AFG1L_HUMAN
ID AFG1L_HUMAN Reviewed; 481 AA.
AC Q8WV93; Q8N6A3;
DT 06-MAR-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2004, sequence version 2.
DT 03-AUG-2022, entry version 152.
DE RecName: Full=AFG1-like ATPase {ECO:0000312|HGNC:HGNC:16411};
DE AltName: Full=Lactation elevated protein 1 {ECO:0000303|PubMed:12079282};
DE EC=3.6.-.- {ECO:0000305};
DE AltName: Full=Protein AFG1 homolog;
GN Name=AFG1L {ECO:0000312|HGNC:HGNC:16411};
GN Synonyms=AFG1, LACE1 {ECO:0000303|PubMed:12079282};
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Retinoblastoma;
RX PubMed=12079282; DOI=10.1006/geno.2002.6795;
RA Abrahams B.S., Mak G.M., Berry M.L., Palmquist D.L., Saionz J.R., Tay A.,
RA Tan Y.H., Brenner S., Simpson E.M., Venkatesh B.;
RT "Novel vertebrate genes and putative regulatory elements identified at
RT kidney disease and NR2E1/fierce loci.";
RL Genomics 80:45-53(2002).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=14574404; DOI=10.1038/nature02055;
RA Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L.,
RA Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R.,
RA Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D.,
RA Andrews T.D., Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H.,
RA Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J.,
RA Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V.,
RA Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J.,
RA Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E.,
RA Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J.,
RA French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J.,
RA Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C.,
RA Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A.,
RA Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R.,
RA Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M.,
RA Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K.,
RA Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R.,
RA Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M.,
RA Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A.,
RA Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L.,
RA Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I.,
RA Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y.,
RA Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E.,
RA Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A.,
RA Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W.,
RA Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M.,
RA West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J.,
RA Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M.,
RA Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I.,
RA Rogers J., Beck S.;
RT "The DNA sequence and analysis of human chromosome 6.";
RL Nature 425:805-811(2003).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Eye;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP SUBCELLULAR LOCATION, FUNCTION, MUTAGENESIS OF LYS-142; THR-143 AND
RP GLU-214, INTERACTION WITH YME1L1, AND COX4I1 AND COX5A.
RX PubMed=26759378; DOI=10.1042/bj20151029;
RA Cesnekova J., Rodinova M., Hansikova H., Houstek J., Zeman J., Stiburek L.;
RT "The mammalian homologue of yeast Afg1 ATPase (lactation elevated 1)
RT mediates degradation of nuclear-encoded complex IV subunits.";
RL Biochem. J. 473:797-804(2016).
RN [5]
RP INTERACTION WITH TP53, SUBCELLULAR LOCATION, AND FUNCTION.
RX PubMed=27323408; DOI=10.18632/oncotarget.9959;
RA Cesnekova J., Spacilova J., Hansikova H., Houstek J., Zeman J.,
RA Stiburek L.;
RT "LACE1 interacts with p53 and mediates its mitochondrial translocation and
RT apoptosis.";
RL Oncotarget 7:47687-47698(2016).
CC -!- FUNCTION: Putative mitochondrial ATPase. Plays a role in mitochondrial
CC morphology and mitochondrial protein metabolism. Promotes degradation
CC of excess nuclear-encoded complex IV subunits (COX4I1, COX5A and
CC COX6A1) and normal activity of complexes III and IV of the respiratory
CC chain (PubMed:26759378, PubMed:27323408). Mediates mitochondrial
CC translocation of TP53 and its transcription-independent apoptosis in
CC response to genotoxic stress (PubMed:27323408).
CC {ECO:0000269|PubMed:26759378, ECO:0000269|PubMed:27323408}.
CC -!- SUBUNIT: Found in several complexes of 140-500 kDa. Interacts with
CC YME1L1 (PubMed:26759378). Interacts with COX4I1 (PubMed:26759378).
CC Interacts with COX5A (PubMed:26759378). Interacts with TP53; mediates
CC mitochondrial translocation of TP53 in response to genotoxic stress
CC such as mitomycin C treatment (PubMed:27323408).
CC {ECO:0000269|PubMed:26759378, ECO:0000269|PubMed:27323408}.
CC -!- INTERACTION:
CC Q8WV93; Q8N9N5: BANP; NbExp=3; IntAct=EBI-2865743, EBI-744695;
CC Q8WV93; Q9UHD4: CIDEB; NbExp=3; IntAct=EBI-2865743, EBI-7062247;
CC -!- SUBCELLULAR LOCATION: Mitochondrion membrane
CC {ECO:0000269|PubMed:26759378}.
CC -!- SIMILARITY: Belongs to the AFG1 ATPase family. {ECO:0000305}.
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DR EMBL; AF520418; AAM74228.1; -; mRNA.
DR EMBL; AL356121; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; Z98742; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL353706; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL139106; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC018445; AAH18445.2; -; mRNA.
DR CCDS; CCDS5067.1; -.
DR RefSeq; NP_001309934.1; NM_001323005.1.
DR RefSeq; NP_660358.2; NM_145315.4.
DR AlphaFoldDB; Q8WV93; -.
DR BioGRID; 128885; 10.
DR IntAct; Q8WV93; 10.
DR STRING; 9606.ENSP00000357973; -.
DR iPTMnet; Q8WV93; -.
DR PhosphoSitePlus; Q8WV93; -.
DR BioMuta; AFG1L; -.
DR DMDM; 74762631; -.
DR EPD; Q8WV93; -.
DR jPOST; Q8WV93; -.
DR MassIVE; Q8WV93; -.
DR MaxQB; Q8WV93; -.
DR PaxDb; Q8WV93; -.
DR PeptideAtlas; Q8WV93; -.
DR PRIDE; Q8WV93; -.
DR ProteomicsDB; 74765; -.
DR Antibodypedia; 32213; 178 antibodies from 21 providers.
DR DNASU; 246269; -.
DR Ensembl; ENST00000368977.9; ENSP00000357973.3; ENSG00000135537.17.
DR GeneID; 246269; -.
DR KEGG; hsa:246269; -.
DR MANE-Select; ENST00000368977.9; ENSP00000357973.3; NM_145315.5; NP_660358.2.
DR UCSC; uc003psj.4; human.
DR CTD; 246269; -.
DR DisGeNET; 246269; -.
DR GeneCards; AFG1L; -.
DR HGNC; HGNC:16411; AFG1L.
DR HPA; ENSG00000135537; Low tissue specificity.
DR MIM; 617469; gene.
DR neXtProt; NX_Q8WV93; -.
DR OpenTargets; ENSG00000135537; -.
DR PharmGKB; PA38404; -.
DR VEuPathDB; HostDB:ENSG00000135537; -.
DR eggNOG; KOG2383; Eukaryota.
DR GeneTree; ENSGT00390000013227; -.
DR HOGENOM; CLU_008681_3_1_1; -.
DR InParanoid; Q8WV93; -.
DR OMA; QKREYWE; -.
DR OrthoDB; 702840at2759; -.
DR PhylomeDB; Q8WV93; -.
DR TreeFam; TF314551; -.
DR PathwayCommons; Q8WV93; -.
DR SignaLink; Q8WV93; -.
DR BioGRID-ORCS; 246269; 17 hits in 1079 CRISPR screens.
DR ChiTaRS; LACE1; human.
DR GenomeRNAi; 246269; -.
DR Pharos; Q8WV93; Tbio.
DR PRO; PR:Q8WV93; -.
DR Proteomes; UP000005640; Chromosome 6.
DR RNAct; Q8WV93; protein.
DR Bgee; ENSG00000135537; Expressed in left testis and 100 other tissues.
DR ExpressionAtlas; Q8WV93; baseline and differential.
DR Genevisible; Q8WV93; HS.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0031966; C:mitochondrial membrane; IDA:UniProtKB.
DR GO; GO:0005739; C:mitochondrion; IDA:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0016887; F:ATP hydrolysis activity; IBA:GO_Central.
DR GO; GO:0006123; P:mitochondrial electron transport, cytochrome c to oxygen; IMP:UniProtKB.
DR GO; GO:0035694; P:mitochondrial protein catabolic process; IMP:UniProtKB.
DR GO; GO:0007005; P:mitochondrion organization; IMP:UniProtKB.
DR Gene3D; 3.40.50.300; -; 1.
DR InterPro; IPR005654; ATPase_AFG1-like.
DR InterPro; IPR027417; P-loop_NTPase.
DR PANTHER; PTHR12169; PTHR12169; 1.
DR Pfam; PF03969; AFG1_ATPase; 1.
DR SUPFAM; SSF52540; SSF52540; 1.
PE 1: Evidence at protein level;
KW ATP-binding; Hydrolase; Membrane; Mitochondrion; Nucleotide-binding;
KW Reference proteome.
FT CHAIN 1..481
FT /note="AFG1-like ATPase"
FT /id="PRO_0000279521"
FT BINDING 136..143
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000305"
FT BINDING 209..214
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000305"
FT MUTAGEN 142
FT /note="K->A: Does not affect mitochondrial targeting.
FT Increased amount of unprocessed protein form. Fails to
FT rescue the increased accumulation of complex IV subunits in
FT AFG1L-deficient cell line. Reduces mitochondrial targeting;
FT when associated with V-143."
FT /evidence="ECO:0000269|PubMed:26759378"
FT MUTAGEN 143
FT /note="T->V: Reduces mitochondrial targeting. Increased
FT amount of unprocessed protein form. Reduces mitochondrial
FT targeting; when associated with A-142."
FT /evidence="ECO:0000269|PubMed:26759378"
FT MUTAGEN 214
FT /note="E->Q: Does not affect subcellular location. Fails to
FT rescue the increased accumulation of complex IV subunits in
FT AFG1L-deficient cell line."
FT /evidence="ECO:0000269|PubMed:26759378"
SQ SEQUENCE 481 AA; 54845 MW; 5B612E3B657DCA12 CRC64;
MAASWSLLVT LRPLAQSPLR GRCVGCGAWA AALAPLATAP GKPFWKAYTV QTSESMTPTA
TSETYLKALA VCHGPLDHYD FLIKAHELKD DEHQRRVIQC LQKLHEDLKG YNIEAEGLFS
KLFSRSKPPR GLYVYGDVGT GKTMVMDMFY AYVEMKRKKR VHFHGFMLDV HKRIHRLKQS
LPKRKPGFMA KSYDPIAPIA EEISEEACLL CFDEFQVTDI ADAMILKQLF ENLFKNGVVV
VATSNRPPED LYKNGLQRAN FVPFIAVLKE YCNTVQLDSG IDYRKRELPA AGKLYYLTSE
ADVEAVMDKL FDELAQKQND LTRPRILKVQ GRELRLNKAC GTVADCTFEE LCERPLGASD
YLELSKNFDT IFLRNIPQFT LANRTQGRRF ITLIDNFYDL KVRIICSAST PISSLFLHQH
HDSELEQSRI LMDDLGLSQD SAEGLSMFTG EEEIFAFQRT ISRLTEMQTE QYWNEGDRTK
K
