UniProtKB - O00522 (KRIT1_HUMAN)
Krev interaction trapped protein 1
KRIT1
Functioni
GO - Molecular functioni
- GTPase regulator activity Source: ProtInc
- microtubule binding Source: UniProtKB
- phosphatidylinositol-4,5-bisphosphate binding Source: UniProtKB
GO - Biological processi
- angiogenesis Source: UniProtKB-KW
- cell redox homeostasis Source: UniProtKB
- negative regulation of angiogenesis Source: UniProtKB
- negative regulation of endothelial cell apoptotic process Source: UniProtKB
- negative regulation of endothelial cell migration Source: UniProtKB
- negative regulation of endothelial cell proliferation Source: UniProtKB
- regulation of establishment of cell polarity Source: UniProtKB
- small GTPase mediated signal transduction Source: ProtInc
Keywordsi
Biological process | Angiogenesis |
Enzyme and pathway databases
BioCyci | MetaCyc:ENSG00000001631-MONOMER |
PathwayCommonsi | O00522 |
Names & Taxonomyi
Protein namesi | Recommended name: Krev interaction trapped protein 1Short name: Krev interaction trapped 1 Alternative name(s): Cerebral cavernous malformations 1 protein |
Gene namesi | Name:KRIT1 Synonyms:CCM1 |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:1573, KRIT1 |
MIMi | 604214, gene |
neXtProti | NX_O00522 |
VEuPathDBi | HostDB:ENSG00000001631.14 |
Subcellular locationi
Plasma membrane
Cytoskeleton
Other locations
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.
Cytoskeleton
- cytoskeleton Source: UniProtKB-SubCell
Extracellular region or secreted
- extracellular space Source: UniProtKB
Plasma Membrane
- plasma membrane Source: UniProtKB
Other locations
- cell-cell junction Source: UniProtKB
- cytoplasm Source: UniProtKB-KW
Keywords - Cellular componenti
Cell junction, Cell membrane, Cytoplasm, Cytoskeleton, MembranePathology & Biotechi
Involvement in diseasei
Cerebral cavernous malformations 1 (CCM1)1 Publication
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_023573 | 97 | F → S in CCM1. 1 Publication | 1 | |
Natural variantiVAR_023574 | 569 | K → E in CCM1. 1 Publication | 1 |
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 47 – 50 | KKRK → AAAA: Reduces interaction with microtubules, but not with ITGB1BP1. 1 Publication | 4 | |
Mutagenesisi | 176 | A → D: Strongly reduces ITGB1BP1 binding; when associated with D-182. 1 Publication | 1 | |
Mutagenesisi | 179 | R → A: Strongly reduces ITGB1BP1 binding; when associated with A-179. 1 Publication | 1 | |
Mutagenesisi | 182 | P → D: Strongly reduces ITGB1BP1 binding; when associated with D-176. 1 Publication | 1 | |
Mutagenesisi | 185 | R → A: Strongly reduces ITGB1BP1 binding; when associated with A-179. 1 Publication | 1 | |
Mutagenesisi | 192 – 195 | NPAY → APAA: Reduces interaction with ITGB1BP1. 1 Publication | 4 | |
Mutagenesisi | 192 | N → A: Reduces ITGB1BP1 binding; when associated with A-195. 3 Publications | 1 | |
Mutagenesisi | 195 | Y → A: Reduces ITGB1BP1 binding; when associated with A-192. 3 Publications | 1 | |
Mutagenesisi | 430 | S → E: Impairs interaction with RAP1B. 1 Publication | 1 | |
Mutagenesisi | 432 | R → E: Impairs interaction with RAP1B. 1 Publication | 1 | |
Mutagenesisi | 452 | R → E: 40-fold-reduced affinity for Rap1A. 2 Publications | 1 | |
Mutagenesisi | 452 | R → E: Impairs interaction with RAP1B. 2 Publications | 1 | |
Mutagenesisi | 717 | L → A: Strongly reduced affinity for HEG1; when associated with A-721. 1 Publication | 1 | |
Mutagenesisi | 721 | L → A: Strongly reduced affinity for HEG1; when associated with A-717. 1 Publication | 1 |
Keywords - Diseasei
Disease variantOrganism-specific databases
DisGeNETi | 889 |
GeneReviewsi | KRIT1 |
MalaCardsi | KRIT1 |
MIMi | 116860, phenotype |
OpenTargetsi | ENSG00000001631 |
Orphaneti | 221061, Familial cerebral cavernous malformation |
PharmGKBi | PA26144 |
Miscellaneous databases
Pharosi | O00522, Tbio |
Genetic variation databases
BioMutai | KRIT1 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000067023 | 1 – 736 | Krev interaction trapped protein 1Add BLAST | 736 |
Proteomic databases
EPDi | O00522 |
jPOSTi | O00522 |
MassIVEi | O00522 |
MaxQBi | O00522 |
PaxDbi | O00522 |
PeptideAtlasi | O00522 |
PRIDEi | O00522 |
ProteomicsDBi | 47953 [O00522-1] 47954 [O00522-2] 47955 [O00522-3] |
PTM databases
iPTMneti | O00522 |
PhosphoSitePlusi | O00522 |
Expressioni
Tissue specificityi
Gene expression databases
Bgeei | ENSG00000001631, Expressed in calcaneal tendon and 120 other tissues |
ExpressionAtlasi | O00522, baseline and differential |
Genevisiblei | O00522, HS |
Organism-specific databases
HPAi | ENSG00000001631, Low tissue specificity |
Interactioni
Subunit structurei
Interacts with CDH5 (PubMed:20332120).
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 FERM domain) with RAP1B.
Interacts (via N-terminus NPXY motif) with ITGB1BP1; the interaction induces the opening conformation of KRIT1 and competes with ITGB1 for ITGB1BP1 interaction.
Interacts with HEG1 and CCM2; greatly facilitates CCM2-binding to HEG1. Associates (via N-terminus and C-terminus regions) with microtubules; the interaction is inhibited in presence of ITGB1BP1 and active GTP-bound RAP1A.
9 PublicationsBinary interactionsi
Hide detailsO00522
GO - Molecular functioni
- microtubule binding Source: UniProtKB
Protein-protein interaction databases
BioGRIDi | 107330, 19 interactors |
ComplexPortali | CPX-983, ICAP1-KRIT1 integrin activation complex CPX-984, CCM endothelial permeability complex |
CORUMi | O00522 |
DIPi | DIP-40610N |
IntActi | O00522, 10 interactors |
STRINGi | 9606.ENSP00000378015 |
Miscellaneous databases
RNActi | O00522, protein |
Structurei
Secondary structure
3D structure databases
SMRi | O00522 |
ModBasei | Search... |
PDBe-KBi | Search... |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Repeati | 287 – 316 | ANK 1Sequence analysisAdd BLAST | 30 | |
Repeati | 320 – 350 | ANK 2Sequence analysisAdd BLAST | 31 | |
Repeati | 354 – 383 | ANK 3Sequence analysisAdd BLAST | 30 | |
Repeati | 388 – 419 | ANK 4Sequence analysisAdd BLAST | 32 | |
Domaini | 420 – 734 | FERMPROSITE-ProRule annotationAdd BLAST | 315 |
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 1 – 170 | N-terminal domain similar to Nudix hydrolase domainAdd BLAST | 170 | |
Regioni | 172 – 195 | Interaction with ITGB1BP1Add BLAST | 24 | |
Regioni | 430 – 452 | Interaction with RAP1B1 PublicationAdd BLAST | 23 |
Domaini
Keywords - Domaini
ANK repeat, RepeatPhylogenomic databases
eggNOGi | KOG4335, Eukaryota |
GeneTreei | ENSGT00530000063721 |
HOGENOMi | CLU_022188_0_0_1 |
InParanoidi | O00522 |
OMAi | HKPLQHI |
OrthoDBi | 839317at2759 |
PhylomeDBi | O00522 |
TreeFami | TF317921 |
Family and domain databases
CDDi | cd14473, FERM_B-lobe, 1 hit cd13197, FERM_C_CCM1, 1 hit |
DisProti | DP01333 |
Gene3Di | 1.20.80.10, 1 hit 1.25.40.20, 1 hit 2.30.29.30, 1 hit 3.30.70.2240, 2 hits |
InterProi | View protein in InterPro IPR002110, Ankyrin_rpt IPR020683, Ankyrin_rpt-contain_dom IPR036770, Ankyrin_rpt-contain_sf IPR019749, Band_41_domain IPR014352, FERM/acyl-CoA-bd_prot_sf IPR035963, FERM_2 IPR019748, FERM_central IPR000299, FERM_domain IPR041791, KRIT1_FERM_C IPR032022, NUDIX IPR043058, NUDIX_sf IPR011993, PH-like_dom_sf |
Pfami | View protein in Pfam PF00373, FERM_M, 1 hit PF16705, NUDIX_5, 1 hit |
SMARTi | View protein in SMART SM00248, ANK, 3 hits SM00295, B41, 1 hit |
SUPFAMi | SSF47031, SSF47031, 1 hit SSF48403, SSF48403, 1 hit |
PROSITEi | View protein in PROSITE PS50297, ANK_REP_REGION, 1 hit PS50088, ANK_REPEAT, 1 hit PS50057, FERM_3, 1 hit |
s (3+)i Sequence
Sequence statusi: Complete.
This entry describes 3 produced by isoformsialternative splicing. AlignAdd to basketThis entry has 3 described isoforms and 13 potential isoforms that are computationally mapped.Show allAlign All
This isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
10 20 30 40 50
MGNPENIEDA YVAVIRPKNT ASLNSREYRA KSYEILLHEV PIEGQKKKRK
60 70 80 90 100
KVLLETKLQG NSEITQGILD YVVETTKPIS PANQGIRGKR VVLMKKFPLD
110 120 130 140 150
GEKMGREASL FIVPSVVKDN TKYTYTPGCP IFYCLQDIMR VCSESSTHFA
160 170 180 190 200
TLTARMLIAL DKWLDERHAQ SHFIPALFRP SPLERIKTNV INPAYATESG
210 220 230 240 250
QTENSLHMGY SALEIKSKML ALEKADTCIY NPLFGSDLQY TNRVDKVVIN
260 270 280 290 300
PYFGLGAPDY SKIQIPKQEK WQRSMSSVTE DKERQWVDDF PLHRSACEGD
310 320 330 340 350
SELLSRLLSE RFSVNQLDSD HWAPIHYACW YGKVEATRIL LEKGKCNPNL
360 370 380 390 400
LNGQLSSPLH FAAGGGHAEI VQILLNHPET DRHITDQQGR SPLNICEENK
410 420 430 440 450
QNNWEEAAKL LKEAINKPYE KVRIYRMDGS YRSVELKHGN NTTVQQIMEG
460 470 480 490 500
MRLSQETQQY FTIWICSENL SLQLKPYHKP LQHVRDWPEI LAELTNLDPQ
510 520 530 540 550
RETPQLFLRR DVRLPLEVEK QIEDPLAILI LFDEARYNLL KGFYTAPDAK
560 570 580 590 600
LITLASLLLQ IVYGNYESKK HKQGFLNEEN LKSIVPVTKL KSKAPHWTNR
610 620 630 640 650
ILHEYKNLST SEGVSKEMHH LQRMFLQNCW EIPTYGAAFF TGQIFTKASP
660 670 680 690 700
SNHKVIPVYV GVNIKGLHLL NMETKALLIS LKYGCFMWQL GDTDTCFQIH
710 720 730
SMENKMSFIV HTKQAGLVVK LLMKLNGQLM PTERNS
Computationally mapped potential isoform sequencesi
There are 13 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketC9JIY2 | C9JIY2_HUMAN | Krev interaction trapped protein 1 | KRIT1 | 164 | Annotation score: | ||
C9J3W7 | C9J3W7_HUMAN | Krev interaction trapped protein 1 | KRIT1 | 69 | Annotation score: | ||
C9J718 | C9J718_HUMAN | Krev interaction trapped protein 1 | KRIT1 | 162 | Annotation score: | ||
C9JF32 | C9JF32_HUMAN | Krev interaction trapped protein 1 | KRIT1 | 184 | Annotation score: | ||
C9JBN7 | C9JBN7_HUMAN | Krev interaction trapped protein 1 | KRIT1 | 97 | Annotation score: | ||
C9JD81 | C9JD81_HUMAN | Krev interaction trapped protein 1 | KRIT1 | 65 | Annotation score: | ||
C9JEW7 | C9JEW7_HUMAN | Krev interaction trapped protein 1 | KRIT1 | 112 | Annotation score: | ||
C9JI47 | C9JI47_HUMAN | Krev interaction trapped protein 1 | KRIT1 | 25 | Annotation score: | ||
C9JJM9 | C9JJM9_HUMAN | Krev interaction trapped protein 1 | KRIT1 | 58 | Annotation score: | ||
C9JSG7 | C9JSG7_HUMAN | Krev interaction trapped protein 1 | KRIT1 | 38 | Annotation score: | ||
There are more potential isoformsShow all |
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 138 | I → T in AAQ94072 (Ref. 5) Curated | 1 | |
Sequence conflicti | 234 | F → G in AAB58582 (PubMed:9285558).Curated | 1 | |
Sequence conflicti | 731 | P → A in AAB58582 (PubMed:9285558).Curated | 1 | |
Sequence conflicti | 731 | P → A in AAG47774 (PubMed:11161791).Curated | 1 | |
Sequence conflicti | 731 | P → A in AAQ94072 (Ref. 5) Curated | 1 |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_023573 | 97 | F → S in CCM1. 1 Publication | 1 | |
Natural variantiVAR_023574 | 569 | K → E in CCM1. 1 Publication | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_015800 | 1 – 207 | Missing in isoform 2. 1 PublicationAdd BLAST | 207 | |
Alternative sequenceiVSP_043327 | 283 – 330 | Missing in isoform 3. 1 PublicationAdd BLAST | 48 |
Sequence databases
Genome annotation databases
Ensembli | ENST00000340022; ENSP00000344668; ENSG00000001631 [O00522-1] ENST00000394503; ENSP00000378011; ENSG00000001631 [O00522-3] ENST00000394505; ENSP00000378013; ENSG00000001631 [O00522-1] ENST00000394507; ENSP00000378015; ENSG00000001631 [O00522-1] ENST00000412043; ENSP00000410909; ENSG00000001631 [O00522-1] ENST00000458177; ENSP00000391675; ENSG00000001631 [O00522-1] |
GeneIDi | 889 |
KEGGi | hsa:889 |
UCSCi | uc003ulr.2, human [O00522-1] |
Keywords - Coding sequence diversityi
Alternative splicingSimilar proteinsi
Cross-referencesi
Sequence databases
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
3U7D | X-ray | 2.49 | A/C | 417-736 | [»] | |
4DX8 | X-ray | 2.54 | H/I/J/K | 1-198 | [»] | |
4DXA | X-ray | 1.95 | B | 420-736 | [»] | |
4HDO | X-ray | 1.67 | A | 417-736 | [»] | |
4HDQ | X-ray | 1.95 | A | 417-736 | [»] | |
4JIF | X-ray | 1.70 | B | 170-198 | [»] | |
4TKN | X-ray | 3.00 | D/E/F | 225-237 | [»] | |
5D68 | X-ray | 2.91 | A/B/C | 259-736 | [»] | |
6OQ3 | X-ray | 1.85 | A | 417-736 | [»] | |
6OQ4 | X-ray | 1.75 | A | 417-736 | [»] | |
6UZK | X-ray | 1.92 | A | 417-736 | [»] | |
SMRi | O00522 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 107330, 19 interactors |
ComplexPortali | CPX-983, ICAP1-KRIT1 integrin activation complex CPX-984, CCM endothelial permeability complex |
CORUMi | O00522 |
DIPi | DIP-40610N |
IntActi | O00522, 10 interactors |
STRINGi | 9606.ENSP00000378015 |
PTM databases
iPTMneti | O00522 |
PhosphoSitePlusi | O00522 |
Genetic variation databases
BioMutai | KRIT1 |
Proteomic databases
EPDi | O00522 |
jPOSTi | O00522 |
MassIVEi | O00522 |
MaxQBi | O00522 |
PaxDbi | O00522 |
PeptideAtlasi | O00522 |
PRIDEi | O00522 |
ProteomicsDBi | 47953 [O00522-1] 47954 [O00522-2] 47955 [O00522-3] |
Protocols and materials databases
Antibodypediai | 15587, 200 antibodies |
Genome annotation databases
Ensembli | ENST00000340022; ENSP00000344668; ENSG00000001631 [O00522-1] ENST00000394503; ENSP00000378011; ENSG00000001631 [O00522-3] ENST00000394505; ENSP00000378013; ENSG00000001631 [O00522-1] ENST00000394507; ENSP00000378015; ENSG00000001631 [O00522-1] ENST00000412043; ENSP00000410909; ENSG00000001631 [O00522-1] ENST00000458177; ENSP00000391675; ENSG00000001631 [O00522-1] |
GeneIDi | 889 |
KEGGi | hsa:889 |
UCSCi | uc003ulr.2, human [O00522-1] |
Organism-specific databases
CTDi | 889 |
DisGeNETi | 889 |
GeneCardsi | KRIT1 |
GeneReviewsi | KRIT1 |
HGNCi | HGNC:1573, KRIT1 |
HPAi | ENSG00000001631, Low tissue specificity |
MalaCardsi | KRIT1 |
MIMi | 116860, phenotype 604214, gene |
neXtProti | NX_O00522 |
OpenTargetsi | ENSG00000001631 |
Orphaneti | 221061, Familial cerebral cavernous malformation |
PharmGKBi | PA26144 |
VEuPathDBi | HostDB:ENSG00000001631.14 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG4335, Eukaryota |
GeneTreei | ENSGT00530000063721 |
HOGENOMi | CLU_022188_0_0_1 |
InParanoidi | O00522 |
OMAi | HKPLQHI |
OrthoDBi | 839317at2759 |
PhylomeDBi | O00522 |
TreeFami | TF317921 |
Enzyme and pathway databases
BioCyci | MetaCyc:ENSG00000001631-MONOMER |
PathwayCommonsi | O00522 |
Miscellaneous databases
BioGRID-ORCSi | 889, 10 hits in 1004 CRISPR screens |
ChiTaRSi | KRIT1, human |
GeneWikii | KRIT1 |
GenomeRNAii | 889 |
Pharosi | O00522, Tbio |
PROi | PR:O00522 |
RNActi | O00522, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000001631, Expressed in calcaneal tendon and 120 other tissues |
ExpressionAtlasi | O00522, baseline and differential |
Genevisiblei | O00522, HS |
Family and domain databases
CDDi | cd14473, FERM_B-lobe, 1 hit cd13197, FERM_C_CCM1, 1 hit |
DisProti | DP01333 |
Gene3Di | 1.20.80.10, 1 hit 1.25.40.20, 1 hit 2.30.29.30, 1 hit 3.30.70.2240, 2 hits |
InterProi | View protein in InterPro IPR002110, Ankyrin_rpt IPR020683, Ankyrin_rpt-contain_dom IPR036770, Ankyrin_rpt-contain_sf IPR019749, Band_41_domain IPR014352, FERM/acyl-CoA-bd_prot_sf IPR035963, FERM_2 IPR019748, FERM_central IPR000299, FERM_domain IPR041791, KRIT1_FERM_C IPR032022, NUDIX IPR043058, NUDIX_sf IPR011993, PH-like_dom_sf |
Pfami | View protein in Pfam PF00373, FERM_M, 1 hit PF16705, NUDIX_5, 1 hit |
SMARTi | View protein in SMART SM00248, ANK, 3 hits SM00295, B41, 1 hit |
SUPFAMi | SSF47031, SSF47031, 1 hit SSF48403, SSF48403, 1 hit |
PROSITEi | View protein in PROSITE PS50297, ANK_REP_REGION, 1 hit PS50088, ANK_REPEAT, 1 hit PS50057, FERM_3, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | KRIT1_HUMAN | |
Accessioni | O00522Primary (citable) accession number: O00522 Secondary accession number(s): A6NNU0 Q9HAX5 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | April 27, 2001 |
Last sequence update: | October 11, 2005 | |
Last modified: | April 7, 2021 | |
This is version 195 of the entry and version 2 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care. |
Miscellaneousi
Keywords - Technical termi
3D-structure, Reference proteomeDocuments
- Human chromosome 7
Human chromosome 7: entries, gene names and cross-references to MIM - Human entries with genetic variants
List of human entries with genetic variants - Human variants curated from literature reports
Index of human variants curated from literature reports - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - PDB cross-references
Index of Protein Data Bank (PDB) cross-references