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Protein

Krev interaction trapped protein 1

Gene

Krit1

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

Organism-specific databases

MGIiMGI:1930618. Krit1.

Subcellular locationi

  • Cytoplasmcytoskeleton By similarity
  • Cell membrane By similarity; Peripheral membrane protein By similarity
  • Cell junction By similarity

  • 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 an ITGB1BP1-dependent manner (By similarity).By similarity

GO - Cellular componenti

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

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.By similarity1 Publication

GO - Molecular functioni

Protein-protein interaction databases

BioGridi219753. 1 interactor.
STRINGi10090.ENSMUSP00000078985.

Structurei

3D structure databases

ProteinModelPortaliQ6S5J6.
SMRiQ6S5J6.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Repeati287 – 316ANK 1Add BLAST30
Repeati320 – 350ANK 2Add BLAST31
Repeati351 – 384ANK 3Add BLAST34
Repeati388 – 419ANK 4Add 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).By similarity

Sequence similaritiesi

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

Keywords - Domaini

ANK repeat, Repeat

Phylogenomic databases

eggNOGiKOG4335. Eukaryota.
ENOG410ZV6V. LUCA.
GeneTreeiENSGT00530000063721.
HOGENOMiHOG000252958.
HOVERGENiHBG052292.
InParanoidiQ6S5J6.
KOiK17705.
OMAiVCEENKQ.
OrthoDBiEOG091G0IG7.
PhylomeDBiQ6S5J6.
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.
IPR032022. NUDIX.
[Graphical view]
PfamiPF00373. FERM_M. 1 hit.
PF16705. NUDIX_5. 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. 2 hits.
PS50057. FERM_3. 1 hit.
[Graphical view]

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

Cross-referencesi

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.

3D structure databases

ProteinModelPortaliQ6S5J6.
SMRiQ6S5J6.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi219753. 1 interactor.
STRINGi10090.ENSMUSP00000078985.

PTM databases

iPTMnetiQ6S5J6.
PhosphoSitePlusiQ6S5J6.

Proteomic databases

PaxDbiQ6S5J6.
PRIDEiQ6S5J6.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

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]

Organism-specific databases

CTDi889.
MGIiMGI:1930618. Krit1.

Phylogenomic databases

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

Miscellaneous databases

PROiQ6S5J6.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000000600.
CleanExiMM_KRIT1.
ExpressionAtlasiQ6S5J6. baseline and differential.
GenevisibleiQ6S5J6. MM.

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.
IPR032022. NUDIX.
[Graphical view]
PfamiPF00373. FERM_M. 1 hit.
PF16705. NUDIX_5. 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. 2 hits.
PS50057. FERM_3. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiKRIT1_MOUSE
AccessioniPrimary (citable) accession number: Q6S5J6
Secondary accession number(s): Q6VSV2
, Q7TPR8, Q8C9Q6, Q9EPY2, Q9ERH0
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 11, 2005
Last sequence update: July 5, 2004
Last modified: November 2, 2016
This is version 126 of the entry and version 1 of the sequence. [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
  2. SIMILARITY comments
    Index of protein domains and families

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 one 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.