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Q9Y4W6

- AFG32_HUMAN

UniProt

Q9Y4W6 - AFG32_HUMAN

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Protein

AFG3-like protein 2

Gene

AFG3L2

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli

Functioni

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

Cofactori

Zn2+CuratedNote: 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. unfolded protein binding Source: ProtInc
  4. 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
Complete GO annotation...

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

Topology

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

GO - Cellular componenti

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

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

BgeeiQ9Y4W6.
CleanExiHS_AFG3L2.
ExpressionAtlasiQ9Y4W6. baseline and differential.
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. 16 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 – 1695Combined sources
Helixi172 – 1787Combined sources
Helixi180 – 1823Combined sources
Beta strandi185 – 1917Combined sources
Turni192 – 1943Combined sources
Beta strandi195 – 2006Combined sources
Turni202 – 2043Combined sources
Beta strandi212 – 2154Combined sources
Helixi219 – 23214Combined sources
Turni237 – 2393Combined sources
Beta strandi243 – 2453Combined sources

3D structure databases

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

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.
GeneTreeiENSGT00730000110911.
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

        10         20         30         40         50
MAHRCLRLWG RGGCWPRGLQ QLLVPGGVGP GEQPCLRTLY RFVTTQARAS
60 70 80 90 100
RNSLLTDIIA AYQRFCSRPP KGFEKYFPNG KNGKKASEPK EVMGEKKESK
110 120 130 140 150
PAATTRSSGG GGGGGGKRGG KKDDSHWWSR FQKGDIPWDD KDFRMFFLWT
160 170 180 190 200
ALFWGGVMFY LLLKRSGREI TWKDFVNNYL SKGVVDRLEV VNKRFVRVTF
210 220 230 240 250
TPGKTPVDGQ YVWFNIGSVD TFERNLETLQ QELGIEGENR VPVVYIAESD
260 270 280 290 300
GSFLLSMLPT VLIIAFLLYT IRRGPAGIGR TGRGMGGLFS VGETTAKVLK
310 320 330 340 350
DEIDVKFKDV AGCEEAKLEI MEFVNFLKNP KQYQDLGAKI PKGAILTGPP
360 370 380 390 400
GTGKTLLAKA TAGEANVPFI TVSGSEFLEM FVGVGPARVR DLFALARKNA
410 420 430 440 450
PCILFIDEID AVGRKRGRGN FGGQSEQENT LNQLLVEMDG FNTTTNVVIL
460 470 480 490 500
AGTNRPDILD PALLRPGRFD RQIFIGPPDI KGRASIFKVH LRPLKLDSTL
510 520 530 540 550
EKDKLARKLA SLTPGFSGAD VANVCNEAAL IAARHLSDSI NQKHFEQAIE
560 570 580 590 600
RVIGGLEKKT QVLQPEEKKT VAYHEAGHAV AGWYLEHADP LLKVSIIPRG
610 620 630 640 650
KGLGYAQYLP KEQYLYTKEQ LLDRMCMTLG GRVSEEIFFG RITTGAQDDL
660 670 680 690 700
RKVTQSAYAQ IVQFGMNEKV GQISFDLPRQ GDMVLEKPYS EATARLIDDE
710 720 730 740 750
VRILINDAYK RTVALLTEKK ADVEKVALLL LEKEVLDKND MVELLGPRPF
760 770 780 790
AEKSTYEEFV EGTGSLDEDT SLPEGLKDWN KEREKEKEEP PGEKVAN
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:
EMBLi
GenBanki
DDBJi
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:
EMBLi
GenBanki
DDBJi
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:
PDBei
RCSB PDBi
PDBji
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. 16 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.
GeneTreei ENSGT00730000110911.
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

Bgeei Q9Y4W6.
CleanExi HS_AFG3L2.
ExpressionAtlasi Q9Y4W6. baseline and differential.
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

« Hide 'large scale' publications
  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: November 26, 2014
This is version 144 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