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Protein

Amyloid-like protein 1

Gene

APLP1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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

Miscellaneous

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

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionHeparin-binding
Biological processApoptosis, Cell adhesion, Endocytosis
LigandCopper, Metal-binding, Zinc

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

EuPathDBiHostDB:ENSG00000105290.11
HGNCiHGNC:597 APLP1
MIMi104775 gene
neXtProtiNX_P51693

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

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

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
Disulfide bondi60 ↔ 84PROSITE-ProRule annotation
Disulfide bondi95 ↔ 140PROSITE-ProRule annotation
Disulfide bondi120 ↔ 128PROSITE-ProRule annotation
Disulfide bondi156 ↔ 210PROSITE-ProRule annotation
Disulfide bondi167 ↔ 197PROSITE-ProRule annotation
Disulfide bondi181 ↔ 209PROSITE-ProRule annotation
Glycosylationi215O-linked (GalNAc...) threonine1 Publication1
Glycosylationi227O-linked (GalNAc...) serine1 Publication1
Glycosylationi228O-linked (GalNAc...) threonine1 Publication1
Glycosylationi337N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi461N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi551N-linked (GlcNAc...) asparagineSequence 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

Disulfide bond, Glycoprotein

Proteomic databases

PaxDbiP51693
PeptideAtlasiP51693
PRIDEiP51693
ProteomicsDBi56379
56380 [P51693-2]
TopDownProteomicsiP51693-2 [P51693-2]

PTM databases

GlyConnecti716
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 Expressed in 147 organ(s), highest expression level in C1 segment of cervical spinal cord
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

GO - Molecular functioni

Protein-protein interaction databases

BioGridi106830, 46 interactors
DIPiDIP-30846N
IntActiP51693, 42 interactors
MINTiP51693
STRINGi9606.ENSP00000221891

Structurei

Secondary structure

1650
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliP51693
SMRiP51693
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP51693

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini50 – 212E1PROSITE-ProRule annotationAdd BLAST163
Domaini293 – 484E2PROSITE-ProRule annotationAdd BLAST192

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni50 – 146GFLD subdomainPROSITE-ProRule annotationAdd BLAST97
Regioni154 – 212CuBD subdomainPROSITE-ProRule annotationAdd BLAST59
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.PROSITE-ProRule annotation

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

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

Family and domain databases

Gene3Di1.20.120.770, 1 hit
3.30.1490.140, 1 hit
3.90.570.10, 1 hit
InterProiView protein in InterPro
IPR036669 Amyloid_Cu-bd_sf
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
IPR036454 Amyloid_glyco_heparin-bd_sf
IPR019745 Amyloid_glyco_intracell_CS
IPR019543 APP_amyloid_C
IPR036176 E2_sf
PANTHERiPTHR23103 PTHR23103, 1 hit
PfamiView protein in Pfam
PF10515 APP_amyloid, 1 hit
PF12924 APP_Cu_bd, 1 hit
PF12925 APP_E2, 1 hit
PF02177 APP_N, 1 hit
PRINTSiPR00203 AMYLOIDA4
SMARTiView protein in SMART
SM00006 A4_EXTRA, 1 hit
SUPFAMiSSF109843 SSF109843, 1 hit
SSF56491 SSF56491, 1 hit
SSF89811 SSF89811, 1 hit
PROSITEiView protein in PROSITE
PS00319 APP_CUBD, 1 hit
PS51869 APP_E1, 1 hit
PS51870 APP_E2, 1 hit
PS00320 APP_INTRA, 1 hit

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

This entry has 2 described isoforms and 7 potential isoforms that are computationally mapped.Show allAlign All

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

Computationally mapped potential isoform sequencesi

There are 7 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
B7Z4G8B7Z4G8_HUMAN
cDNA FLJ56046, highly similar to Am...
APLP1
644Annotation score:
F5GZ08F5GZ08_HUMAN
Amyloid-like protein 1
APLP1
611Annotation score:
K7EQJ4K7EQJ4_HUMAN
Amyloid-like protein 1
APLP1
294Annotation score:
K7ELK0K7ELK0_HUMAN
Amyloid-like protein 1
APLP1
173Annotation score:
S4R3U6S4R3U6_HUMAN
Amyloid-like protein 1
APLP1
289Annotation score:
K7EMN4K7EMN4_HUMAN
Amyloid-like protein 1
APLP1
221Annotation score:
K7EMS1K7EMS1_HUMAN
Amyloid-like protein 1
APLP1
118Annotation score:

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

Similar proteinsi

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
MINTiP51693
STRINGi9606.ENSP00000221891

PTM databases

GlyConnecti716
iPTMnetiP51693
PhosphoSitePlusiP51693

Polymorphism and mutation databases

BioMutaiAPLP1
DMDMi28558769

Proteomic databases

PaxDbiP51693
PeptideAtlasiP51693
PRIDEiP51693
ProteomicsDBi56379
56380 [P51693-2]
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
EuPathDBiHostDB:ENSG00000105290.11
GeneCardsiAPLP1
HGNCiHGNC:597 APLP1
HPAiHPA028970
HPA028971
MIMi104775 gene
neXtProtiNX_P51693
OpenTargetsiENSG00000105290
PharmGKBiPA24884
GenAtlasiSearch...

Phylogenomic databases

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

Miscellaneous databases

ChiTaRSiAPLP1 human
EvolutionaryTraceiP51693
GeneWikiiAPLP1
GenomeRNAii333
PROiPR:P51693
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000105290 Expressed in 147 organ(s), highest expression level in C1 segment of cervical spinal cord
CleanExiHS_APLP1
ExpressionAtlasiP51693 baseline and differential
GenevisibleiP51693 HS

Family and domain databases

Gene3Di1.20.120.770, 1 hit
3.30.1490.140, 1 hit
3.90.570.10, 1 hit
InterProiView protein in InterPro
IPR036669 Amyloid_Cu-bd_sf
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
IPR036454 Amyloid_glyco_heparin-bd_sf
IPR019745 Amyloid_glyco_intracell_CS
IPR019543 APP_amyloid_C
IPR036176 E2_sf
PANTHERiPTHR23103 PTHR23103, 1 hit
PfamiView protein in Pfam
PF10515 APP_amyloid, 1 hit
PF12924 APP_Cu_bd, 1 hit
PF12925 APP_E2, 1 hit
PF02177 APP_N, 1 hit
PRINTSiPR00203 AMYLOIDA4
SMARTiView protein in SMART
SM00006 A4_EXTRA, 1 hit
SUPFAMiSSF109843 SSF109843, 1 hit
SSF56491 SSF56491, 1 hit
SSF89811 SSF89811, 1 hit
PROSITEiView protein in PROSITE
PS00319 APP_CUBD, 1 hit
PS51869 APP_E1, 1 hit
PS51870 APP_E2, 1 hit
PS00320 APP_INTRA, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiAPLP1_HUMAN
AccessioniPrimary (citable) accession number: P51693
Secondary accession number(s): O00113, Q96A92
Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: February 22, 2003
Last modified: November 7, 2018
This is version 175 of the entry and version 3 of the sequence. See 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

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

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