Reviewed, UniProtKB/Swiss-Prot Q9BZZ5 (API5_HUMAN)

Names and origin

Protein names

Recommended name:
    Apoptosis inhibitor 5
      Short name=API-5
Alternative name(s):
    Fibroblast growth factor 2-interacting factor
      Short name=FIF
    Protein XAGL
    Antiapoptosis clone 11 protein
      Short name=AAC-11
    Cell migration-inducing gene 8 protein

Gene names

Name:	API5
ORF Names:	MIG8

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	510 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Antiapoptotic factor that may have a role in protein assembly. Negatively regulates ACIN1. By binding to ACIN1, it suppresses ACIN1 cleavage from CASP3 and ACIN1-mediated DNA fragmentation. Also known to efficiently suppress E2F1-induced apoptosis. Its depletion enhances the cytotoxic action of the chemotherapeutic drugs. Ref.9 Ref.13 Ref.16
Subunit structure	Homooligomer. Interacts with FGF2 and ACIN1. Ref.16 Ref.3
Subcellular location	Nucleus. Cytoplasm. Note: Mainly nuclear. Can also be cytoplasmic. Ref.3 Isoform 3: Cytoplasm.
Tissue specificity	Expressed in all tissues tested, including heart, brain, placenta, lung, liver, skeletal muscle, kidney and pancreas. Highest levels in heart, pancreas and placenta. Highly expressed in several cancers. Preferentially expressed in squamous cell carcinoma versus adenocarcinoma in non-small cell lung cancer. Ref.9 Ref.16 Ref.3 Ref.10 Ref.14
Domain	Two regions, an N-terminal (aa 96-107) and a C-terminal (aa 274-311) are required for binding FGF2.
Sequence similarities	Belongs to the API5 family.
Sequence caution	The sequence AAB86528.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened. The sequence AAB86528.1 differs from that shown. Reason: Frameshift at several positions.

Ontologies

Keywords
Biological process	Apoptosis
Cellular component	Cytoplasm Nucleus
Coding sequence diversity	Alternative splicing Polymorphism
PTM	Acetylation Phosphoprotein
Technical term	Complete proteome Direct protein sequencing
Gene Ontology (GO)
Biological process	anti-apoptosis Ref.1 Ref.3 Ref.9 Inferred from mutant phenotype. Source: UniProtKB apoptosis Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	cytoplasm Ref.3 Non-traceable author statement. Source: UniProtKB spliceosomal complex Inferred from sequence or structural similarity. Source: UniProtKB
Molecular function	fibroblast growth factor binding Ref.3 Inferred from physical interaction. Source: UniProtKB
Complete GO annotation...

Alternative products

This entry describes 4 isoforms produced by alternative splicing. [Align] [Select]

Note: Additional isoforms seem to exist.

Isoform 1 (identifier: Q9BZZ5-1)

Also known as: FIF-510;

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.

Isoform 2 (identifier: Q9BZZ5-2)

Also known as: FIF-504;

The sequence of this isoform differs from the canonical sequence as follows:
     498-510: GERFRLGTRNMRD → ERSLQGK

Isoform 3 (identifier: Q9BZZ5-3)

Also known as: FIF C1;

The sequence of this isoform differs from the canonical sequence as follows:
     371-373: KDF → HES
     374-510: Missing.

Note: No experimental confirmation available.

Isoform 4 (identifier: Q9BZZ5-4)

The sequence of this isoform differs from the canonical sequence as follows:
     371-373: KDF → HES
     498-510: GERFRLGTRNMRD → ERSLQGK

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Initiator methionine	1	1	Removed Ref.8
	Chain	2 – 510	509	Apoptosis inhibitor 5		PRO_0000064634
Regions
	Domain	370 – 391	22	Leucine-zipper
Sites
	Site	2	1	Not acetylated
Amino acid modifications
	Modified residue	28	1	Phosphotyrosine
	Modified residue	251	1	N6-acetyllysine Ref.17
	Modified residue	464	1	Phosphoserine Ref.11 Ref.12
Natural variations
	Alternative sequence	371 – 373	3	KDF → HES in isoform 3 and isoform 4.		VSP_013196
	Alternative sequence	374 – 510	137	Missing in isoform 3.		VSP_013197
	Alternative sequence	498 – 510	13	GERFR…RNMRD → ERSLQGK in isoform 2 and isoform 4.		VSP_013198
	Natural variant	276	1	P → S		VAR_021519
	Natural variant	300	1	M → V: dbSNP rs5743240. Ref.6		VAR_021520
	Natural variant	493	1	G → S: dbSNP rs2862934. Ref.6		VAR_021521

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (FIF-510) [UniParc]. Last modified April 12, 2005. Version 2. Checksum: B2C9CBA1FFA70FEF	FASTA	510	57,561
	10 20 30 40 50 60 MPTVEELYRN YGILADATEQ VGQHKDAYQV ILDGVKGGTK EKRLAAQFIP KFFKHFPELA 70 80 90 100 110 120 DSAINAQLDL CEDEDVSIRR QAIKELPQFA TGENLPRVAD ILTQLLQTDD SAEFNLVNNA 130 140 150 160 170 180 LLSIFKMDAK GTLGGLFSQI LQGEDIVRER AIKFLSTKLK TLPDEVLTKE VEELILTESK 190 200 210 220 230 240 KVLEDVTGEE FVLFMKILSG LKSLQTVSGR QQLVELVAEQ ADLEQTFNPS DPDCVDRLLQ 250 260 270 280 290 300 CTRQAVPLFS KNVHSTRFVT YFCEQVLPNL GTLTTPVEGL DIQLEVLKLL AEMSSFCGDM 310 320 330 340 350 360 EKLETNLRKL FDKLLEYMPL PPEEAENGEN AGNEEPKLQF SYVECLLYSF HQLGRKLPDF 370 380 390 400 410 420 LTAKLNAEKL KDFKIRLQYF ARGLQVYIRQ LRLALQGKTG EALKTEENKI KVVALKITNN 430 440 450 460 470 480 INVLIKDLFH IPPSYKSTVT LSWKPVQKVE IGQKRASEDT TSGSPPKKSS AGPKRDARQI 490 500 510 YNPPSGKYSS NLGNFNYGER FRLGTRNMRD
	Isoform 2 (FIF-504). Checksum: D4A0D283CDFC4A87	FASTA	504	56,770
	10 20 30 40 50 60 MPTVEELYRN YGILADATEQ VGQHKDAYQV ILDGVKGGTK EKRLAAQFIP KFFKHFPELA 70 80 90 100 110 120 DSAINAQLDL CEDEDVSIRR QAIKELPQFA TGENLPRVAD ILTQLLQTDD SAEFNLVNNA 130 140 150 160 170 180 LLSIFKMDAK GTLGGLFSQI LQGEDIVRER AIKFLSTKLK TLPDEVLTKE VEELILTESK 190 200 210 220 230 240 KVLEDVTGEE FVLFMKILSG LKSLQTVSGR QQLVELVAEQ ADLEQTFNPS DPDCVDRLLQ 250 260 270 280 290 300 CTRQAVPLFS KNVHSTRFVT YFCEQVLPNL GTLTTPVEGL DIQLEVLKLL AEMSSFCGDM 310 320 330 340 350 360 EKLETNLRKL FDKLLEYMPL PPEEAENGEN AGNEEPKLQF SYVECLLYSF HQLGRKLPDF 370 380 390 400 410 420 LTAKLNAEKL KDFKIRLQYF ARGLQVYIRQ LRLALQGKTG EALKTEENKI KVVALKITNN 430 440 450 460 470 480 INVLIKDLFH IPPSYKSTVT LSWKPVQKVE IGQKRASEDT TSGSPPKKSS AGPKRDARQI 490 500 YNPPSGKYSS NLGNFNYERS LQGK
	Isoform 3 (FIF C1). Checksum: FA4891B09A10552F	FASTA	373	42,020
	10 20 30 40 50 60 MPTVEELYRN YGILADATEQ VGQHKDAYQV ILDGVKGGTK EKRLAAQFIP KFFKHFPELA 70 80 90 100 110 120 DSAINAQLDL CEDEDVSIRR QAIKELPQFA TGENLPRVAD ILTQLLQTDD SAEFNLVNNA 130 140 150 160 170 180 LLSIFKMDAK GTLGGLFSQI LQGEDIVRER AIKFLSTKLK TLPDEVLTKE VEELILTESK 190 200 210 220 230 240 KVLEDVTGEE FVLFMKILSG LKSLQTVSGR QQLVELVAEQ ADLEQTFNPS DPDCVDRLLQ 250 260 270 280 290 300 CTRQAVPLFS KNVHSTRFVT YFCEQVLPNL GTLTTPVEGL DIQLEVLKLL AEMSSFCGDM 310 320 330 340 350 360 EKLETNLRKL FDKLLEYMPL PPEEAENGEN AGNEEPKLQF SYVECLLYSF HQLGRKLPDF 370 LTAKLNAEKL HES
	Isoform 4. Checksum: 7BB0D2C973142435	FASTA	504	56,733
	10 20 30 40 50 60 MPTVEELYRN YGILADATEQ VGQHKDAYQV ILDGVKGGTK EKRLAAQFIP KFFKHFPELA 70 80 90 100 110 120 DSAINAQLDL CEDEDVSIRR QAIKELPQFA TGENLPRVAD ILTQLLQTDD SAEFNLVNNA 130 140 150 160 170 180 LLSIFKMDAK GTLGGLFSQI LQGEDIVRER AIKFLSTKLK TLPDEVLTKE VEELILTESK 190 200 210 220 230 240 KVLEDVTGEE FVLFMKILSG LKSLQTVSGR QQLVELVAEQ ADLEQTFNPS DPDCVDRLLQ 250 260 270 280 290 300 CTRQAVPLFS KNVHSTRFVT YFCEQVLPNL GTLTTPVEGL DIQLEVLKLL AEMSSFCGDM 310 320 330 340 350 360 EKLETNLRKL FDKLLEYMPL PPEEAENGEN AGNEEPKLQF SYVECLLYSF HQLGRKLPDF 370 380 390 400 410 420 LTAKLNAEKL HESKIRLQYF ARGLQVYIRQ LRLALQGKTG EALKTEENKI KVVALKITNN 430 440 450 460 470 480 INVLIKDLFH IPPSYKSTVT LSWKPVQKVE IGQKRASEDT TSGSPPKKSS AGPKRDARQI 490 500 YNPPSGKYSS NLGNFNYERS LQGK

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"AAC-11, a novel cDNA that inhibits apoptosis after growth factor withdrawal." Tewari M., Yu M., Ross B., Dean C., Giordano A., Rubin R. Cancer Res. 57:4063-4069(1997) [PubMed: 9307294] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 4).
[2]	"Molecular cloning and fine mapping of API5L1, a novel human gene strongly related to an antiapoptotic gene." Gianfrancesco F., Esposito T., Ciccodicola A., D'Esposito M., Mazzarella R., D'Urso M., Forabosco A. Cytogenet. Cell Genet. 84:164-166(1999) [PubMed: 10393420] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
[3]	"FIF [fibroblast growth factor-2 (FGF-2)-interacting-factor], a nuclear putatively antiapoptotic factor, interacts specifically with FGF-2." Van den Berghe L., Laurell H., Huez I., Zanibellato C., Prats H., Bugler B. Mol. Endocrinol. 14:1709-1724(2000) [PubMed: 11075807] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2 AND 3), SUBCELLULAR LOCATION, TISSUE SPECIFICITY, INTERACTION WITH FGF2. Tissue: Liver.
[4]	"Identification of a human cell migration gene." Kim J.W. Submitted (JUN-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
[5]	"Cloning of human full-length CDSs in BD Creator(TM) system donor vector." Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A. Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
[6]	NIEHS SNPs program Submitted (MAR-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS SER-276; VAL-300 AND SER-493.
[7]	"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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). Tissue: Lymph.
[8]	Bienvenut W.V., Lilla S., von Kriegsheim A., Lempens A., Kolch W. Submitted (DEC-2008) to UniProtKB Cited for: PROTEIN SEQUENCE OF 2-9; 26-36; 131-148; 161-169; 244-251 AND 427-436, CLEAVAGE OF INITIATOR METHIONINE, LACK OF N-TERMINAL ACETYLATION, MASS SPECTROMETRY. Tissue: Ovarian carcinoma.
[9]	"AAC-11 overexpression induces invasion and protects cervical cancer cells from apoptosis." Kim J.W., Cho H.S., Kim J.H., Hur S.Y., Kim T.E., Lee J.M., Kim I.K., Namkoong S.E. Lab. Invest. 80:587-594(2000) [PubMed: 10780674] [Abstract] Cited for: FUNCTION, TISSUE SPECIFICITY.
[10]	"Expression of the antiapoptosis gene, AAC-11, as a prognosis marker in non-small cell lung cancer." Sasaki H., Moriyama S., Yukiue H., Kobayashi Y., Nakashima Y., Kaji M., Fukai I., Kiriyama M., Yamakawa Y., Fujii Y. Lung Cancer 34:53-57(2001) [PubMed: 11557113] [Abstract] Cited for: TISSUE SPECIFICITY.
[11]	"Global phosphoproteome of HT-29 human colon adenocarcinoma cells." Kim J.-E., Tannenbaum S.R., White F.M. J. Proteome Res. 4:1339-1346(2005) [PubMed: 16083285] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-464, MASS SPECTROMETRY.
[12]	"Global, in vivo, and site-specific phosphorylation dynamics in signaling networks." Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M. Cell 127:635-648(2006) [PubMed: 17081983] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-464, MASS SPECTROMETRY. Tissue: Epithelium.
[13]	"Functional identification of Api5 as a suppressor of E2F-dependent apoptosis in vivo." Morris E.J., Michaud W.A., Ji J.Y., Moon N.S., Rocco J.W., Dyson N.J. PLoS Genet. 2:E196-E196(2006) [PubMed: 17112319] [Abstract] Cited for: FUNCTION.
[14]	"The antiapoptotic protein Api5 and its partner, high molecular weight FGF2, are up-regulated in B cell chronic lymphoid leukemia." Krejci P., Pejchalova K., Rosenbloom B.E., Rosenfelt F.P., Tran E.L., Laurell H., Wilcox W.R. J. Leukoc. Biol. 82:1363-1364(2007) [PubMed: 17827341] [Abstract] Cited for: TISSUE SPECIFICITY.
[15]	"Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach." Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S. Anal. Chem. 81:4493-4501(2009) [PubMed: 19413330] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-28 AND SER-464, MASS SPECTROMETRY.
[16]	"The antiapoptotic protein AAC-11 interacts with and regulates Acinus-mediated DNA fragmentation." Rigou P., Piddubnyak V., Faye A., Rain J.-C., Michel L., Calvo F., Poyet J.-L. EMBO J. 28:1576-1588(2009) [PubMed: 19387494] [Abstract] Cited for: FUNCTION, INTERACTION WITH ACIN1, TISSUE SPECIFICITY.
[17]	"Lysine acetylation targets protein complexes and co-regulates major cellular functions." Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T., Olsen J.V., Mann M. Science 325:834-840(2009) [PubMed: 19608861] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-251, MASS SPECTROMETRY.
+	Additional computationally mapped references.

Web resources

NIEHS-SNPs

Cross-references

Sequence databases
EMBLGenBankDDBJ	U83857 mRNA. Translation: AAB86528.1. Sequence problems. Y15906 mRNA. Translation: CAA75867.1. AF229253 mRNA. Translation: AAK00737.1. AF229254 mRNA. Translation: AAK00738.1. AY311389 mRNA. Translation: AAQ76714.1. BT007093 mRNA. Translation: AAP35756.1. AY265973 Genomic DNA. Translation: AAO89077.1. BC017709 mRNA. Translation: AAH17709.1.
IPI	IPI00554742. IPI00555572. IPI00555743. IPI00855856.
RefSeq	NP_001136402.1. NP_001136403.1. NP_006586.1.
UniGene	Hs.435771
3D structure databases
ModBase	Search...
Protein-protein interaction databases
IntAct	Q9BZZ5. 1 interaction.
STRING	Q9BZZ5.
PTM databases
PhosphoSite	Q9BZZ5.
Proteomic databases
PRIDE	Q9BZZ5.
Genome annotation databases
Ensembl	ENST00000455725; ENSP00000399341; ENSG00000166181; Homo sapiens. [Genome view]
GeneID	8539.
KEGG	hsa:8539.
UCSC	uc001mxf.1. human. uc001mxg.2. human.
Organism-specific databases
CTD	8539.
GeneCards	GC11P043290.
H-InvDB	HIX0009571.
HGNC	HGNC:594. API5.
HPA	HPA026598.
MIM	609774. gene.
PharmGKB	PA24881.
GenAtlas	Search...
Phylogenomic databases
HOVERGEN	Q9BZZ5.
Gene expression databases
ArrayExpress	Q9BZZ5.
Bgee	Q9BZZ5.
CleanEx	HS_API5.
Genevestigator	Q9BZZ5.
Family and domain databases
InterPro	IPR008383. API5. IPR016024. ARM-type_fold. [Graphical view]
PANTHER	PTHR12758:SF11. API5. 1 hit.
Pfam	PF05918. API5. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	31984.
SOURCE	Search...

Entry information

Entry name

API5_HUMAN

Accession

Primary (citable) accession number: Q9BZZ5
Secondary accession number(s): O15441, Q9Y4J7

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 12, 2005
Last sequence update:	April 12, 2005
Last modified:	November 24, 2009
This is version 59 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

Disclaimer

Any 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.