APLP2 amyloid beta (A4) precursor-like protein 2 [Homo sapiens] - Gene

Help top of page

Summary

Official Symbol: APLP2provided by HGNC
Official Full Name: amyloid beta (A4) precursor-like protein 2provided by HGNC
Primary source: HGNC:598
See related: Ensembl:ENSG00000084234; HPRD:00103; MIM:104776; Vega:OTTHUMG00000165767
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: APPH; APPL2; CDEBP; APLP-2
Summary: This gene encodes amyloid precursor- like protein 2 (APLP2), which is a member of the APP (amyloid precursor protein) family including APP, APLP1 and APLP2. This protein is ubiquitously expressed. It contains heparin-, copper- and zinc- binding domains at the N-terminus, BPTI/Kunitz inhibitor and E2 domains in the middle region, and transmembrane and intracellular domains at the C-terminus. This protein interacts with major histocompatibility complex (MHC) class I molecules. The synergy of this protein and the APP is required to mediate neuromuscular transmission, spatial learning and synaptic plasticity. This protein has been implicated in the pathogenesis of Alzheimer's disease. Multiple alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Aug 2011]

Help top of page

Genomic context

Location :: 11q24

Sequence :: Chromosome: 11; NC_000011.9 (129939716..130014706)

See APLP2 in Epigenomics, MapViewer

Chromosome 11 - NC_000011.9 Genomic Context describing neighboring genes

Help top of page

Genomic regions, transcripts, and products

Genomic Sequence

Go to nucleotideGraphics FASTA GenBank

Go to reference sequence details

Help top of page

Bibliography

GeneRIFs: Gene References Into Functions What's a GeneRIF?

APLP-2 (and APLP1) are capable of activating gene transcription via binding to Mint3.
Title: Signaling via amyloid precursor-like proteins APLP1 and APLP2.
Regulation of major histocompatibility complex class I molecule expression on cancer cells by amyloid precursor-like protein 2.
Title: Regulation of major histocompatibility complex class I molecule expression on cancer cells by amyloid precursor-like protein 2.
proteolytic cleavage sites of the amyloid precursor-like protein 2 by the proteases ADAM10, BACE1 and gamma-secretase
Title: Determination of the proteolytic cleavage sites of the amyloid precursor-like protein 2 by the proteases ADAM10, BACE1 and γ-secretase.
The interaction between APLP2 and ataxin-7 and proteolytic processing of APLP2 may contribute to the pathogenesis of spinocerebellar ataxia type 7.
Title: Amyloid precursor-like protein 2 cleavage contributes to neuronal intranuclear inclusions and cytotoxicity in spinocerebellar ataxia-7 (SCA7).
Clinical trial of gene-disease association and gene-environment interaction. (HuGE Navigator)
Title: Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score.
APLP2 has a multistep trafficking function that influences the expression of major histocompatibility complex class I molecules at the plasma membrane
Title: Mechanism for amyloid precursor-like protein 2 enhancement of major histocompatibility complex class I molecule degradation.
Coexpression of APP with APLP1 or APLP2 leads to diminished generation of Abeta42
Title: Subcellular localization and dimerization of APLP1 are strikingly different from APP and APLP2.
APLP2/MHC association is influenced by multiple domains of the MHC class I heavy chain and by beta(2)m's effects on the conformation of the heavy chain.
Title: Specificity of amyloid precursor-like protein 2 interactions with MHC class I molecules.
APLP2 modulates the stability and endocytosis of K(d) molecules
Title: Amyloid precursor-like protein 2 increases the endocytosis, instability, and turnover of the H2-K(d) MHC class I molecule.
YWK-II (APLP2 protein) is a G(o)-coupled receptor for Mullerian inhibiting substance in mediating ERK1/2 activation leading to anti-apoptotic activity or cell survival.
Title: YWK-II protein as a novel G(o)-coupled receptor for Müllerian inhibiting substance in cell survival.

Submit: New GeneRIF Correction See all (20)

Help top of page

Phenotypes

Review eQTL and phenotype association data in this region using PheGenI

Help top of page

Products	Interactant	Other Gene	Source	Pubs	Description
Q06481	P31749	AKT1	HPRD	PubMed
Q06481	O00213	APBB1	HPRD	PubMed
Q06481	Q92870	APBB2	HPRD	PubMed
Q06481	O95704	APBB3	HPRD	PubMed
Q06481	Q06481	APLP2	HPRD	PubMed
Q06481	P06493	CDK1	HPRD	PubMed
Q06481	O75553	DAB1	HPRD	PubMed
Q06481	P01891	HLA-A	HPRD	PubMed
Q06481	P42336	PIK3CA	HPRD	PubMed
Q06481	P17252	PRKCA	HPRD	PubMed
Q06481	P04156	PRNP	HPRD	PubMed
BioGRID:106831	BioGRID:106819	APBB1	BioGRID	PubMed	Affinity Capture-Western; Reconstituted Complex
BioGRID:106831	BioGRID:115593	APBB3	BioGRID	PubMed	Reconstituted Complex
BioGRID:106831	BioGRID:198141	Apbb1	BioGRID	PubMed	Two-hybrid
BioGRID:106831	BioGRID:107140	BRCA1	BioGRID	PubMed	Far Western
BioGRID:106831	BioGRID:107970	DAB1	BioGRID	PubMed	Reconstituted Complex
BioGRID:106831	BioGRID:107971	DAB2	BioGRID	PubMed	Reconstituted Complex
BioGRID:106831	BioGRID:115331	HDAC5	BioGRID	PubMed	Affinity Capture-MS
BioGRID:106831	BioGRID:114593	HGS	BioGRID	PubMed	Reconstituted Complex
BioGRID:106831	BioGRID:109928	JUN	BioGRID	PubMed	Two-hybrid
BioGRID:106831	BioGRID:112171	RYK	BioGRID	PubMed	Affinity Capture-MS
BioGRID:106831	BioGRID:109072	SFN	BioGRID	PubMed	Affinity Capture-MS
BioGRID:106831	BioGRID:113164	UBC	BioGRID	PubMed	Affinity Capture-MS

Function	Evidence Code	Pubs
DNA binding	NAS Non-traceable Author Statement more info	PubMed
heparin binding	IEA Inferred from Electronic Annotation more info
identical protein binding	IPI Inferred from Physical Interaction more info	PubMed
peptidase inhibitor activity	IEA Inferred from Electronic Annotation more info
protein binding	IPI Inferred from Physical Interaction more info
serine-type endopeptidase inhibitor activity	IEA Inferred from Electronic Annotation more info
transition metal ion binding	IEA Inferred from Electronic Annotation more info

Process	Evidence Code	Pubs
G-protein coupled receptor signaling pathway	NAS Non-traceable Author Statement more info	PubMed
cellular copper ion homeostasis	IEA Inferred from Electronic Annotation more info
embryo development	IEA Inferred from Electronic Annotation more info
extracellular matrix organization	IEA Inferred from Electronic Annotation more info
forebrain development	IEA Inferred from Electronic Annotation more info
locomotory behavior	IEA Inferred from Electronic Annotation more info
mating behavior	IEA Inferred from Electronic Annotation more info
midbrain development	IEA Inferred from Electronic Annotation more info
neuromuscular process controlling balance	IEA Inferred from Electronic Annotation more info
regulation of epidermal growth factor-activated receptor activity	IEA Inferred from Electronic Annotation more info
suckling behavior	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
integral to membrane	NAS Non-traceable Author Statement more info	PubMed
nucleus	IDA Inferred from Direct Assay more info	PubMed
plasma membrane	IEA Inferred from Electronic Annotation more info

General protein information

Preferred Names: amyloid-like protein 2

Names: amyloid-like protein 2; CDEI box-binding protein; amyloid precursor protein homolog HSD-2

Help top of page

NCBI Reference Sequences (RefSeq)

RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_029770.1 RefSeqGene

Range

5001..79991

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001142276.1 → NP_001135748.1 amyloid-like protein 2 isoform 2 precursor

Status: REVIEWED

Description

Transcript Variant: This variant (2) lacks an in-frame exon in the 3' coding region, compared to variant 1. It encodes isoform 2 which lacks an internal segment in the C-terminal region, compared to isoform 1.

Source sequence(s)

AK056883, BC000373, BM992563, DC336210

Consensus CDS

CCDS44773.1

UniProtKB/Swiss-Prot

Q06481

Related

ENSP00000345444, OTTHUMP00000230929, ENST00000338167, OTTHUMT00000386111

Conserved Domains (6) summary

cd00109
Location:308 – 361
Blast Score: 210

KU; BPTI/Kunitz family of serine protease inhibitors; Structure is a disulfide rich alpha+beta fold. BPTI (bovine pancreatic trypsin inhibitor) is an extensively studied model structure.

smart00006
Location:42 – 204
Blast Score: 781

A4_EXTRA; amyloid A4

pfam10515
Location:703 – 747
Blast Score: 233

APP_amyloid; beta-amyloid precursor protein C-terminus

pfam02177
Location:48 – 147
Blast Score: 424

APP_N; Amyloid A4 N-terminal heparin-binding

pfam12924
Location:148 – 204
Blast Score: 300

APP_Cu_bd; Copper-binding of amyloid precursor, CuBD

pfam12925
Location:365 – 548
Blast Score: 674

APP_E2; E2 domain of amyloid precursor protein
NM_001142277.1 → NP_001135749.1 amyloid-like protein 2 isoform 3 precursor

Status: REVIEWED

Description

Transcript Variant: This variant (3) lacks two in-frame exons in the coding region, compared to variant 1. It encodes isoform 3 which lacks two internal segments, compared to isoform 1.

Source sequence(s)

AK056883, AK304736, BM992563, DC336210

Consensus CDS

CCDS44774.1

UniProtKB/TrEMBL

B4E3I5

UniProtKB/Swiss-Prot

Q06481

Related

ENSP00000435914, OTTHUMP00000230926, ENST00000528499, OTTHUMT00000386108

Conserved Domains (5) summary

smart00006
Location:42 – 204
Blast Score: 790

A4_EXTRA; amyloid A4

pfam10515
Location:647 – 691
Blast Score: 230

APP_amyloid; beta-amyloid precursor protein C-terminus

pfam02177
Location:48 – 147
Blast Score: 428

APP_N; Amyloid A4 N-terminal heparin-binding

pfam12924
Location:148 – 204
Blast Score: 306

APP_Cu_bd; Copper-binding of amyloid precursor, CuBD

pfam12925
Location:308 – 492
Blast Score: 659

APP_E2; E2 domain of amyloid precursor protein
NM_001142278.1 → NP_001135750.1 amyloid-like protein 2 isoform 4 precursor

Status: REVIEWED

Description

Transcript Variant: This variant (4) lacks multiple exons in the coding region, compared to variant 1. The reading frame is not affected, and this variant encodes isoform 4 which lacks two internal segments, compared to isoform 1.

Source sequence(s)

AK056883, BC004371, BM992563, DC336210

Consensus CDS

CCDS44775.1

UniProtKB/Swiss-Prot

Q06481

Related

ENSP00000263575, OTTHUMP00000230928, ENST00000345598, OTTHUMT00000386110

Conserved Domains (3) summary

pfam10515
Location:474 – 518
Blast Score: 227

APP_amyloid; beta-amyloid precursor protein C-terminus

pfam02177
Location:48 – 137
Blast Score: 372

APP_N; Amyloid A4 N-terminal heparin-binding

pfam12925
Location:135 – 319
Blast Score: 633

APP_E2; E2 domain of amyloid precursor protein
NM_001243299.1 → NP_001230228.1 amyloid-like protein 2 isoform 5

Status: REVIEWED

Description

Transcript Variant: This variant (7) differs in the 5' exon and also lacks an in-frame exon in the 3' coding region, compared to variant 1. It encodes isoform 5 which has a different N-terminus and lacks an internal segment in the C-terminal region, compared to isoform 1.

Source sequence(s)

AK056883, AK128162, BC000373, BM992563

UniProtKB/TrEMBL

B3KXX9

UniProtKB/TrEMBL

H7BXI4

UniProtKB/Swiss-Prot

Q06481

Conserved Domains (6) summary

cd00109
Location:318 – 371
Blast Score: 208

KU; BPTI/Kunitz family of serine protease inhibitors; Structure is a disulfide rich alpha+beta fold. BPTI (bovine pancreatic trypsin inhibitor) is an extensively studied model structure.

smart00006
Location:52 – 214
Blast Score: 776

A4_EXTRA; amyloid A4

pfam10515
Location:713 – 757
Blast Score: 236

APP_amyloid; beta-amyloid precursor protein C-terminus

pfam02177
Location:58 – 157
Blast Score: 424

APP_N; Amyloid A4 N-terminal heparin-binding

pfam12924
Location:158 – 214
Blast Score: 298

APP_Cu_bd; Copper-binding of amyloid precursor, CuBD

pfam12925
Location:375 – 558
Blast Score: 683

APP_E2; E2 domain of amyloid precursor protein
NM_001642.2 → NP_001633.1 amyloid-like protein 2 isoform 1 precursor

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents the longest transcript and encodes the longest isoform (1).

Source sequence(s)

AK056883, BM992563, DC336210, Z22572

Consensus CDS

CCDS8486.1

UniProtKB/Swiss-Prot

Q06481

Related

ENSP00000263574, OTTHUMP00000230927, ENST00000263574, OTTHUMT00000386109

Conserved Domains (6) summary

cd00109
Location:308 – 361
Blast Score: 211

KU; BPTI/Kunitz family of serine protease inhibitors; Structure is a disulfide rich alpha+beta fold. BPTI (bovine pancreatic trypsin inhibitor) is an extensively studied model structure.

smart00006
Location:42 – 204
Blast Score: 780

A4_EXTRA; amyloid A4

pfam10515
Location:715 – 759
Blast Score: 232

APP_amyloid; beta-amyloid precursor protein C-terminus

pfam02177
Location:48 – 147
Blast Score: 424

APP_N; Amyloid A4 N-terminal heparin-binding

pfam12924
Location:148 – 204
Blast Score: 300

APP_Cu_bd; Copper-binding of amyloid precursor, CuBD

pfam12925
Location:365 – 548
Blast Score: 672

APP_E2; E2 domain of amyloid precursor protein

RNA

NR_024515.1 RNA Sequence

Description

Transcript Variant: This variant (5) differs in multiple regions, compared to variant 1. The transcript is a candidate for nonsense-mediated decay (NMD).

Source sequence(s)

AK056883, BM992563, DC336210, Z22572
NR_024516.1 RNA Sequence

Description

Transcript Variant: This variant (6) differs in multiple regions, compared to variant 1. The transcript is a candidate for nonsense-mediated decay (NMD).

Source sequence(s)

AK056883, AK300378, BM992563, DC336210

RefSeqs of Annotated Genomes: Build 37.3

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh37.p5 Primary Assembly

Genomic

NC_000011.9 Reference GRCh37.p5 Primary Assembly

Range

129939716..130014706

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate HuRef

Genomic

AC_000143.1 Alternate HuRef

Range

125891358..125966057

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Help top of page

Related Sequences

Nucleotide		Protein
Heading	Accession and Version	Protein
genomic	AB015751.1	BAA34958.1
genomic	AP001183.6 (40288..45595)	None
genomic	AP003041.3 (118580..188171)	None
genomic	CH471065.1	EAW67768.1
		EAW67769.1
		EAW67770.1
		EAW67771.1
		EAW67772.1
		EAW67773.1
		EAW67774.1
mRNA	AF168956.1	AAD47291.1
mRNA	AK056883.1	None
mRNA	AK122834.1	None
mRNA	AK124457.1	None
mRNA	AK128162.1	BAG54641.1
mRNA	AK225283.1	None
mRNA	AK296765.1	BAG59345.1
mRNA	AK300378.1	BAG62113.1
mRNA	AK304736.1	BAG65497.1
mRNA	AK308248.1	None
mRNA	AK308932.1	None
mRNA	BC000373.2	AAH00373.1
mRNA	BC004371.1	AAH04371.1
mRNA	BM992563.1	None
mRNA	BX647107.1	None
mRNA	DC336210.1	None
mRNA	L09209.1	AAA35526.1
mRNA	L19597.1	AAA35601.1
mRNA	L23113.1	AAA36032.1
mRNA	L23114.1	AAA36130.1
mRNA	L27631.1	AAC41701.1
mRNA	S60099.1	AAC60589.1
mRNA	Z22572.1	CAA80295.1
other-genetic	EU176299.1	ABW03750.1
other-genetic	EU176627.1	ABW03428.1