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Protein

SH3 and multiple ankyrin repeat domains protein 2

Gene

Shank2

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Seems to be an adapter protein in the postsynaptic density (PSD) of excitatory synapses that interconnects receptors of the postsynaptic membrane including NMDA-type and metabotropic glutamate receptors, and the actin-based cytoskeleton. May play a role in the structural and functional organization of the dendritic spine and synaptic junction (By similarity).By similarity

GO - Molecular functioni

  • ionotropic glutamate receptor binding Source: BHF-UCL
  • SH3 domain binding Source: UniProtKB-KW

GO - Biological processi

  • adult behavior Source: BHF-UCL
  • exploration behavior Source: BHF-UCL
  • learning Source: BHF-UCL
  • long term synaptic depression Source: BHF-UCL
  • long-term synaptic potentiation Source: BHF-UCL
  • memory Source: BHF-UCL
  • positive regulation of synaptic transmission, glutamatergic Source: CACAO
  • social behavior Source: BHF-UCL
  • synapse assembly Source: BHF-UCL
  • vocalization behavior Source: BHF-UCL

Enzyme and pathway databases

ReactomeiR-MMU-6794361 Neurexins and neuroligins

Names & Taxonomyi

Protein namesi
Recommended name:
SH3 and multiple ankyrin repeat domains protein 2
Short name:
Shank2
Alternative name(s):
Cortactin-binding protein 1
Short name:
CortBP1
Gene namesi
Name:Shank2
Synonyms:Cortbp1, Kiaa1022
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 7

Organism-specific databases

MGIiMGI:2671987 Shank2

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, Cell projection, Cytoplasm, Membrane, Postsynaptic cell membrane, Synapse

Pathology & Biotechi

Disruption phenotypei

Mutants are viable, but with reduced body weight and a lower survival rate compared to their wild-type littermates. They are extremely hiperactive and display profound autistic-like behavioral alterations including repetitive grooming as well as abnormalities in vocal and social behaviors. Mutants exhibit fewer dendritic spines and show reduced basal synaptic transmission, a reduced frequency of miniature excitatory postsynaptic currents and enhanced NMDA receptor-mediated excitatory currents at the physiological level. They also show a brain-region-specific up-regulation of ionotropic glutamate receptors and increased levels of SHANK3.1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002477601 – 1476SH3 and multiple ankyrin repeat domains protein 2Add BLAST1476

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei456PhosphoserineCombined sources1
Modified residuei485PhosphothreonineCombined sources1
Modified residuei586PhosphoserineCombined sources1
Modified residuei724PhosphoserineCombined sources1
Modified residuei903PhosphothreonineCombined sources1
Glycosylationi1292O-linked (GlcNAc) threonine1 Publication1
Modified residuei1334PhosphoserineCombined sources1
Modified residuei1338PhosphoserineCombined sources1
Isoform 3 (identifier: Q80Z38-3)
Modified residuei162PhosphoserineCombined sources1
Isoform 2 (identifier: Q80Z38-2)
Modified residuei372PhosphoserineCombined sources1

Keywords - PTMi

Glycoprotein, Phosphoprotein

Proteomic databases

PaxDbiQ80Z38
PeptideAtlasiQ80Z38
PRIDEiQ80Z38

PTM databases

iPTMnetiQ80Z38
PhosphoSitePlusiQ80Z38

Expressioni

Tissue specificityi

Detected in brain (at protein level), where it is highly expressed in Purkinje cells.3 Publications

Gene expression databases

BgeeiENSMUSG00000037541
CleanExiMM_SHANK2
ExpressionAtlasiQ80Z38 baseline and differential

Interactioni

Subunit structurei

Is part of a complex with DLG4/PSD-95 and DLGAP1/GKAP. Interacts with CTTN/cortactin SH3 domain, DLGAP1/GKAP and alpha-latrotoxin receptor 1. Interacts with DNM2, DBNL, GRID2, BAIAP2, SLC9A3, PLCB3 and CFTR. Interacts (via proline-rich region) with PDE4D. Interacts with ABI1 (via SH3 domain).2 Publications

GO - Molecular functioni

  • ionotropic glutamate receptor binding Source: BHF-UCL
  • SH3 domain binding Source: UniProtKB-KW

Protein-protein interaction databases

BioGridi229144, 9 interactors
CORUMiQ80Z38
IntActiQ80Z38, 11 interactors
MINTiQ80Z38
STRINGi10090.ENSMUSP00000095542

Structurei

3D structure databases

ProteinModelPortaliQ80Z38
SMRiQ80Z38
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini147 – 206SH3PROSITE-ProRule annotationAdd BLAST60
Domaini247 – 341PDZPROSITE-ProRule annotationAdd BLAST95
Domaini1413 – 1476SAMPROSITE-ProRule annotationAdd BLAST64

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi1169 – 1175SH3-bindingSequence analysis7

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi24 – 27Poly-Arg4
Compositional biasi355 – 358Poly-Pro4
Compositional biasi513 – 560Pro-richAdd BLAST48
Compositional biasi1017 – 1020Poly-Pro4
Compositional biasi1169 – 1211Pro-richAdd BLAST43
Compositional biasi1348 – 1353Poly-Pro6

Domaini

The PDZ domain is required for interaction with GRID2, PLCB3, SLC9A3 and CFTR.

Sequence similaritiesi

Belongs to the SHANK family.Curated

Keywords - Domaini

SH3 domain, SH3-binding

Phylogenomic databases

eggNOGiKOG0504 Eukaryota
COG0666 LUCA
GeneTreeiENSGT00510000046474
HOGENOMiHOG000293276
HOVERGENiHBG054027
InParanoidiQ80Z38
KOiK15009

Family and domain databases

InterProiView protein in InterPro
IPR001478 PDZ
IPR036034 PDZ_sf
IPR001660 SAM
IPR013761 SAM/pointed_sf
IPR036028 SH3-like_dom_sf
IPR001452 SH3_domain
PfamiView protein in Pfam
PF00595 PDZ, 1 hit
PF00536 SAM_1, 1 hit
PF07653 SH3_2, 1 hit
SMARTiView protein in SMART
SM00228 PDZ, 1 hit
SM00454 SAM, 1 hit
SM00326 SH3, 1 hit
SUPFAMiSSF47769 SSF47769, 1 hit
SSF50044 SSF50044, 1 hit
SSF50156 SSF50156, 1 hit
PROSITEiView protein in PROSITE
PS50106 PDZ, 1 hit
PS50105 SAM_DOMAIN, 1 hit
PS50002 SH3, 1 hit

Sequences (3)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q80Z38-1) [UniParc]FASTAAdd to basket
Also known as: E

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
MKSLLNAFTK KEVPFREAPA YSNRRRRPPN TLAAPRVLLR SNSDNNLNAG
60 70 80 90 100
APEWAVCSAA TSHRSLSPQL LQQTPSKPDG ATKSLGSYTP GPRSRSPSLN
110 120 130 140 150
RLGGTAEDGK RTQPHWHVGS PFTPGANKDS LSTFEYPGPR RKLYSAVPGR
160 170 180 190 200
LFVAVKPYQP QVDGEIPLHR GDRVKVLSIG EGGFWEGSAR GHIGWFPAEC
210 220 230 240 250
VEEVQCKPRD SQAETRADRS KKLFRHYTVG SYDSFDAASD CIIEDKTVVL
260 270 280 290 300
QKKDNEGFGF VLRGAKADTP IEEFTPTPAF PALQYLESVD EGGVAWQAGL
310 320 330 340 350
RTGDFLIEVN NENVVKVGHR QVVNMIRQGG NHLILKVVTV TRNLDPDDTA
360 370 380 390 400
RKKAPPPPKR APTTALTLRS KSMTAELEEL GLSLVDKASV RKKKDKPEEI
410 420 430 440 450
VPASKPSRTA ENVAIESRVA TIKQRPTSRC FPAASDVNSV YERQGIAVMT
460 470 480 490 500
PTVPGSPKGP FLGLPRGTMR RQKSIDSRIF LSGITEEERQ FLAPPMLKFT
510 520 530 540 550
RSLSMPDTSE DIPPPPQSVP PSPPPPSPTT YNCPRSPTPR VYGTIKPAFN
560 570 580 590 600
QNPVVAKVPP ATRSDTVATM MREKGMFYRR ELDRFSLDSE DVYSRSPAPQ
610 620 630 640 650
AAFRTKRGQM PENPYSEVGK IASKAVYVPA KPARRKGVLV KQSNVEDSPE
660 670 680 690 700
KTCSIPIPTI IVKEPSTSSS GKSSQGSSME IDPQATEPGQ LRPDDSLTVS
710 720 730 740 750
SPFAAAIAGA VRDREKRLEA RRNSPAFLST DLGDEDVGLG PPAPRMQASK
760 770 780 790 800
FPEEGGFGDE DETEQPLLPT PGAAPRELEN HFLGGGEAGA QGEAGGPLSS
810 820 830 840 850
TSKAKGPESG PAAPLKSSSP AGPENYVHPL TGRLLDPSSP LALALSARDR
860 870 880 890 900
AMQESQQGHK GEAPKADLNK PLYIDTKMRP SVESGFPPVT RQNTRGPLRR
910 920 930 940 950
QETENKYETD LGKDRRADDK KNMLINIVDT AQQKSAGLLM VHTVDVPMAG
960 970 980 990 1000
PPLEEEEDRE DGDTKPDHSP STVPEGVPKT EGALQISAAP EPAVAPGRTI
1010 1020 1030 1040 1050
VAAGSVEEAV ILPFRIPPPP LASVDLDEDF LFTEPLPPPL EFANSFDIPD
1060 1070 1080 1090 1100
DRAASVPALA DLVKQKKNDT SQPPTLNSSQ PANSTDSKKP AGISNCLPSS
1110 1120 1130 1140 1150
FLPPPESFDA VTDSGIEEVD SRSSSDHHLE TTSTISTVSS ISTLSSEGGE
1160 1170 1180 1190 1200
SMDTCTVYAD GQAFVVDKPP VPPKPKMKPI VHKSNALYQD TLPEEDTDGF
1210 1220 1230 1240 1250
VIPPPAPPPP PGSAQAGVAK VIQPRTSKLW GDVPEVKSPI LSGPKANVIS
1260 1270 1280 1290 1300
ELNSILQQMN RGKSVKPGEG LELPVGAKSA NLAPRSPEVM STVSGTRSTT
1310 1320 1330 1340 1350
VTFTVRPGTS QPITLQSRPP DYESRTSGPR RAPSPVVSPT ELSKEILPTP
1360 1370 1380 1390 1400
PPPSATAASP SPTLSDVFSL PSQSPAGDLF GLNPAGRSRS PSPSILQQPI
1410 1420 1430 1440 1450
SNKPFTTKPV HLWTKPDVAD WLESLNLGEH KETFMDNEID GSHLPNLQKE
1460 1470
DLIDLGVTRV GHRMNIERAL KQLLDR
Length:1,476
Mass (Da):158,969
Last modified:July 27, 2011 - v2
Checksum:i0B5B0EBDFD6BAAA7
GO
Isoform 2 (identifier: Q80Z38-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     380-383: Missing.

Show »
Length:1,472
Mass (Da):158,599
Checksum:i0BBCF1E8E351834C
GO
Isoform 3 (identifier: Q80Z38-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-210: Missing.
     211-238: SQAETRADRSKKLFRHYTVGSYDSFDAA → MMSVPGGGAATVMMTGYNNGRYPRNSLY
     380-383: Missing.

Show »
Length:1,262
Mass (Da):135,412
Checksum:iBF3B96EFA165D7B9
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti1071S → P in BAC58120 (PubMed:15207857).Curated1
Sequence conflicti1071S → P in BAD90424 (Ref. 5) Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0416141 – 210Missing in isoform 3. 1 PublicationAdd BLAST210
Alternative sequenceiVSP_041615211 – 238SQAET…SFDAA → MMSVPGGGAATVMMTGYNNG RYPRNSLY in isoform 3. 1 PublicationAdd BLAST28
Alternative sequenceiVSP_020040380 – 383Missing in isoform 2 and isoform 3. 2 Publications4

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB099695 mRNA Translation: BAC58120.1
AC124520 Genomic DNA No translation available.
AC127546 Genomic DNA No translation available.
AC140268 Genomic DNA No translation available.
AC152166 Genomic DNA No translation available.
BC167171 mRNA Translation: AAI67171.1
AK139360 mRNA Translation: BAE23976.1
AK220363 mRNA Translation: BAD90424.1
CCDSiCCDS40201.1 [Q80Z38-3]
CCDS85484.1 [Q80Z38-2]
RefSeqiNP_001074839.2, NM_001081370.2
NP_001106844.2, NM_001113373.2
XP_006508596.1, XM_006508533.1 [Q80Z38-1]
UniGeneiMm.483624

Genome annotation databases

EnsembliENSMUST00000105900; ENSMUSP00000101520; ENSMUSG00000037541 [Q80Z38-2]
ENSMUST00000146006; ENSMUSP00000146440; ENSMUSG00000037541 [Q80Z38-3]
GeneIDi210274
KEGGimmu:210274
UCSCiuc009kqe.2 mouse [Q80Z38-2]
uc009kqf.1 mouse [Q80Z38-3]
uc009kqg.1 mouse [Q80Z38-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiSHAN2_MOUSE
AccessioniPrimary (citable) accession number: Q80Z38
Secondary accession number(s): E9QPH7, Q3UTK4, Q5DU07
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 25, 2006
Last sequence update: July 27, 2011
Last modified: May 23, 2018
This is version 119 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

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