CPLM 1.0 - Compendium of Protein Lysine Modification
TagContent
CPLM ID CPLM-000099
UniProt Accession
Genbank Protein ID
Genbank Nucleotide ID
Protein Name
 Krev interaction trapped protein 1 
Protein Synonyms/Alias
 Krev interaction trapped 1; Cerebral cavernous malformations 1 protein 
Gene Name
 KRIT1 
Gene Synonyms/Alias
 CCM1 
Created Date
 July 27, 2013 
Organism
 Homo sapiens (Human) 
NCBI Taxa ID
 9606 
Lysine Modification
Position
Peptide
Type
References
122SVVKDNTKYTYTPGCubiquitination[1]
262LGAPDYSKIQIPKQEubiquitination[1]
400LNICEENKQNNWEEAubiquitination[1]
Reference
 [1] Refined preparation and use of anti-diglycine remnant (K-ε-GG) antibody enables routine quantification of 10,000s of ubiquitination sites in single proteomics experiments.
 Udeshi ND, Svinkina T, Mertins P, Kuhn E, Mani DR, Qiao JW, Carr SA.
 Mol Cell Proteomics. 2013 Mar;12(3):825-31. [PMID: 23266961] 
Functional Description
 Component of the CCM signaling pathway which is a crucial regulator of heart and vessel formation and integrity (By similarity). Negative regulator of angiogenesis. Inhibits endothelial proliferation, apoptosis, migration, lumen formation and sprouting angiogenesis in primary endothelial cells. Promotes AKT phosphorylation in a NOTCH-dependent and independent manner, and inhibits EKR1/2 phosphorylation indirectly through activation of the DELTA-NOTCH cascade. Acts in concert with CDH5 to establish and maintain correct endothelial cell polarity and vascular lumen and these effects are mediated by recruitment and activation of the Par polarity complex and RAP1B. Required for the localization of phosphorylated PRKCZ, PARD3, TIAM1 and RAP1B to the cell junction, and cell junction stabilization. Plays a role in integrin signaling via its interaction with ITGB1BP1; this prevents the interaction between ITGB1 and ITGB1BP1. Microtubule- associated protein that binds to phosphatidylinositol 4,5- bisphosphate (PIP2)-containing membranes in a GTP-bound RAP1- dependent manner. Plays an important role in the maintenance of the intracellular reactive oxygen species (ROS) homeostasis to prevent oxidative cellular damage. Regulates the homeostasis of intracellular ROS through an antioxidant pathway involving FOXO1 and SOD2. Facilitates the down-regulation of cyclin-D1 (CCND1) levels required for cell transition from proliferative growth to quiescence by preventing the accumulation of intracellular ROS through the modulation of FOXO1 and SOD2 levels. 
Sequence Annotation
 REPEAT 287 316 ANK 1.
 REPEAT 320 350 ANK 2.
 REPEAT 354 383 ANK 3.
 REPEAT 388 419 ANK 4.
 DOMAIN 420 734 FERM.
 REGION 1 170 N-terminal domain similar to Nudix
 REGION 172 195 Interaction with ITGB1BP1.
 REGION 430 452 Interaction with RAP1B.  
Keyword
 3D-structure; Alternative splicing; Angiogenesis; ANK repeat; Cell junction; Cell membrane; Complete proteome; Cytoplasm; Cytoskeleton; Disease mutation; Membrane; Reference proteome; Repeat. 
Sequence Source
 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 
Protein Length
 736 AA 
Protein Sequence
MGNPENIEDA YVAVIRPKNT ASLNSREYRA KSYEILLHEV PIEGQKKKRK KVLLETKLQG 60
NSEITQGILD YVVETTKPIS PANQGIRGKR VVLMKKFPLD GEKMGREASL FIVPSVVKDN 120
TKYTYTPGCP IFYCLQDIMR VCSESSTHFA TLTARMLIAL DKWLDERHAQ SHFIPALFRP 180
SPLERIKTNV INPAYATESG QTENSLHMGY SALEIKSKML ALEKADTCIY NPLFGSDLQY 240
TNRVDKVVIN PYFGLGAPDY SKIQIPKQEK WQRSMSSVTE DKERQWVDDF PLHRSACEGD 300
SELLSRLLSE RFSVNQLDSD HWAPIHYACW YGKVEATRIL LEKGKCNPNL LNGQLSSPLH 360
FAAGGGHAEI VQILLNHPET DRHITDQQGR SPLNICEENK QNNWEEAAKL LKEAINKPYE 420
KVRIYRMDGS YRSVELKHGN NTTVQQIMEG MRLSQETQQY FTIWICSENL SLQLKPYHKP 480
LQHVRDWPEI LAELTNLDPQ RETPQLFLRR DVRLPLEVEK QIEDPLAILI LFDEARYNLL 540
KGFYTAPDAK LITLASLLLQ IVYGNYESKK HKQGFLNEEN LKSIVPVTKL KSKAPHWTNR 600
ILHEYKNLST SEGVSKEMHH LQRMFLQNCW EIPTYGAAFF TGQIFTKASP SNHKVIPVYV 660
GVNIKGLHLL NMETKALLIS LKYGCFMWQL GDTDTCFQIH SMENKMSFIV HTKQAGLVVK 720
LLMKLNGQLM PTERNS 736 
Gene Ontology
 GO:0005911; C:cell-cell junction; IDA:UniProtKB.
 GO:0005737; C:cytoplasm; IEA:UniProtKB-KW.
 GO:0005874; C:microtubule; IDA:UniProtKB.
 GO:0005886; C:plasma membrane; IDA:UniProtKB.
 GO:0008017; F:microtubule binding; IDA:UniProtKB.
 GO:0005546; F:phosphatidylinositol-4,5-bisphosphate binding; IDA:UniProtKB.
 GO:0032403; F:protein complex binding; IDA:UniProtKB.
 GO:0005083; F:small GTPase regulator activity; TAS:ProtInc.
 GO:0001525; P:angiogenesis; IEA:UniProtKB-KW.
 GO:0045454; P:cell redox homeostasis; IMP:UniProtKB.
 GO:0016525; P:negative regulation of angiogenesis; IMP:UniProtKB.
 GO:2000352; P:negative regulation of endothelial cell apoptotic process; IMP:UniProtKB.
 GO:0010596; P:negative regulation of endothelial cell migration; IMP:UniProtKB.
 GO:0001937; P:negative regulation of endothelial cell proliferation; IMP:UniProtKB.
 GO:0032092; P:positive regulation of protein binding; IEA:Compara.
 GO:2000114; P:regulation of establishment of cell polarity; IMP:UniProtKB.
 GO:0007264; P:small GTPase mediated signal transduction; TAS:ProtInc. 
Interpro
 IPR002110; Ankyrin_rpt.
 IPR020683; Ankyrin_rpt-contain_dom.
 IPR019749; Band_41_domain.
 IPR014352; FERM/acyl-CoA-bd_prot_3-hlx.
 IPR019748; FERM_central.
 IPR000299; FERM_domain. 
Pfam
 PF00023; Ank
 PF12796; Ank_2
 PF00373; FERM_M 
SMART
 SM00248; ANK
 SM00295; B41 
PROSITE
 PS50297; ANK_REP_REGION
 PS50088; ANK_REPEAT
 PS00660; FERM_1
 PS00661; FERM_2
 PS50057; FERM_3 
PRINTS