O00522 (KRIT1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	736 AA.
Sequence status	Complete.
Protein existence	Evidence 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 EKR1/2 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. 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.12 Ref.13 Ref.14 Ref.17
Subunit structure	Interacts with CDH5 By similarity. Interacts with RAP1A. Interacts (via FERM domain) with RAP1B. Interacts with ITGB1BP1. Interacts with HEG1 and CCM2; greatly facilitates CCM2-binding to HEG1. Ref.1 Ref.11 Ref.14 Ref.15 Ref.16 Ref.17
Subcellular location	Cytoplasm › cytoskeleton. 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. Ref.11 Ref.14 Ref.16
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. Ref.17 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. Ref.17
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 process	Angiogenesis
Cellular component	Cell junction Cell membrane Cytoplasm Cytoskeleton Membrane
Coding sequence diversity	Alternative splicing
Disease	Disease mutation
Domain	ANK repeat Repeat
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	angiogenesis Inferred from electronic annotation. Source: UniProtKB-KW cell redox homeostasis Inferred from mutant phenotype Ref.12. Source: UniProtKB negative regulation of angiogenesis Inferred from mutant phenotype Ref.13. Source: UniProtKB negative regulation of endothelial cell apoptotic process Inferred from mutant phenotype Ref.13. Source: UniProtKB negative regulation of endothelial cell migration Inferred from mutant phenotype Ref.13. Source: UniProtKB negative regulation of endothelial cell proliferation Inferred from mutant phenotype Ref.13. Source: UniProtKB positive regulation of protein binding Inferred from electronic annotation. Source: Compara regulation of establishment of cell polarity Inferred from mutant phenotype Ref.11. Source: UniProtKB small GTPase mediated signal transduction Traceable author statement Ref.1. Source: ProtInc
Cellular_component	cell-cell junction Inferred from direct assay Ref.11. Source: UniProtKB cytoplasm Inferred from electronic annotation. Source: UniProtKB-KW cytoskeleton Inferred from electronic annotation. Source: UniProtKB-SubCell plasma membrane Inferred from electronic annotation. Source: UniProtKB-SubCell protein complex Inferred from electronic annotation. Source: Compara
Molecular_function	small GTPase regulator activity Traceable author statement Ref.1. Source: ProtInc
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
CCM2	Q9BSQ5	3	EBI-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 key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 736

736

Krev interaction trapped protein 1

PRO_0000067023

Regions

Repeat

287 – 316

30

ANK 1

Repeat

320 – 350

31

ANK 2

Repeat

354 – 383

30

ANK 3

Repeat

388 – 419

32

ANK 4

Domain

420 – 734

315

FERM

Region

1 – 170

170

N-terminal domain similar to Nudix hydrolase domain

Region

172 – 195

24

Interaction with ITGB1BP1

Region

430 – 452

23

Interaction with RAP1B

Natural variations

Alternative sequence

1 – 207

207

Missing in isoform 2.

VSP_015800

Alternative sequence

283 – 330

48

Missing in isoform 3.

VSP_043327

Natural variant

97

1

F → S in CCM1. Ref.4

VAR_023573

Natural variant

569

1

K → E in CCM1. Ref.4

VAR_023574

Experimental info

Mutagenesis

176

1

A → D: Strongly reduces ITGB1BP1 binding; when associated with D-182. Ref.17

Mutagenesis

179

1

R → A: Strongly reduces ITGB1BP1 binding; when associated with A-179. Ref.17

Mutagenesis

182

1

P → D: Strongly reduces ITGB1BP1 binding; when associated with D-176. Ref.17

Mutagenesis

185

1

R → A: Strongly reduces ITGB1BP1 binding; when associated with A-179. Ref.17

Mutagenesis

192

1

N → A: Reduces ITGB1BP1 binding; when associated with A-195. Ref.17

Mutagenesis

195

1

Y → A: Reduces ITGB1BP1 binding; when associated with A-192. Ref.17

Mutagenesis

430

1

S → E: Impairs interaction with RAP1B. Ref.15

Mutagenesis

432

1

R → E: Impairs interaction with RAP1B. Ref.15

Mutagenesis

452

1

R → E: 40-fold-reduced affinity for Rap1A. Ref.14 Ref.15

Mutagenesis

452

1

R → E: Impairs interaction with RAP1B. Ref.14 Ref.15

Mutagenesis

717

1

L → A: Strongly reduced affinity for HEG1; when associated with A-721. Ref.16

Mutagenesis

721

1

L → A: Strongly reduced affinity for HEG1; when associated with A-717. Ref.16

Sequence conflict

138

1

I → T in AAQ94072. Ref.5

Sequence conflict

234

1

F → G in AAB58582. Ref.1

Sequence conflict

731

1

P → A in AAB58582. Ref.1

Sequence conflict

731

1

P → A in AAG47774. Ref.2

Sequence conflict

731

1

P → A in AAQ94072. Ref.5

Secondary structure

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736

Helix Strand Turn

Details...

Beta strand

9 – 17

9

Helix

30 – 32

3

Beta strand

33 – 39

7

Beta strand

54 – 57

4

Helix

64 – 75

12

Beta strand

92 – 98

7

Beta strand

107 – 114

8

Beta strand

131 – 134

4

Helix

135 – 141

7

Helix

151 – 170

20

Helix

173 – 178

6

Helix

182 – 185

4

Beta strand

186 – 191

6

Helix

193 – 195

3

Beta strand

421 – 425

5

Beta strand

431 – 435

5

Helix

439 – 441

3

Helix

444 – 448

5

Helix

457 – 460

4

Beta strand

461 – 466

6

Beta strand

471 – 473

3

Helix

480 – 485

6

Helix

487 – 494

8

Beta strand

505 – 510

6

Helix

516 – 519

4

Helix

525 – 541

17

Helix

548 – 563

16

Helix

568 – 571

4

Beta strand

572 – 574

3

Helix

578 – 581

4

Turn

582 – 584

3

Turn

587 – 593

7

Helix

594 – 596

3

Helix

598 – 609

12

Beta strand

612 – 614

3

Helix

618 – 630

13

Turn

633 – 636

4

Beta strand

638 – 645

8

Beta strand

655 – 662

8

Beta strand

664 – 671

8

Turn

672 – 674

3

Beta strand

677 – 682

6

Beta strand

685 – 690

6

Beta strand

696 – 704

9

Beta strand

707 – 711

5

Helix

715 – 727

13

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified October 11, 2005. Version 2. Checksum: D11F75ED629E85AC	FASTA	736	84,348
	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
	Isoform 2 [UniParc]. Checksum: D56082828EEB7094	FASTA	529	60,945
	10 20 30 40 50 60 MGYSALEIKS KMLALEKADT CIYNPLFGSD LQYTNRVDKV VINPYFGLGA PDYSKIQIPK 70 80 90 100 110 120 QEKWQRSMSS VTEDKERQWV DDFPLHRSAC EGDSELLSRL LSERFSVNQL DSDHWAPIHY 130 140 150 160 170 180 ACWYGKVEAT RILLEKGKCN PNLLNGQLSS PLHFAAGGGH AEIVQILLNH PETDRHITDQ 190 200 210 220 230 240 QGRSPLNICE ENKQNNWEEA AKLLKEAINK PYEKVRIYRM DGSYRSVELK HGNNTTVQQI 250 260 270 280 290 300 MEGMRLSQET QQYFTIWICS ENLSLQLKPY HKPLQHVRDW PEILAELTNL DPQRETPQLF 310 320 330 340 350 360 LRRDVRLPLE VEKQIEDPLA ILILFDEARY NLLKGFYTAP DAKLITLASL LLQIVYGNYE 370 380 390 400 410 420 SKKHKQGFLN EENLKSIVPV TKLKSKAPHW TNRILHEYKN LSTSEGVSKE MHHLQRMFLQ 430 440 450 460 470 480 NCWEIPTYGA AFFTGQIFTK ASPSNHKVIP VYVGVNIKGL HLLNMETKAL LISLKYGCFM 490 500 510 520 WQLGDTDTCF QIHSMENKMS FIVHTKQAGL VVKLLMKLNG QLMPTERNS
	Isoform 3 [UniParc]. Checksum: E62A1A28360F87F1	FASTA	688	78,650
	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 DKYGKVEATR ILLEKGKCNP 310 320 330 340 350 360 NLLNGQLSSP LHFAAGGGHA EIVQILLNHP ETDRHITDQQ GRSPLNICEE NKQNNWEEAA 370 380 390 400 410 420 KLLKEAINKP YEKVRIYRMD GSYRSVELKH GNNTTVQQIM EGMRLSQETQ QYFTIWICSE 430 440 450 460 470 480 NLSLQLKPYH KPLQHVRDWP EILAELTNLD PQRETPQLFL RRDVRLPLEV EKQIEDPLAI 490 500 510 520 530 540 LILFDEARYN LLKGFYTAPD AKLITLASLL LQIVYGNYES KKHKQGFLNE ENLKSIVPVT 550 560 570 580 590 600 KLKSKAPHWT NRILHEYKNL STSEGVSKEM HHLQRMFLQN CWEIPTYGAA FFTGQIFTKA 610 620 630 640 650 660 SPSNHKVIPV YVGVNIKGLH LLNMETKALL ISLKYGCFMW QLGDTDTCFQ IHSMENKMSF 670 680 IVHTKQAGLV VKLLMKLNGQ LMPTERNS

References

	« Hide 'large scale' referencesShow '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. , 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]	"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.
[12]	"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.
[13]	"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.
[14]	"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.
[15]	"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.
[16]	"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.
[17]	"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.

Web resources

GeneReviews

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.

IPI

IPI00418142.
IPI00554504.
IPI00651671.

RefSeq

NP_001013424.1. NM_001013406.1.
NP_004903.2. NM_004912.3.
NP_919436.1. NM_194454.1.
NP_919437.1. NM_194455.1.
NP_919438.1. NM_194456.1.

UniGene

Hs.531987.

3D structure databases

PDBe
RCSB PDB
PDBj

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	[»]

ProteinModelPortal

O00522.

ModBase

Search...

Protein-protein interaction databases

IntAct

O00522. 4 interactions.

STRING

9606.ENSP00000344668.

PTM databases

PhosphoSite

O00522.

Proteomic databases

PaxDb

O00522.

PRIDE

O00522.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000340022; ENSP00000344668; ENSG00000001631.
ENST00000394503; ENSP00000378011; ENSG00000001631.
ENST00000394505; ENSP00000378013; ENSG00000001631.
ENST00000394507; ENSP00000378015; ENSG00000001631.
ENST00000412043; ENSP00000410909; ENSG00000001631.
ENST00000458177; ENSP00000391675; ENSG00000001631.

GeneID

889.

KEGG

hsa:889.

UCSC

uc003ulq.1. human.

Organism-specific databases

CTD

889.

GeneCards

GC07M091828.

HGNC

HGNC:1573. KRIT1.

HPA

HPA049606.

MIM

116860. phenotype.
604214. gene.

neXtProt

NX_O00522.

Orphanet

221061. Hereditary cerebral cavernous malformation.

PharmGKB

PA26144.

GenAtlas

Search...

Phylogenomic databases

eggNOG

KOG4335.

HOGENOM

HOG000252958.

HOVERGEN

HBG052292.

InParanoid

O00522.

OMA

SKKHKQG.

OrthoDB

EOG4V1706.

PhylomeDB

O00522.

Gene expression databases

ArrayExpress

O00522.

Bgee

O00522.

CleanEx

HS_KRIT1.

Genevestigator

O00522.

GermOnline

ENSG00000001631. Homo sapiens.

Family and domain databases

Gene3D

1.20.80.10. 1 hit.
1.25.40.20. 1 hit.

InterPro

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]

Pfam

PF00023. Ank. 1 hit.
PF12796. Ank_2. 1 hit.
PF00373. FERM_M. 1 hit.
[Graphical view]

SMART

SM00248. ANK. 3 hits.
SM00295. B41. 1 hit.
[Graphical view]

SUPFAM

SSF48403. ANK. 1 hit.
SSF47031. FERM_3-hlx. 1 hit.

PROSITE

PS50297. ANK_REP_REGION. 1 hit.
PS50088. ANK_REPEAT. 1 hit.
PS00660. FERM_1. False negative.
PS00661. FERM_2. False negative.
PS50057. FERM_3. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

GenomeRNAi

889.

NextBio

3670.

SOURCE

Search...

Entry information

Entry name

KRIT1_HUMAN

Accession

Primary (citable) accession number: O00522
Secondary accession number(s): A6NNU0 , 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:	May 1, 2013
This is version 125 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.