CCM2_HUMAN
ID CCM2_HUMAN Reviewed; 444 AA.
AC Q9BSQ5; A4D2L4; B3KUV0; D3DVL4; E9PDJ3; F5H0E1; F5H551; Q71RE5; Q8TAT4;
DT 11-OCT-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2001, sequence version 1.
DT 03-AUG-2022, entry version 166.
DE RecName: Full=Cerebral cavernous malformations 2 protein;
DE AltName: Full=Malcavernin {ECO:0000303|PubMed:12853948};
GN Name=CCM2; Synonyms=C7orf22; ORFNames=PP10187;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Thymus;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RX PubMed=15498874; DOI=10.1073/pnas.0404089101;
RA Wan D., Gong Y., Qin W., Zhang P., Li J., Wei L., Zhou X., Li H., Qiu X.,
RA Zhong F., He L., Yu J., Yao G., Jiang H., Qian L., Yu Y., Shu H., Chen X.,
RA Xu H., Guo M., Pan Z., Chen Y., Ge C., Yang S., Gu J.;
RT "Large-scale cDNA transfection screening for genes related to cancer
RT development and progression.";
RL Proc. Natl. Acad. Sci. U.S.A. 101:15724-15729(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=12853948; DOI=10.1038/nature01782;
RA Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H.,
RA Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K.,
RA Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A.,
RA Delehaunty K.D., Miner T.L., Nash W.E., Cordes M., Du H., Sun H.,
RA Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A.,
RA Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P.,
RA Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M.,
RA Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S.,
RA Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R.,
RA Strowmatt C., Latreille P., Miller N., Johnson D., Murray J.,
RA Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W.,
RA Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A.,
RA Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E.,
RA Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E.,
RA Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A.,
RA Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A.,
RA Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R.,
RA McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H.,
RA Wilson R.K.;
RT "The DNA sequence of human chromosome 7.";
RL Nature 424:157-164(2003).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=12690205; DOI=10.1126/science.1083423;
RA Scherer S.W., Cheung J., MacDonald J.R., Osborne L.R., Nakabayashi K.,
RA Herbrick J.-A., Carson A.R., Parker-Katiraee L., Skaug J., Khaja R.,
RA Zhang J., Hudek A.K., Li M., Haddad M., Duggan G.E., Fernandez B.A.,
RA Kanematsu E., Gentles S., Christopoulos C.C., Choufani S., Kwasnicka D.,
RA Zheng X.H., Lai Z., Nusskern D.R., Zhang Q., Gu Z., Lu F., Zeesman S.,
RA Nowaczyk M.J., Teshima I., Chitayat D., Shuman C., Weksberg R.,
RA Zackai E.H., Grebe T.A., Cox S.R., Kirkpatrick S.J., Rahman N.,
RA Friedman J.M., Heng H.H.Q., Pelicci P.G., Lo-Coco F., Belloni E.,
RA Shaffer L.G., Pober B., Morton C.C., Gusella J.F., Bruns G.A.P., Korf B.R.,
RA Quade B.J., Ligon A.H., Ferguson H., Higgins A.W., Leach N.T.,
RA Herrick S.R., Lemyre E., Farra C.G., Kim H.-G., Summers A.M., Gripp K.W.,
RA Roberts W., Szatmari P., Winsor E.J.T., Grzeschik K.-H., Teebi A.,
RA Minassian B.A., Kere J., Armengol L., Pujana M.A., Estivill X.,
RA Wilson M.D., Koop B.F., Tosi S., Moore G.E., Boright A.P., Zlotorynski E.,
RA Kerem B., Kroisel P.M., Petek E., Oscier D.G., Mould S.J., Doehner H.,
RA Doehner K., Rommens J.M., Vincent J.B., Venter J.C., Li P.W., Mural R.J.,
RA Adams M.D., Tsui L.-C.;
RT "Human chromosome 7: DNA sequence and biology.";
RL Science 300:767-772(2003).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain, and Kidney;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [7]
RP INVOLVEMENT IN CCM2.
RX PubMed=14624391; DOI=10.1086/380314;
RA Liquori C.L., Berg M.J., Siegel A.M., Huang E., Zawistowski J.S.,
RA Stoffer T., Verlaan D., Balogun F., Hughes L., Leedom T.P., Plummer N.W.,
RA Cannella M., Maglione V., Squitieri F., Johnson E.W., Rouleau G.A.,
RA Ptacek L., Marchuk D.A.;
RT "Mutations in a gene encoding a novel protein containing a phosphotyrosine-
RT binding domain cause type 2 cerebral cavernous malformations.";
RL Am. J. Hum. Genet. 73:1459-1464(2003).
RN [8]
RP INTERACTION WITH PDCD10.
RX PubMed=20489202; DOI=10.1074/jbc.m110.128470;
RA Li X., Zhang R., Zhang H., He Y., Ji W., Min W., Boggon T.J.;
RT "Crystal structure of CCM3, a cerebral cavernous malformation protein
RT critical for vascular integrity.";
RL J. Biol. Chem. 285:24099-24107(2010).
RN [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-15, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-164, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [11]
RP X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 283-379, PARTIAL PROTEIN SEQUENCE,
RP DOMAIN, AND INTERACTION WITH PDCD10.
RX PubMed=23266514; DOI=10.1016/j.febslet.2012.12.011;
RA Fisher O.S., Zhang R., Li X., Murphy J.W., Demeler B., Boggon T.J.;
RT "Structural studies of cerebral cavernous malformations 2 (CCM2) reveal a
RT folded helical domain at its C-terminus.";
RL FEBS Lett. 587:272-277(2013).
RN [12]
RP VARIANT CCM2 ARG-198, AND VARIANTS ILE-53 AND ILE-120.
RX PubMed=14740320; DOI=10.1086/381718;
RA Denier C., Goutagny S., Labauge P., Krivosic V., Arnoult M., Cousin A.,
RA Benabid A.L., Comoy J., Frerebeau P., Gilbert B., Houtteville J.P., Jan M.,
RA Lapierre F., Loiseau H., Menei P., Mercier P., Moreau J.J.,
RA Nivelon-Chevallier A., Parker F., Redondo A.M., Scarabin J.M.,
RA Tremoulet M., Zerah M., Maciazek J., Tournier-Lasserve E.;
RT "Mutations within the MGC4607 gene cause cerebral cavernous
RT malformations.";
RL Am. J. Hum. Genet. 74:326-337(2004).
RN [13]
RP VARIANTS CCM2 HIS-215 AND GLN-229.
RX PubMed=22415356; DOI=10.1007/s12031-012-9741-5;
RA Mosca L., Pileggi S., Avemaria F., Tarlarini C., Cigoli M.S., Capra V.,
RA De Marco P., Pavanello M., Marocchi A., Penco S.;
RT "De Novo MGC4607 gene heterozygous missense variants in a child with
RT multiple cerebral cavernous malformations.";
RL J. Mol. Neurosci. 47:475-480(2012).
CC -!- FUNCTION: Component of the CCM signaling pathway which is a crucial
CC regulator of heart and vessel formation and integrity. May act through
CC the stabilization of endothelial cell junctions (By similarity). May
CC function as a scaffold protein for MAP2K3-MAP3K3 signaling. Seems to
CC play a major role in the modulation of MAP3K3-dependent p38 activation
CC induced by hyperosmotic shock (By similarity). {ECO:0000250}.
CC -!- SUBUNIT: Part of a complex with MAP2K3, MAP3K3 and RAC1. Binds RAC1
CC directly and independently of its nucleotide-bound state (By
CC similarity). Interacts with HEG1 and KRIT1; KRIT1 greatly facilitates
CC the interaction with HEG1 (By similarity). Interacts with PDCD10.
CC {ECO:0000250, ECO:0000269|PubMed:20489202,
CC ECO:0000269|PubMed:23266514}.
CC -!- INTERACTION:
CC Q9BSQ5; Q8TEW6: DOK4; NbExp=3; IntAct=EBI-1573056, EBI-6918542;
CC Q9BSQ5; P31273: HOXC8; NbExp=3; IntAct=EBI-1573056, EBI-1752118;
CC Q9BSQ5; O00522: KRIT1; NbExp=15; IntAct=EBI-1573056, EBI-1573121;
CC Q9BSQ5; Q9BUL8: PDCD10; NbExp=5; IntAct=EBI-1573056, EBI-740195;
CC Q9BSQ5; Q13671: RIN1; NbExp=3; IntAct=EBI-1573056, EBI-366017;
CC Q9BSQ5; Q9H1K6: TLNRD1; NbExp=3; IntAct=EBI-1573056, EBI-12344941;
CC Q9BSQ5; Q8WVJ9: TWIST2; NbExp=3; IntAct=EBI-1573056, EBI-1797313;
CC Q9BSQ5; Q96N03: VSTM2L; NbExp=3; IntAct=EBI-1573056, EBI-948213;
CC Q9BSQ5-1; O00522: KRIT1; NbExp=2; IntAct=EBI-16157769, EBI-1573121;
CC Q9BSQ5-1; Q99759: MAP3K3; NbExp=6; IntAct=EBI-16157769, EBI-307281;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=1;
CC IsoId=Q9BSQ5-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9BSQ5-2; Sequence=VSP_024402;
CC Name=3;
CC IsoId=Q9BSQ5-3; Sequence=VSP_046696;
CC Name=4;
CC IsoId=Q9BSQ5-4; Sequence=VSP_046695;
CC -!- DOMAIN: The C-terminal region constitutes an independently folded
CC domain that has structural similarity with the USH1C (harmonin) N-
CC terminus, despite very low sequence similarity.
CC {ECO:0000269|PubMed:23266514}.
CC -!- DISEASE: Cerebral cavernous malformations 2 (CCM2) [MIM:603284]: A form
CC of cerebral cavernous malformations, a congenital vascular anomaly of
CC the central nervous system that can result in hemorrhagic stroke,
CC seizures, recurrent headaches, and focal neurologic deficits. The
CC lesions are characterized by grossly enlarged blood vessels consisting
CC of a single layer of endothelium and without any intervening neural
CC tissue, ranging in diameter from a few millimeters to several
CC centimeters. CCM2 inheritance is autosomal dominant.
CC {ECO:0000269|PubMed:14624391, ECO:0000269|PubMed:14740320,
CC ECO:0000269|PubMed:22415356}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the CCM2 family. {ECO:0000305}.
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DR EMBL; AK098005; BAG53562.1; -; mRNA.
DR EMBL; AF370392; AAQ15228.1; -; mRNA.
DR EMBL; AC004847; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC013416; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH236960; EAL23746.1; -; Genomic_DNA.
DR EMBL; CH471128; EAW61061.1; -; Genomic_DNA.
DR EMBL; CH471128; EAW61064.1; -; Genomic_DNA.
DR EMBL; BC004903; AAH04903.1; -; mRNA.
DR EMBL; BC008859; AAH08859.1; -; mRNA.
DR EMBL; BC016832; AAH16832.1; -; mRNA.
DR EMBL; BC025958; AAH25958.1; -; mRNA.
DR CCDS; CCDS34630.1; -. [Q9BSQ5-2]
DR CCDS; CCDS5500.1; -. [Q9BSQ5-1]
DR CCDS; CCDS55108.1; -. [Q9BSQ5-3]
DR CCDS; CCDS55109.1; -. [Q9BSQ5-4]
DR RefSeq; NP_001025006.1; NM_001029835.2. [Q9BSQ5-2]
DR RefSeq; NP_001161406.1; NM_001167934.1. [Q9BSQ5-4]
DR RefSeq; NP_001161407.1; NM_001167935.1. [Q9BSQ5-3]
DR RefSeq; NP_113631.1; NM_031443.3. [Q9BSQ5-1]
DR PDB; 4FQN; X-ray; 1.90 A; A/B/C/D=283-379.
DR PDB; 4TVQ; X-ray; 2.80 A; E=224-239.
DR PDB; 4WJ7; X-ray; 2.75 A; A/B/C/D=51-228.
DR PDB; 4Y5O; X-ray; 2.35 A; A=283-379.
DR PDB; 4YKC; X-ray; 2.70 A; A=290-444.
DR PDB; 4YKD; X-ray; 1.93 A; A=290-376.
DR PDB; 4YL6; X-ray; 2.10 A; A=290-376.
DR PDBsum; 4FQN; -.
DR PDBsum; 4TVQ; -.
DR PDBsum; 4WJ7; -.
DR PDBsum; 4Y5O; -.
DR PDBsum; 4YKC; -.
DR PDBsum; 4YKD; -.
DR PDBsum; 4YL6; -.
DR AlphaFoldDB; Q9BSQ5; -.
DR SMR; Q9BSQ5; -.
DR BioGRID; 123696; 38.
DR ComplexPortal; CPX-984; CCM endothelial permeability complex.
DR CORUM; Q9BSQ5; -.
DR DIP; DIP-40609N; -.
DR IntAct; Q9BSQ5; 18.
DR MINT; Q9BSQ5; -.
DR STRING; 9606.ENSP00000370503; -.
DR GlyGen; Q9BSQ5; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q9BSQ5; -.
DR PhosphoSitePlus; Q9BSQ5; -.
DR BioMuta; CCM2; -.
DR DMDM; 74733042; -.
DR EPD; Q9BSQ5; -.
DR jPOST; Q9BSQ5; -.
DR MassIVE; Q9BSQ5; -.
DR MaxQB; Q9BSQ5; -.
DR PaxDb; Q9BSQ5; -.
DR PeptideAtlas; Q9BSQ5; -.
DR PRIDE; Q9BSQ5; -.
DR ProteomicsDB; 19677; -.
DR ProteomicsDB; 25314; -.
DR ProteomicsDB; 26772; -.
DR ProteomicsDB; 78919; -. [Q9BSQ5-1]
DR ProteomicsDB; 78920; -. [Q9BSQ5-2]
DR Antibodypedia; 13519; 346 antibodies from 30 providers.
DR DNASU; 83605; -.
DR Ensembl; ENST00000258781.11; ENSP00000258781.7; ENSG00000136280.17. [Q9BSQ5-1]
DR Ensembl; ENST00000381112.7; ENSP00000370503.3; ENSG00000136280.17. [Q9BSQ5-2]
DR Ensembl; ENST00000541586.5; ENSP00000444725.1; ENSG00000136280.17. [Q9BSQ5-4]
DR Ensembl; ENST00000544363.5; ENSP00000438035.1; ENSG00000136280.17. [Q9BSQ5-3]
DR GeneID; 83605; -.
DR KEGG; hsa:83605; -.
DR MANE-Select; ENST00000258781.11; ENSP00000258781.7; NM_031443.4; NP_113631.1.
DR UCSC; uc003tmo.4; human. [Q9BSQ5-1]
DR CTD; 83605; -.
DR DisGeNET; 83605; -.
DR GeneCards; CCM2; -.
DR GeneReviews; CCM2; -.
DR HGNC; HGNC:21708; CCM2.
DR HPA; ENSG00000136280; Low tissue specificity.
DR MalaCards; CCM2; -.
DR MIM; 603284; phenotype.
DR MIM; 607929; gene.
DR neXtProt; NX_Q9BSQ5; -.
DR OpenTargets; ENSG00000136280; -.
DR Orphanet; 221061; Familial cerebral cavernous malformation.
DR PharmGKB; PA26145; -.
DR VEuPathDB; HostDB:ENSG00000136280; -.
DR eggNOG; ENOG502QSZM; Eukaryota.
DR GeneTree; ENSGT00390000016168; -.
DR InParanoid; Q9BSQ5; -.
DR OMA; EPYETET; -.
DR OrthoDB; 1446057at2759; -.
DR PhylomeDB; Q9BSQ5; -.
DR TreeFam; TF328517; -.
DR PathwayCommons; Q9BSQ5; -.
DR SignaLink; Q9BSQ5; -.
DR SIGNOR; Q9BSQ5; -.
DR BioGRID-ORCS; 83605; 23 hits in 1081 CRISPR screens.
DR ChiTaRS; CCM2; human.
DR GeneWiki; CCM2; -.
DR GenomeRNAi; 83605; -.
DR Pharos; Q9BSQ5; Tbio.
DR PRO; PR:Q9BSQ5; -.
DR Proteomes; UP000005640; Chromosome 7.
DR RNAct; Q9BSQ5; protein.
DR Bgee; ENSG00000136280; Expressed in putamen and 170 other tissues.
DR ExpressionAtlas; Q9BSQ5; baseline and differential.
DR Genevisible; Q9BSQ5; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005739; C:mitochondrion; IDA:HPA.
DR GO; GO:0032991; C:protein-containing complex; IEA:Ensembl.
DR GO; GO:0060837; P:blood vessel endothelial cell differentiation; IEA:Ensembl.
DR GO; GO:0045216; P:cell-cell junction organization; IEA:Ensembl.
DR GO; GO:0001885; P:endothelial cell development; IEA:Ensembl.
DR GO; GO:0061154; P:endothelial tube morphogenesis; IMP:MGI.
DR GO; GO:0003158; P:endothelium development; IC:ComplexPortal.
DR GO; GO:0007507; P:heart development; IBA:GO_Central.
DR GO; GO:0001701; P:in utero embryonic development; IEA:Ensembl.
DR GO; GO:0048839; P:inner ear development; IEA:Ensembl.
DR GO; GO:0007229; P:integrin-mediated signaling pathway; TAS:UniProtKB.
DR GO; GO:0035264; P:multicellular organism growth; IEA:Ensembl.
DR GO; GO:0060039; P:pericardium development; IEA:Ensembl.
DR GO; GO:0045765; P:regulation of angiogenesis; IC:ComplexPortal.
DR GO; GO:0051403; P:stress-activated MAPK cascade; TAS:UniProtKB.
DR GO; GO:0001570; P:vasculogenesis; IMP:UniProtKB.
DR GO; GO:0048845; P:venous blood vessel morphogenesis; IEA:Ensembl.
DR CDD; cd13516; HHD_CCM2; 1.
DR DisProt; DP02978; -.
DR Gene3D; 2.30.29.30; -; 1.
DR InterPro; IPR032375; CCM2_C.
DR InterPro; IPR026159; Malcavernin.
DR InterPro; IPR011993; PH-like_dom_sf.
DR InterPro; IPR006020; PTB/PI_dom.
DR PANTHER; PTHR21642; PTHR21642; 1.
DR Pfam; PF16545; CCM2_C; 1.
DR PROSITE; PS01179; PID; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Cytoplasm; Developmental protein;
KW Direct protein sequencing; Disease variant; Phosphoprotein;
KW Reference proteome.
FT CHAIN 1..444
FT /note="Cerebral cavernous malformations 2 protein"
FT /id="PRO_0000089424"
FT DOMAIN 59..248
FT /note="PID"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00148"
FT REGION 1..37
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 283..376
FT /note="Harmonin homology domain"
FT REGION 391..423
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 21..37
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 391..412
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 15
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 164
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 384
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8K2Y9"
FT MOD_RES 393
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8K2Y9"
FT MOD_RES 394
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q8K2Y9"
FT MOD_RES 396
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8K2Y9"
FT MOD_RES 399
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q8K2Y9"
FT VAR_SEQ 1..10
FT /note="MEEEGKKGKK -> MHSSCRQRRNQNLSKEIPQTEFHTGYSMENE (in
FT isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_024402"
FT VAR_SEQ 11..68
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000305"
FT /id="VSP_046695"
FT VAR_SEQ 158..248
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000305"
FT /id="VSP_046696"
FT VARIANT 53
FT /note="V -> I (in dbSNP:rs2107732)"
FT /evidence="ECO:0000269|PubMed:14740320"
FT /id="VAR_023575"
FT VARIANT 120
FT /note="V -> I (in dbSNP:rs11552377)"
FT /evidence="ECO:0000269|PubMed:14740320"
FT /id="VAR_023576"
FT VARIANT 198
FT /note="L -> R (in CCM2; dbSNP:rs137852843)"
FT /evidence="ECO:0000269|PubMed:14740320"
FT /id="VAR_023577"
FT VARIANT 215
FT /note="Q -> H (in CCM2; associated with Q-229)"
FT /evidence="ECO:0000269|PubMed:22415356"
FT /id="VAR_067352"
FT VARIANT 229
FT /note="L -> Q (in CCM2; associated with H-215)"
FT /evidence="ECO:0000269|PubMed:22415356"
FT /id="VAR_067353"
FT VARIANT 289
FT /note="S -> N (in dbSNP:rs2289366)"
FT /id="VAR_050768"
FT CONFLICT 268
FT /note="F -> C (in Ref. 1; BAG53562)"
FT /evidence="ECO:0000305"
FT CONFLICT 440
FT /note="D -> A (in Ref. 2; AAQ15228)"
FT /evidence="ECO:0000305"
FT CONFLICT 444
FT /note="A -> ALWTVDGGAPTPSAQLS (in Ref. 2; AAQ15228)"
FT /evidence="ECO:0000305"
FT TURN 57..60
FT /evidence="ECO:0007829|PDB:4WJ7"
FT STRAND 63..76
FT /evidence="ECO:0007829|PDB:4WJ7"
FT HELIX 85..97
FT /evidence="ECO:0007829|PDB:4WJ7"
FT STRAND 110..115
FT /evidence="ECO:0007829|PDB:4WJ7"
FT STRAND 117..127
FT /evidence="ECO:0007829|PDB:4WJ7"
FT STRAND 130..135
FT /evidence="ECO:0007829|PDB:4WJ7"
FT HELIX 136..138
FT /evidence="ECO:0007829|PDB:4WJ7"
FT STRAND 139..146
FT /evidence="ECO:0007829|PDB:4WJ7"
FT STRAND 151..157
FT /evidence="ECO:0007829|PDB:4WJ7"
FT STRAND 193..202
FT /evidence="ECO:0007829|PDB:4WJ7"
FT HELIX 203..219
FT /evidence="ECO:0007829|PDB:4WJ7"
FT HELIX 225..238
FT /evidence="ECO:0007829|PDB:4TVQ"
FT HELIX 288..291
FT /evidence="ECO:0007829|PDB:4FQN"
FT HELIX 293..306
FT /evidence="ECO:0007829|PDB:4FQN"
FT TURN 307..309
FT /evidence="ECO:0007829|PDB:4FQN"
FT HELIX 312..326
FT /evidence="ECO:0007829|PDB:4FQN"
FT HELIX 331..342
FT /evidence="ECO:0007829|PDB:4FQN"
FT HELIX 344..356
FT /evidence="ECO:0007829|PDB:4FQN"
FT HELIX 359..371
FT /evidence="ECO:0007829|PDB:4FQN"
FT TURN 373..375
FT /evidence="ECO:0007829|PDB:4YL6"
FT HELIX 422..435
FT /evidence="ECO:0007829|PDB:4YKC"
SQ SEQUENCE 444 AA; 48837 MW; 43F9C153B4DE460E CRC64;
MEEEGKKGKK PGIVSPFKRV FLKGEKSRDK KAHEKVTERR PLHTVVLSLP ERVEPDRLLS
DYIEKEVKYL GQLTSIPGYL NPSSRTEILH FIDNAKRAHQ LPGHLTQEHD AVLSLSAYNV
KLAWRDGEDI ILRVPIHDIA AVSYVRDDAA HLVVLKTAQD PGISPSQSLC AESSRGLSAG
SLSESAVGPV EACCLVILAA ESKVAAEELC CLLGQVFQVV YTESTIDFLD RAIFDGASTP
THHLSLHSDD SSTKVDIKET YEVEASTFCF PESVDVGGAS PHSKTISESE LSASATELLQ
DYMLTLRTKL SSQEIQQFAA LLHEYRNGAS IHEFCINLRQ LYGDSRKFLL LGLRPFIPEK
DSQHFENFLE TIGVKDGRGI ITDSFGRHRR ALSTTSSSTT NGNRATGSSD DRSAPSEGDE
WDRMISDISS DIEALGCSMD QDSA
