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Protein

Krev interaction trapped protein 1

Gene

KRIT1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

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

  • GTPase regulator activity Source: ProtInc
  • microtubule binding Source: UniProtKB
  • phosphatidylinositol-4,5-bisphosphate binding Source: UniProtKB
  • protein complex 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
  • positive regulation of protein binding Source: Ensembl
  • regulation of catalytic activity Source: GOC
  • regulation of establishment of cell polarity Source: UniProtKB
  • small GTPase mediated signal transduction Source: ProtInc
Complete GO annotation...

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 Componenti: Chromosome 7

Organism-specific databases

HGNCiHGNC:1573. KRIT1.

Subcellular locationi

GO - Cellular componenti

  • cell-cell junction Source: UniProtKB
  • cytoplasm Source: UniProtKB-KW
  • extracellular space Source: UniProtKB
  • microtubule Source: UniProtKB
  • plasma membrane Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cell junction, Cell membrane, Cytoplasm, Cytoskeleton, Membrane

Pathology & Biotechi

Involvement in diseasei

Cerebral cavernous malformations 1 (CCM1)1 Publication

The disease is caused by mutations affecting the gene represented in this entry.

Disease descriptionA 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.

See also OMIM:116860
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. 1 Publication
Mutagenesisi179 – 1791R → A: Strongly reduces ITGB1BP1 binding; when associated with A-179. 1 Publication
Mutagenesisi182 – 1821P → D: Strongly reduces ITGB1BP1 binding; when associated with D-176. 1 Publication
Mutagenesisi185 – 1851R → A: Strongly reduces ITGB1BP1 binding; when associated with A-179. 1 Publication
Mutagenesisi192 – 1954NPAY → APAA: Reduces interaction with ITGB1BP1. 1 Publication
Mutagenesisi192 – 1921N → A: Reduces ITGB1BP1 binding; when associated with A-195. 3 Publications
Mutagenesisi195 – 1951Y → A: Reduces ITGB1BP1 binding; when associated with A-192. 3 Publications
Mutagenesisi430 – 4301S → E: Impairs interaction with RAP1B. 1 Publication
Mutagenesisi432 – 4321R → E: Impairs interaction with RAP1B. 1 Publication
Mutagenesisi452 – 4521R → E: 40-fold-reduced affinity for Rap1A. 2 Publications
Mutagenesisi452 – 4521R → E: Impairs interaction with RAP1B. 2 Publications
Mutagenesisi717 – 7171L → A: Strongly reduced affinity for HEG1; when associated with A-721. 1 Publication
Mutagenesisi721 – 7211L → A: Strongly reduced affinity for HEG1; when associated with A-717. 1 Publication

Keywords - Diseasei

Disease mutation

Organism-specific databases

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

Polymorphism and mutation databases

BioMutaiKRIT1.

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

BgeeiO00522.
CleanExiHS_KRIT1.
ExpressionAtlasiO00522. baseline.
GenevisibleiO00522. HS.

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
CCM2Q9BSQ54EBI-1573121,EBI-1573056

Protein-protein interaction databases

BioGridi107330. 13 interactions.
IntActiO00522. 5 interactions.
STRINGi9606.ENSP00000344668.

Structurei

Secondary structure

1
736
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi9 – 179Combined sources
Helixi30 – 323Combined sources
Beta strandi33 – 397Combined sources
Beta strandi54 – 574Combined sources
Helixi64 – 7512Combined sources
Beta strandi92 – 987Combined sources
Beta strandi107 – 1148Combined sources
Beta strandi131 – 1344Combined sources
Helixi135 – 1417Combined sources
Helixi151 – 17020Combined sources
Helixi173 – 1786Combined sources
Helixi182 – 1854Combined sources
Beta strandi186 – 1916Combined sources
Helixi193 – 1953Combined sources
Turni232 – 2354Combined sources
Beta strandi421 – 4255Combined sources
Beta strandi431 – 4355Combined sources
Helixi439 – 4413Combined sources
Helixi444 – 4496Combined sources
Helixi455 – 4584Combined sources
Beta strandi461 – 4677Combined sources
Beta strandi470 – 4734Combined sources
Helixi480 – 4856Combined sources
Helixi487 – 4948Combined sources
Helixi499 – 5013Combined sources
Beta strandi505 – 5106Combined sources
Helixi516 – 5194Combined sources
Helixi525 – 54117Combined sources
Helixi548 – 56316Combined sources
Helixi568 – 5714Combined sources
Beta strandi572 – 5743Combined sources
Helixi578 – 5814Combined sources
Turni582 – 5843Combined sources
Helixi587 – 5893Combined sources
Turni590 – 5934Combined sources
Helixi594 – 5963Combined sources
Helixi598 – 61013Combined sources
Beta strandi612 – 6143Combined sources
Helixi618 – 62912Combined sources
Turni633 – 6364Combined sources
Beta strandi638 – 6458Combined sources
Turni650 – 6523Combined sources
Beta strandi655 – 6628Combined sources
Beta strandi664 – 6718Combined sources
Turni672 – 6743Combined sources
Beta strandi677 – 6826Combined sources
Beta strandi685 – 6906Combined sources
Beta strandi694 – 7018Combined sources
Turni702 – 7054Combined sources
Beta strandi706 – 7116Combined sources
Helixi715 – 72814Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
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[»]
4TKNX-ray3.00D/E/F225-237[»]
ProteinModelPortaliO00522.
SMRiO00522. Positions 8-197, 291-413, 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.
GeneTreeiENSGT00530000063721.
HOGENOMiHOG000252958.
HOVERGENiHBG052292.
InParanoidiO00522.
KOiK17705.
OMAiNHPEVDR.
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. AlignAdd to basket

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

        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
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 (Ref. 5) Curated
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 (Ref. 5) Curated

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:
EMBLi
GenBanki
DDBJi
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_005250660.2. [O00522-1]
XP_005250719.1. XM_005250662.2. [O00522-1]
XP_005250721.1. XM_005250664.2. [O00522-1]
XP_005250722.1. XM_005250665.2. [O00522-1]
XP_005250723.1. XM_005250666.2. [O00522-1]
XP_005250724.1. XM_005250667.2. [O00522-1]
XP_005250725.1. XM_005250668.2. [O00522-1]
XP_005250726.1. XM_005250669.2. [O00522-1]
XP_006716223.1. XM_006716160.2. [O00522-1]
XP_006716224.1. XM_006716161.2. [O00522-1]
XP_006716225.1. XM_006716162.2. [O00522-1]
XP_006716226.1. XM_006716163.2. [O00522-1]
XP_011514953.1. XM_011516651.1. [O00522-1]
XP_011514954.1. XM_011516652.1. [O00522-1]
XP_011514955.1. XM_011516653.1. [O00522-1]
XP_011514956.1. XM_011516654.1. [O00522-1]
XP_011514957.1. XM_011516655.1. [O00522-1]
XP_011514958.1. XM_011516656.1. [O00522-1]
XP_011514959.1. XM_011516657.1. [O00522-1]
XP_011514960.1. XM_011516658.1. [O00522-1]
XP_011514961.1. XM_011516659.1. [O00522-1]
XP_011514962.1. XM_011516660.1. [O00522-1]
XP_011514963.1. XM_011516661.1. [O00522-1]
UniGeneiHs.531987.

Genome annotation databases

EnsembliENST00000340022; ENSP00000344668; ENSG00000001631.
ENST00000394503; ENSP00000378011; ENSG00000001631. [O00522-3]
ENST00000394505; ENSP00000378013; ENSG00000001631.
ENST00000394507; ENSP00000378015; ENSG00000001631.
ENST00000412043; ENSP00000410909; 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:
EMBLi
GenBanki
DDBJi
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_005250660.2. [O00522-1]
XP_005250719.1. XM_005250662.2. [O00522-1]
XP_005250721.1. XM_005250664.2. [O00522-1]
XP_005250722.1. XM_005250665.2. [O00522-1]
XP_005250723.1. XM_005250666.2. [O00522-1]
XP_005250724.1. XM_005250667.2. [O00522-1]
XP_005250725.1. XM_005250668.2. [O00522-1]
XP_005250726.1. XM_005250669.2. [O00522-1]
XP_006716223.1. XM_006716160.2. [O00522-1]
XP_006716224.1. XM_006716161.2. [O00522-1]
XP_006716225.1. XM_006716162.2. [O00522-1]
XP_006716226.1. XM_006716163.2. [O00522-1]
XP_011514953.1. XM_011516651.1. [O00522-1]
XP_011514954.1. XM_011516652.1. [O00522-1]
XP_011514955.1. XM_011516653.1. [O00522-1]
XP_011514956.1. XM_011516654.1. [O00522-1]
XP_011514957.1. XM_011516655.1. [O00522-1]
XP_011514958.1. XM_011516656.1. [O00522-1]
XP_011514959.1. XM_011516657.1. [O00522-1]
XP_011514960.1. XM_011516658.1. [O00522-1]
XP_011514961.1. XM_011516659.1. [O00522-1]
XP_011514962.1. XM_011516660.1. [O00522-1]
XP_011514963.1. XM_011516661.1. [O00522-1]
UniGeneiHs.531987.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
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[»]
4TKNX-ray3.00D/E/F225-237[»]
ProteinModelPortaliO00522.
SMRiO00522. Positions 8-197, 291-413, 419-729.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi107330. 13 interactions.
IntActiO00522. 5 interactions.
STRINGi9606.ENSP00000344668.

PTM databases

PhosphoSiteiO00522.

Polymorphism and mutation databases

BioMutaiKRIT1.

Proteomic databases

MaxQBiO00522.
PaxDbiO00522.
PRIDEiO00522.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000340022; ENSP00000344668; ENSG00000001631.
ENST00000394503; ENSP00000378011; ENSG00000001631. [O00522-3]
ENST00000394505; ENSP00000378013; ENSG00000001631.
ENST00000394507; ENSP00000378015; ENSG00000001631.
ENST00000412043; ENSP00000410909; ENSG00000001631.
GeneIDi889.
KEGGihsa:889.
UCSCiuc003ulq.1. human. [O00522-1]
uc003ult.1. human. [O00522-3]

Organism-specific databases

CTDi889.
GeneCardsiGC07M091828.
GeneReviewsiKRIT1.
HGNCiHGNC:1573. KRIT1.
HPAiHPA049606.
MIMi116860. phenotype.
604214. gene.
neXtProtiNX_O00522.
Orphaneti221061. Hereditary cerebral cavernous malformation.
PharmGKBiPA26144.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG4335.
GeneTreeiENSGT00530000063721.
HOGENOMiHOG000252958.
HOVERGENiHBG052292.
InParanoidiO00522.
KOiK17705.
OMAiNHPEVDR.
OrthoDBiEOG7SR4KS.
PhylomeDBiO00522.
TreeFamiTF317921.

Miscellaneous databases

GeneWikiiKRIT1.
GenomeRNAii889.
NextBioi3670.
PROiO00522.
SOURCEiSearch...

Gene expression databases

BgeeiO00522.
CleanExiHS_KRIT1.
ExpressionAtlasiO00522. baseline.
GenevisibleiO00522. HS.

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]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  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: July 22, 2015
This is version 150 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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.