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Protein

AP-4 complex subunit mu-1

Gene

AP4M1

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

Functioni

Component of the AP-4 complex, a novel type of clathrin- or non-clathrin-associated protein coat involved in targeting proteins from the trans-Golgi network (TGN) to the endosomal-lysosomal system. Plays a role in the intracellular trafficking of APP from the trans-Golgi network (TGN) to endosomes, and thereby inhibits amyloidogenic processing of APP.2 Publications

GO - Molecular functioni

  • transporter activity Source: ProtInc

GO - Biological processi

  • Golgi to endosome transport Source: UniProtKB
  • intracellular protein transport Source: UniProtKB
  • vesicle-mediated transport Source: ProtInc
Complete GO annotation...

Keywords - Biological processi

Protein transport, Transport

Enzyme and pathway databases

BioCyciZFISH:G66-32960-MONOMER.
ReactomeiR-HSA-432720. Lysosome Vesicle Biogenesis.
SignaLinkiO00189.

Names & Taxonomyi

Protein namesi
Recommended name:
AP-4 complex subunit mu-1
Alternative name(s):
AP-4 adaptor complex mu subunit
Adaptor-related protein complex 4 subunit mu-1
Mu subunit of AP-4
Mu-adaptin-related protein 2
Short name:
mu-ARP2
Mu4-adaptin
Short name:
mu4
Gene namesi
Name:AP4M1
Synonyms:MUARP2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 7

Organism-specific databases

HGNCiHGNC:574. AP4M1.

Subcellular locationi

GO - Cellular componenti

  • AP-type membrane coat adaptor complex Source: ProtInc
  • clathrin adaptor complex Source: InterPro
  • cytosol Source: GOC
  • endosome lumen Source: Reactome
  • extracellular exosome Source: UniProtKB
  • Golgi trans cisterna Source: ProtInc
  • trans-Golgi network Source: UniProtKB
  • trans-Golgi network membrane Source: Reactome
Complete GO annotation...

Keywords - Cellular componenti

Endosome, Golgi apparatus

Pathology & Biotechi

Involvement in diseasei

Spastic paraplegia 50, autosomal recessive (SPG50)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA form of spastic paraplegia, a neurodegenerative disorder characterized by a slow, gradual, progressive weakness and spasticity of the lower limbs. Rate of progression and the severity of symptoms are quite variable. Initial symptoms may include difficulty with balance, weakness and stiffness in the legs, muscle spasms, and dragging the toes when walking. In some forms of the disorder, bladder symptoms (such as incontinence) may appear, or the weakness and stiffness may spread to other parts of the body. SPG50 affected individuals present postnatally with early infantile hypotonia, delayed psychomotor development, strabismus, lack of independent walking and severe mental retardation. They develop progressive spasticity of all limbs with generalized hypertonia, hyperreflexia, and extensor plantar responses by the end of the first year of life. Speech is absent or limited. Pseudobulbar signs, such as drooling, stereotypic laughter, and exaggerated jaw jerk, are part of the clinical picture.
See also OMIM:612936

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi255F → A: Abolishes interaction with APP. 1 Publication1
Mutagenesisi283R → D: Strongly reduced interaction with APP. 1 Publication1

Keywords - Diseasei

Hereditary spastic paraplegia, Neurodegeneration

Organism-specific databases

DisGeNETi9179.
MalaCardsiAP4M1.
MIMi612936. phenotype.
OpenTargetsiENSG00000221838.
Orphaneti280763. Severe intellectual disability and progressive spastic paraplegia.
PharmGKBiPA24866.

Polymorphism and mutation databases

BioMutaiAP4M1.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001937871 – 453AP-4 complex subunit mu-1Add BLAST453

Proteomic databases

EPDiO00189.
MaxQBiO00189.
PaxDbiO00189.
PeptideAtlasiO00189.
PRIDEiO00189.
TopDownProteomicsiO00189.

PTM databases

iPTMnetiO00189.
PhosphoSitePlusiO00189.

Expressioni

Tissue specificityi

Ubiquitous. Highly expressed in testis and lowly expressed in brain and lung.2 Publications

Gene expression databases

BgeeiENSG00000221838.
CleanExiHS_AP4M1.
ExpressionAtlasiO00189. baseline and differential.
GenevisibleiO00189. HS.

Interactioni

Subunit structurei

Adaptor protein complex 4 (AP-4) is a heterotetramer composed of two large adaptins (epsilon-type subunit AP4E1 and beta-type subunit AP4B1), a medium adaptin (mu-type subunit AP4M1) and a small adaptin (sigma-type AP4S1). Interacts with the C-terminal domain of GRID2 (By similarity). Interacts with tyrosine-based sorting signals on the cytoplasmic tail of cargo proteins, such as LAMP2 and APP. Interacts with NAGPA.By similarity4 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
USP47Q96K763EBI-3914106,EBI-2514143

Protein-protein interaction databases

BioGridi114616. 32 interactors.
IntActiO00189. 31 interactors.
STRINGi9606.ENSP00000352603.

Structurei

Secondary structure

1453
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi186 – 199Combined sources14
Beta strandi205 – 218Combined sources14
Beta strandi225 – 230Combined sources6
Beta strandi235 – 237Combined sources3
Turni240 – 242Combined sources3
Beta strandi246 – 256Combined sources11
Helixi264 – 267Combined sources4
Beta strandi269 – 272Combined sources4
Beta strandi276 – 286Combined sources11
Beta strandi295 – 304Combined sources10
Turni306 – 308Combined sources3
Beta strandi309 – 319Combined sources11
Beta strandi326 – 335Combined sources10
Beta strandi341 – 349Combined sources9
Beta strandi353 – 357Combined sources5
Beta strandi360 – 365Combined sources6
Beta strandi373 – 381Combined sources9
Beta strandi405 – 412Combined sources8
Beta strandi421 – 427Combined sources7
Beta strandi437 – 451Combined sources15

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3L81X-ray1.60A160-453[»]
4MDRX-ray1.85A160-453[»]
ProteinModelPortaliO00189.
SMRiO00189.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiO00189.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini184 – 452MHDPROSITE-ProRule annotationAdd BLAST269

Sequence similaritiesi

Contains 1 MHD (mu homology) domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiKOG0937. Eukaryota.
ENOG410XPFS. LUCA.
GeneTreeiENSGT00530000062779.
HOGENOMiHOG000173245.
HOVERGENiHBG102734.
InParanoidiO00189.
KOiK12402.
PhylomeDBiO00189.
TreeFamiTF329745.

Family and domain databases

InterProiIPR022775. AP_mu_sigma_su.
IPR001392. Clathrin_mu.
IPR018240. Clathrin_mu_CS.
IPR011012. Longin-like_dom.
IPR028565. MHD.
[Graphical view]
PfamiPF00928. Adap_comp_sub. 1 hit.
PF01217. Clat_adaptor_s. 1 hit.
[Graphical view]
PIRSFiPIRSF005992. Clathrin_mu. 1 hit.
PRINTSiPR00314. CLATHRINADPT.
SUPFAMiSSF49447. SSF49447. 1 hit.
SSF64356. SSF64356. 1 hit.
PROSITEiPS00991. CLAT_ADAPTOR_M_2. 1 hit.
PS51072. MHD. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

O00189-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MISQFFILSS KGDPLIYKDF RGDSGGRDVA ELFYRKLTGL PGDESPVVMH
60 70 80 90 100
HHGRHFIHIR HSGLYLVVTT SENVSPFSLL ELLSRLATLL GDYCGSLGEG
110 120 130 140 150
TISRNVALVY ELLDEVLDYG YVQTTSTEML RNFIQTEAVV SKPFSLFDLS
160 170 180 190 200
SVGLFGAETQ QSKVAPSSAA SRPVLSSRSD QSQKNEVFLD VVERLSVLIA
210 220 230 240 250
SNGSLLKVDV QGEIRLKSFL PSGSEMRIGL TEEFCVGKSE LRGYGPGIRV
260 270 280 290 300
DEVSFHSSVN LDEFESHRIL RLQPPQGELT VMRYQLSDDL PSPLPFRLFP
310 320 330 340 350
SVQWDRGSGR LQVYLKLRCD LLSKSQALNV RLHLPLPRGV VSLSQELSSP
360 370 380 390 400
EQKAELAEGA LRWDLPRVQG GSQLSGLFQM DVPGPPGPPS HGLSTSASPL
410 420 430 440 450
GLGPASLSFE LPRHTCSGLQ VRFLRLAFRP CGNANPHKWV RHLSHSDAYV

IRI
Length:453
Mass (Da):49,977
Last modified:April 17, 2007 - v2
Checksum:iAE3DCA8C5AED08B7
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti338R → G in AAD43328 (PubMed:10436028).Curated1
Sequence conflicti345Q → R in CAA69667 (PubMed:9013859).Curated1
Sequence conflicti345Q → R in AAD25869 (PubMed:11139587).Curated1
Sequence conflicti400L → M in AAD43328 (PubMed:10436028).Curated1
Sequence conflicti417S → C in AAD43328 (PubMed:10436028).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
Y08387 mRNA. Translation: CAA69667.1.
AF155158 mRNA. Translation: AAD43328.1.
AF020796 mRNA. Translation: AAD25869.1.
CH471091 Genomic DNA. Translation: EAW76594.1.
CH471091 Genomic DNA. Translation: EAW76597.1.
BC018705 mRNA. Translation: AAH18705.1.
CCDSiCCDS5685.1.
RefSeqiNP_004713.2. NM_004722.3.
UniGeneiHs.632317.

Genome annotation databases

EnsembliENST00000359593; ENSP00000352603; ENSG00000221838.
ENST00000421755; ENSP00000412185; ENSG00000221838.
GeneIDi9179.
KEGGihsa:9179.
UCSCiuc003utb.5. human.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
Y08387 mRNA. Translation: CAA69667.1.
AF155158 mRNA. Translation: AAD43328.1.
AF020796 mRNA. Translation: AAD25869.1.
CH471091 Genomic DNA. Translation: EAW76594.1.
CH471091 Genomic DNA. Translation: EAW76597.1.
BC018705 mRNA. Translation: AAH18705.1.
CCDSiCCDS5685.1.
RefSeqiNP_004713.2. NM_004722.3.
UniGeneiHs.632317.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3L81X-ray1.60A160-453[»]
4MDRX-ray1.85A160-453[»]
ProteinModelPortaliO00189.
SMRiO00189.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi114616. 32 interactors.
IntActiO00189. 31 interactors.
STRINGi9606.ENSP00000352603.

PTM databases

iPTMnetiO00189.
PhosphoSitePlusiO00189.

Polymorphism and mutation databases

BioMutaiAP4M1.

Proteomic databases

EPDiO00189.
MaxQBiO00189.
PaxDbiO00189.
PeptideAtlasiO00189.
PRIDEiO00189.
TopDownProteomicsiO00189.

Protocols and materials databases

DNASUi9179.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000359593; ENSP00000352603; ENSG00000221838.
ENST00000421755; ENSP00000412185; ENSG00000221838.
GeneIDi9179.
KEGGihsa:9179.
UCSCiuc003utb.5. human.

Organism-specific databases

CTDi9179.
DisGeNETi9179.
GeneCardsiAP4M1.
HGNCiHGNC:574. AP4M1.
MalaCardsiAP4M1.
MIMi602296. gene.
612936. phenotype.
neXtProtiNX_O00189.
OpenTargetsiENSG00000221838.
Orphaneti280763. Severe intellectual disability and progressive spastic paraplegia.
PharmGKBiPA24866.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0937. Eukaryota.
ENOG410XPFS. LUCA.
GeneTreeiENSGT00530000062779.
HOGENOMiHOG000173245.
HOVERGENiHBG102734.
InParanoidiO00189.
KOiK12402.
PhylomeDBiO00189.
TreeFamiTF329745.

Enzyme and pathway databases

BioCyciZFISH:G66-32960-MONOMER.
ReactomeiR-HSA-432720. Lysosome Vesicle Biogenesis.
SignaLinkiO00189.

Miscellaneous databases

ChiTaRSiAP4M1. human.
EvolutionaryTraceiO00189.
GeneWikiiAP4M1.
GenomeRNAii9179.
PROiO00189.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000221838.
CleanExiHS_AP4M1.
ExpressionAtlasiO00189. baseline and differential.
GenevisibleiO00189. HS.

Family and domain databases

InterProiIPR022775. AP_mu_sigma_su.
IPR001392. Clathrin_mu.
IPR018240. Clathrin_mu_CS.
IPR011012. Longin-like_dom.
IPR028565. MHD.
[Graphical view]
PfamiPF00928. Adap_comp_sub. 1 hit.
PF01217. Clat_adaptor_s. 1 hit.
[Graphical view]
PIRSFiPIRSF005992. Clathrin_mu. 1 hit.
PRINTSiPR00314. CLATHRINADPT.
SUPFAMiSSF49447. SSF49447. 1 hit.
SSF64356. SSF64356. 1 hit.
PROSITEiPS00991. CLAT_ADAPTOR_M_2. 1 hit.
PS51072. MHD. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiAP4M1_HUMAN
AccessioniPrimary (citable) accession number: O00189
Secondary accession number(s): D6W5U1, Q8WV65, Q9UHK9
Entry historyi
Integrated into UniProtKB/Swiss-Prot: April 27, 2001
Last sequence update: April 17, 2007
Last modified: November 30, 2016
This is version 146 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

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 7
    Human chromosome 7: 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.