Reviewed, UniProtKB/Swiss-Prot Q96CW1 (AP2M1_HUMAN)

Names and origin

Protein names

Recommended name:
    AP-2 complex subunit mu
Alternative name(s):
    Adapter-related protein complex 2 mu subunit
    Adaptor protein complex AP-2 subunit mu
    Adaptin-mu2
    AP-2 mu chain
    Plasma membrane adaptor AP-2 50 kDa protein
    HA2 50 kDa subunit
    Clathrin assembly protein complex 2 medium chain
    Clathrin coat assembly protein AP50
    Clathrin coat-associated protein AP50

Gene names

Name:	AP2M1
Synonyms:	CLAPM1, KIAA0109

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	435 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Component of the adaptor protein complex 2 (AP-2). Adaptor protein complexes function in protein transport via transport vesicles in different membrane traffic pathways. Adaptor protein complexes are vesicle coat components and appear to be involved in cargo selection and vesicle formation. AP-2 is involved in clathrin-dependent endocytosis in which cargo proteins are incorporated into vesicles surrrounded by clathrin (clathrin-coated vesicles, CCVs) which are destined for fusion with the early endosome. The clathrin lattice serves as a mechanical scaffold but is itself unable to bind directly to membrane components. Clathrin-associated adaptor protein (AP) complexes which can bind directly to both the clathrin lattice and to the lipid and protein components of membranes are considered to be the major clathrin adaptors contributing the CCV formation. AP-2 also serves as a cargo receptor to selectively sort the membrane proteins involved in receptor-mediated endocytosis. AP-2 seems to play a role in the recycling of synaptic vesicle membranes from the presynaptic surface. AP-2 recognizes Y-X-X-[FILMV] (Y-X-X-Phi) and [ED]-X-X-X-L-[LI] endocytosis signal motifs within the cytosolic tails of transmembrane cargo molecules. AP-2 may also play a role in maintaining normal post-endocytic trafficking through the ARF6-regulated, non-clathrin pathway. The AP-2 mu subunit binds to transmembrane cargo proteins; it recognizes the Y-X-X-Phi motifs. The surface region interacting with to the Y-X-X-Phi motif is inaccessible in cytosolic AP-2, but becomes accessible through a conformational change following phosphorylation of AP-2 mu subunit at 'Tyr-156' in membrane-associated AP-2. The membrane-specific phosphorylation event appears to involve assembled clathrin which activates the AP-2 mu kinase AAK1 By similarity. Ref.8 Ref.9 Ref.10 Ref.11 Ref.12 Ref.13 Ref.15
Subunit structure	Adaptor protein complex 2 (AP-2) is an heterotetramer composed of two large adaptins (alpha-type subunit AP2A1 or AP2A2 and beta-type subunit AP2B1), a medium adaptin (mu-type subunit AP2M1) and a small adaptin (sigma-type subunit AP2S1). Interacts with ATP6V1H and MEGF10. Interacts with EGFR. Interacts with F2R. Interacts with PIP5K1C; tyrosine phosphorylation of PIP5K1C weakens the interaction By similarity. Ref.13 Ref.7 Ref.14
Subcellular location	Cell membrane. Membrane › coated pit; Peripheral membrane protein; Cytoplasmic side. Note: AP-2 appears to be excluded from internalizing CCVs and to disengage from sites of endocytosis seconds before internalization of the nascent CCV By similarity.
Sequence similarities	Belongs to the adaptor complexes medium subunit family. Contains 1 MHD (mu homology) domain.

Ontologies

Keywords
Biological process	Protein transport Transport
Cellular component	Cell membrane Coated pit Membrane
Coding sequence diversity	Alternative splicing
Ligand	Lipid-binding
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome
Gene Ontology (GO)
Biological process	intracellular protein transport Inferred from electronic annotation. Source: InterPro regulation of defense response to virus by virus Inferred from Experiment. Source: Reactome vesicle-mediated transport Inferred from electronic annotation. Source: InterPro
Cellular component	clathrin adaptor complex Inferred from electronic annotation. Source: InterPro clathrin coat of coated pit Inferred from electronic annotation. Source: InterPro cytosol Inferred from Experiment. Source: Reactome endocytic vesicle membrane Inferred from Experiment. Source: Reactome extrinsic to membrane Inferred from electronic annotation. Source: UniProtKB-SubCell peroxisomal membrane Inferred from Experiment. Source: Reactome
Molecular function	lipid binding Inferred from electronic annotation. Source: UniProtKB-KW protein binding Ref.7 Inferred from physical interaction. Source: UniProtKB transporter activity Traceable author statement. Source: ProtInc
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
NDRG1	Q92597	1	EBI-297683,EBI-716486
STK11	Q15831	1	EBI-297683,EBI-306838

Alternative products

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

Isoform 1 (identifier: Q96CW1-1)

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: Q96CW1-2)

The sequence of this isoform differs from the canonical sequence as follows:
     141-142: Missing.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 435

435

AP-2 complex subunit mu

PRO_0000193774

Regions

Domain

167 – 435

269

MHD

Sites

Binding site

341

1

Phosphatidylinositol lipid headgroup By similarity

Binding site

343

1

Phosphatidylinositol lipid headgroup By similarity

Binding site

345

1

Phosphatidylinositol lipid headgroup By similarity

Binding site

354

1

Phosphatidylinositol lipid headgroup By similarity

Binding site

356

1

Phosphatidylinositol lipid headgroup By similarity

Amino acid modifications

Modified residue

45

1

Phosphoserine Ref.16

Modified residue

156

1

Phosphothreonine Ref.16 Ref.18

Natural variations

Alternative sequence

141 – 142

2

Missing in isoform 2.

VSP_034599

Experimental info

Sequence conflict

106

1

V → L in AAA93254. Ref.1

Secondary structure

1

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435

Helix Strand Turn

Details...

Beta strand

172 – 185

14

Beta strand

187 – 189

3

Beta strand

193 – 196

4

Beta strand

199 – 205

7

Beta strand

212 – 214

3

Beta strand

271 – 275

5

Beta strand

290 – 294

5

Beta strand

297 – 309

13

Beta strand

317 – 325

9

Beta strand

332 – 336

5

Beta strand

338 – 342

5

Turn

346 – 349

4

Beta strand

350 – 358

9

Beta strand

363 – 371

9

Beta strand

386 – 394

9

Beta strand

409 – 412

4

Helix

415 – 417

3

Beta strand

418 – 433

16

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified August 16, 2004. Version 2. Checksum: 82803219BA279954	FASTA	435	49,655
	10 20 30 40 50 60 MIGGLFIYNH KGEVLISRVY RDDIGRNAVD AFRVNVIHAR QQVRSPVTNI ARTSFFHVKR 70 80 90 100 110 120 SNIWLAAVTK QNVNAAMVFE FLYKMCDVMA AYFGKISEEN IKNNFVLIYE LLDEILDFGY 130 140 150 160 170 180 PQNSETGALK TFITQQGIKS QHQTKEEQSQ ITSQVTGQIG WRREGIKYRR NELFLDVLES 190 200 210 220 230 240 VNLLMSPQGQ VLSAHVSGRV VMKSYLSGMP ECKFGMNDKI VIEKQGKGTA DETSKSGKQS 250 260 270 280 290 300 IAIDDCTFHQ CVRLSKFDSE RSISFIPPDG EFELMRYRTT KDIILPFRVI PLVREVGRTK 310 320 330 340 350 360 LEVKVVIKSN FKPSLLAQKI EVRIPTPLNT SGVQVICMKG KAKYKASENA IVWKIKRMAG 370 380 390 400 410 420 MKESQISAEI ELLPTNDKKK WARPPISMNF EVPFAPSGLK VRYLKVFEPK LNYSDHDVIK 430 WVRYIGRSGI YETRC
	Isoform 2. Checksum: 76399E78B0AC7E8A	FASTA	433	49,389
	10 20 30 40 50 60 MIGGLFIYNH KGEVLISRVY RDDIGRNAVD AFRVNVIHAR QQVRSPVTNI ARTSFFHVKR 70 80 90 100 110 120 SNIWLAAVTK QNVNAAMVFE FLYKMCDVMA AYFGKISEEN IKNNFVLIYE LLDEILDFGY 130 140 150 160 170 180 PQNSETGALK TFITQQGIKS QTKEEQSQIT SQVTGQIGWR REGIKYRRNE LFLDVLESVN 190 200 210 220 230 240 LLMSPQGQVL SAHVSGRVVM KSYLSGMPEC KFGMNDKIVI EKQGKGTADE TSKSGKQSIA 250 260 270 280 290 300 IDDCTFHQCV RLSKFDSERS ISFIPPDGEF ELMRYRTTKD IILPFRVIPL VREVGRTKLE 310 320 330 340 350 360 VKVVIKSNFK PSLLAQKIEV RIPTPLNTSG VQVICMKGKA KYKASENAIV WKIKRMAGMK 370 380 390 400 410 420 ESQISAEIEL LPTNDKKKWA RPPISMNFEV PFAPSGLKVR YLKVFEPKLN YSDHDVIKWV 430 RYIGRSGIYE TRC

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Molecular cloning and sequence analysis of the cDNA for human 50 kDa subunit of the clathrin assembly complex AP-2 (AP50)." Tsui S.K.W., Waye M.M.Y., Liew C.C., Fung K., Lee C.Y. Submitted (APR-1996) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Tissue: Heart.
[2]	"Prediction of the coding sequences of unidentified human genes. III. The coding sequences of 40 new genes (KIAA0081-KIAA0120) deduced by analysis of cDNA clones from human cell line KG-1." Nagase T., Miyajima N., Tanaka A., Sazuka T., Seki N., Sato S., Tabata S., Ishikawa K., Kawarabayasi Y., Kotani H., Nomura N. DNA Res. 2:37-43(1995) [PubMed: 7788527] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Bone marrow.
[3]	"Cloning of human full-length CDSs in BD Creator(TM) system donor vector." Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A. Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
[4]	"The DNA sequence, annotation and analysis of human chromosome 3." Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R., Buhay C.J., Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J. , Jackson A., Khan Z.M., Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., Morgan M.B., Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D., Wei S., Wheeler D.A., Wright M.W., Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z., Clendenning J., Clerc-Blankenburg K.P., Chen R., Chen Z., Davis C., Delgado O., Dinh H.H., Dong W., Draper H., Ernst S., Fu G., Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J., Hao B., Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W., Jackson L.R., Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B., Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., Palmeiri A., Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B., Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H., Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J., Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J., Zhang X., Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H., Reinhardt R., Naylor S.L., Yang H., Olson M., Weinstock G., Gibbs R.A. Nature 440:1194-1198(2006) [PubMed: 16641997] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	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 (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	"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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2). Tissue: Kidney, Placenta and Skin.
[7]	"Subunit H of the V-ATPase binds to the medium chain of adaptor protein complex 2 and connects Nef to the endocytic machinery." Geyer M., Yu H., Mandic R., Linnemann T., Zheng Y.-H., Fackler O.T., Peterlin B.M. J. Biol. Chem. 277:28521-28529(2002) [PubMed: 12032142] [Abstract] Cited for: INTERACTION WITH ATP6V1H.
[8]	"Adaptor protein complexes as the key regulators of protein sorting in the post-Golgi network." Nakatsu F., Ohno H. Cell Struct. Funct. 28:419-429(2003) [PubMed: 14745134] [Abstract] Cited for: FUNCTION OF THE AP-2 COMPLEX IN CLATHRIN-MEDIATED ENDOCYTOSIS.
[9]	"Clathrin-mediated endocytosis in AP-2-depleted cells." Motley A., Bright N.A., Seaman M.N.J., Robinson M.S. J. Cell Biol. 162:909-918(2003) [PubMed: 12952941] [Abstract] Cited for: FUNCTION IN CLATHRIN-MEDIATED ENDOCYTOSIS.
[10]	"Endocytosis of the viral chemokine receptor US28 does not require beta-arrestins but is dependent on the clathrin-mediated pathway." Fraile-Ramos A., Kohout T.A., Waldhoer M., Marsh M. Traffic 4:243-253(2003) [PubMed: 12694563] [Abstract] Cited for: FUNCTION IN CLATHRIN-MEDIATED ENDOCYTOSIS.
[11]	"Adaptors for clathrin coats: structure and function." Owen D.J., Collins B.M., Evans P.R. Annu. Rev. Cell Dev. Biol. 20:153-191(2004) [PubMed: 15473838] [Abstract] Cited for: FUNCTION OF THE AP-2 COMPLEX IN CLATHRIN-MEDIATED ENDOCYTOSIS.
[12]	"Analysis of clathrin-mediated endocytosis of epidermal growth factor receptor by RNA interference." Huang F., Khvorova A., Marshall W., Sorkin A. J. Biol. Chem. 279:16657-16661(2004) [PubMed: 14985334] [Abstract] Cited for: FUNCTION IN CLATHRIN-MEDIATED ENDOCYTOSIS.
[13]	"Clathrin adaptor AP2 regulates thrombin receptor constitutive internalization and endothelial cell resensitization." Paing M.M., Johnston C.A., Siderovski D.P., Trejo J. Mol. Cell. Biol. 26:3231-3242(2006) [PubMed: 16581796] [Abstract] Cited for: FUNCTION IN RECEPTOR INTERNALIZATION, INTERACTION WITH F2R.
[14]	"MEGF10 is a mammalian ortholog of CED-1 that interacts with clathrin assembly protein complex 2 medium chain and induces large vacuole formation." Suzuki E., Nakayama M. Exp. Cell Res. 313:3729-3742(2007) [PubMed: 17643423] [Abstract] Cited for: INTERACTION WITH MEGF10.
[15]	"The adaptor complex AP-2 regulates post-endocytic trafficking through the non-clathrin Arf6-dependent endocytic pathway." Lau A.W., Chou M.M. J. Cell Sci. 121:4008-4017(2008) [PubMed: 19033387] [Abstract] Cited for: FUNCTION OF THE AP-2 COMPLEX IN NON-CLATHRIN-DEPENDENT ENDOCYTOSIS.
[16]	"Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle." Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., Greff Z., Keri G., Stemmann O., Mann M. Mol. Cell 31:438-448(2008) [PubMed: 18691976] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-45 AND THR-156, MASS SPECTROMETRY.
[17]	Colinge J., Superti-Furga G., Bennett K.L. Submitted (OCT-2008) to UniProtKB Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
[18]	"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions." Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K. Sci. Signal. 2:RA46-RA46(2009) [PubMed: 19690332] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-156, MASS SPECTROMETRY. Tissue: T-cell.
[19]	"Study of the interaction of the medium chain mu 2 subunit of the clathrin-associated adapter protein complex 2 with cytotoxic T-lymphocyte antigen 4 and CD28." Follows E.R., McPheat J.C., Minshull C., Moore N.C., Pauptit R.A., Rowsell S., Stacey C.L., Stanway J.J., Taylor I.W.F., Abbott W.M. Biochem. J. 359:427-434(2001) [PubMed: 11583591] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (3.6 ANGSTROMS) OF 167-435 IN COMPLEX WITH CTLA4 INTERNALIZATION SIGNAL.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

U36188 mRNA. Translation: AAA93254.1.
D63475 mRNA. Translation: BAA09762.2. Different initiation.
BT007308 mRNA. Translation: AAP35972.1.
AC131235 Genomic DNA. No translation available.
CH471052 Genomic DNA. Translation: EAW78290.1.
BC004996 mRNA. Translation: AAH04996.1.
BC013796 mRNA. Translation: AAH13796.1.
BC014030 mRNA. Translation: AAH14030.1.

IPI

IPI00022256.
IPI00619900.

PIR

G02088.

RefSeq

NP_001020376.1.
NP_004059.2.

UniGene

Hs.518460

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1H6E	X-ray	3.60	A	164-435	[»]

SMR

Q96CW1. Positions 1-435.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q96CW1. 17 interactions.

STRING

Q96CW1.

PTM databases

PhosphoSite

Q96CW1.

Proteomic databases

PRIDE

Q96CW1.

Genome annotation databases

Ensembl

ENST00000292807; ENSP00000292807; ENSG00000161203; Homo sapiens. [Genome view]

GeneID

1173.

KEGG

hsa:1173.

UCSC

uc003fmw.1. human.
uc010hxu.1. human.

Organism-specific databases

CTD

1173.

GeneCards

GC03P185375.

H-InvDB

HIX0003919.

HGNC

HGNC:564. AP2M1.

MIM

601024. gene.

PharmGKB

PA24855.

HUGE

Search...

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG08321.

HOVERGEN

Q96CW1.

InParanoid

Q96CW1.

OrthoDB

EOG99363N.

PhylomeDB

Q96CW1.

Enzyme and pathway databases

Pathway_Interaction_DB

arf_3pathway. Arf1 pathway.

Reactome

REACT_11061. Signalling by NGF.
REACT_13685. Synaptic Transmission.
REACT_6185. HIV Infection.
REACT_9417. Signaling by EGFR.
REACT_9480. Gap junction trafficking and regulation.

Gene expression databases

ArrayExpress

Q96CW1.

Bgee

Q96CW1.

CleanEx

HS_AP2M1.

Genevestigator

Q96CW1.

GermOnline

ENSG00000161203. Homo sapiens.

Family and domain databases

InterPro

IPR015629. Clathrin_AP50.
IPR001392. Clathrin_mu.
IPR008968. Clathrin_mu_C.
IPR018240. Clathrin_mu_CS.
IPR011012. Longin-like.
[Graphical view]

PANTHER

PTHR11998:SF12. Clathrin_coat_assem_AP50. 1 hit.

Pfam

PF00928. Adap_comp_sub. 1 hit.
[Graphical view]

PIRSF

PIRSF005992. Clathrin_mu. 1 hit.

PRINTS

PR00314. CLATHRINADPT.

PROSITE

PS00990. CLAT_ADAPTOR_M_1. 1 hit.
PS00991. CLAT_ADAPTOR_M_2. 1 hit.
PS51072. MHD. 1 hit.
[Graphical view]

ProtoNet

Search...

Other Resources

NextBio

4844.

SOURCE

Search...

Entry information

Entry name

AP2M1_HUMAN

Accession

Primary (citable) accession number: Q96CW1
Secondary accession number(s): A6NE12, P20172, P53679

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 16, 2004
Last sequence update:	August 16, 2004
Last modified:	February 9, 2010
This is version 77 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

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.