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Q9UPX8 (SHAN2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 133. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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 names
Name:SHANK2
Synonyms:CORTBP1, KIAA1022, PROSAP1
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length1470 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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.

Subunit structure

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). Ref.8 Ref.9 Ref.10

Subcellular location

Apical cell membrane By similarity. Cytoplasm By similarity. Cell junctionsynapse By similarity. Cell junctionsynapsepostsynaptic cell membranepostsynaptic density By similarity. Cell projectiongrowth cone By similarity. Cell projectiondendritic spine By similarity. Note: Colocalizes with cortactin in growth cones in differentiating hippocampal neurons. Colocalized with PDE4D to the apical membrane of colonic crypt cells By similarity.

Tissue specificity

Isoform 3 is present in epithelial colonic cells (at protein level). Ref.4 Ref.10

Domain

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

Involvement in disease

Autism 17 (AUTS17) [MIM:613436]: A 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.
Note: Disease susceptibility is associated with variations affecting the gene represented in this entry. Ref.11

Sequence similarities

Belongs to the SHANK family.

Contains 1 PDZ (DHR) domain.

Contains 1 SAM (sterile alpha motif) domain.

Contains 1 SH3 domain.

Ontologies

Keywords
   Cellular componentCell junction
Cell membrane
Cell projection
Cytoplasm
Membrane
Postsynaptic cell membrane
Synapse
   Coding sequence diversityAlternative splicing
   DomainSH3-binding
   PTMGlycoprotein
Phosphoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processadult behavior

Inferred from mutant phenotype Ref.11. Source: BHF-UCL

learning

Inferred from mutant phenotype Ref.11. Source: BHF-UCL

long term synaptic depression

Inferred from sequence or structural similarity PubMed 22699620. Source: BHF-UCL

long-term synaptic potentiation

Inferred from sequence or structural similarity PubMed 22699620. Source: BHF-UCL

social behavior

Inferred from mutant phenotype Ref.11. Source: BHF-UCL

synapse assembly

Inferred from sequence or structural similarity PubMed 22699620. Source: BHF-UCL

vocalization behavior

Inferred from mutant phenotype Ref.11. Source: BHF-UCL

   Cellular_componentapical plasma membrane

Inferred from sequence or structural similarity. Source: BHF-UCL

brush border membrane

Inferred from sequence or structural similarity. Source: BHF-UCL

cell junction

Inferred from electronic annotation. Source: UniProtKB-KW

ciliary membrane

Inferred from sequence or structural similarity. Source: BHF-UCL

cytoplasm

Inferred from electronic annotation. Source: UniProtKB-SubCell

dendritic spine

Inferred from sequence or structural similarity. Source: BHF-UCL

growth cone

Inferred from sequence or structural similarity. Source: BHF-UCL

neuron projection

Inferred from sequence or structural similarity. Source: BHF-UCL

neuronal cell body

Inferred from sequence or structural similarity. Source: BHF-UCL

photoreceptor inner segment

Inferred from sequence or structural similarity. Source: BHF-UCL

photoreceptor outer segment

Inferred from sequence or structural similarity. Source: BHF-UCL

plasma membrane

Inferred from sequence or structural similarity. Source: BHF-UCL

postsynaptic density

Inferred from sequence or structural similarity. Source: BHF-UCL

postsynaptic membrane

Inferred from electronic annotation. Source: UniProtKB-KW

   Molecular_functionGKAP/Homer scaffold activity

Non-traceable author statement Ref.6. Source: UniProtKB

ionotropic glutamate receptor binding

Inferred from sequence or structural similarity. Source: BHF-UCL

protein binding

Inferred from physical interaction Ref.8. Source: UniProtKB

Complete GO annotation...

Alternative products

This entry describes 4 isoforms produced by alternative splicing. [Align] [Select]

Note: Additional isoforms seem to exist.
Isoform 1 (identifier: Q9UPX8-1)

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.
Isoform 2 (identifier: Q9UPX8-2)

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.
Isoform 3 (identifier: Q9UPX8-3)

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.
Isoform 4 (identifier: Q9UPX8-4)

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.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 14701470SH3 and multiple ankyrin repeat domains protein 2
PRO_0000174673

Regions

Domain147 – 20660SH3
Domain247 – 34195PDZ
Domain1407 – 147064SAM
Motif948 – 9547SH3-binding Potential
Compositional bias509 – 53527Pro-rich

Amino acid modifications

Modified residue5811Phosphoserine By similarity
Modified residue8991Phosphothreonine By similarity
Glycosylation12881O-linked (GlcNAc) By similarity

Natural variations

Alternative sequence1 – 237237Missing in isoform 2 and isoform 4.
VSP_037793
Alternative sequence1 – 1212MKSLL…FTKKE → MPRSPTSSEDEMAQSFSDYS VGSESDSSKEETIYDTIRAT AEKPGGARTEESQGNTLVIR VVIHDLQQTKCIRFNPDATV WVAKQRILCTLTQSLKDVLN YGLFQPASNGRDGKFLDEER LLREYPQPVGEGVPSLEFRY KKRVYKQASLDEKQLAKLHT KTNLKKCMDHIQHRLVEKIT KMLDRGLDPNFHDPETGETP LTLAAQLDDSVEVIKALKNG GAHLDFRAKDGMTALHKAAR ARNQVALKTLLELGASPDYK DSYGLTPLYHTAIVGGDPYC CELLLHEHATVCCKDENGWH EIHQACRYGHVQHLEHLLFY GADMSAQNASGNTALHICAL YNQDSCARVLLFRGGNKELK NYNSQTPFQVAIIAGNFELA EYIKNHKETDI in isoform 3.
VSP_037794
Alternative sequence2381S → MMMNVPGGGAAAVMMTGYNN GRCPRNSLY in isoform 2 and isoform 4.
VSP_037795
Alternative sequence383 – 3897Missing in isoform 4.
VSP_037796
Alternative sequence472 – 49019DSRIF…QFLAP → GKKCGTPPQKLPLGFQTQP in isoform 2.
VSP_037797
Alternative sequence491 – 1470980Missing in isoform 2.
VSP_037798

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 (A) [UniParc].

Last modified July 28, 2009. Version 3.
Checksum: 7322993CB9FE0929

FASTA1,470158,822
        10         20         30         40         50         60 
MKSLLNAFTK KEVPFREAPA YSNRRRRPPN TLAAPRVLLR SNSDNNLNAS APDWAVCSTA 

        70         80         90        100        110        120 
TSHRSLSPQL LQQMPSKPEG AAKTIGSYVP GPRSRSPSLN RLGGAGEDGK RPQPLWHVGS 

       130        140        150        160        170        180 
PFALGANKDS LSAFEYPGPK RKLYSAVPGR LFVAVKPYQP QVDGEIPLHR GDRVKVLSIG 

       190        200        210        220        230        240 
EGGFWEGSAR GHIGWFPAEC VEEVQCKPRD SQAETRADRS KKLFRHYTVG SYDSFDTSSD 

       250        260        270        280        290        300 
CIIEEKTVVL QKKDNEGFGF VLRGAKADTP IEEFTPTPAF PALQYLESVD EGGVAWQAGL 

       310        320        330        340        350        360 
RTGDFLIEVN NENVVKVGHR QVVNMIRQGG NHLVLKVVTV TRNLDPDDTA RKKAPPPPKR 

       370        380        390        400        410        420 
APTTALTLRS KSMTSELEEL VDKASVRKKK DKPEEIVPAS KPSRAAENMA VEPRVATIKQ 

       430        440        450        460        470        480 
RPSSRCFPAG SDMNSVYERQ GIAVMTPTVP GSPKAPFLGI PRGTMRRQKS IDSRIFLSGI 

       490        500        510        520        530        540 
TEEERQFLAP PMLKFTRSLS MPDTSEDIPP PPQSVPPSPP PPSPTTYNCP KSPTPRVYGT 

       550        560        570        580        590        600 
IKPAFNQNSA AKVSPATRSD TVATMMREKG MYFRRELDRY SLDSEDLYSR NAGPQANFRN 

       610        620        630        640        650        660 
KRGQMPENPY SEVGKIASKA VYVPAKPARR KGMLVKQSNV EDSPEKTCSI PIPTIIVKEP 

       670        680        690        700        710        720 
STSSSGKSSQ GSSMEIDPQA PEPPSQLRPD ESLTVSSPFA AAIAGAVRDR EKRLEARRNS 

       730        740        750        760        770        780 
PAFLSTDLGD EDVGLGPPAP RTRPSMFPEE GDFADEDSAE QLSSPMPSAT PREPENHFVG 

       790        800        810        820        830        840 
GAEASAPGEA GRPLNSTSKA QGPESSPAVP SASSGTAGPG NYVHPLTGRL LDPSSPLALA 

       850        860        870        880        890        900 
LSARDRAMKE SQQGPKGEAP KADLNKPLYI DTKMRPSLDA GFPTVTRQNT RGPLRRQETE 

       910        920        930        940        950        960 
NKYETDLGRD RKGDDKKNML IDIMDTSQQK SAGLLMVHTV DATKLDNALQ EEDEKAEVEM 

       970        980        990       1000       1010       1020 
KPDSSPSEVP EGVSETEGAL QISAAPEPTT VPGRTIVAVG SMEEAVILPF RIPPPPLASV 

      1030       1040       1050       1060       1070       1080 
DLDEDFIFTE PLPPPLEFAN SFDIPDDRAA SVPALSDLVK QKKSDTPQSP SLNSSQPTNS 

      1090       1100       1110       1120       1130       1140 
ADSKKPASLS NCLPASFLPP PESFDAVADS GIEEVDSRSS SDHHLETTST ISTVSSISTL 

      1150       1160       1170       1180       1190       1200 
SSEGGENVDT CTVYADGQAF MVDKPPVPPK PKMKPIIHKS NALYQDALVE EDVDSFVIPP 

      1210       1220       1230       1240       1250       1260 
PAPPPPPGSA QPGMAKVLQP RTSKLWGDVT EIKSPILSGP KANVISELNS ILQQMNREKL 

      1270       1280       1290       1300       1310       1320 
AKPGEGLDSP MGAKSASLAP RSPEIMSTIS GTRSTTVTFT VRPGTSQPIT LQSRPPDYES 

      1330       1340       1350       1360       1370       1380 
RTSGTRRAPS PVVSPTEMNK ETLPAPLSAA TASPSPALSD VFSLPSQPPS GDLFGLNPAG 

      1390       1400       1410       1420       1430       1440 
RSRSPSPSIL QQPISNKPFT TKPVHLWTKP DVADWLESLN LGEHKEAFMD NEIDGSHLPN 

      1450       1460       1470 
LQKEDLIDLG VTRVGHRMNI ERALKQLLDR 

« Hide

Isoform 2 (C) [UniParc].

Checksum: BD2ECD1A98B92FF4
Show »

FASTA28130,564
Isoform 3 (E) [UniParc].

Checksum: 45550DC5D5701399
Show »

FASTA1,849201,261
Isoform 4 (B) [UniParc].

Checksum: F9D53FB165A65E0A
Show »

FASTA1,254134,931

References

« Hide 'large scale' references
[1]"A molecular scaffolding protein, Shank2, is a potent tumor suppressor in esophageal squamous cell carcinoma."
Akahane T., Hosoda F., Arai Y., Fujisawa N., Kitabayashi I., Ohta T., Aoyagi K., Sasaki H., Nakanishi Y., Hirohashi S., Ohki M.
Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 3).
[2]"Human chromosome 11 DNA sequence and analysis including novel gene identification."
Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K., Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T., Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G. expand/collapse author list , Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C., Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A., Hattori M., Rogers J., Lander E.S., Sakaki Y.
Nature 440:497-500(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]"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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
Tissue: Brain.
[4]"Shank2 associates with and regulates Na+/H+ exchanger 3."
Han W., Kim K.H., Jo M.J., Lee J.H., Yang J., Doctor R.B., Moe O.W., Lee J., Kim E., Lee M.G.
J. Biol. Chem. 281:1461-1469(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1-328 (ISOFORM 3), TISSUE SPECIFICITY.
[5]"Prediction of the coding sequences of unidentified human genes. XIV. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro."
Kikuno R., Nagase T., Ishikawa K., Hirosawa M., Miyajima N., Tanaka A., Kotani H., Nomura N., Ohara O.
DNA Res. 6:197-205(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: PARTIAL NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 4).
Tissue: Brain.
[6]"Characterization of the shank family of synaptic proteins. Multiple genes, alternative splicing, and differential expression in brain and development."
Lim S., Naisbitt S., Yoon J., Hwang J.-I., Suh P.-G., Sheng M., Kim E.
J. Biol. Chem. 274:29510-29518(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: PARTIAL NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
[7]"The Shank family of scaffold proteins."
Sheng M., Kim E.
J. Cell Sci. 113:1851-1856(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW.
[8]"Dynamin isoform-specific interaction with the shank/ProSAP scaffolding proteins of the postsynaptic density and actin cytoskeleton."
Okamoto P.M., Gamby C., Wells D., Fallon J., Vallee R.B.
J. Biol. Chem. 276:48458-48465(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH DNM2.
[9]"The insulin receptor substrate IRSp53 links postsynaptic shank1 to the small G-protein cdc42."
Soltau M., Richter D., Kreienkamp H.-J.
Mol. Cell. Neurosci. 21:575-583(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH BAIAP2.
[10]"Dynamic regulation of cystic fibrosis transmembrane conductance regulator by competitive interactions of molecular adaptors."
Lee J.H., Richter W., Namkung W., Kim K.H., Kim E., Conti M., Lee M.G.
J. Biol. Chem. 282:10414-10422(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH PDE4D, TISSUE SPECIFICITY.
[11]"Mutations in the SHANK2 synaptic scaffolding gene in autism spectrum disorder and mental retardation."
Berkel S., Marshall C.R., Weiss B., Howe J., Roeth R., Moog U., Endris V., Roberts W., Szatmari P., Pinto D., Bonin M., Riess A., Engels H., Sprengel R., Scherer S.W., Rappold G.A.
Nat. Genet. 42:489-491(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: INVOLVEMENT IN AUTS17.
[12]"System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation."
Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.
Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
RefSeqNP_036441.2. NM_012309.4. [Q9UPX8-3]
NP_573573.2. NM_133266.4.
XP_005277987.1. XM_005277930.1. [Q9UPX8-3]
XP_005277989.1. XM_005277932.1. [Q9UPX8-1]
UniGeneHs.268726.

3D structure databases

ProteinModelPortalQ9UPX8.
SMRQ9UPX8. Positions 148-205, 240-343, 1404-1467.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid116598. 15 interactions.
DIPDIP-52255N.
IntActQ9UPX8. 10 interactions.
MINTMINT-2822695.
STRING9606.ENSP00000345193.

Polymorphism databases

DMDM254763402.

Proteomic databases

MaxQBQ9UPX8.
PaxDbQ9UPX8.
PRIDEQ9UPX8.

Protocols and materials databases

DNASU22941.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000423696; ENSP00000394536; ENSG00000162105. [Q9UPX8-1]
ENST00000449833; ENSP00000399423; ENSG00000162105. [Q9UPX8-4]
GeneID22941.
KEGGhsa:22941.
UCSCuc001opz.3. human. [Q9UPX8-4]
uc001oqc.3. human. [Q9UPX8-3]

Organism-specific databases

CTD22941.
GeneCardsGC11M070313.
GeneReviewsSHANK2.
H-InvDBHIX0171293.
HGNCHGNC:14295. SHANK2.
HPAHPA008174.
MIM603290. gene.
613436. phenotype.
neXtProtNX_Q9UPX8.
Orphanet106. Autism.
PharmGKBPA37867.
HUGESearch...
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG265246.
HOGENOMHOG000293276.
HOVERGENHBG054027.
KOK15009.
PhylomeDBQ9UPX8.

Enzyme and pathway databases

SignaLinkQ9UPX8.

Gene expression databases

ArrayExpressQ9UPX8.
BgeeQ9UPX8.
CleanExHS_SHANK2.
GenevestigatorQ9UPX8.

Family and domain databases

Gene3D1.10.150.50. 1 hit.
2.30.42.10. 1 hit.
InterProIPR001478. PDZ.
IPR001660. SAM.
IPR013761. SAM/pointed.
IPR021129. SAM_type1.
IPR011511. SH3_2.
IPR001452. SH3_domain.
[Graphical view]
PfamPF00595. PDZ. 1 hit.
PF00536. SAM_1. 1 hit.
PF07653. SH3_2. 1 hit.
[Graphical view]
SMARTSM00228. PDZ. 1 hit.
SM00454. SAM. 1 hit.
SM00326. SH3. 1 hit.
[Graphical view]
SUPFAMSSF47769. SSF47769. 1 hit.
SSF50044. SSF50044. 1 hit.
SSF50156. SSF50156. 1 hit.
PROSITEPS50106. PDZ. 1 hit.
PS50105. SAM_DOMAIN. 1 hit.
PS50002. SH3. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiSHANK2.
GenomeRNAi22941.
NextBio43691.
PROQ9UPX8.
SOURCESearch...

Entry information

Entry nameSHAN2_HUMAN
AccessionPrimary (citable) accession number: Q9UPX8
Secondary accession number(s): C0SPG8 expand/collapse secondary AC list , C0SPG9, Q3Y8G9, Q52LK2, Q9UKP1
Entry history
Integrated into UniProtKB/Swiss-Prot: July 26, 2002
Last sequence update: July 28, 2009
Last modified: July 9, 2014
This is version 133 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human chromosome 11

Human chromosome 11: entries, gene names and cross-references to MIM