Q9UPM8 (AP4E1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
AP-4 complex subunit epsilon-1

Alternative name(s):
AP-4 adapter complex subunit epsilon
Adapter-related protein complex 4 subunit epsilon-1
Epsilon subunit of AP-4
Epsilon-adaptin

Gene names

Name:

AP4E1

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	1137 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Subunit of 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.
Subunit structure	Adapter-like 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).
Subcellular location	Golgi apparatus › trans-Golgi network. Note: Associated with the trans-Golgi network. Found in soma and dendritic shafts of neuronal cells.
Tissue specificity	Widely expressed.
Involvement in disease	Cerebral palsy, spastic quadriplegic 4 (CPSQ4) [MIM:613744]: A non-progressive disorder of movement and/or posture resulting from defects in the developing central nervous system. Affected individuals manifest motor and posture impairments often associated with epilepsy and disturbances of cognition, behavior, sensation, and communication. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.9
Sequence similarities	Belongs to the adaptor complexes large subunit family.

Ontologies

Keywords
Biological process	Protein transport Transport
Cellular component	Golgi apparatus
Coding sequence diversity	Alternative splicing Polymorphism
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	intracellular protein transport Inferred from electronic annotation. Source: InterPro vesicle-mediated transport Inferred from electronic annotation. Source: InterPro
Cellular_component	COPI vesicle coat Inferred from electronic annotation. Source: InterPro
Molecular_function	structural molecule activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q9UPM8-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: Q9UPM8-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-75: Missing.

Note: No experimental confirmation available.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 1137	1137	AP-4 complex subunit epsilon-1		PRO_0000193769
Amino acid modifications
	Modified residue	857	1	Phosphoserine Ref.8
Natural variations
	Alternative sequence	1 – 75	75	Missing in isoform 2.		VSP_046009
	Natural variant	163	1	C → R. Ref.3 Ref.4 Ref.7 Corresponds to variant rs2306331 [ dbSNP | Ensembl ].		VAR_031621
Experimental info
	Sequence conflict	30	1	A → G in AAD43326. Ref.1
	Sequence conflict	46	1	L → F in AAD43326. Ref.1
	Sequence conflict	214	1	L → P in AAD43326. Ref.1
	Sequence conflict	262 – 265	4	EFNY → NF in AAD43326. Ref.1
	Sequence conflict	678	1	A → V in CAH18399. Ref.4
	Sequence conflict	794	1	R → G in CAH18399. Ref.4
	Sequence conflict	991	1	S → G in CAH18399. Ref.4

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified April 17, 2007. Version 2. Checksum: 1784E886EC922875	FASTA	1,137	127,287
	10 20 30 40 50 60 MSDIVEKTLT ALPGLFLQNQ PGGGPAAAKA SFSSRLGSLV RGITALTSKH EEEKLIQQEL 70 80 90 100 110 120 SSLKATVSAP TTTLKMMKEC MVRLIYCEML GYDASFGYIH AIKLAQQGNL LEKRVGYLAV 130 140 150 160 170 180 SLFLHESHEL LLLLVNTVVK DLQSTNLVEV CMALTVVSQI FPCEMIPAVL PLIEDKLQHS 190 200 210 220 230 240 KEIVRRKAVL ALYKFHLIAP NQVQHIHIKF RKALCDRDVG VMAASLHIYL RMIKENSSGY 250 260 270 280 290 300 KDLTGSFVTI LKQVVGGKLP VEFNYHSVPA PWLQIQLLRI LGLLGKDDQR TSELMYDVLD 310 320 330 340 350 360 ESLRRAELNH NVTYAILFEC VHTVYSIYPK SELLEKAAKC IGKFVLSPKI NLKYLGLKAL 370 380 390 400 410 420 TYVIQQDPTL ALQHQMTIIE CLDHPDPIIK RETLELLYRI TNAQNITVIV QKMLEYLHQS 430 440 450 460 470 480 KEEYVIVNLV GKIAELAEKY APDNAWFIQT MNAVFSVGGD VMHPDIPNNF LRLLAEGFDD 490 500 510 520 530 540 ETEDQQLRLY AVQSYLTLLD MENVFYPQRF LQVMSWVLGE YSYLLDKETP EEVIAKLYKL 550 560 570 580 590 600 LMNDSVSSET KAWLIAAVTK LTSQAHSSNT VERLIHEFTI SLDTCMRQHA FELKHLHENV 610 620 630 640 650 660 ELMKSLLPVD RSCEDLVVDA SLSFLDGFVA EGLSQGAAPY KPPHQRQEEK LSQEKVLNFE 670 680 690 700 710 720 PYGLSFSSSG FTGRQSPAGI SLGSDVSGNS AETGLKETNS LKLEGIKKLW GKEGYLPKKE 730 740 750 760 770 780 SKTGDESGAL PVPQESIMEN VDQAITKKDQ SQVLTQSKEE KEKQLLASSL FVGLGSESTI 790 800 810 820 830 840 NLLGKADTVS HKFRRKSKVK EAKSGETTST HNMTCSSFSS LSNVAYEDDY YSNTLHDTGD 850 860 870 880 890 900 KELKKFSLTS ELLDSESLTE LPLVEKFSYC SLSTPSLFAN NNMEIFHPPQ STAASVAKES 910 920 930 940 950 960 SLASSFLEET TEYIHSNAME VCNNETISVS SYKIWKDDCL LMVWSVTNKS GLELKSADLE 970 980 990 1000 1010 1020 IFPAENFKVT EQPGCCLPVM EAESTKSFQY SVQIEKPFTE GNLTGFISYH MMDTHSAQLE 1030 1040 1050 1060 1070 1080 FSVNLSLLDF IRPLKISSDD FGKLWLSFAN DVKQNVKMSE SQAALPSALK TLQQKLRLHI 1090 1100 1110 1120 1130 IEIIGNEGLL ACQLLPSIPC LLHCRVHADV LALWFRSSCS TLPDYLLYQC QKVMEGS
	Isoform 2 [UniParc]. Checksum: 14CBDA9A25B63BFF	FASTA	1,062	119,482
	10 20 30 40 50 60 MMKECMVRLI YCEMLGYDAS FGYIHAIKLA QQGNLLEKRV GYLAVSLFLH ESHELLLLLV 70 80 90 100 110 120 NTVVKDLQST NLVEVCMALT VVSQIFPCEM IPAVLPLIED KLQHSKEIVR RKAVLALYKF 130 140 150 160 170 180 HLIAPNQVQH IHIKFRKALC DRDVGVMAAS LHIYLRMIKE NSSGYKDLTG SFVTILKQVV 190 200 210 220 230 240 GGKLPVEFNY HSVPAPWLQI QLLRILGLLG KDDQRTSELM YDVLDESLRR AELNHNVTYA 250 260 270 280 290 300 ILFECVHTVY SIYPKSELLE KAAKCIGKFV LSPKINLKYL GLKALTYVIQ QDPTLALQHQ 310 320 330 340 350 360 MTIIECLDHP DPIIKRETLE LLYRITNAQN ITVIVQKMLE YLHQSKEEYV IVNLVGKIAE 370 380 390 400 410 420 LAEKYAPDNA WFIQTMNAVF SVGGDVMHPD IPNNFLRLLA EGFDDETEDQ QLRLYAVQSY 430 440 450 460 470 480 LTLLDMENVF YPQRFLQVMS WVLGEYSYLL DKETPEEVIA KLYKLLMNDS VSSETKAWLI 490 500 510 520 530 540 AAVTKLTSQA HSSNTVERLI HEFTISLDTC MRQHAFELKH LHENVELMKS LLPVDRSCED 550 560 570 580 590 600 LVVDASLSFL DGFVAEGLSQ GAAPYKPPHQ RQEEKLSQEK VLNFEPYGLS FSSSGFTGRQ 610 620 630 640 650 660 SPAGISLGSD VSGNSAETGL KETNSLKLEG IKKLWGKEGY LPKKESKTGD ESGALPVPQE 670 680 690 700 710 720 SIMENVDQAI TKKDQSQVLT QSKEEKEKQL LASSLFVGLG SESTINLLGK ADTVSHKFRR 730 740 750 760 770 780 KSKVKEAKSG ETTSTHNMTC SSFSSLSNVA YEDDYYSNTL HDTGDKELKK FSLTSELLDS 790 800 810 820 830 840 ESLTELPLVE KFSYCSLSTP SLFANNNMEI FHPPQSTAAS VAKESSLASS FLEETTEYIH 850 860 870 880 890 900 SNAMEVCNNE TISVSSYKIW KDDCLLMVWS VTNKSGLELK SADLEIFPAE NFKVTEQPGC 910 920 930 940 950 960 CLPVMEAEST KSFQYSVQIE KPFTEGNLTG FISYHMMDTH SAQLEFSVNL SLLDFIRPLK 970 980 990 1000 1010 1020 ISSDDFGKLW LSFANDVKQN VKMSESQAAL PSALKTLQQK LRLHIIEIIG NEGLLACQLL 1030 1040 1050 1060 PSIPCLLHCR VHADVLALWF RSSCSTLPDY LLYQCQKVME GS

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"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] (ISOFORM 1). Tissue: Heart and Testis.
[2]	Hirst J., Robinson M.S. Submitted (FEB-2000) to the EMBL/GenBank/DDBJ databases Cited for: SEQUENCE REVISION.
[3]	"Similar subunit interactions contribute to assembly of clathrin adaptor complexes and COPI complex: analysis using yeast three-hybrid system." Takatsu H., Futatsumori M., Yoshino K., Yoshida Y., Shin H.W., Nakayama K. Biochem. Biophys. Res. Commun. 284:1083-1089(2001) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANT ARG-163.
[4]	"The full-ORF clone resource of the German cDNA consortium." Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., Wiemann S., Schupp I. BMC Genomics 8:399-399(2007) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), VARIANT ARG-163. Tissue: Uterine endothelium.
[5]	"Analysis of the DNA sequence and duplication history of human chromosome 15." Zody M.C., Garber M., Sharpe T., Young S.K., Rowen L., O'Neill K., Whittaker C.A., Kamal M., Chang J.L., Cuomo C.A., Dewar K., FitzGerald M.G., Kodira C.D., Madan A., Qin S., Yang X., Abbasi N., Abouelleil A. , Arachchi H.M., Baradarani L., Birditt B., Bloom S., Bloom T., Borowsky M.L., Burke J., Butler J., Cook A., DeArellano K., DeCaprio D., Dorris L. III, Dors M., Eichler E.E., Engels R., Fahey J., Fleetwood P., Friedman C., Gearin G., Hall J.L., Hensley G., Johnson E., Jones C., Kamat A., Kaur A., Locke D.P., Madan A., Munson G., Jaffe D.B., Lui A., Macdonald P., Mauceli E., Naylor J.W., Nesbitt R., Nicol R., O'Leary S.B., Ratcliffe A., Rounsley S., She X., Sneddon K.M.B., Stewart S., Sougnez C., Stone S.M., Topham K., Vincent D., Wang S., Zimmer A.R., Birren B.W., Hood L., Lander E.S., Nusbaum C. Nature 440:671-675(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	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. , 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 (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]	"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] (ISOFORM 1), VARIANT ARG-163.
[8]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-857, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[9]	"Adaptor protein complex-4 (AP-4) deficiency causes a novel autosomal recessive cerebral palsy syndrome with microcephaly and intellectual disability." Moreno-De-Luca A., Helmers S.L., Mao H., Burns T.G., Melton A.M., Schmidt K.R., Fernhoff P.M., Ledbetter D.H., Martin C.L. J. Med. Genet. 48:141-144(2011) [PubMed] [Europe PMC] [Abstract] Cited for: INVOLVEMENT IN CPSQ4.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF155156 mRNA. Translation: AAD43326.2. AB030653 mRNA. Translation: BAA82969.1. CR749604 mRNA. Translation: CAH18399.1. AC021752 Genomic DNA. No translation available. AC022407 Genomic DNA. No translation available. AC073964 Genomic DNA. No translation available. CH471082 Genomic DNA. Translation: EAW77411.1. BC126308 mRNA. Translation: AAI26309.1. BC130466 mRNA. Translation: AAI30467.1.
IPI	IPI00010213.
RefSeq	NP_001239056.1. NM_001252127.1. NP_031373.2. NM_007347.4.
UniGene	Hs.413366.
3D structure databases
ProteinModelPortal	Q9UPM8.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q9UPM8. 1 interaction.
STRING	9606.ENSP00000261842.
PTM databases
PhosphoSite	Q9UPM8.
Polymorphism databases
DMDM	145559441.
Proteomic databases
PaxDb	Q9UPM8.
PRIDE	Q9UPM8.
Protocols and materials databases
DNASU	23431.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000261842; ENSP00000261842; ENSG00000081014. ENST00000560508; ENSP00000452976; ENSG00000081014.
GeneID	23431.
KEGG	hsa:23431.
UCSC	uc001zyx.2. human.
Organism-specific databases
CTD	23431.
GeneCards	GC15P051200.
HGNC	HGNC:573. AP4E1.
HPA	HPA041749. HPA041891.
MIM	607244. gene. 613744. phenotype.
neXtProt	NX_Q9UPM8.
Orphanet	280763. Severe intellectual deficit and progressive spastic paraplegia.
PharmGKB	PA24865.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG303101.
HOGENOM	HOG000231886.
HOVERGEN	HBG050522.
InParanoid	Q9UPM8.
KO	K12400.
OMA	KYAPDNA.
OrthoDB	EOG4QFWCJ.
Enzyme and pathway databases
Reactome	REACT_11123. Membrane Trafficking.
Gene expression databases
ArrayExpress	Q9UPM8.
Bgee	Q9UPM8.
CleanEx	HS_AP4E1.
Genevestigator	Q9UPM8.
GermOnline	ENSG00000081014. Homo sapiens.
Family and domain databases
Gene3D	1.25.10.10. 1 hit.
InterPro	IPR017109. AP4_complex_esu. IPR011989. ARM-like. IPR016024. ARM-type_fold. IPR002553. Clathrin/coatomer_adapt-like_N. IPR011710. Coatomer_bsu_C. [Graphical view]
PANTHER	PTHR22780:SF6. PTHR22780:SF6. 1 hit.
Pfam	PF01602. Adaptin_N. 1 hit. PF07718. Coatamer_beta_C. 1 hit. [Graphical view]
PIRSF	PIRSF037097. AP4_complex_epsilon. 1 hit.
SUPFAM	SSF48371. ARM-type_fold. 1 hit.
ProtoNet	Search...
Other
GenomeRNAi	23431.
NextBio	45677.
SOURCE	Search...

Entry information

Entry name

AP4E1_HUMAN

Accession

Primary (citable) accession number: Q9UPM8
Secondary accession number(s): A0AVD6 , A1L4A9, A6NNX7, H0YKX4, Q68D31, Q9Y588

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 27, 2001
Last sequence update:	April 17, 2007
Last modified:	May 1, 2013
This is version 106 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.