Q8K3W3 (CASC3_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Protein CASC3

Alternative name(s):
Cancer susceptibility candidate gene 3 protein homolog
Metastatic lymph node gene 51 protein homolog
Short name=MLN 51 homolog
Protein barentsz
Short name=Btz
Short name=mBtz

Gene names

Name:	Casc3
Synonyms:	Mln51

Organism

Mus musculus (Mouse)

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	698 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Component of a splicing-dependent multiprotein exon junction complex (EJC) deposited at splice junction on mRNAs. The EJC is a dynamic structure consisting of a few core proteins and several more peripheral nuclear and cytoplasmic associated factors that join the complex only transiently either during EJC assembly or during subsequent mRNA metabolism. Core components of the EJC, that remains bound to spliced mRNAs throughout all stages of mRNA metabolism, functions to mark the position of the exon-exon junction in the mature mRNA and thereby influences downstream processes of gene expression including mRNA splicing, nuclear mRNA export, subcellular mRNA localization, translation efficiency and nonsense-mediated mRNA decay (NMD). Stimulates the ATPase and RNA-helicase activities of EIF4A3. Plays a role in the stress response by participating in cytoplasmic stress granules assembly and by favouring cell recovery following stress. Binds spliced mRNA in sequence-independent manner, 20-24 nucleotides upstream of mRNA exon-exon junctions. Binds poly(G) and poly(U) RNA homopolymer. Component of the dendritic ribonucleoprotein particles (RNPs) in hippocampal neurons. May play a role in mRNA transport By similarity.
Subunit structure	Forms homooligomers. Part of the EJC core complex that contains CASC3, EIF4A3, MAGOH and RBM8A. Found in a mRNA splicing-dependent exon junction complex (EJC), at least composed of ACIN1, CASC3, EIF4A3, MAGOH, PNN, RBM8A, RNPS1, SAP18 and THOC4. Interacts with EIF4A3, MAGOH, NXF1 and RBM8A By similarity. Interacts with STAU1 in an RNA-dependent manner. Ref.2
Subcellular location	Cytoplasm › perinuclear region. Nucleus. Nucleus speckle By similarity. Note: Travels to the cytoplasm as part of the exon junction complex (EJC) bound to mRNA. Shuttles between the cytoplasm and the stress granules. More specifically found in nuclear intrachromatin granules clusters (IGC), also called nuclear speckles, which are storage compartments for nuclear proteins involved in mRNA processing. Colocalizes in nuclear speckles with MAGOH. Under stress condition, colocalizes with FMR1 and TIA1, but not MAGOH and RBM8A EJC core factors, in cytoplasmic stress granules, which contain stored mRNAs whose translation is stopped in response to stress By similarity. Predominantly found in the perinuclear region. Shuttles between the nucleus and the cytoplasm in a CRM1-dependent manner. Ref.2
Tissue specificity	High levels in heart, brain, including hippocampus and cerebellum, liver, kidney and testis; lower levels in muscle, lung and spleen. Ref.2
Domain	The coiled coil domain may be involved in oligomerization By similarity.
Post-translational modification	ADP-ribosylated by tankyrase TNKS and TNKS2. Poly-ADP-ribosylated protein is recognized by RNF146, followed by ubiquitination By similarity. Ubiquitinated by RNF146 when poly-ADP-ribosylated, leading to its degradation By similarity.
Sequence similarities	Belongs to the CASC3 family.
Sequence caution	The sequence AAH60672.1 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
Biological process	Nonsense-mediated mRNA decay Stress response Translation regulation Transport mRNA processing mRNA splicing mRNA transport
Cellular component	Cytoplasm Nucleus
Domain	Coiled coil
Ligand	RNA-binding
PTM	ADP-ribosylation Phosphoprotein Ubl conjugation
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	RNA splicing Inferred from electronic annotation. Source: UniProtKB-KW intracellular mRNA localization Inferred from direct assay Ref.2. Source: MGI mRNA processing Inferred from electronic annotation. Source: UniProtKB-KW mRNA transport Inferred from electronic annotation. Source: UniProtKB-KW nuclear-transcribed mRNA catabolic process, nonsense-mediated decay Inferred from electronic annotation. Source: UniProtKB-KW regulation of translation Inferred from electronic annotation. Source: UniProtKB-KW response to stress Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	nuclear speck Inferred from electronic annotation. Source: UniProtKB-SubCell perinuclear region of cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell ribonucleoprotein complex Inferred from direct assay Ref.2. Source: MGI
Molecular function	RNA binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 698	698	Protein CASC3		PRO_0000089325
Regions
	Region	134 – 280	147	Necessary for RNA-binding, interaction with MAGOH and localization in nucleus speckles By similarity
	Region	134 – 280	147	Sufficient to form the EJC By similarity
	Region	374 – 698	325	Necessary for localization in cytoplasmic stress granules By similarity
	Coiled coil	98 – 127	30	Potential
	Motif	201 – 207	7	Nuclear localization signal 1 Potential
	Motif	251 – 259	9	Nuclear localization signal 2 Potential
	Motif	457 – 466	10	Nuclear export signal
	Compositional bias	40 – 45	6	Poly-Gly
	Compositional bias	638 – 642	5	Poly-Pro
	Compositional bias	686 – 689	4	Poly-Pro
Amino acid modifications
	Modified residue	36	1	Phosphoserine By similarity
	Modified residue	44	1	Phosphoserine By similarity
	Modified residue	145	1	Phosphoserine Ref.9
	Modified residue	263	1	Phosphoserine Ref.7
	Modified residue	360	1	Phosphoserine Ref.8
	Modified residue	370	1	Phosphoserine By similarity
	Modified residue	472	1	Phosphoserine By similarity
Experimental info
	Mutagenesis	464	1	L → A: Accumulation in the nucleus. Ref.2
	Sequence conflict	297	1	N → D in BAE24081. Ref.3
	Sequence conflict	474	1	S → G in AAH34533. Ref.6
	Sequence conflict	589	1	L → V in BAE24081. Ref.3
	Sequence conflict	638	1	Missing in CAC27775. Ref.2
	Sequence conflict	638	1	Missing in AAH60672. Ref.6

Sequences

	Sequence		Length	Mass (Da)
	Q8K3W3 [UniParc]. Last modified July 7, 2009. Version 3. Checksum: 3B718FC297A5E0F3	FASTA	698	75,770
	10 20 30 40 50 60 MADRRRQRAS QDTEDEESGA SGSDSGSPAR GGGSCSGSVG GGGSGSLPSQ RGGRGGGLHL 70 80 90 100 110 120 RRVESGGAKS AEESECESED GMEGDAVLSD YESAEDSEGE EDYSEEENSK VELKSEANDA 130 140 150 160 170 180 ADSSAKEKGE EKPESKGTVT GERQSGDGQE STEPVENKVG KKGPKHLDDD EDRKNPAYIP 190 200 210 220 230 240 RKGLFFEHDL RGQTQEEEVR PKGRQRKLWK DEGRWEHDKF REDEQAPKSR QELIALYGYD 250 260 270 280 290 300 IRSAHNPDDI KPRRIRKPRF GSSPQRDPNW IGDRSSKSHR HQGPGGNLPP RTFINRNTAG 310 320 330 340 350 360 TGRMSASRNY SRSGGFKDGR TSFRPVEVAG QHGGRSAETL KHEASYRSRR LEQTPVRDPS 370 380 390 400 410 420 PEPDAPLLGS PEKEEVASET PAAVPDITPP APDRPIEKKS YSRARRTRTK VGDAVKAAEE 430 440 450 460 470 480 VPPPSEGLAS TATVPETTPA AKTGNWEAPV DSTTGGLEQD VAQLNIAEQS WSPSQPSFLQ 490 500 510 520 530 540 PRELRGVPNH IHMGAGPPPQ FNRMEEMGVQ SGRAKRYSSQ RQRPVPEPPA PPVHISIMEG 550 560 570 580 590 600 HYYDPLQFQG PIYTHGDSPA PLPPQGMIVQ PEMHLPHPGL HPHQSPGPLP NPGLYPPPVS 610 620 630 640 650 660 MSPGQPPPQQ LLAPTYFSAP GVMNFGNPNY PYAPGALPPP PPPHLYPNTQ APPQVYGGVT 670 680 690 YYNPAQQQVQ PKPSPPRRTP QPVSIKPPPP EVVSRGSS

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Metastatic lymph node 51, a novel nucleo-cytoplasmic protein overexpressed in breast cancer." Degot S.F., Regnier C.H., Wendling C., Chenard M.-P., Rio M.-C., Tomasetto C.L. Oncogene 21:4422-4434(2002) [PubMed: 12080473] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"Barentsz, a new component of the Staufen-containing ribonucleoprotein particles in mammalian cells, interacts with Staufen in an RNA-dependent manner." Macchi P., Kroening S., Palacios I.M., Baldassa S., Grunewald B., Ambrosino C., Goetze B., Lupas A., St Johnston D., Kiebler M. J. Neurosci. 23:5778-5788(2003) [PubMed: 12843282] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], INTERACTION WITH STAU1, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, MUTAGENESIS OF LEU-464. Strain: BALB/c.
[3]	"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: 16141072] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Strain: C57BL/6J. Tissue: Egg.
[4]	"Lineage-specific biology revealed by a finished genome assembly of the mouse." Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X., Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y., Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S. , Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R., Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K., Eichler E.E., Ponting C.P. PLoS Biol. 7:E1000112-E1000112(2009) [PubMed: 19468303] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: C57BL/6J.
[5]	Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	"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] OF 40-697. Strain: Czech II and FVB/N. Tissue: Brain, Kidney and Mammary tumor.
[7]	"Large-scale phosphorylation analysis of mouse liver." Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007) [PubMed: 17242355] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-263, MASS SPECTROMETRY. Tissue: Liver.
[8]	"Solid tumor proteome and phosphoproteome analysis by high resolution mass spectrometry." Zanivan S., Gnad F., Wickstroem S.A., Geiger T., Macek B., Cox J., Faessler R., Mann M. J. Proteome Res. 7:5314-5326(2008) [PubMed: 19367708] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-360, MASS SPECTROMETRY. Tissue: Melanoma.
[9]	"Large scale localization of protein phosphorylation by use of electron capture dissociation mass spectrometry." Sweet S.M., Bailey C.M., Cunningham D.L., Heath J.K., Cooper H.J. Mol. Cell. Proteomics 8:904-912(2009) [PubMed: 19131326] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-145, MASS SPECTROMETRY. Tissue: Embryonic fibroblast.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF526276 mRNA. Translation: AAM88396.1. AJ292072 mRNA. Translation: CAC27775.1. AK139608 mRNA. Translation: BAE24081.1. AL590963 Genomic DNA. Translation: CAM46181.1. CH466556 Genomic DNA. Translation: EDL16170.1. BC034533 mRNA. Translation: AAH34533.1. BC060672 mRNA. Translation: AAH60672.1. Different initiation. BC141296 mRNA. Translation: AAI41297.1.
IPI	IPI00877339.
RefSeq	NP_619601.2. NM_138660.2.
UniGene	Mm.40120.
3D structure databases
ProteinModelPortal	Q8K3W3.
SMR	Q8K3W3. Positions 165-245.
ModBase	Search...
Protein-protein interaction databases
STRING	Q8K3W3.
PTM databases
PhosphoSite	Q8K3W3.
Proteomic databases
PRIDE	Q8K3W3.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000017384; ENSMUSP00000017384; ENSMUSG00000078676. ENSMUST00000169695; ENSMUSP00000130926; ENSMUSG00000078676.
GeneID	192160.
KEGG	mmu:192160.
UCSC	uc007lhq.1. mouse.
Organism-specific databases
CTD	22794.
MGI	MGI:2179723. Casc3.
Phylogenomic databases
GeneTree	ENSGT00390000006930.
HOGENOM	HBG715340.
HOVERGEN	HBG050799.
InParanoid	Q8K3W3.
OMA	RSGGFKE.
OrthoDB	EOG4P5K9B.
PhylomeDB	Q8K3W3.
Gene expression databases
ArrayExpress	Q8K3W3.
Bgee	Q8K3W3.
CleanEx	MM_CASC3.
Genevestigator	Q8K3W3.
GermOnline	ENSMUSG00000052915. Mus musculus.
Family and domain databases
InterPro	IPR018545. Btz_dom. [Graphical view]
KO	K14323.
Pfam	PF09405. Btz. 1 hit. [Graphical view]
SMART	SM01044. Btz. 1 hit. [Graphical view]
ProtoNet	Search...
Other
SOURCE	Search...

Entry information

Entry name

CASC3_MOUSE

Accession

Primary (citable) accession number: Q8K3W3
Secondary accession number(s): A3KFP7 , Q3UT99, Q8K219, Q99NF0

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 13, 2004
Last sequence update:	July 7, 2009
Last modified:	January 25, 2012
This is version 79 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program