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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

GO - Biological processi

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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
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 Expressed in 136 organ(s), highest expression level in right testis
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-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

3D structure databases

ProteinModelPortaliO00189
SMRiO00189
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiO00189

Family & Domainsi

Domains and Repeats

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

Sequence similaritiesi

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

Sequence (1+)i

Sequence statusi: Complete.

This entry has 1 described isoform and 10 potential isoforms that are computationally mapped.Show allAlign All

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

Computationally mapped potential isoform sequencesi

There are 10 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
C9JC87C9JC87_HUMAN
AP-4 complex subunit mu-1
AP4M1
460Annotation score:
C9JWL4C9JWL4_HUMAN
AP-4 complex subunit mu-1
AP4M1
311Annotation score:
C9IZL5C9IZL5_HUMAN
AP-4 complex subunit mu-1
AP4M1
325Annotation score:
C9JMG3C9JMG3_HUMAN
AP-4 complex subunit mu-1
AP4M1
265Annotation score:
H7BZV3H7BZV3_HUMAN
AP-4 complex subunit mu-1
AP4M1
160Annotation score:
F8WCR6F8WCR6_HUMAN
AP-4 complex subunit mu-1
AP4M1
218Annotation score:
H0Y6K1H0Y6K1_HUMAN
AP-4 complex subunit mu-1
AP4M1
193Annotation score:
H7C0A0H7C0A0_HUMAN
AP-4 complex subunit mu-1
AP4M1
138Annotation score:
F8WCC5F8WCC5_HUMAN
AP-4 complex subunit mu-1
AP4M1
97Annotation score:
F8WDR3F8WDR3_HUMAN
AP-4 complex subunit mu-1
AP4M1
64Annotation score:

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

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, 34 interactors
CORUMiO00189
IntActiO00189, 31 interactors
MINTiO00189
STRINGi9606.ENSP00000352603

PTM databases

iPTMnetiO00189
PhosphoSitePlusiO00189

Polymorphism and mutation databases

BioMutaiAP4M1

Proteomic databases

EPDiO00189
MaxQBiO00189
PaxDbiO00189
PeptideAtlasiO00189
PRIDEiO00189
ProteomicsDBi47769
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
EuPathDBiHostDB:ENSG00000221838.9
GeneCardsiAP4M1
HGNCiHGNC:574 AP4M1
HPAiHPA066774
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

ReactomeiR-HSA-432720 Lysosome Vesicle Biogenesis
SignaLinkiO00189

Miscellaneous databases

ChiTaRSiAP4M1 human
EvolutionaryTraceiO00189
GeneWikiiAP4M1
GenomeRNAii9179
PROiPR:O00189
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000221838 Expressed in 136 organ(s), highest expression level in right testis
CleanExiHS_AP4M1
ExpressionAtlasiO00189 baseline and differential
GenevisibleiO00189 HS

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
ProtoNetiSearch...

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: September 12, 2018
This is version 155 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. 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. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  4. Human chromosome 7
    Human chromosome 7: entries, gene names and cross-references to MIM
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