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Protein

SH3 and multiple ankyrin repeat domains protein 2

Gene

SHANK2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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.

GO - Molecular functioni

  • GKAP/Homer scaffold activity Source: UniProtKB
  • ionotropic glutamate receptor binding Source: BHF-UCL

GO - Biological processi

  • adult behavior Source: BHF-UCL
  • learning Source: BHF-UCL
  • long term synaptic depression Source: BHF-UCL
  • long-term synaptic potentiation Source: BHF-UCL
  • social behavior Source: BHF-UCL
  • synapse assembly Source: BHF-UCL
  • vocalization behavior Source: BHF-UCL
Complete GO annotation...

Enzyme and pathway databases

BioCyciZFISH:ENSG00000162105-MONOMER.
ReactomeiR-HSA-6794361. Interactions of neurexins and neuroligins at synapses.
SignaLinkiQ9UPX8.

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
Proline-rich synapse-associated protein 1
Gene namesi
Name:SHANK2
Synonyms:CORTBP1, KIAA1022, PROSAP1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 11

Organism-specific databases

HGNCiHGNC:14295. SHANK2.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

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

Pathology & Biotechi

Involvement in diseasei

Autism 17 (AUTS17)1 Publication
Disease susceptibility is associated with variations affecting the gene represented in this entry.
Disease descriptionA complex multifactorial, pervasive developmental disorder characterized by impairments in reciprocal social interaction and communication, restricted and stereotyped patterns of interests and activities, and the presence of developmental abnormalities by 3 years of age. Most individuals with autism also manifest moderate mental retardation.
See also OMIM:613436

Keywords - Diseasei

Autism, Autism spectrum disorder

Organism-specific databases

DisGeNETi22941.
MalaCardsiSHANK2.
MIMi613436. phenotype.
OpenTargetsiENSG00000162105.
Orphaneti106. Autism.
PharmGKBiPA37867.

Polymorphism and mutation databases

BioMutaiSHANK2.
DMDMi254763402.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001746731 – 1470SH3 and multiple ankyrin repeat domains protein 2Add BLAST1470

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei452PhosphoserineBy similarity1
Modified residuei481PhosphothreonineBy similarity1
Modified residuei581PhosphoserineBy similarity1
Modified residuei643PhosphoserineBy similarity1
Modified residuei720PhosphoserineBy similarity1
Modified residuei899PhosphothreonineBy similarity1
Glycosylationi1288O-linked (GlcNAc)By similarity1
Modified residuei1330PhosphoserineBy similarity1
Modified residuei1334PhosphoserineBy similarity1

Keywords - PTMi

Glycoprotein, Phosphoprotein

Proteomic databases

PaxDbiQ9UPX8.
PeptideAtlasiQ9UPX8.
PRIDEiQ9UPX8.

PTM databases

iPTMnetiQ9UPX8.
PhosphoSitePlusiQ9UPX8.

Expressioni

Tissue specificityi

Isoform 3 is present in epithelial colonic cells (at protein level).2 Publications

Gene expression databases

BgeeiENSG00000162105.
CleanExiHS_SHANK2.
ExpressionAtlasiQ9UPX8. baseline and differential.
GenevisibleiQ9UPX8. HS.

Organism-specific databases

HPAiHPA008174.

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).3 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
CRKP461082EBI-1570571,EBI-886
GRB2P629932EBI-1570571,EBI-401755
NCK1P163336EBI-1570571,EBI-389883
PIK3R1P279862EBI-1570571,EBI-79464
PLCG1P191744EBI-1570571,EBI-79387

GO - Molecular functioni

  • GKAP/Homer scaffold activity Source: UniProtKB
  • ionotropic glutamate receptor binding Source: BHF-UCL

Protein-protein interaction databases

BioGridi116598. 16 interactors.
DIPiDIP-52255N.
IntActiQ9UPX8. 16 interactors.
MINTiMINT-2822695.
STRINGi9606.ENSP00000345193.

Structurei

3D structure databases

ProteinModelPortaliQ9UPX8.
SMRiQ9UPX8.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini147 – 206SH3PROSITE-ProRule annotationAdd BLAST60
Domaini247 – 341PDZPROSITE-ProRule annotationAdd BLAST95
Domaini1407 – 1470SAMPROSITE-ProRule annotationAdd BLAST64

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi948 – 954SH3-bindingSequence analysis7

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi509 – 535Pro-richAdd BLAST27

Domaini

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

Sequence similaritiesi

Belongs to the SHANK family.Curated
Contains 1 PDZ (DHR) domain.PROSITE-ProRule annotation
Contains 1 SAM (sterile alpha motif) domain.PROSITE-ProRule annotation
Contains 1 SH3 domain.PROSITE-ProRule annotation

Keywords - Domaini

SH3-binding

Phylogenomic databases

eggNOGiKOG0504. Eukaryota.
KOG4375. Eukaryota.
COG0666. LUCA.
GeneTreeiENSGT00510000046474.
HOGENOMiHOG000293276.
HOVERGENiHBG054027.
InParanoidiQ9UPX8.
KOiK15009.
OMAiTTYNCPK.
OrthoDBiEOG091G00OW.
PhylomeDBiQ9UPX8.

Family and domain databases

Gene3Di1.10.150.50. 1 hit.
2.30.42.10. 1 hit.
InterProiIPR001478. PDZ.
IPR001660. SAM.
IPR013761. SAM/pointed.
IPR011511. SH3_2.
IPR001452. SH3_domain.
[Graphical view]
PfamiPF00595. PDZ. 1 hit.
PF00536. SAM_1. 1 hit.
PF07653. SH3_2. 1 hit.
[Graphical view]
SMARTiSM00228. PDZ. 1 hit.
SM00454. SAM. 1 hit.
SM00326. SH3. 1 hit.
[Graphical view]
SUPFAMiSSF47769. SSF47769. 1 hit.
SSF50044. SSF50044. 1 hit.
SSF50156. SSF50156. 1 hit.
PROSITEiPS50106. PDZ. 1 hit.
PS50105. SAM_DOMAIN. 1 hit.
PS50002. SH3. 1 hit.
[Graphical view]

Sequences (4)i

Sequence statusi: Complete.

This entry describes 4 isoformsi produced by alternative splicing. AlignAdd to basket

Note: Additional isoforms seem to exist.
Isoform 1 (identifier: Q9UPX8-1) [UniParc]FASTAAdd to basket
Also known as: A

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 SNSDNNLNAS
60 70 80 90 100
APDWAVCSTA TSHRSLSPQL LQQMPSKPEG AAKTIGSYVP GPRSRSPSLN
110 120 130 140 150
RLGGAGEDGK RPQPLWHVGS PFALGANKDS LSAFEYPGPK RKLYSAVPGR
160 170 180 190 200
LFVAVKPYQP QVDGEIPLHR GDRVKVLSIG EGGFWEGSAR GHIGWFPAEC
210 220 230 240 250
VEEVQCKPRD SQAETRADRS KKLFRHYTVG SYDSFDTSSD CIIEEKTVVL
260 270 280 290 300
QKKDNEGFGF VLRGAKADTP IEEFTPTPAF PALQYLESVD EGGVAWQAGL
310 320 330 340 350
RTGDFLIEVN NENVVKVGHR QVVNMIRQGG NHLVLKVVTV TRNLDPDDTA
360 370 380 390 400
RKKAPPPPKR APTTALTLRS KSMTSELEEL VDKASVRKKK DKPEEIVPAS
410 420 430 440 450
KPSRAAENMA VEPRVATIKQ RPSSRCFPAG SDMNSVYERQ GIAVMTPTVP
460 470 480 490 500
GSPKAPFLGI PRGTMRRQKS IDSRIFLSGI TEEERQFLAP PMLKFTRSLS
510 520 530 540 550
MPDTSEDIPP PPQSVPPSPP PPSPTTYNCP KSPTPRVYGT IKPAFNQNSA
560 570 580 590 600
AKVSPATRSD TVATMMREKG MYFRRELDRY SLDSEDLYSR NAGPQANFRN
610 620 630 640 650
KRGQMPENPY SEVGKIASKA VYVPAKPARR KGMLVKQSNV EDSPEKTCSI
660 670 680 690 700
PIPTIIVKEP STSSSGKSSQ GSSMEIDPQA PEPPSQLRPD ESLTVSSPFA
710 720 730 740 750
AAIAGAVRDR EKRLEARRNS PAFLSTDLGD EDVGLGPPAP RTRPSMFPEE
760 770 780 790 800
GDFADEDSAE QLSSPMPSAT PREPENHFVG GAEASAPGEA GRPLNSTSKA
810 820 830 840 850
QGPESSPAVP SASSGTAGPG NYVHPLTGRL LDPSSPLALA LSARDRAMKE
860 870 880 890 900
SQQGPKGEAP KADLNKPLYI DTKMRPSLDA GFPTVTRQNT RGPLRRQETE
910 920 930 940 950
NKYETDLGRD RKGDDKKNML IDIMDTSQQK SAGLLMVHTV DATKLDNALQ
960 970 980 990 1000
EEDEKAEVEM KPDSSPSEVP EGVSETEGAL QISAAPEPTT VPGRTIVAVG
1010 1020 1030 1040 1050
SMEEAVILPF RIPPPPLASV DLDEDFIFTE PLPPPLEFAN SFDIPDDRAA
1060 1070 1080 1090 1100
SVPALSDLVK QKKSDTPQSP SLNSSQPTNS ADSKKPASLS NCLPASFLPP
1110 1120 1130 1140 1150
PESFDAVADS GIEEVDSRSS SDHHLETTST ISTVSSISTL SSEGGENVDT
1160 1170 1180 1190 1200
CTVYADGQAF MVDKPPVPPK PKMKPIIHKS NALYQDALVE EDVDSFVIPP
1210 1220 1230 1240 1250
PAPPPPPGSA QPGMAKVLQP RTSKLWGDVT EIKSPILSGP KANVISELNS
1260 1270 1280 1290 1300
ILQQMNREKL AKPGEGLDSP MGAKSASLAP RSPEIMSTIS GTRSTTVTFT
1310 1320 1330 1340 1350
VRPGTSQPIT LQSRPPDYES RTSGTRRAPS PVVSPTEMNK ETLPAPLSAA
1360 1370 1380 1390 1400
TASPSPALSD VFSLPSQPPS GDLFGLNPAG RSRSPSPSIL QQPISNKPFT
1410 1420 1430 1440 1450
TKPVHLWTKP DVADWLESLN LGEHKEAFMD NEIDGSHLPN LQKEDLIDLG
1460 1470
VTRVGHRMNI ERALKQLLDR
Length:1,470
Mass (Da):158,822
Last modified:July 28, 2009 - v3
Checksum:i7322993CB9FE0929
GO
Isoform 2 (identifier: Q9UPX8-2) [UniParc]FASTAAdd to basket
Also known as: C

The sequence of this isoform differs from the canonical sequence as follows:
     1-237: Missing.
     238-238: S → MMMNVPGGGAAAVMMTGYNNGRCPRNSLY
     472-490: DSRIFLSGITEEERQFLAP → GKKCGTPPQKLPLGFQTQP
     491-1470: Missing.

Show »
Length:281
Mass (Da):30,564
Checksum:iBD2ECD1A98B92FF4
GO
Isoform 3 (identifier: Q9UPX8-3) [UniParc]FASTAAdd to basket
Also known as: E

The sequence of this isoform differs from the canonical sequence as follows:
     1-12: MKSLLNAFTKKE → MPRSPTSSED...YIKNHKETDI

Note: Contains 6 ANK repeats at positions 196-226, 230-259, 263-293, 297-326, 330-359, 363-393.
Show »
Length:1,849
Mass (Da):201,261
Checksum:i45550DC5D5701399
GO
Isoform 4 (identifier: Q9UPX8-4) [UniParc]FASTAAdd to basket
Also known as: B

The sequence of this isoform differs from the canonical sequence as follows:
     1-237: Missing.
     238-238: S → MMMNVPGGGAAAVMMTGYNNGRCPRNSLY
     383-389: Missing.

Show »
Length:1,254
Mass (Da):134,931
Checksum:iF9D53FB165A65E0A
GO

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0377931 – 237Missing in isoform 2 and isoform 4. 1 PublicationAdd BLAST237
Alternative sequenceiVSP_0377941 – 12MKSLL…FTKKE → MPRSPTSSEDEMAQSFSDYS VGSESDSSKEETIYDTIRAT AEKPGGARTEESQGNTLVIR VVIHDLQQTKCIRFNPDATV WVAKQRILCTLTQSLKDVLN YGLFQPASNGRDGKFLDEER LLREYPQPVGEGVPSLEFRY KKRVYKQASLDEKQLAKLHT KTNLKKCMDHIQHRLVEKIT KMLDRGLDPNFHDPETGETP LTLAAQLDDSVEVIKALKNG GAHLDFRAKDGMTALHKAAR ARNQVALKTLLELGASPDYK DSYGLTPLYHTAIVGGDPYC CELLLHEHATVCCKDENGWH EIHQACRYGHVQHLEHLLFY GADMSAQNASGNTALHICAL YNQDSCARVLLFRGGNKELK NYNSQTPFQVAIIAGNFELA EYIKNHKETDI in isoform 3. 2 PublicationsAdd BLAST12
Alternative sequenceiVSP_037795238S → MMMNVPGGGAAAVMMTGYNN GRCPRNSLY in isoform 2 and isoform 4. 1 Publication1
Alternative sequenceiVSP_037796383 – 389Missing in isoform 4. Curated7
Alternative sequenceiVSP_037797472 – 490DSRIF…QFLAP → GKKCGTPPQKLPLGFQTQP in isoform 2. 1 PublicationAdd BLAST19
Alternative sequenceiVSP_037798491 – 1470Missing in isoform 2. 1 PublicationAdd BLAST980

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB208025 mRNA. Translation: BAH37016.1.
AB208026 mRNA. Translation: BAH37017.1.
AP000590 Genomic DNA. No translation available.
AP001271 Genomic DNA. No translation available.
AP003783 Genomic DNA. No translation available.
AP005401 Genomic DNA. No translation available.
BC093885 mRNA. Translation: AAH93885.1.
BC112097 mRNA. Translation: AAI12098.1.
DQ152234 mRNA. Translation: AAZ77790.1.
AB028945 mRNA. Translation: BAA82974.1.
AF141901 mRNA. Translation: AAF02496.1.
RefSeqiNP_036441.2. NM_012309.4. [Q9UPX8-3]
NP_573573.2. NM_133266.4.
XP_005277989.1. XM_005277932.3. [Q9UPX8-1]
XP_016872876.1. XM_017017387.1. [Q9UPX8-3]
XP_016872877.1. XM_017017388.1. [Q9UPX8-3]
UniGeneiHs.268726.

Genome annotation databases

EnsembliENST00000409530; ENSP00000387324; ENSG00000162105. [Q9UPX8-2]
ENST00000601538; ENSP00000469689; ENSG00000162105. [Q9UPX8-3]
GeneIDi22941.
KEGGihsa:22941.
UCSCiuc058etm.1. human. [Q9UPX8-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB208025 mRNA. Translation: BAH37016.1.
AB208026 mRNA. Translation: BAH37017.1.
AP000590 Genomic DNA. No translation available.
AP001271 Genomic DNA. No translation available.
AP003783 Genomic DNA. No translation available.
AP005401 Genomic DNA. No translation available.
BC093885 mRNA. Translation: AAH93885.1.
BC112097 mRNA. Translation: AAI12098.1.
DQ152234 mRNA. Translation: AAZ77790.1.
AB028945 mRNA. Translation: BAA82974.1.
AF141901 mRNA. Translation: AAF02496.1.
RefSeqiNP_036441.2. NM_012309.4. [Q9UPX8-3]
NP_573573.2. NM_133266.4.
XP_005277989.1. XM_005277932.3. [Q9UPX8-1]
XP_016872876.1. XM_017017387.1. [Q9UPX8-3]
XP_016872877.1. XM_017017388.1. [Q9UPX8-3]
UniGeneiHs.268726.

3D structure databases

ProteinModelPortaliQ9UPX8.
SMRiQ9UPX8.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi116598. 16 interactors.
DIPiDIP-52255N.
IntActiQ9UPX8. 16 interactors.
MINTiMINT-2822695.
STRINGi9606.ENSP00000345193.

PTM databases

iPTMnetiQ9UPX8.
PhosphoSitePlusiQ9UPX8.

Polymorphism and mutation databases

BioMutaiSHANK2.
DMDMi254763402.

Proteomic databases

PaxDbiQ9UPX8.
PeptideAtlasiQ9UPX8.
PRIDEiQ9UPX8.

Protocols and materials databases

DNASUi22941.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000409530; ENSP00000387324; ENSG00000162105. [Q9UPX8-2]
ENST00000601538; ENSP00000469689; ENSG00000162105. [Q9UPX8-3]
GeneIDi22941.
KEGGihsa:22941.
UCSCiuc058etm.1. human. [Q9UPX8-1]

Organism-specific databases

CTDi22941.
DisGeNETi22941.
GeneCardsiSHANK2.
GeneReviewsiSHANK2.
H-InvDBHIX0171293.
HGNCiHGNC:14295. SHANK2.
HPAiHPA008174.
MalaCardsiSHANK2.
MIMi603290. gene.
613436. phenotype.
neXtProtiNX_Q9UPX8.
OpenTargetsiENSG00000162105.
Orphaneti106. Autism.
PharmGKBiPA37867.
HUGEiSearch...
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0504. Eukaryota.
KOG4375. Eukaryota.
COG0666. LUCA.
GeneTreeiENSGT00510000046474.
HOGENOMiHOG000293276.
HOVERGENiHBG054027.
InParanoidiQ9UPX8.
KOiK15009.
OMAiTTYNCPK.
OrthoDBiEOG091G00OW.
PhylomeDBiQ9UPX8.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000162105-MONOMER.
ReactomeiR-HSA-6794361. Interactions of neurexins and neuroligins at synapses.
SignaLinkiQ9UPX8.

Miscellaneous databases

ChiTaRSiSHANK2. human.
GeneWikiiSHANK2.
GenomeRNAii22941.
PROiQ9UPX8.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000162105.
CleanExiHS_SHANK2.
ExpressionAtlasiQ9UPX8. baseline and differential.
GenevisibleiQ9UPX8. HS.

Family and domain databases

Gene3Di1.10.150.50. 1 hit.
2.30.42.10. 1 hit.
InterProiIPR001478. PDZ.
IPR001660. SAM.
IPR013761. SAM/pointed.
IPR011511. SH3_2.
IPR001452. SH3_domain.
[Graphical view]
PfamiPF00595. PDZ. 1 hit.
PF00536. SAM_1. 1 hit.
PF07653. SH3_2. 1 hit.
[Graphical view]
SMARTiSM00228. PDZ. 1 hit.
SM00454. SAM. 1 hit.
SM00326. SH3. 1 hit.
[Graphical view]
SUPFAMiSSF47769. SSF47769. 1 hit.
SSF50044. SSF50044. 1 hit.
SSF50156. SSF50156. 1 hit.
PROSITEiPS50106. PDZ. 1 hit.
PS50105. SAM_DOMAIN. 1 hit.
PS50002. SH3. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiSHAN2_HUMAN
AccessioniPrimary (citable) accession number: Q9UPX8
Secondary accession number(s): C0SPG8
, C0SPG9, Q3Y8G9, Q52LK2, Q9UKP1
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 26, 2002
Last sequence update: July 28, 2009
Last modified: November 30, 2016
This is version 155 of the entry and version 3 of the sequence. [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

Complete proteome, Reference proteome

Documents

  1. Human chromosome 11
    Human chromosome 11: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.