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Protein

Amyloid-like protein 2

Gene

APLP2

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 the regulation of hemostasis. The soluble form may have inhibitory properties towards coagulation factors. May interact with cellular G-protein signaling pathways. May bind to the DNA 5'-GTCACATG-3'(CDEI box). Inhibits trypsin, chymotrypsin, plasmin, factor XIA and plasma and glandular kallikrein. Modulates the Cu/Zn nitric oxide-catalyzed autodegradation of GPC1 heparan sulfate side chains in fibroblasts (By similarity).By similarity1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei320 – 321Reactive bondBy similarity2

GO - Molecular functioni

GO - Biological processi

  • G-protein coupled receptor signaling pathway Source: UniProtKB
  • platelet degranulation Source: Reactome
Complete GO annotation...

Keywords - Molecular functioni

Protease inhibitor, Serine protease inhibitor

Keywords - Ligandi

DNA-binding

Enzyme and pathway databases

BioCyciZFISH:ENSG00000084234-MONOMER.
ReactomeiR-HSA-114608. Platelet degranulation.
SignaLinkiQ06481.
SIGNORiQ06481.

Protein family/group databases

MEROPSiI02.016.

Names & Taxonomyi

Protein namesi
Recommended name:
Amyloid-like protein 2
Short name:
APLP-2
Alternative name(s):
APPH
Amyloid protein homolog
CDEI box-binding protein
Short name:
CDEBP
Gene namesi
Name:APLP2
Synonyms:APPL2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 11

Organism-specific databases

HGNCiHGNC:598. APLP2.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini32 – 692ExtracellularSequence analysisAdd BLAST661
Transmembranei693 – 716HelicalSequence analysisAdd BLAST24
Topological domaini717 – 763CytoplasmicSequence analysisAdd BLAST47

GO - Cellular componenti

  • extracellular exosome Source: UniProtKB
  • integral component of membrane Source: UniProtKB
  • membrane Source: UniProtKB
  • nucleus Source: UniProtKB
  • plasma membrane Source: Reactome
  • platelet alpha granule membrane Source: Reactome
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane, Nucleus

Pathology & Biotechi

Organism-specific databases

DisGeNETi334.
OpenTargetsiENSG00000084234.
PharmGKBiPA24885.

Polymorphism and mutation databases

BioMutaiAPLP2.
DMDMi1703344.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 31Sequence analysisAdd BLAST31
ChainiPRO_000000020732 – 763Amyloid-like protein 2Add BLAST732

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi310 ↔ 360PROSITE-ProRule annotation
Disulfide bondi319 ↔ 343PROSITE-ProRule annotation
Disulfide bondi335 ↔ 356PROSITE-ProRule annotation
Modified residuei590Phosphoserine; by FAM20C1 Publication1

Post-translational modificationi

The BPTI/Kunitz inhibitor domain is O-glycosylated.1 Publication

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein

Proteomic databases

EPDiQ06481.
MaxQBiQ06481.
PaxDbiQ06481.
PeptideAtlasiQ06481.
PRIDEiQ06481.
TopDownProteomicsiQ06481-5. [Q06481-5]

PTM databases

iPTMnetiQ06481.
PhosphoSitePlusiQ06481.

Miscellaneous databases

PMAP-CutDBQ06481.

Expressioni

Tissue specificityi

Expressed in placenta, brain, heart, lung, liver, kidney and endothelial tissues.

Gene expression databases

BgeeiENSG00000084234.
CleanExiHS_APLP2.
HS_APPL2.
ExpressionAtlasiQ06481. baseline and differential.
GenevisibleiQ06481. HS.

Organism-specific databases

HPAiHPA039319.

Interactioni

Subunit structurei

Interacts with CPEB1. Interacts (via NPXY motif) with DAB2 (via PID domain); the interaction is impaired by tyrosine phosphorylation of the NPXY motif (By similarity).By similarity

Binary interactionsi

WithEntry#Exp.IntActNotes
itself3EBI-79306,EBI-79306
APLP1P516932EBI-79306,EBI-74648
APPP05067-42EBI-79306,EBI-302641
DEDDO756183EBI-79306,EBI-1043164
ETS1P149212EBI-79306,EBI-913209
JUNP054123EBI-79306,EBI-852823
MED12Q930742EBI-79306,EBI-394357

Protein-protein interaction databases

BioGridi106831. 28 interactors.
DIPiDIP-31047N.
IntActiQ06481. 21 interactors.
MINTiMINT-1186713.
STRINGi9606.ENSP00000263574.

Structurei

3D structure databases

ProteinModelPortaliQ06481.
SMRiQ06481.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini306 – 364BPTI/Kunitz inhibitorPROSITE-ProRule annotationAdd BLAST59

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni749 – 763Interaction with DAB2By similarityAdd BLAST15

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi750 – 755NPXY motif6

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi215 – 280Asp/Glu-rich (highly acidic)Add BLAST66
Compositional biasi215 – 231Poly-GluAdd BLAST17

Sequence similaritiesi

Belongs to the APP family.Curated
Contains 1 BPTI/Kunitz inhibitor domain.PROSITE-ProRule annotation

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG3540. Eukaryota.
ENOG410ZW2A. LUCA.
GeneTreeiENSGT00530000063252.
HOGENOMiHOG000232190.
HOVERGENiHBG000051.
InParanoidiQ06481.
KOiK08117.
OMAiTLYSYGM.
OrthoDBiEOG091G0UW4.
PhylomeDBiQ06481.
TreeFamiTF317274.

Family and domain databases

Gene3Di3.30.1490.140. 1 hit.
3.90.570.10. 1 hit.
4.10.410.10. 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.
IPR002223. Kunitz_BPTI.
IPR020901. Prtase_inh_Kunz-CS.
[Graphical view]
PfamiPF10515. APP_amyloid. 1 hit.
PF12924. APP_Cu_bd. 1 hit.
PF12925. APP_E2. 1 hit.
PF02177. APP_N. 1 hit.
PF00014. Kunitz_BPTI. 1 hit.
[Graphical view]
PRINTSiPR00203. AMYLOIDA4.
PR00759. BASICPTASE.
SMARTiSM00006. A4_EXTRA. 1 hit.
SM00131. KU. 1 hit.
[Graphical view]
SUPFAMiSSF109843. SSF109843. 1 hit.
SSF56491. SSF56491. 1 hit.
SSF57362. SSF57362. 1 hit.
SSF89811. SSF89811. 1 hit.
PROSITEiPS00319. A4_EXTRA. 1 hit.
PS00320. A4_INTRA. 1 hit.
PS00280. BPTI_KUNITZ_1. 1 hit.
PS50279. BPTI_KUNITZ_2. 1 hit.
[Graphical view]

Sequences (6)i

Sequence statusi: Complete.

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

This entry describes 6 isoformsi produced by alternative splicing. AlignAdd to basket

Note: Additional isoforms seem to exist.
Isoform 1 (identifier: Q06481-1) [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
MAATGTAAAA ATGRLLLLLL VGLTAPALAL AGYIEALAAN AGTGFAVAEP
60 70 80 90 100
QIAMFCGKLN MHVNIQTGKW EPDPTGTKSC FETKEEVLQY CQEMYPELQI
110 120 130 140 150
TNVMEANQRV SIDNWCRRDK KQCKSRFVTP FKCLVGEFVS DVLLVPEKCQ
160 170 180 190 200
FFHKERMEVC ENHQHWHTVV KEACLTQGMT LYSYGMLLPC GVDQFHGTEY
210 220 230 240 250
VCCPQTKIIG SVSKEEEEED EEEEEEEDEE EDYDVYKSEF PTEADLEDFT
260 270 280 290 300
EAAVDEDDED EEEGEEVVED RDYYYDTFKG DDYNEENPTE PGSDGTMSDK
310 320 330 340 350
EITHDVKAVC SQEAMTGPCR AVMPRWYFDL SKGKCVRFIY GGCGGNRNNF
360 370 380 390 400
ESEDYCMAVC KAMIPPTPLP TNDVDVYFET SADDNEHARF QKAKEQLEIR
410 420 430 440 450
HRNRMDRVKK EWEEAELQAK NLPKAERQTL IQHFQAMVKA LEKEAASEKQ
460 470 480 490 500
QLVETHLARV EAMLNDRRRM ALENYLAALQ SDPPRPHRIL QALRRYVRAE
510 520 530 540 550
NKDRLHTIRH YQHVLAVDPE KAAQMKSQVM THLHVIEERR NQSLSLLYKV
560 570 580 590 600
PYVAQEIQEE IDELLQEQRA DMDQFTASIS ETPVDVRVSS EESEEIPPFH
610 620 630 640 650
PFHPFPALPE NEDTQPELYH PMKKGSGVGE QDGGLIGAEE KVINSKNKVD
660 670 680 690 700
ENMVIDETLD VKEMIFNAER VGGLEEERES VGPLREDFSL SSSALIGLLV
710 720 730 740 750
IAVAIATVIV ISLVMLRKRQ YGTISHGIVE VDPMLTPEER HLNKMQNHGY
760
ENPTYKYLEQ MQI
Length:763
Mass (Da):86,956
Last modified:October 1, 1996 - v2
Checksum:iCA3A7D6DDB8A28D0
GO
Isoform 2 (identifier: Q06481-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     308-363: Missing.

Show »
Length:707
Mass (Da):80,721
Checksum:i1F45B94DAE88BC23
GO
Isoform 3 (identifier: Q06481-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     613-624: Missing.

Show »
Length:751
Mass (Da):85,487
Checksum:i788BCDC6E4487E18
GO
Isoform 4 (identifier: Q06481-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     308-363: Missing.
     364-364: I → V
     613-624: Missing.

Show »
Length:695
Mass (Da):79,238
Checksum:i728CA8ACBB7594FB
GO
Isoform 5 (identifier: Q06481-5) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     136-364: Missing.
     613-624: Missing.

Note: No experimental confirmation available.
Show »
Length:522
Mass (Da):59,151
Checksum:i993641BFC15ED6E0
GO
Isoform 6 (identifier: Q06481-6) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-35: MAATGTAAAAATGRLLLLLLVGLTAPALALAGYIE → MLRAPGELPR...ASVDRGNPLW
     613-624: Missing.

Show »
Length:761
Mass (Da):87,215
Checksum:iE87786F52F076C41
GO

Sequence cautioni

The sequence BAG54641 differs from that shown. Reason: Frameshift at position 81.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti224E → D in AAD47291 (PubMed:7651835).Curated1
Sequence conflicti226 – 227Missing in BAG54641 (PubMed:14702039).Curated2
Sequence conflicti543S → I in AAA35526 (PubMed:8485127).Curated1
Sequence conflicti543S → T in AAH04371 (PubMed:15489334).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_022039632D → N.Corresponds to variant rs3740881dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0468811 – 35MAATG…AGYIE → MLRAPGELPRQAARCSLCRL GPGRGRAFFKWRCLPASVDR GNPLW in isoform 6. CuratedAdd BLAST35
Alternative sequenceiVSP_030921136 – 364Missing in isoform 5. 1 PublicationAdd BLAST229
Alternative sequenceiVSP_000018308 – 363Missing in isoform 2 and isoform 4. 1 PublicationAdd BLAST56
Alternative sequenceiVSP_046882364I → V in isoform 4. 1 Publication1
Alternative sequenceiVSP_000019613 – 624Missing in isoform 3, isoform 4, isoform 5 and isoform 6. 3 PublicationsAdd BLAST12

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
S60099 mRNA. Translation: AAC60589.1.
L09209 mRNA. Translation: AAA35526.1.
L27631 mRNA. Translation: AAC41701.1.
Z22572 mRNA. Translation: CAA80295.1.
AK128162 mRNA. Translation: BAG54641.1. Frameshift.
L19597 mRNA. Translation: AAA35601.1.
L23113 mRNA. Translation: AAA36032.1.
L23114 mRNA. Translation: AAA36130.1.
AF168956 mRNA. Translation: AAD47291.1.
AP001183 Genomic DNA. No translation available.
AP003041 Genomic DNA. No translation available.
BC000373 mRNA. Translation: AAH00373.1.
BC004371 mRNA. Translation: AAH04371.1.
CCDSiCCDS44773.1. [Q06481-3]
CCDS44774.1. [Q06481-4]
CCDS44775.1. [Q06481-5]
CCDS58196.1. [Q06481-6]
CCDS8486.1. [Q06481-1]
PIRiA49321.
S41082.
RefSeqiNP_001135748.1. NM_001142276.1. [Q06481-3]
NP_001135749.1. NM_001142277.1. [Q06481-4]
NP_001135750.1. NM_001142278.1. [Q06481-5]
NP_001230228.1. NM_001243299.1. [Q06481-6]
NP_001633.1. NM_001642.2. [Q06481-1]
UniGeneiHs.370247.

Genome annotation databases

EnsembliENST00000263574; ENSP00000263574; ENSG00000084234. [Q06481-1]
ENST00000278756; ENSP00000278756; ENSG00000084234. [Q06481-6]
ENST00000338167; ENSP00000345444; ENSG00000084234. [Q06481-3]
ENST00000345598; ENSP00000263575; ENSG00000084234. [Q06481-5]
ENST00000528499; ENSP00000435914; ENSG00000084234. [Q06481-4]
GeneIDi334.
KEGGihsa:334.
UCSCiuc001qfp.4. human. [Q06481-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
S60099 mRNA. Translation: AAC60589.1.
L09209 mRNA. Translation: AAA35526.1.
L27631 mRNA. Translation: AAC41701.1.
Z22572 mRNA. Translation: CAA80295.1.
AK128162 mRNA. Translation: BAG54641.1. Frameshift.
L19597 mRNA. Translation: AAA35601.1.
L23113 mRNA. Translation: AAA36032.1.
L23114 mRNA. Translation: AAA36130.1.
AF168956 mRNA. Translation: AAD47291.1.
AP001183 Genomic DNA. No translation available.
AP003041 Genomic DNA. No translation available.
BC000373 mRNA. Translation: AAH00373.1.
BC004371 mRNA. Translation: AAH04371.1.
CCDSiCCDS44773.1. [Q06481-3]
CCDS44774.1. [Q06481-4]
CCDS44775.1. [Q06481-5]
CCDS58196.1. [Q06481-6]
CCDS8486.1. [Q06481-1]
PIRiA49321.
S41082.
RefSeqiNP_001135748.1. NM_001142276.1. [Q06481-3]
NP_001135749.1. NM_001142277.1. [Q06481-4]
NP_001135750.1. NM_001142278.1. [Q06481-5]
NP_001230228.1. NM_001243299.1. [Q06481-6]
NP_001633.1. NM_001642.2. [Q06481-1]
UniGeneiHs.370247.

3D structure databases

ProteinModelPortaliQ06481.
SMRiQ06481.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi106831. 28 interactors.
DIPiDIP-31047N.
IntActiQ06481. 21 interactors.
MINTiMINT-1186713.
STRINGi9606.ENSP00000263574.

Protein family/group databases

MEROPSiI02.016.

PTM databases

iPTMnetiQ06481.
PhosphoSitePlusiQ06481.

Polymorphism and mutation databases

BioMutaiAPLP2.
DMDMi1703344.

Proteomic databases

EPDiQ06481.
MaxQBiQ06481.
PaxDbiQ06481.
PeptideAtlasiQ06481.
PRIDEiQ06481.
TopDownProteomicsiQ06481-5. [Q06481-5]

Protocols and materials databases

DNASUi334.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000263574; ENSP00000263574; ENSG00000084234. [Q06481-1]
ENST00000278756; ENSP00000278756; ENSG00000084234. [Q06481-6]
ENST00000338167; ENSP00000345444; ENSG00000084234. [Q06481-3]
ENST00000345598; ENSP00000263575; ENSG00000084234. [Q06481-5]
ENST00000528499; ENSP00000435914; ENSG00000084234. [Q06481-4]
GeneIDi334.
KEGGihsa:334.
UCSCiuc001qfp.4. human. [Q06481-1]

Organism-specific databases

CTDi334.
DisGeNETi334.
GeneCardsiAPLP2.
HGNCiHGNC:598. APLP2.
HPAiHPA039319.
MIMi104776. gene.
neXtProtiNX_Q06481.
OpenTargetsiENSG00000084234.
PharmGKBiPA24885.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG3540. Eukaryota.
ENOG410ZW2A. LUCA.
GeneTreeiENSGT00530000063252.
HOGENOMiHOG000232190.
HOVERGENiHBG000051.
InParanoidiQ06481.
KOiK08117.
OMAiTLYSYGM.
OrthoDBiEOG091G0UW4.
PhylomeDBiQ06481.
TreeFamiTF317274.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000084234-MONOMER.
ReactomeiR-HSA-114608. Platelet degranulation.
SignaLinkiQ06481.
SIGNORiQ06481.

Miscellaneous databases

ChiTaRSiAPLP2. human.
GeneWikiiAPLP2.
GenomeRNAii334.
PMAP-CutDBQ06481.
PROiQ06481.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000084234.
CleanExiHS_APLP2.
HS_APPL2.
ExpressionAtlasiQ06481. baseline and differential.
GenevisibleiQ06481. HS.

Family and domain databases

Gene3Di3.30.1490.140. 1 hit.
3.90.570.10. 1 hit.
4.10.410.10. 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.
IPR002223. Kunitz_BPTI.
IPR020901. Prtase_inh_Kunz-CS.
[Graphical view]
PfamiPF10515. APP_amyloid. 1 hit.
PF12924. APP_Cu_bd. 1 hit.
PF12925. APP_E2. 1 hit.
PF02177. APP_N. 1 hit.
PF00014. Kunitz_BPTI. 1 hit.
[Graphical view]
PRINTSiPR00203. AMYLOIDA4.
PR00759. BASICPTASE.
SMARTiSM00006. A4_EXTRA. 1 hit.
SM00131. KU. 1 hit.
[Graphical view]
SUPFAMiSSF109843. SSF109843. 1 hit.
SSF56491. SSF56491. 1 hit.
SSF57362. SSF57362. 1 hit.
SSF89811. SSF89811. 1 hit.
PROSITEiPS00319. A4_EXTRA. 1 hit.
PS00320. A4_INTRA. 1 hit.
PS00280. BPTI_KUNITZ_1. 1 hit.
PS50279. BPTI_KUNITZ_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiAPLP2_HUMAN
AccessioniPrimary (citable) accession number: Q06481
Secondary accession number(s): B3KXX9
, H7BXI4, Q13861, Q14594, Q14662, Q71U10, Q7M4L3, Q9BT36
Entry historyi
Integrated into UniProtKB/Swiss-Prot: June 1, 1994
Last sequence update: October 1, 1996
Last modified: November 2, 2016
This is version 175 of the entry and version 2 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

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 11
    Human chromosome 11: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. 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.