Q8WUF5 (IASPP_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
RelA-associated inhibitor

Alternative name(s):
Inhibitor of ASPP protein
Short name=Protein iASPP
NFkB-interacting protein 1
PPP1R13B-like protein

Gene names

Name:	PPP1R13L
Synonyms:	IASPP, NKIP1, PPP1R13BL, RAI

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	828 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Regulator that plays a central role in regulation of apoptosis and transcription via its interaction with NF-kappa-B and p53/TP53 proteins. Blocks transcription of HIV-1 virus by inhibiting the action of both NF-kappa-B and SP1. Also inhibits p53/TP53 function, possibly by preventing the association between p53/TP53 and ASPP1 or ASPP2, and therefore suppressing the subsequent activation of apoptosis. Ref.1 Ref.5 Ref.6 Ref.7
Subunit structure	Interacts with RELA NF-kappa-B subunit and with SP1 via its C-terminus part. Interacts with p53/TP53, TP63 and TP73. Ref.1 Ref.5 Ref.6 Ref.7 Ref.15
Subcellular location	Cytoplasm. Nucleus. Note: Predominantly cytoplasmic but also nuclear. Ref.1 Ref.5
Tissue specificity	Highly expressed in heart, placenta and prostate. Weakly expressed in brain, liver, skeletal muscle, testis and peripheral blood leukocyte. Ref.5
Domain	Isoform 1 N-terminal region is required for cytoplasmic localization.
Sequence similarities	Belongs to the ASPP family. Contains 2 ANK repeats. Contains 1 SH3 domain.
Sequence caution	The sequence AAD27004.1 differs from that shown. Reason: Frameshift at positions 439, 483, 562 and 591. The sequence AAD27005.1 differs from that shown. Reason: Frameshift at positions 483, 562 and 591. The sequence AAD27005.1 differs from that shown. Reason: Probable cloning artifact.

Ontologies

Keywords
Biological process	Apoptosis Transcription Transcription regulation
Cellular component	Cytoplasm Nucleus
Domain	ANK repeat Repeat SH3 domain
Molecular function	Repressor
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	apoptotic process Inferred from electronic annotation. Source: UniProtKB-KW cardiac muscle contraction Inferred from electronic annotation. Source: Compara cardiac right ventricle morphogenesis Inferred from electronic annotation. Source: Compara embryonic camera-type eye development Inferred from electronic annotation. Source: Compara hair cycle Inferred from electronic annotation. Source: Compara multicellular organism growth Inferred from electronic annotation. Source: Compara multicellular organismal homeostasis Inferred from electronic annotation. Source: Compara negative regulation of transcription from RNA polymerase II promoter Inferred from electronic annotation. Source: Compara post-embryonic development Inferred from electronic annotation. Source: Compara transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW ventricular cardiac muscle tissue development Inferred from electronic annotation. Source: Compara
Cellular_component	cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell nucleus Traceable author statement Ref.5. Source: ProtInc
Molecular_function	transcription corepressor activity Traceable author statement Ref.5. Source: ProtInc transcription factor binding Traceable author statement Ref.5. Source: ProtInc
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
TP53	P04637	3	EBI-5550163,EBI-366083

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 828

828

RelA-associated inhibitor

PRO_0000066966

Regions

Repeat

659 – 691

33

ANK 1

Repeat

692 – 724

33

ANK 2

Domain

758 – 820

63

SH3

Compositional bias

54 – 602

549

Pro-rich

Compositional bias

407 – 444

38

Gln-rich

Amino acid modifications

Modified residue

102

1

Phosphoserine Ref.11

Modified residue

110

1

Phosphoserine Ref.9 Ref.11 Ref.13

Modified residue

113

1

Phosphoserine Ref.9 Ref.11 Ref.13

Modified residue

119

1

Phosphoserine Ref.11

Modified residue

120

1

Phosphoserine Ref.11

Modified residue

123

1

Phosphothreonine Ref.11

Modified residue

134

1

Phosphoserine Ref.11

Modified residue

183

1

Phosphoserine Ref.9 Ref.12 Ref.13

Modified residue

187

1

Phosphoserine Ref.9 Ref.12 Ref.13

Modified residue

203

1

Phosphoserine Ref.11

Modified residue

280

1

Phosphoserine Ref.13

Modified residue

308

1

Phosphothreonine By similarity

Modified residue

316

1

Phosphoserine Ref.11

Modified residue

332

1

Phosphoserine Ref.11

Modified residue

526

1

Phosphoserine Ref.11

Modified residue

567

1

Phosphoserine Ref.8 Ref.10 Ref.11 Ref.13

Modified residue

597

1

Phosphoserine Ref.11

Experimental info

Sequence conflict

198

1

P → S in AAH64913. Ref.4

Sequence conflict

223

1

L → I in AAW51146. Ref.2

Sequence conflict

317 – 318

2

PL → AA in AAD27004. Ref.5

Sequence conflict

321

1

D → T in AAD27004. Ref.5

Sequence conflict

369

1

P → S in AAW51146. Ref.2

Sequence conflict

372

1

Missing in AAW51146. Ref.2

Sequence conflict

426

1

P → Q in AAD27004. Ref.5

Sequence conflict

439 – 440

2

PQ → HP in AAD27004. Ref.5

Sequence conflict

747

1

Y → S in AAW51146. Ref.2

Secondary structure

1

.

.

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.

.

.

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.

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.

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828

Helix Strand Turn

Details...

Helix

627 – 637

11

Helix

640 – 649

10

Helix

663 – 669

7

Helix

673 – 681

9

Helix

696 – 702

7

Helix

706 – 713

8

Turn

714 – 716

3

Helix

731 – 733

3

Helix

741 – 754

14

Turn

755 – 757

3

Helix

759 – 761

3

Beta strand

762 – 767

6

Beta strand

784 – 791

8

Beta strand

796 – 803

8

Beta strand

806 – 811

6

Helix

812 – 814

3

Beta strand

815 – 818

4

Sequences

	Sequence		Length	Mass (Da)
	Q8WUF5 [UniParc]. Last modified April 4, 2006. Version 4. Checksum: 7BEEF239B7CA9C70	FASTA	828	89,091
	10 20 30 40 50 60 MDSEAFQSAR DFLDMNFQSL AMKHMDLKQM ELDTAAAKVD ELTKQLESLW SDSPAPPGPQ 70 80 90 100 110 120 AGPPSRPPRY SSSSIPEPFG SRGSPRKAAT DGADTPFGRS ESAPTLHPYS PLSPKGRPSS 130 140 150 160 170 180 PRTPLYLQPD AYGSLDRATS PRPRAFDGAG SSLGRAPSPR PGPGPLRQQG PPTPFDFLGR 190 200 210 220 230 240 AGSPRGSPLA EGPQAFFPER GPSPRPPATA YDAPASAFGS SLLGSGGSAF APPLRAQDDL 250 260 270 280 290 300 TLRRRPPKAW NESDLDVAYE KKPSQTASYE RLDVFARPAS PSLQLLPWRE SSLDGLGGTG 310 320 330 340 350 360 KDNLTSATLP RNYKVSPLAS DRRSDAGSYR RSLGSAGPSG TLPRSWQPVS RIPMPPSSPQ 370 380 390 400 410 420 PRGAPRQRPI PLSMIFKLQN AFWEHGASRA MLPGSPLFTR APPPKLQPQP QPQPQPQSQP 430 440 450 460 470 480 QPQLPPQPQT QPQTPTPAPQ HPQQTWPPVN EGPPKPPTEL EPEPEIEGLL TPVLEAGDVD 490 500 510 520 530 540 EGPVARPLSP TRLQPALPPE AQSVPELEEV ARVLAEIPRP LKRRGSMEQA PAVALPPTHK 550 560 570 580 590 600 KQYQQIISRL FHRHGGPGPG GPEPELSPIT EGSEARAGPP APAPPAPIPP PAPSQSSPPE 610 620 630 640 650 660 QPQSMEMRSV LRKAGSPRKA RRARLNPLVL LLDAALTGEL EVVQQAVKEM NDPSQPNEEG 670 680 690 700 710 720 ITALHNAICG ANYSIVDFLI TAGANVNSPD SHGWTPLHCA ASCNDTVICM ALVQHGAAIF 730 740 750 760 770 780 ATTLSDGATA FEKCDPYREG YADCATYLAD VEQSMGLMNS GAVYALWDYS AEFGDELSFR 790 800 810 820 EGESVTVLRR DGPEETDWWW AALHGQEGYV PRNYFGLFPR VKPQRSKV

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"The N-terminus of a novel isoform of human iASPP is required for its cytoplasmic localization." Slee E.A., Gillotin S., Bergamaschi D., Royer C., Llanos S., Ali S., Jin B., Trigiante G., Lu X. Oncogene 23:9007-9016(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH TP53.
[2]	Herron B.J., Rao C., Beier D.R. Submitted (DEC-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]	NHLBI resequencing and genotyping service (RS&G) Submitted (DEC-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[4]	"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]. Tissue: Liver, Placenta and Testis.
[5]	"Identification of a novel inhibitor of nuclear factor-kappaB, RelA-associated inhibitor." Yang J.-P., Hori M., Sanda T., Okamoto T. J. Biol. Chem. 274:15662-15670(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 317-828, FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, INTERACTION WITH RELA. Tissue: Placenta.
[6]	"RelA-associated inhibitor blocks transcription of human immunodeficiency virus type 1 by inhibiting NF-kappaB and Sp1 actions." Takada N., Sanda T., Okamoto H., Yang J.-P., Asamitsu K., Sarol L., Kimura G., Uranishi H., Tetsuka T., Okamoto T. J. Virol. 76:8019-8030(2002) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH SP1.
[7]	"iASPP oncoprotein is a key inhibitor of p53 conserved from worm to human." Bergamaschi D., Samuels Y., O'Neil N.J., Trigiante G., Crook T., Hsieh J.-K., O'Connor D.J., Zhong S., Campargue I., Tomlinson M.L., Kuwabara P.E., Lu X. Nat. Genet. 33:162-167(2003) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH TP53.
[8]	"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] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-567, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[9]	"A probability-based approach for high-throughput protein phosphorylation analysis and site localization." Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P. Nat. Biotechnol. 24:1285-1292(2006) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-110; SER-113; SER-183 AND SER-187, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[10]	"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 SER-567, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[11]	"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) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-102; SER-110; SER-113; SER-119; SER-120; THR-123; SER-134; SER-203; SER-316; SER-332; SER-526; SER-567 AND SER-597, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[12]	"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions." Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K. Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-183 AND SER-187, MASS SPECTROMETRY. Tissue: Leukemic T-cell.
[13]	"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis." Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M. Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-110; SER-113; SER-183; SER-187; SER-280 AND SER-567, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[14]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[15]	"Biochemical and structural studies of ASPP proteins reveal differential binding to p53, p63, and p73." Robinson R.A., Lu X., Jones E.Y., Siebold C. Structure 16:259-268(2008) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 607-828, INTERACTION WITH TP53/P53; TP63 AND TP73.
+	Additional computationally mapped references.

Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AJ888472 mRNA. Translation: CAI60219.1.
AY869712 mRNA. Translation: AAW51146.1.
DQ314886 Genomic DNA. Translation: ABC40745.1.
BC001475 mRNA. Translation: AAH01475.1.
BC020589 mRNA. Translation: AAH20589.1.
BC032298 mRNA. Translation: AAH32298.1.
BC064913 mRNA. Translation: AAH64913.1.
AF078036 mRNA. Translation: AAD27004.1. Frameshift.
AF078037 mRNA. Translation: AAD27005.1. Sequence problems.

IPI

IPI00439948.
IPI01018117.

RefSeq

NP_001135974.1. NM_001142502.1.
NP_006654.2. NM_006663.3.

UniGene

Hs.466937.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2VGE	X-ray	2.10	A	607-828	[»]

ProteinModelPortal

Q8WUF5.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-29586N.

IntAct

Q8WUF5. 2 interactions.

MINT

MINT-7034564.

STRING

9606.ENSP00000354218.

PTM databases

PhosphoSite

Q8WUF5.

Polymorphism databases

DMDM

92090607.

Proteomic databases

PaxDb

Q8WUF5.

PRIDE

Q8WUF5.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000360957; ENSP00000354218; ENSG00000104881.
ENST00000418234; ENSP00000403902; ENSG00000104881.

GeneID

10848.

KEGG

hsa:10848.

UCSC

uc002pbn.3. human.

Organism-specific databases

CTD

10848.

GeneCards

GC19M045883.

HGNC

HGNC:18838. PPP1R13L.

HPA

CAB005016.

MIM

607463. gene.

neXtProt

NX_Q8WUF5.

PharmGKB

PA34195.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG237939.

HOVERGEN

HBG055210.

InParanoid

Q8WUF5.

OMA

MGLMHNG.

OrthoDB

EOG4PG60W.

Gene expression databases

Bgee

Q8WUF5.

CleanEx

HS_PPP1R13L.

Genevestigator

Q8WUF5.

GermOnline

ENSG00000104881. Homo sapiens.

Family and domain databases

Gene3D

1.25.40.20. 1 hit.

InterPro

IPR002110. Ankyrin_rpt.
IPR020683. Ankyrin_rpt-contain_dom.
IPR001452. SH3_domain.
[Graphical view]

Pfam

PF12796. Ank_2. 1 hit.
PF00018. SH3_1. 1 hit.
[Graphical view]

PRINTS

PR00452. SH3DOMAIN.

SMART

SM00248. ANK. 2 hits.
SM00326. SH3. 1 hit.
[Graphical view]

SUPFAM

SSF48403. ANK. 1 hit.
SSF50044. SH3. 1 hit.

PROSITE

PS50297. ANK_REP_REGION. 1 hit.
PS50088. ANK_REPEAT. 2 hits.
PS50002. SH3. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

Q8WUF5.

GenomeRNAi

10848.

NextBio

41185.

PMAP-CutDB

Q8WUF5.

SOURCE

Search...

Entry information

Entry name

IASPP_HUMAN

Accession

Primary (citable) accession number: Q8WUF5
Secondary accession number(s): Q2PNZ9 , Q5DU71, Q5I1X4, Q6P1R7, Q6PKF8, Q9Y290

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 15, 2003
Last sequence update:	April 4, 2006
Last modified:	May 1, 2013
This is version 108 of the entry and version 4 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

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.