Reviewed, UniProtKB/Swiss-Prot P51693 (APLP1_HUMAN)

Names and origin

Protein names

Recommended name:
    Amyloid-like protein 1
Alternative name(s):
    APLP-1
      Short name=APLP
Cleaved into the following chain:
    1- Recommended name:
            C30

Gene names

Name:

APLP1

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › 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. The gamma-CTF peptide, C30, is a potent enhancer of neuronal apoptosis By similarity.
Subunit structure	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 By similarity.
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.4
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.
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
Disease	Neurodegeneration
Domain	Signal Transmembrane
Ligand	Copper Heparin-binding Metal-binding Zinc
PTM	Glycoprotein
Technical term	Complete proteome
Gene Ontology (GO)
Biological process	apoptosis Inferred from electronic annotation. Source: UniProtKB-KW cell adhesion Inferred from electronic annotation. Source: UniProtKB-KW endocytosis Inferred from electronic annotation. Source: UniProtKB-KW organ morphogenesis Ref.2 Traceable author statement. Source: ProtInc
Cellular component	basement membrane Ref.2 Traceable author statement. Source: ProtInc cytoplasm Inferred from electronic annotation. Source: UniProtKB-KW integral to membrane Inferred from electronic annotation. Source: UniProtKB-SubCell plasma membrane Inferred from electronic annotation. Source: UniProtKB-KW
Molecular function	copper ion binding Inferred from electronic annotation. Source: UniProtKB-KW heparin binding Inferred from electronic annotation. Source: UniProtKB-KW identical protein binding Inferred from physical interaction. Source: IntAct zinc ion binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
itself		2	EBI-74648,EBI-74648
APLP2	Q06481	1	EBI-74648,EBI-79306
APP	P05067-4	1	EBI-74648,EBI-302641
CNTN3	Q9P232	1	EBI-74648,EBI-2028361
CNTN4	Q8IWV2	1	EBI-74648,EBI-2028276
CNTN5	O94779	1	EBI-74648,EBI-2028625
Slc5a7	Q8BGY9	1	EBI-74648,EBI-2010752	From a different organism.
SPON1	Q9HCB6	1	EBI-74648,EBI-2431846
Tom1	O88746	1	EBI-74648,EBI-74264	From a different organism.
ZNF24	P17028	1	EBI-74648,EBI-707773

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	Potential
	Topological domain	604 – 650	47	Cytoplasmic Potential
	Region	158 – 178	21	Copper-binding By similarity
	Region	204 – 211	8	Zinc-binding
	Region	310 – 342	33	Heparin-binding By similarity
	Region	410 – 441	32	Heparin-binding By similarity
	Region	442 – 459	18	Collagen-binding 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	337	1	N-linked (GlcNAc...) Potential
	Glycosylation	461	1	N-linked (GlcNAc...) Potential
	Glycosylation	551	1	N-linked (GlcNAc...) Potential
Experimental info
	Sequence conflict	48	1	A → P in AAB96331. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	P51693-1 [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

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: 9428684] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[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: 9521588] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]	"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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Ovary.
[4]	"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: 7494461] [Abstract] Cited for: POSSIBLE FUNCTION, TISSUE SPECIFICITY.
[5]	"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: 7929392] [Abstract] Cited for: HEPARIN AND ZINC-BINDING.
[6]	"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: 9890987] [Abstract] Cited for: INTERACTION WITH APBA2.
[7]	"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: 12135352] [Abstract] Cited for: EXTRACELLULAR COPPER-BINDING.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBLGenBankDDBJ	U48437 mRNA. Translation: AAB96331.1. AD000864 Genomic DNA. Translation: AAB50173.1. BC012889 mRNA. Translation: AAH12889.1.
IPI	IPI00020012.
RefSeq	NP_001019978.1. NP_005157.1.
UniGene	Hs.74565
3D structure databases
ModBase	Search...
Protein-protein interaction databases
IntAct	P51693. 30 interactions.
STRING	P51693.
PTM databases
PhosphoSite	P51693.
Proteomic databases
PRIDE	P51693.
Genome annotation databases
Ensembl	ENST00000221891; ENSP00000221891; ENSG00000105290; Homo sapiens. [Genome view]
GeneID	333.
KEGG	hsa:333.
NMPDR	fig|9606.3.peg.16291.
UCSC	uc002oce.1. human.
Organism-specific databases
CTD	333.
GeneCards	GC19P041051.
H-InvDB	HIX0017982.
HGNC	HGNC:597. APLP1.
MIM	104775. gene.
PharmGKB	PA24884.
GenAtlas	Search...
Phylogenomic databases
HOGENOM	P51693.
HOVERGEN	P51693.
Gene expression databases
ArrayExpress	P51693.
Bgee	P51693.
CleanEx	HS_APLP1.
Genevestigator	P51693.
GermOnline	ENSG00000105290. Homo sapiens.
Family and domain databases
InterPro	IPR008155. Amyloid_glyco. IPR011178. Amyloid_glyco_Cu-bd. IPR008154. Amyloid_glyco_extra. IPR019744. Amyloid_glyco_extracell_CS. IPR015849. Amyloid_glyco_heparin-bd. IPR019745. Amyloid_glyco_intracell_CS. IPR019543. APP_amyloid. [Graphical view]
Gene3D	G3DSA:3.30.1490.140. Amyloid_glyco_Cu-bd. 1 hit. G3DSA:3.90.570.10. Amyloid_glyco_heparin-bd. 1 hit.
Pfam	PF02177. A4_EXTRA. 1 hit. PF10515. APP_amyloid. 1 hit. [Graphical view]
PRINTS	PR00203. AMYLOIDA4.
SMART	SM00006. A4_EXTRA. 1 hit. [Graphical view]
PROSITE	PS00319. A4_EXTRA. 1 hit. PS00320. A4_INTRA. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
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:	November 24, 2009
This is version 95 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

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.