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Protein

Apoptosis-inducing factor 1, mitochondrial

Gene

AIFM1

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

Functioni

Functions both as NADH oxidoreductase and as regulator of apoptosis. In response to apoptotic stimuli, it is released from the mitochondrion intermembrane space into the cytosol and to the nucleus, where it functions as a proapoptotic factor in a caspase-independent pathway. In contrast, functions as an antiapoptotic factor in normal mitochondria via its NADH oxidoreductase activity. The soluble form (AIFsol) found in the nucleus induces 'parthanatos' i.e. caspase-independent fragmentation of chromosomal DNA. Interacts with EIF3G,and thereby inhibits the EIF3 machinery and protein synthesis, and activates casapse-7 to amplify apoptosis. Plays a critical role in caspase-independent, pyknotic cell death in hydrogen peroxide-exposed cells. Binds to DNA in a sequence-independent manner.4 Publications

Cofactori

FAD1 Publication

Kineticsi

  1. KM=1.53 mM for NADH1 Publication
  2. KM=26 µM for cytochrome c1 Publication

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Binding sitei172 – 1721FAD2 Publications
    Binding sitei177 – 1771FAD2 Publications
    Binding sitei233 – 2331FAD; via amide nitrogen and carbonyl oxygen2 Publications
    Binding sitei285 – 2851FAD2 Publications
    Binding sitei438 – 4381FAD2 Publications
    Binding sitei483 – 4831FAD; via carbonyl oxygen2 Publications

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Nucleotide bindingi138 – 1425FAD2 Publications
    Nucleotide bindingi164 – 1652FAD2 Publications
    Nucleotide bindingi454 – 4552FAD2 Publications

    GO - Molecular functioni

    • DNA binding Source: UniProtKB-KW
    • electron carrier activity Source: ProtInc
    • FAD binding Source: Ensembl
    • NAD(P)H oxidase activity Source: UniProtKB
    • oxidoreductase activity, acting on NAD(P)H Source: UniProtKB

    GO - Biological processi

    • activation of cysteine-type endopeptidase activity involved in apoptotic process Source: UniProtKB
    • apoptotic DNA fragmentation Source: ProtInc
    • apoptotic process Source: UniProtKB
    • cell redox homeostasis Source: InterPro
    • chromosome condensation Source: UniProtKB
    • DNA catabolic process Source: UniProtKB
    • intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress Source: UniProtKB
    • mitochondrial respiratory chain complex I assembly Source: UniProtKB
    • neuron apoptotic process Source: Ensembl
    • neuron differentiation Source: UniProtKB
    • positive regulation of apoptotic process Source: UniProtKB
    • regulation of apoptotic DNA fragmentation Source: Ensembl
    Complete GO annotation...

    Keywords - Molecular functioni

    Oxidoreductase

    Keywords - Biological processi

    Apoptosis

    Keywords - Ligandi

    DNA-binding, FAD, Flavoprotein, NAD

    Enzyme and pathway databases

    SABIO-RKO95831.
    SignaLinkiO95831.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Apoptosis-inducing factor 1, mitochondrial (EC:1.1.1.-)
    Alternative name(s):
    Programmed cell death protein 8
    Gene namesi
    Name:AIFM1
    Synonyms:AIF, PDCD8
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640 Componenti: Chromosome X

    Organism-specific databases

    HGNCiHGNC:8768. AIFM1.

    Subcellular locationi

    • Mitochondrion intermembrane space
    • Mitochondrion inner membrane
    • Cytoplasm
    • Nucleus
    • Cytoplasmperinuclear region

    • Note: Proteolytic cleavage during or just after translocation into the mitochondrial intermembrane space (IMS) results in the formation of an inner-membrane-anchored mature form (AIFmit). During apoptosis, further proteolytic processing leads to a mature form, which is confined to the mitochondrial IMS in a soluble form (AIFsol). AIFsol is released to the cytoplasm in response to specific death signals, and translocated to the nucleus, where it induces nuclear apoptosis. Colocalizes with EIF3G in the nucleus and perinuclear region.
    Isoform 3 :
    Isoform 5 :

    GO - Cellular componenti

    • cytosol Source: UniProtKB
    • mitochondrial inner membrane Source: UniProtKB
    • mitochondrial intermembrane space Source: UniProtKB
    • mitochondrion Source: UniProtKB
    • nucleus Source: UniProtKB
    • perinuclear region of cytoplasm Source: UniProtKB-SubCell
    Complete GO annotation...

    Keywords - Cellular componenti

    Cytoplasm, Membrane, Mitochondrion, Mitochondrion inner membrane, Nucleus

    Pathology & Biotechi

    Involvement in diseasei

    Combined oxidative phosphorylation deficiency 6 (COXPD6)2 Publications

    The disease is caused by mutations affecting the gene represented in this entry.

    Disease descriptionA mitochondrial disease resulting in a neurodegenerative disorder characterized by psychomotor delay, hypotonia, areflexia, muscle weakness and wasting. Some patients manifest prenatal ventriculomegaly and severe postnatal encephalomyopathy.

    See also OMIM:300816
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti201 – 2011Missing in COXPD6; higher DNA binding affinity, partially impaired flavin binding and association with increased parthanatos-linked cell death. 1 Publication
    VAR_063827
    Natural varianti308 – 3081G → E in COXPD6; with prenatal ventriculomegaly and severe postnatal encephalomyopathy. 1 Publication
    VAR_067334
    Cowchock syndrome (COWCK)1 Publication

    The disease is caused by mutations affecting the gene represented in this entry.

    Disease descriptionAn X-linked recessive neuromuscular disorder characterized by early childhood onset of a slowly progressive axonal sensorimotor neuropathy associated in some patients with sensorineural deafness and cognitive impairment.

    See also OMIM:310490
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti493 – 4931E → V in COWCK; increases affinity for NADH and electron transfer activity. Increases affinity for DNA, resulting in increased apoptosis. 1 Publication
    VAR_069468

    Keywords - Diseasei

    Charcot-Marie-Tooth disease, Deafness, Disease mutation, Mental retardation, Neurodegeneration, Neuropathy

    Organism-specific databases

    MIMi300816. phenotype.
    310490. phenotype.
    Orphaneti238329. Severe X-linked mitochondrial encephalomyopathy.
    101078. X-linked Charcot-Marie-Tooth disease type 4.
    PharmGKBiPA162376129.

    Chemistry

    DrugBankiDB03147. Flavin adenine dinucleotide.

    Polymorphism and mutation databases

    BioMutaiAIFM1.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transit peptidei1 – 5454Mitochondrion2 PublicationsAdd
    BLAST
    Propeptidei55 – 10147Removed in mature form1 PublicationPRO_0000401935Add
    BLAST
    Chaini102 – 613512Apoptosis-inducing factor 1, mitochondrialPRO_0000022030Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei105 – 1051Phosphothreonine1 Publication
    Modified residuei109 – 1091N6-succinyllysineBy similarity
    Modified residuei116 – 1161Phosphoserine1 Publication
    Modified residuei118 – 1181Phosphoserine1 Publication
    Cross-linki255 – 255Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication
    Modified residuei268 – 2681Phosphoserine2 Publications
    Modified residuei371 – 3711Phosphoserine1 Publication
    Modified residuei388 – 3881N6-acetyllysineBy similarity
    Modified residuei521 – 5211Phosphothreonine1 Publication
    Modified residuei524 – 5241Phosphoserine1 Publication
    Modified residuei530 – 5301Phosphoserine1 Publication
    Modified residuei593 – 5931N6-acetyllysineBy similarity

    Post-translational modificationi

    Under normal conditions, a 54-residue N-terminal segment is first proteolytically removed during or just after translocation into the mitochondrial intermembrane space (IMS) by the mitochondrial processing peptidase (MPP) to form the inner-membrane-anchored mature form (AIFmit). During apoptosis, it is further proteolytically processed at amino-acid position 101 leading to the generation of the mature form, which is confined to the mitochondrial IMS in a soluble form (AIFsol). AIFsol is released to the cytoplasm in response to specific death signals, and translocated to the nucleus, where it induces nuclear apoptosis in a caspase-independent manner.1 Publication
    Ubiquitination by XIAP/BIRC4 does not lead to proteasomal degradation. Ubiquitination at Lys-255 by XIAP/BIRC4 blocks its ability to bind DNA and induce chromatin degradation, thereby inhibiting its ability to induce cell death.2 Publications

    Keywords - PTMi

    Acetylation, Isopeptide bond, Phosphoprotein, Ubl conjugation

    Proteomic databases

    MaxQBiO95831.
    PaxDbiO95831.
    PRIDEiO95831.

    2D gel databases

    REPRODUCTION-2DPAGEIPI00157908.
    UCD-2DPAGEO95831.

    PTM databases

    PhosphoSiteiO95831.

    Expressioni

    Tissue specificityi

    Detected in muscle and skin fibroblasts (at protein level). Isoform 5 is frequently down-regulated in human cancers.2 Publications

    Gene expression databases

    BgeeiO95831.
    CleanExiHS_AIFM1.
    ExpressionAtlasiO95831. baseline and differential.
    GenevestigatoriO95831.

    Organism-specific databases

    HPAiCAB003764.
    HPA030611.

    Interactioni

    Subunit structurei

    Monomer (oxidized form). Homodimer (reduced form). Also dimerizes with isoform 3 preventing its release from mitochondria. Interacts with XIAP/BIRC4. Interacts (via N-terminus) with EIF3G (via C-terminus). Interacts with PRELID1.6 Publications

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    EIF3GO758219EBI-356440,EBI-366632
    KANK2Q63ZY32EBI-356440,EBI-2556193
    KANK2Q63ZY3-24EBI-356440,EBI-6244894
    TSC22D4Q9Y3Q82EBI-356440,EBI-739485

    Protein-protein interaction databases

    BioGridi114579. 61 interactions.
    119252. 13 interactions.
    IntActiO95831. 31 interactions.
    MINTiMINT-209209.
    STRINGi9606.ENSP00000287295.

    Structurei

    Secondary structure

    1
    613
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Beta strandi130 – 1389Combined sources
    Helixi141 – 15313Combined sources
    Beta strandi158 – 16710Combined sources
    Helixi173 – 1764Combined sources
    Helixi178 – 1803Combined sources
    Helixi187 – 1904Combined sources
    Beta strandi192 – 1943Combined sources
    Beta strandi200 – 2067Combined sources
    Helixi208 – 2103Combined sources
    Turni214 – 2196Combined sources
    Beta strandi224 – 2296Combined sources
    Beta strandi233 – 2375Combined sources
    Turni238 – 2414Combined sources
    Beta strandi242 – 2454Combined sources
    Beta strandi250 – 2589Combined sources
    Beta strandi262 – 2643Combined sources
    Helixi268 – 2714Combined sources
    Helixi275 – 2795Combined sources
    Beta strandi281 – 2833Combined sources
    Helixi287 – 29913Combined sources
    Beta strandi301 – 3066Combined sources
    Helixi310 – 32617Combined sources
    Beta strandi329 – 3335Combined sources
    Beta strandi335 – 3384Combined sources
    Turni339 – 3435Combined sources
    Helixi346 – 35712Combined sources
    Turni358 – 3603Combined sources
    Beta strandi362 – 3643Combined sources
    Beta strandi369 – 3757Combined sources
    Beta strandi378 – 3836Combined sources
    Beta strandi388 – 3969Combined sources
    Beta strandi400 – 4023Combined sources
    Helixi407 – 4104Combined sources
    Turni416 – 4183Combined sources
    Beta strandi420 – 4223Combined sources
    Beta strandi428 – 4303Combined sources
    Beta strandi433 – 4353Combined sources
    Helixi437 – 4393Combined sources
    Beta strandi440 – 4445Combined sources
    Turni445 – 4473Combined sources
    Beta strandi448 – 4503Combined sources
    Helixi455 – 46915Combined sources
    Beta strandi481 – 4877Combined sources
    Beta strandi491 – 4966Combined sources
    Beta strandi504 – 5096Combined sources
    Beta strandi513 – 5153Combined sources
    Helixi517 – 5248Combined sources
    Helixi529 – 5324Combined sources
    Beta strandi562 – 5698Combined sources
    Beta strandi572 – 5809Combined sources
    Helixi585 – 59410Combined sources
    Helixi604 – 6074Combined sources

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    1M6IX-ray1.80A121-613[»]
    4BURX-ray2.88A/B/C/D103-613[»]
    4BV6X-ray1.80A121-613[»]
    4FDCX-ray2.40B103-613[»]
    4LIIX-ray1.88A100-611[»]
    ProteinModelPortaliO95831.
    SMRiO95831. Positions 127-610.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiO95831.

    Family & Domainsi

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni134 – 483350FAD-dependent oxidoreductaseBy similarityAdd
    BLAST

    Motif

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Motifi446 – 4516Nuclear localization signalSequence Analysis

    Sequence similaritiesi

    Keywords - Domaini

    Transit peptide

    Phylogenomic databases

    eggNOGiCOG0446.
    GeneTreeiENSGT00530000063416.
    HOGENOMiHOG000124580.
    HOVERGENiHBG053538.
    InParanoidiO95831.
    KOiK04727.
    OMAiEGVNVMP.
    OrthoDBiEOG7C2R0V.
    PhylomeDBiO95831.
    TreeFamiTF314028.

    Family and domain databases

    Gene3Di3.30.390.30. 1 hit.
    InterProiIPR029324. AIF_C.
    IPR016156. FAD/NAD-linked_Rdtase_dimer.
    IPR004099. Pyr_nucl-diS_OxRdtase_dimer.
    IPR023753. Pyr_nucl-diS_OxRdtase_FAD/NAD.
    IPR001327. Pyr_OxRdtase_NAD-bd_dom.
    [Graphical view]
    PfamiPF14721. AIF_C. 1 hit.
    PF00070. Pyr_redox. 1 hit.
    PF07992. Pyr_redox_2. 1 hit.
    [Graphical view]
    SUPFAMiSSF55424. SSF55424. 1 hit.

    Sequences (6)i

    Sequence statusi: Complete.

    Sequence processingi: The displayed sequence is further processed into a mature form.

    This entry describes 6 isoformsi produced by alternative splicing. AlignAdd to basket

    Isoform 1 (identifier: O95831-1) [UniParc]FASTAAdd to basket

    Also known as: AIF

    This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

    « Hide

            10         20         30         40         50
    MFRCGGLAAG ALKQKLVPLV RTVCVRSPRQ RNRLPGNLFQ RWHVPLELQM
    60 70 80 90 100
    TRQMASSGAS GGKIDNSVLV LIVGLSTVGA GAYAYKTMKE DEKRYNERIS
    110 120 130 140 150
    GLGLTPEQKQ KKAALSASEG EEVPQDKAPS HVPFLLIGGG TAAFAAARSI
    160 170 180 190 200
    RARDPGARVL IVSEDPELPY MRPPLSKELW FSDDPNVTKT LRFKQWNGKE
    210 220 230 240 250
    RSIYFQPPSF YVSAQDLPHI ENGGVAVLTG KKVVQLDVRD NMVKLNDGSQ
    260 270 280 290 300
    ITYEKCLIAT GGTPRSLSAI DRAGAEVKSR TTLFRKIGDF RSLEKISREV
    310 320 330 340 350
    KSITIIGGGF LGSELACALG RKARALGTEV IQLFPEKGNM GKILPEYLSN
    360 370 380 390 400
    WTMEKVRREG VKVMPNAIVQ SVGVSSGKLL IKLKDGRKVE TDHIVAAVGL
    410 420 430 440 450
    EPNVELAKTG GLEIDSDFGG FRVNAELQAR SNIWVAGDAA CFYDIKLGRR
    460 470 480 490 500
    RVEHHDHAVV SGRLAGENMT GAAKPYWHQS MFWSDLGPDV GYEAIGLVDS
    510 520 530 540 550
    SLPTVGVFAK ATAQDNPKSA TEQSGTGIRS ESETESEASE ITIPPSTPAV
    560 570 580 590 600
    PQAPVQGEDY GKGVIFYLRD KVVVGIVLWN IFNRMPIARK IIKDGEQHED
    610
    LNEVAKLFNI HED
    Length:613
    Mass (Da):66,901
    Last modified:May 1, 1999 - v1
    Checksum:iA156762BC64E6340
    GO
    Isoform 2 (identifier: O95831-2) [UniParc]FASTAAdd to basket

    The sequence of this isoform differs from the canonical sequence as follows:
         36-322: Missing.

    Show »
    Length:326
    Mass (Da):35,638
    Checksum:iA87ACDC0A0556040
    GO
    Isoform 3 (identifier: O95831-3) [UniParc]FASTAAdd to basket

    Also known as: AIF-exB, AIF2

    The sequence of this isoform differs from the canonical sequence as follows:
         36-82: GNLFQRWHVP...VGLSTVGAGA → VVQSHHLGSP...GATVTGAGVY

    Note: Brain-specific.

    Show »
    Length:609
    Mass (Da):66,295
    Checksum:i313ADD6FA4E5D61A
    GO
    Isoform 4 (identifier: O95831-4) [UniParc]FASTAAdd to basket

    Also known as: AIFsh2

    The sequence of this isoform differs from the canonical sequence as follows:
         323-324: AR → DI
         325-613: Missing.

    Note: Does not induce nuclear apoptosis.

    Show »
    Length:324
    Mass (Da):35,384
    Checksum:i259AA55812C2F07E
    GO
    Isoform 5 (identifier: O95831-5) [UniParc]FASTAAdd to basket

    Also known as: AIFsh

    The sequence of this isoform differs from the canonical sequence as follows:
         1-352: Missing.

    Note: Pro-apoptotic isoform, strongly down-regulated in many tumor cells, up-regulated by gamma-irradiation.

    Show »
    Length:261
    Mass (Da):28,404
    Checksum:iB05C9E9F3AA3F2E3
    GO
    Isoform 6 (identifier: O95831-6) [UniParc]FASTAAdd to basket

    The sequence of this isoform differs from the canonical sequence as follows:
         1-87: Missing.
         323-324: AR → DI
         325-613: Missing.

    Show »
    Length:237
    Mass (Da):26,033
    Checksum:iC1DDF16F42339374
    GO

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti201 – 2011Missing in COXPD6; higher DNA binding affinity, partially impaired flavin binding and association with increased parthanatos-linked cell death. 1 Publication
    VAR_063827
    Natural varianti243 – 2431V → L Probable disease-associated mutation found in patient with severe myopathy; myopathic changes with partial type II fiber hypotrophy; reduced protein amount in muscle compared to controls. 1 Publication
    VAR_072791
    Natural varianti308 – 3081G → E in COXPD6; with prenatal ventriculomegaly and severe postnatal encephalomyopathy. 1 Publication
    VAR_067334
    Natural varianti493 – 4931E → V in COWCK; increases affinity for NADH and electron transfer activity. Increases affinity for DNA, resulting in increased apoptosis. 1 Publication
    VAR_069468

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei1 – 352352Missing in isoform 5. 1 PublicationVSP_046248Add
    BLAST
    Alternative sequencei1 – 8787Missing in isoform 6. 1 PublicationVSP_047646Add
    BLAST
    Alternative sequencei36 – 322287Missing in isoform 2. 1 PublicationVSP_004357Add
    BLAST
    Alternative sequencei36 – 8247GNLFQ…VGAGA → VVQSHHLGSPSRSLASTGAS GKDGSNLVYFLIVGATVTGA GVY in isoform 3. 3 PublicationsVSP_022953Add
    BLAST
    Alternative sequencei323 – 3242AR → DI in isoform 4 and isoform 6. 1 PublicationVSP_043637
    Alternative sequencei325 – 613289Missing in isoform 4 and isoform 6. 1 PublicationVSP_043638Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    AF100928 mRNA. Translation: AAD16436.1.
    DQ016496 mRNA. Translation: AAY84737.1.
    DQ016498 mRNA. Translation: AAY84739.1.
    DQ016500 mRNA. Translation: AAY84741.1.
    AL049703 mRNA. Translation: CAB41267.1.
    AL049704 mRNA. Translation: CAB41268.1.
    AK314446 mRNA. Translation: BAG37055.1.
    CR457379 mRNA. Translation: CAG33660.1.
    AL139234 Genomic DNA. Translation: CAI42778.1.
    AL139234 Genomic DNA. Translation: CAI42779.1.
    AL139234 Genomic DNA. Translation: CAI42780.1.
    CH471107 Genomic DNA. Translation: EAX11811.1.
    CH471107 Genomic DNA. Translation: EAX11812.1.
    CH471107 Genomic DNA. Translation: EAX11810.1.
    BC111065 mRNA. Translation: AAI11066.1.
    BC139738 mRNA. Translation: AAI39739.1.
    AF131759 mRNA. Translation: AAD20036.1.
    CCDSiCCDS14618.1. [O95831-1]
    CCDS14619.1. [O95831-3]
    CCDS48167.1. [O95831-4]
    RefSeqiNP_001124318.1. NM_001130846.2. [O95831-5]
    NP_001124319.1. NM_001130847.3. [O95831-4]
    NP_004199.1. NM_004208.3. [O95831-1]
    NP_665811.1. NM_145812.2. [O95831-3]
    NP_665812.1. NM_145813.2. [O95831-2]
    UniGeneiHs.424932.

    Genome annotation databases

    EnsembliENST00000287295; ENSP00000287295; ENSG00000156709. [O95831-1]
    ENST00000319908; ENSP00000315122; ENSG00000156709. [O95831-3]
    ENST00000346424; ENSP00000316320; ENSG00000156709. [O95831-2]
    ENST00000416073; ENSP00000402535; ENSG00000156709. [O95831-4]
    ENST00000535724; ENSP00000446113; ENSG00000156709. [O95831-4]
    GeneIDi9131.
    KEGGihsa:9131.
    UCSCiuc004evg.3. human. [O95831-1]
    uc004evh.3. human. [O95831-3]
    uc004evi.3. human. [O95831-2]
    uc004evk.3. human.
    uc011mus.2. human. [O95831-4]

    Keywords - Coding sequence diversityi

    Alternative splicing

    Cross-referencesi

    Web resourcesi

    Atlas of Genetics and Cytogenetics in Oncology and Haematology

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    AF100928 mRNA. Translation: AAD16436.1.
    DQ016496 mRNA. Translation: AAY84737.1.
    DQ016498 mRNA. Translation: AAY84739.1.
    DQ016500 mRNA. Translation: AAY84741.1.
    AL049703 mRNA. Translation: CAB41267.1.
    AL049704 mRNA. Translation: CAB41268.1.
    AK314446 mRNA. Translation: BAG37055.1.
    CR457379 mRNA. Translation: CAG33660.1.
    AL139234 Genomic DNA. Translation: CAI42778.1.
    AL139234 Genomic DNA. Translation: CAI42779.1.
    AL139234 Genomic DNA. Translation: CAI42780.1.
    CH471107 Genomic DNA. Translation: EAX11811.1.
    CH471107 Genomic DNA. Translation: EAX11812.1.
    CH471107 Genomic DNA. Translation: EAX11810.1.
    BC111065 mRNA. Translation: AAI11066.1.
    BC139738 mRNA. Translation: AAI39739.1.
    AF131759 mRNA. Translation: AAD20036.1.
    CCDSiCCDS14618.1. [O95831-1]
    CCDS14619.1. [O95831-3]
    CCDS48167.1. [O95831-4]
    RefSeqiNP_001124318.1. NM_001130846.2. [O95831-5]
    NP_001124319.1. NM_001130847.3. [O95831-4]
    NP_004199.1. NM_004208.3. [O95831-1]
    NP_665811.1. NM_145812.2. [O95831-3]
    NP_665812.1. NM_145813.2. [O95831-2]
    UniGeneiHs.424932.

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    1M6IX-ray1.80A121-613[»]
    4BURX-ray2.88A/B/C/D103-613[»]
    4BV6X-ray1.80A121-613[»]
    4FDCX-ray2.40B103-613[»]
    4LIIX-ray1.88A100-611[»]
    ProteinModelPortaliO95831.
    SMRiO95831. Positions 127-610.
    ModBaseiSearch...
    MobiDBiSearch...

    Protein-protein interaction databases

    BioGridi114579. 61 interactions.
    119252. 13 interactions.
    IntActiO95831. 31 interactions.
    MINTiMINT-209209.
    STRINGi9606.ENSP00000287295.

    Chemistry

    DrugBankiDB03147. Flavin adenine dinucleotide.

    PTM databases

    PhosphoSiteiO95831.

    Polymorphism and mutation databases

    BioMutaiAIFM1.

    2D gel databases

    REPRODUCTION-2DPAGEIPI00157908.
    UCD-2DPAGEO95831.

    Proteomic databases

    MaxQBiO95831.
    PaxDbiO95831.
    PRIDEiO95831.

    Protocols and materials databases

    DNASUi51060.
    Structural Biology KnowledgebaseSearch...

    Genome annotation databases

    EnsembliENST00000287295; ENSP00000287295; ENSG00000156709. [O95831-1]
    ENST00000319908; ENSP00000315122; ENSG00000156709. [O95831-3]
    ENST00000346424; ENSP00000316320; ENSG00000156709. [O95831-2]
    ENST00000416073; ENSP00000402535; ENSG00000156709. [O95831-4]
    ENST00000535724; ENSP00000446113; ENSG00000156709. [O95831-4]
    GeneIDi9131.
    KEGGihsa:9131.
    UCSCiuc004evg.3. human. [O95831-1]
    uc004evh.3. human. [O95831-3]
    uc004evi.3. human. [O95831-2]
    uc004evk.3. human.
    uc011mus.2. human. [O95831-4]

    Organism-specific databases

    CTDi9131.
    GeneCardsiGC0XM129263.
    HGNCiHGNC:8768. AIFM1.
    HPAiCAB003764.
    HPA030611.
    MIMi300169. gene.
    300816. phenotype.
    310490. phenotype.
    neXtProtiNX_O95831.
    Orphaneti238329. Severe X-linked mitochondrial encephalomyopathy.
    101078. X-linked Charcot-Marie-Tooth disease type 4.
    PharmGKBiPA162376129.
    GenAtlasiSearch...

    Phylogenomic databases

    eggNOGiCOG0446.
    GeneTreeiENSGT00530000063416.
    HOGENOMiHOG000124580.
    HOVERGENiHBG053538.
    InParanoidiO95831.
    KOiK04727.
    OMAiEGVNVMP.
    OrthoDBiEOG7C2R0V.
    PhylomeDBiO95831.
    TreeFamiTF314028.

    Enzyme and pathway databases

    SABIO-RKO95831.
    SignaLinkiO95831.

    Miscellaneous databases

    ChiTaRSiAIFM1. human.
    EvolutionaryTraceiO95831.
    GeneWikiiAIFM1.
    GenomeRNAii9131.
    NextBioi34229.
    PROiO95831.
    SOURCEiSearch...

    Gene expression databases

    BgeeiO95831.
    CleanExiHS_AIFM1.
    ExpressionAtlasiO95831. baseline and differential.
    GenevestigatoriO95831.

    Family and domain databases

    Gene3Di3.30.390.30. 1 hit.
    InterProiIPR029324. AIF_C.
    IPR016156. FAD/NAD-linked_Rdtase_dimer.
    IPR004099. Pyr_nucl-diS_OxRdtase_dimer.
    IPR023753. Pyr_nucl-diS_OxRdtase_FAD/NAD.
    IPR001327. Pyr_OxRdtase_NAD-bd_dom.
    [Graphical view]
    PfamiPF14721. AIF_C. 1 hit.
    PF00070. Pyr_redox. 1 hit.
    PF07992. Pyr_redox_2. 1 hit.
    [Graphical view]
    SUPFAMiSSF55424. SSF55424. 1 hit.
    ProtoNetiSearch...

    Publicationsi

    « Hide 'large scale' publications
    1. Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
    2. "AIFsh, a novel apoptosis-inducing factor (AIF) pro-apoptotic isoform with potential pathological relevance in human cancer."
      Delettre C., Yuste V.J., Moubarak R.S., Bras M., Lesbordes-Brion J.-C., Petres S., Bellalou J., Susin S.A.
      J. Biol. Chem. 281:6413-6427(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 5), PROTEIN SEQUENCE OF N-TERMINUS, SUBCELLULAR LOCATION (ISOFORM 5), TISSUE SPECIFICITY.
    3. "Identification and characterization of AIFsh2, a mitochondrial apoptosis-inducing factor (AIF) isoform with NADH oxidase activity."
      Delettre C., Yuste V.J., Moubarak R.S., Bras M., Robert N., Susin S.A.
      J. Biol. Chem. 281:18507-18518(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 4 AND 6), ALTERNATIVE SPLICING.
    4. Rhodes S.
      Submitted (APR-1999) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 2 AND 3).
    5. "Complete sequencing and characterization of 21,243 full-length human cDNAs."
      Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.
      , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
      Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
      Tissue: Kidney.
    6. "Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)."
      Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.
      Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
    7. "The DNA sequence of the human X chromosome."
      Ross M.T., Grafham D.V., Coffey A.J., Scherer S., McLay K., Muzny D., Platzer M., Howell G.R., Burrows C., Bird C.P., Frankish A., Lovell F.L., Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G., Jones M.C.
      , Hurles M.E., Andrews T.D., Scott C.E., Searle S., Ramser J., Whittaker A., Deadman R., Carter N.P., Hunt S.E., Chen R., Cree A., Gunaratne P., Havlak P., Hodgson A., Metzker M.L., Richards S., Scott G., Steffen D., Sodergren E., Wheeler D.A., Worley K.C., Ainscough R., Ambrose K.D., Ansari-Lari M.A., Aradhya S., Ashwell R.I., Babbage A.K., Bagguley C.L., Ballabio A., Banerjee R., Barker G.E., Barlow K.F., Barrett I.P., Bates K.N., Beare D.M., Beasley H., Beasley O., Beck A., Bethel G., Blechschmidt K., Brady N., Bray-Allen S., Bridgeman A.M., Brown A.J., Brown M.J., Bonnin D., Bruford E.A., Buhay C., Burch P., Burford D., Burgess J., Burrill W., Burton J., Bye J.M., Carder C., Carrel L., Chako J., Chapman J.C., Chavez D., Chen E., Chen G., Chen Y., Chen Z., Chinault C., Ciccodicola A., Clark S.Y., Clarke G., Clee C.M., Clegg S., Clerc-Blankenburg K., Clifford K., Cobley V., Cole C.G., Conquer J.S., Corby N., Connor R.E., David R., Davies J., Davis C., Davis J., Delgado O., Deshazo D., Dhami P., Ding Y., Dinh H., Dodsworth S., Draper H., Dugan-Rocha S., Dunham A., Dunn M., Durbin K.J., Dutta I., Eades T., Ellwood M., Emery-Cohen A., Errington H., Evans K.L., Faulkner L., Francis F., Frankland J., Fraser A.E., Galgoczy P., Gilbert J., Gill R., Gloeckner G., Gregory S.G., Gribble S., Griffiths C., Grocock R., Gu Y., Gwilliam R., Hamilton C., Hart E.A., Hawes A., Heath P.D., Heitmann K., Hennig S., Hernandez J., Hinzmann B., Ho S., Hoffs M., Howden P.J., Huckle E.J., Hume J., Hunt P.J., Hunt A.R., Isherwood J., Jacob L., Johnson D., Jones S., de Jong P.J., Joseph S.S., Keenan S., Kelly S., Kershaw J.K., Khan Z., Kioschis P., Klages S., Knights A.J., Kosiura A., Kovar-Smith C., Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L., Liu W., Lloyd C., Lloyd D.M., Loulseged H., Loveland J.E., Lovell J.D., Lozado R., Lu J., Lyne R., Ma J., Maheshwari M., Matthews L.H., McDowall J., McLaren S., McMurray A., Meidl P., Meitinger T., Milne S., Miner G., Mistry S.L., Morgan M., Morris S., Mueller I., Mullikin J.C., Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N., Okwuonu G., Palmer S., Pandian R., Parker D., Parrish J., Pasternak S., Patel D., Pearce A.V., Pearson D.M., Pelan S.E., Perez L., Porter K.M., Ramsey Y., Reichwald K., Rhodes S., Ridler K.A., Schlessinger D., Schueler M.G., Sehra H.K., Shaw-Smith C., Shen H., Sheridan E.M., Shownkeen R., Skuce C.D., Smith M.L., Sotheran E.C., Steingruber H.E., Steward C.A., Storey R., Swann R.M., Swarbreck D., Tabor P.E., Taudien S., Taylor T., Teague B., Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S., Tromans A.C., d'Urso M., Verduzco D., Villasana D., Waldron L., Wall M., Wang Q., Warren J., Warry G.L., Wei X., West A., Whitehead S.L., Whiteley M.N., Wilkinson J.E., Willey D.L., Williams G., Williams L., Williamson A., Williamson H., Wilming L., Woodmansey R.L., Wray P.W., Yen J., Zhang J., Zhou J., Zoghbi H., Zorilla S., Buck D., Reinhardt R., Poustka A., Rosenthal A., Lehrach H., Meindl A., Minx P.J., Hillier L.W., Willard H.F., Wilson R.K., Waterston R.H., Rice C.M., Vaudin M., Coulson A., Nelson D.L., Weinstock G., Sulston J.E., Durbin R.M., Hubbard T., Gibbs R.A., Beck S., Rogers J., Bentley D.R.
      Nature 434:325-337(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    8. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    9. "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] (ISOFORMS 1 AND 3).
      Tissue: Brain.
    10. "Export of mitochondrial AIF in response to proapoptotic stimuli depends on processing at the intermembrane space."
      Otera H., Ohsakaya S., Nagaura Z., Ishihara N., Mihara K.
      EMBO J. 24:1375-1386(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: PROTEIN SEQUENCE OF 55-59, SUBCELLULAR LOCATION, PROTEOLYTIC CLEAVAGE.
    11. Mei G., Yu W., Gibbs R.A.
      Submitted (FEB-1999) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 171-613.
      Tissue: Brain.
    12. "Apoptosis-inducing factor (AIF): a ubiquitous mitochondrial oxidoreductase involved in apoptosis."
      Daugas E., Nochy D., Ravagnan L., Loeffler M., Susin S.A., Zamzami N., Kroemer G.
      FEBS Lett. 476:118-123(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: REVIEW.
    13. "Apoptosis-inducing factor (AIF) inhibits protein synthesis by interacting with the eukaryotic translation initiation factor 3 subunit p44 (eIF3g)."
      Kim J.T., Kim K.D., Song E.Y., Lee H.G., Kim J.W., Kim J.W., Chae S.K., Kim E., Lee M.S., Yang Y., Lim J.S.
      FEBS Lett. 580:6375-6383(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH EIF3G.
    14. "Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle."
      Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., Greff Z., Keri G., Stemmann O., Mann M.
      Mol. Cell 31:438-448(2008) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-105, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
      Tissue: Cervix carcinoma.
    15. "Apoptosis-inducing factor is a target for ubiquitination through interaction with XIAP."
      Wilkinson J.C., Wilkinson A.S., Galban S., Csomos R.A., Duckett C.S.
      Mol. Cell. Biol. 28:237-247(2008) [PubMed] [Europe PMC] [Abstract]
      Cited for: UBIQUITINATION BY XIAP/BIRC4, INTERACTION WITH XIAP/BIRC4.
    16. Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-268, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
      Tissue: Cervix carcinoma.
    17. "Apoptosis-inducing factor plays a critical role in caspase-independent, pyknotic cell death in hydrogen peroxide-exposed cells."
      Son Y.O., Jang Y.S., Heo J.S., Chung W.T., Choi K.C., Lee J.C.
      Apoptosis 14:796-808(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.
    18. Cited for: ALTERNATIVE SPLICING (ISOFORM 3), SUBCELLULAR LOCATION (ISOFORM 3), SUBUNIT.
    19. Cited for: INTERACTION WITH PRELID1.
    20. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    21. "Nondegradative ubiquitination of apoptosis inducing factor (AIF) by X-linked inhibitor of apoptosis at a residue critical for AIF-mediated chromatin degradation."
      Lewis E.M., Wilkinson A.S., Davis N.Y., Horita D.A., Wilkinson J.C.
      Biochemistry 50:11084-11096(2011) [PubMed] [Europe PMC] [Abstract]
      Cited for: UBIQUITINATION AT LYS-255 BY XIAP/BIRC4.
    22. "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome."
      Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., Ye M., Zou H.
      J. Proteomics 96:253-262(2014) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-116; SER-118; SER-268; SER-371; THR-521; SER-524 AND SER-530, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
      Tissue: Liver.
    23. "DNA binding is required for the apoptogenic action of apoptosis inducing factor."
      Ye H., Cande C., Stephanou N.C., Jiang S., Gurbuxani S., Larochette N., Daugas E., Garrido C., Kroemer G., Wu H.
      Nat. Struct. Biol. 9:680-684(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 121-613 IN COMPLEX WITH FAD, SUBCELLULAR LOCATION, DNA-BINDING.
    24. Cited for: X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 103-613 IN COMPLEX WITH FAD, FUNCTION, COFACTOR, BIOPHYSICOCHEMICAL PROPERTIES, DNA-BINDING, SUBUNIT, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, VARIANT COWCK VAL-493, CHARACTERIZATION OF VARIANT COWCK VAL-493.
    25. "Severe X-linked mitochondrial encephalomyopathy associated with a mutation in apoptosis-inducing factor."
      Ghezzi D., Sevrioukova I., Invernizzi F., Lamperti C., Mora M., D'Adamo P., Novara F., Zuffardi O., Uziel G., Zeviani M.
      Am. J. Hum. Genet. 86:639-649(2010) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANT COXPD6 ARG-201 DEL, CHARACTERIZATION OF VARIANT COXPD6 ARG-201 DEL, FUNCTION.
    26. "Early prenatal ventriculomegaly due to an AIFM1 mutation identified by linkage analysis and whole exome sequencing."
      Berger I., Ben-Neriah Z., Dor-Wolman T., Shaag A., Saada A., Zenvirt S., Raas-Rothschild A., Nadjari M., Kaestner K.H., Elpeleg O.
      Mol. Genet. Metab. 104:517-520(2011) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANT COXPD6 GLU-308.
    27. "From ventriculomegaly to severe muscular atrophy: Expansion of the clinical spectrum related to mutations in AIFM1."
      Kettwig M., Schubach M., Zimmermann F.A., Klinge L., Mayr J.A., Biskup S., Sperl W., Gaertner J., Huppke P.
      Mitochondrion 21C:12-18(2015) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANT LEU-243, CHARACTERIZATION OF VARIANT LEU-243.

    Entry informationi

    Entry nameiAIFM1_HUMAN
    AccessioniPrimary (citable) accession number: O95831
    Secondary accession number(s): A4QPB4
    , B1ALN1, B2RB08, D3DTE9, Q1L6K4, Q1L6K6, Q2QKE4, Q5JUZ7, Q6I9X6, Q9Y3I3, Q9Y3I4
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: April 27, 2001
    Last sequence update: May 1, 1999
    Last modified: May 27, 2015
    This is version 158 of the entry and version 1 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, Direct protein sequencing, Reference proteome

    Documents

    1. Human chromosome X
      Human chromosome X: 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. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3

    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 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.