dbPTM

AIFM1_HUMAN - PTM Information in dbPTM

Basic Information of Protein

Overview of Protein Modification Sites with Functional and Structural Information
UniProt ID	AIFM1_HUMAN
UniProt AC	O95831
Protein Name	Apoptosis-inducing factor 1, mitochondrial
Gene Name	AIFM1
Organism	Homo sapiens (Human).
Sequence Length	613
Subcellular Localization	Mitochondrion intermembrane space. Mitochondrion inner membrane. Cytoplasm. Nucleus. Cytoplasm, perinuclear region. Proteolytic cleavage during or just after translocation into the mitochondrial intermembrane space (IMS) results in the formation of a
Protein Description	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..
Protein Sequence	MFRCGGLAAGALKQKLVPLVRTVCVRSPRQRNRLPGNLFQRWHVPLELQMTRQMASSGASGGKIDNSVLVLIVGLSTVGAGAYAYKTMKEDEKRYNERISGLGLTPEQKQKKAALSASEGEEVPQDKAPSHVPFLLIGGGTAAFAAARSIRARDPGARVLIVSEDPELPYMRPPLSKELWFSDDPNVTKTLRFKQWNGKERSIYFQPPSFYVSAQDLPHIENGGVAVLTGKKVVQLDVRDNMVKLNDGSQITYEKCLIATGGTPRSLSAIDRAGAEVKSRTTLFRKIGDFRSLEKISREVKSITIIGGGFLGSELACALGRKARALGTEVIQLFPEKGNMGKILPEYLSNWTMEKVRREGVKVMPNAIVQSVGVSSGKLLIKLKDGRKVETDHIVAAVGLEPNVELAKTGGLEIDSDFGGFRVNAELQARSNIWVAGDAACFYDIKLGRRRVEHHDHAVVSGRLAGENMTGAAKPYWHQSMFWSDLGPDVGYEAIGLVDSSLPTVGVFAKATAQDNPKSATEQSGTGIRSESETESEASEITIPPSTPAVPQAPVQGEDYGKGVIFYLRDKVVVGIVLWNIFNRMPIARKIIKDGEQHEDLNEVAKLFNIHED

Experimental Post-Translational Modification Sites

* ASA = Accessible Surface Area

Locations	Modification	Substrate Peptides & Secondary Structure	ASA (%)	Reference
41 (in isoform 2)	Phosphorylation	-	20.38	20068231
56	Phosphorylation	QMTRQMASSGASGGK HHHHHHHHCCCCCCC	24.78	-
57	Phosphorylation	MTRQMASSGASGGKI HHHHHHHCCCCCCCC	28.92	-
60	Phosphorylation	QMASSGASGGKIDNS HHHHCCCCCCCCCCC	52.16	-
60	O-linked_Glycosylation	QMASSGASGGKIDNS HHHHCCCCCCCCCCC	52.16	29351928
75 (in isoform 2)	Ubiquitination	-	2.41	-
87	Phosphorylation	AGAYAYKTMKEDEKR HHHHHHHHCHHHHHH	22.31	24719451
95	Phosphorylation	MKEDEKRYNERISGL CHHHHHHHHHHCCCC	32.23	24719451
100	Phosphorylation	KRYNERISGLGLTPE HHHHHHCCCCCCCHH	33.90	28857561
101 (in isoform 3)	Phosphorylation	-	22.76	-
105	Phosphorylation	RISGLGLTPEQKQKK HCCCCCCCHHHHHHH	23.99	25159151
105 (in isoform 2)	Ubiquitination	-	23.99	20972266
105 (in isoform 3)	Ubiquitination	-	23.99	21890473
109	Ubiquitination	LGLTPEQKQKKAALS CCCCHHHHHHHHHHH	63.52	21890473
109	Succinylation	LGLTPEQKQKKAALS CCCCHHHHHHHHHHH	63.52	-
109	Malonylation	LGLTPEQKQKKAALS CCCCHHHHHHHHHHH	63.52	26320211
109	Succinylation	LGLTPEQKQKKAALS CCCCHHHHHHHHHHH	63.52	-
109	Ubiquitination	LGLTPEQKQKKAALS CCCCHHHHHHHHHHH	63.52	21890473
109 (in isoform 1)	Ubiquitination	-	63.52	21890473
109	Ubiquitination	LGLTPEQKQKKAALS CCCCHHHHHHHHHHH	63.52	21890473
111	Ubiquitination	LTPEQKQKKAALSAS CCHHHHHHHHHHHHC	51.95	-
112	Malonylation	TPEQKQKKAALSASE CHHHHHHHHHHHHCC	36.08	32601280
116	Phosphorylation	KQKKAALSASEGEEV HHHHHHHHHCCCCCC	25.64	29255136
118	Phosphorylation	KKAALSASEGEEVPQ HHHHHHHCCCCCCCC	42.64	29255136
176	Phosphorylation	PYMRPPLSKELWFSD CCCCCCCCCCCCCCC	29.83	27251275
182	Phosphorylation	LSKELWFSDDPNVTK CCCCCCCCCCCCCCE	29.53	23312004
185 (in isoform 3)	Ubiquitination	-	42.03	21890473
188	Phosphorylation	FSDDPNVTKTLRFKQ CCCCCCCCEEEEEEE	25.59	23312004
189 (in isoform 1)	Ubiquitination	-	41.08	21890473
189	Ubiquitination	SDDPNVTKTLRFKQW CCCCCCCEEEEEEEC	41.08	21890473
189	Acetylation	SDDPNVTKTLRFKQW CCCCCCCEEEEEEEC	41.08	26051181
189	2-Hydroxyisobutyrylation	SDDPNVTKTLRFKQW CCCCCCCEEEEEEEC	41.08	-
189	Ubiquitination	SDDPNVTKTLRFKQW CCCCCCCEEEEEEEC	41.08	21890473
189	Ubiquitination	SDDPNVTKTLRFKQW CCCCCCCEEEEEEEC	41.08	21890473
190	Phosphorylation	DDPNVTKTLRFKQWN CCCCCCEEEEEEECC	17.50	23312004
194	Ubiquitination	VTKTLRFKQWNGKER CCEEEEEEECCCCCC	48.22	-
199	Acetylation	RFKQWNGKERSIYFQ EEEECCCCCCEEEEC	46.90	26051181
231 (in isoform 2)	Ubiquitination	-	36.84	-
232	Ubiquitination	VAVLTGKKVVQLDVR EEEEECCEEEEEECC	49.32	-
232	Acetylation	VAVLTGKKVVQLDVR EEEEECCEEEEEECC	49.32	27452117
244	Acetylation	DVRDNMVKLNDGSQI ECCCCEEECCCCCEE	30.70	26051181
249	Phosphorylation	MVKLNDGSQITYEKC EEECCCCCEEEEEEE	22.67	26437602
252	Phosphorylation	LNDGSQITYEKCLIA CCCCCEEEEEEEEEE	20.28	26437602
255	Ubiquitination	GSQITYEKCLIATGG CCEEEEEEEEEECCC	24.75	2210334
260	Phosphorylation	YEKCLIATGGTPRSL EEEEEEECCCCCCCH	29.20	26074081
263	Phosphorylation	CLIATGGTPRSLSAI EEEECCCCCCCHHHH	19.51	28985074
264 (in isoform 3)	Phosphorylation	-	27.43	-
266	Phosphorylation	ATGGTPRSLSAIDRA ECCCCCCCHHHHHHC	28.07	30266825
268	Phosphorylation	GGTPRSLSAIDRAGA CCCCCCHHHHHHCCC	25.15	29255136
278	2-Hydroxyisobutyrylation	DRAGAEVKSRTTLFR HHCCCCHHCCHHHHH	26.23	-
278	Ubiquitination	DRAGAEVKSRTTLFR HHCCCCHHCCHHHHH	26.23	-
279	Phosphorylation	RAGAEVKSRTTLFRK HCCCCHHCCHHHHHH	39.78	20833797
291 (in isoform 3)	Acetylation	-	45.10	-
291	Acetylation	FRKIGDFRSLEKISR HHHHCCCCCHHHHHH	45.10	19608861
292	Phosphorylation	RKIGDFRSLEKISRE HHHCCCCCHHHHHHH	40.65	28355574
295	Acetylation	GDFRSLEKISREVKS CCCCCHHHHHHHCCE	51.80	19608861
302	Phosphorylation	KISREVKSITIIGGG HHHHHCCEEEEECCC	30.09	25867546
304	Phosphorylation	SREVKSITIIGGGFL HHHCCEEEEECCCCH	17.40	25867546
324 (in isoform 3)	Phosphorylation	-	33.12	-
328	Phosphorylation	RKARALGTEVIQLFP HHHHHHCCEEHHHCC	28.12	20068231
337	Acetylation	VIQLFPEKGNMGKIL EHHHCCCCCCHHHCH	56.68	25953088
337	2-Hydroxyisobutyrylation	VIQLFPEKGNMGKIL EHHHCCCCCCHHHCH	56.68	-
337	Ubiquitination	VIQLFPEKGNMGKIL EHHHCCCCCCHHHCH	56.68	-
347	Phosphorylation	MGKILPEYLSNWTME HHHCHHHHHHCCCHH	17.31	26503892
349	Phosphorylation	KILPEYLSNWTMEKV HCHHHHHHCCCHHHH	29.44	26503892
352	Phosphorylation	PEYLSNWTMEKVRRE HHHHHCCCHHHHHHC	21.50	24247654
355	2-Hydroxyisobutyrylation	LSNWTMEKVRREGVK HHCCCHHHHHHCCCE	30.16	-
364	Sulfoxidation	RREGVKVMPNAIVQS HHCCCEECCCCEEEE	1.43	21406390
371	Phosphorylation	MPNAIVQSVGVSSGK CCCCEEEEECCCCCE	15.22	28258704
375	Phosphorylation	IVQSVGVSSGKLLIK EEEEECCCCCEEEEE	27.69	21406692
376	Phosphorylation	VQSVGVSSGKLLIKL EEEECCCCCEEEEEE	37.22	21406692
388	Acetylation	IKLKDGRKVETDHIV EEECCCCEEECCEEE	50.37	26051181
388	2-Hydroxyisobutyrylation	IKLKDGRKVETDHIV EEECCCCEEECCEEE	50.37	-
388	Malonylation	IKLKDGRKVETDHIV EEECCCCEEECCEEE	50.37	26320211
416	Phosphorylation	TGGLEIDSDFGGFRV CCCCEECCCCCCEEE	40.27	28857561
431	Phosphorylation	NAELQARSNIWVAGD CCEEEECCCEEEEEC	35.37	28348404
443	Phosphorylation	AGDAACFYDIKLGRR EECCEEEEECEECCC	19.35	-
512	Phosphorylation	VGVFAKATAQDNPKS CEEEEEEECCCCCCC	24.93	30108239
518	Ubiquitination	ATAQDNPKSATEQSG EECCCCCCCHHHCCC	60.00	-
519	Phosphorylation	TAQDNPKSATEQSGT ECCCCCCCHHHCCCC	41.50	25849741
521	Phosphorylation	QDNPKSATEQSGTGI CCCCCCHHHCCCCCC	41.47	25849741
524	Phosphorylation	PKSATEQSGTGIRSE CCCHHHCCCCCCCCC	31.90	25849741
526	Phosphorylation	SATEQSGTGIRSESE CHHHCCCCCCCCCCC	34.38	26471730
530	Phosphorylation	QSGTGIRSESETESE CCCCCCCCCCCCCCC	43.48	24275569
532	Phosphorylation	GTGIRSESETESEAS CCCCCCCCCCCCCCC	51.57	24275569
542	Phosphorylation	ESEASEITIPPSTPA CCCCCCCCCCCCCCC	24.31	-
546	Phosphorylation	SEITIPPSTPAVPQA CCCCCCCCCCCCCCC	41.49	-
547	O-linked_Glycosylation	EITIPPSTPAVPQAP CCCCCCCCCCCCCCC	22.50	OGP
547	Phosphorylation	EITIPPSTPAVPQAP CCCCCCCCCCCCCCC	22.50	-
569	Methylation	KGVIFYLRDKVVVGI CEEEEEECCCEEEEH	30.26	115486751
593	Ubiquitination	PIARKIIKDGEQHED HHHHHHHCCCCCCCC	64.25	-
593	Acetylation	PIARKIIKDGEQHED HHHHHHHCCCCCCCC	64.25	23954790
593	Succinylation	PIARKIIKDGEQHED HHHHHHHCCCCCCCC	64.25	23954790
593	Malonylation	PIARKIIKDGEQHED HHHHHHHCCCCCCCC	64.25	26320211
606	Acetylation	EDLNEVAKLFNIHED CCHHHHHHHHCCCCC	59.80	25038526
606	Ubiquitination	EDLNEVAKLFNIHED CCHHHHHHHHCCCCC	59.80	-

Upstream regulatory proteins (kinases for phosphorylation sites, E3 ubiquitin ligases of ubiquitination sites, ...)

Modified Location	Modified Residue	Modification	Type of Upstream Proteins	Gene Name of Upstream Proteins	UniProt AC of Upstream Proteins	Sources
-	K	Ubiquitination	E3 ubiquitin ligase	XIAP	P98170	PMID:22103349

Functions of PTM Sites

Modified Location	Modified Residue	Modification	Function	Reference
255	K	ubiquitylation		22103349
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.

Disease-associated PTM Sites based on SAP

* Distance = the distance between SAP position and PTM sites.

Modified Location	Modification	Variant Position (Distance <= 10)	Residue Change	SAP	Related Disease	Reference
Oops, there are no SNP-PTM records of AIFM1_HUMAN !!

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference
SETB1_HUMAN	SETDB1	physical	16169070
STC2_HUMAN	STC2	physical	16169070
XIAP_HUMAN	XIAP	physical	17967870
BAG6_HUMAN	BAG6	physical	18056262
T22D4_HUMAN	TSC22D4	physical	16713569
FSCN1_HUMAN	FSCN1	physical	22939629
THTR_HUMAN	TST	physical	22939629
HEM6_HUMAN	CPOX	physical	22939629
BAG6_HUMAN	BAG6	physical	23077592
GRP75_HUMAN	HSPA9	physical	27218139
PGAM5_HUMAN	PGAM5	physical	27218139
ADT2_HUMAN	SLC25A5	physical	27218139
SFXN1_HUMAN	SFXN1	physical	27218139
M2OM_HUMAN	SLC25A11	physical	27218139
MPCP_HUMAN	SLC25A3	physical	27218139
RM18_HUMAN	MRPL18	physical	27218139
EFTU_HUMAN	TUFM	physical	27218139
MIC27_HUMAN	APOOL	physical	28514442
SCMC3_HUMAN	SLC25A23	physical	28514442
S20A2_HUMAN	SLC20A2	physical	28514442
ACD10_HUMAN	ACAD10	physical	28514442
F91A1_HUMAN	FAM91A1	physical	28514442
ALR_HUMAN	GFER	physical	28514442
KAD2_HUMAN	AK2	physical	28514442
COT2_HUMAN	NR2F2	physical	28514442

Drug and Disease Associations

Kegg Disease
H00891	Combined oxidative phosphorylation deficiency (COXPD)
OMIM Disease
300816	Combined oxidative phosphorylation deficiency 6 (COXPD6)
310490	Cowchock syndrome (COWCK)
Kegg Drug
There are no disease associations of PTM sites.
DrugBank
DB03147	Flavin adenine dinucleotide

Regulatory Network of AIFM1_HUMAN

Related Literatures of Post-Translational Modification

Acetylation
Reference	PubMed
"Lysine acetylation targets protein complexes and co-regulates majorcellular functions."; Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.,Olsen J.V., Mann M.; Science 325:834-840(2009). Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-295, AND MASS SPECTROMETRY.	19608861 [Abstract]
Phosphorylation
Reference	PubMed
"A quantitative atlas of mitotic phosphorylation."; Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,Elledge S.J., Gygi S.P.; Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008). Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-268, AND MASSSPECTROMETRY.	18669648 [Abstract]
"Kinase-selective enrichment enables quantitative phosphoproteomics ofthe 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). Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-105 AND SER-268, ANDMASS SPECTROMETRY.	18691976 [Abstract]
Ubiquitylation
Reference	PubMed
"Nondegradative ubiquitination of apoptosis inducing factor (AIF) byX-linked inhibitor of apoptosis at a residue critical for AIF-mediatedchromatin degradation."; Lewis E.M., Wilkinson A.S., Davis N.Y., Horita D.A., Wilkinson J.C.; Biochemistry 50:11084-11096(2011). Cited for: UBIQUITINATION AT LYS-255 BY XIAP/BIRC4.	22103349 [Abstract]

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