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Protein

Lysosome-associated membrane glycoprotein 2

Gene

Lamp2

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Plays an important role in chaperone-mediated autophagy, a process that mediates lysosomal degradation of proteins in response to various stresses and as part of the normal turnover of proteins with a long biological half-live (PubMed:10972293). Functions by binding target proteins, such as GAPDH and MLLT11, and targeting them for lysosomal degradation (By similarity). Required for the fusion of autophagosomes with lysosomes during autophagy (PubMed:27628032). Cells that lack LAMP2 express normal levels of VAMP8, but fail to accumulate STX17 on autophagosomes, which is the most likely explanation for the lack of fusion between autophagosomes and lysosomes (PubMed:27628032). Required for normal degradation of the contents of autophagosomes (PubMed:10972293, PubMed:12221139). Plays a role in lysosomal protein degradation in response to starvation (PubMed:27628032). Required for efficient MHCII-mediated presentation of exogenous antigens via its function in lysosomal protein degradation; antigenic peptides generated by proteases in the endosomal/lysosomal compartment are captured by nascent MHCII subunits. Is not required for efficient MHCII-mediated presentation of endogenous antigens (By similarity).By similarity3 Publications

GO - Molecular functioni

  • enzyme binding Source: MGI
  • protein domain specific binding Source: UniProtKB

GO - Biological processi

  • autophagosome maturation Source: UniProtKB
  • autophagy Source: UniProtKB
  • cellular response to starvation Source: UniProtKB
  • chaperone-mediated autophagy Source: UniProtKB
  • lysosomal protein catabolic process Source: UniProtKB
  • muscle cell cellular homeostasis Source: MGI
  • negative regulation of protein homooligomerization Source: MGI
  • protein stabilization Source: UniProtKB
  • protein targeting Source: UniProtKB
  • protein targeting to lysosome involved in chaperone-mediated autophagy Source: UniProtKB
  • regulation of protein stability Source: MGI

Keywordsi

Biological processAutophagy

Enzyme and pathway databases

ReactomeiR-MMU-114608 Platelet degranulation
R-MMU-6798695 Neutrophil degranulation

Names & Taxonomyi

Protein namesi
Recommended name:
Lysosome-associated membrane glycoprotein 2
Short name:
LAMP-2
Short name:
Lysosome-associated membrane protein 2
Alternative name(s):
CD107 antigen-like family member B
Lysosomal membrane glycoprotein type B
Short name:
LGP-B
CD_antigen: CD107b
Gene namesi
Name:Lamp2
Synonyms:Lamp-2
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome X

Organism-specific databases

MGIiMGI:96748 Lamp2

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 domaini26 – 379LumenalSequence analysisAdd BLAST354
Transmembranei380 – 404HelicalPROSITE-ProRule annotationAdd BLAST25
Topological domaini405 – 415CytoplasmicPROSITE-ProRule annotationAdd BLAST11

Keywords - Cellular componenti

Cell membrane, Cytoplasmic vesicle, Endosome, Lysosome, Membrane

Pathology & Biotechi

Disruption phenotypei

About half of the mutant mice die between 20 and 40 days after birth. Survivors are smaller, weigh 10 to 15 % less than their littermates, but show normal lifespan. Both mice that die early and long-time survivors display an accumulation of autophagic vacuoles in liver, pancreas, cardiac and skeletal muscle. Mutant mice display an increased ratio of heart weight to body weight and severely impaired contractile function of the heart muscle. Hepatocytes from mutant mice show a decreased rate of degradation of long-lived proteins.1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 25Add BLAST25
ChainiPRO_000001711126 – 415Lysosome-associated membrane glycoprotein 2Add BLAST390

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi29N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi37 ↔ 75PROSITE-ProRule annotation
Glycosylationi45N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi54N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi57N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi97N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi115N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi149 ↔ 185PROSITE-ProRule annotation
Glycosylationi175N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi227N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi234N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi237 ↔ 270PROSITE-ProRule annotation
Glycosylationi247N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi265N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi280N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi312N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi317N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi322N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi336 ↔ 373PROSITE-ProRule annotation
Glycosylationi361N-linked (GlcNAc...) asparagineSequence analysis1

Post-translational modificationi

Extensively N-glycosylated. Contains a minor proportion of O-linked glycans.1 Publication

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

MaxQBiP17047
PaxDbiP17047
PeptideAtlasiP17047
PRIDEiP17047

PTM databases

iPTMnetiP17047
PhosphoSitePlusiP17047
SwissPalmiP17047

Expressioni

Tissue specificityi

Detected in liver and kidney (at protein level). Detected in liver and kidney.1 Publication

Gene expression databases

BgeeiENSMUSG00000016534
CleanExiMM_LAMP2
ExpressionAtlasiP17047 baseline and differential
GenevisibleiP17047 MM

Interactioni

Subunit structurei

Monomer. Forms large homooligomers. Interacts (via its cytoplasmic region) with HSPA8. Interacts with HSP90 in the lysosome lumen; this enhances LAMP2 stability (By similarity). Interacts with MLLT11 (By similarity).By similarity

GO - Molecular functioni

  • enzyme binding Source: MGI
  • protein domain specific binding Source: UniProtKB

Protein-protein interaction databases

BioGridi201106, 3 interactors
IntActiP17047, 7 interactors
MINTiP17047
STRINGi10090.ENSMUSP00000016678

Structurei

Secondary structure

1415
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi26 – 32Combined sources7
Beta strandi35 – 52Combined sources18
Turni53 – 55Combined sources3
Beta strandi56 – 63Combined sources8
Beta strandi83 – 88Combined sources6
Turni89 – 91Combined sources3
Beta strandi92 – 100Combined sources9
Beta strandi102 – 115Combined sources14
Turni119 – 121Combined sources3
Beta strandi125 – 127Combined sources3
Beta strandi129 – 134Combined sources6
Beta strandi139 – 141Combined sources3
Beta strandi145 – 149Combined sources5
Beta strandi153 – 157Combined sources5
Beta strandi160 – 172Combined sources13
Beta strandi182 – 184Combined sources3
Helixi186 – 188Combined sources3

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
5GV3X-ray2.10A/B26-189[»]
ProteinModelPortaliP17047
SMRiP17047
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni26 – 188First lumenal domainAdd BLAST163
Regioni189 – 233HingeAdd BLAST45
Regioni234 – 379Second lumenal domainAdd BLAST146
Regioni406 – 409Important for binding and subsequent lysosomal degradation of target proteinsBy similarity4

Sequence similaritiesi

Belongs to the LAMP family.PROSITE-ProRule annotation

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG4818 Eukaryota
ENOG410XQ96 LUCA
GeneTreeiENSGT00530000063068
HOGENOMiHOG000230942
HOVERGENiHBG052303
InParanoidiP17047
KOiK06528
OMAiPIIHTTV
TreeFamiTF316339

Family and domain databases

InterProiView protein in InterPro
IPR018134 LAMP_CS
IPR002000 Lysosome-assoc_membr_glycop
PANTHERiPTHR11506 PTHR11506, 1 hit
PfamiView protein in Pfam
PF01299 Lamp, 1 hit
PRINTSiPR00336 LYSASSOCTDMP
PROSITEiView protein in PROSITE
PS00310 LAMP_1, 1 hit
PS00311 LAMP_2, 1 hit
PS51407 LAMP_3, 1 hit

Sequences (3)i

Sequence statusi: Complete.

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

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform LAMP-2A (identifier: P17047-1) [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
MCLSPVKGAK LILIFLFLGA VQSNALIVNL TDSKGTCLYA EWEMNFTITY
60 70 80 90 100
ETTNQTNKTI TIAVPDKATH DGSSCGDDRN SAKIMIQFGF AVSWAVNFTK
110 120 130 140 150
EASHYSIHDI VLSYNTSDST VFPGAVAKGV HTVKNPENFK VPLDVIFKCN
160 170 180 190 200
SVLTYNLTPV VQKYWGIHLQ AFVQNGTVSK NEQVCEEDQT PTTVAPIIHT
210 220 230 240 250
TAPSTTTTLT PTSTPTPTPT PTPTVGNYSI RNGNTTCLLA TMGLQLNITE
260 270 280 290 300
EKVPFIFNIN PATTNFTGSC QPQSAQLRLN NSQIKYLDFI FAVKNEKRFY
310 320 330 340 350
LKEVNVYMYL ANGSAFNISN KNLSFWDAPL GSSYMCNKEQ VLSVSRAFQI
360 370 380 390 400
NTFNLKVQPF NVTKGQYSTA QDCSADEDNF LVPIAVGAAL GGVLILVLLA
410
YFIGLKRHHT GYEQF
Length:415
Mass (Da):45,681
Last modified:May 31, 2011 - v2
Checksum:i053A874B4DF67C88
GO
Isoform LAMP-2B (identifier: P17047-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     371-415: QDCSADEDNF...KRHHTGYEQF → EECAADSDLN...RKSRTGYQSV

Show »
Length:416
Mass (Da):45,797
Checksum:iF6FE0E2F2B5689E2
GO
Isoform LAMP-2C (identifier: P17047-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     372-415: DCSADEDNFL...KRHHTGYEQF → ECSLDDDTIL...RKTYAGYQTL

Show »
Length:415
Mass (Da):45,655
Checksum:iFF0021CBFDEED589
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti272P → H in BAE34951 (PubMed:16141072).Curated1
Sequence conflicti289F → L in AAA39412 (PubMed:2318880).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_003045371 – 415QDCSA…GYEQF → EECAADSDLNFLIPVAVGVA LGFLIIAVFISYMIGRRKSR TGYQSV in isoform LAMP-2B. 2 PublicationsAdd BLAST45
Alternative sequenceiVSP_003046372 – 415DCSAD…GYEQF → ECSLDDDTILIPIIVGAGLS GLIIVIVIAYLIGRRKTYAG YQTL in isoform LAMP-2C. CuratedAdd BLAST44

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
J05287 mRNA Translation: AAA39412.1
AK159272 mRNA Translation: BAE34951.1
AK032974 mRNA Translation: BAC28106.1
AK163933 mRNA Translation: BAE37543.1
AL513356 Genomic DNA Translation: CAM17143.1
AL513356 Genomic DNA Translation: CAM17144.1
CH466570 Genomic DNA Translation: EDL29016.1
CH466570 Genomic DNA Translation: EDL29018.1
BC138718 mRNA Translation: AAI38719.1
BC138723 mRNA Translation: AAI38724.1
M32017 mRNA Translation: AAA39429.1
M32018 Genomic DNA Translation: AAA39430.1
CCDSiCCDS30092.1 [P17047-1]
CCDS30093.1 [P17047-3]
CCDS72369.1 [P17047-2]
PIRiA35560
RefSeqiNP_001017959.1, NM_001017959.2 [P17047-1]
NP_034815.2, NM_010685.4 [P17047-3]
UniGeneiMm.414016
Mm.486

Genome annotation databases

EnsembliENSMUST00000016678; ENSMUSP00000016678; ENSMUSG00000016534 [P17047-1]
ENSMUST00000061755; ENSMUSP00000052283; ENSMUSG00000016534 [P17047-3]
ENSMUST00000074913; ENSMUSP00000074448; ENSMUSG00000016534 [P17047-2]
GeneIDi16784
KEGGimmu:16784
UCSCiuc009szw.2 mouse [P17047-1]
uc009szx.2 mouse [P17047-3]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiLAMP2_MOUSE
AccessioniPrimary (citable) accession number: P17047
Secondary accession number(s): A2A430, Q3TXG5, Q8BSG8
Entry historyiIntegrated into UniProtKB/Swiss-Prot: August 1, 1990
Last sequence update: May 31, 2011
Last modified: March 28, 2018
This is version 150 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health