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Protein

Krev interaction trapped protein 1

Gene

Krit1

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Component of the CCM signaling pathway which is a crucial regulator of heart and vessel formation and integrity. Negative regulator of angiogenesis. Inhibits endothelial proliferation, apoptosis, migration, lumen formation and sprouting angiogenesis in primary endothelial cells. Promotes AKT phosphorylation in a NOTCH-dependent and independent manner, and inhibits ERK1/2 phosphorylation indirectly through activation of the DELTA-NOTCH cascade. Acts in concert with CDH5 to establish and maintain correct endothelial cell polarity and vascular lumen and these effects are mediated by recruitment and activation of the Par polarity complex and RAP1B. Required for the localization of phosphorylated PRKCZ, PARD3, TIAM1 and RAP1B to the cell junction, and cell junction stabilization. Plays a role in integrin signaling via its interaction with ITGB1BP1; this prevents the interaction between ITGB1 and ITGB1BP1. Microtubule-associated protein that binds to phosphatidylinositol 4,5-bisphosphate (PIP2)-containing membranes in a GTP-bound RAP1-dependent manner (By similarity). Plays an important role in the maintenance of the intracellular reactive oxygen species (ROS) homeostasis to prevent oxidative cellular damage. Regulates the homeostasis of intracellular ROS through an antioxidant pathway involving FOXO1 and SOD2. Facilitates the down-regulation of cyclin-D1 (CCND1) levels required for cell transition from proliferative growth to quiescence by preventing the accumulation of intracellular ROS through the modulation of FOXO1 and SOD2 levels.By similarity3 Publications

GO - Molecular functioni

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: MGI
  • regulation of establishment of cell polarity Source: UniProtKB

Keywordsi

Biological processAngiogenesis

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 homolog
Gene namesi
Name:Krit1
Synonyms:Ccm1
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 5

Organism-specific databases

MGIiMGI:1930618 Krit1

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cell junction, Cell membrane, Cytoplasm, Cytoskeleton, Membrane

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000670241 – 736Krev interaction trapped protein 1Add BLAST736

Proteomic databases

PaxDbiQ6S5J6
PRIDEiQ6S5J6

PTM databases

iPTMnetiQ6S5J6
PhosphoSitePlusiQ6S5J6

Expressioni

Tissue specificityi

Expressed in heart, brain, spleen, lung, thymus, kidney and testis. Isoform 2 was more frequently expressed in the thymus than isoform 1.2 Publications

Developmental stagei

At stage 9.5 dpc ubiquitously expressed, at 12.5 dpc expressed in structures of the CNS, especially in zones of the proliferative active ventricular zones of the brain and in the spinal cord. Expression increased in organs that were in the state of organ expansion like lung and liver. At 17.5 dpc, expression was strongly reduced in endoderm-derived tissues. In early postnatal development, strongly expressed in regions of ossification.1 Publication

Gene expression databases

BgeeiENSMUSG00000000600
CleanExiMM_KRIT1
ExpressionAtlasiQ6S5J6 baseline and differential
GenevisibleiQ6S5J6 MM

Interactioni

Subunit structurei

Found in a complex, at least composed of ITGB1BP1, KRIT1 and RAP1A. Interacts (via C-terminus FERM domain) with RAP1A (active GTP-bound form preferentially); the interaction does not induce the opening conformation of KRIT1. Interacts (via N-terminus NPXY motif) with ITGB1BP1; the interaction induces the opening conformation of KRIT1 and competes with ITGB1 for ITGB1BP1 interaction. Associates (via N-terminus and C-terminus regions) with microtubules; the interaction is inhibited in presence of ITGB1BP1 and active GTP-bound RAP1A. Interacts (via FERM domain) with RAP1B. Interacts with CDH5. Interacts with RAP1A (By similarity). Interacts with HEG1 and CCM2; greatly facilitates CCM2-binding to HEG1 (PubMed:19151727).By similarity1 Publication

GO - Molecular functioni

Protein-protein interaction databases

BioGridi219753, 1 interactor
CORUMiQ6S5J6
STRINGi10090.ENSMUSP00000078985

Structurei

3D structure databases

ProteinModelPortaliQ6S5J6
SMRiQ6S5J6
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Repeati287 – 316ANK 1Sequence analysisAdd BLAST30
Repeati320 – 350ANK 2Sequence analysisAdd BLAST31
Repeati354 – 384ANK 3Sequence analysisAdd BLAST31
Repeati388 – 419ANK 4Sequence analysisAdd BLAST32
Domaini420 – 736FERMPROSITE-ProRule annotationAdd BLAST317

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 170N-terminal domain similar to Nudix hydrolase domainBy similarityAdd BLAST170
Regioni172 – 195Interaction with ITGB1BP1By similarityAdd BLAST24
Regioni430 – 452Interaction with RAP1BBy similarityAdd BLAST23

Domaini

The FERM domain mediates binding to RAP1A and RAP1B and is necessary for binding to phosphatidylinositol 4,5-bisphosphate (PIP2).By similarity
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.By similarity
Contains 4 ANK repeats that precede the FERM domain.By similarity

Keywords - Domaini

ANK repeat, Repeat

Phylogenomic databases

eggNOGiKOG4335 Eukaryota
ENOG410ZV6V LUCA
GeneTreeiENSGT00530000063721
HOGENOMiHOG000252958
HOVERGENiHBG052292
InParanoidiQ6S5J6
KOiK17705
OMAiVCEENKQ
OrthoDBiEOG091G0IG7
PhylomeDBiQ6S5J6
TreeFamiTF317921

Family and domain databases

CDDicd00204 ANK, 1 hit
cd14473 FERM_B-lobe, 1 hit
Gene3Di1.20.80.10, 1 hit
1.25.40.20, 1 hit
2.30.29.30, 1 hit
InterProiView 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
IPR032022 NUDIX
IPR011993 PH-like_dom_sf
PfamiView protein in Pfam
PF00373 FERM_M, 1 hit
PF16705 NUDIX_5, 1 hit
SMARTiView protein in SMART
SM00248 ANK, 3 hits
SM00295 B41, 1 hit
SUPFAMiSSF47031 SSF47031, 1 hit
SSF48403 SSF48403, 1 hit
PROSITEiView protein in PROSITE
PS50297 ANK_REP_REGION, 1 hit
PS50088 ANK_REPEAT, 2 hits
PS50057 FERM_3, 1 hit

Sequences (4)i

Sequence statusi: Complete.

This entry describes 4 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q6S5J6-1) [UniParc]FASTAAdd to basket
Also known as: Krit1A

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
KVLLETKLQS NSEIAQGILD YVVETTKPIS PANQGIKGKR VVLMRKFPLD
110 120 130 140 150
GEKTGREAAL FIVPSVVKDN TKYAYTPGCP IFYCLQDIMR VCSESSTHFA
160 170 180 190 200
TLTARMLIAL DKWLDERHAQ SHFIPALFRP SPLERIKTNV INPAYAAELG
210 220 230 240 250
QVDNSLHMGY SALEIKSKML ALEKADTCIY NPLFGSDLQY TNRVDKVVIN
260 270 280 290 300
PYFGLGAPDY SKIQIPKQEK WQRSMSSVVE DKERQWVDDF PLHRNACEGD
310 320 330 340 350
SELLSHLLDK GLSVNQLDND HWAPIHYACW YGKVEATRIL LEKGKCNPNL
360 370 380 390 400
LNGQLSSPLH FAAGGGHAEI VQILLTHPDI DRHITDQQGR SPLNVCEENK
410 420 430 440 450
QNNWEEAAKL LKDAINKPYE KVRIYRMDGS YRSVELKHGN NTTAQQIMEG
460 470 480 490 500
MRLSQETQRY FTIWICSENL SLQFKPYHKP LQQVHDWPEI LAELTNLDPQ
510 520 530 540 550
RETPQLFLRR DVGLPLEVEK KIEDPLAILI LFDEARYNLL KGFYTAPDAK
560 570 580 590 600
LITLASLLLQ IVYGNYESKK HKQGFLNEET LKSIVPITKL KSKAPHWINR
610 620 630 640 650
ILHEYKNLSL SEGVSKEMHH LQRMFLQNCW EIPTYGAAFF TGQIFTKASP
660 670 680 690 700
SNHKVIPVYV GVNIKGLHLL NMETKALLIS LKYCCFTWQL GDAGTCFQIH
710 720 730
SMENKMSFIV HTKQAGLVVK LLMKLNGQLM PSERNS
Length:736
Mass (Da):83,982
Last modified:July 5, 2004 - v1
Checksum:i441333F62A1D208A
GO
Isoform 2 (identifier: Q6S5J6-2) [UniParc]FASTAAdd to basket
Also known as: Krit1B

The sequence of this isoform differs from the canonical sequence as follows:
     676-714: Missing.

Show »
Length:697
Mass (Da):79,506
Checksum:iC3706363D586A5FB
GO
Isoform 3 (identifier: Q6S5J6-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     295-300: Missing.

Show »
Length:730
Mass (Da):83,392
Checksum:iDB485504450EF4FA
GO
Isoform 4 (identifier: Q6S5J6-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     330-736: Missing.

Show »
Length:329
Mass (Da):37,297
Checksum:i18D5A4F97B85F36D
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti47K → E in AAG18456 (PubMed:12172908).Curated1
Sequence conflicti319N → D in AAG18456 (PubMed:12172908).Curated1
Sequence conflicti515P → R in AAG47775 (PubMed:11161791).Curated1
Sequence conflicti550 – 552KLI → RLD in AAG47775 (PubMed:11161791).Curated3
Sequence conflicti665K → R in AAG47775 (PubMed:11161791).Curated1
Sequence conflicti684 – 689CCFTWQ → WLLTWA in AAG47775 (PubMed:11161791).Curated6

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_015801295 – 300Missing in isoform 3. 1 Publication6
Alternative sequenceiVSP_015802330 – 736Missing in isoform 4. CuratedAdd BLAST407
Alternative sequenceiVSP_015803676 – 714Missing in isoform 2. 2 PublicationsAdd BLAST39

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF310134 mRNA Translation: AAG47775.1
AF306509 mRNA Translation: AAG18456.1
AY328895 mRNA Translation: AAQ92980.1
AY464945 mRNA Translation: AAR24089.1
BC054819 mRNA Translation: AAH54819.1
AK041574 mRNA Translation: BAC30991.1
CCDSiCCDS39002.1 [Q6S5J6-1]
CCDS51409.1 [Q6S5J6-2]
RefSeqiNP_001164023.1, NM_001170552.1 [Q6S5J6-2]
NP_109600.2, NM_030675.3 [Q6S5J6-1]
XP_006503680.1, XM_006503617.3 [Q6S5J6-1]
XP_006503681.1, XM_006503618.3 [Q6S5J6-1]
UniGeneiMm.32368
Mm.482273

Genome annotation databases

EnsembliENSMUST00000080085; ENSMUSP00000078985; ENSMUSG00000000600 [Q6S5J6-1]
ENSMUST00000171023; ENSMUSP00000132375; ENSMUSG00000000600 [Q6S5J6-2]
ENSMUST00000200577; ENSMUSP00000143776; ENSMUSG00000000600 [Q6S5J6-4]
GeneIDi79264
KEGGimmu:79264
UCSCiuc008whs.2 mouse [Q6S5J6-1]
uc008whv.2 mouse [Q6S5J6-2]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiKRIT1_MOUSE
AccessioniPrimary (citable) accession number: Q6S5J6
Secondary accession number(s): Q6VSV2
, Q7TPR8, Q8C9Q6, Q9EPY2, Q9ERH0
Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 11, 2005
Last sequence update: July 5, 2004
Last modified: May 23, 2018
This is version 138 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot

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