Y4W6 (AFG32_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 140. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
AFG3-like protein 2

EC=3.4.24.-
Alternative name(s):
Paraplegin-like protein
Gene names
Name:AFG3L2
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length797 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

ATP-dependent protease which is essential for axonal development By similarity. HAMAP-Rule MF_01458

Cofactor

Binds 1 zinc ion per subunit Potential.

Subunit structure

Homooligomer. Interacts with SPG7; the interaction is required for the efficient assembly of mitochondrial complex I. Ref.3 Ref.4

Subcellular location

Mitochondrion membrane; Multi-pass membrane protein Ref.1.

Tissue specificity

Ubiquitous. Highly expressed in the cerebellar Purkinje cells. Ref.9

Involvement in disease

Spinocerebellar ataxia 28 (SCA28) [MIM:610246]: Spinocerebellar ataxia is a clinically and genetically heterogeneous group of cerebellar disorders. Patients show progressive incoordination of gait and often poor coordination of hands, speech and eye movements, due to degeneration of the cerebellum with variable involvement of the brainstem and spinal cord. SCA28 is an autosomal dominant cerebellar ataxia (ADCA) with a slow progressive course and no evidence of sensory involvement or cognitive impairment.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.7 Ref.8 Ref.9

Spastic ataxia 5, autosomal recessive (SPAX5) [MIM:614487]: A neurodegenerative disorder characterized by early onset spasticity, peripheral neuropathy, ptosis, oculomotor apraxia, dystonia, cerebellar atrophy, and progressive myoclonic epilepsy.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.10

Sequence similarities

In the N-terminal section; belongs to the AAA ATPase family.

In the C-terminal section; belongs to the peptidase M41 family.

Ontologies

Keywords
   Cellular componentMembrane
Mitochondrion
   DiseaseDisease mutation
Neurodegeneration
Spinocerebellar ataxia
   DomainTransmembrane
Transmembrane helix
   LigandATP-binding
Metal-binding
Nucleotide-binding
Zinc
   Molecular functionHydrolase
Metalloprotease
Protease
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processaxonogenesis

Inferred from electronic annotation. Source: Ensembl

cell death

Inferred from electronic annotation. Source: UniProtKB-KW

cristae formation

Inferred from electronic annotation. Source: Ensembl

mitochondrial fusion

Inferred from electronic annotation. Source: Ensembl

mitochondrial protein processing

Inferred from electronic annotation. Source: Ensembl

muscle fiber development

Inferred from electronic annotation. Source: Ensembl

myelination

Inferred from electronic annotation. Source: Ensembl

nerve development

Inferred from electronic annotation. Source: Ensembl

neuromuscular junction development

Inferred from electronic annotation. Source: Ensembl

regulation of multicellular organism growth

Inferred from electronic annotation. Source: Ensembl

righting reflex

Inferred from electronic annotation. Source: Ensembl

   Cellular_componentintegral component of membrane

Inferred from electronic annotation. Source: UniProtKB-KW

mitochondrial inner membrane

Inferred from electronic annotation. Source: Ensembl

mitochondrion

Inferred from direct assay. Source: HPA

   Molecular_functionATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

metalloendopeptidase activity

Inferred from electronic annotation. Source: InterPro

nucleoside-triphosphatase activity

Inferred from electronic annotation. Source: InterPro

protein binding

Inferred from physical interaction Ref.3. Source: UniProtKB

unfolded protein binding

Traceable author statement Ref.1. Source: ProtInc

zinc ion binding

Inferred from electronic annotation. Source: InterPro

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 797797AFG3-like protein 2 HAMAP-Rule MF_01458
PRO_0000084673

Regions

Transmembrane143 – 16321Helical; Potential
Transmembrane251 – 27121Helical; Potential
Nucleotide binding348 – 3558ATP Potential

Sites

Active site5751 By similarity
Metal binding5741Zinc; catalytic By similarity
Metal binding5781Zinc; catalytic By similarity
Metal binding6491Zinc; catalytic By similarity

Amino acid modifications

Modified residue1171N6-succinyllysine By similarity

Natural variations

Natural variant4321N → T in SCA28. Ref.9
VAR_063544
Natural variant6161Y → C in SPAX5; hypomorphic mutation; results in impaired oligomerization with itself and SPG7; retains ATPase and proteolytic activities. Ref.10
VAR_067330
Natural variant6541T → I in SCA28. Ref.8
VAR_064402
Natural variant6661M → R in SCA28. Ref.8
VAR_064403
Natural variant6661M → T in SCA28. Ref.8
VAR_064404
Natural variant6661M → V in SCA28. Ref.8
VAR_064405
Natural variant6711G → E in SCA28. Ref.8
VAR_064406
Natural variant6711G → R in SCA28. Ref.8
VAR_064407
Natural variant6911E → K in SCA28. Ref.9
VAR_063545
Natural variant6941A → E in SCA28. Ref.9
VAR_063546
Natural variant7001E → K in SCA28. Ref.7
VAR_064408
Natural variant7021R → Q in SCA28. Ref.9
VAR_063547

Experimental info

Sequence conflict741E → G in CAB48398. Ref.1
Sequence conflict6331V → A in CAB48398. Ref.1

Secondary structure

..................... 797
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Q9Y4W6 [UniParc].

Last modified February 20, 2007. Version 2.
Checksum: EACBB7C5F2EE5E08

FASTA79788,584
        10         20         30         40         50         60 
MAHRCLRLWG RGGCWPRGLQ QLLVPGGVGP GEQPCLRTLY RFVTTQARAS RNSLLTDIIA 

        70         80         90        100        110        120 
AYQRFCSRPP KGFEKYFPNG KNGKKASEPK EVMGEKKESK PAATTRSSGG GGGGGGKRGG 

       130        140        150        160        170        180 
KKDDSHWWSR FQKGDIPWDD KDFRMFFLWT ALFWGGVMFY LLLKRSGREI TWKDFVNNYL 

       190        200        210        220        230        240 
SKGVVDRLEV VNKRFVRVTF TPGKTPVDGQ YVWFNIGSVD TFERNLETLQ QELGIEGENR 

       250        260        270        280        290        300 
VPVVYIAESD GSFLLSMLPT VLIIAFLLYT IRRGPAGIGR TGRGMGGLFS VGETTAKVLK 

       310        320        330        340        350        360 
DEIDVKFKDV AGCEEAKLEI MEFVNFLKNP KQYQDLGAKI PKGAILTGPP GTGKTLLAKA 

       370        380        390        400        410        420 
TAGEANVPFI TVSGSEFLEM FVGVGPARVR DLFALARKNA PCILFIDEID AVGRKRGRGN 

       430        440        450        460        470        480 
FGGQSEQENT LNQLLVEMDG FNTTTNVVIL AGTNRPDILD PALLRPGRFD RQIFIGPPDI 

       490        500        510        520        530        540 
KGRASIFKVH LRPLKLDSTL EKDKLARKLA SLTPGFSGAD VANVCNEAAL IAARHLSDSI 

       550        560        570        580        590        600 
NQKHFEQAIE RVIGGLEKKT QVLQPEEKKT VAYHEAGHAV AGWYLEHADP LLKVSIIPRG 

       610        620        630        640        650        660 
KGLGYAQYLP KEQYLYTKEQ LLDRMCMTLG GRVSEEIFFG RITTGAQDDL RKVTQSAYAQ 

       670        680        690        700        710        720 
IVQFGMNEKV GQISFDLPRQ GDMVLEKPYS EATARLIDDE VRILINDAYK RTVALLTEKK 

       730        740        750        760        770        780 
ADVEKVALLL LEKEVLDKND MVELLGPRPF AEKSTYEEFV EGTGSLDEDT SLPEGLKDWN 

       790 
KEREKEKEEP PGEKVAN 

« Hide

References

« Hide 'large scale' references
[1]"Identification and characterization of AFG3L2, a novel paraplegin-related gene."
Banfi S., Bassi M.T., Andolfi G., Marchitiello A., Zanotta S., Ballabio A., Casari G., Franco B.
Genomics 59:51-58(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], SUBCELLULAR LOCATION.
[2]"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: Eye.
[3]"Loss of m-AAA protease in mitochondria causes complex I deficiency and increased sensitivity to oxidative stress in hereditary spastic paraplegia."
Atorino L., Silvestri L., Koppen M., Cassina L., Ballabio A., Marconi R., Langer T., Casari G.
J. Cell Biol. 163:777-787(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH SPG7.
[4]"Variable and tissue-specific subunit composition of mitochondrial m-AAA protease complexes linked to hereditary spastic paraplegia."
Koppen M., Metodiev M.D., Casari G., Rugarli E.I., Langer T.
Mol. Cell. Biol. 27:758-767(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBUNIT.
[5]"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].
[6]"Northeast structural genomics consortium target HR6741A."
Northeast structural genomics consortium (NESG)
Submitted (MAR-2012) to the PDB data bank
Cited for: STRUCTURE BY NMR OF 164-251.
[7]"Early onset and slow progression of SCA28, a rare dominant ataxia in a large four-generation family with a novel AFG3L2 mutation."
Edener U., Wollner J., Hehr U., Kohl Z., Schilling S., Kreuz F., Bauer P., Bernard V., Gillessen-Kaesbach G., Zuhlke C.
Eur. J. Hum. Genet. 18:965-968(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT SCA28 LYS-700.
[8]"Missense mutations in the AFG3L2 proteolytic domain account for approximately 1.5% of European autosomal dominant cerebellar ataxias."
Cagnoli C., Stevanin G., Brussino A., Barberis M., Mancini C., Margolis R.L., Holmes S.E., Nobili M., Forlani S., Padovan S., Pappi P., Zaros C., Leber I., Ribai P., Pugliese L., Assalto C., Brice A., Migone N., Durr A., Brusco A.
Hum. Mutat. 31:1117-1124(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS SCA28 ILE-654; VAL-666; ARG-666; THR-666; ARG-671 AND GLU-671.
[9]"Mutations in the mitochondrial protease gene AFG3L2 cause dominant hereditary ataxia SCA28."
Di Bella D., Lazzaro F., Brusco A., Plumari M., Battaglia G., Pastore A., Finardi A., Cagnoli C., Tempia F., Frontali M., Veneziano L., Sacco T., Boda E., Brussino A., Bonn F., Castellotti B., Baratta S., Mariotti C. expand/collapse author list , Gellera C., Fracasso V., Magri S., Langer T., Plevani P., Di Donato S., Muzi-Falconi M., Taroni F.
Nat. Genet. 42:313-321(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS SCA28 THR-432; LYS-691; GLU-694 AND GLN-702, TISSUE SPECIFICITY.
[10]"Whole-exome sequencing identifies homozygous AFG3L2 mutations in a spastic ataxia-neuropathy syndrome linked to mitochondrial m-AAA proteases."
Pierson T.M., Adams D., Bonn F., Martinelli P., Cherukuri P.F., Teer J.K., Hansen N.F., Cruz P., Mullikin J.C., Blakesley R.W., Golas G., Kwan J., Sandler A., Fuentes Fajardo K., Markello T., Tifft C., Blackstone C., Rugarli E.I. expand/collapse author list , Langer T., Gahl W.A., Toro C.
PLoS Genet. 7:E1002325-E1002325(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT SPAX5 CYS-616, CHARACTERIZATION OF VARIANT SPAX5 CYS-616.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
Y18314 mRNA. Translation: CAB48398.1.
BC065016 mRNA. Translation: AAH65016.1.
CCDSCCDS11859.1.
RefSeqNP_006787.2. NM_006796.2.
UniGeneHs.726355.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2LNANMR-A164-251[»]
ProteinModelPortalQ9Y4W6.
SMRQ9Y4W6. Positions 163-251, 296-750.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid116139. 15 interactions.
IntActQ9Y4W6. 16 interactions.
MINTMINT-1161944.
STRING9606.ENSP00000269143.

Chemistry

DrugBankDB00171. Adenosine triphosphate.

Protein family/group databases

MEROPSM41.007.

PTM databases

PhosphoSiteQ9Y4W6.

Polymorphism databases

DMDM126302516.

Proteomic databases

MaxQBQ9Y4W6.
PaxDbQ9Y4W6.
PeptideAtlasQ9Y4W6.
PRIDEQ9Y4W6.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000269143; ENSP00000269143; ENSG00000141385.
GeneID10939.
KEGGhsa:10939.
UCSCuc002kqz.2. human.

Organism-specific databases

CTD10939.
GeneCardsGC18M012328.
GeneReviewsAFG3L2.
H-InvDBHIX0027367.
HGNCHGNC:315. AFG3L2.
HPAHPA004479.
HPA004480.
MIM604581. gene.
610246. phenotype.
614487. phenotype.
neXtProtNX_Q9Y4W6.
Orphanet313772. Early-onset spastic ataxia-neuropathy syndrome.
101109. Spinocerebellar ataxia type 28.
PharmGKBPA24612.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0465.
HOVERGENHBG050184.
InParanoidQ9Y4W6.
KOK08956.
OMAMAHRCLR.
OrthoDBEOG7NW68F.
PhylomeDBQ9Y4W6.
TreeFamTF105004.

Gene expression databases

ArrayExpressQ9Y4W6.
BgeeQ9Y4W6.
CleanExHS_AFG3L2.
GenevestigatorQ9Y4W6.

Family and domain databases

Gene3D3.40.50.300. 1 hit.
HAMAPMF_01458. FtsH.
InterProIPR003593. AAA+_ATPase.
IPR003959. ATPase_AAA_core.
IPR003960. ATPase_AAA_CS.
IPR005936. FtsH.
IPR027417. P-loop_NTPase.
IPR011546. Pept_M41_FtsH_extracell.
IPR000642. Peptidase_M41.
[Graphical view]
PfamPF00004. AAA. 1 hit.
PF06480. FtsH_ext. 1 hit.
PF01434. Peptidase_M41. 1 hit.
[Graphical view]
SMARTSM00382. AAA. 1 hit.
[Graphical view]
SUPFAMSSF52540. SSF52540. 1 hit.
TIGRFAMsTIGR01241. FtsH_fam. 1 hit.
PROSITEPS00674. AAA. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiAFG3L2.
GenomeRNAi10939.
NextBio41551.
PROQ9Y4W6.
SOURCESearch...

Entry information

Entry nameAFG32_HUMAN
AccessionPrimary (citable) accession number: Q9Y4W6
Secondary accession number(s): Q6P1L0
Entry history
Integrated into UniProtKB/Swiss-Prot: April 27, 2001
Last sequence update: February 20, 2007
Last modified: July 9, 2014
This is version 140 of the entry and version 2 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

Peptidase families

Classification of peptidase families and list of entries

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

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

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 18

Human chromosome 18: entries, gene names and cross-references to MIM