KRIT1
entrez
889
canonical
uniprot
O00522
canonical
ensembl
ENSG00000001631
resolver
ensp
ENSP00000344668
resolver
ensp
ENSP00000378011
resolver
ensp
ENSP00000378013
resolver
ensp
ENSP00000378015
resolver
ensp
ENSP00000388076
resolver
ensp
ENSP00000391675
resolver
ensp
ENSP00000404790
resolver
ensp
ENSP00000410909
resolver
ensp
ENSP00000508543
resolver
ensp
ENSP00000508564
resolver
ensp
ENSP00000509139
resolver
ensp
ENSP00000509209
resolver
ensp
ENSP00000509514
resolver
ensp
ENSP00000509617
resolver
ensp
ENSP00000509832
resolver
ensp
ENSP00000510015
resolver
ensp
ENSP00000510733
resolver
ensp
ENSP00000575099
resolver
ensp
ENSP00000637317
resolver
genesymbol
KRIT1
resolver
genesymbol_syn
CCM1
resolver
hgnc
HGNC:1573
resolver
uniprot
A4D1F7
resolver
uniprot
A6NNU0
resolver
uniprot
O43894
resolver
uniprot
Q506L6
resolver
uniprot
Q6U276
resolver
uniprot
Q75N19
resolver
uniprot
Q9H180
resolver
uniprot
Q9H264
resolver
uniprot
Q9HAX5
resolver
uniprot_entry
A4D1F7_HUMAN
resolver
uniprot_entry
KRIT1_HUMAN
resolver
uniprot_sec
A6NNU0
resolver
uniprot_sec
O43894
resolver
uniprot_sec
Q506L6
resolver
uniprot_sec
Q6U276
resolver
uniprot_sec
Q75N19
resolver
uniprot_sec
Q9H180
resolver
uniprot_sec
Q9H264
resolver
uniprot_sec
Q9HAX5
resolver
amino_acid_sequence
MGNPENIEDAYVAVIRPKNTASLNSREYRAKSYEILLHEVPIEGQKKKRKKVLLETKLQGNSEITQGILDYVVETTKPISPANQGIRGKRVVLMKKFPLDGEKMGREASLFIVPSVVKDNTKYTYTPGCPIFYCLQDIMRVCSESSTHFATLTARMLIALDKWLDERHAQSHFIPALFRPSPLERIKTNVINPAYATESGQTENSLHMGYSALEIKSKMLALEKADTCIYNPLFGSDLQYTNRVDKVVINPYFGLGAPDYSKIQIPKQEKWQRSMSSVTEDKERQWVDDFPLHRSACEGDSELLSRLLSERFSVNQLDSDHWAPIHYACWYGKVEATRILLEKGKCNPNLLNGQLSSPLHFAAGGGHAEIVQILLNHPETDRHITDQQGRSPLNICEENKQNNWEEAAKLLKEAINKPYEKVRIYRMDGSYRSVELKHGNNTTVQQIMEGMRLSQETQQYFTIWICSENLSLQLKPYHKPLQHVRDWPEILAELTNLDPQRETPQLFLRRDVRLPLEVEKQIEDPLAILILFDEARYNLLKGFYTAPDAKLITLASLLLQIVYGNYESKKHKQGFLNEENLKSIVPVTKLKSKAPHWTNRILHEYKNLSTSEGVSKEMHHLQRMFLQNCWEIPTYGAAFFTGQIFTKASPSNHKVIPVYVGVNIKGLHLLNMETKALLISLKYGCFMWQLGDTDTCFQIHSMENKMSFIVHTKQAGLVVKLLMKLNGQLMPTERNS
uniprot
proteins
disease_involvement
DISEASE: Cerebral cavernous malformations 1 (CCM1) [MIM:116860]: A form of cerebral cavernous malformations, a congenital vascular anomaly of the central nervous system that can result in hemorrhagic stroke, seizures, recurrent headaches, and focal neurologic deficits. The lesions are characterized by grossly enlarged blood vessels consisting of a single layer of endothelium and without any intervening neural tissue, ranging in diameter from a few millimeters to several centimeters. CCM1 inheritance is autosomal dominant. {ECO:0000269|PubMed:12172908}. Note=The disease is caused by variants affecting the gene represented in this entry.
uniprot
proteins
function
FUNCTION: 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 ERK1/2 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. May play a role in the regulation of macroautophagy through the down-regulation of the mTOR pathway (PubMed:26417067). {ECO:0000250|UniProtKB:Q6S5J6, ECO:0000269|PubMed:11741838, ECO:0000269|PubMed:17916086, ECO:0000269|PubMed:20332120, ECO:0000269|PubMed:20616044, ECO:0000269|PubMed:20668652, ECO:0000269|PubMed:21633110, ECO:0000269|PubMed:23317506, ECO:0000269|PubMed:26417067}.
uniprot
proteins
mass_dalton
84348
uniprot
proteins
mutagenesis
MUTAGEN 47..50; /note="KKRK->AAAA: Reduces interaction with microtubules, but not with ITGB1BP1."; /evidence="ECO:0000269|PubMed:17916086"; MUTAGEN 176; /note="A->D: Strongly reduces ITGB1BP1 binding; when associated with D-182."; /evidence="ECO:0000269|PubMed:23317506"; MUTAGEN 179; /note="R->A: Strongly reduces ITGB1BP1 binding; when associated with A-179."; /evidence="ECO:0000269|PubMed:23317506"; MUTAGEN 182; /note="P->D: Strongly reduces ITGB1BP1 binding; when associated with D-176."; /evidence="ECO:0000269|PubMed:23317506"; MUTAGEN 185; /note="R->A: Strongly reduces ITGB1BP1 binding; when associated with A-179."; /evidence="ECO:0000269|PubMed:23317506"; MUTAGEN 192..195; /note="NPAY->APAA: Reduces interaction with ITGB1BP1."; /evidence="ECO:0000269|PubMed:17916086"; MUTAGEN 192; /note="N->A: Reduces ITGB1BP1 binding; when associated with A-195."; /evidence="ECO:0000269|PubMed:11741838, ECO:0000269|PubMed:11854171, ECO:0000269|PubMed:23317506"; MUTAGEN 195; /note="Y->A: Reduces ITGB1BP1 binding; when associated with A-192."; /evidence="ECO:0000269|PubMed:11741838, ECO:0000269|PubMed:11854171, ECO:0000269|PubMed:23317506"; MUTAGEN 430; /note="S->E: Impairs interaction with RAP1B."; /evidence="ECO:0000269|PubMed:22577140"; MUTAGEN 432; /note="R->E: Impairs interaction with RAP1B."; /evidence="ECO:0000269|PubMed:22577140"; MUTAGEN 452; /note="R->E: 40-fold-reduced affinity for Rap1A."; /evidence="ECO:0000269|PubMed:21633110, ECO:0000269|PubMed:22577140"; MUTAGEN 452; /note="R->E: Impairs interaction with RAP1B."; /evidence="ECO:0000269|PubMed:21633110, ECO:0000269|PubMed:22577140"; MUTAGEN 717; /note="L->A: Strongly reduced affinity for HEG1; when associated with A-721."; /evidence="ECO:0000269|PubMed:23007647"; MUTAGEN 721; /note="L->A: Strongly reduced affinity for HEG1; when associated with A-717."; /evidence="ECO:0000269|PubMed:23007647
uniprot
proteins
pubmed
11161791
uniprot
proteins
pubmed
11161805
uniprot
proteins
pubmed
11342228
uniprot
proteins
pubmed
11741838
uniprot
proteins
pubmed
11854171
uniprot
proteins
pubmed
12172908
uniprot
proteins
pubmed
12853948
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
17916086
uniprot
proteins
pubmed
20332120
uniprot
proteins
pubmed
20616044
uniprot
proteins
pubmed
20668652
uniprot
proteins
pubmed
21633110
uniprot
proteins
pubmed
22577140
uniprot
proteins
pubmed
23007647
uniprot
proteins
pubmed
23317506
uniprot
proteins
pubmed
26417067
uniprot
proteins
pubmed
26458359
uniprot
proteins
pubmed
9285558
uniprot
proteins
sequence_length
736
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton. Cell membrane; Peripheral membrane protein. Cell junction. Note=KRIT1 and CDH5 reciprocally regulate their localization to endothelial cell-cell junctions. Association with RAP1 relocalizes KRIT1 from microtubules to cell junction membranes. Translocates from the cytoplasm along microtubules to the cell membrane in a ITGB1BP1-dependent manner.
uniprot
proteins