Selected-GenAtlas references	SOURCE	GeneCards	NCBI Gene	Swiss-Prot	Ensembl
	HGNC	UniGene	Nucleotide	OMIM	UCSC

Home Page

FLASH GENE

Symbol

CIB1

contributors: mct - updated : 08-10-2018

HGNC name	calcium and integrin binding 1 (calmyrin)
HGNC id	16920

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

Location	15q26.1      Physical location : 90.773.477 - 90.777.279
Synonym name	calmyrin
	calcium and integrin binding protein
	DNA-PK interacting protein
	SNK-interacting protein 2-28
	calmyrin
	kinase-interacting protein
Synonym symbol(s)	SIP28, PRKDCIP, KIP, SIP2-28, CALMYRIN, CIB, CaMy1

DNA

TYPE	functioning gene
STRUCTURE	35.50 kb     7 Exon(s)

10 Kb 5' upstream gene genomic sequence study

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_006384 7 - 995 NP_006375 22 191 - 2017 28542214 CIB1 NM_001277764 7 - 1104 NP_001264693 - 231 - 2017 28542214 CIB1A CIB1A is a novel mediator of PRKD2-driven carcinogenesis and a potentially interesting therapeutic target

EXPRESSION

Type	ubiquitous

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 Cardiovascular heart       predominantly Homo sapiens Endocrine parathyroid       highly Lymphoid/Immune tonsils       highly Nervous brain       highly Homo sapiens

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Muscular striatum cardiac myocardium moderately Homo sapiens

cells

System Cell Pubmed Species Stage Rna symbol Nervous neuron Homo sapiens

cell lineage

cell lines

fluid/secretion

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	four EF-hand calcium-binding domains, although only the third and fourth C-terminal EF hands functionally bind Ca2+ at physiologic concentrations
	myristoylation site(s) (can be myristoylated at its N-terminus to mediate plasma membrane localization in multiple cell types)
	a hydrophobic pocket that has been implicated in ligand binding
	two canonical Ca2+-binding EF-hand motifs in the C-terminal globular domain

conjugated

Other

mono polymer

heteromer

HOMOLOGY

interspecies

ortholog to murine Cibkip pending

intraspecies	homolog to kip2
	homolog to calcineurin B
	homolog to calmodulin

Homologene

FAMILY

calcium-binding protein family

CATEGORY

adhesion , regulatory

SUBCELLULAR LOCALIZATION	plasma membrane
	intracellular
	intracellular,cytoplasm,organelle,membrane
	intracellular,cytoplasm,organelle,endoplasmic reticulum
	intracellular,cytoplasm,organelle,Golgi
	intracellular,cytoplasm,cytoskeleton,microtubule,centrosome
	intracellular,nucleus,nucleoplasm
text	membrane-associated colocalized with PS2
	shifting from nucleus to perinuclear compartment when coexpressed with M17S2
	localizes primarily to the sarcolemma in myocardium, where it anchors calcineurin to control its activation in coordination with the L-type Ca2+ channel
	localizes to the plasma membrane in fibroblasts, human venous endothelial cells

basic FUNCTION	playing a role in kinase-phosphatase regulation of DNA and joining
	converting the inactive conformation of integrin alpha-IIB/beta 3 to an active form through the binding to the integrin cytoplasmic domain
	playing a dynamic role in signaling, cell death and Alzheimer's disease
	negative regulator for PLK2 activity
	regulates platelet aggregation in hemostasis through a specific interaction with the alphaIIb cytoplasmic domain of platelet integrin alphaIIbbeta3
	potential role of the CIB1/LMO3 complex is to inhibit cell proliferation
	functions as a Ca2+-sensitive negative regulator of MAP3K5-mediated signaling events
	binds many other proteins including presenilin 2, DNA-dependent protein kinase, the polo-like kinases PLK3 and PLK2
	having a function working as a Ca2+-sensitive antagonist of stress-induced signaling events
	functions as a previously undescribed regulator of cardiac hypertrophy through its ability to regulate the association of calcineurin with the sarcolemma and its activation
	regulator of calcineurin-NFAT signaling and cardiac hypertrophy
	necessary for pathological but not physiological hypertrophy and contributes to cardiac dysfunction during pressure overload
	unique regulator of pathological cardiac hypertrophy and calcineurin-NFAT signaling in cardiac myocytes
	required for permitting activation of calcineurin during maladaptive cardiac hypertrophy
	EF-hand Ca(2+)-binding protein expressed in several cell types, including brain neurons
	CIB1 regulates endomitosis
	emerging roles of CIB1 in regulating cancer cell survival and angiogenesis
	is an EF-hand calcium binding protein, which is involved in many cellular processes, including calcium signaling, cell survival and proliferation, cell migration, cell adhesion and apoptosis

CELLULAR PROCESS	cell life, cell death/apoptosis
	nucleotide, repair

PHYSIOLOGICAL PROCESS

development

text	double-stand break repair, nervous system

PATHWAY

metabolism

signaling

signal transduction

a component

regulatory subunit for integrin alpha II beta 3

INTERACTION

DNA

RNA

small molecule	metal binding,
	Ca2+

protein	DNA-dependent protein kianase (PRKDC)
	cytoplasmic domain of alpha II b in the heterodimer integrin alpha Iib/beta3
	presenilin 2 (PS2)
	activating and inhibiting protein ligand of ITPR1
	CABP1 and CIB1 are two myristoylated proteins that bind the MYO1C regulatory domain
	bind integrin alphaIIb and may be involved in outside-in-signaling in platelets
	calcium- and integrin-binding protein CIB1 is an LMO3-binding protein, which binds via the second LIM domain (LIM2) of LMO3
	targeting apoptosis signal-regulating kinase 1 (MAP3K5), and negatively regulates stress-activated MAPK signaling pathways
	interacting with NBR1 (M17S2) and FEZ1 suggesting a role in neural development
	activating and inhibiting protein ligand of ITPR1
	interacting with PLK2
	CIB1 via STMN2 couples Ca(2+) signals with the dynamics of microtubules during neuronal outgrowth in the developing brain
	CIB1 is involved in regulating endomitosis, perhaps through its interaction with PLK3
	CIB1 could bind to all integrin complexes and act as a broad regulator of integrin function
	CIB1 may be involved in the pathogenesis of oligoasthenozoospermia by the CDK1 signaling pathway
	role for CIB1 in neoplastic transformation, revaeling a novel mechanism facilitating oncogenic signalling by HRAS and PAPSS1

cell & other

REGULATION

ASSOCIATED DISORDERS

corresponding disease(s)

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function constitutional     --low   in the oligoasthenozoospermia patients

Susceptibility

may be Alzheimer disease

Variant & Polymorphism

Candidate gene
Marker	significant correlation between the urine CIB1 and serum pro-BNP levels in patients with acute ischemic heart failure (significantly higher)
Therapy target	potential molecular target for the development of new therapeutics specific for human disorders whose pathogenesis is linked to MAP3K5-mediated signaling events
	System Type Disorder Pubmed cancer reproductive breast is a novel therapeutic target for triple-negative breast cancer cardiovascular aquired heart failure new strategy for treating hypertrophic heart disease through inhibition of CIB1 or its interaction with calcineurin

ANIMAL & CELL MODELS

	Cib1-deleted mice showed a marked reduction in myocardial hypertrophy, fibrosis, cardiac dysfunction and calcineurin–nuclear factor of activated T cells (NFAT) activity after pressure overload, whereas the degree of physiologic hypertrophy after swimming exercise was not altered
	Cib1 expression is increased in primary mouse megakaryocytes compared to mononuclear bone marrow cells