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Protein

Cerebral cavernous malformations protein 2 homolog

Gene

Ccm2

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

Functioni

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.2 Publications

GO - Biological processi

  • blood vessel development Source: MGI
  • blood vessel endothelial cell differentiation Source: MGI
  • cell-cell junction organization Source: MGI
  • endothelial cell development Source: MGI
  • endothelial tube morphogenesis Source: MGI
  • heart development Source: MGI
  • inner ear development Source: MGI
  • in utero embryonic development Source: MGI
  • multicellular organism growth Source: MGI
  • pericardium development Source: MGI
  • vasculature development Source: MGI
  • vasculogenesis Source: MGI
  • venous blood vessel morphogenesis Source: MGI
Complete GO annotation...

Names & Taxonomyi

Protein namesi
Recommended name:
Cerebral cavernous malformations protein 2 homolog
Alternative name(s):
MalcaverninBy similarity
Osmosensing scaffold for MEKK31 Publication
Gene namesi
Name:Ccm2
Synonyms:Osm
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 11

Organism-specific databases

MGIiMGI:2384924. Ccm2.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: MGI
  • protein complex Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 453453Cerebral cavernous malformations protein 2 homologPRO_0000089425Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei15 – 151PhosphoserineBy similarity
Modified residuei164 – 1641PhosphoserineBy similarity
Modified residuei393 – 3931PhosphoserineCombined sources
Modified residuei402 – 4021PhosphoserineCombined sources
Modified residuei403 – 4031PhosphothreonineCombined sources
Modified residuei405 – 4051PhosphoserineCombined sources
Modified residuei408 – 4081PhosphothreonineCombined sources

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiQ8K2Y9.
MaxQBiQ8K2Y9.
PaxDbiQ8K2Y9.
PRIDEiQ8K2Y9.

PTM databases

iPTMnetiQ8K2Y9.
PhosphoSiteiQ8K2Y9.

Expressioni

Tissue specificityi

Highly expressed in heart, lower expression in kidney, lung and liver (at protein level).1 Publication

Developmental stagei

Expressed primarily in the developing neural tube at 10.5 dpc.1 Publication

Gene expression databases

BgeeiQ8K2Y9.
CleanExiMM_CCM2.
MM_OSM.
ExpressionAtlasiQ8K2Y9. baseline and differential.
GenevisibleiQ8K2Y9. MM.

Interactioni

Subunit structurei

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.By similarity2 Publications

Protein-protein interaction databases

BioGridi229755. 1 interaction.
STRINGi10090.ENSMUSP00000000388.

Structurei

3D structure databases

ProteinModelPortaliQ8K2Y9.
SMRiQ8K2Y9. Positions 55-221, 299-445.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini59 – 248190PIDPROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni292 – 38594Harmonin homology domainAdd
BLAST

Domaini

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 similaritiesi

Belongs to the CCM2 family.Curated
Contains 1 PID domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiENOG410IHRT. Eukaryota.
ENOG410ZBNR. LUCA.
GeneTreeiENSGT00390000016168.
HOGENOMiHOG000231916.
HOVERGENiHBG054451.
InParanoidiQ8K2Y9.
OMAiCSMDRDS.
OrthoDBiEOG7SFHXM.
PhylomeDBiQ8K2Y9.
TreeFamiTF328517.

Family and domain databases

Gene3Di2.30.29.30. 1 hit.
InterProiIPR032375. CCM2_C.
IPR026159. Malcavernin.
IPR011993. PH_dom-like.
IPR006020. PTB/PI_dom.
[Graphical view]
PANTHERiPTHR21642:SF4. PTHR21642:SF4. 1 hit.
PfamiPF16545. CCM2_C. 1 hit.
[Graphical view]
PROSITEiPS01179. PID. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q8K2Y9-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MEEEGKKGKK PGIVSPFKRV FLKGEKSRDK KAHEKVTERR PLHTVVLALP
60 70 80 90 100
ERVEPDRLLS DYIEKEVKYL GQLTSIPGYL NPSSRTEILH FIDKAKRSHQ
110 120 130 140 150
LPGHLTQEHD AVLSLSAYNV KLAWRDGEDI ILRVPIHDIA AVSYVRDDAA
160 170 180 190 200
HLVVLKTAQD PGISPSQSLC AESSRGLSAG SLSESAVGPV EACCLVIMAT
210 220 230 240 250
ESKVAAEELC SLLSQVFQIV YTESTIDFLD RAIFDGASTP THHLSLHSDD
260 270 280 290 300
SSTKVDMKDS YDADASTFCF PDSGDVGGLP PLPFCMQTSP HSKTVSESEL
310 320 330 340 350
STSATELLQD YMLTLRTKLS SQEIQQFAAL LHEYRNGASI HEFCISLRQL
360 370 380 390 400
YGDSRKFLLL GLRPFIPEKD SQHFENFLET IGVKDGRGII TDSFGRHRRA
410 420 430 440 450
LSTTSTSTIN GNRTTGSPDD RSAPSEGDEW DRMISDISSD IEALGCSMDQ

DSA
Length:453
Mass (Da):49,917
Last modified:October 1, 2002 - v1
Checksum:i51F165291E52691F
GO
Isoform 2 (identifier: Q8K2Y9-2) [UniParc]FASTAAdd to basket

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

Show »
Length:438
Mass (Da):48,248
Checksum:iADD5A5CA486B38D5
GO

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 1010MEEEGKKGKK → MENE in isoform 2. CuratedVSP_024404
Alternative sequencei279 – 2879Missing in isoform 2. CuratedVSP_024405

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS24422.1. [Q8K2Y9-1]
RefSeqiNP_666126.1. NM_146014.3. [Q8K2Y9-1]
UniGeneiMm.221271.

Genome annotation databases

EnsembliENSMUST00000000388; ENSMUSP00000000388; ENSMUSG00000000378. [Q8K2Y9-1]
GeneIDi216527.
KEGGimmu:216527.
UCSCiuc007hyv.2. mouse. [Q8K2Y9-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS24422.1. [Q8K2Y9-1]
RefSeqiNP_666126.1. NM_146014.3. [Q8K2Y9-1]
UniGeneiMm.221271.

3D structure databases

ProteinModelPortaliQ8K2Y9.
SMRiQ8K2Y9. Positions 55-221, 299-445.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi229755. 1 interaction.
STRINGi10090.ENSMUSP00000000388.

PTM databases

iPTMnetiQ8K2Y9.
PhosphoSiteiQ8K2Y9.

Proteomic databases

EPDiQ8K2Y9.
MaxQBiQ8K2Y9.
PaxDbiQ8K2Y9.
PRIDEiQ8K2Y9.

Protocols and materials databases

DNASUi216527.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000000388; ENSMUSP00000000388; ENSMUSG00000000378. [Q8K2Y9-1]
GeneIDi216527.
KEGGimmu:216527.
UCSCiuc007hyv.2. mouse. [Q8K2Y9-1]

Organism-specific databases

CTDi83605.
MGIiMGI:2384924. Ccm2.

Phylogenomic databases

eggNOGiENOG410IHRT. Eukaryota.
ENOG410ZBNR. LUCA.
GeneTreeiENSGT00390000016168.
HOGENOMiHOG000231916.
HOVERGENiHBG054451.
InParanoidiQ8K2Y9.
OMAiCSMDRDS.
OrthoDBiEOG7SFHXM.
PhylomeDBiQ8K2Y9.
TreeFamiTF328517.

Miscellaneous databases

ChiTaRSiCcm2. mouse.
PROiQ8K2Y9.
SOURCEiSearch...

Gene expression databases

BgeeiQ8K2Y9.
CleanExiMM_CCM2.
MM_OSM.
ExpressionAtlasiQ8K2Y9. baseline and differential.
GenevisibleiQ8K2Y9. MM.

Family and domain databases

Gene3Di2.30.29.30. 1 hit.
InterProiIPR032375. CCM2_C.
IPR026159. Malcavernin.
IPR011993. PH_dom-like.
IPR006020. PTB/PI_dom.
[Graphical view]
PANTHERiPTHR21642:SF4. PTHR21642:SF4. 1 hit.
PfamiPF16545. CCM2_C. 1 hit.
[Graphical view]
PROSITEiPS01179. PID. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, INTERACTION WITH MAP3K3; MAP2K3 AND RAC1.
    Strain: C57BL/6J.
    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. 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. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Liver.
  6. "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.
  7. Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-393; SER-402; THR-403; SER-405 AND THR-408, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Brown adipose tissue, Kidney, Lung and Spleen.

Entry informationi

Entry nameiCCM2_MOUSE
AccessioniPrimary (citable) accession number: Q8K2Y9
Secondary accession number(s): Q5SUA3
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 11, 2005
Last sequence update: October 1, 2002
Last modified: July 6, 2016
This is version 112 of the entry and version 1 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
  2. SIMILARITY comments
    Index of protein domains and families

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.