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O00522

- KRIT1_HUMAN

UniProt

O00522 - KRIT1_HUMAN

Protein

Krev interaction trapped protein 1

Gene

KRIT1

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 140 (01 Oct 2014)
      Sequence version 2 (11 Oct 2005)
      Previous versions | rss
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    Functioni

    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.By similarity7 Publications

    GO - Molecular functioni

    1. microtubule binding Source: UniProtKB
    2. phosphatidylinositol-4,5-bisphosphate binding Source: UniProtKB
    3. protein binding Source: UniProtKB
    4. protein complex binding Source: UniProtKB
    5. small GTPase regulator activity Source: ProtInc

    GO - Biological processi

    1. angiogenesis Source: UniProtKB-KW
    2. cell redox homeostasis Source: UniProtKB
    3. negative regulation of angiogenesis Source: UniProtKB
    4. negative regulation of endothelial cell apoptotic process Source: UniProtKB
    5. negative regulation of endothelial cell migration Source: UniProtKB
    6. negative regulation of endothelial cell proliferation Source: UniProtKB
    7. positive regulation of protein binding Source: Ensembl
    8. regulation of catalytic activity Source: GOC
    9. regulation of establishment of cell polarity Source: UniProtKB
    10. small GTPase mediated signal transduction Source: ProtInc

    Keywords - Biological processi

    Angiogenesis

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Krev interaction trapped protein 1
    Short name:
    Krev interaction trapped 1
    Alternative name(s):
    Cerebral cavernous malformations 1 protein
    Gene namesi
    Name:KRIT1
    Synonyms:CCM1
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 7

    Organism-specific databases

    HGNCiHGNC:1573. KRIT1.

    Subcellular locationi

    Cytoplasmcytoskeleton. 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.

    GO - Cellular componenti

    1. cell-cell junction Source: UniProtKB
    2. cytoplasm Source: UniProtKB-KW
    3. extracellular space Source: UniProt
    4. microtubule Source: UniProtKB
    5. plasma membrane Source: UniProtKB

    Keywords - Cellular componenti

    Cell junction, Cell membrane, Cytoplasm, Cytoskeleton, Membrane

    Pathology & Biotechi

    Involvement in diseasei

    Cerebral cavernous malformations 1 (CCM1) [MIM:116860]: 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.1 Publication
    Note: The disease is caused by mutations affecting the gene represented in this entry.
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti97 – 971F → S in CCM1. 1 Publication
    VAR_023573
    Natural varianti569 – 5691K → E in CCM1. 1 Publication
    VAR_023574

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi47 – 504KKRK → AAAA: Reduces interaction with microtubules, but not with ITGB1BP1. 1 Publication
    Mutagenesisi176 – 1761A → D: Strongly reduces ITGB1BP1 binding; when associated with D-182. 2 Publications
    Mutagenesisi179 – 1791R → A: Strongly reduces ITGB1BP1 binding; when associated with A-179. 2 Publications
    Mutagenesisi182 – 1821P → D: Strongly reduces ITGB1BP1 binding; when associated with D-176. 2 Publications
    Mutagenesisi185 – 1851R → A: Strongly reduces ITGB1BP1 binding; when associated with A-179. 2 Publications
    Mutagenesisi192 – 1954NPAY → APAA: Reduces interaction with ITGB1BP1. 4 Publications
    Mutagenesisi192 – 1921N → A: Reduces ITGB1BP1 binding; when associated with A-195. 4 Publications
    Mutagenesisi195 – 1951Y → A: Reduces ITGB1BP1 binding; when associated with A-192. 4 Publications
    Mutagenesisi430 – 4301S → E: Impairs interaction with RAP1B. 2 Publications
    Mutagenesisi432 – 4321R → E: Impairs interaction with RAP1B. 2 Publications
    Mutagenesisi452 – 4521R → E: 40-fold-reduced affinity for Rap1A. 3 Publications
    Mutagenesisi452 – 4521R → E: Impairs interaction with RAP1B. 3 Publications
    Mutagenesisi717 – 7171L → A: Strongly reduced affinity for HEG1; when associated with A-721. 2 Publications
    Mutagenesisi721 – 7211L → A: Strongly reduced affinity for HEG1; when associated with A-717. 2 Publications

    Keywords - Diseasei

    Disease mutation

    Organism-specific databases

    MIMi116860. phenotype.
    Orphaneti221061. Hereditary cerebral cavernous malformation.
    PharmGKBiPA26144.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 736736Krev interaction trapped protein 1PRO_0000067023Add
    BLAST

    Proteomic databases

    MaxQBiO00522.
    PaxDbiO00522.
    PRIDEiO00522.

    PTM databases

    PhosphoSiteiO00522.

    Expressioni

    Tissue specificityi

    Low levels in brain. Very weak expression found in heart and muscle.1 Publication

    Gene expression databases

    ArrayExpressiO00522.
    BgeeiO00522.
    CleanExiHS_KRIT1.
    GenevestigatoriO00522.

    Organism-specific databases

    HPAiHPA049606.

    Interactioni

    Subunit structurei

    Interacts with CDH5 By similarity. 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.By similarity9 Publications

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    CCM2Q9BSQ53EBI-1573121,EBI-1573056

    Protein-protein interaction databases

    BioGridi107330. 12 interactions.
    IntActiO00522. 4 interactions.
    STRINGi9606.ENSP00000344668.

    Structurei

    Secondary structure

    1
    736
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Beta strandi9 – 179
    Helixi30 – 323
    Beta strandi33 – 397
    Beta strandi54 – 574
    Helixi64 – 7512
    Beta strandi92 – 987
    Beta strandi107 – 1148
    Beta strandi131 – 1344
    Helixi135 – 1417
    Helixi151 – 17020
    Helixi173 – 1786
    Helixi182 – 1854
    Beta strandi186 – 1916
    Helixi193 – 1953
    Beta strandi421 – 4255
    Beta strandi431 – 4355
    Helixi439 – 4413
    Helixi444 – 4496
    Helixi455 – 4584
    Beta strandi461 – 4677
    Beta strandi470 – 4734
    Helixi480 – 4856
    Helixi487 – 4948
    Helixi499 – 5013
    Beta strandi505 – 5106
    Helixi516 – 5194
    Helixi525 – 54117
    Helixi548 – 56316
    Helixi568 – 5714
    Beta strandi572 – 5743
    Helixi578 – 5814
    Turni582 – 5843
    Helixi587 – 5893
    Turni590 – 5934
    Helixi594 – 5963
    Helixi598 – 61013
    Beta strandi612 – 6143
    Helixi618 – 62912
    Turni633 – 6364
    Beta strandi638 – 6458
    Turni650 – 6523
    Beta strandi655 – 6628
    Beta strandi664 – 6718
    Turni672 – 6743
    Beta strandi677 – 6826
    Beta strandi685 – 6906
    Beta strandi694 – 7018
    Turni702 – 7054
    Beta strandi706 – 7116
    Helixi715 – 72814

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    3U7DX-ray2.49A/C417-736[»]
    4DX8X-ray2.54H/I/J/K1-198[»]
    4DXAX-ray1.95B420-736[»]
    4HDOX-ray1.67A417-736[»]
    4HDQX-ray1.95A417-736[»]
    4JIFX-ray1.70B170-198[»]
    ProteinModelPortaliO00522.
    SMRiO00522. Positions 8-413, 419-729.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Repeati287 – 31630ANK 1Add
    BLAST
    Repeati320 – 35031ANK 2Add
    BLAST
    Repeati354 – 38330ANK 3Add
    BLAST
    Repeati388 – 41932ANK 4Add
    BLAST
    Domaini420 – 734315FERMPROSITE-ProRule annotationAdd
    BLAST

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni1 – 170170N-terminal domain similar to Nudix hydrolase domainAdd
    BLAST
    Regioni172 – 19524Interaction with ITGB1BP1Add
    BLAST
    Regioni430 – 45223Interaction with RAP1BAdd
    BLAST

    Domaini

    The FERM domain mediates binding to RAP1A and RAP1B and is necessary for binding to phosphatidylinositol 4,5-bisphosphate (PIP2).1 Publication
    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.1 Publication

    Sequence similaritiesi

    Contains 4 ANK repeats.PROSITE-ProRule annotation
    Contains 1 FERM domain.PROSITE-ProRule annotation

    Keywords - Domaini

    ANK repeat, Repeat

    Phylogenomic databases

    eggNOGiKOG4335.
    HOGENOMiHOG000252958.
    HOVERGENiHBG052292.
    InParanoidiO00522.
    KOiK17705.
    OMAiSKKHKQG.
    OrthoDBiEOG7SR4KS.
    PhylomeDBiO00522.
    TreeFamiTF317921.

    Family and domain databases

    Gene3Di1.20.80.10. 1 hit.
    1.25.40.20. 1 hit.
    InterProiIPR002110. 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.
    [Graphical view]
    PfamiPF00023. Ank. 1 hit.
    PF12796. Ank_2. 1 hit.
    PF00373. FERM_M. 1 hit.
    [Graphical view]
    SMARTiSM00248. ANK. 3 hits.
    SM00295. B41. 1 hit.
    [Graphical view]
    SUPFAMiSSF47031. SSF47031. 1 hit.
    SSF48403. SSF48403. 1 hit.
    PROSITEiPS50297. ANK_REP_REGION. 1 hit.
    PS50088. ANK_REPEAT. 1 hit.
    PS50057. FERM_3. 1 hit.
    [Graphical view]

    Sequences (3)i

    Sequence statusi: Complete.

    This entry describes 3 isoformsi produced by alternative splicing. Align

    Isoform 1 (identifier: O00522-1) [UniParc]FASTAAdd to Basket

    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.

    « Hide

    MGNPENIEDA YVAVIRPKNT ASLNSREYRA KSYEILLHEV PIEGQKKKRK    50
    KVLLETKLQG NSEITQGILD YVVETTKPIS PANQGIRGKR VVLMKKFPLD 100
    GEKMGREASL FIVPSVVKDN TKYTYTPGCP IFYCLQDIMR VCSESSTHFA 150
    TLTARMLIAL DKWLDERHAQ SHFIPALFRP SPLERIKTNV INPAYATESG 200
    QTENSLHMGY SALEIKSKML ALEKADTCIY NPLFGSDLQY TNRVDKVVIN 250
    PYFGLGAPDY SKIQIPKQEK WQRSMSSVTE DKERQWVDDF PLHRSACEGD 300
    SELLSRLLSE RFSVNQLDSD HWAPIHYACW YGKVEATRIL LEKGKCNPNL 350
    LNGQLSSPLH FAAGGGHAEI VQILLNHPET DRHITDQQGR SPLNICEENK 400
    QNNWEEAAKL LKEAINKPYE KVRIYRMDGS YRSVELKHGN NTTVQQIMEG 450
    MRLSQETQQY FTIWICSENL SLQLKPYHKP LQHVRDWPEI LAELTNLDPQ 500
    RETPQLFLRR DVRLPLEVEK QIEDPLAILI LFDEARYNLL KGFYTAPDAK 550
    LITLASLLLQ IVYGNYESKK HKQGFLNEEN LKSIVPVTKL KSKAPHWTNR 600
    ILHEYKNLST SEGVSKEMHH LQRMFLQNCW EIPTYGAAFF TGQIFTKASP 650
    SNHKVIPVYV GVNIKGLHLL NMETKALLIS LKYGCFMWQL GDTDTCFQIH 700
    SMENKMSFIV HTKQAGLVVK LLMKLNGQLM PTERNS 736
    Length:736
    Mass (Da):84,348
    Last modified:October 11, 2005 - v2
    Checksum:iD11F75ED629E85AC
    GO
    Isoform 2 (identifier: O00522-2) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         1-207: Missing.

    Show »
    Length:529
    Mass (Da):60,945
    Checksum:iD56082828EEB7094
    GO
    Isoform 3 (identifier: O00522-3) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         283-330: Missing.

    Note: No experimental confirmation available.

    Show »
    Length:688
    Mass (Da):78,650
    Checksum:iE62A1A28360F87F1
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti138 – 1381I → T in AAQ94072. 1 PublicationCurated
    Sequence conflicti234 – 2341F → G in AAB58582. (PubMed:9285558)Curated
    Sequence conflicti731 – 7311P → A in AAB58582. (PubMed:9285558)Curated
    Sequence conflicti731 – 7311P → A in AAG47774. (PubMed:11161791)Curated
    Sequence conflicti731 – 7311P → A in AAQ94072. 1 PublicationCurated

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti97 – 971F → S in CCM1. 1 Publication
    VAR_023573
    Natural varianti569 – 5691K → E in CCM1. 1 Publication
    VAR_023574

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei1 – 207207Missing in isoform 2. 1 PublicationVSP_015800Add
    BLAST
    Alternative sequencei283 – 33048Missing in isoform 3. 1 PublicationVSP_043327Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    U90268 mRNA. Translation: AAB58582.1.
    U90269 Genomic DNA. Translation: AAC01535.1.
    AF310133 mRNA. Translation: AAG47774.1.
    AF296765 mRNA. Translation: AAG10220.2.
    AF388384 mRNA. Translation: AAM19465.1.
    AY380057 mRNA. Translation: AAQ94072.1.
    AK055305 mRNA. Translation: BAG51497.1.
    AC000120 Genomic DNA. Translation: AAS07420.1.
    BC094684 mRNA. Translation: AAH94684.1.
    BC098442 mRNA. Translation: AAH98442.1.
    AJ294850 mRNA. Translation: CAC17608.1.
    AY993945 Genomic DNA. Translation: AAY25568.1.
    CCDSiCCDS34679.1. [O00522-3]
    CCDS5624.1. [O00522-1]
    RefSeqiNP_001013424.1. NM_001013406.1. [O00522-3]
    NP_004903.2. NM_004912.3. [O00522-1]
    NP_919436.1. NM_194454.1. [O00522-1]
    NP_919437.1. NM_194455.1. [O00522-1]
    NP_919438.1. NM_194456.1. [O00522-1]
    XP_005250717.1. XM_005250660.1. [O00522-1]
    XP_005250719.1. XM_005250662.1. [O00522-1]
    XP_005250720.1. XM_005250663.1. [O00522-1]
    XP_005250721.1. XM_005250664.1. [O00522-1]
    XP_005250722.1. XM_005250665.1. [O00522-1]
    XP_005250723.1. XM_005250666.1. [O00522-1]
    XP_005250724.1. XM_005250667.1. [O00522-1]
    XP_005250725.1. XM_005250668.1. [O00522-1]
    XP_005250726.1. XM_005250669.1. [O00522-1]
    XP_006716223.1. XM_006716160.1. [O00522-1]
    XP_006716224.1. XM_006716161.1. [O00522-1]
    XP_006716225.1. XM_006716162.1. [O00522-1]
    XP_006716226.1. XM_006716163.1. [O00522-1]
    XP_006716227.1. XM_006716164.1. [O00522-3]
    UniGeneiHs.531987.

    Genome annotation databases

    EnsembliENST00000340022; 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.
    GeneIDi889.
    KEGGihsa:889.
    UCSCiuc003ulq.1. human. [O00522-1]
    uc003ult.1. human. [O00522-3]

    Keywords - Coding sequence diversityi

    Alternative splicing

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    U90268 mRNA. Translation: AAB58582.1 .
    U90269 Genomic DNA. Translation: AAC01535.1 .
    AF310133 mRNA. Translation: AAG47774.1 .
    AF296765 mRNA. Translation: AAG10220.2 .
    AF388384 mRNA. Translation: AAM19465.1 .
    AY380057 mRNA. Translation: AAQ94072.1 .
    AK055305 mRNA. Translation: BAG51497.1 .
    AC000120 Genomic DNA. Translation: AAS07420.1 .
    BC094684 mRNA. Translation: AAH94684.1 .
    BC098442 mRNA. Translation: AAH98442.1 .
    AJ294850 mRNA. Translation: CAC17608.1 .
    AY993945 Genomic DNA. Translation: AAY25568.1 .
    CCDSi CCDS34679.1. [O00522-3 ]
    CCDS5624.1. [O00522-1 ]
    RefSeqi NP_001013424.1. NM_001013406.1. [O00522-3 ]
    NP_004903.2. NM_004912.3. [O00522-1 ]
    NP_919436.1. NM_194454.1. [O00522-1 ]
    NP_919437.1. NM_194455.1. [O00522-1 ]
    NP_919438.1. NM_194456.1. [O00522-1 ]
    XP_005250717.1. XM_005250660.1. [O00522-1 ]
    XP_005250719.1. XM_005250662.1. [O00522-1 ]
    XP_005250720.1. XM_005250663.1. [O00522-1 ]
    XP_005250721.1. XM_005250664.1. [O00522-1 ]
    XP_005250722.1. XM_005250665.1. [O00522-1 ]
    XP_005250723.1. XM_005250666.1. [O00522-1 ]
    XP_005250724.1. XM_005250667.1. [O00522-1 ]
    XP_005250725.1. XM_005250668.1. [O00522-1 ]
    XP_005250726.1. XM_005250669.1. [O00522-1 ]
    XP_006716223.1. XM_006716160.1. [O00522-1 ]
    XP_006716224.1. XM_006716161.1. [O00522-1 ]
    XP_006716225.1. XM_006716162.1. [O00522-1 ]
    XP_006716226.1. XM_006716163.1. [O00522-1 ]
    XP_006716227.1. XM_006716164.1. [O00522-3 ]
    UniGenei Hs.531987.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    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 [» ]
    ProteinModelPortali O00522.
    SMRi O00522. Positions 8-413, 419-729.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 107330. 12 interactions.
    IntActi O00522. 4 interactions.
    STRINGi 9606.ENSP00000344668.

    PTM databases

    PhosphoSitei O00522.

    Proteomic databases

    MaxQBi O00522.
    PaxDbi O00522.
    PRIDEi O00522.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    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 .
    GeneIDi 889.
    KEGGi hsa:889.
    UCSCi uc003ulq.1. human. [O00522-1 ]
    uc003ult.1. human. [O00522-3 ]

    Organism-specific databases

    CTDi 889.
    GeneCardsi GC07M091828.
    GeneReviewsi KRIT1.
    HGNCi HGNC:1573. KRIT1.
    HPAi HPA049606.
    MIMi 116860. phenotype.
    604214. gene.
    neXtProti NX_O00522.
    Orphaneti 221061. Hereditary cerebral cavernous malformation.
    PharmGKBi PA26144.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi KOG4335.
    HOGENOMi HOG000252958.
    HOVERGENi HBG052292.
    InParanoidi O00522.
    KOi K17705.
    OMAi SKKHKQG.
    OrthoDBi EOG7SR4KS.
    PhylomeDBi O00522.
    TreeFami TF317921.

    Miscellaneous databases

    GeneWikii KRIT1.
    GenomeRNAii 889.
    NextBioi 3670.
    PROi O00522.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi O00522.
    Bgeei O00522.
    CleanExi HS_KRIT1.
    Genevestigatori O00522.

    Family and domain databases

    Gene3Di 1.20.80.10. 1 hit.
    1.25.40.20. 1 hit.
    InterProi 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.
    [Graphical view ]
    Pfami PF00023. Ank. 1 hit.
    PF12796. Ank_2. 1 hit.
    PF00373. FERM_M. 1 hit.
    [Graphical view ]
    SMARTi SM00248. ANK. 3 hits.
    SM00295. B41. 1 hit.
    [Graphical view ]
    SUPFAMi SSF47031. SSF47031. 1 hit.
    SSF48403. SSF48403. 1 hit.
    PROSITEi PS50297. ANK_REP_REGION. 1 hit.
    PS50088. ANK_REPEAT. 1 hit.
    PS50057. FERM_3. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "Association of Krev-1/rap1a with Krit1, a novel ankyrin repeat-containing protein encoded by a gene mapping to 7q21-22."
      Serebriiskii I., Estojak J., Sonoda G., Testa J.R., Golemis E.A.
      Oncogene 15:1043-1049(1997) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), TISSUE SPECIFICITY, INTERACTION WITH RAP1A.
      Tissue: Kidney and Mammary cancer.
    2. "Cloning of the murine Krit1 cDNA reveals novel mammalian 5' coding exons."
      Zhang J., Clatterbuck R.E., Rigamonti D., Dietz H.C.
      Genomics 70:392-395(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
    3. "Computational and experimental analyses reveal previously undetected coding exons of the KRIT1 (CCM1) gene."
      Sahoo T., Goenaga-Diaz E., Serebriiskii I.G., Thomas J.W., Kotova E., Cuellar J.G., Peloquin J.M., Golemis E., Beitinjaneh F., Green E.D., Johnson E.W., Marchuk D.A.
      Genomics 71:123-126(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), ALTERNATIVE SPLICING.
    4. "Mutation and expression analysis of the KRIT1 gene associated with cerebral cavernous malformations (CCM1)."
      Kehrer-Sawatzki H., Wilda M., Braun V.M., Richter H.-P., Hameister H.
      Acta Neuropathol. 104:231-240(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), ALTERNATIVE SPLICING, VARIANTS CCM1 SER-97 AND GLU-569.
    5. "Four novel and three known KRIT1 mutations in CCM Italian patients: Characterization at mRNA and protein level."
      Ferrera L., Marini V., Dorcaratto A., Pigatto F., Alberti F., Forni M., Cama A., Viale G., Origone P., Mareni C., Garre' C.
      Submitted (SEP-2003) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
    6. "Complete sequencing and characterization of 21,243 full-length human cDNAs."
      Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.
      , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
      Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
      Tissue: Brain.
    7. "The DNA sequence of human chromosome 7."
      Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H., Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K., Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A., Delehaunty K.D., Miner T.L.
      , Nash W.E., Cordes M., Du H., Sun H., Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A., Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P., Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M., Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S., Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R., Strowmatt C., Latreille P., Miller N., Johnson D., Murray J., Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W., Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A., Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E., Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E., Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A., Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A., Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R., McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H., Wilson R.K.
      Nature 424:157-164(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    8. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
      The MGC Project Team
      Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
      Tissue: Brain and Uterus.
    9. "Identification of eight novel 5`-exons in cerebral capillary malformation gene-1 (CCM1) encoding KRIT1."
      Eerola I., McIntyre B., Vikkula M.
      Biochim. Biophys. Acta 1517:464-467(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1-243, ALTERNATIVE SPLICING.
    10. "Six novel and three known KRIT1 mutations in CCM patients: characterization at mRNA level."
      Marini V., Ferrera L., Dorcaratto A., Forni M., Capra V., Origone P., Mareni C., Garre' C.
      Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 244-281.
    11. "Interaction between krit1 and icap1alpha infers perturbation of integrin beta1-mediated angiogenesis in the pathogenesis of cerebral cavernous malformation."
      Zhang J., Clatterbuck R.E., Rigamonti D., Chang D.D., Dietz H.C.
      Hum. Mol. Genet. 10:2953-2960(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, INTERACTION WITH ITGB1 AND ITGB1BP1, MUTAGENESIS OF ASN-192 AND TYR-195.
    12. "KRIT1 association with the integrin-binding protein ICAP-1: a new direction in the elucidation of cerebral cavernous malformations (CCM1) pathogenesis."
      Zawistowski J.S., Serebriiskii I.G., Lee M.F., Golemis E.A., Marchuk D.A.
      Hum. Mol. Genet. 11:389-396(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH ITGB1BP1, MUTAGENESIS OF ASN-192 AND TYR-195.
    13. "Krit 1 interactions with microtubules and membranes are regulated by Rap1 and integrin cytoplasmic domain associated protein-1."
      Beraud-Dufour S., Gautier R., Albiges-Rizo C., Chardin P., Faurobert E.
      FEBS J. 274:5518-5532(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, IDENTIFICATION IN A COMPLEX WITH ITGB1BP1 AND RAP1A, INTERACTION WITH ITGB1BP1 AND RAP1A, SUBCELLULAR LOCATION, MUTAGENESIS OF 47-LYS--LYS-50 AND 192-ASN--TYR-195.
    14. "CCM1 regulates vascular-lumen organization by inducing endothelial polarity."
      Lampugnani M.G., Orsenigo F., Rudini N., Maddaluno L., Boulday G., Chapon F., Dejana E.
      J. Cell Sci. 123:1073-1080(2010) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH CDH5.
    15. "KRIT1 regulates the homeostasis of intracellular reactive oxygen species."
      Goitre L., Balzac F., Degani S., Degan P., Marchi S., Pinton P., Retta S.F.
      PLoS ONE 5:E11786-E11786(2010) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.
    16. "Cerebral cavernous malformation protein CCM1 inhibits sprouting angiogenesis by activating DELTA-NOTCH signaling."
      Wuestehube J., Bartol A., Liebler S.S., Bruetsch R., Zhu Y., Felbor U., Sure U., Augustin H.G., Fischer A.
      Proc. Natl. Acad. Sci. U.S.A. 107:12640-12645(2010) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.
    17. "A mechanism of Rap1-induced stabilization of endothelial cell--cell junctions."
      Liu J.J., Stockton R.A., Gingras A.R., Ablooglu A.J., Han J., Bobkov A.A., Ginsberg M.H.
      Mol. Biol. Cell 22:2509-2519(2011) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH RAP1A, MUTAGENESIS OF ARG-452.
    18. "Structural basis for small G protein effector interaction of Ras-related protein 1 (Rap1) and adaptor protein Krev interaction trapped 1 (KRIT1)."
      Li X., Zhang R., Draheim K.M., Liu W., Calderwood D.A., Boggon T.J.
      J. Biol. Chem. 287:22317-22327(2012) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (1.95 ANGSTROMS) OF 420-736 IN COMPLEX WITH RAP1B, MUTAGENESIS OF SER-430; ARG-432 AND ARG-452, INTERACTION WITH RAP1B.
    19. "Structural basis of the junctional anchorage of the cerebral cavernous malformations complex."
      Gingras A.R., Liu J.J., Ginsberg M.H.
      J. Cell Biol. 199:39-48(2012) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (2.49 ANGSTROMS) OF 417-736 IN COMPLEX WITH HEG1, INTERACTION WITH HEG1; RAP1A AND CCM2, SUBCELLULAR LOCATION, MUTAGENESIS OF LEU-717 AND LEU-721.
    20. "Mechanism for KRIT1 release of ICAP1-mediated suppression of integrin activation."
      Liu W., Draheim K.M., Zhang R., Calderwood D.A., Boggon T.J.
      Mol. Cell 0:0-0(2013)
      Cited for: X-RAY CRYSTALLOGRAPHY (2.54 ANGSTROMS) OF 1-198 IN COMPLEX WITH ITGB1BP1, INTERACTION WITH ITGB1BP1, FUNCTION, DOMAIN, MUTAGENESIS OF ALA-176; ARG-179; PRO-182; ARG-185; ASN-192 AND TYR-195.

    Entry informationi

    Entry nameiKRIT1_HUMAN
    AccessioniPrimary (citable) accession number: O00522
    Secondary accession number(s): A6NNU0
    , O43894, Q506L6, Q6U276, Q75N19, Q9H180, Q9H264, Q9HAX5
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: April 27, 2001
    Last sequence update: October 11, 2005
    Last modified: October 1, 2014
    This is version 140 of the entry and version 2 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program
    DisclaimerAny 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, Complete proteome, Reference proteome

    Documents

    1. Human chromosome 7
      Human chromosome 7: entries, gene names and cross-references to MIM
    2. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    3. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    4. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    5. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    6. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3