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FLASH GENE

Symbol

TMPO

contributors: mct - updated : 28-09-2016

HGNC name	thymopoietin
HGNC id	11875

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

Corresponding disease	CMD1T cardiomyopathy dilated 1T
Location	12q23.1      Physical location : 98.909.350 - 98.944.157
Synonym name	Lamin A/C binding protein 2
	lamina associated polypeptide 2
Synonym symbol(s)	TP, LAP2, CMD1T, LEMD4, PRO0868, LAP2alpha

DNA

TYPE	functioning gene
STRUCTURE	34.81 kb     4 Exon(s)

10 Kb 5' upstream gene genomic sequence study

MAPPING

cloned

Y

linked

status

confirmed

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_003276 4 splicing 3690 NP_003267 75 694 primary skin fibroblasts in a growth-dependent manner 1994 7517549 LAP2 alpha nuclear isoform splicing of the exon4 contains sequences encoding a putative basic nuclear localization motif a binding partner of lamins A/C multiple and distinct functions of LAP2 alpha in muscle stem cell maintenance, early phases of myogenic differentiation, and muscle remodeling (PMID: 20039368) NM_001032283 9 splicing 4186 NP_001027454 51 454 over-expressed in gastric cancer tissues 1994 7517549 LAP2 beta in the nuclear membrane splicing of the exon 8 a hydrophobic putative membrane-spanning domain that is thought to target these 2 gene products to the nuclear membrane regulates motility of cancer cells NM_001032284 6 splicing 3853 NP_001027455 39 345 - 1994 7517549 LAP2 gamma in the nuclear membrane splicing of the exon 8 a hydrophobic putative membrane-spanning domain that is thought to target these 2 gene products to the nuclear membrane NM_001307975 8 - 4066 NP_001294904 - 414 - 1994 7517549

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 Lymphoid/Immune lymph node       highly   thymus       highly Reproductive male system testis     highly Urinary bladder       highly

cell lineage

cell lines

fluid/secretion

at STAGE

physiological period

fetal

Text

liver

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains

a N terminal LEM (LAP2, emerin, MAN1) globular domain of 40 AAs, LEM-like domain, which binds DNA

HOMOLOGY

Homologene

FAMILY

LAP2 (lamina-associated protein 2) family

CATEGORY

signaling hormone

SUBCELLULAR LOCALIZATION	plasma membrane,junction,adherens
	intracellular
	intracellular,cytoplasm,organelle,membrane
	intracellular,cytoplasm,organelle,endoplasmic reticulum
	intracellular,cytoplasm,cytoskeleton,microtubule,mitotic spindle
	intracellular,nucleus,chromatin/chromosome
	intracellular,nuclear envelope,int
text	dynamically associating with chromatin during the cell cycle
	nuclear periphery proteins LMNA, TMPO and BANF1 relocate to the spindle and the cell cortex in mitosis

basic FUNCTION	playing an important role, together with LMNA, in the nuclear anchorage of RB1
	may be involved in the structural organization of the nucleus and in the post-mitotic nuclear assembly
	playing a role with OIP5 during cell cycle exit, in which OIP5 acts upstream of TMPO
	serves likely as a transcriptional co-regulator, which controls muscle specific gene expression during muscle regeneration, muscle remodeling and stress response
	nuclear protein that connects the nuclear lamina with chromatin
	and nucleoplasmic lamins are regulators of adult stem cell function and tissue homeostas
	LMNA, TMPO and BANF1 are assembled into a protein complex during mitosis in order to regulate assembly and positioning of the mitotic spindle
	in addition to its cell cycle-inhibiting function with LMNA, TMPO can also regulate extracellular matrix components independently of LMNA, which may help explain the proliferation-promoting function of TMPO in cells expressing progerin (pMID: 26443848)
	novel role of nucleoplasmic lamin A/C and TMPO in regulating euchromatin

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

a component

TMPO-LMNA complex negatively affects cell proliferation

INTERACTION

DNA

RNA

small molecule

protein	hypophosphorylated RB is anchored in the nucleus by the interaction of pocket C with LAP2alpha-LMNA complexes
	BANF1 and RB1 and with chromosomes
	TMPO over-expression increased, while additional WNT4 secretion suppressed PPARG expression
	N-terminal domain of HMGN5 interacts with the C-terminal domain of TMPO and these proteins reciprocally alter their interaction with chromatin
	localizes throughout the nucleoplasm and interacts with the fraction of LMNA that is not associated with the peripheral nuclear lamina
	LMNA localizes throughout the nucleus, where it associates with the chromatin-binding protein TMPO

cell & other

REGULATION

activated by

during G1 phase in proliferating cells and upon cell cycle exit in quiescence, senescence and differentiation

ASSOCIATED DISORDERS

corresponding disease(s)

CMD1T

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function constitutional germinal mutation       of the LAP2 alpha isoform, in the LMNA binding region, in familial dilated cardiomyopathy

Susceptibility

Variant & Polymorphism

Candidate gene
Marker	LAP2beta may have utility for diagnostics and therapeutics in digestive tract cancers
Therapy target

ANIMAL & CELL MODELS

in cardiac tissue, deletion of Tmpo caused systolic dysfunction in young mice with an increased susceptibility for fibrosis in old animals