P51693 (APLP1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Amyloid-like protein 1
Short name=APLP
Short name=APLP-1

Cleaved into the following chain:

1. C30

Gene names

Name:

APLP1

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	650 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	May play a role in postsynaptic function. The C-terminal gamma-secretase processed fragment, ALID1, activates transcription activation through APBB1 (Fe65) binding By similarity. Couples to JIP signal transduction through C-terminal binding. May interact with cellular G-protein signaling pathways. Can regulate neurite outgrowth through binding to components of the extracellular matrix such as heparin and collagen I. Ref.5 The gamma-CTF peptide, C30, is a potent enhancer of neuronal apoptosis By similarity. Ref.5
Subunit structure	Monomer and homodimer. Heparin binding promotes homodimerization. Binds, via its C-terminus, to the PID domain of several cytoplasmic proteins, including APBB and APBA family members, MAPK8IP1 and Dab1 By similarity. Binding to Dab1 inhibits its serine phosphorylation By similarity. Interacts with CPEB1. Interacts (via NPXY motif) with DAB2 (via PID domain); the interaction is impaired by tyrosine phosphorylation of the NPXY motif. Interacts (via NPXY motif) with DAB1 By similarity. Ref.7 Ref.11
Subcellular location	Cell membrane; Single-pass type I membrane protein. C30: Cytoplasm. Note: C-terminally processed in the Golgi complex.
Tissue specificity	Expressed in the cerebral cortex where it is localized to the postsynaptic density (PSD). Ref.5
Domain	The NPXY sequence motif found in many tyrosine-phosphorylated proteins is required for the specific binding of the PID domain. However, additional amino acids either N- or C-terminal to the NPXY motif are often required for complete interaction. The NPXY site is also involved in clathrin-mediated endocytosis.
Post-translational modification	Proteolytically cleaved by caspases during neuronal apoptosis. Cleaved, in vitro, at Asp-620 by caspase-3 By similarity. N- and O-glycosylated. O-glycosylation with core 1 or possibly core 8 glycans. Glycosylation on Ser-227 is the preferred site to Thr-228. Ref.10
Miscellaneous	Binds zinc and copper in the extracellular domain. Zinc-binding increases heparin binding. No Cu2+ reducing activity with copper-binding.
Sequence similarities	Belongs to the APP family.

Ontologies

Keywords
Biological process	Apoptosis Cell adhesion Endocytosis
Cellular component	Cell membrane Cytoplasm Membrane
Coding sequence diversity	Alternative splicing
Disease	Neurodegeneration
Domain	Signal Transmembrane Transmembrane helix
Ligand	Copper Heparin-binding Metal-binding Zinc
PTM	Glycoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	adenylate cyclase-inhibiting G-protein coupled receptor signaling pathway Inferred by curator PubMed 16531006. Source: BHF-UCL apoptotic process Inferred from electronic annotation. Source: UniProtKB-KW cell adhesion Inferred from electronic annotation. Source: UniProtKB-KW cellular response to norepinephrine stimulus Inferred from direct assay PubMed 16531006. Source: BHF-UCL endocytosis Inferred from electronic annotation. Source: UniProtKB-KW extracellular matrix organization Inferred from electronic annotation. Source: Compara forebrain development Inferred from electronic annotation. Source: Compara mRNA polyadenylation Inferred from electronic annotation. Source: Compara negative regulation of cAMP biosynthetic process Inferred from direct assay PubMed 16531006. Source: BHF-UCL nervous system development Traceable author statement Ref.2. Source: ProtInc organ morphogenesis Traceable author statement Ref.2. Source: ProtInc regulation of translation Inferred from electronic annotation. Source: Compara
Cellular_component	Golgi apparatus Inferred from electronic annotation. Source: Compara basement membrane Traceable author statement Ref.2. Source: ProtInc integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW perinuclear region of cytoplasm Inferred from direct assay PubMed 16531006. Source: BHF-UCL plasma membrane Inferred from direct assay PubMed 16531006. Source: BHF-UCL
Molecular_function	heparin binding Inferred from electronic annotation. Source: UniProtKB-KW transition metal ion binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
itself		3	EBI-74648,EBI-74648
APLP2	Q06481	2	EBI-74648,EBI-79306
APP	P05067-4	2	EBI-74648,EBI-302641
ZNF24	P17028	2	EBI-74648,EBI-707773

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: P51693-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: P51693-2)

The sequence of this isoform differs from the canonical sequence as follows:
     517-517: D → DA

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 38

38

Potential

Chain

39 – 650

612

Amyloid-like protein 1

PRO_0000000203

Peptide

621 – 650

30

C30 By similarity

PRO_0000000204

Regions

Topological domain

39 – 580

542

Extracellular Potential

Transmembrane

581 – 603

23

Helical; Potential

Topological domain

604 – 650

47

Cytoplasmic Potential

Region

158 – 178

21

Copper-binding By similarity

Region

204 – 211

8

Zinc-binding

Region

285 – 305

21

O-glycosylated at three sites

Region

310 – 342

33

Heparin-binding By similarity

Region

410 – 441

32

Heparin-binding By similarity

Region

442 – 459

18

Collagen-binding By similarity

Region

632 – 649

18

Interaction with DAB1 By similarity

Region

636 – 650

15

Interaction with DAB2 By similarity

Motif

604 – 615

12

Basolateral sorting signal By similarity

Motif

640 – 643

4

Clathrin-binding Potential

Motif

640 – 643

4

NPXY motif; contains endocytosis signal

Compositional bias

241 – 247

7

Poly-Glu

Compositional bias

264 – 268

5

Poly-Glu

Sites

Site

167

1

Required for Cu(2+) reduction By similarity

Site

620 – 621

2

Cleavage; by caspase-3 By similarity

Amino acid modifications

Glycosylation

215

1

O-linked (GalNAc...) Ref.9

Glycosylation

227

1

O-linked (GalNAc...) Probable

Glycosylation

228

1

O-linked (GalNAc...) Probable

Glycosylation

337

1

N-linked (GlcNAc...) Potential

Glycosylation

461

1

N-linked (GlcNAc...) Potential

Glycosylation

551

1

N-linked (GlcNAc...) Potential

Natural variations

Alternative sequence

517

1

D → DA in isoform 2.

VSP_039100

Experimental info

Mutagenesis

426

1

H → A: Reduced affinity for heparin. Reduces homodimerization. Ref.11

Mutagenesis

429

1

R → A: Strongly reduced affinity for heparin. Strongly reduced homodimerization. Ref.11

Mutagenesis

433

1

H → A: Reduced affinity for heparin. Reduces homodimerization. Ref.11

Sequence conflict

48

1

A → P in AAB96331. Ref.1

Sequence conflict

78

1

P → S in BC013850. Ref.4

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

650

Helix Strand Turn

Details...

Helix

293 – 298

6

Helix

306 – 337

32

Turn

338 – 341

4

Helix

344 – 399

56

Beta strand

401 – 403

3

Helix

406 – 437

32

Helix

439 – 442

4

Turn

443 – 445

3

Helix

446 – 467

22

Helix

471 – 485

15

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified February 22, 2003. Version 3. Checksum: B95F0F4D1C5CBAC7	FASTA	650	72,176
	10 20 30 40 50 60 MGPASPAARG LSRRPGQPPL PLLLPLLLLL LRAQPAIGSL AGGSPGAAEA PGSAQVAGLC 70 80 90 100 110 120 GRLTLHRDLR TGRWEPDPQR SRRCLRDPQR VLEYCRQMYP ELQIARVEQA TQAIPMERWC 130 140 150 160 170 180 GGSRSGSCAH PHHQVVPFRC LPGEFVSEAL LVPEGCRFLH QERMDQCESS TRRHQEAQEA 190 200 210 220 230 240 CSSQGLILHG SGMLLPCGSD RFRGVEYVCC PPPGTPDPSG TAVGDPSTRS WPPGSRVEGA 250 260 270 280 290 300 EDEEEEESFP QPVDDYFVEP PQAEEEEETV PPPSSHTLAV VGKVTPTPRP TDGVDIYFGM 310 320 330 340 350 360 PGEISEHEGF LRAKMDLEER RMRQINEVMR EWAMADNQSK NLPKADRQAL NEHFQSILQT 370 380 390 400 410 420 LEEQVSGERQ RLVETHATRV IALINDQRRA ALEGFLAALQ ADPPQAERVL LALRRYLRAE 430 440 450 460 470 480 QKEQRHTLRH YQHVAAVDPE KAQQMRFQVH THLQVIEERV NQSLGLLDQN PHLAQELRPQ 490 500 510 520 530 540 IQELLHSEHL GPSELEAPAP GGSSEDKGGL QPPDSKDDTP MTLPKGSTEQ DAASPEKEKM 550 560 570 580 590 600 NPLEQYERKV NASVPRGFPF HSSEIQRDEL APAGTGVSRE AVSGLLIMGA GGGSLIVLSM 610 620 630 640 650 LLLRRKKPYG AISHGVVEVD PMLTLEEQQL RELQRHGYEN PTYRFLEERP
	Isoform 2 [UniParc]. Checksum: EEF2FB97BDDF6A66	FASTA	651	72,247
	10 20 30 40 50 60 MGPASPAARG LSRRPGQPPL PLLLPLLLLL LRAQPAIGSL AGGSPGAAEA PGSAQVAGLC 70 80 90 100 110 120 GRLTLHRDLR TGRWEPDPQR SRRCLRDPQR VLEYCRQMYP ELQIARVEQA TQAIPMERWC 130 140 150 160 170 180 GGSRSGSCAH PHHQVVPFRC LPGEFVSEAL LVPEGCRFLH QERMDQCESS TRRHQEAQEA 190 200 210 220 230 240 CSSQGLILHG SGMLLPCGSD RFRGVEYVCC PPPGTPDPSG TAVGDPSTRS WPPGSRVEGA 250 260 270 280 290 300 EDEEEEESFP QPVDDYFVEP PQAEEEEETV PPPSSHTLAV VGKVTPTPRP TDGVDIYFGM 310 320 330 340 350 360 PGEISEHEGF LRAKMDLEER RMRQINEVMR EWAMADNQSK NLPKADRQAL NEHFQSILQT 370 380 390 400 410 420 LEEQVSGERQ RLVETHATRV IALINDQRRA ALEGFLAALQ ADPPQAERVL LALRRYLRAE 430 440 450 460 470 480 QKEQRHTLRH YQHVAAVDPE KAQQMRFQVH THLQVIEERV NQSLGLLDQN PHLAQELRPQ 490 500 510 520 530 540 IQELLHSEHL GPSELEAPAP GGSSEDKGGL QPPDSKDADT PMTLPKGSTE QDAASPEKEK 550 560 570 580 590 600 MNPLEQYERK VNASVPRGFP FHSSEIQRDE LAPAGTGVSR EAVSGLLIMG AGGGSLIVLS 610 620 630 640 650 MLLLRRKKPY GAISHGVVEV DPMLTLEEQQ LRELQRHGYE NPTYRFLEER P

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Human amyloid precursor-like protein 1 -- cDNA cloning, ectopic expression in COS-7 cells and identification of soluble forms in the cerebrospinal fluid." Paliga K., Peraus G., Kreger S., Duwrrwang U., Hesse L., Multhaup G., Masters C.L., Beyreuther K., Weidemann A. Eur. J. Biochem. 250:354-363(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[2]	"Structure of the human amyloid-precursor-like protein gene APLP1 at 19q13.1." Lenkkeri U., Kestila M., Lamerdin J.E., McCready P., Adamson A., Olsen A., Tryggvason K. Hum. Genet. 102:192-196(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 1).
[3]	"The DNA sequence and biology of human chromosome 19." Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E., Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A., Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S., Carrano A.V. , Caoile C., Chan Y.M., Christensen M., Cleland C.A., Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J., Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M., Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V., Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D., McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I., Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L., Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M., Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J., Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E., Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M., Rubin E.M., Lucas S.M. Nature 428:529-535(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2). Tissue: Brain and Ovary.
[5]	"Selective localization of amyloid precursor-like protein 1 in the cerebral cortex postsynaptic density." Kim T.-W., Wu K., Xu J.-L., McAuliffe G., Tanzi R.E., Wasco W., Black I.B. Brain Res. Mol. Brain Res. 32:36-44(1995) [PubMed] [Europe PMC] [Abstract] Cited for: POSSIBLE FUNCTION, TISSUE SPECIFICITY.
[6]	"The amyloid beta-protein precursor and its mammalian homologues. Evidence for a zinc-modulated heparin-binding superfamily." Bush A.I., Pettingell W.H. Jr., de Paradis M., Tanzi R.E., Wasco W. J. Biol. Chem. 269:26618-26621(1994) [PubMed] [Europe PMC] [Abstract] Cited for: HEPARIN AND ZINC-BINDING.
[7]	"Interaction of a neuron-specific protein containing PDZ domains with Alzheimer's amyloid precursor protein." Tomita S., Ozaki T., Taru H., Oguchi S., Takeda S., Yagi Y., Sakiyama S., Kirino Y., Suzuki T. J. Biol. Chem. 274:2243-2254(1999) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH APBA2.
[8]	"Evidence for a copper-binding superfamily of the amyloid precursor protein." Simons A., Ruppert T., Schmidt C., Schlicksupp A., Pipkorn R., Reed J., Masters C.L., White A.R., Cappai R., Beyreuther K., Bayer T.A., Multhaup G. Biochemistry 41:9310-9320(2002) [PubMed] [Europe PMC] [Abstract] Cited for: EXTRACELLULAR COPPER-BINDING.
[9]	"Enrichment of glycopeptides for glycan structure and attachment site identification." Nilsson J., Rueetschi U., Halim A., Hesse C., Carlsohn E., Brinkmalm G., Larson G. Nat. Methods 6:809-811(2009) [PubMed] [Europe PMC] [Abstract] Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT THR-215; SER-227 AND THR-228, STRUCTURE OF CARBOHYDRATES, MASS SPECTROMETRY. Tissue: Cerebrospinal fluid.
[10]	"LC-MS/MS characterization of O-glycosylation sites and glycan structures of human cerebrospinal fluid glycoproteins." Halim A., Ruetschi U., Larson G., Nilsson J. J. Proteome Res. 12:573-584(2013) [PubMed] [Europe PMC] [Abstract] Cited for: GLYCOSYLATION, MASS SPECTROMETRY.
[11]	"The E2 Domains of APP and APLP1 Share a Conserved Mode of Dimerization." Lee S., Xue Y., Hu J., Wang Y., Liu X., Demeler B., Ha Y. Biochemistry 50:5453-5464(2011) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.11 ANGSTROMS) OF 285-499, HEPARIN-BINDING, MUTAGENESIS OF HIS-426; ARG-429 AND HIS-433, SUBUNIT.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

U48437 mRNA. Translation: AAB96331.1.
AD000864 Genomic DNA. Translation: AAB50173.1.
BC012889 mRNA. Translation: AAH12889.1.
BC013850 mRNA. No translation available.

IPI

IPI00020012.
IPI00607600.

RefSeq

NP_001019978.1. NM_001024807.1.
NP_005157.1. NM_005166.3.

UniGene

Hs.74565.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
3PMR	X-ray	2.11	A/B	285-499	[»]
3Q7G	X-ray	2.30	A/B	285-494	[»]
3Q7L	X-ray	2.20	A/B	285-494	[»]
3QMK	X-ray	2.21	A/B	285-494	[»]

ProteinModelPortal

P51693.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-30846N.

IntAct

P51693. 30 interactions.

MINT

MINT-1395075.

STRING

9606.ENSP00000221891.

PTM databases

PhosphoSite

P51693.

Polymorphism databases

DMDM

28558769.

Proteomic databases

PaxDb

P51693.

PRIDE

P51693.

Protocols and materials databases

DNASU

333.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000221891; ENSP00000221891; ENSG00000105290.

GeneID

333.

KEGG

hsa:333.

UCSC

uc002oce.3. human.
uc002ocf.3. human.

Organism-specific databases

CTD

333.

GeneCards

GC19P036359.

HGNC

HGNC:597. APLP1.

HPA

HPA028971.

MIM

104775. gene.

neXtProt

NX_P51693.

PharmGKB

PA24884.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG289770.

HOGENOM

HOG000232190.

HOVERGEN

HBG000051.

InParanoid

P51693.

KO

K05639.

OMA

KDADTPM.

OrthoDB

EOG47PX5W.

PhylomeDB

P51693.

Gene expression databases

ArrayExpress

P51693.

Bgee

P51693.

CleanEx

HS_APLP1.

Genevestigator

P51693.

GermOnline

ENSG00000105290. Homo sapiens.

Family and domain databases

Gene3D

3.30.1490.140. 1 hit.
3.90.570.10. 1 hit.

InterPro

IPR008155. Amyloid_glyco.
IPR011178. Amyloid_glyco_Cu-bd.
IPR024329. Amyloid_glyco_E2_domain.
IPR008154. Amyloid_glyco_extra.
IPR019744. Amyloid_glyco_extracell_CS.
IPR015849. Amyloid_glyco_heparin-bd.
IPR019745. Amyloid_glyco_intracell_CS.
IPR019543. APP_amyloid_C.
[Graphical view]

Pfam

PF10515. APP_amyloid. 1 hit.
PF12924. APP_Cu_bd. 1 hit.
PF12925. APP_E2. 1 hit.
PF02177. APP_N. 1 hit.
[Graphical view]

PRINTS

PR00203. AMYLOIDA4.

SMART

SM00006. A4_EXTRA. 1 hit.
[Graphical view]

SUPFAM

SSF56491. A4_extra. 1 hit.
SSF89811. Amyloid_glyco_Cu-bd. 1 hit.
SSF109843. SSF109843. 1 hit.

PROSITE

PS00319. A4_EXTRA. 1 hit.
PS00320. A4_INTRA. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

ChiTaRS

APLP1. human.

EvolutionaryTrace

P51693.

GenomeRNAi

333.

NextBio

1377.

SOURCE

Search...

Entry information

Entry name

APLP1_HUMAN

Accession

Primary (citable) accession number: P51693
Secondary accession number(s): O00113, Q96A92

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1996
Last sequence update:	February 22, 2003
Last modified:	May 1, 2013
This is version 131 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.