Skip Header

You are using a version of Internet Explorer that may not display all features of this website. Please upgrade to a modern browser.
Contribute Send feedback
Read comments (?) or add your own

O00189 (AP4M1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 120. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (4) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
AP-4 complex subunit mu-1
Alternative name(s):
AP-4 adapter complex mu subunit
Adapter-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 names
Name:AP4M1
Synonyms:MUARP2
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length453 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.3 Ref.7

Subunit structure

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. Ref.2 Ref.3 Ref.7

Subcellular location

Golgi apparatustrans-Golgi network. Membranecoated pit. Note: Associated with the trans-Golgi network. Found in soma and dendritic shafts of neuronal cells. Ref.3 Ref.7

Tissue specificity

Ubiquitous. Highly expressed in testis and lowly expressed in brain and lung. Ref.1 Ref.2

Involvement in disease

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.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.6

Sequence similarities

Belongs to the adaptor complexes medium subunit family.

Contains 1 MHD (mu homology) domain.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 453453AP-4 complex subunit mu-1
PRO_0000193787

Regions

Domain184 – 452269MHD

Experimental info

Mutagenesis2551F → A: Abolishes interaction with APP. Ref.7
Mutagenesis2831R → D: Strongly reduced interaction with APP. Ref.7
Sequence conflict3381R → G in AAD43328. Ref.2
Sequence conflict3451Q → R in CAA69667. Ref.1
Sequence conflict3451Q → R in AAD25869. Ref.3
Sequence conflict4001L → M in AAD43328. Ref.2
Sequence conflict4171S → C in AAD43328. Ref.2

Secondary structure

........................................ 453
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
O00189 [UniParc].

Last modified April 17, 2007. Version 2.
Checksum: AE3DCA8C5AED08B7

FASTA45349,977
        10         20         30         40         50         60 
MISQFFILSS KGDPLIYKDF RGDSGGRDVA ELFYRKLTGL PGDESPVVMH HHGRHFIHIR 

        70         80         90        100        110        120 
HSGLYLVVTT SENVSPFSLL ELLSRLATLL GDYCGSLGEG TISRNVALVY ELLDEVLDYG 

       130        140        150        160        170        180 
YVQTTSTEML RNFIQTEAVV SKPFSLFDLS SVGLFGAETQ QSKVAPSSAA SRPVLSSRSD 

       190        200        210        220        230        240 
QSQKNEVFLD VVERLSVLIA SNGSLLKVDV QGEIRLKSFL PSGSEMRIGL TEEFCVGKSE 

       250        260        270        280        290        300 
LRGYGPGIRV DEVSFHSSVN LDEFESHRIL RLQPPQGELT VMRYQLSDDL PSPLPFRLFP 

       310        320        330        340        350        360 
SVQWDRGSGR LQVYLKLRCD LLSKSQALNV RLHLPLPRGV VSLSQELSSP EQKAELAEGA 

       370        380        390        400        410        420 
LRWDLPRVQG GSQLSGLFQM DVPGPPGPPS HGLSTSASPL GLGPASLSFE LPRHTCSGLQ 

       430        440        450 
VRFLRLAFRP CGNANPHKWV RHLSHSDAYV IRI 

« Hide

References

« Hide 'large scale' references
[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]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
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]"Mutation in the AP4M1 gene provides a model for neuroaxonal injury in cerebral palsy."
Verkerk A.J., Schot R., Dumee B., Schellekens K., Swagemakers S., Bertoli-Avella A.M., Lequin M.H., Dudink J., Govaert P., van Zwol A.L., Hirst J., Wessels M.W., Catsman-Berrevoets C., Verheijen F.W., de Graaff E., de Coo I.F., Kros J.M., Willemsen R. expand/collapse author list , Willems P.J., van der Spek P.J., Mancini G.M.
Am. J. Hum. Genet. 85:40-52(2009) [PubMed] [Europe PMC] [Abstract]
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.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
RefSeqNP_004713.2. NM_004722.3.
UniGeneHs.632317.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
3L81X-ray1.60A160-453[»]
ProteinModelPortalO00189.
SMRO00189. Positions 1-453.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid114616. 7 interactions.
IntActO00189. 3 interactions.
STRING9606.ENSP00000352603.

PTM databases

PhosphoSiteO00189.

Proteomic databases

PaxDbO00189.
PRIDEO00189.

Protocols and materials databases

DNASU9179.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000359593; ENSP00000352603; ENSG00000221838.
ENST00000421755; ENSP00000412185; ENSG00000221838.
GeneID9179.
KEGGhsa:9179.
UCSCuc003utb.4. human.

Organism-specific databases

CTD9179.
GeneCardsGC07P099699.
HGNCHGNC:574. AP4M1.
MIM602296. gene.
612936. phenotype.
neXtProtNX_O00189.
Orphanet280763. Severe intellectual deficit and progressive spastic paraplegia.
PharmGKBPA24866.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG281769.
HOGENOMHOG000173245.
HOVERGENHBG102734.
InParanoidO00189.
KOK12402.
PhylomeDBO00189.
TreeFamTF329745.

Enzyme and pathway databases

SignaLinkO00189.

Gene expression databases

ArrayExpressO00189.
BgeeO00189.
CleanExHS_AP4M1.
GenevestigatorO00189.

Family and domain databases

InterProIPR022775. AP_mu_sigma_su.
IPR001392. Clathrin_mu.
IPR008968. Clathrin_mu_C.
IPR018240. Clathrin_mu_CS.
IPR011012. Longin-like_dom.
IPR028565. MHD.
[Graphical view]
PfamPF00928. Adap_comp_sub. 1 hit.
PF01217. Clat_adaptor_s. 1 hit.
[Graphical view]
PIRSFPIRSF005992. Clathrin_mu. 1 hit.
PRINTSPR00314. CLATHRINADPT.
SUPFAMSSF49447. SSF49447. 1 hit.
SSF64356. SSF64356. 1 hit.
PROSITEPS00991. CLAT_ADAPTOR_M_2. 1 hit.
PS51072. MHD. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSAP4M1. human.
EvolutionaryTraceO00189.
GeneWikiAP4M1.
GenomeRNAi9179.
NextBio34413.
PROO00189.
SOURCESearch...

Entry information

Entry nameAP4M1_HUMAN
AccessionPrimary (citable) accession number: O00189
Secondary accession number(s): D6W5U1, Q8WV65, Q9UHK9
Entry history
Integrated into UniProtKB/Swiss-Prot: April 27, 2001
Last sequence update: April 17, 2007
Last modified: April 16, 2014
This is version 120 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human chromosome 7

Human chromosome 7: entries, gene names and cross-references to MIM