Q8K2Y9 (CCM2_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Malcavernin

Alternative name(s):
Cerebral cavernous malformations protein 2 homolog
Osmosensing scaffold for MEKK3

Gene names

Name:	Ccm2
Synonyms:	Osm

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	453 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Component of the CCM signaling pathway which is a crucial regulator of heart and vessel formation and integrity. May act through the stabilization of endothelial cell junctions. May also function as a scaffold protein for MAP2K3-MAP3K3 signaling. Seems to play a major role in the modulation of MAP3K3-dependent p38 activation induced by hyperosmotic shock. Ref.1 Ref.5
Subunit structure	Part of a complex with MAP2K3, MAP3K3 and RAC1. Binds RAC1 directly and independently of its nucleotide-bound state. Interacts with PDCD10 By similarity. Interacts with HEG1 and KRIT1; KRIT1 greatly facilitates the interaction with HEG1. Ref.1 Ref.5
Subcellular location	Cytoplasm. Note: Treatment with sorbitol caused relocalization to ruffle-like structures. Ref.1
Tissue specificity	Highly expressed in heart, lower expression in kidney, lung and liver (at protein level). Ref.1
Developmental stage	Expressed primarily in the developing neural tube at 10.5 dpc. Ref.5
Domain	The C-terminal region constitutes an independently folded domain that has structural similarity with the USH1C (harmonin) N-terminus, despite very low sequence similarity By similarity.
Sequence similarities	Belongs to the CCM2 family. Contains 1 PID domain.

Ontologies

Keywords
Cellular component	Cytoplasm
Coding sequence diversity	Alternative splicing
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	blood vessel endothelial cell differentiation Inferred from mutant phenotype Ref.5. Source: MGI cell-cell junction organization Inferred from mutant phenotype Ref.5. Source: MGI endothelial cell development Inferred from mutant phenotype Ref.5. Source: MGI endothelial tube morphogenesis Inferred from sequence orthology Ref.5. Source: MGI in utero embryonic development Inferred from mutant phenotype Ref.5. Source: MGI inner ear development Inferred from direct assay PubMed 21795542. Source: MGI multicellular organism growth Inferred from mutant phenotype Ref.5. Source: MGI pericardium development Inferred from mutant phenotype Ref.5. Source: MGI vasculogenesis Inferred from genetic interaction Ref.5. Source: MGI venous blood vessel morphogenesis Inferred from mutant phenotype Ref.5. Source: MGI
Cellular_component	cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell protein complex Inferred from direct assay Ref.5. Source: MGI
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q8K2Y9-1)

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: Q8K2Y9-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-10: MEEEGKKGKK → MENE
     279-287: Missing.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 453	453	Malcavernin		PRO_0000089425
Regions
	Domain	59 – 248	190	PID
	Region	292 – 385	94	Harmonin homology domain
Amino acid modifications
	Modified residue	393	1	Phosphoserine By similarity
Natural variations
	Alternative sequence	1 – 10	10	MEEEGKKGKK → MENE in isoform 2.		VSP_024404
	Alternative sequence	279 – 287	9	Missing in isoform 2.		VSP_024405

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified October 1, 2002. Version 1. Checksum: 51F165291E52691F	FASTA	453	49,917
	10 20 30 40 50 60 MEEEGKKGKK PGIVSPFKRV FLKGEKSRDK KAHEKVTERR PLHTVVLALP ERVEPDRLLS 70 80 90 100 110 120 DYIEKEVKYL GQLTSIPGYL NPSSRTEILH FIDKAKRSHQ LPGHLTQEHD AVLSLSAYNV 130 140 150 160 170 180 KLAWRDGEDI ILRVPIHDIA AVSYVRDDAA HLVVLKTAQD PGISPSQSLC AESSRGLSAG 190 200 210 220 230 240 SLSESAVGPV EACCLVIMAT ESKVAAEELC SLLSQVFQIV YTESTIDFLD RAIFDGASTP 250 260 270 280 290 300 THHLSLHSDD SSTKVDMKDS YDADASTFCF PDSGDVGGLP PLPFCMQTSP HSKTVSESEL 310 320 330 340 350 360 STSATELLQD YMLTLRTKLS SQEIQQFAAL LHEYRNGASI HEFCISLRQL YGDSRKFLLL 370 380 390 400 410 420 GLRPFIPEKD SQHFENFLET IGVKDGRGII TDSFGRHRRA LSTTSTSTIN GNRTTGSPDD 430 440 450 RSAPSEGDEW DRMISDISSD IEALGCSMDQ DSA
	Isoform 2 [UniParc]. Checksum: ADD5A5CA486B38D5	FASTA	438	48,248
	10 20 30 40 50 60 MENEPGIVSP FKRVFLKGEK SRDKKAHEKV TERRPLHTVV LALPERVEPD RLLSDYIEKE 70 80 90 100 110 120 VKYLGQLTSI PGYLNPSSRT EILHFIDKAK RSHQLPGHLT QEHDAVLSLS AYNVKLAWRD 130 140 150 160 170 180 GEDIILRVPI HDIAAVSYVR DDAAHLVVLK TAQDPGISPS QSLCAESSRG LSAGSLSESA 190 200 210 220 230 240 VGPVEACCLV IMATESKVAA EELCSLLSQV FQIVYTESTI DFLDRAIFDG ASTPTHHLSL 250 260 270 280 290 300 HSDDSSTKVD MKDSYDADAS TFCFPDSGDV GGTSPHSKTV SESELSTSAT ELLQDYMLTL 310 320 330 340 350 360 RTKLSSQEIQ QFAALLHEYR NGASIHEFCI SLRQLYGDSR KFLLLGLRPF IPEKDSQHFE 370 380 390 400 410 420 NFLETIGVKD GRGIITDSFG RHRRALSTTS TSTINGNRTT GSPDDRSAPS EGDEWDRMIS 430 DISSDIEALG CSMDQDSA

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Rac-MEKK3-MKK3 scaffolding for p38 MAPK activation during hyperosmotic shock." Uhlik M.T., Abell A.N., Johnson N.L., Sun W., Cuevas B.D., Lobel-Rice K.E., Horne E.A., Dell'Acqua M.L., Johnson G.L. Nat. Cell Biol. 5:1104-1110(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, INTERACTION WITH MAP3K3; MAP2K3 AND RAC1. Strain: C57BL/6. Tissue: T-cell lymphoma.
[2]	"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] (ISOFORM 1). Strain: NOD. Tissue: Dendritic cell.
[3]	"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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], ALTERNATIVE SPLICING (ISOFORMS 1 AND 2). Strain: C57BL/6J.
[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] (ISOFORM 1). Strain: FVB/N. Tissue: Mammary tumor.
[5]	"Regulation of cardiovascular development and integrity by the heart of glass-cerebral cavernous malformation protein pathway." Kleaveland B., Zheng X., Liu J.J., Blum Y., Tung J.J., Zou Z., Sweeney S.M., Chen M., Guo L., Lu M.M., Zhou D., Kitajewski J., Affolter M., Ginsberg M.H., Kahn M.L. Nat. Med. 15:169-176(2009) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH HEG1 AND KRIT1, DEVELOPMENTAL STAGE.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AY442689 mRNA. Translation: AAR29082.1. AK155145 mRNA. Translation: BAE33075.1. AL603787, AL646047 Genomic DNA. Translation: CAI24218.1. AL603787, AL646047 Genomic DNA. Translation: CAI24220.1. AL646047, AL603787 Genomic DNA. Translation: CAI25990.1. AL646047, AL603787 Genomic DNA. Translation: CAI25992.1. BC029157 mRNA. Translation: AAH29157.1.
IPI	IPI00170037. IPI00649501.
RefSeq	NP_666126.1. NM_146014.3.
UniGene	Mm.221271.
3D structure databases
ProteinModelPortal	Q8K2Y9.
SMR	Q8K2Y9. Positions 63-220, 308-384.
ModBase	Search...
PTM databases
PhosphoSite	Q8K2Y9.
Proteomic databases
PaxDb	Q8K2Y9.
PRIDE	Q8K2Y9.
Protocols and materials databases
DNASU	216527.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000000388; ENSMUSP00000000388; ENSMUSG00000000378.
GeneID	216527.
KEGG	mmu:216527.
UCSC	uc007hyv.2. mouse.
Organism-specific databases
CTD	83605.
MGI	MGI:2384924. Ccm2.
Phylogenomic databases
eggNOG	NOG39125.
GeneTree	ENSGT00390000016168.
HOGENOM	HOG000231916.
HOVERGEN	HBG054451.
InParanoid	Q8K2Y9.
OMA	AVSYIRD.
OrthoDB	EOG4RFKSP.
Gene expression databases
ArrayExpress	Q8K2Y9.
Bgee	Q8K2Y9.
CleanEx	MM_CCM2. MM_OSM.
Genevestigator	Q8K2Y9.
GermOnline	ENSMUSG00000000378. Mus musculus.
Family and domain databases
Gene3D	2.30.29.30. 1 hit.
InterPro	IPR026159. Malcavernin. IPR011993. PH_like_dom. IPR006020. PTyr_interaction_dom. [Graphical view]
PANTHER	PTHR21642. PTHR21642. 1 hit.
PROSITE	PS01179. PID. 1 hit. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	CCM2. mouse.
NextBio	375194.
SOURCE	Search...

Entry information

Entry name

CCM2_MOUSE

Accession

Primary (citable) accession number: Q8K2Y9
Secondary accession number(s): Q5SUA3

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 11, 2005
Last sequence update:	October 1, 2002
Last modified:	May 1, 2013
This is version 84 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program