Seroatlas · Human Serome Atlas

KRIT1

Krev interaction trapped protein 1

Also known as: CAM, CCM1, KRIT1_HUMAN

Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene

Protein identityUniProt · HPA

UniProt accession: O00522
Gene: KRIT1
Ensembl: ENSG00000001631
Chromosome: 7
Canonical length: 736 aa
Protein class: Disease related genes, Human disease related genes, Predicted intracellular proteins
Subcellular location: Vesicles

OverviewNCBI Gene

This gene encodes a protein containing four ankyrin repeats, a band 4.1/ezrin/radixin/moesin (FERM) domain, and multiple NPXY sequences. The encoded protein is localized in the nucleus and cytoplasm. It binds to integrin cytoplasmic domain-associated protein-1 alpha (ICAP1alpha), and plays a critical role in beta1-integrin-mediated cell proliferation. It associates with junction proteins and RAS-related protein 1A (Rap1A), which requires the encoded protein for maintaining the integrity of endothelial junctions. It is also a microtubule-associated protein and may play a role in microtubule targeting. Mutations in this gene result in cerebral cavernous malformations. Multiple alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Sep 2009]

Canonical amino-acid sequenceUniProt

736 residues, UniProt reviewed canonical sequence.

>O00522|KRIT1
     1  MGNPENIEDA YVAVIRPKNT ASLNSREYRA KSYEILLHEV PIEGQKKKRK KVLLETKLQG
    61  NSEITQGILD YVVETTKPIS PANQGIRGKR VVLMKKFPLD GEKMGREASL FIVPSVVKDN
   121  TKYTYTPGCP IFYCLQDIMR VCSESSTHFA TLTARMLIAL DKWLDERHAQ SHFIPALFRP
   181  SPLERIKTNV INPAYATESG QTENSLHMGY SALEIKSKML ALEKADTCIY NPLFGSDLQY
   241  TNRVDKVVIN PYFGLGAPDY SKIQIPKQEK WQRSMSSVTE DKERQWVDDF PLHRSACEGD
   301  SELLSRLLSE RFSVNQLDSD HWAPIHYACW YGKVEATRIL LEKGKCNPNL LNGQLSSPLH
   361  FAAGGGHAEI VQILLNHPET DRHITDQQGR SPLNICEENK QNNWEEAAKL LKEAINKPYE
   421  KVRIYRMDGS YRSVELKHGN NTTVQQIMEG MRLSQETQQY FTIWICSENL SLQLKPYHKP
   481  LQHVRDWPEI LAELTNLDPQ RETPQLFLRR DVRLPLEVEK QIEDPLAILI LFDEARYNLL
   541  KGFYTAPDAK LITLASLLLQ IVYGNYESKK HKQGFLNEEN LKSIVPVTKL KSKAPHWTNR
   601  ILHEYKNLST SEGVSKEMHH LQRMFLQNCW EIPTYGAAFF TGQIFTKASP SNHKVIPVYV
   661  GVNIKGLHLL NMETKALLIS LKYGCFMWQL GDTDTCFQIH SMENKMSFIV HTKQAGLVVK
   721  LLMKLNGQLM PTERNS

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against KRIT1 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability: Cell surface
Secreted: No
Transmembrane segments: 0
Mean surface accessibility (rSASA): 0.31
Highest tissue expression: 15 nTPM

Expression across tissuesHPA

Tissue

parathyroid gland: 15 nTPM
tongue: 13 nTPM
thyroid gland: 12 nTPM
heart muscle: 12 nTPM
testis: 12 nTPM
thymus: 10 nTPM

Single-cell type

distal convoluted tubule cells: 120 nCPM
proximal tubule cells: 111 nCPM
renal collecting duct intercalated cells: 107 nCPM
podocytes: 107 nCPM
loop of henle epithelial cells: 96 nCPM
renal connecting tubule cells: 91 nCPM

Immune cell

NK-cell: 8.6 nTPM
memory B-cell: 5.5 nTPM
memory CD8 T-cell: 5.1 nTPM
plasmacytoid DC: 5.1 nTPM
naive CD4 T-cell: 4.4 nTPM
naive CD8 T-cell: 4.2 nTPM

Brain region

cerebellum: 3 nTPM
hypothalamus: 3 nTPM
white matter: 3 nTPM
midbrain: 2.8 nTPM
cerebral cortex: 2.4 nTPM
medulla oblongata: 2.4 nTPM

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about KRIT1.

Disease | AllUniProt

Conditions KRIT1 is implicated in, by any mechanism.

Cerebral cavernous malformations 1 (CCM1) MIM:116860

Disease | GeneticClinVar

356 pathogenic / likely-pathogenic of 823 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

Cerebral cavernous malformation
KRIT1-related disorder
Cerebral cavernous malformation 1
Inborn genetic diseases
Hereditary cavernous hemangioma of brain

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance): 0.5
gnomAD pLI: 0
gnomAD missense Z: 1.43
DepMap mean gene effect: -0.01
DepMap dependency class: selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 12% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

Molecular functions

Cellular components

Protein domainsUniProt · Pfam · InterPro

FERM domain
Ankyrin repeat
PH-like domain superfamily
FERM/acyl-CoA-binding protein superfamily
FERM central domain
Band 4.1 domain
FERM superfamily, second domain
Ankyrin repeat-containing domain superfamily
KRIT1/FRMD8
KRIT1/FRMD8, FERM domain C-lobe
FERM central domain
KRIT1/FRMD8, FERM domain C-lobe
KRIT, N-terminal NPxY motif-rich region
Krev interaction trapped protein 1, FERM domain C-lobe
KRIT, N-terminal NPxY motif-rich domain superfamily
KRIT1, ARM-repeats domain
NUDIX, or N-terminal NPxY motif-rich, region of KRIT
KRIT1 ankyrin-repeats domain

KeywordsUniProt

InteractionsUniProt · HPA

Protein binding partners of KRIT1 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

Antibody and autoantibody relevanceSeroatlas analysis

Seroatlas reads KRIT1 as an antibody target. Whether an autoantibody or antibody against KRIT1 could matter depends on whether native KRIT1 is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.

KRIT1 is annotated at the cell surface, where native KRIT1 is exposed to circulating antibodies and is a prime autoantibody target that could block, deplete, or overstimulate it.

Annotation status

The present source text does not explicitly label KRIT1 as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.

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