Protein:KRIT1 |
Protein Summary |
 Gene summary |
| Gene name: KRIT1 | ASpdb.0 ID: 889 | Gene | Gene symbol | KRIT1 | Gene ID | 889 |
| Gene name | KRIT1 ankyrin repeat containing |
| Synonyms | CAM|CCM1 |
| Cytomap | 7q21.2 |
| Type of gene | protein-coding |
| Description | krev interaction trapped protein 1ankyrin repeat-containing protein Krit1cerebral cavernous malformations 1 proteinkrev interaction trapped 1 |
| Modification date | 20240305 |
| UniProtAcc | O00522 |
| Gene ontology of this gene with evidence of Inferred from Direct Assay (IDA) from Entrez |
| Partner | Gene | GO ID | GO term | PubMed ID |
| Gene | KRIT1 | GO:0005546 | phosphatidylinositol-4,5-bisphosphate binding | 17916086 |
| Gene | KRIT1 | GO:0005886 | plasma membrane | 17916086 |
| Gene | KRIT1 | GO:0005911 | cell-cell junction | 20332120|23007647 |
| Gene | KRIT1 | GO:0008017 | microtubule binding | 17916086 |
| Gene | KRIT1 | GO:0033622 | integrin activation | 23317506 |
AS Summary |
| Information of the canonical protein with experimentally identified structure from PDB (2023). |
| UniProt Acc | File name | PDB ID | Method | Resolution | Chain | Start | End |
| O00522-1 | O00522-1_5d68_B.pdb | 5D68 | X-ray | 2.91 | B | 288 | 736 |
| ASpdb's canonical and alternatively spliced isoform information. |
| accession_id | gene_name | canonical_id | alternative_id | canonical_length | alternative_length | canonical_start | canonical_end | type | originalSEQ | variationSEQ | alternative_start | alternative_end |
| O00522 | KRIT1 | O00522-1 | O00522-2 | 736 | 529 | 1 | 207 | Deletion | none | none | 0 | 0 |
| O00522 | KRIT1 | O00522-1 | O00522-3 | 736 | 688 | 283 | 330 | Deletion | none | none | 282 | 282 |
| Multiple sequence alignment of our canonical and alternatively spliced KRIT1 |
| Matched gene isoform IDs with Ensembl and RefSeq of our canonical and alternative spliced genes of KRIT1 |
| UniProt-id | ENSG | ENST | ENSP |
| O00522-1 | ENSG00000001631.17 | ENST00000340022.6 | ENSP00000344668.2 |
| O00522-1 | ENSG00000001631.17 | ENST00000394505.7 | ENSP00000378013.2 |
| O00522-1 | ENSG00000001631.17 | ENST00000394507.5 | ENSP00000378015.1 |
| O00522-1 | ENSG00000001631.17 | ENST00000412043.6 | ENSP00000410909.2 |
| O00522-1 | ENSG00000001631.17 | ENST00000425073.2 | ENSP00000404790.2 |
| O00522-1 | ENSG00000001631.17 | ENST00000444960.6 | ENSP00000388076.2 |
| O00522-1 | ENSG00000001631.17 | ENST00000458177.7 | ENSP00000391675.2 |
| O00522-1 | ENSG00000001631.17 | ENST00000686094.1 | ENSP00000510015.1 |
| O00522-1 | ENSG00000001631.17 | ENST00000686527.1 | ENSP00000509139.1 |
| O00522-1 | ENSG00000001631.17 | ENST00000687135.1 | ENSP00000509617.1 |
| O00522-1 | ENSG00000001631.17 | ENST00000688404.1 | ENSP00000509939.1 |
| O00522-1 | ENSG00000001631.17 | ENST00000688665.1 | ENSP00000509209.1 |
| O00522-1 | ENSG00000001631.17 | ENST00000690529.1 | ENSP00000510733.1 |
| O00522-1 | ENSG00000001631.17 | ENST00000690720.1 | ENSP00000509832.1 |
| O00522-1 | ENSG00000001631.17 | ENST00000692157.1 | ENSP00000509514.1 |
| O00522-1 | ENSG00000001631.17 | ENST00000692807.1 | ENSP00000508564.1 |
| O00522-3 | ENSG00000001631.17 | ENST00000394503.6 | ENSP00000378011.2 |
| O00522-3 | ENSG00000001631.17 | ENST00000689556.1 | ENSP00000508543.1 |
| O00522-3 | ENSG00000001631.17 | ENST00000690908.1 | ENSP00000510110.1 |
| UniProt-id | NM ID | NP ID |
| O00522-1 | NM_004912.3 | NP_004903.2 |
| O00522-1 | NM_194454.1 | NP_919436.1 |
| O00522-1 | NM_194455.1 | NP_919437.1 |
| O00522-1 | NM_194456.1 | NP_919438.1 |
| O00522-3 | NM_001013406.1 | NP_001013424.1 |
| Amino acid sequences of our canonical and alternatively spliced KRIT1 |
| accession_id | Protein sequence |
| O00522-1 | MGNPENIEDAYVAVIRPKNTASLNSREYRAKSYEILLHEVPIEGQKKKRKKVLLETKLQGNSEITQGILDYVVETTKPISPANQGIRGKR VVLMKKFPLDGEKMGREASLFIVPSVVKDNTKYTYTPGCPIFYCLQDIMRVCSESSTHFATLTARMLIALDKWLDERHAQSHFIPALFRP SPLERIKTNVINPAYATESGQTENSLHMGYSALEIKSKMLALEKADTCIYNPLFGSDLQYTNRVDKVVINPYFGLGAPDYSKIQIPKQEK WQRSMSSVTEDKERQWVDDFPLHRSACEGDSELLSRLLSERFSVNQLDSDHWAPIHYACWYGKVEATRILLEKGKCNPNLLNGQLSSPLH FAAGGGHAEIVQILLNHPETDRHITDQQGRSPLNICEENKQNNWEEAAKLLKEAINKPYEKVRIYRMDGSYRSVELKHGNNTTVQQIMEG MRLSQETQQYFTIWICSENLSLQLKPYHKPLQHVRDWPEILAELTNLDPQRETPQLFLRRDVRLPLEVEKQIEDPLAILILFDEARYNLL KGFYTAPDAKLITLASLLLQIVYGNYESKKHKQGFLNEENLKSIVPVTKLKSKAPHWTNRILHEYKNLSTSEGVSKEMHHLQRMFLQNCW EIPTYGAAFFTGQIFTKASPSNHKVIPVYVGVNIKGLHLLNMETKALLISLKYGCFMWQLGDTDTCFQIHSMENKMSFIVHTKQAGLVVK |
| O00522-2 | MGYSALEIKSKMLALEKADTCIYNPLFGSDLQYTNRVDKVVINPYFGLGAPDYSKIQIPKQEKWQRSMSSVTEDKERQWVDDFPLHRSAC EGDSELLSRLLSERFSVNQLDSDHWAPIHYACWYGKVEATRILLEKGKCNPNLLNGQLSSPLHFAAGGGHAEIVQILLNHPETDRHITDQ QGRSPLNICEENKQNNWEEAAKLLKEAINKPYEKVRIYRMDGSYRSVELKHGNNTTVQQIMEGMRLSQETQQYFTIWICSENLSLQLKPY HKPLQHVRDWPEILAELTNLDPQRETPQLFLRRDVRLPLEVEKQIEDPLAILILFDEARYNLLKGFYTAPDAKLITLASLLLQIVYGNYE SKKHKQGFLNEENLKSIVPVTKLKSKAPHWTNRILHEYKNLSTSEGVSKEMHHLQRMFLQNCWEIPTYGAAFFTGQIFTKASPSNHKVIP |
| O00522-3 | MGNPENIEDAYVAVIRPKNTASLNSREYRAKSYEILLHEVPIEGQKKKRKKVLLETKLQGNSEITQGILDYVVETTKPISPANQGIRGKR VVLMKKFPLDGEKMGREASLFIVPSVVKDNTKYTYTPGCPIFYCLQDIMRVCSESSTHFATLTARMLIALDKWLDERHAQSHFIPALFRP SPLERIKTNVINPAYATESGQTENSLHMGYSALEIKSKMLALEKADTCIYNPLFGSDLQYTNRVDKVVINPYFGLGAPDYSKIQIPKQEK WQRSMSSVTEDKYGKVEATRILLEKGKCNPNLLNGQLSSPLHFAAGGGHAEIVQILLNHPETDRHITDQQGRSPLNICEENKQNNWEEAA KLLKEAINKPYEKVRIYRMDGSYRSVELKHGNNTTVQQIMEGMRLSQETQQYFTIWICSENLSLQLKPYHKPLQHVRDWPEILAELTNLD PQRETPQLFLRRDVRLPLEVEKQIEDPLAILILFDEARYNLLKGFYTAPDAKLITLASLLLQIVYGNYESKKHKQGFLNEENLKSIVPVT KLKSKAPHWTNRILHEYKNLSTSEGVSKEMHHLQRMFLQNCWEIPTYGAAFFTGQIFTKASPSNHKVIPVYVGVNIKGLHLLNMETKALL |
Protein Functional Features |
| Main function of this protein. (from UniProt) |
| KRIT1 (go to UniProt):O00522 |
| Retention analysis result of protein across 39 protein features of UniProt such as six molecule processing features, 13 region features, four site features, six amino acid modification features, two natural variation features, five experimental info features, and 3 secondary structure features. Here, because of limited space for viewing, we only show the protein feature retention information belong to the 13 regional features. All retention annotation result can be downloaded at * Minus value of BPloci means that the break pointn is located before the CDS. |
| - Retained protein feature among the 13 regional features. |
| Accession_id | Subsection | Start | End | Funcitonal feature | Splicing information |
| O00522 | Repeat | 287 | 316 | Note=ANK 1;Ontology_term=ECO:0000255;evidence=ECO:0000255 | Type=Deletion;Start=283;End=330 |
| O00522 | Repeat | 320 | 350 | Note=ANK 2;Ontology_term=ECO:0000255;evidence=ECO:0000255 | Type=Deletion;Start=283;End=330 |
| O00522 | Region | 1 | 170 | Note=N-terminal domain similar to Nudix hydrolase domain | Type=Deletion;Start=1;End=207 |
| O00522 | Region | 172 | 195 | Note=Interaction with ITGB1BP1 | Type=Deletion;Start=1;End=207 |
Gene Isoform Structures and Expression Levels for KRIT1 |
| Gene structures of our canonical and alternative spliced genes of KRIT1 * Click on the image to open the UCSC genome browser with custom track showing this image in a new window. |
| Expression levels of gene isoforms across GTEx. |
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| Expression levels of gene isoforms across TCGA. |
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Protein Structures |
| PDB and CIF files of the predicted protein structures * Here we show the 3D structure of the proteins using Mol*. AlphaFold produces a per-residue confidence score (pLDDT) between 0 and 100. Model confidence is shown from the pLDDT values per residue. pLDDT corresponds to the model’s prediction of its score on the local Distance Difference Test. It is a measure of local accuracy (from AlphfaFold website). To color code individual residues, we transformed individual PDB files into CIF format. |
| 3D view using mol* of O00522-1 |
| 3D view using mol* of O00522-2 |
| 3D view using mol* of O00522-3 |
pLDDT Score Distribution |
| pLDDT score distribution of the predicted protein structures from AlphaFold2 * AlphaFold produces a per-residue confidence score (pLDDT) between 0 and 100. |
| pLDDT distribution across the protein length of O00522-1 |
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| pLDDT distribution across the protein length of O00522-2 |
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| pLDDT distribution across the protein length of O00522-3 |
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Ramachandran Plot of Protein Structures |
| Ramachandran plot of the torsional angles - phi (φ)and psi (ψ) - of the residues (amino acids) contained in this protein peptide. |
| Ramachandran plot of O00522-1 |
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Potential Active Site Information |
| The potential binding sites of these proteins were identified using SiteMap, a module of the Schrodinger suite. |
| UniProt-id | Site score | Size | D score | Volume | Exposure | Enclosure | Contact | Phobic | Philic | Balance | Don/Acc | Residues |
| O00522-1 | 1.033 | 105 | 1.041 | 287.777 | 0.578 | 0.747 | 0.966 | 0.64 | 1.066 | 0.601 | 0.856 | 427,464,466,467,468,469,470,471,501,502,503,505,50 7,509,534,537,538,541,543,636,637,638,639,640,641, 659,675,714 |
| O00522-2 | 1.047 | 120 | 1.09 | 321.048 | 0.496 | 0.713 | 0.957 | 1.099 | 0.851 | 1.292 | 0.973 | 257,264,265,266,267,268,269,270,271,276,283,286,28 7,305,306,431,433,483,487,506,509,510,513,514,517 |
| O00522-3 | 1.069 | 109 | 1.106 | 332.71 | 0.498 | 0.755 | 1.034 | 1.394 | 0.881 | 1.583 | 0.833 | 423,424,425,426,427,428,430,435,442,446,464,465,59 0,592,646,665,666,667,668,669,672,673,676 |
Protein Structure and Feature Comparision |
| Protein Structure Comparision Using Template Modeling Scores (TM-score). |
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| Protein Structure Comparision Visualization with mol*. between Canonical predicted structure (AF2)(orange) vs Canonical validated structure (PDB)(green) |
| 3D view using mol* of O00522-1_O00522-1_5d68_B.pdb |
| Protein Structure Comparision Visualization with mol*. between Canonical validated structure (PDB)(orange) vs Alternative predicted structure (AF2)(green) |
| 3D view using mol* of O00522-1_5d68_B_O00522-2.pdb |
| 3D view using mol* of O00522-1_5d68_B_O00522-3.pdb |
| Protein Structure Comparision Visualization with mol*. between Canonical predicted structure (AF2)(orange) vs Alternative predicted structure (AF2)(green) |
| 3D view using mol* of O00522-1_O00522-2.pdb |
| 3D view using mol* of O00522-1_O00522-3.pdb |
| Protein Feature Comparison of the protein sequendary structures among the protiens. |
| ./stats/secondary_structure/figure/O00522-1_vs_O00522-2.png |
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| ./stats/secondary_structure/figure/O00522-1_vs_O00522-3.png |
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| Protein Feature Comparison of the relative accessible surface area (ASA) among the protiens. |
| ./stats/relative_asa/O00522-1_vs_O00522-2.png |
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| ./stats/relative_asa/O00522-1_vs_O00522-3.png |
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Protein-Protein Interaction |
| Interactors from UniProt. |
| Accession_id | Subsection | Start | End | Funcitonal feature | Splicing information |
| O00522 | Region | 172 | 195 | Note=Interaction with ITGB1BP1 | Type=Deletion;Start=1;End=207 |
| Interactors from STRING. |
| Gene name | Interactors |
Related Drugs to KRIT1 |
| Drugs targeting this gene/protein. (DrugBank) |
| UniProt accession | Gene name | DrugBank ID | Drug name | Drug group | Actions |
Related Diseases to KRIT1 |
| Previous studies relating to the alternative splicing of KRIT1 and disease information from the MeSH term (PubMed) |
| Gene | PMID | Title | Abstract | MeSH ID | MeSH term |
| KRIT1 | 11741838 | Interaction between krit1 and icap1alpha infers perturbation of integrin beta1-mediated angiogenesis in the pathogenesis of cerebral cavernous malformation. | Cerebral cavernous malformation (CCM) is a common autosomal dominant disorder characterized by venous sinusoids that predispose to intracranial hemorrhage. CCM is genetically heterogeneous, with loci at 7q, 7p and 3q. Mutations in KRIT1 account for all cases linked to 7q (CCM1), but the pathogenesis of CCM is not understood. Krev Interaction Trapped 1 (krit1) was originally identified through its interaction with the Ras-family GTPase krev1/rap1a in a two-hybrid screen, inferring a role in GTPase signaling cascades. We demonstrated additional 5'-coding exons for krit1, extending the N-terminus by 207 amino acids compared to the previously reported protein. Remarkably, by two-hybrid analysis and co-immunoprecipitation, full-length krit1 fails to interact with krev1/rap1a but shows strong interaction with integrin cytoplasmic domain-associated protein-1 (icap1). Icap1 binds to a NPXY motif in the cytoplasmic domain of beta1 integrin and participates in beta1-mediated cell adhesion and migration. The novel N-terminus of krit1 contains a NPXY motif that it is required for icap1 interaction. Like beta1 integrin, krit1 interacts with the 200 amino acid isoform of icap1 (icap1alpha), but not a 150 amino acid form that results from alternative splicing (icap1beta). In a competition assay, induced expression of krit1 diminishes the interaction between icap1alpha and beta1 integrin. Taken together, these data suggest that beta1 integrin and krit1 compete for the same site on icap1alpha, perhaps constituting a regulatory mechanism. Loss-of-function KRIT1 mutations, as observed in CCM1, would shift the balance with predicted consequences for endothelial cell performance during integrin beta1-dependent angiogenesis. | D016543 | Central Nervous System Neoplasms |
| KRIT1 | 11741838 | Interaction between krit1 and icap1alpha infers perturbation of integrin beta1-mediated angiogenesis in the pathogenesis of cerebral cavernous malformation. | Cerebral cavernous malformation (CCM) is a common autosomal dominant disorder characterized by venous sinusoids that predispose to intracranial hemorrhage. CCM is genetically heterogeneous, with loci at 7q, 7p and 3q. Mutations in KRIT1 account for all cases linked to 7q (CCM1), but the pathogenesis of CCM is not understood. Krev Interaction Trapped 1 (krit1) was originally identified through its interaction with the Ras-family GTPase krev1/rap1a in a two-hybrid screen, inferring a role in GTPase signaling cascades. We demonstrated additional 5'-coding exons for krit1, extending the N-terminus by 207 amino acids compared to the previously reported protein. Remarkably, by two-hybrid analysis and co-immunoprecipitation, full-length krit1 fails to interact with krev1/rap1a but shows strong interaction with integrin cytoplasmic domain-associated protein-1 (icap1). Icap1 binds to a NPXY motif in the cytoplasmic domain of beta1 integrin and participates in beta1-mediated cell adhesion and migration. The novel N-terminus of krit1 contains a NPXY motif that it is required for icap1 interaction. Like beta1 integrin, krit1 interacts with the 200 amino acid isoform of icap1 (icap1alpha), but not a 150 amino acid form that results from alternative splicing (icap1beta). In a competition assay, induced expression of krit1 diminishes the interaction between icap1alpha and beta1 integrin. Taken together, these data suggest that beta1 integrin and krit1 compete for the same site on icap1alpha, perhaps constituting a regulatory mechanism. Loss-of-function KRIT1 mutations, as observed in CCM1, would shift the balance with predicted consequences for endothelial cell performance during integrin beta1-dependent angiogenesis. | D020786 | Hemangioma, Cavernous, Central Nervous System |
| KRIT1 | 11741838 | Interaction between krit1 and icap1alpha infers perturbation of integrin beta1-mediated angiogenesis in the pathogenesis of cerebral cavernous malformation. | Cerebral cavernous malformation (CCM) is a common autosomal dominant disorder characterized by venous sinusoids that predispose to intracranial hemorrhage. CCM is genetically heterogeneous, with loci at 7q, 7p and 3q. Mutations in KRIT1 account for all cases linked to 7q (CCM1), but the pathogenesis of CCM is not understood. Krev Interaction Trapped 1 (krit1) was originally identified through its interaction with the Ras-family GTPase krev1/rap1a in a two-hybrid screen, inferring a role in GTPase signaling cascades. We demonstrated additional 5'-coding exons for krit1, extending the N-terminus by 207 amino acids compared to the previously reported protein. Remarkably, by two-hybrid analysis and co-immunoprecipitation, full-length krit1 fails to interact with krev1/rap1a but shows strong interaction with integrin cytoplasmic domain-associated protein-1 (icap1). Icap1 binds to a NPXY motif in the cytoplasmic domain of beta1 integrin and participates in beta1-mediated cell adhesion and migration. The novel N-terminus of krit1 contains a NPXY motif that it is required for icap1 interaction. Like beta1 integrin, krit1 interacts with the 200 amino acid isoform of icap1 (icap1alpha), but not a 150 amino acid form that results from alternative splicing (icap1beta). In a competition assay, induced expression of krit1 diminishes the interaction between icap1alpha and beta1 integrin. Taken together, these data suggest that beta1 integrin and krit1 compete for the same site on icap1alpha, perhaps constituting a regulatory mechanism. Loss-of-function KRIT1 mutations, as observed in CCM1, would shift the balance with predicted consequences for endothelial cell performance during integrin beta1-dependent angiogenesis. | D009389 | Neovascularization, Pathologic |
Clinically important variants in KRIT1 |
| (ClinVar, 04/20/2024) |
| accession_id | uniprot_id | gene_name | Type | Variant | Clinical_significance |
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