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Q9Y4W6

- AFG32_HUMAN

UniProt

Q9Y4W6 - AFG32_HUMAN

Protein

AFG3-like protein 2

Gene

AFG3L2

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 142 (01 Oct 2014)
      Sequence version 2 (20 Feb 2007)
      Previous versions | rss
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    Functioni

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

    Cofactori

    Binds 1 zinc ion per subunit.Curated

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Metal bindingi574 – 5741Zinc; catalyticBy similarity
    Active sitei575 – 5751By similarity
    Metal bindingi578 – 5781Zinc; catalyticBy similarity
    Metal bindingi649 – 6491Zinc; catalyticBy similarity

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Nucleotide bindingi348 – 3558ATPSequence Analysis

    GO - Molecular functioni

    1. ATP binding Source: UniProtKB-KW
    2. metalloendopeptidase activity Source: InterPro
    3. nucleoside-triphosphatase activity Source: InterPro
    4. protein binding Source: UniProtKB
    5. unfolded protein binding Source: ProtInc
    6. zinc ion binding Source: InterPro

    GO - Biological processi

    1. axonogenesis Source: Ensembl
    2. cell death Source: UniProtKB-KW
    3. cristae formation Source: Ensembl
    4. mitochondrial fusion Source: Ensembl
    5. mitochondrial protein processing Source: Ensembl
    6. muscle fiber development Source: Ensembl
    7. myelination Source: Ensembl
    8. nerve development Source: Ensembl
    9. neuromuscular junction development Source: Ensembl
    10. regulation of multicellular organism growth Source: Ensembl
    11. righting reflex Source: Ensembl

    Keywords - Molecular functioni

    Hydrolase, Metalloprotease, Protease

    Keywords - Ligandi

    ATP-binding, Metal-binding, Nucleotide-binding, Zinc

    Protein family/group databases

    MEROPSiM41.007.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    AFG3-like protein 2 (EC:3.4.24.-)
    Alternative name(s):
    Paraplegin-like protein
    Gene namesi
    Name:AFG3L2
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 18

    Organism-specific databases

    HGNCiHGNC:315. AFG3L2.

    Subcellular locationi

    Mitochondrion membrane 1 Publication; Multi-pass membrane protein 1 Publication

    GO - Cellular componenti

    1. integral component of membrane Source: UniProtKB-KW
    2. mitochondrial inner membrane Source: Ensembl
    3. mitochondrion Source: HPA

    Keywords - Cellular componenti

    Membrane, Mitochondrion

    Pathology & Biotechi

    Involvement in diseasei

    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.3 Publications
    Note: The disease is caused by mutations affecting the gene represented in this entry.
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti432 – 4321N → T in SCA28. 1 Publication
    VAR_063544
    Natural varianti654 – 6541T → I in SCA28. 1 Publication
    VAR_064402
    Natural varianti666 – 6661M → R in SCA28. 1 Publication
    VAR_064403
    Natural varianti666 – 6661M → T in SCA28. 1 Publication
    VAR_064404
    Natural varianti666 – 6661M → V in SCA28. 1 Publication
    VAR_064405
    Natural varianti671 – 6711G → E in SCA28. 1 Publication
    VAR_064406
    Natural varianti671 – 6711G → R in SCA28. 1 Publication
    VAR_064407
    Natural varianti691 – 6911E → K in SCA28. 1 Publication
    VAR_063545
    Natural varianti694 – 6941A → E in SCA28. 1 Publication
    VAR_063546
    Natural varianti700 – 7001E → K in SCA28. 1 Publication
    VAR_064408
    Natural varianti702 – 7021R → Q in SCA28. 1 Publication
    VAR_063547
    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.1 Publication
    Note: The disease is caused by mutations affecting the gene represented in this entry.
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti616 – 6161Y → C in SPAX5; hypomorphic mutation; results in impaired oligomerization with itself and SPG7; retains ATPase and proteolytic activities. 1 Publication
    VAR_067330

    Keywords - Diseasei

    Disease mutation, Neurodegeneration, Spinocerebellar ataxia

    Organism-specific databases

    MIMi610246. phenotype.
    614487. phenotype.
    Orphaneti313772. Early-onset spastic ataxia-neuropathy syndrome.
    101109. Spinocerebellar ataxia type 28.
    PharmGKBiPA24612.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 797797AFG3-like protein 2PRO_0000084673Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei117 – 1171N6-succinyllysineBy similarity

    Proteomic databases

    MaxQBiQ9Y4W6.
    PaxDbiQ9Y4W6.
    PeptideAtlasiQ9Y4W6.
    PRIDEiQ9Y4W6.

    PTM databases

    PhosphoSiteiQ9Y4W6.

    Expressioni

    Tissue specificityi

    Ubiquitous. Highly expressed in the cerebellar Purkinje cells.1 Publication

    Gene expression databases

    ArrayExpressiQ9Y4W6.
    BgeeiQ9Y4W6.
    CleanExiHS_AFG3L2.
    GenevestigatoriQ9Y4W6.

    Organism-specific databases

    HPAiHPA004479.
    HPA004480.

    Interactioni

    Subunit structurei

    Homooligomer. Interacts with SPG7; the interaction is required for the efficient assembly of mitochondrial complex I.2 Publications

    Protein-protein interaction databases

    BioGridi116139. 15 interactions.
    IntActiQ9Y4W6. 17 interactions.
    MINTiMINT-1161944.
    STRINGi9606.ENSP00000269143.

    Structurei

    Secondary structure

    1
    797
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Beta strandi165 – 1695
    Helixi172 – 1787
    Helixi180 – 1823
    Beta strandi185 – 1917
    Turni192 – 1943
    Beta strandi195 – 2006
    Turni202 – 2043
    Beta strandi212 – 2154
    Helixi219 – 23214
    Turni237 – 2393
    Beta strandi243 – 2453

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    2LNANMR-A164-251[»]
    ProteinModelPortaliQ9Y4W6.
    SMRiQ9Y4W6. Positions 163-251, 296-750.
    ModBaseiSearch...
    MobiDBiSearch...

    Transmembrane

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transmembranei143 – 16321HelicalSequence AnalysisAdd
    BLAST
    Transmembranei251 – 27121HelicalSequence AnalysisAdd
    BLAST

    Family & Domainsi

    Sequence similaritiesi

    In the N-terminal section; belongs to the AAA ATPase family.Curated
    In the C-terminal section; belongs to the peptidase M41 family.Curated

    Keywords - Domaini

    Transmembrane, Transmembrane helix

    Phylogenomic databases

    eggNOGiCOG0465.
    HOVERGENiHBG050184.
    InParanoidiQ9Y4W6.
    KOiK08956.
    OMAiMAHRCLR.
    OrthoDBiEOG7NW68F.
    PhylomeDBiQ9Y4W6.
    TreeFamiTF105004.

    Family and domain databases

    Gene3Di3.40.50.300. 1 hit.
    HAMAPiMF_01458. FtsH.
    InterProiIPR003593. 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]
    PfamiPF00004. AAA. 1 hit.
    PF06480. FtsH_ext. 1 hit.
    PF01434. Peptidase_M41. 1 hit.
    [Graphical view]
    SMARTiSM00382. AAA. 1 hit.
    [Graphical view]
    SUPFAMiSSF52540. SSF52540. 1 hit.
    TIGRFAMsiTIGR01241. FtsH_fam. 1 hit.
    PROSITEiPS00674. AAA. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    Q9Y4W6-1 [UniParc]FASTAAdd to Basket

    « Hide

    MAHRCLRLWG RGGCWPRGLQ QLLVPGGVGP GEQPCLRTLY RFVTTQARAS    50
    RNSLLTDIIA AYQRFCSRPP KGFEKYFPNG KNGKKASEPK EVMGEKKESK 100
    PAATTRSSGG GGGGGGKRGG KKDDSHWWSR FQKGDIPWDD KDFRMFFLWT 150
    ALFWGGVMFY LLLKRSGREI TWKDFVNNYL SKGVVDRLEV VNKRFVRVTF 200
    TPGKTPVDGQ YVWFNIGSVD TFERNLETLQ QELGIEGENR VPVVYIAESD 250
    GSFLLSMLPT VLIIAFLLYT IRRGPAGIGR TGRGMGGLFS VGETTAKVLK 300
    DEIDVKFKDV AGCEEAKLEI MEFVNFLKNP KQYQDLGAKI PKGAILTGPP 350
    GTGKTLLAKA TAGEANVPFI TVSGSEFLEM FVGVGPARVR DLFALARKNA 400
    PCILFIDEID AVGRKRGRGN FGGQSEQENT LNQLLVEMDG FNTTTNVVIL 450
    AGTNRPDILD PALLRPGRFD RQIFIGPPDI KGRASIFKVH LRPLKLDSTL 500
    EKDKLARKLA SLTPGFSGAD VANVCNEAAL IAARHLSDSI NQKHFEQAIE 550
    RVIGGLEKKT QVLQPEEKKT VAYHEAGHAV AGWYLEHADP LLKVSIIPRG 600
    KGLGYAQYLP KEQYLYTKEQ LLDRMCMTLG GRVSEEIFFG RITTGAQDDL 650
    RKVTQSAYAQ IVQFGMNEKV GQISFDLPRQ GDMVLEKPYS EATARLIDDE 700
    VRILINDAYK RTVALLTEKK ADVEKVALLL LEKEVLDKND MVELLGPRPF 750
    AEKSTYEEFV EGTGSLDEDT SLPEGLKDWN KEREKEKEEP PGEKVAN 797
    Length:797
    Mass (Da):88,584
    Last modified:February 20, 2007 - v2
    Checksum:iEACBB7C5F2EE5E08
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti74 – 741E → G in CAB48398. (PubMed:10395799)Curated
    Sequence conflicti633 – 6331V → A in CAB48398. (PubMed:10395799)Curated

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti432 – 4321N → T in SCA28. 1 Publication
    VAR_063544
    Natural varianti616 – 6161Y → C in SPAX5; hypomorphic mutation; results in impaired oligomerization with itself and SPG7; retains ATPase and proteolytic activities. 1 Publication
    VAR_067330
    Natural varianti654 – 6541T → I in SCA28. 1 Publication
    VAR_064402
    Natural varianti666 – 6661M → R in SCA28. 1 Publication
    VAR_064403
    Natural varianti666 – 6661M → T in SCA28. 1 Publication
    VAR_064404
    Natural varianti666 – 6661M → V in SCA28. 1 Publication
    VAR_064405
    Natural varianti671 – 6711G → E in SCA28. 1 Publication
    VAR_064406
    Natural varianti671 – 6711G → R in SCA28. 1 Publication
    VAR_064407
    Natural varianti691 – 6911E → K in SCA28. 1 Publication
    VAR_063545
    Natural varianti694 – 6941A → E in SCA28. 1 Publication
    VAR_063546
    Natural varianti700 – 7001E → K in SCA28. 1 Publication
    VAR_064408
    Natural varianti702 – 7021R → Q in SCA28. 1 Publication
    VAR_063547

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    Y18314 mRNA. Translation: CAB48398.1.
    BC065016 mRNA. Translation: AAH65016.1.
    CCDSiCCDS11859.1.
    RefSeqiNP_006787.2. NM_006796.2.
    UniGeneiHs.726355.

    Genome annotation databases

    EnsembliENST00000269143; ENSP00000269143; ENSG00000141385.
    GeneIDi10939.
    KEGGihsa:10939.
    UCSCiuc002kqz.2. human.

    Polymorphism databases

    DMDMi126302516.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    Y18314 mRNA. Translation: CAB48398.1 .
    BC065016 mRNA. Translation: AAH65016.1 .
    CCDSi CCDS11859.1.
    RefSeqi NP_006787.2. NM_006796.2.
    UniGenei Hs.726355.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    2LNA NMR - A 164-251 [» ]
    ProteinModelPortali Q9Y4W6.
    SMRi Q9Y4W6. Positions 163-251, 296-750.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 116139. 15 interactions.
    IntActi Q9Y4W6. 17 interactions.
    MINTi MINT-1161944.
    STRINGi 9606.ENSP00000269143.

    Chemistry

    DrugBanki DB00171. Adenosine triphosphate.

    Protein family/group databases

    MEROPSi M41.007.

    PTM databases

    PhosphoSitei Q9Y4W6.

    Polymorphism databases

    DMDMi 126302516.

    Proteomic databases

    MaxQBi Q9Y4W6.
    PaxDbi Q9Y4W6.
    PeptideAtlasi Q9Y4W6.
    PRIDEi Q9Y4W6.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000269143 ; ENSP00000269143 ; ENSG00000141385 .
    GeneIDi 10939.
    KEGGi hsa:10939.
    UCSCi uc002kqz.2. human.

    Organism-specific databases

    CTDi 10939.
    GeneCardsi GC18M012328.
    GeneReviewsi AFG3L2.
    H-InvDB HIX0027367.
    HGNCi HGNC:315. AFG3L2.
    HPAi HPA004479.
    HPA004480.
    MIMi 604581. gene.
    610246. phenotype.
    614487. phenotype.
    neXtProti NX_Q9Y4W6.
    Orphaneti 313772. Early-onset spastic ataxia-neuropathy syndrome.
    101109. Spinocerebellar ataxia type 28.
    PharmGKBi PA24612.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi COG0465.
    HOVERGENi HBG050184.
    InParanoidi Q9Y4W6.
    KOi K08956.
    OMAi MAHRCLR.
    OrthoDBi EOG7NW68F.
    PhylomeDBi Q9Y4W6.
    TreeFami TF105004.

    Miscellaneous databases

    GeneWikii AFG3L2.
    GenomeRNAii 10939.
    NextBioi 41551.
    PROi Q9Y4W6.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi Q9Y4W6.
    Bgeei Q9Y4W6.
    CleanExi HS_AFG3L2.
    Genevestigatori Q9Y4W6.

    Family and domain databases

    Gene3Di 3.40.50.300. 1 hit.
    HAMAPi MF_01458. FtsH.
    InterProi IPR003593. 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 ]
    Pfami PF00004. AAA. 1 hit.
    PF06480. FtsH_ext. 1 hit.
    PF01434. Peptidase_M41. 1 hit.
    [Graphical view ]
    SMARTi SM00382. AAA. 1 hit.
    [Graphical view ]
    SUPFAMi SSF52540. SSF52540. 1 hit.
    TIGRFAMsi TIGR01241. FtsH_fam. 1 hit.
    PROSITEi PS00674. AAA. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    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. 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. 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.
      , 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.

    Entry informationi

    Entry nameiAFG32_HUMAN
    AccessioniPrimary (citable) accession number: Q9Y4W6
    Secondary accession number(s): Q6P1L0
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: April 27, 2001
    Last sequence update: February 20, 2007
    Last modified: October 1, 2014
    This is version 142 of the entry and version 2 of the sequence. [Complete history]
    Entry statusiReviewed (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.

    Miscellaneousi

    Keywords - Technical termi

    3D-structure, Complete proteome, Reference proteome

    Documents

    1. Human chromosome 18
      Human chromosome 18: entries, gene names and cross-references to MIM
    2. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    3. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    4. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    5. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    6. Peptidase families
      Classification of peptidase families and list of entries
    7. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3