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Protein

Amyloid-like protein 1

Gene

APLP1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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.By similarity
The gamma-CTF peptide, C30, is a potent enhancer of neuronal apoptosis.By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei167Required for Cu(2+) reductionBy similarity1

GO - Molecular functioni

  • alpha-2A adrenergic receptor binding Source: BHF-UCL
  • alpha-2B adrenergic receptor binding Source: BHF-UCL
  • alpha-2C adrenergic receptor binding Source: BHF-UCL
  • heparin binding Source: UniProtKB-KW
  • transition metal ion binding Source: InterPro

GO - Biological processi

  • adenylate cyclase-inhibiting G-protein coupled receptor signaling pathway Source: BHF-UCL
  • animal organ morphogenesis Source: ProtInc
  • apoptotic process Source: UniProtKB-KW
  • cell adhesion Source: UniProtKB-KW
  • cellular response to norepinephrine stimulus Source: BHF-UCL
  • endocytosis Source: UniProtKB-KW
  • negative regulation of cAMP biosynthetic process Source: BHF-UCL
  • nervous system development Source: ProtInc
Complete GO annotation...

Keywords - Biological processi

Apoptosis, Cell adhesion, Endocytosis

Keywords - Ligandi

Copper, Heparin-binding, Metal-binding, Zinc

Enzyme and pathway databases

BioCyciZFISH:ENSG00000105290-MONOMER.

Names & Taxonomyi

Protein namesi
Recommended name:
Amyloid-like protein 1
Short name:
APLP
Short name:
APLP-1
Cleaved into the following chain:
Gene namesi
Name:APLP1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 19

Organism-specific databases

HGNCiHGNC:597. APLP1.

Subcellular locationi

C30 :
  • Cytoplasm

  • Note: C-terminally processed in the Golgi complex.

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini39 – 580ExtracellularSequence analysisAdd BLAST542
Transmembranei581 – 603HelicalSequence analysisAdd BLAST23
Topological domaini604 – 650CytoplasmicSequence analysisAdd BLAST47

GO - Cellular componenti

  • basement membrane Source: ProtInc
  • integral component of membrane Source: UniProtKB-KW
  • perinuclear region of cytoplasm Source: BHF-UCL
  • plasma membrane Source: BHF-UCL
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi426H → A: Reduced affinity for heparin. Reduces homodimerization. 1 Publication1
Mutagenesisi429R → A: Strongly reduced affinity for heparin. Strongly reduced homodimerization. 1 Publication1
Mutagenesisi433H → A: Reduced affinity for heparin. Reduces homodimerization. 1 Publication1

Keywords - Diseasei

Neurodegeneration

Organism-specific databases

DisGeNETi333.
OpenTargetsiENSG00000105290.
PharmGKBiPA24884.

Polymorphism and mutation databases

BioMutaiAPLP1.
DMDMi28558769.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 38Sequence analysisAdd BLAST38
ChainiPRO_000000020339 – 650Amyloid-like protein 1Add BLAST612
PeptideiPRO_0000000204621 – 650C30By similarityAdd BLAST30

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi215O-linked (GalNAc...)1 Publication1
Glycosylationi227O-linked (GalNAc...)1 Publication1
Glycosylationi228O-linked (GalNAc...)1 Publication1
Glycosylationi337N-linked (GlcNAc...)Sequence analysis1
Glycosylationi461N-linked (GlcNAc...)Sequence analysis1
Glycosylationi551N-linked (GlcNAc...)Sequence analysis1

Post-translational modificationi

Proteolytically cleaved by caspases during neuronal apoptosis. Cleaved, in vitro, at Asp-620 by caspase-3 (By similarity).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-228.2 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei620 – 621Cleavage; by caspase-3By similarity2

Keywords - PTMi

Glycoprotein

Proteomic databases

PaxDbiP51693.
PeptideAtlasiP51693.
PRIDEiP51693.
TopDownProteomicsiP51693-2. [P51693-2]

PTM databases

iPTMnetiP51693.
PhosphoSitePlusiP51693.

Expressioni

Tissue specificityi

Expressed in the cerebral cortex where it is localized to the postsynaptic density (PSD).1 Publication

Gene expression databases

BgeeiENSG00000105290.
CleanExiHS_APLP1.
ExpressionAtlasiP51693. baseline and differential.
GenevisibleiP51693. HS.

Organism-specific databases

HPAiHPA028970.
HPA028971.

Interactioni

Subunit structurei

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).By similarity

Binary interactionsi

WithEntry#Exp.IntActNotes
itself3EBI-74648,EBI-74648
APLP2Q064812EBI-74648,EBI-79306
APPP05067-42EBI-74648,EBI-302641
MED12Q930742EBI-74648,EBI-394357
ZNF24P170282EBI-74648,EBI-707773

GO - Molecular functioni

  • alpha-2A adrenergic receptor binding Source: BHF-UCL
  • alpha-2B adrenergic receptor binding Source: BHF-UCL
  • alpha-2C adrenergic receptor binding Source: BHF-UCL

Protein-protein interaction databases

BioGridi106830. 46 interactors.
DIPiDIP-30846N.
IntActiP51693. 42 interactors.
MINTiMINT-1395075.
STRINGi9606.ENSP00000221891.

Structurei

Secondary structure

1650
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi293 – 298Combined sources6
Beta strandi302 – 304Combined sources3
Helixi306 – 337Combined sources32
Turni338 – 341Combined sources4
Helixi344 – 399Combined sources56
Beta strandi401 – 403Combined sources3
Helixi406 – 437Combined sources32
Helixi439 – 442Combined sources4
Turni443 – 445Combined sources3
Helixi446 – 467Combined sources22
Helixi471 – 485Combined sources15

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3PMRX-ray2.11A/B285-499[»]
3Q7GX-ray2.30A/B285-494[»]
3Q7LX-ray2.20A/B285-494[»]
3QMKX-ray2.21A/B285-494[»]
4RD9X-ray2.60A/B292-494[»]
4RDAX-ray2.50A/B290-495[»]
ProteinModelPortaliP51693.
SMRiP51693.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP51693.

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni158 – 178Copper-bindingBy similarityAdd BLAST21
Regioni204 – 211Zinc-binding8
Regioni285 – 305O-glycosylated at three sitesAdd BLAST21
Regioni310 – 342Heparin-bindingBy similarityAdd BLAST33
Regioni410 – 441Heparin-bindingBy similarityAdd BLAST32
Regioni442 – 459Collagen-bindingBy similarityAdd BLAST18
Regioni632 – 649Interaction with DAB1By similarityAdd BLAST18
Regioni636 – 650Interaction with DAB2By similarityAdd BLAST15

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi604 – 615Basolateral sorting signalBy similarityAdd BLAST12
Motifi640 – 643Clathrin-bindingSequence analysis4
Motifi640 – 643NPXY motif; contains endocytosis signal4

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi241 – 247Poly-Glu7
Compositional biasi264 – 268Poly-Glu5

Domaini

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.

Sequence similaritiesi

Belongs to the APP family.Curated

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiENOG410IT8P. Eukaryota.
ENOG4111MXY. LUCA.
GeneTreeiENSGT00530000063252.
HOGENOMiHOG000232190.
HOVERGENiHBG000051.
InParanoidiP51693.
KOiK05639.
OMAiPCGSDRF.
OrthoDBiEOG091G0UW4.
PhylomeDBiP51693.
TreeFamiTF317274.

Family and domain databases

Gene3Di3.30.1490.140. 1 hit.
3.90.570.10. 1 hit.
InterProiIPR008155. 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]
PfamiPF10515. APP_amyloid. 1 hit.
PF12924. APP_Cu_bd. 1 hit.
PF12925. APP_E2. 1 hit.
PF02177. APP_N. 1 hit.
[Graphical view]
PRINTSiPR00203. AMYLOIDA4.
SMARTiSM00006. A4_EXTRA. 1 hit.
[Graphical view]
SUPFAMiSSF109843. SSF109843. 1 hit.
SSF56491. SSF56491. 1 hit.
SSF89811. SSF89811. 1 hit.
PROSITEiPS00319. A4_EXTRA. 1 hit.
PS00320. A4_INTRA. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P51693-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MGPASPAARG LSRRPGQPPL PLLLPLLLLL LRAQPAIGSL AGGSPGAAEA
60 70 80 90 100
PGSAQVAGLC GRLTLHRDLR TGRWEPDPQR SRRCLRDPQR VLEYCRQMYP
110 120 130 140 150
ELQIARVEQA TQAIPMERWC GGSRSGSCAH PHHQVVPFRC LPGEFVSEAL
160 170 180 190 200
LVPEGCRFLH QERMDQCESS TRRHQEAQEA CSSQGLILHG SGMLLPCGSD
210 220 230 240 250
RFRGVEYVCC PPPGTPDPSG TAVGDPSTRS WPPGSRVEGA EDEEEEESFP
260 270 280 290 300
QPVDDYFVEP PQAEEEEETV PPPSSHTLAV VGKVTPTPRP TDGVDIYFGM
310 320 330 340 350
PGEISEHEGF LRAKMDLEER RMRQINEVMR EWAMADNQSK NLPKADRQAL
360 370 380 390 400
NEHFQSILQT LEEQVSGERQ RLVETHATRV IALINDQRRA ALEGFLAALQ
410 420 430 440 450
ADPPQAERVL LALRRYLRAE QKEQRHTLRH YQHVAAVDPE KAQQMRFQVH
460 470 480 490 500
THLQVIEERV NQSLGLLDQN PHLAQELRPQ IQELLHSEHL GPSELEAPAP
510 520 530 540 550
GGSSEDKGGL QPPDSKDDTP MTLPKGSTEQ DAASPEKEKM NPLEQYERKV
560 570 580 590 600
NASVPRGFPF HSSEIQRDEL APAGTGVSRE AVSGLLIMGA GGGSLIVLSM
610 620 630 640 650
LLLRRKKPYG AISHGVVEVD PMLTLEEQQL RELQRHGYEN PTYRFLEERP
Length:650
Mass (Da):72,176
Last modified:February 22, 2003 - v3
Checksum:iB95F0F4D1C5CBAC7
GO
Isoform 2 (identifier: P51693-2) [UniParc]FASTAAdd to basket

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

Show »
Length:651
Mass (Da):72,247
Checksum:iEEF2FB97BDDF6A66
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti48A → P in AAB96331 (PubMed:9428684).Curated1
Sequence conflicti78P → S in BC013850 (PubMed:15489334).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_039100517D → DA in isoform 2. 1 Publication1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U48437 mRNA. Translation: AAB96331.1.
AD000864 Genomic DNA. Translation: AAB50173.1.
BC012889 mRNA. Translation: AAH12889.1.
BC013850 mRNA. No translation available.
CCDSiCCDS32997.1. [P51693-2]
RefSeqiNP_001019978.1. NM_001024807.2. [P51693-2]
NP_005157.1. NM_005166.4. [P51693-1]
UniGeneiHs.74565.

Genome annotation databases

EnsembliENST00000221891; ENSP00000221891; ENSG00000105290. [P51693-2]
GeneIDi333.
KEGGihsa:333.
UCSCiuc002ocf.4. human. [P51693-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U48437 mRNA. Translation: AAB96331.1.
AD000864 Genomic DNA. Translation: AAB50173.1.
BC012889 mRNA. Translation: AAH12889.1.
BC013850 mRNA. No translation available.
CCDSiCCDS32997.1. [P51693-2]
RefSeqiNP_001019978.1. NM_001024807.2. [P51693-2]
NP_005157.1. NM_005166.4. [P51693-1]
UniGeneiHs.74565.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3PMRX-ray2.11A/B285-499[»]
3Q7GX-ray2.30A/B285-494[»]
3Q7LX-ray2.20A/B285-494[»]
3QMKX-ray2.21A/B285-494[»]
4RD9X-ray2.60A/B292-494[»]
4RDAX-ray2.50A/B290-495[»]
ProteinModelPortaliP51693.
SMRiP51693.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi106830. 46 interactors.
DIPiDIP-30846N.
IntActiP51693. 42 interactors.
MINTiMINT-1395075.
STRINGi9606.ENSP00000221891.

PTM databases

iPTMnetiP51693.
PhosphoSitePlusiP51693.

Polymorphism and mutation databases

BioMutaiAPLP1.
DMDMi28558769.

Proteomic databases

PaxDbiP51693.
PeptideAtlasiP51693.
PRIDEiP51693.
TopDownProteomicsiP51693-2. [P51693-2]

Protocols and materials databases

DNASUi333.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000221891; ENSP00000221891; ENSG00000105290. [P51693-2]
GeneIDi333.
KEGGihsa:333.
UCSCiuc002ocf.4. human. [P51693-1]

Organism-specific databases

CTDi333.
DisGeNETi333.
GeneCardsiAPLP1.
HGNCiHGNC:597. APLP1.
HPAiHPA028970.
HPA028971.
MIMi104775. gene.
neXtProtiNX_P51693.
OpenTargetsiENSG00000105290.
PharmGKBiPA24884.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IT8P. Eukaryota.
ENOG4111MXY. LUCA.
GeneTreeiENSGT00530000063252.
HOGENOMiHOG000232190.
HOVERGENiHBG000051.
InParanoidiP51693.
KOiK05639.
OMAiPCGSDRF.
OrthoDBiEOG091G0UW4.
PhylomeDBiP51693.
TreeFamiTF317274.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000105290-MONOMER.

Miscellaneous databases

ChiTaRSiAPLP1. human.
EvolutionaryTraceiP51693.
GeneWikiiAPLP1.
GenomeRNAii333.
PROiP51693.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000105290.
CleanExiHS_APLP1.
ExpressionAtlasiP51693. baseline and differential.
GenevisibleiP51693. HS.

Family and domain databases

Gene3Di3.30.1490.140. 1 hit.
3.90.570.10. 1 hit.
InterProiIPR008155. 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]
PfamiPF10515. APP_amyloid. 1 hit.
PF12924. APP_Cu_bd. 1 hit.
PF12925. APP_E2. 1 hit.
PF02177. APP_N. 1 hit.
[Graphical view]
PRINTSiPR00203. AMYLOIDA4.
SMARTiSM00006. A4_EXTRA. 1 hit.
[Graphical view]
SUPFAMiSSF109843. SSF109843. 1 hit.
SSF56491. SSF56491. 1 hit.
SSF89811. SSF89811. 1 hit.
PROSITEiPS00319. A4_EXTRA. 1 hit.
PS00320. A4_INTRA. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiAPLP1_HUMAN
AccessioniPrimary (citable) accession number: P51693
Secondary accession number(s): O00113, Q96A92
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: February 22, 2003
Last modified: November 2, 2016
This is version 160 of the entry and version 3 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Miscellaneousi

Miscellaneous

Binds zinc and copper in the extracellular domain. Zinc-binding increases heparin binding. No Cu2+ reducing activity with copper-binding.

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 19
    Human chromosome 19: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  4. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.