AiPD: Autoinhibited Protein Database

P39687

Gene name	ANP32A (C15orf1, LANP, MAPM, PHAP1)
Protein name	Acidic leucine-rich nuclear phosphoprotein 32 family member A
Names	Anaplastic lymphoma kinase, Acidic nuclear phosphoprotein pp32, pp32, Leucine-rich acidic nuclear protein, LANP, Mapmodulin, Potent heat-stable protein phosphatase 2A inhibitor I1PP2A, Putative HLA-DR-associated protein I, PHAPI
Species	Homo sapiens (Human)
KEGG Pathway	hsa:8125
EC number
Protein Class	ACIDIC LEUCINE-RICH NUCLEAR PHOSPHOPROTEIN 32 (PTHR11375)

Descriptions

ANP32A(I1^PP2A) regulates PP2A activity by functioning as a non-competitive inhibitor of this enzyme. PP2A is a major regulator of the phosphorylation of Tau. The activity of PP2A is compromised in Alzheimer's disease brain. ANP32A has an autoinhibitory domain that negatively affects the interaction of ANP32A with PP2Ac and its ability to modulate the PP2A activity, which lies within amino acid residues 121-163. The inhibitory role of the autoinhibitory region might be regulated through the phosphorylation of Ser-158 or both Ser-158 and Ser-204 by casein kinase II. The autoinhibition is disrupted by C-terminal region.

Autoinhibitory domains (AIDs)

Target domain	1-163 (Leucine-rich region)
Relief mechanism	PTM, Others
Assay	Deletion assay

AID

121-163 (Autoinhibitory domain)

Target domain

1-163 (Leucine-rich region)

Relief mechanism

PTM (Phosphorylation of Ser158 or both Ser158 and Ser204), Others (C-terminal acidic region-mediated neutralization)

Assay

Deletion assay

Accessory elements

No accessory elements

References

Chen S et al. (2008) "I1PP2A affects tau phosphorylation via association with the catalytic subunit of protein phosphatase 2A", The Journal of biological chemistry, 283, 10513-21

Autoinhibited structure

Activated structure

5 structures for P39687

Entry ID	Method	Resolution	Chain	Position	Source
2JE0	X-ray	240 A	A/B/C/D/E/F	1-149	PDB
2JE1	X-ray	269 A	A/B/C/D	1-149	PDB
4XOS	X-ray	156 A	A/B	1-149	PDB
6XZQ	EM	360 A	G	1-249	PDB
AF-P39687-F1	Predicted				AlphaFoldDB

88 variants for P39687

Variant ID(s)	Position	Change	Description	Diseaes Association	Provenance
CA272982104 rs897519849	2	E>G		No	ClinGen Ensembl
rs934738438 CA272982103	5	R>K		No	ClinGen TOPMed gnomAD
CA393216143 rs1380056390	6	R>W		No	ClinGen gnomAD
CA393216129 rs1265524068	8	H>Y		No	ClinGen TOPMed
CA272982102 rs200749145	14	R>G		No	ClinGen 1000Genomes
CA393216079 rs1392657083	15	T>M		No	ClinGen gnomAD
CA393216034 rs1567034816	20	K>E		No	ClinGen Ensembl
rs1440774890 CA393215977	28	R>W		No	ClinGen gnomAD
rs956184651 CA272978213	29	S>L		No	ClinGen Ensembl
rs746761102 CA7633015	33	K>R		No	ClinGen ExAC gnomAD
rs778857524 CA7633011	42	E>V		No	ClinGen ExAC gnomAD
rs778006443 CA7633008	49	T>I		No	ClinGen ExAC gnomAD
rs200174860 CA272978212	51	N>S		No	ClinGen 1000Genomes TOPMed
CA7633006 rs753007661	52	V>I		No	ClinGen ExAC gnomAD
rs767935426 CA7633005	55	T>I		No	ClinGen ExAC gnomAD
CA7633003 rs752173392	57	I>V		No	ClinGen ExAC gnomAD
rs776311932 CA7633000	58	A>S		No	ClinGen ExAC gnomAD
COSM1517603 CA7633001 rs776311932	58	A>T	lung [Cosmic]	No	ClinGen cosmic curated ExAC gnomAD
rs763791718 CA7632999	58	A>V		No	ClinGen ExAC
CA393215776 rs1567034774	59	N>H		No	ClinGen Ensembl
CA393215751 rs1177021555	62	K>R		No	ClinGen TOPMed
rs775360610 CA7632997	65	K>R		No	ClinGen ExAC gnomAD
CA393215661 rs1347102087	73	D>G		No	ClinGen gnomAD
CA393215625 rs1272953996	78	G>A		No	ClinGen gnomAD
rs1489954326 CA393215556	88	P>L		No	ClinGen TOPMed
CA393215554 rs545923966	89	N>D		No	ClinGen 1000Genomes ExAC gnomAD
rs1160503154 CA393215552	89	N>S		No	ClinGen gnomAD
CA7632974 rs545923966	89	N>Y		No	ClinGen 1000Genomes ExAC gnomAD
rs1420337867 CA393215546	90	L>V		No	ClinGen gnomAD
rs773212886 CA7632973	91	T>M		No	ClinGen ExAC gnomAD
rs1022611408 CA272978180	94	N>Y		No	ClinGen Ensembl
rs1487090108 CA393215436	106	I>V		No	ClinGen TOPMed gnomAD
CA393217239 rs1219469044	110	K>T		No	ClinGen gnomAD
CA393217227 rs1373554025	111	K>N		No	ClinGen TOPMed
rs567352237 CA7632947	113	E>D		No	ClinGen 1000Genomes ExAC gnomAD
CA393217218 rs1378608990	113	E>Q		No	ClinGen gnomAD
rs771143708 CA272977869	130	D>N		No	ClinGen Ensembl
rs751239680 CA7632942	132	R>Q		No	ClinGen ExAC gnomAD
CA393217065 rs1567034093	134	N>S		No	ClinGen Ensembl
CA7632941 rs766150688	135	V>A		No	ClinGen ExAC gnomAD
rs1171022580 CA393217059	135	V>L		No	ClinGen gnomAD
CA393217044 rs1183131394	137	K>R		No	ClinGen gnomAD
CA393217006 rs1176622208	143	T>S		No	ClinGen TOPMed gnomAD
CA393216955 rs776705409	150	R>L		No	ClinGen ExAC TOPMed gnomAD
rs776705409 CA7632936	150	R>Q		No	ClinGen ExAC TOPMed gnomAD
rs116525439 CA7632935	151	D>E		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
CA7632933 rs775900569	155	A>V		No	ClinGen ExAC gnomAD
rs772530468 CA7632932	158	S>A		No	ClinGen ExAC TOPMed gnomAD
rs772530468 CA272977864	158	S>T		No	ClinGen ExAC TOPMed gnomAD
rs1020600388 CA272977862	160	A>V		No	ClinGen TOPMed gnomAD
rs377739961 CA7632929	164	V>M		No	ClinGen ESP ExAC TOPMed gnomAD
rs1347783850 CA393216857	165	E>G		No	ClinGen gnomAD
rs749768201 CA7632928	169	D>E		No	ClinGen ExAC gnomAD
rs1408780419 CA393216821	170	E>D		No	ClinGen TOPMed gnomAD
rs1002129178 CA272977861	170	E>G		No	ClinGen Ensembl
CA7632927 rs780752451	170	E>K		No	ClinGen ExAC gnomAD
CA7632926 rs373629775	171	E>K		No	ClinGen ESP ExAC TOPMed gnomAD
CA393216699 rs1567033759	183	A>T		No	ClinGen Ensembl
rs757978703 CA7632901	183	A>V		No	ClinGen ExAC gnomAD
rs1360602291 CA393216689	184	Q>R		No	ClinGen gnomAD
CA272977706 rs954693786	185	V>I		No	ClinGen TOPMed
rs536312245 CA393216660	188	D>E		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
CA393216659 rs1349772391	189	E>K		No	ClinGen TOPMed
CA7632899 rs778664827	191	D>N		No	ClinGen ExAC gnomAD
rs1218477454 CA393216636	192	E>K		No	ClinGen TOPMed gnomAD
CA7632898 rs79955319	193	D>E		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
rs1478880011 CA393216583	199	E>K		No	ClinGen gnomAD
rs753775506 CA393216550	203	V>L		No	ClinGen ExAC gnomAD
CA7632897 rs753775506	203	V>M		No	ClinGen ExAC gnomAD
rs763894993 CA7632896	206	E>Q		No	ClinGen ExAC gnomAD
CA393216516 rs1204733581	208	E>K		No	ClinGen gnomAD
CA393216512 rs1317616653	208	E>V		No	ClinGen gnomAD
rs199755017 CA272977429	209	E>G		No	ClinGen 1000Genomes
rs200253787 CA7632886	213	G>S		No	ClinGen 1000Genomes ExAC gnomAD
CA272977428 rs371236865	222	E>K		No	ClinGen ESP TOPMed
CA393216354 rs1432826574	227	E>D		No	ClinGen gnomAD
CA7632880 rs778469088	228	L>P		No	ClinGen ExAC gnomAD
rs1170463075 CA393216347	229	G>S		No	ClinGen TOPMed
CA7632859 rs748971233	233	R>G		No	ClinGen ExAC
rs1012536396 CA272977408	239	R>Q		No	ClinGen TOPMed
CA393216256 rs1419179146	240	E>G		No	ClinGen TOPMed
CA393216235 rs1288082671	243	D>G		No	ClinGen gnomAD
rs748079337 CA7632855	243	D>H		No	ClinGen ExAC TOPMed gnomAD
CA393216220 rs1432619633	245	G>E		No	ClinGen TOPMed gnomAD
rs754998040 CA7632853	246	E>D		No	ClinGen ExAC gnomAD
rs751546166 CA7632852	248	D>N		No	ClinGen ExAC gnomAD
CA393216194 rs1347646398	249	D>N		No	ClinGen gnomAD
CA393216195 rs1347646398	249	D>Y		No	ClinGen gnomAD

No associated diseases with P39687

2 regional properties for P39687

Type	Name	Position	InterPro Accession
repeat	Leucine-rich repeat	89 - 110	IPR001611
domain	U2A'/phosphoprotein 32 family A, C-terminal	128 - 146	IPR003603

Functions

		Description
EC Number
Subcellular Localization	Nucleus Cytoplasm Endoplasmic reticulum	Translocates to the cytoplasm during the process of neuritogenesis (By similarity) Shuttles between nucleus and cytoplasm
PANTHER Family	PTHR11375	ACIDIC LEUCINE-RICH NUCLEAR PHOSPHOPROTEIN 32
PANTHER Subfamily	PTHR11375:SF1	ACIDIC LEUCINE-RICH NUCLEAR PHOSPHOPROTEIN 32 FAMILY MEMBER A
PANTHER Protein Class	chromatin/chromatin-binding, or -regulatory protein
PANTHER Pathway Category	No pathway information available

5 GO annotations of cellular component

Name	Definition
cytoplasm	The contents of a cell excluding the plasma membrane and nucleus, but including other subcellular structures.
endoplasmic reticulum	The irregular network of unit membranes, visible only by electron microscopy, that occurs in the cytoplasm of many eukaryotic cells. The membranes form a complex meshwork of tubular channels, which are often expanded into slitlike cavities called cisternae. The ER takes two forms, rough (or granular), with ribosomes adhering to the outer surface, and smooth (with no ribosomes attached).
nucleoplasm	That part of the nuclear content other than the chromosomes or the nucleolus.
nucleus	A membrane-bounded organelle of eukaryotic cells in which chromosomes are housed and replicated. In most cells, the nucleus contains all of the cell's chromosomes except the organellar chromosomes, and is the site of RNA synthesis and processing. In some species, or in specialized cell types, RNA metabolism or DNA replication may be absent.
perinuclear region of cytoplasm	Cytoplasm situated near, or occurring around, the nucleus.

2 GO annotations of molecular function

Name	Definition
histone binding	Binding to a histone, any of a group of water-soluble proteins found in association with the DNA of eukaryotic or archaeal chromosomes. They are involved in the condensation and coiling of chromosomes during cell division and have also been implicated in gene regulation and DNA replication. They may be chemically modified (methylated, acetlyated and others) to regulate gene transcription.
RNA binding	Binding to an RNA molecule or a portion thereof.

3 GO annotations of biological process

Name	Definition
intracellular signal transduction	The process in which a signal is passed on to downstream components within the cell, which become activated themselves to further propagate the signal and finally trigger a change in the function or state of the cell.
nucleocytoplasmic transport	The directed movement of molecules between the nucleus and the cytoplasm.
regulation of apoptotic process	Any process that modulates the occurrence or rate of cell death by apoptotic process.

20 homologous proteins in AiPD

UniProt AC	Gene Name	Protein Name	Species	Evidence Code
Q3SZC6	ANP32B	Acidic leucine-rich nuclear phosphoprotein 32 family member B	Bos taurus (Bovine)	SS
P51122	ANP32A	Acidic leucine-rich nuclear phosphoprotein 32 family member A	Bos taurus (Bovine)	SS
Q5F4A3	ANP32E	Acidic leucine-rich nuclear phosphoprotein 32 family member E	Gallus gallus (Chicken)	SS
Q5ZMN0	ANP32B	Acidic leucine-rich nuclear phosphoprotein 32 family member B	Gallus gallus (Chicken)	SS
Q8HY67	ANP32A	Acidic leucine-rich nuclear phosphoprotein 32 family member A	Canis lupus familiaris (Dog) (Canis familiaris)	SS
Q9V895	Anp32a	Acidic leucine-rich nuclear phosphoprotein 32 family member A	Drosophila melanogaster (Fruit fly)	SS
Q9BTT0	ANP32E	Acidic leucine-rich nuclear phosphoprotein 32 family member E	Homo sapiens (Human)	SS
Q92688	ANP32B	Acidic leucine-rich nuclear phosphoprotein 32 family member B	Homo sapiens (Human)	SS
O43423	ANP32CP	Putative uncharacterized protein ANP32CP	Homo sapiens (Human)	SS
P97822	Anp32e	Acidic leucine-rich nuclear phosphoprotein 32 family member E	Mus musculus (Mouse)	SS
Q9EST5	Anp32b	Acidic leucine-rich nuclear phosphoprotein 32 family member B	Mus musculus (Mouse)	SS
O35381	Anp32a	Acidic leucine-rich nuclear phosphoprotein 32 family member A	Mus musculus (Mouse)	SS
Q9EST6	Anp32b	Acidic leucine-rich nuclear phosphoprotein 32 family member B	Rattus norvegicus (Rat)	SS
Q5XIE0	Anp32e	Acidic leucine-rich nuclear phosphoprotein 32 family member E	Rattus norvegicus (Rat)	SS
P49911	Anp32a	Acidic leucine-rich nuclear phosphoprotein 32 family member A	Rattus norvegicus (Rat)	SS
Q7Y180	Os03g0668900	Acidic leucine-rich nuclear phosphoprotein 32-related protein 2	Oryza sativa subsp. japonica (Rice)	SS
Q9SCQ7	At3g50690	Acidic leucine-rich nuclear phosphoprotein 32-related protein	Arabidopsis thaliana (Mouse-ear cress)	SS
Q6P1U7	anp32b	Acidic leucine-rich nuclear phosphoprotein 32 family member B	Xenopus tropicalis (Western clawed frog) (Silurana tropicalis)	SS
Q6NUW5	anp32e	Acidic leucine-rich nuclear phosphoprotein 32 family member E	Danio rerio (Zebrafish) (Brachydanio rerio)	SS
Q7ZUP0	anp32a	Acidic leucine-rich nuclear phosphoprotein 32 family member A	Danio rerio (Zebrafish) (Brachydanio rerio)	SS

10	20	30	40	50	60
MEMGRRIHLE	LRNRTPSDVK	ELVLDNSRSN	EGKLEGLTDE	FEELEFLSTI	NVGLTSIANL
70	80	90	100	110	120
PKLNKLKKLE	LSDNRVSGGL	EVLAEKCPNL	THLNLSGNKI	KDLSTIEPLK	KLENLKSLDL
130	140	150	160	170	180
FNCEVTNLND	YRENVFKLLP	QLTYLDGYDR	DDKEAPDSDA	EGYVEGLDDE	EEDEDEEEYD
190	200	210	220	230	240
EDAQVVEDEE	DEDEEEEGEE	EDVSGEEEED	EEGYNDGEVD	DEEDEEELGE	EERGQKRKRE

PEDEGEDDD