Reviewed, UniProtKB/Swiss-Prot Q96CW1 (AP2M1_HUMAN)

Names and origin

Protein names

Recommended name:
    AP-2 complex subunit mu-1
Alternative name(s):
    Adaptin-mu2
    AP-2 mu-2 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)

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.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Component of the adaptor complexes which link clathrin to receptors in coated vesicles. Clathrin-associated protein complexes are believed to interact with the cytoplasmic tails of membrane proteins, leading to their selection and concentration. AP50 is a subunit of the plasma membrane adaptor. The complex binds polyphosphoinositide-containing lipids.
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). Component of a complex composed at least of ACTB, AP2M1, AP2A1, AP2A2, MEGF10 and VIM. Interacts with ATP6V1H and MEGF10.
Subcellular location	Cell membrane. Membrane › coated pit; Peripheral membrane protein; Cytoplasmic side. Note= Component of the coat surrounding the cytoplasmic face of coated vesicles in the plasma membrane.
Post-translational modification	Phosphorylated By similarity.
Sequence similarities	Belongs to the adaptor complexes medium subunit family. Contains 1 MHD (mu homology) domain.

Ontologies

Keywords
Cellular component	Cell membrane Coated pit Membrane
Coding sequence diversity	Alternative splicing
Ligand	Lipid-binding
PTM	Phosphoprotein
Technical term	3D-structure
Gene Ontology (GO)
Biological process	regulation of defense response to virus by virus Inferred from Experiment. Source: Reactome
Cellular component	cytosol Inferred from Experiment. Source: Reactome peroxisomal membrane Inferred from Experiment. Source: Reactome plasma membrane Inferred from Experiment. Source: Reactome
Molecular function	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

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

Molecule processing

Chain

1 – 435

435

AP-2 complex subunit mu-1

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

156

1

Phosphothreonine By similarity

Natural variations

Alternative sequence

141 – 142

2

Missing in isoform 2.

Experimental info

Sequence conflict

106

1

V → L in AAA93254. Ref.1

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

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 [UniParc]. Checksum: 76399E78B0AC7E8A		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]	"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: IDENTIFICATION IN A COMPLEX WITH ACTB; AP2A1; AP2A2; MEGF10 AND VIM, INTERCTION WITH MEGF10.
[9]	"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

EMBLGenBankDDBJ

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.

PIR

G02088.

RefSeq

NP_001020376.1.
NP_004059.2.

UniGene

Hs.518460

3D structure databases

PDBMSD

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.

PTM databases

PhosphoSite

Q96CW1.

Genome annotation databases

Ensembl

ENSG00000161203. Homo sapiens. [Contig view]

GeneID

1173.

KEGG

hsa:1173.

Organism-specific databases

H-InvDB

HIX0003919.

HGNC

HGNC:564. AP2M1.

MIM

601024. gene.

PharmGKB

PA24855.

HUGE

Search...

GenAtlas

Search...

GeneCards

Search...

Phylogenomic databases

HOGENOM

Q96CW1.

HOVERGEN

Q96CW1.

Enzyme and pathway databases

Reactome

REACT_6185. HIV Infection.
REACT_9480. Gap junction trafficking and regulation.

Gene expression databases

ArrayExpress

Q96CW1.

CleanEx

HS_AP2M1.

GermOnline

ENSG00000161203. Homo sapiens.

Family and domain databases

InterPro

IPR015629. Clathrin_AP50.
IPR001392. Clathrin_mu.
IPR008968. Clathrin_mu_C.
[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]

ProDom

Q96CW1.
[Graphical view] [Entries sharing at least one domain]

BLOCKS

Search...

Other Resources

SOURCE

Search...

ProtoNet

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:	July 22, 2008
This is version 58 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)