Q6S5J6 · KRIT1_MOUSE
- ProteinKrev interaction trapped protein 1
- GeneKrit1
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids736 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Component of the CCM signaling pathway which is a crucial regulator of heart and vessel formation and integrity. 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 (By similarity).
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).
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).
GO annotations
all annotations | all molecular function | virus receptor activity | dna binding | rna binding | cytoskeletal motor activity | catalytic activity | gtpase activity | structural molecule activity | transporter activity | cytoskeletal protein binding | lipid binding | cyclase activity | antioxidant activity | oxidoreductase activity | transferase activity | hydrolase activity | lyase activity | isomerase activity | ligase activity | protein tag activity | cargo receptor activity | histone binding | protein folding chaperone | translation regulator activity | nutrient reservoir activity | receptor ligand activity | molecular transducer activity | molecular adaptor activity | toxin activity | cell adhesion mediator activity | molecular function regulator activity | virus coreceptor activity | catalytic activity, acting on a protein | catalytic activity, acting on dna | catalytic activity, acting on rna | molecular carrier activity | transcription regulator activity | general transcription initiation factor activity | molecular sensor activity | molecular sequestering activity | atp-dependent activity | other molecular function | all biological process | mitotic cell cycle | cytokinesis | cytoplasmic translation | immune system process | muscle system process | circulatory system process | renal system process | respiratory system process | carbohydrate metabolic process | generation of precursor metabolites and energy | dna replication | dna repair | dna recombination | chromatin organization | dna-templated transcription | regulation of dna-templated transcription | trna metabolic process | protein folding | protein glycosylation | amino acid metabolic process | modified amino acid metabolic process | lipid metabolic process | vitamin metabolic process | sulfur compound metabolic process | intracellular protein transport | nucleocytoplasmic transport | autophagy | inflammatory response | mitochondrion organization | cytoskeleton organization | microtubule-based movement | peroxisome organization | lysosome organization | chromosome segregation | cell adhesion | establishment or maintenance of cell polarity | programmed cell death | photosynthesis | mrna metabolic process | snrna metabolic process | vesicle-mediated transport | reproductive process | digestive system process | signaling | cell differentiation | protein catabolic process | extracellular matrix organization | regulatory ncrna-mediated gene silencing | telomere organization | cell junction organization | wound healing | ribosome biogenesis | cilium organization | anatomical structure development | cell motility | nervous system process | endocrine process | protein maturation | transmembrane transport | nucleobase-containing small molecule metabolic process | hepaticobiliary system process | membrane organization | protein-containing complex assembly | cell wall organization or biogenesis | nitrogen cycle metabolic process | protein localization to plasma membrane | defense response to other organism | detoxification | meiotic nuclear division | mitotic nuclear division | mitochondrial gene expression | carbohydrate derivative metabolic process | other biological process | all cellular component | nuclear chromosome | extracellular region | extracellular space | cell wall | nucleus | nuclear envelope | nucleoplasm | chromosome | nucleolus | mitochondrion | lysosome | endosome | vacuole | peroxisome | endoplasmic reticulum | golgi apparatus | lipid droplet | microtubule organizing center | cytosol | ribosome | cytoskeleton | plasma membrane | cilium | plastid | thylakoid | external encapsulating structure | extracellular matrix | cytoplasmic vesicle | organelle | other cellular component | |||
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Aspect | Term | |
---|---|---|
Cellular Component | cell-cell junction | |
Cellular Component | cytoplasm | |
Cellular Component | cytoskeleton | |
Cellular Component | plasma membrane | |
Cellular Component | protein-containing complex | |
Molecular Function | GTPase regulator activity | |
Molecular Function | microtubule binding | |
Molecular Function | phosphatidylinositol-4,5-bisphosphate binding | |
Biological Process | angiogenesis | |
Biological Process | cell redox homeostasis | |
Biological Process | endothelium development | |
Biological Process | integrin activation | |
Biological Process | negative regulation of angiogenesis | |
Biological Process | negative regulation of endothelial cell apoptotic process | |
Biological Process | negative regulation of endothelial cell migration | |
Biological Process | negative regulation of endothelial cell proliferation | |
Biological Process | regulation of angiogenesis | |
Biological Process | regulation of establishment of cell polarity |
Keywords
- Biological process
Names & Taxonomy
Protein names
- Recommended nameKrev interaction trapped protein 1
- Short namesKrev interaction trapped 1
- Alternative names
Gene names
Organism names
- Organism
- Strains
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Mus > Mus
Accessions
- Primary accessionQ6S5J6
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Cell membrane ; Peripheral membrane protein
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 an ITGB1BP1-dependent manner (By similarity).
Keywords
- Cellular component
PTM/Processing
Features
Showing features for chain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000067024 | 1-736 | Krev interaction trapped protein 1 | |||
Sequence: MGNPENIEDAYVAVIRPKNTASLNSREYRAKSYEILLHEVPIEGQKKKRKKVLLETKLQSNSEIAQGILDYVVETTKPISPANQGIKGKRVVLMRKFPLDGEKTGREAALFIVPSVVKDNTKYAYTPGCPIFYCLQDIMRVCSESSTHFATLTARMLIALDKWLDERHAQSHFIPALFRPSPLERIKTNVINPAYAAELGQVDNSLHMGYSALEIKSKMLALEKADTCIYNPLFGSDLQYTNRVDKVVINPYFGLGAPDYSKIQIPKQEKWQRSMSSVVEDKERQWVDDFPLHRNACEGDSELLSHLLDKGLSVNQLDNDHWAPIHYACWYGKVEATRILLEKGKCNPNLLNGQLSSPLHFAAGGGHAEIVQILLTHPDIDRHITDQQGRSPLNVCEENKQNNWEEAAKLLKDAINKPYEKVRIYRMDGSYRSVELKHGNNTTAQQIMEGMRLSQETQRYFTIWICSENLSLQFKPYHKPLQQVHDWPEILAELTNLDPQRETPQLFLRRDVGLPLEVEKKIEDPLAILILFDEARYNLLKGFYTAPDAKLITLASLLLQIVYGNYESKKHKQGFLNEETLKSIVPITKLKSKAPHWINRILHEYKNLSLSEGVSKEMHHLQRMFLQNCWEIPTYGAAFFTGQIFTKASPSNHKVIPVYVGVNIKGLHLLNMETKALLISLKYCCFTWQLGDAGTCFQIHSMENKMSFIVHTKQAGLVVKLLMKLNGQLMPSERNS |
Proteomic databases
PTM databases
Expression
Tissue specificity
Expressed in heart, brain, spleen, lung, thymus, kidney and testis. Isoform 2 was more frequently expressed in the thymus than isoform 1.
Developmental stage
At stage 9.5 dpc ubiquitously expressed, at 12.5 dpc expressed in structures of the CNS, especially in zones of the proliferative active ventricular zones of the brain and in the spinal cord. Expression increased in organs that were in the state of organ expansion like lung and liver. At 17.5 dpc, expression was strongly reduced in endoderm-derived tissues. In early postnatal development, strongly expressed in regions of ossification.
Gene expression databases
Interaction
Subunit
Found in a complex, at least composed of ITGB1BP1, KRIT1 and RAP1A. Interacts (via C-terminus FERM domain) with RAP1A (active GTP-bound form preferentially); the interaction does not induce the opening conformation of KRIT1. Interacts (via N-terminus NPXY motif) with ITGB1BP1; the interaction induces the opening conformation of KRIT1 and competes with ITGB1 for ITGB1BP1 interaction. Associates (via N-terminus and C-terminus regions) with microtubules; the interaction is inhibited in presence of ITGB1BP1 and active GTP-bound RAP1A. Interacts (via FERM domain) with RAP1B. Interacts with CDH5. Interacts with RAP1A (By similarity).
Interacts with HEG1 and CCM2; greatly facilitates CCM2-binding to HEG1 (PubMed:19151727).
Interacts with HEG1 and CCM2; greatly facilitates CCM2-binding to HEG1 (PubMed:19151727).
Protein-protein interaction databases
Miscellaneous
Structure
Family & Domains
Features
Showing features for region, repeat, domain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 1-170 | N-terminal domain similar to Nudix hydrolase domain | ||||
Sequence: MGNPENIEDAYVAVIRPKNTASLNSREYRAKSYEILLHEVPIEGQKKKRKKVLLETKLQSNSEIAQGILDYVVETTKPISPANQGIKGKRVVLMRKFPLDGEKTGREAALFIVPSVVKDNTKYAYTPGCPIFYCLQDIMRVCSESSTHFATLTARMLIALDKWLDERHAQ | ||||||
Region | 172-195 | Interaction with ITGB1BP1 | ||||
Sequence: HFIPALFRPSPLERIKTNVINPAY | ||||||
Repeat | 287-316 | ANK 1 | ||||
Sequence: VDDFPLHRNACEGDSELLSHLLDKGLSVNQ | ||||||
Repeat | 320-350 | ANK 2 | ||||
Sequence: DHWAPIHYACWYGKVEATRILLEKGKCNPNL | ||||||
Repeat | 354-384 | ANK 3 | ||||
Sequence: QLSSPLHFAAGGGHAEIVQILLTHPDIDRHI | ||||||
Repeat | 388-419 | ANK 4 | ||||
Sequence: QGRSPLNVCEENKQNNWEEAAKLLKDAINKPY | ||||||
Domain | 420-736 | FERM | ||||
Sequence: EKVRIYRMDGSYRSVELKHGNNTTAQQIMEGMRLSQETQRYFTIWICSENLSLQFKPYHKPLQQVHDWPEILAELTNLDPQRETPQLFLRRDVGLPLEVEKKIEDPLAILILFDEARYNLLKGFYTAPDAKLITLASLLLQIVYGNYESKKHKQGFLNEETLKSIVPITKLKSKAPHWINRILHEYKNLSLSEGVSKEMHHLQRMFLQNCWEIPTYGAAFFTGQIFTKASPSNHKVIPVYVGVNIKGLHLLNMETKALLISLKYCCFTWQLGDAGTCFQIHSMENKMSFIVHTKQAGLVVKLLMKLNGQLMPSERNS | ||||||
Region | 430-452 | Interaction with RAP1B | ||||
Sequence: SYRSVELKHGNNTTAQQIMEGMR |
Domain
The FERM domain mediates binding to RAP1A and RAP1B and is necessary for binding to phosphatidylinositol 4,5-bisphosphate (PIP2).
The N-terminal domain has structural similarity to the nudix hydrolase domain, despite the absence of a nudix box and low sequence similarity with nudix hydrolase domains. The N-terminus and the C-terminus part associate together via the NPAY binding motif and adopt a lose conformation that is disrupted by ITGB1BP1, but not by RAP1A.
Contains 4 ANK repeats that precede the FERM domain.
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence & Isoforms
- Sequence statusComplete
This entry describes 4 isoforms produced by Alternative splicing.
Q6S5J6-1
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.
- Name1
- SynonymsKrit1A
- Length736
- Mass (Da)83,982
- Last updated2004-07-05 v1
- Checksum441333F62A1D208A
Q6S5J6-2
- Name2
- SynonymsKrit1B
- Differences from canonical
- 676-714: Missing
Q6S5J6-3
- Name3
- Differences from canonical
- 295-300: Missing
Q6S5J6-4
- Name4
- Differences from canonical
- 330-736: Missing
Computationally mapped potential isoform sequences
There are 2 potential isoforms mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
A0A0G2JGG7 | A0A0G2JGG7_MOUSE | Krit1 | 647 | ||
A0A0G2JE71 | A0A0G2JE71_MOUSE | Krit1 | 132 |
Features
Showing features for sequence conflict, alternative sequence.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Sequence conflict | 47 | in Ref. 2; AAG18456 | ||||
Sequence: K → E | ||||||
Alternative sequence | VSP_015801 | 295-300 | in isoform 3 | |||
Sequence: Missing | ||||||
Sequence conflict | 319 | in Ref. 2; AAG18456 | ||||
Sequence: N → D | ||||||
Alternative sequence | VSP_015802 | 330-736 | in isoform 4 | |||
Sequence: Missing | ||||||
Sequence conflict | 515 | in Ref. 1; AAG47775 | ||||
Sequence: P → R | ||||||
Sequence conflict | 550-552 | in Ref. 1; AAG47775 | ||||
Sequence: KLI → RLD | ||||||
Sequence conflict | 665 | in Ref. 1; AAG47775 | ||||
Sequence: K → R | ||||||
Alternative sequence | VSP_015803 | 676-714 | in isoform 2 | |||
Sequence: Missing | ||||||
Sequence conflict | 684-689 | in Ref. 1; AAG47775 | ||||
Sequence: CCFTWQ → WLLTWA |
Keywords
- Coding sequence diversity
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AF310134 EMBL· GenBank· DDBJ | AAG47775.1 EMBL· GenBank· DDBJ | mRNA | ||
AF306509 EMBL· GenBank· DDBJ | AAG18456.1 EMBL· GenBank· DDBJ | mRNA | ||
AY328895 EMBL· GenBank· DDBJ | AAQ92980.1 EMBL· GenBank· DDBJ | mRNA | ||
AY464945 EMBL· GenBank· DDBJ | AAR24089.1 EMBL· GenBank· DDBJ | mRNA | ||
BC054819 EMBL· GenBank· DDBJ | AAH54819.1 EMBL· GenBank· DDBJ | mRNA | ||
AK041574 EMBL· GenBank· DDBJ | BAC30991.1 EMBL· GenBank· DDBJ | mRNA |