Reviewed, UniProtKB/Swiss-Prot Q02410 (APBA1_HUMAN)

Names and origin

Protein names

Recommended name:
    Amyloid beta A4 precursor protein-binding family A member 1
Alternative name(s):
    Neuron-specific X11 protein
    Neuronal Munc18-1-interacting protein 1
      Short name=Mint-1
    Adapter protein X11alpha

Gene names

Name:	APBA1
Synonyms:	MINT1, X11

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	837 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Putative function in synaptic vesicle exocytosis by binding to Munc18-1, an essential component of the synaptic vesicle exocytotic machinery. May modulate processing of the beta-amyloid precursor protein (APP) and hence formation of beta-APP.
Subunit structure	Part of a multimeric complex containing Munc18-1 and syntaxin-1. Also part of the brain-specific heterotrimeric complex LIN-10/X11-alpha, LIN-2/CASK, and LIN7. Binds to the cytoplasmic domain of amyloid protein (APP).
Tissue specificity	Brain and spinal cord.
Domain	Composed of an N-terminal domain that binds Munc18-1 and LIN-2/CASK, a middle phosphotyrosine-binding domain (PID/PTB) that mediates binding with the cytoplasmic domain of the beta-amyloid precursor protein, and two C-terminal PDZ domains thought to attach proteins to the plasma membrane.
Sequence similarities	Contains 2 PDZ (DHR) domains. Contains 1 PID domain.

Ontologies

Keywords
Biological process	Protein transport Transport
Domain	Repeat
Technical term	3D-structure
Gene Ontology (GO)
Biological process	axon cargo transport Traceable author statement. Source: ProtInc cell adhesion Traceable author statement. Source: ProtInc intracellular protein transport Ref.2 Traceable author statement. Source: ProtInc nervous system development Traceable author statement. Source: ProtInc protein complex assembly Ref.2 Traceable author statement. Source: ProtInc synaptic transmission Traceable author statement. Source: ProtInc
Cellular component	synaptic vesicle Traceable author statement. Source: ProtInc
Molecular function	protein binding Ref.5 Inferred from physical interaction. Source: IntAct
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
APP	P05067	2	EBI-368690,EBI-77613

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 837

837

Amyloid beta A4 precursor protein-binding family A member 1

PRO_0000064614

Regions

Domain

457 – 643

187

PID

Domain

656 – 742

87

PDZ 1

Domain

747 – 822

76

PDZ 2

Region

226 – 314

89

Munc-18-1 binding

Region

373 – 436

64

LIN-2/CASK binding

Compositional bias

67 – 70

4

Poly-Glu

Compositional bias

294 – 328

35

Pro-rich

Compositional bias

368 – 452

85

Pro-rich

Experimental info

Mutagenesis

608

1

F → V: Diminishes interaction with APP

Sequence conflict

164

1

A → V in AAA61307. Ref.4

Sequence conflict

208

1

D → H in AAC05304. Ref.1

Sequence conflict

427 – 429

3

AST → VPI in AAC05304. Ref.1

Sequence conflict

427 – 429

3

AST → VPI in AAA61307. Ref.4

Sequence conflict

522

1

S → L in AAC05304. Ref.1

Sequence conflict

522

1

S → L in AAA61307. Ref.4

Sequence conflict

563

1

M → I in AAC05304. Ref.1

Sequence conflict

563

1

M → I in AAA61307. Ref.4

Sequence conflict

730

1

K → E in AAC05304. Ref.1

Sequence conflict

730

1

K → E in AAA61307. Ref.4

Secondary structure

1

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837

Helix Strand Turn

Details...

Turn

455 – 457

3

Beta strand

459 – 472

14

Helix

479 – 498

20

Beta strand

516 – 521

6

Beta strand

523 – 530

8

Turn

531 – 533

3

Beta strand

536 – 541

6

Helix

542 – 544

3

Beta strand

545 – 551

7

Beta strand

554 – 559

6

Beta strand

586 – 593

8

Helix

597 – 616

20

Beta strand

655 – 660

6

Beta strand

669 – 672

4

Beta strand

676 – 679

4

Beta strand

684 – 688

5

Helix

693 – 697

5

Beta strand

705 – 709

5

Helix

719 – 727

9

Beta strand

730 – 740

11

Beta strand

746 – 756

11

Beta strand

760 – 764

5

Beta strand

767 – 771

5

Helix

777 – 780

4

Beta strand

786 – 788

3

Helix

796 – 798

3

Helix

801 – 809

9

Beta strand

813 – 821

9

Sequences

	Sequence		Length	Mass (Da)
	Q02410-1 [UniParc]. Last modified October 17, 2006. Version 3. Checksum: 29C3620BBC89534B	FASTA	837	92,865
	10 20 30 40 50 60 MNHLEGSAEV EVTDEAAGGE VNESVEADLE HPEVEEEQQQ PPQQQHYVGR HQRGRALEDL 70 80 90 100 110 120 RAQLGQEEEE RGECLARSAS TESGFHNHTD TAEGDVIAAA RDGYDAERAQ DPEDESAYAV 130 140 150 160 170 180 QYRPEAEEYT EQAEAEHAEA THRRALPNHL HFHSLEHEEA MNAAYSGYVY THRLFHRGED 190 200 210 220 230 240 EPYSEPYADY GGLQEHVYEE IGDAPELDAR DGLRLYEQER DEAAAYRQEA LGARLHHYDE 250 260 270 280 290 300 RSDGESDSPE KEAEFAPYPR MDSYEQEEDI DQIVAEVKQS MSSQSLDKAA EDMPEAEQDL 310 320 330 340 350 360 ERPPTPAGGR PDSPGLQAPA GQQRAVGPAG GGEAGQRYSK EKRDAISLAI KDIKEAIEEV 370 380 390 400 410 420 KTRTIRSPYT PDEPKEPIWV MRQDISPTRD CDDQRPMDGD SPSPGSSSPL GAESSSTSLH 430 440 450 460 470 480 PSDPVEASTN KESRKSLASF PTYVEVPGPC DPEDLIDGII FAANYLGSTQ LLSDKTPSKN 490 500 510 520 530 540 VRMMQAQEAV SRIKMAQKLA KSRKKAPEGE SQPMTEVDLF ISTQRIKVLN ADTQETMMDH 550 560 570 580 590 600 PLRTISYIAD IGNIVVLMAR RRMPRSNSQE NVEASHPSQD GKRQYKMICH VFESEDAQLI 610 620 630 640 650 660 AQSIGQAFSV AYQEFLRANG INPEDLSQKE YSDLLNTQDM YNDDLIHFSK SENCKDVFIE 670 680 690 700 710 720 KQKGEILGVV IVESGWGSIL PTVIIANMMH GGPAEKSGKL NIGDQIMSIN GTSLVGLPLS 730 740 750 760 770 780 TCQSIIKGLK NQSRVKLNIV RCPPVTTVLI RRPDLRYQLG FSVQNGIICS LMRGGIAERG 790 800 810 820 830 GVRVGHRIIE INGQSVVATP HEKIVHILSN AVGEIHMKTM PAAMYRLLTA QEQPVYI

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Mints, Munc18-interacting proteins in synaptic vesicle exocytosis." Okamoto M., Suedhof T.C. J. Biol. Chem. 272:31459-31464(1997) [PubMed: 9395480] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Brain.
[2]	"The X11alpha protein slows cellular amyloid precursor protein processing and reduces Abeta40 and Abeta42 secretion." Borg J.-P., Yang Y., De Taddeo-Borg M., Margolis B., Turner R.S. J. Biol. Chem. 273:14761-14766(1998) [PubMed: 9614075] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Brain.
[3]	"DNA sequence and analysis of human chromosome 9." Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L., Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R., Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S., Bagguley C.L. , Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y., Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E., Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M., Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J., Frankish A., Frankland J.A., French L., Fricker D.G., Garner P., Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S., Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E., Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D., Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E., Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K., Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J., Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E., McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V., Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S., Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K., Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J., Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M., West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L., Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M., Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J., Dunham I. Nature 429:369-374(2004) [PubMed: 15164053] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	"Gene in the region of the Friedreich ataxia locus encodes a putative transmembrane protein expressed in the nervous system." Duclos F., Koenig M., Boschert U., Sirugo G., Hen R., Mandel J.-L. Proc. Natl. Acad. Sci. U.S.A. 90:109-113(1993) [PubMed: 7678331] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 130-837. Tissue: Fetal brain.
[5]	"The phosphotyrosine interaction domains of X11 and FE65 bind to distinct sites on the YENPTY motif of amyloid precursor protein." Borg J.-P., Ooi J., Levy E., Margolis B. Mol. Cell. Biol. 16:6229-6241(1996) [PubMed: 8887653] [Abstract] Cited for: MUTAGENESIS OF PHE-608.
[6]	"Sequence-specific recognition of the internalization motif of the Alzheimer's amyloid precursor protein by the X11 PTB domain." Zhang Z., Lee C.-H., Mandiyan V., Borg J.-P., Margolis B., Schlessinger J., Kuriyan J. EMBO J. 16:6141-6150(1997) [PubMed: 9321393] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 452-617.
[7]	"Solution structure of the first PDZ domain of amyloid beta A4 precursor protein-binding family A, member 1." RIKEN structural genomics initiative (RSGI) Submitted (NOV-2005) to the PDB data bank Cited for: STRUCTURE BY NMR OF 656-740.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBLGenBankDDBJ

AF029106 mRNA. Translation: AAC05304.1.
AF047347 mRNA. Translation: AAC39766.1.
AL353693, AL355140 Genomic DNA. Translation: CAH74104.1.
AL355140, AL353693 Genomic DNA. Translation: CAI15443.1.
L04953 mRNA. Translation: AAA61307.1.

PIR

A47176.

RefSeq

NP_001154.2.

UniGene

Hs.695952

3D structure databases

PDBMSD

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1AQC	X-ray	2.30	A/B	453-623	[»]
1U37	NMR	-	A	655-741	[»]
1U38	NMR	-	A	655-741	[»]
1U39	NMR	-	A	743-822	[»]
1U3B	NMR	-	A	655-837	[»]
1X11	X-ray	2.50	A/B	453-623	[»]
1X45	NMR	-	A	656-740	[»]
1Y7N	NMR	-	A	745-823	[»]

ModBase

Search...

Protein-protein interaction databases

IntAct

Q02410.

PTM databases

PhosphoSite

Q02410.

Genome annotation databases

Ensembl

ENSG00000107282. Homo sapiens. [Contig view]

GeneID

320.

KEGG

hsa:320.

Organism-specific databases

HGNC

HGNC:578. APBA1.

MIM

602414. gene.

PharmGKB

PA24869.

GenAtlas

Search...

GeneCards

Search...

Phylogenomic databases

HOGENOM

Q02410.