Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

CASP8-associated protein 2

Gene

Casp8ap2

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Participates in TNF-alpha-induced blockade of glucocorticoid receptor (GR) transactivation at the nuclear receptor coactivator level, upstream and independently of NF-kappa-B. Suppresses both NCOA2- and NCOA3-induced enhancement of GR transactivation (By similarity). Required for histone gene transcription and progression through S phase (By similarity). Required for histone gene transcription and S phase progression (By similarity). Involved in TNF-alpha-induced activation of NF-kappa-B via a TRAF2-dependent pathway. Acts as a downstream mediator for CASP8-induced activation of NF-kappa-B. Required for the activation of CASP8 in FAS-mediated apoptosis.By similarity2 Publications

GO - Molecular functioni

  • cysteine-type endopeptidase activator activity involved in apoptotic process Source: MGI
  • DNA binding Source: InterPro
  • identical protein binding Source: MGI
  • protease binding Source: UniProtKB
  • SUMO polymer binding Source: UniProtKB
  • transcription corepressor activity Source: UniProtKB

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Activator, Repressor

Keywords - Biological processi

Apoptosis, Cell cycle, Transcription, Transcription regulation

Names & Taxonomyi

Protein namesi
Recommended name:
CASP8-associated protein 2
Alternative name(s):
FLICE-associated huge protein
Gene namesi
Name:Casp8ap2Imported
Synonyms:FlashImported
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 4

Organism-specific databases

MGIiMGI:1349399. Casp8ap2.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Mitochondrion, Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Initiator methionineiRemovedBy similarity
Chaini2 – 19621961CASP8-associated protein 2PRO_0000076189Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei2 – 21N-acetylalanineBy similarity
Modified residuei20 – 201PhosphoserineBy similarity
Cross-linki92 – 92Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity
Modified residuei560 – 5601PhosphoserineBy similarity
Modified residuei798 – 7981PhosphoserineBy similarity
Modified residuei858 – 8581PhosphoserineBy similarity
Modified residuei923 – 9231PhosphoserineBy similarity
Modified residuei1323 – 13231N6-acetyllysineCombined sources

Keywords - PTMi

Acetylation, Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiQ9WUF3.
MaxQBiQ9WUF3.
PaxDbiQ9WUF3.
PeptideAtlasiQ9WUF3.
PRIDEiQ9WUF3.

PTM databases

iPTMnetiQ9WUF3.
PhosphoSiteiQ9WUF3.

Expressioni

Tissue specificityi

Highly expressed in heart, brain, thymus, lung, testis and spleen.1 Publication

Gene expression databases

BgeeiQ9WUF3.
CleanExiMM_CASP8AP2.
ExpressionAtlasiQ9WUF3. baseline and differential.
GenevisibleiQ9WUF3. MM.

Interactioni

Subunit structurei

Self-associates. Interacts with NPAT (By similarity). Interacts with SRRT (By similarity). Interacts (via SIM domains) with SUMO1 and SUMO2 (By similarity). Interacts with SP100; may negatively regulate CASP8AP2 export from the nucleus to the cytoplasm (By similarity). Interacts with NCOA2 and NCOA3 (By similarity). Component of the death-inducing signaling complex (DISC) with CASP8, FADD and FAS. Interacts with TRAF2.By similarity3 Publications

GO - Molecular functioni

  • identical protein binding Source: MGI
  • protease binding Source: UniProtKB
  • SUMO polymer binding Source: UniProtKB

Protein-protein interaction databases

BioGridi205038. 1 interaction.
IntActiQ9WUF3. 3 interactions.
MINTiMINT-91554.
STRINGi10090.ENSMUSP00000029950.

Structurei

3D structure databases

ProteinModelPortaliQ9WUF3.
SMRiQ9WUF3. Positions 1896-1962.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni1688 – 1962275NCOA2-bindingBy similarityAdd
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi1716 – 17205SUMO interaction motif 1 (SIM); mediates the binding to polysumoylated substratesBy similarity

Phylogenomic databases

eggNOGiENOG410IEBH. Eukaryota.
ENOG410YRSQ. LUCA.
GeneTreeiENSGT00620000088063.
HOGENOMiHOG000049238.
HOVERGENiHBG080371.
InParanoidiQ9WUF3.
OMAiKLHQVWE.
OrthoDBiEOG7J4460.
TreeFamiTF332487.

Family and domain databases

Gene3Di1.10.10.60. 1 hit.
InterProiIPR009057. Homeodomain-like.
[Graphical view]

Sequencei

Sequence statusi: Complete.

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

Q9WUF3-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MAADDDNGDG TGLFDVCPAS PLKNNDEGSL DIYAGLDSAV SDSTARSCVS
60 70 80 90 100
FRNCLDLYEE ILTEEGTAKE ATYNDLQIEY GKCQQQMKDL MKRFKEIQTQ
110 120 130 140 150
NLNLKNENQS LKKNISALIK TARVEINRKD EEINHLHQRL SEFPHFRNNH
160 170 180 190 200
KTARTKDSQS TSPHLDDCSK TDHGVKSDVQ KDVHPNTAQP NLEKEGKSHS
210 220 230 240 250
EAQNPLHLST GVEKHCANNV WSRSPYQVGE GNSNEDNRRG RSGTRHSQCS
260 270 280 290 300
RGTDRTQKDL HSSCNDSEPR DKEANSRLQG HPEKHGNSEA RTESKISESK
310 320 330 340 350
SSTGMGYKSE RSASSWEKET SRERPHTRVE SQHDKNLEKQ NERLQNMHRK
360 370 380 390 400
ELPSQDKTER KVDVKFKPAG EEQGHRGRVD RALPPHPKND VKHYGFNKYH
410 420 430 440 450
PEERRGREDC KRDRGMNSHG FQDRRCSSFL SSNRNSKYPH SKEVSVAHQW
460 470 480 490 500
ENTPFKAERH RTEDRRKRER ENKEESRHVK SDKKSPPEHL QRTHKDTKKS
510 520 530 540 550
TADGKRQTEP KHGKGAVSNS ELSKGTDSKE GATKVESGPN EAKGKDLKLS
560 570 580 590 600
FMEKLNLTLS PAKKQPACQD NPHQITGVPE PSGTCDSRSL ETTGTVACLP
610 620 630 640 650
SGSEHNREET KSELPEPKEA LLATSQLRIS IPENKMKEEK RLLFKSVENT
660 670 680 690 700
VPCELLACGT EISLPAPVEI EQARCLLGSV EVEETCGGAR TAASVVMHVL
710 720 730 740 750
PEHASEDASQ ELDTKRHDGI NACAISEGVK TKVILSPKAA AASESHLAPL
760 770 780 790 800
VEEPSISLVN CSGDNNPKLE PSLEERPIVE TKSCPLESCL PKETFVPSPQ
810 820 830 840 850
KTELIDHKIE TGESNSVYQD DDNSVLSIDF NNLRPIPDPI SPLNSPVRPV
860 870 880 890 900
CKVVSMESSC AIPLYDSSHK DEFPSNSTLS TFKSQSDLNK ENEKPVPKFD
910 920 930 940 950
KCSEADSCKH LSLDELEEGE IRSDDEESVA QKRLEKSARP RVSAEVQPGK
960 970 980 990 1000
SSPGSRRSTV HVHKDNGRTA VKLPRDRLTW SKRSSESRPS NTERKSKTMS
1010 1020 1030 1040 1050
ISSLEKILPL ILVPSSLWEV MHMLRLLGKH VRKNYMKFKI KFSLTQFHRI
1060 1070 1080 1090 1100
IESAILSFTS LVKCLDLSKI CKSVSTLQKS LCEVIESNLK QVKKNGIVDR
1110 1120 1130 1140 1150
LFEQQQTDMK KKLWKFVDEQ LDYLFEKLKK ILLKFCDSVN FENENSEGKL
1160 1170 1180 1190 1200
GKKYKERTQH SNCQKKKMDN KEIRREKVLK SENTVNFKSS LGCEKSEEKH
1210 1220 1230 1240 1250
QDQNKTNASI VKHDVKRTFS TCSDNTKNAE CKEQFLEKSC PSTPRPGKDE
1260 1270 1280 1290 1300
GHTEEEAQAA QHASAKSERS FEILTEQQAS SLTFNLVSDA QMGEIFKSLL
1310 1320 1330 1340 1350
QGSDLLDTSG TEKAEWELKT PEKQLLESLK CESAPACATE ELVSEGASLC
1360 1370 1380 1390 1400
PKVISDDNWS LLSSEKGPSL SSGLSLPVHP DVLDENCMFE VSSNTALGKD
1410 1420 1430 1440 1450
NVYSSEKSKP CISSILLEDL AVSLTVPSPL KSDGHLSFLK PEVLSTSTPE
1460 1470 1480 1490 1500
EVISAHFSED ALLEEEDASE QDIHLALESD NSSSKSSCSS WTSRSVASGF
1510 1520 1530 1540 1550
QYHPNLPMHA VIMEKSNDHF IVKIRRATPS TSPGLKHGVV AEESLTSLPR
1560 1570 1580 1590 1600
TGKEAGVATE KEPNLFQSTV LKPVKDLENT DKNIDKSKLT HEEQNSIVQT
1610 1620 1630 1640 1650
QVPDIYEFLK DASNKVVHCD QVVDDCFKLH QVWEPKVSEN LQELPSMEKI
1660 1670 1680 1690 1700
PHSLDNHLPD THIDLTKDSA TETKSLGELM EVTVLNVDHL ECSQTNLDQD
1710 1720 1730 1740 1750
AEITCSSLQP DTIDAFIDLT HDASSESKNE GSEPVLAVEG MGCQVICIDE
1760 1770 1780 1790 1800
DTNKEGKMGR ANSPLESIVE ETCIDLTSES PGSCEIKRHN LKSEPPSKLD
1810 1820 1830 1840 1850
CLELPETLGN GHKKRKNSPG VSHSSQKKQR KDIDLSSEKT QRLSPNSDRN
1860 1870 1880 1890 1900
GDAHRKQASK KREPAVNETS LSSEASPEVK GSTAVLAASP ASLSAKNVIK
1910 1920 1930 1940 1950
KKGEIIVSWT RNDDREILLE CQKRMPSLKT FTYLAVKLNK NPNQVSERFQ
1960
QLKKLFEKSK CR
Length:1,962
Mass (Da):219,091
Last modified:July 27, 2011 - v2
Checksum:i7B3FC637BB98D9EF
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti152 – 1521T → A in AAD29045 (PubMed:10235259).Curated
Sequence conflicti1062 – 10621V → I in AAD29045 (PubMed:10235259).Curated
Sequence conflicti1766 – 17661E → K in BAB27860 (PubMed:16141072).Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF132726 mRNA. Translation: AAD29045.1.
AL805973 Genomic DNA. Translation: CAM26639.1.
BC138022 mRNA. Translation: AAI38023.1.
BC138041 mRNA. Translation: AAI38042.1.
AK011818 mRNA. Translation: BAB27860.1.
CCDSiCCDS18016.1.
RefSeqiNP_001116450.1. NM_001122978.2.
NP_036127.2. NM_011997.3.
UniGeneiMm.22279.

Genome annotation databases

EnsembliENSMUST00000029950; ENSMUSP00000029950; ENSMUSG00000028282.
ENSMUST00000178925; ENSMUSP00000136016; ENSMUSG00000028282.
GeneIDi26885.
KEGGimmu:26885.
UCSCiuc008sew.2. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF132726 mRNA. Translation: AAD29045.1.
AL805973 Genomic DNA. Translation: CAM26639.1.
BC138022 mRNA. Translation: AAI38023.1.
BC138041 mRNA. Translation: AAI38042.1.
AK011818 mRNA. Translation: BAB27860.1.
CCDSiCCDS18016.1.
RefSeqiNP_001116450.1. NM_001122978.2.
NP_036127.2. NM_011997.3.
UniGeneiMm.22279.

3D structure databases

ProteinModelPortaliQ9WUF3.
SMRiQ9WUF3. Positions 1896-1962.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi205038. 1 interaction.
IntActiQ9WUF3. 3 interactions.
MINTiMINT-91554.
STRINGi10090.ENSMUSP00000029950.

PTM databases

iPTMnetiQ9WUF3.
PhosphoSiteiQ9WUF3.

Proteomic databases

EPDiQ9WUF3.
MaxQBiQ9WUF3.
PaxDbiQ9WUF3.
PeptideAtlasiQ9WUF3.
PRIDEiQ9WUF3.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000029950; ENSMUSP00000029950; ENSMUSG00000028282.
ENSMUST00000178925; ENSMUSP00000136016; ENSMUSG00000028282.
GeneIDi26885.
KEGGimmu:26885.
UCSCiuc008sew.2. mouse.

Organism-specific databases

CTDi9994.
MGIiMGI:1349399. Casp8ap2.

Phylogenomic databases

eggNOGiENOG410IEBH. Eukaryota.
ENOG410YRSQ. LUCA.
GeneTreeiENSGT00620000088063.
HOGENOMiHOG000049238.
HOVERGENiHBG080371.
InParanoidiQ9WUF3.
OMAiKLHQVWE.
OrthoDBiEOG7J4460.
TreeFamiTF332487.

Miscellaneous databases

ChiTaRSiCasp8ap2. mouse.
PROiQ9WUF3.
SOURCEiSearch...

Gene expression databases

BgeeiQ9WUF3.
CleanExiMM_CASP8AP2.
ExpressionAtlasiQ9WUF3. baseline and differential.
GenevisibleiQ9WUF3. MM.

Family and domain databases

Gene3Di1.10.10.60. 1 hit.
InterProiIPR009057. Homeodomain-like.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "The CED-4-homologous protein FLASH is involved in Fas-mediated activation of caspase-8 during apoptosis."
    Imai Y., Kimura T., Murakami A., Yajima N., Sakamaki K., Yonehara S.
    Nature 398:777-785(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], IDENTIFICATION IN DISC COMPLEX WITH CASP8; FADD AND FAS, TISSUE SPECIFICITY.
    Tissue: T-cell lymphomaImported.
  2. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    Strain: C57BL/6J.
  3. "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: Brain.
  4. "The transcriptional landscape of the mammalian genome."
    Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.
    , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
    Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1766-1962.
    Strain: C57BL/6JImported.
    Tissue: EmbryoImported.
  5. Cited for: FUNCTION, INTERACTION WITH TRAF2.
  6. "Role of FLASH in caspase-8-mediated activation of NF-kappaB: dominant-negative function of FLASH mutant in NF-kappaB signaling pathway."
    Jun J.-I., Chung C.-W., Lee H.-J., Pyo J.-O., Lee K.N., Kim N.-S., Kim Y.S., Yoo H.-S., Lee T.-H., Kim E., Jung Y.-K.
    Oncogene 24:688-696(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  7. Cited for: SUBCELLULAR LOCATION.
  8. "FLASH links the CD95 signaling pathway to the cell nucleus and nuclear bodies."
    Milovic-Holm K., Krieghoff E., Jensen K., Will H., Hofmann T.G.
    EMBO J. 26:391-401(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH CASP8.
  9. "SIRT5-mediated lysine desuccinylation impacts diverse metabolic pathways."
    Park J., Chen Y., Tishkoff D.X., Peng C., Tan M., Dai L., Xie Z., Zhang Y., Zwaans B.M., Skinner M.E., Lombard D.B., Zhao Y.
    Mol. Cell 50:919-930(2013) [PubMed] [Europe PMC] [Abstract]
    Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-1323, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Embryonic fibroblast.

Entry informationi

Entry nameiC8AP2_MOUSE
AccessioniPrimary (citable) accession number: Q9WUF3
Secondary accession number(s): B1AX74, Q9CSW2
Entry historyi
Integrated into UniProtKB/Swiss-Prot: December 20, 2005
Last sequence update: July 27, 2011
Last modified: July 6, 2016
This is version 109 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot

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 one 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.