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O00189

- AP4M1_HUMAN

UniProt

O00189 - AP4M1_HUMAN

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Protein

AP-4 complex subunit mu-1

Gene

AP4M1

Organism
Homo sapiens (Human)
Status
Reviewed - 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

  1. transporter activity Source: ProtInc

GO - Biological processi

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

Keywords - Biological processi

Protein transport, Transport

Enzyme and pathway databases

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
ProteomesiUP000005640: Chromosome 7

Organism-specific databases

HGNCiHGNC:574. AP4M1.

Subcellular locationi

Golgi apparatustrans-Golgi network. Membranecoated pit
Note: Associated with the trans-Golgi network. Found in soma and dendritic shafts of neuronal cells.

GO - Cellular componenti

  1. AP-type membrane coat adaptor complex Source: ProtInc
  2. clathrin adaptor complex Source: InterPro
  3. coated pit Source: UniProtKB-KW
  4. extracellular vesicular exosome Source: UniProt
  5. Golgi trans cisterna Source: ProtInc
  6. trans-Golgi network Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Coated pit, Golgi apparatus, Membrane

Pathology & Biotechi

Involvement in diseasei

Cerebral palsy, spastic quadriplegic 3 (CPSQ3) [MIM:612936]: A non-progressive disorder of movement and/or posture resulting from defects in the developing central nervous system. 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.1 Publication
Note: The disease is caused by mutations affecting the gene represented in this entry.

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi255 – 2551F → A: Abolishes interaction with APP. 1 Publication
Mutagenesisi283 – 2831R → D: Strongly reduced interaction with APP. 1 Publication

Organism-specific databases

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

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 453453AP-4 complex subunit mu-1PRO_0000193787Add
BLAST

Proteomic databases

MaxQBiO00189.
PaxDbiO00189.
PRIDEiO00189.

PTM databases

PhosphoSiteiO00189.

Expressioni

Tissue specificityi

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

Gene expression databases

BgeeiO00189.
CleanExiHS_AP4M1.
ExpressionAtlasiO00189. baseline and differential.
GenevestigatoriO00189.

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.By similarity3 Publications

Protein-protein interaction databases

BioGridi114616. 7 interactions.
IntActiO00189. 4 interactions.
STRINGi9606.ENSP00000352603.

Structurei

Secondary structure

1
453
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi186 – 19914Combined sources
Beta strandi205 – 21814Combined sources
Beta strandi225 – 2306Combined sources
Beta strandi235 – 2373Combined sources
Turni240 – 2423Combined sources
Beta strandi246 – 25611Combined sources
Helixi264 – 2674Combined sources
Beta strandi269 – 2724Combined sources
Beta strandi276 – 28611Combined sources
Beta strandi295 – 30410Combined sources
Turni306 – 3083Combined sources
Beta strandi309 – 31911Combined sources
Beta strandi326 – 33510Combined sources
Beta strandi341 – 3499Combined sources
Beta strandi353 – 3575Combined sources
Beta strandi360 – 3656Combined sources
Beta strandi373 – 3819Combined sources
Beta strandi405 – 4128Combined sources
Beta strandi421 – 4277Combined sources
Beta strandi437 – 45115Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
3L81X-ray1.60A160-453[»]
4MDRX-ray1.85A160-453[»]
ProteinModelPortaliO00189.
SMRiO00189. Positions 1-453.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiO00189.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini184 – 452269MHDPROSITE-ProRule annotationAdd
BLAST

Sequence similaritiesi

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

Phylogenomic databases

eggNOGiNOG281769.
GeneTreeiENSGT00530000062779.
HOGENOMiHOG000173245.
HOVERGENiHBG102734.
InParanoidiO00189.
KOiK12402.
PhylomeDBiO00189.
TreeFamiTF329745.

Family and domain databases

InterProiIPR022775. AP_mu_sigma_su.
IPR001392. Clathrin_mu.
IPR008968. Clathrin_mu_C.
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)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti338 – 3381R → G in AAD43328. (PubMed:10436028)Curated
Sequence conflicti345 – 3451Q → R in CAA69667. (PubMed:9013859)Curated
Sequence conflicti345 – 3451Q → R in AAD25869. (PubMed:11139587)Curated
Sequence conflicti400 – 4001L → M in AAD43328. (PubMed:10436028)Curated
Sequence conflicti417 – 4171S → C in AAD43328. (PubMed:10436028)Curated

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.4. 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 .
CCDSi CCDS5685.1.
RefSeqi NP_004713.2. NM_004722.3.
UniGenei Hs.632317.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
Entry Method Resolution (Å) Chain Positions PDBsum
3L81 X-ray 1.60 A 160-453 [» ]
4MDR X-ray 1.85 A 160-453 [» ]
ProteinModelPortali O00189.
SMRi O00189. Positions 1-453.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 114616. 7 interactions.
IntActi O00189. 4 interactions.
STRINGi 9606.ENSP00000352603.

PTM databases

PhosphoSitei O00189.

Proteomic databases

MaxQBi O00189.
PaxDbi O00189.
PRIDEi O00189.

Protocols and materials databases

DNASUi 9179.
Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000359593 ; ENSP00000352603 ; ENSG00000221838 .
ENST00000421755 ; ENSP00000412185 ; ENSG00000221838 .
GeneIDi 9179.
KEGGi hsa:9179.
UCSCi uc003utb.4. human.

Organism-specific databases

CTDi 9179.
GeneCardsi GC07P099699.
HGNCi HGNC:574. AP4M1.
MIMi 602296. gene.
612936. phenotype.
neXtProti NX_O00189.
Orphaneti 280763. Severe intellectual disability and progressive spastic paraplegia.
PharmGKBi PA24866.
GenAtlasi Search...

Phylogenomic databases

eggNOGi NOG281769.
GeneTreei ENSGT00530000062779.
HOGENOMi HOG000173245.
HOVERGENi HBG102734.
InParanoidi O00189.
KOi K12402.
PhylomeDBi O00189.
TreeFami TF329745.

Enzyme and pathway databases

SignaLinki O00189.

Miscellaneous databases

ChiTaRSi AP4M1. human.
EvolutionaryTracei O00189.
GeneWikii AP4M1.
GenomeRNAii 9179.
NextBioi 34413.
PROi O00189.
SOURCEi Search...

Gene expression databases

Bgeei O00189.
CleanExi HS_AP4M1.
ExpressionAtlasi O00189. baseline and differential.
Genevestigatori O00189.

Family and domain databases

InterProi IPR022775. AP_mu_sigma_su.
IPR001392. Clathrin_mu.
IPR008968. Clathrin_mu_C.
IPR018240. Clathrin_mu_CS.
IPR011012. Longin-like_dom.
IPR028565. MHD.
[Graphical view ]
Pfami PF00928. Adap_comp_sub. 1 hit.
PF01217. Clat_adaptor_s. 1 hit.
[Graphical view ]
PIRSFi PIRSF005992. Clathrin_mu. 1 hit.
PRINTSi PR00314. CLATHRINADPT.
SUPFAMi SSF49447. SSF49447. 1 hit.
SSF64356. SSF64356. 1 hit.
PROSITEi PS00991. CLAT_ADAPTOR_M_2. 1 hit.
PS51072. MHD. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  1. "Identification of two new mu-adaptin-related proteins, mu-ARP1 and mu-ARP2."
    Wang X., Kilimann M.W.
    FEBS Lett. 402:57-61(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY.
    Tissue: Brain.
  2. "Characterization of a fourth adaptor-related protein complex."
    Hirst J., Bright N.A., Rous B., Robinson M.S.
    Mol. Biol. Cell 10:2787-2802(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], SUBUNIT, TISSUE SPECIFICITY.
    Tissue: Brain.
  3. "Signal-binding specificity of the mu4 subunit of the adaptor protein complex, AP-4."
    Aguilar R.C., Boehm M., Gorshkova I., Crouch R.J., Tomita K., Saito T., Ohno H., Bonifacino J.S.
    J. Biol. Chem. 276:13145-13152(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBUNIT, INTERACTION WITH LAMP2, SUBCELLULAR LOCATION.
    Tissue: Spleen.
  4. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  5. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Tissue: Brain.
  6. Cited for: INVOLVEMENT IN CPSQ3.
  7. "Sorting of the Alzheimer's disease amyloid precursor protein mediated by the AP-4 complex."
    Burgos P.V., Mardones G.A., Rojas A.L., daSilva L.L., Prabhu Y., Hurley J.H., Bonifacino J.S.
    Dev. Cell 18:425-436(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (1.6 ANGSTROMS) OF 160-453 IN COMPLEX WITH APP PEPTIDE, FUNCTION, SUBCELLULAR LOCATION, MUTAGENESIS OF PHE-255 AND ARG-283, SUBUNIT.

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: October 29, 2014
This is version 126 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

External Data

Dasty 3