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FLASH GENE

Symbol

NLRP1

contributors: mct/npt/pgu - updated : 07-10-2019

HGNC name	NLR family, pyrin domain containing 1
HGNC id	14374

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

DNA

TYPE	functioning gene
STRUCTURE	83.11 kb     17 Exon(s)

MAPPING

cloned

Y

linked

N

status

provisional

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_033004 17 splicing 5610 NP_127497 165.8 1473 - 2001 11076957 NM_014922 15 splicing 5478 NP_055737 157 1429 peripheral blood leukocytes, chronic myelogenous leukemia, thymus, spleen, heart 2001 11076957 NM_033006 16 splicing 5520 NP_127499 159 1443 spinal cord, leukocytes 2001 11076957 NM_033007 16 splicing 5388 NP_127500 154 1399 - 2001 11076957 lacks two in-frame exons NM_001033053 16 - 5098 NP_001028225 - 1375 - 2001 11076957

EXPRESSION

Type

widely

expressed in

(based on citations)

organ(s)

System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol blood / hematopoietic spleen       moderately   thymus       moderately Cardiovascular heart       moderately Digestive intestine large intestine colon       intestine small intestine         liver       moderately Nervous brain       lowly Reproductive female system uterus         female system ovary     moderately   female system placenta         male system testis     moderately Respiratory lung       moderately

cells

System Cell Pubmed Species Stage Rna symbol Blood/Hematopoietic leukocyte Blood/Hematopoietic monocyte Lymphoid/Immune T cell

cell lineage

cell lines

fluid/secretion

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	a PYD(PAAD/DAPIN/Pyrin) domain at the N terminus
	a NACHT domain
	seven leucine rich repeats (LRR), ribonuclease inhibitor type
	a C-terminal caspase recruitment domain (CARD), with the latter being essential for its association with the downstream effector procaspase-1

HOMOLOGY

intraspecies

homolog to placental ribonuclease inhibitor

Homologene

FAMILY	CED4 family of apoptosis proteins
	Nod-like receptors (NLRs) family

CATEGORY

regulatory

SUBCELLULAR LOCALIZATION	intracellular
	intracellular,cytoplasm,cytosolic
	intracellular,nucleus,nucleoplasm

basic FUNCTION	involved in the induction of apoptosis (by enhancing APAF1 and cytochrome c-dependent activation of caspase 9)
	playing a central role in the activation of inflammatory caspases and processing of pro-IL1b (pro-interleukin-1b
	may have functions in injured neurons
	may be integral components that cause neuronal apoptosis following brain injury or diseases
	implicated in the activation of caspase-1 by the Toll-like receptors (TLRs) during the cells response to microbial infection
	intracellular receptors, such as NLRP1, NLRP3, NLRP6 and NLRC4, which mediate the assembly of inflammasome complexes leading to the activation of procaspase-1
	is a regulator of innate immunity associated with vitiligo
	cytoplasmic protein, involved in autoimmune diseases, mammalian reproduction, neuronal cell death, and stroke
	plays a crucial role in the development of cardiac hypertrophy via positive regulation of the MAPK, NFKB1, and TGFB1/SMAD signaling pathways

CELLULAR PROCESS	cell life, cell death/apoptosis

PHYSIOLOGICAL PROCESS

immunity/defense , inflammation

PATHWAY

metabolism

signaling

signal transduction

a component

component of an inflammatory and apoptotic complex (inflammasome) composed of ASC, CASP1, CASP5 and NALP1

INTERACTION

DNA

RNA

small molecule	nucleotide,
	ATP binding

protein	interacts strongly with caspase 5 and weakly with caspase 2 and 4
	transcriptional target for cAMP-response-element-binding protein (CREBBP) in myeloid leukaemia cells
	binds BCL2 and BCL2L1
	IL17A promoted CASP5 function via facilitation of the NLRP1-inflammasome
	NLRP1 promoted myofibroblast differentiation and excessive ECM production in TGFB1-induced neonatal cardiac fibroblasts through directly targeting TGFB1/SMAD signaling pathways
	DPP9 binds directly to NLRP1 and CARD8, and this interaction may contribute to the inhibition of NLRP1

cell & other

REGULATION

Other

regulated by interactions with antiapoptotic proteins BCL2 and BCL2L1, which suppress NLRP1-mediated activation of caspase-1 and reduce production of the caspase-1 substrate IL1B

ASSOCIATED DISORDERS

corresponding disease(s)

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral     --over   in the bone marrow blast of acute leukaemia tumoral germinal mutation     gain of function in siblings with a syndromic form of recurrent respiratory papillomatosis constitutional       gain of function of the NLRP1 and NLRP3 inflammasomes in Alzheimer disease

Susceptibility

to preeclampsia

Variant & Polymorphism	variant rs12150220 (L155H) was associated with the development of preeclampsia 6)

Candidate gene
Marker
Therapy target
	System Type Disorder Pubmed neurology neurodegenerative   molecular targets for therapeutic intervention in neurodegenerative disorders diabete type 1   modulation of NLRP1 inflammasome might be a promising strategy for Diabetic retinopathy (DR) therapy

ANIMAL & CELL MODELS