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Protein

Membrane-associated guanylate kinase, WW and PDZ domain-containing protein 2

Gene

MAGI2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Seems to act as scaffold molecule at synaptic junctions by assembling neurotransmitter receptors and cell adhesion proteins. May play a role in regulating activin-mediated signaling in neuronal cells. Enhances the ability of PTEN to suppress AKT1 activation. Plays a role in nerve growth factor (NGF)-induced recruitment of RAPGEF2 to late endosomes and neurite outgrowth.1 Publication

GO - Molecular functioni

  • beta-1 adrenergic receptor binding Source: UniProtKB
  • phosphatase binding Source: UniProtKB
  • receptor signaling complex scaffold activity Source: UniProtKB
  • signal transducer activity Source: Ensembl
  • SMAD binding Source: UniProtKB
  • type II activin receptor binding Source: UniProtKB

GO - Biological processi

Keywordsi

Biological processNeurogenesis

Enzyme and pathway databases

ReactomeiR-HSA-373753 Nephrin family interactions
SignaLinkiQ86UL8

Protein family/group databases

TCDBi8.A.24.1.6 the ezrin/radixin/moesin-binding phosphoprotein 50 (ebp50) family

Names & Taxonomyi

Protein namesi
Recommended name:
Membrane-associated guanylate kinase, WW and PDZ domain-containing protein 2
Alternative name(s):
Atrophin-1-interacting protein 1
Short name:
AIP-1
Atrophin-1-interacting protein A
Membrane-associated guanylate kinase inverted 2
Short name:
MAGI-2
Gene namesi
Name:MAGI2
Synonyms:ACVRINP1, AIP1, KIAA0705
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 7

Organism-specific databases

EuPathDBiHostDB:ENSG00000187391.18
HGNCiHGNC:18957 MAGI2
MIMi606382 gene
neXtProtiNX_Q86UL8

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cell junction, Cell membrane, Cytoplasm, Endosome, Membrane, Synapse, Synaptosome

Pathology & Biotechi

Involvement in diseasei

Nephrotic syndrome 15 (NPHS15)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA form of nephrotic syndrome, a renal disease clinically characterized by severe proteinuria, resulting in complications such as hypoalbuminemia, hyperlipidemia and edema. Kidney biopsies show non-specific histologic changes such as focal segmental glomerulosclerosis and diffuse mesangial proliferation. NPHS15 is an autosomal recessive form with onset in the first months of life. Disease severity is variable. Some patients show rapid progression to end-stage renal failure.
See also OMIM:617609

Organism-specific databases

DisGeNETi9863
MalaCardsiMAGI2
MIMi617609 phenotype
OpenTargetsiENSG00000187391
PharmGKBiPA142671484

Polymorphism and mutation databases

BioMutaiMAGI2
DMDMi88909269

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000945861 – 1455Membrane-associated guanylate kinase, WW and PDZ domain-containing protein 2Add BLAST1455

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei362PhosphotyrosineBy similarity1
Modified residuei686PhosphoserineBy similarity1
Modified residuei827PhosphotyrosineBy similarity1
Modified residuei884PhosphoserineBy similarity1
Modified residuei885PhosphoserineBy similarity1
Modified residuei1014PhosphoserineBy similarity1

Keywords - PTMi

Phosphoprotein

Proteomic databases

MaxQBiQ86UL8
PaxDbiQ86UL8
PeptideAtlasiQ86UL8
PRIDEiQ86UL8

PTM databases

iPTMnetiQ86UL8
PhosphoSitePlusiQ86UL8

Expressioni

Tissue specificityi

Specifically expressed in brain.1 Publication

Gene expression databases

BgeeiENSG00000187391
ExpressionAtlasiQ86UL8 baseline and differential
GenevisibleiQ86UL8 HS

Organism-specific databases

HPAiHPA013650

Interactioni

Subunit structurei

Interacts (via its WW domains) with DRPLA (PubMed:9647693). Interacts (via its second PDZ domain) with PTEN (via unphosphorylated C-terminus); this interaction diminishes the degradation rate of PTEN (PubMed:10760291, PubMed:11707428). Interacts (via guanylate kinase domain) with DLGAP1 (By similarity). Interacts (via the PDZ domains) with GRIN2A, GRID2 and NLGN1 (By similarity). Interacts with CTNND2, CTNNB1, MAGUIN-1, ACVR2A, SMAD2 and SMAD3 (By similarity). Part of a complex consisting of AIP1, ACVR2A, ACVR1B and SMAD3 (By similarity). May interact with HTR2A (By similarity). Interacts with IGSF9, RAPGEF2 and HTR4 (By similarity). Identified in a complex with ACTN4, CASK, IQGAP1, NPHS1, SPTAN1 and SPTBN1 (By similarity). Found in a complex, at least composed of KIDINS220, MAGI2, NTRK1 and RAPGEF2; the complex is mainly formed at late endosomes in a NGF-dependent manner (By similarity). Interacts with RAPGEF2; the interaction occurs before or after nerve growth factor (NGF) stimulation (By similarity). Interacts (via PDZ domain) with KIDINS220 (via C-terminal domain) (By similarity). Interacts with DDN (PubMed:16464232). Interacts with DLL1 (By similarity). Found in a complex with IGSF9B and NLGN2; the interaction with IGSF9B is mediated via the PDZ 5 and PDZ 6 domains, while the interaction with NLGN2 is mediated via the WW1, WW2 and PDZ2 domains (PubMed:23751499).By similarity5 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
ADRB1P085882EBI-311035,EBI-991009

GO - Molecular functioni

  • beta-1 adrenergic receptor binding Source: UniProtKB
  • phosphatase binding Source: UniProtKB
  • receptor signaling complex scaffold activity Source: UniProtKB
  • SMAD binding Source: UniProtKB
  • type II activin receptor binding Source: UniProtKB

Protein-protein interaction databases

BioGridi115197, 10 interactors
CORUMiQ86UL8
IntActiQ86UL8, 12 interactors
MINTiQ86UL8
STRINGi9606.ENSP00000346151

Structurei

Secondary structure

11455
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi415 – 417Combined sources3
Beta strandi422 – 430Combined sources9
Beta strandi437 – 441Combined sources5
Beta strandi444 – 447Combined sources4
Beta strandi451 – 455Combined sources5
Helixi460 – 463Combined sources4
Beta strandi472 – 476Combined sources5
Helixi486 – 494Combined sources9
Beta strandi501 – 509Combined sources9
Beta strandi604 – 609Combined sources6
Beta strandi612 – 622Combined sources11
Beta strandi625 – 632Combined sources8
Helixi634 – 636Combined sources3
Beta strandi645 – 649Combined sources5
Helixi659 – 668Combined sources10
Beta strandi673 – 680Combined sources8
Beta strandi774 – 777Combined sources4
Beta strandi780 – 787Combined sources8
Beta strandi790 – 792Combined sources3
Beta strandi803 – 807Combined sources5
Helixi814 – 816Combined sources3
Beta strandi824 – 828Combined sources5
Helixi838 – 851Combined sources14
Beta strandi853 – 861Combined sources9
Beta strandi919 – 924Combined sources6
Beta strandi933 – 936Combined sources4
Beta strandi953 – 957Combined sources5
Helixi964 – 966Combined sources3
Beta strandi974 – 978Combined sources5
Turni983 – 985Combined sources3
Helixi988 – 997Combined sources10
Turni998 – 1000Combined sources3
Beta strandi1001 – 1006Combined sources6
Beta strandi1156 – 1159Combined sources4
Beta strandi1162 – 1164Combined sources3
Turni1165 – 1168Combined sources4
Beta strandi1169 – 1172Combined sources4
Helixi1181 – 1185Combined sources5
Beta strandi1193 – 1197Combined sources5
Helixi1207 – 1217Combined sources11
Beta strandi1219 – 1221Combined sources3
Beta strandi1223 – 1226Combined sources4

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1UEPNMR-A774-863[»]
1UEQNMR-A412-522[»]
1UEWNMR-A915-1015[»]
1UJVNMR-A600-682[»]
1WFVNMR-A1141-1230[»]
ProteinModelPortaliQ86UL8
SMRiQ86UL8
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ86UL8

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini17 – 101PDZ 1PROSITE-ProRule annotationAdd BLAST85
Domaini109 – 283Guanylate kinase-likePROSITE-ProRule annotationAdd BLAST175
Domaini302 – 335WW 1PROSITE-ProRule annotationAdd BLAST34
Domaini348 – 381WW 2PROSITE-ProRule annotationAdd BLAST34
Domaini426 – 510PDZ 2PROSITE-ProRule annotationAdd BLAST85
Domaini605 – 683PDZ 3PROSITE-ProRule annotationAdd BLAST79
Domaini778 – 860PDZ 4PROSITE-ProRule annotationAdd BLAST83
Domaini920 – 1010PDZ 5PROSITE-ProRule annotationAdd BLAST91
Domaini1147 – 1229PDZ 6PROSITE-ProRule annotationAdd BLAST83

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni302 – 381Interaction with DDN1 PublicationAdd BLAST80

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi1015 – 1118Pro-richAdd BLAST104
Compositional biasi1340 – 1430Ala-richAdd BLAST91

Sequence similaritiesi

Belongs to the MAGUK family.Curated

Keywords - Domaini

Repeat

Phylogenomic databases

eggNOGiENOG410ISXI Eukaryota
ENOG410XNXK LUCA
GeneTreeiENSGT00650000092997
HOVERGENiHBG007091
InParanoidiQ86UL8
KOiK05629
OMAiDCPVGSE
OrthoDBiEOG091G0NSY
PhylomeDBiQ86UL8
TreeFamiTF316816

Family and domain databases

CDDicd00201 WW, 2 hits
InterProiView protein in InterPro
IPR008145 GK/Ca_channel_bsu
IPR008144 Guanylate_kin-like_dom
IPR020590 Guanylate_kinase_CS
IPR030036 MAGI2
IPR027417 P-loop_NTPase
IPR001478 PDZ
IPR036034 PDZ_sf
IPR001202 WW_dom
IPR036020 WW_dom_sf
PANTHERiPTHR10316:SF27 PTHR10316:SF27, 3 hits
PfamiView protein in Pfam
PF00625 Guanylate_kin, 1 hit
PF00595 PDZ, 4 hits
PF00397 WW, 1 hit
SMARTiView protein in SMART
SM00072 GuKc, 1 hit
SM00228 PDZ, 6 hits
SM00456 WW, 2 hits
SUPFAMiSSF50156 SSF50156, 6 hits
SSF51045 SSF51045, 2 hits
SSF52540 SSF52540, 1 hit
PROSITEiView protein in PROSITE
PS00856 GUANYLATE_KINASE_1, 1 hit
PS50052 GUANYLATE_KINASE_2, 1 hit
PS50106 PDZ, 6 hits
PS01159 WW_DOMAIN_1, 2 hits
PS50020 WW_DOMAIN_2, 2 hits

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q86UL8-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MSKSLKKKSH WTSKVHESVI GRNPEGQLGF ELKGGAENGQ FPYLGEVKPG
60 70 80 90 100
KVAYESGSKL VSEELLLEVN ETPVAGLTIR DVLAVIKHCK DPLRLKCVKQ
110 120 130 140 150
GGIVDKDLRH YLNLRFQKGS VDHELQQIIR DNLYLRTVPC TTRPHKEGEV
160 170 180 190 200
PGVDYIFITV EDFMELEKSG ALLESGTYED NYYGTPKPPA EPAPLLLNVT
210 220 230 240 250
DQILPGATPS AEGKRKRNKS VSNMEKASIE PPEEEEEERP VVNGNGVVVT
260 270 280 290 300
PESSEHEDKS AGASGEMPSQ PYPAPVYSQP EELKEQMDDT KPTKPEDNEE
310 320 330 340 350
PDPLPDNWEM AYTEKGEVYF IDHNTKTTSW LDPRLAKKAK PPEECKENEL
360 370 380 390 400
PYGWEKIDDP IYGTYYVDHI NRRTQFENPV LEAKRKLQQH NMPHTELGTK
410 420 430 440 450
PLQAPGFREK PLFTRDASQL KGTFLSTTLK KSNMGFGFTI IGGDEPDEFL
460 470 480 490 500
QVKSVIPDGP AAQDGKMETG DVIVYINEVC VLGHTHADVV KLFQSVPIGQ
510 520 530 540 550
SVNLVLCRGY PLPFDPEDPA NSMVPPLAIM ERPPPVMVNG RHNYETYLEY
560 570 580 590 600
ISRTSQSVPD ITDRPPHSLH SMPTDGQLDG TYPPPVHDDN VSMASSGATQ
610 620 630 640 650
AELMTLTIVK GAQGFGFTIA DSPTGQRVKQ ILDIQGCPGL CEGDLIVEIN
660 670 680 690 700
QQNVQNLSHT EVVDILKDCP IGSETSLIIH RGGFFSPWKT PKPIMDRWEN
710 720 730 740 750
QGSPQTSLSA PAIPQNLPFP PALHRSSFPD STEAFDPRKP DPYELYEKSR
760 770 780 790 800
AIYESRQQVP PRTSFRMDSS GPDYKELDVH LRRMESGFGF RILGGDEPGQ
810 820 830 840 850
PILIGAVIAM GSADRDGRLH PGDELVYVDG IPVAGKTHRY VIDLMHHAAR
860 870 880 890 900
NGQVNLTVRR KVLCGGEPCP ENGRSPGSVS THHSSPRSDY ATYTNSNHAA
910 920 930 940 950
PSSNASPPEG FASHSLQTSD VVIHRKENEG FGFVIISSLN RPESGSTITV
960 970 980 990 1000
PHKIGRIIDG SPADRCAKLK VGDRILAVNG QSIINMPHAD IVKLIKDAGL
1010 1020 1030 1040 1050
SVTLRIIPQE ELNSPTSAPS SEKQSPMAQQ SPLAQQSPLA QPSPATPNSP
1060 1070 1080 1090 1100
IAQPAPPQPL QLQGHENSYR SEVKARQDVK PDIRQPPFTD YRQPPLDYRQ
1110 1120 1130 1140 1150
PPGGDYQQPP PLDYRQPPLL DYRQHSPDTR QYPLSDYRQP QDFDYFTVDM
1160 1170 1180 1190 1200
EKGAKGFGFS IRGGREYKMD LYVLRLAEDG PAIRNGRMRV GDQIIEINGE
1210 1220 1230 1240 1250
STRDMTHARA IELIKSGGRR VRLLLKRGTG QVPEYDEPAP WSSPAAAAPG
1260 1270 1280 1290 1300
LPEVGVSLDD GLAPFSPSHP APPSDPSHQI SPGPTWDIKR EHDVRKPKEL
1310 1320 1330 1340 1350
SACGQKKQRL GEQRERSASP QRAARPRLEE APGGQGRPEA GRPASEARAP
1360 1370 1380 1390 1400
GLAAADAADA ARAGGKEAPR AAAGSELCRR EGPGAAPAFA GPGGGGSGAL
1410 1420 1430 1440 1450
EAEGRAGARA GPRPGPRPPG GAPARKAAVA PGPWKVPGSD KLPSVLKPGA

SAASR
Length:1,455
Mass (Da):158,754
Last modified:February 7, 2006 - v3
Checksum:i93E170D070A70A9C
GO
Isoform 2 (identifier: Q86UL8-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     757-771: QQVPPRTSFRMDSSG → R

Show »
Length:1,441
Mass (Da):157,236
Checksum:i505C382255497AFE
GO

Sequence cautioni

The sequence BAA31680 differs from that shown. Reason: Erroneous initiation.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti1234E → Q in AAC05370 (PubMed:9647693).Curated1
Sequence conflicti1250G → C in AAC05370 (PubMed:9647693).Curated1
Sequence conflicti1291E → K in AAC05370 (PubMed:9647693).Curated1
Sequence conflicti1383P → L in AAC05370 (PubMed:9647693).Curated1
Sequence conflicti1389 – 1394FAGPGG → SADPAD in AAC05370 (PubMed:9647693).Curated6
Sequence conflicti1401E → A in AAC05370 (PubMed:9647693).Curated1
Sequence conflicti1411G → A in AAC05370 (PubMed:9647693).Curated1
Sequence conflicti1414 – 1415PG → SV in AAC05370 (PubMed:9647693).Curated2
Sequence conflicti1420G → A in AAC05370 (PubMed:9647693).Curated1
Sequence conflicti1423P → A in AAC05370 (PubMed:9647693).Curated1
Sequence conflicti1426K → R in AAC05370 (PubMed:9647693).Curated1
Sequence conflicti1429V → G in AAC05370 (PubMed:9647693).Curated1
Sequence conflicti1437P → R in AAC05370 (PubMed:9647693).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_008435757 – 771QQVPP…MDSSG → R in isoform 2. 2 PublicationsAdd BLAST15

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF038563 mRNA Translation: AAC05370.1
AB014605 mRNA Translation: BAA31680.2 Different initiation.
AC004808 Genomic DNA Translation: AAC23438.1
AC004945 Genomic DNA Translation: AAC61488.1
AC004990 Genomic DNA Translation: AAC79151.1
AC005246 Genomic DNA Translation: AAC25530.1
AC006043 Genomic DNA Translation: AAD15413.2
AC006324 Genomic DNA Translation: AAF66080.1
AC007237 Genomic DNA Translation: AAP21886.1
AC073200 Genomic DNA Translation: AAP22360.1
CH236949 Genomic DNA Translation: EAL24194.1
BC150277 mRNA Translation: AAI50278.1
CCDSiCCDS5594.1 [Q86UL8-1]
CCDS75623.1 [Q86UL8-2]
RefSeqiNP_001288057.1, NM_001301128.1 [Q86UL8-2]
NP_036433.2, NM_012301.3 [Q86UL8-1]
UniGeneiHs.603842

Genome annotation databases

EnsembliENST00000354212; ENSP00000346151; ENSG00000187391 [Q86UL8-1]
ENST00000419488; ENSP00000405766; ENSG00000187391 [Q86UL8-2]
GeneIDi9863
KEGGihsa:9863
UCSCiuc003ugx.3 human [Q86UL8-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiMAGI2_HUMAN
AccessioniPrimary (citable) accession number: Q86UL8
Secondary accession number(s): A4D1C1
, A7E2C3, O60434, O60510, Q86UI7, Q9NP44, Q9UDQ5, Q9UDU1
Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 3, 2003
Last sequence update: February 7, 2006
Last modified: May 23, 2018
This is version 159 of the entry and version 3 of the sequence. See complete history.
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

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