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O00522 (KRIT1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 139. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Krev interaction trapped protein 1

Short name=Krev interaction trapped 1
Alternative name(s):
Cerebral cavernous malformations 1 protein
Gene names
Name:KRIT1
Synonyms:CCM1
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length736 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.11 Ref.13 Ref.14 Ref.15 Ref.16 Ref.17 Ref.20

Subunit structure

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. Ref.1 Ref.11 Ref.12 Ref.13 Ref.14 Ref.17 Ref.18 Ref.19 Ref.20

Subcellular location

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. Ref.13 Ref.14 Ref.17 Ref.19

Tissue specificity

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

Domain

The FERM domain mediates binding to RAP1A and RAP1B and is necessary for binding to phosphatidylinositol 4,5-bisphosphate (PIP2). Ref.20

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. Ref.20

Involvement in disease

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.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.4

Sequence similarities

Contains 4 ANK repeats.

Contains 1 FERM domain.

Ontologies

Keywords
   Biological processAngiogenesis
   Cellular componentCell junction
Cell membrane
Cytoplasm
Cytoskeleton
Membrane
   Coding sequence diversityAlternative splicing
   DiseaseDisease mutation
   DomainANK repeat
Repeat
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processangiogenesis

Inferred from electronic annotation. Source: UniProtKB-KW

cell redox homeostasis

Inferred from mutant phenotype Ref.15. Source: UniProtKB

negative regulation of angiogenesis

Inferred from mutant phenotype Ref.16. Source: UniProtKB

negative regulation of endothelial cell apoptotic process

Inferred from mutant phenotype Ref.16. Source: UniProtKB

negative regulation of endothelial cell migration

Inferred from mutant phenotype Ref.16. Source: UniProtKB

negative regulation of endothelial cell proliferation

Inferred from mutant phenotype Ref.16. Source: UniProtKB

positive regulation of protein binding

Inferred from electronic annotation. Source: Ensembl

regulation of catalytic activity

Traceable author statement Ref.1. Source: GOC

regulation of establishment of cell polarity

Inferred from mutant phenotype Ref.14. Source: UniProtKB

small GTPase mediated signal transduction

Traceable author statement Ref.1. Source: ProtInc

   Cellular_componentcell-cell junction

Inferred from direct assay Ref.14. Source: UniProtKB

cytoplasm

Inferred from electronic annotation. Source: UniProtKB-KW

extracellular space

Inferred from direct assay PubMed 22664934. Source: UniProt

microtubule

Inferred from direct assay Ref.13. Source: UniProtKB

plasma membrane

Inferred from direct assay Ref.13. Source: UniProtKB

   Molecular_functionmicrotubule binding

Inferred from direct assay Ref.13. Source: UniProtKB

phosphatidylinositol-4,5-bisphosphate binding

Inferred from direct assay Ref.13. Source: UniProtKB

protein binding

Inferred from physical interaction PubMed 16037064Ref.13Ref.14. Source: UniProtKB

protein complex binding

Inferred from direct assay Ref.13. Source: UniProtKB

small GTPase regulator activity

Traceable author statement Ref.1. Source: ProtInc

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

CCM2Q9BSQ53EBI-1573121,EBI-1573056

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: O00522-1)

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.
Isoform 2 (identifier: O00522-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-207: Missing.
Isoform 3 (identifier: O00522-3)

The sequence of this isoform differs from the canonical sequence as follows:
     283-330: Missing.
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 736736Krev interaction trapped protein 1
PRO_0000067023

Regions

Repeat287 – 31630ANK 1
Repeat320 – 35031ANK 2
Repeat354 – 38330ANK 3
Repeat388 – 41932ANK 4
Domain420 – 734315FERM
Region1 – 170170N-terminal domain similar to Nudix hydrolase domain
Region172 – 19524Interaction with ITGB1BP1
Region430 – 45223Interaction with RAP1B

Natural variations

Alternative sequence1 – 207207Missing in isoform 2.
VSP_015800
Alternative sequence283 – 33048Missing in isoform 3.
VSP_043327
Natural variant971F → S in CCM1. Ref.4
VAR_023573
Natural variant5691K → E in CCM1. Ref.4
VAR_023574

Experimental info

Mutagenesis47 – 504KKRK → AAAA: Reduces interaction with microtubules, but not with ITGB1BP1. Ref.13
Mutagenesis1761A → D: Strongly reduces ITGB1BP1 binding; when associated with D-182. Ref.20
Mutagenesis1791R → A: Strongly reduces ITGB1BP1 binding; when associated with A-179. Ref.20
Mutagenesis1821P → D: Strongly reduces ITGB1BP1 binding; when associated with D-176. Ref.20
Mutagenesis1851R → A: Strongly reduces ITGB1BP1 binding; when associated with A-179. Ref.20
Mutagenesis192 – 1954NPAY → APAA: Reduces interaction with ITGB1BP1. Ref.11 Ref.12 Ref.13 Ref.20
Mutagenesis1921N → A: Reduces ITGB1BP1 binding; when associated with A-195. Ref.11 Ref.12 Ref.20
Mutagenesis1951Y → A: Reduces ITGB1BP1 binding; when associated with A-192. Ref.11 Ref.12 Ref.20
Mutagenesis4301S → E: Impairs interaction with RAP1B. Ref.18
Mutagenesis4321R → E: Impairs interaction with RAP1B. Ref.18
Mutagenesis4521R → E: 40-fold-reduced affinity for Rap1A. Ref.17 Ref.18
Mutagenesis4521R → E: Impairs interaction with RAP1B. Ref.17 Ref.18
Mutagenesis7171L → A: Strongly reduced affinity for HEG1; when associated with A-721. Ref.19
Mutagenesis7211L → A: Strongly reduced affinity for HEG1; when associated with A-717. Ref.19
Sequence conflict1381I → T in AAQ94072. Ref.5
Sequence conflict2341F → G in AAB58582. Ref.1
Sequence conflict7311P → A in AAB58582. Ref.1
Sequence conflict7311P → A in AAG47774. Ref.2
Sequence conflict7311P → A in AAQ94072. Ref.5

Secondary structure

........................................................................................... 736
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified October 11, 2005. Version 2.
Checksum: D11F75ED629E85AC

FASTA73684,348
        10         20         30         40         50         60 
MGNPENIEDA YVAVIRPKNT ASLNSREYRA KSYEILLHEV PIEGQKKKRK KVLLETKLQG 

        70         80         90        100        110        120 
NSEITQGILD YVVETTKPIS PANQGIRGKR VVLMKKFPLD GEKMGREASL FIVPSVVKDN 

       130        140        150        160        170        180 
TKYTYTPGCP IFYCLQDIMR VCSESSTHFA TLTARMLIAL DKWLDERHAQ SHFIPALFRP 

       190        200        210        220        230        240 
SPLERIKTNV INPAYATESG QTENSLHMGY SALEIKSKML ALEKADTCIY NPLFGSDLQY 

       250        260        270        280        290        300 
TNRVDKVVIN PYFGLGAPDY SKIQIPKQEK WQRSMSSVTE DKERQWVDDF PLHRSACEGD 

       310        320        330        340        350        360 
SELLSRLLSE RFSVNQLDSD HWAPIHYACW YGKVEATRIL LEKGKCNPNL LNGQLSSPLH 

       370        380        390        400        410        420 
FAAGGGHAEI VQILLNHPET DRHITDQQGR SPLNICEENK QNNWEEAAKL LKEAINKPYE 

       430        440        450        460        470        480 
KVRIYRMDGS YRSVELKHGN NTTVQQIMEG MRLSQETQQY FTIWICSENL SLQLKPYHKP 

       490        500        510        520        530        540 
LQHVRDWPEI LAELTNLDPQ RETPQLFLRR DVRLPLEVEK QIEDPLAILI LFDEARYNLL 

       550        560        570        580        590        600 
KGFYTAPDAK LITLASLLLQ IVYGNYESKK HKQGFLNEEN LKSIVPVTKL KSKAPHWTNR 

       610        620        630        640        650        660 
ILHEYKNLST SEGVSKEMHH LQRMFLQNCW EIPTYGAAFF TGQIFTKASP SNHKVIPVYV 

       670        680        690        700        710        720 
GVNIKGLHLL NMETKALLIS LKYGCFMWQL GDTDTCFQIH SMENKMSFIV HTKQAGLVVK 

       730 
LLMKLNGQLM PTERNS 

« Hide

Isoform 2 [UniParc].

Checksum: D56082828EEB7094
Show »

FASTA52960,945
Isoform 3 [UniParc].

Checksum: E62A1A28360F87F1
Show »

FASTA68878,650

References

« Hide 'large scale' references
[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. expand/collapse author list , 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. expand/collapse author list , 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.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
CCDSCCDS34679.1. [O00522-3]
CCDS5624.1. [O00522-1]
RefSeqNP_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]
UniGeneHs.531987.

3D structure databases

PDBe
RCSB-PDB
PDBj
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[»]
ProteinModelPortalO00522.
SMRO00522. Positions 8-413, 419-729.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid107330. 12 interactions.
IntActO00522. 4 interactions.
STRING9606.ENSP00000344668.

PTM databases

PhosphoSiteO00522.

Proteomic databases

MaxQBO00522.
PaxDbO00522.
PRIDEO00522.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000340022; 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.
GeneID889.
KEGGhsa:889.
UCSCuc003ulq.1. human. [O00522-1]
uc003ult.1. human. [O00522-3]

Organism-specific databases

CTD889.
GeneCardsGC07M091828.
GeneReviewsKRIT1.
HGNCHGNC:1573. KRIT1.
HPAHPA049606.
MIM116860. phenotype.
604214. gene.
neXtProtNX_O00522.
Orphanet221061. Hereditary cerebral cavernous malformation.
PharmGKBPA26144.
GenAtlasSearch...

Phylogenomic databases

eggNOGKOG4335.
HOGENOMHOG000252958.
HOVERGENHBG052292.
InParanoidO00522.
KOK17705.
OMASKKHKQG.
OrthoDBEOG7SR4KS.
PhylomeDBO00522.
TreeFamTF317921.

Gene expression databases

ArrayExpressO00522.
BgeeO00522.
CleanExHS_KRIT1.
GenevestigatorO00522.

Family and domain databases

Gene3D1.20.80.10. 1 hit.
1.25.40.20. 1 hit.
InterProIPR002110. 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]
PfamPF00023. Ank. 1 hit.
PF12796. Ank_2. 1 hit.
PF00373. FERM_M. 1 hit.
[Graphical view]
SMARTSM00248. ANK. 3 hits.
SM00295. B41. 1 hit.
[Graphical view]
SUPFAMSSF47031. SSF47031. 1 hit.
SSF48403. SSF48403. 1 hit.
PROSITEPS50297. ANK_REP_REGION. 1 hit.
PS50088. ANK_REPEAT. 1 hit.
PS50057. FERM_3. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiKRIT1.
GenomeRNAi889.
NextBio3670.
PROO00522.
SOURCESearch...

Entry information

Entry nameKRIT1_HUMAN
AccessionPrimary (citable) accession number: O00522
Secondary accession number(s): A6NNU0 expand/collapse secondary AC list , O43894, Q506L6, Q6U276, Q75N19, Q9H180, Q9H264, Q9HAX5
Entry history
Integrated into UniProtKB/Swiss-Prot: April 27, 2001
Last sequence update: October 11, 2005
Last modified: July 9, 2014
This is version 139 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 7

Human chromosome 7: entries, gene names and cross-references to MIM