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UniProtKB - O00189 (AP4M1_HUMAN)

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Protein

AP-4 complex subunit mu-1

Gene

AP4M1

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

Functioni

Component of the adaptor protein complex 4 (AP-4). Adaptor protein complexes are vesicle coat components involved both in vesicle formation and cargo selection. They control the vesicular transport of proteins in different trafficking pathways (PubMed:10436028, PubMed:11139587, PubMed:10066790, PubMed:11802162, PubMed:20230749). AP-4 forms a non clathrin-associated coat on vesicles departing the trans-Golgi network (TGN) and may be involved in the targeting of proteins from the trans-Golgi network (TGN) to the endosomal-lysosomal system (PubMed:11139587, PubMed:20230749). It is also involved in protein sorting to the basolateral membrane in epithelial cells and the proper asymmetric localization of somatodendritic proteins in neurons (By similarity). Within AP-4, the mu-type subunit AP4M1 is directly involved in the recognition and binding of tyrosine-based sorting signals found in the cytoplasmic part of cargos (PubMed:10436028, PubMed:11139587, PubMed:26544806, PubMed:20230749). The adaptor protein complex 4 (AP-4) may also recognize other types of sorting signal (By similarity).By similarity6 Publications

GO - Molecular functioni

  • protein domain specific binding Source: UniProtKB
View the complete GO annotation on QuickGO ...

GO - Biological processi

  • Golgi to endosome transport Source: UniProtKB
  • Golgi to lysosome transport Source: UniProtKB
  • intracellular protein transport Source: UniProtKB
  • protein localization Source: UniProtKB
  • protein localization to basolateral plasma membrane Source: UniProtKB
  • protein targeting Source: UniProtKB
  • protein targeting to lysosome Source: UniProtKB
View the complete GO annotation on QuickGO ...

Keywordsi

Biological processProtein transport, Transport

Enzyme and pathway databases

ReactomeiR-HSA-432720 Lysosome Vesicle Biogenesis
SignaLinkiO00189

Names & Taxonomyi

Protein namesi
Recommended name:
AP-4 complex subunit mu-1Curated
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:AP4M1Imported
Synonyms:MUARP2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo
Proteomesi
  • UP000005640 Componenti: Chromosome 7

Organism-specific databases

EuPathDBiHostDB:ENSG00000221838.9
HGNCiHGNC:574 AP4M1
MIMi602296 gene
neXtProtiNX_O00189

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

Keywords - Cellular componenti

Endosome, Golgi apparatus, Membrane

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
ProteomicsDBi47769
TopDownProteomicsiO00189

PTM databases

iPTMnetiO00189
PhosphoSitePlusiO00189

Expressioni

Tissue specificityi

Ubiquitous. Highly expressed in testis and lowly expressed in brain and lung.1 Publication

Gene expression databases

BgeeiENSG00000221838
CleanExiHS_AP4M1
ExpressionAtlasiO00189 baseline and differential
GenevisibleiO00189 HS

Organism-specific databases

HPAiHPA066774

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) (PubMed:10436028, PubMed:10066790, PubMed:11802162). Interacts with tyrosine-based sorting signals on the cytoplasmic tail of cargo proteins such as APP, LAMP2 and NAGPA (PubMed:11139587, PubMed:26544806, PubMed:20230749). Interacts with the C-terminal domain of GRID2 (By similarity). Interacts with GRIA1 and GRIA2; the interaction is indirect via CACNG3 (By similarity). Interacts with CACNG3; CACNG3 associates GRIA1 and GRIA2 with the adaptor protein complex 4 (AP-4) to target them to the somatodendritic compartment of neurons (By similarity).By similarity6 Publications

Binary interactionsi

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

GO - Molecular functioni

  • protein domain specific binding Source: UniProtKB
View the complete GO annotation on QuickGO ...

Protein-protein interaction databases

BioGridi114616, 34 interactors
CORUMiO00189
IntActiO00189, 31 interactors
MINTiO00189
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

Belongs to the adaptor complexes medium subunit family.Curated

Phylogenomic databases

eggNOGiKOG0937 Eukaryota
ENOG410XPFS LUCA
GeneTreeiENSGT00530000062779
HOGENOMiHOG000173245
HOVERGENiHBG102734
InParanoidiO00189
KOiK12402
PhylomeDBiO00189
TreeFamiTF329745

Family and domain databases

InterProiView protein in InterPro
IPR036168 AP2_Mu_C_sf
IPR022775 AP_mu_sigma_su
IPR001392 Clathrin_mu
IPR018240 Clathrin_mu_CS
IPR011012 Longin-like_dom_sf
IPR028565 MHD
PfamiView protein in Pfam
PF00928 Adap_comp_sub, 1 hit
PF01217 Clat_adaptor_s, 1 hit
PIRSFiPIRSF005992 Clathrin_mu, 1 hit
PRINTSiPR00314 CLATHRINADPT
SUPFAMiSSF49447 SSF49447, 1 hit
SSF64356 SSF64356, 1 hit
PROSITEiView protein in PROSITE
PS00991 CLAT_ADAPTOR_M_2, 1 hit
PS51072 MHD, 1 hit

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

Similar proteinsi

Entry informationi

Entry nameiAP4M1_HUMAN
AccessioniPrimary (citable) accession number: O00189
Secondary accession number(s): D6W5U1, Q8WV65, Q9UHK9
Entry historyiIntegrated into UniProtKB/Swiss-Prot: April 27, 2001
Last sequence update: April 17, 2007
Last modified: June 20, 2018
This is version 154 of the entry and version 2 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. 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

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