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Protein

AFG3-like protein 2

Gene

AFG3L2

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

Functioni

ATP-dependent protease which is essential for axonal and neuron development. In neurons, mediates degradation of SMDT1/EMRE before its assembly with the uniporter complex, limiting the availability of SMDT1/EMRE for MCU assembly and promoting efficient assembly of gatekeeper subunits with MCU.1 Publication

Cofactori

Zn2+By similarityNote: Binds 1 zinc ion per subunit.By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi574Zinc; catalyticBy similarity1
Active sitei575By similarity1
Metal bindingi578Zinc; catalyticBy similarity1
Metal bindingi649Zinc; catalyticBy similarity1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi348 – 355ATPSequence analysis8

GO - Molecular functioni

  • ATP binding Source: UniProtKB-KW
  • ATP-dependent peptidase activity Source: GO_Central
  • metalloendopeptidase activity Source: InterPro
  • metallopeptidase activity Source: UniProtKB
  • unfolded protein binding Source: ProtInc
  • zinc ion binding Source: InterPro

GO - Biological processi

  • axonogenesis Source: UniProtKB
  • calcium ion transmembrane import into mitochondrion Source: UniProtKB
  • cristae formation Source: GO_Central
  • mitochondrial calcium ion homeostasis Source: UniProtKB
  • mitochondrial fusion Source: GO_Central
  • mitochondrial protein processing Source: GO_Central
  • muscle fiber development Source: Ensembl
  • myelination Source: Ensembl
  • nerve development Source: GO_Central
  • neuromuscular junction development Source: Ensembl
  • protein complex assembly Source: GO_Central
  • protein import into mitochondrial intermembrane space Source: GO_Central
  • proteolysis Source: UniProtKB
  • regulation of multicellular organism growth Source: Ensembl
  • righting reflex Source: Ensembl
Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Metalloprotease, Protease

Keywords - Ligandi

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

Enzyme and pathway databases

BioCyciZFISH:ENSG00000141385-MONOMER.
BRENDAi3.4.24.B18. 2681.

Protein family/group databases

MEROPSiM41.007.

Names & Taxonomyi

Protein namesi
Recommended name:
AFG3-like protein 2 (EC:3.4.24.-1 Publication)
Alternative name(s):
Paraplegin-like protein
Gene namesi
Name:AFG3L2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 18

Organism-specific databases

HGNCiHGNC:315. AFG3L2.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Transmembranei143 – 163HelicalSequence analysisAdd BLAST21
Transmembranei251 – 271HelicalSequence analysisAdd BLAST21

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Membrane, Mitochondrion

Pathology & Biotechi

Involvement in diseasei

Spinocerebellar ataxia 28 (SCA28)5 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionSpinocerebellar 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.
See also OMIM:610246
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_063544432N → T in SCA28. 1 PublicationCorresponds to variant rs151344512dbSNPEnsembl.1
Natural variantiVAR_064402654T → I in SCA28. 1 PublicationCorresponds to variant rs151344513dbSNPEnsembl.1
Natural variantiVAR_064403666M → R in SCA28. 1 PublicationCorresponds to variant rs151344515dbSNPEnsembl.1
Natural variantiVAR_064404666M → T in SCA28. 1 PublicationCorresponds to variant rs151344515dbSNPEnsembl.1
Natural variantiVAR_064405666M → V in SCA28. 1 PublicationCorresponds to variant rs151344514dbSNPEnsembl.1
Natural variantiVAR_064406671G → E in SCA28. 1 PublicationCorresponds to variant rs151344518dbSNPEnsembl.1
Natural variantiVAR_064407671G → R in SCA28. 1 PublicationCorresponds to variant rs151344517dbSNPEnsembl.1
Natural variantiVAR_075198689Y → H in SCA28. 1 Publication1
Natural variantiVAR_075199689Y → N in SCA28. 1 Publication1
Natural variantiVAR_063545691E → K in SCA28. 1 PublicationCorresponds to variant rs151344520dbSNPEnsembl.1
Natural variantiVAR_063546694A → E in SCA28. 1 PublicationCorresponds to variant rs151344521dbSNPEnsembl.1
Natural variantiVAR_064408700E → K in SCA28. 1 PublicationCorresponds to variant rs151344522dbSNPEnsembl.1
Natural variantiVAR_063547702R → Q in SCA28. 1 PublicationCorresponds to variant rs151344523dbSNPEnsembl.1
Spastic ataxia 5, autosomal recessive (SPAX5)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA neurodegenerative disorder characterized by early onset spasticity, peripheral neuropathy, ptosis, oculomotor apraxia, dystonia, cerebellar atrophy, and progressive myoclonic epilepsy.
See also OMIM:614487
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_067330616Y → C in SPAX5; hypomorphic mutation; results in impaired oligomerization with itself and SPG7; retains ATPase and proteolytic activities. 1 PublicationCorresponds to variant rs387906889dbSNPEnsembl.1

Keywords - Diseasei

Disease mutation, Neurodegeneration, Spinocerebellar ataxia

Organism-specific databases

DisGeNETi10939.
MalaCardsiAFG3L2.
MIMi610246. phenotype.
614487. phenotype.
OpenTargetsiENSG00000141385.
Orphaneti313772. Early-onset spastic ataxia-neuropathy syndrome.
101109. Spinocerebellar ataxia type 28.
PharmGKBiPA24612.

Chemistry databases

DrugBankiDB00171. Adenosine triphosphate.

Polymorphism and mutation databases

BioMutaiAFG3L2.
DMDMi126302516.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000846731 – 797AFG3-like protein 2Add BLAST797

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei117N6-succinyllysineBy similarity1

Proteomic databases

EPDiQ9Y4W6.
MaxQBiQ9Y4W6.
PaxDbiQ9Y4W6.
PeptideAtlasiQ9Y4W6.
PRIDEiQ9Y4W6.
TopDownProteomicsiQ9Y4W6.

PTM databases

iPTMnetiQ9Y4W6.
PhosphoSitePlusiQ9Y4W6.
SwissPalmiQ9Y4W6.

Expressioni

Tissue specificityi

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

Gene expression databases

BgeeiENSG00000141385.
CleanExiHS_AFG3L2.
ExpressionAtlasiQ9Y4W6. baseline and differential.
GenevisibleiQ9Y4W6. HS.

Organism-specific databases

HPAiHPA004479.
HPA004480.

Interactioni

Subunit structurei

Homooligomer (PubMed:17101804). Interacts with SPG7; the interaction is required for the efficient assembly of mitochondrial complex I (PubMed:14623864). Interacts with C2orf47/MAIP1 (PubMed:27499296, PubMed:27642048).4 Publications

GO - Molecular functioni

  • unfolded protein binding Source: ProtInc

Protein-protein interaction databases

BioGridi116139. 64 interactors.
IntActiQ9Y4W6. 43 interactors.
MINTiMINT-1161944.
STRINGi9606.ENSP00000269143.

Structurei

Secondary structure

1797
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi165 – 169Combined sources5
Helixi172 – 178Combined sources7
Helixi180 – 182Combined sources3
Beta strandi185 – 191Combined sources7
Turni192 – 194Combined sources3
Beta strandi195 – 200Combined sources6
Turni202 – 204Combined sources3
Beta strandi212 – 215Combined sources4
Helixi219 – 232Combined sources14
Turni237 – 239Combined sources3
Beta strandi243 – 245Combined sources3

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2LNANMR-A164-251[»]
ProteinModelPortaliQ9Y4W6.
SMRiQ9Y4W6.
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

eggNOGiKOG0731. Eukaryota.
COG0465. LUCA.
GeneTreeiENSGT00860000133808.
HOVERGENiHBG050184.
InParanoidiQ9Y4W6.
KOiK08956.
OMAiCLRLWGR.
OrthoDBiEOG091G03EQ.
PhylomeDBiQ9Y4W6.
TreeFamiTF105004.

Family and domain databases

Gene3Di3.40.50.300. 1 hit.
HAMAPiMF_01458. FtsH. 1 hit.
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)DescriptionActionsGraphical viewLength
Sequence conflicti74E → G in CAB48398 (PubMed:10395799).Curated1
Sequence conflicti633V → A in CAB48398 (PubMed:10395799).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_063544432N → T in SCA28. 1 PublicationCorresponds to variant rs151344512dbSNPEnsembl.1
Natural variantiVAR_067330616Y → C in SPAX5; hypomorphic mutation; results in impaired oligomerization with itself and SPG7; retains ATPase and proteolytic activities. 1 PublicationCorresponds to variant rs387906889dbSNPEnsembl.1
Natural variantiVAR_064402654T → I in SCA28. 1 PublicationCorresponds to variant rs151344513dbSNPEnsembl.1
Natural variantiVAR_064403666M → R in SCA28. 1 PublicationCorresponds to variant rs151344515dbSNPEnsembl.1
Natural variantiVAR_064404666M → T in SCA28. 1 PublicationCorresponds to variant rs151344515dbSNPEnsembl.1
Natural variantiVAR_064405666M → V in SCA28. 1 PublicationCorresponds to variant rs151344514dbSNPEnsembl.1
Natural variantiVAR_064406671G → E in SCA28. 1 PublicationCorresponds to variant rs151344518dbSNPEnsembl.1
Natural variantiVAR_064407671G → R in SCA28. 1 PublicationCorresponds to variant rs151344517dbSNPEnsembl.1
Natural variantiVAR_075198689Y → H in SCA28. 1 Publication1
Natural variantiVAR_075199689Y → N in SCA28. 1 Publication1
Natural variantiVAR_063545691E → K in SCA28. 1 PublicationCorresponds to variant rs151344520dbSNPEnsembl.1
Natural variantiVAR_063546694A → E in SCA28. 1 PublicationCorresponds to variant rs151344521dbSNPEnsembl.1
Natural variantiVAR_064408700E → K in SCA28. 1 PublicationCorresponds to variant rs151344522dbSNPEnsembl.1
Natural variantiVAR_063547702R → Q in SCA28. 1 PublicationCorresponds to variant rs151344523dbSNPEnsembl.1

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.3. human.

Cross-referencesi

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.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2LNANMR-A164-251[»]
ProteinModelPortaliQ9Y4W6.
SMRiQ9Y4W6.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi116139. 64 interactors.
IntActiQ9Y4W6. 43 interactors.
MINTiMINT-1161944.
STRINGi9606.ENSP00000269143.

Chemistry databases

DrugBankiDB00171. Adenosine triphosphate.

Protein family/group databases

MEROPSiM41.007.

PTM databases

iPTMnetiQ9Y4W6.
PhosphoSitePlusiQ9Y4W6.
SwissPalmiQ9Y4W6.

Polymorphism and mutation databases

BioMutaiAFG3L2.
DMDMi126302516.

Proteomic databases

EPDiQ9Y4W6.
MaxQBiQ9Y4W6.
PaxDbiQ9Y4W6.
PeptideAtlasiQ9Y4W6.
PRIDEiQ9Y4W6.
TopDownProteomicsiQ9Y4W6.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000269143; ENSP00000269143; ENSG00000141385.
GeneIDi10939.
KEGGihsa:10939.
UCSCiuc002kqz.3. human.

Organism-specific databases

CTDi10939.
DisGeNETi10939.
GeneCardsiAFG3L2.
GeneReviewsiAFG3L2.
H-InvDBHIX0027367.
HGNCiHGNC:315. AFG3L2.
HPAiHPA004479.
HPA004480.
MalaCardsiAFG3L2.
MIMi604581. gene.
610246. phenotype.
614487. phenotype.
neXtProtiNX_Q9Y4W6.
OpenTargetsiENSG00000141385.
Orphaneti313772. Early-onset spastic ataxia-neuropathy syndrome.
101109. Spinocerebellar ataxia type 28.
PharmGKBiPA24612.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0731. Eukaryota.
COG0465. LUCA.
GeneTreeiENSGT00860000133808.
HOVERGENiHBG050184.
InParanoidiQ9Y4W6.
KOiK08956.
OMAiCLRLWGR.
OrthoDBiEOG091G03EQ.
PhylomeDBiQ9Y4W6.
TreeFamiTF105004.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000141385-MONOMER.
BRENDAi3.4.24.B18. 2681.

Miscellaneous databases

GeneWikiiAFG3L2.
GenomeRNAii10939.
PROiQ9Y4W6.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000141385.
CleanExiHS_AFG3L2.
ExpressionAtlasiQ9Y4W6. baseline and differential.
GenevisibleiQ9Y4W6. HS.

Family and domain databases

Gene3Di3.40.50.300. 1 hit.
HAMAPiMF_01458. FtsH. 1 hit.
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]
ProtoNetiSearch...

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 30, 2016
This is version 165 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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.