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Q9BYB0 (SHAN3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 118. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | 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 3

Short name=Shank3
Alternative name(s):
Proline-rich synapse-associated protein 2
Short name=ProSAP2
Gene names
Name:SHANK3
Synonyms:KIAA1650, PROSAP2, PSAP2
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length1731 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Major scaffold postsynaptic density protein which interacts with multiple proteins and complexes to orchestrate the dendritic spine and synapse formation, maturation and maintenance. Interconnects receptors of the postsynaptic membrane including NMDA-type and metabotropic glutamate receptors via complexes with GKAP/PSD-95 and HOMER, respectively, and the actin-based cytoskeleton. Plays a role in the structural and functional organization of the dendritic spine and synaptic junction through the interaction with Arp2/3 and WAVE1 complex as well as the promotion of the F-actin clusters. By way of this control of actin dynamics, participates in the regulation of developing neurons growth cone motility and the NMDA receptor-signaling. Also modulates GRIA1 exocytosis and GRM5/MGLUR5 expression and signaling to control the AMPA and metabotropic glutamate receptor-mediated synaptic transmission and plasticity. May be required at an early stage of synapse formation and be inhibited by IGF1 to promote synapse maturation. Ref.14

Subunit structure

May homomultimerize via its SAM domain. Interacts with BAIAP2, DBNL and SLC17A7/VGLUT1. Interacts with DLGAP1/GKAP, GRM1/MGLUR1, GRM5/MGLUR5 and LZTS3 C-termini via its PDZ domain. Interacts with ABI1, HOMER1, HOMER2, HOMER3 and CTTN/cortactin SH3 domain. Is part of a complex with DLG4/PSD-95 and DLGAP1/GKAP. Interacts (via PDZ domain) with the GRIA1 subunit of the AMPA receptor (via PDZ-binding motif). Interacts with WASF1 and CYFIP2; the interactions mediate the association of SHANK3 with the WAVE1 complex. Interacts with ARPC2; the interaction probably mediates the association of SHANK3 with the Arp2/3 complex. Interacts (via ANK repeats) with SHARPIN and SPTAN1. Interacts (via PDZ domain) with ARHGAP44 (probably via PDZ-binding motif); the interaction takes place in dendritic spines and promotes GRIA1 exocytosis By similarity. Ref.10

Subcellular location

Cytoplasm. Cell junctionsynapsepostsynaptic cell membranepostsynaptic density. Cell projectiondendritic spine By similarity. Note: In neuronal cells, extends into the region subjacent to the postsynaptic density (PSD) By similarity. Ref.14

Tissue specificity

Expressed in the cerebral cortex and the cerebellum.

Domain

In isoform 1, the N-terminal region preceding the ANK repeats interacts with the 6 ANK repeats in an intramolecular manner, thereby restricting access to ligands, such as SHARPIN and SPTAN1 By similarity.

Involvement in disease

A chromosomal aberration involving SHANK3 is found in patients with chromosome 22q13.3 deletion syndrome. Translocation t(12;22)(q24.1;q13.3) with APPL2/DIP13B.

Defects in SHANK3 are associated with neuropsychiatric disorders such as autism spectrum disorders (ASD), bipolar affective disorders and early dementia onset. ASD are characterized by impairments in reciprocal social interaction and communication as well as restricted and stereotyped patterns of interest and activities. ASD include forms with moderate to severe cognitive impairment and milder forms with higher cognitive ability (Asperger syndrome). Gene duplication is associated with hyperkinetic neuropsychiatric disorders (Ref.13) such as hyperactivity, auditory overstimulation, epilepsy and bipolar affective disorders, among others.

Phelan-McDermid syndrome (PHEDE) [MIM:606232]: A developmental disorder with variable features. Common features include neonatal hypotonia, global developmental delay, normal to accelerated growth, absent to severely delayed speech, autistic behavior, and minor dysmorphic features.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.12 Ref.14 Ref.18

Schizophrenia 15 (SCZD15) [MIM:613950]: A complex, multifactorial psychotic disorder or group of disorders characterized by disturbances in the form and content of thought (e.g. delusions, hallucinations), in mood (e.g. inappropriate affect), in sense of self and relationship to the external world (e.g. loss of ego boundaries, withdrawal), and in behavior (e.g bizarre or apparently purposeless behavior). Although it affects emotions, it is distinguished from mood disorders in which such disturbances are primary. Similarly, there may be mild impairment of cognitive function, and it is distinguished from the dementias in which disturbed cognitive function is considered primary. Some patients manifest schizophrenic as well as bipolar disorder symptoms and are often given the diagnosis of schizoaffective disorder.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.17

Sequence similarities

Contains 6 ANK repeats.

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 promoter usage
Chromosomal rearrangement
Polymorphism
   DiseaseDisease mutation
Schizophrenia
   DomainANK repeat
Coiled coil
Repeat
SH3 domain
SH3-binding
   LigandActin-binding
   PTMPhosphoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processMAPK cascade

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

N-methyl-D-aspartate receptor clustering

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

adult behavior

Inferred from mutant phenotype Ref.16PubMed 21378602. Source: BHF-UCL

alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate selective glutamate receptor clustering

Inferred from sequence or structural similarity PubMed 21795692. Source: BHF-UCL

brain morphogenesis

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

dendritic spine morphogenesis

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

guanylate kinase-associated protein clustering

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

learning

Inferred from mutant phenotype Ref.16PubMed 21378602. Source: BHF-UCL

memory

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

negative regulation of actin filament bundle assembly

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

negative regulation of cell volume

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

positive regulation of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate selective glutamate receptor activity

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

positive regulation of dendritic spine development

Inferred from sequence or structural similarity PubMed 21795692. Source: BHF-UCL

positive regulation of excitatory postsynaptic membrane potential

Inferred from sequence or structural similarity PubMed 21795692. Source: BHF-UCL

positive regulation of glutamate receptor signaling pathway

Inferred from sequence or structural similarity PubMed 21795692. Source: BHF-UCL

positive regulation of long-term neuronal synaptic plasticity

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

positive regulation of synapse structural plasticity

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

positive regulation of synaptic transmission, glutamatergic

Inferred from sequence or structural similarity PubMed 21795692. Source: BHF-UCL

postsynaptic density assembly

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

regulation of dendritic spine morphogenesis

Inferred from sequence or structural similarity PubMed 21795692. Source: BHF-UCL

regulation of long term synaptic depression

Inferred from sequence or structural similarity PubMed 21795692. Source: BHF-UCL

regulation of long-term synaptic potentiation

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

social behavior

Inferred from mutant phenotype Ref.16PubMed 21378602. Source: BHF-UCL

striatal medium spiny neuron differentiation

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

synapse assembly

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

vocal learning

Inferred from mutant phenotype Ref.16PubMed 21378602. Source: BHF-UCL

vocalization behavior

Inferred from mutant phenotype Ref.16PubMed 21378602. Source: BHF-UCL

   Cellular_componentcell 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 electronic annotation. Source: UniProtKB-SubCell

neuron projection

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

neuron spine

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

neuronal postsynaptic density

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

plasma membrane

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

postsynaptic membrane

Inferred from electronic annotation. Source: UniProtKB-KW

   Molecular_functionGKAP/Homer scaffold activity

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

SH3 domain binding

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

identical protein binding

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

ionotropic glutamate receptor binding

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

protein C-terminus binding

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

protein binding

Inferred from physical interaction PubMed 17474147PubMed 21988832. Source: IntAct

scaffold protein binding

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

zinc ion binding

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

Complete GO annotation...

Binary interactions

Alternative products

This entry describes 2 isoforms produced by alternative promoter usage. [Align] [Select]

Note: Additional isoforms seem to exist. These isoforms may be the product of multiple intragenic promoter and/or alternative splicing.
Isoform 1 (identifier: Q9BYB0-1)

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.
Note: Primarily expressed in neurons.
Isoform 2 (identifier: Q9BYB0-3)

Also known as: B;

The sequence of this isoform differs from the canonical sequence as follows:
     1-119: Missing.
Note: Produced by alternative promoter usage.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 17311731SH3 and multiple ankyrin repeat domains protein 3
PRO_0000174675

Regions

Repeat148 – 17831ANK 1
Repeat182 – 21130ANK 2
Repeat215 – 24531ANK 3
Repeat249 – 27830ANK 4
Repeat282 – 31130ANK 5
Repeat315 – 34531ANK 6
Domain471 – 53060SH3
Domain571 – 66595PDZ
Domain1668 – 173164SAM
Region1 – 7575Intramolecular interaction with the ANK repeats By similarity
Region678 – 6858Required for interaction with ABI1 By similarity
Coiled coil1494 – 151421 Potential
Motif1410 – 14167SH3-binding Potential
Compositional bias678 – 6814Poly-Pro
Compositional bias719 – 7224Poly-Ala
Compositional bias814 – 930117Pro-rich
Compositional bias1232 – 1349118Pro-rich

Amino acid modifications

Modified residue1221Phosphotyrosine By similarity
Modified residue4831Phosphoserine By similarity
Modified residue5561Phosphotyrosine By similarity
Modified residue11581Phosphoserine Ref.5
Modified residue11621Phosphoserine Ref.5
Modified residue12341Phosphothreonine Ref.6
Modified residue12531Phosphoserine Ref.6
Modified residue16341Phosphoserine By similarity

Natural variations

Alternative sequence1 – 119119Missing in isoform 2.
VSP_053605
Natural variant121R → C Found in patients with neuropsychiatric disorders; unknown pathological significance; disrupts synaptic localization; may disrupt transsynaptic signaling and spine maturation. Ref.16
VAR_032804
Natural variant1411P → A in PHEDE. Ref.18
VAR_070259
Natural variant1981A → G. Ref.16
VAR_032805
Natural variant2241A → T. Ref.16
VAR_032806
Natural variant2451I → T. Ref.17
Corresponds to variant rs9616915 [ dbSNP | Ensembl ].
VAR_032807
Natural variant3001R → C Found in patients with neuropsychiatric disorders; unknown pathological significance; disrupts synaptic localization; may disrupt transsynaptic signaling and spine maturation. Ref.16
VAR_032808
Natural variant3211Q → R Found in a patient with neuropsychiatric disorders; unknown pathological significance; may disrupt transsynaptic signaling, spine maturation and axonal growth cone motility. Ref.15
VAR_070260
Natural variant3411S → L Found in patient with neuropsychiatric disorders; unknown pathological significance. Ref.15
VAR_070261
Natural variant4931H → Q. Ref.17
VAR_065799
Natural variant5361R → W in SCZD15. Ref.17
VAR_065800
Natural variant7201A → T. Ref.17
VAR_065801
Natural variant9521S → T. Ref.17
VAR_065802
Natural variant9631A → G. Ref.16
VAR_070262
Natural variant9701A → S Found in a patient with neuropsychiatric disorders; unknown pathological significance. Ref.15
VAR_070263
Natural variant10101G → V. Ref.17
VAR_065803
Natural variant10111G → V. Ref.16
VAR_070264
Natural variant11341P → H.
VAR_065804
Natural variant11731A → T Found in a patient with neuropsychiatric disorders; unknown pathological significance. Ref.15
VAR_070265
Natural variant12311R → H. Ref.16
VAR_070266
Natural variant12631P → L Found in a patient with neuropsychiatric disorders; unknown pathological significance. Ref.15
VAR_070267
Natural variant12981R → K. Ref.17
VAR_065805
Natural variant13331V → G. Ref.17
VAR_065806
Natural variant14061L → V Found in a patient with neuropsychiatric disorders; unknown pathological significance. Ref.15
VAR_070268
Natural variant14431M → T Found in a patient with neuropsychiatric disorders; unknown pathological significance. Ref.15
VAR_070269
Natural variant14521A → S in PHEDE. Ref.18
VAR_070270
Natural variant15461I → V. Ref.17
VAR_065807
Natural variant15571G → S Found in a patient with neuropsychiatric disorders; unknown pathological significance. Ref.15
VAR_070271
Natural variant15661S → G. Ref.16
VAR_070272
Natural variant16451P → T. Ref.17
VAR_065808
Natural variant16541P → T Found in patients with neuropsychiatric disorders; unknown pathological significance. Ref.15 Ref.16
VAR_070273

Sequences

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

Last modified February 19, 2014. Version 3.
Checksum: 781936CE60988D08

FASTA1,731184,667
        10         20         30         40         50         60 
MDGPGASAVV VRVGIPDLQQ TKCLRLDPAA PVWAAKQRVL CALNHSLQDA LNYGLFQPPS 

        70         80         90        100        110        120 
RGRAGKFLDE ERLLQEYPPN LDTPLPYLEF RYKRRVYAQN LIDDKQFAKL HTKANLKKFM 

       130        140        150        160        170        180 
DYVQLHSTDK VARLLDKGLD PNFHDPDSGE CPLSLAAQLD NATDLLKVLK NGGAHLDFRT 

       190        200        210        220        230        240 
RDGLTAVHCA TRQRNAAALT TLLDLGASPD YKDSRGLTPL YHSALGGGDA LCCELLLHDH 

       250        260        270        280        290        300 
AQLGITDENG WQEIHQACRF GHVQHLEHLL FYGADMGAQN ASGNTALHIC ALYNQESCAR 

       310        320        330        340        350        360 
VLLFRGANRD VRNYNSQTAF QVAIIAGNFE LAEVIKTHKD SDVVPFRETP SYAKRRRLAG 

       370        380        390        400        410        420 
PSGLASPRPL QRSASDINLK GEAQPAASPG PSLRSLPHQL LLQRLQEEKD RDRDADQESN 

       430        440        450        460        470        480 
ISGPLAGRAG QSKISPSGPG GPGPAPGPGP APPAPPAPPP RGPKRKLYSA VPGRKFIAVK 

       490        500        510        520        530        540 
AHSPQGEGEI PLHRGEAVKV LSIGEGGFWE GTVKGRTGWF PADCVEEVQM RQHDTRPETR 

       550        560        570        580        590        600 
EDRTKRLFRH YTVGSYDSLT SHSDYVIDDK VAVLQKRDHE GFGFVLRGAK AETPIEEFTP 

       610        620        630        640        650        660 
TPAFPALQYL ESVDVEGVAW RAGLRTGDFL IEVNGVNVVK VGHKQVVALI RQGGNRLVMK 

       670        680        690        700        710        720 
VVSVTRKPEE DGARRRAPPP PKRAPSTTLT LRSKSMTAEL EELASIRRRK GEKLDEMLAA 

       730        740        750        760        770        780 
AAEPTLRPDI ADADSRAATV KQRPTSRRIT PAEISSLFER QGLPGPEKLP GSLRKGIPRT 

       790        800        810        820        830        840 
KSVGEDEKLA SLLEGRFPRS TSMQDPVREG RGIPPPPQTA PPPPPAPYYF DSGPPPAFSP 

       850        860        870        880        890        900 
PPPPGRAYDT VRSSFKPGLE ARLGAGAAGL YEPGAALGPL PYPERQKRAR SMIILQDSAP 

       910        920        930        940        950        960 
ESGDAPRPPP AATPPERPKR RPRPPGPDSP YANLGAFSAS LFAPSKPQRR KSPLVKQLQV 

       970        980        990       1000       1010       1020 
EDAQERAALA VGSPGPGGGS FAREPSPTHR GPRPGGLDYG AGDGPGLAFG GPGPAKDRRL 

      1030       1040       1050       1060       1070       1080 
EERRRSTVFL SVGAIEGSAP GADLPSLQPS RSIDERLLGT GPTAGRDLLL PSPVSALKPL 

      1090       1100       1110       1120       1130       1140 
VSGPSLGPSG STFIHPLTGK PLDPSSPLAL ALAARERALA SQAPSRSPTP VHSPDADRPG 

      1150       1160       1170       1180       1190       1200 
PLFVDVQARD PERGSLASPA FSPRSPAWIP VPARREAEKV PREERKSPED KKSMILSVLD 

      1210       1220       1230       1240       1250       1260 
TSLQRPAGLI VVHATSNGQE PSRLGGAEEE RPGTPELAPA PMQSAAVAEP LPSPRAQPPG 

      1270       1280       1290       1300       1310       1320 
GTPADAGPGQ GSSEEEPELV FAVNLPPAQL SSSDEETREE LARIGLVPPP EEFANGVLLA 

      1330       1340       1350       1360       1370       1380 
TPLAGPGPSP TTVPSPASGK PSSEPPPAPE SAADSGVEEA DTRSSSDPHL ETTSTISTVS 

      1390       1400       1410       1420       1430       1440 
SMSTLSSESG ELTDTHTSFA DGHTFLLEKP PVPPKPKLKS PLGKGPVTFR DPLLKQSSDS 

      1450       1460       1470       1480       1490       1500 
ELMAQQHHAA SAGLASAAGP ARPRYLFQRR SKLWGDPVES RGLPGPEDDK PTVISELSSR 

      1510       1520       1530       1540       1550       1560 
LQQLNKDTRS LGEEPVGGLG SLLDPAKKSP IAAARLFSSL GELSSISAQR SPGGPGGGAS 

      1570       1580       1590       1600       1610       1620 
YSVRPSGRYP VARRAPSPVK PASLERVEGL GAGAGGAGRP FGLTPPTILK SSSLSIPHEP 

      1630       1640       1650       1660       1670       1680 
KEVRFVVRSV SARSRSPSPS PLPSPASGPG PGAPGPRRPF QQKPLQLWSK FDVGDWLESI 

      1690       1700       1710       1720       1730 
HLGEHRDRFE DHEIEGAHLP ALTKDDFVEL GVTRVGHRMN IERALRQLDG S 

« Hide

Isoform 2 (B) [UniParc].

Checksum: B5D0BACA602434C6
Show »

FASTA1,612171,151

References

« Hide 'large scale' references
[1]"Novel veriants of human SHANK3 gene."
Uchino S., Waga C., Kohsaka S.
Submitted (JUN-2010) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[2]"The DNA sequence of human chromosome 22."
Dunham I., Hunt A.R., Collins J.E., Bruskiewich R., Beare D.M., Clamp M., Smink L.J., Ainscough R., Almeida J.P., Babbage A.K., Bagguley C., Bailey J., Barlow K.F., Bates K.N., Beasley O.P., Bird C.P., Blakey S.E., Bridgeman A.M. expand/collapse author list , Buck D., Burgess J., Burrill W.D., Burton J., Carder C., Carter N.P., Chen Y., Clark G., Clegg S.M., Cobley V.E., Cole C.G., Collier R.E., Connor R., Conroy D., Corby N.R., Coville G.J., Cox A.V., Davis J., Dawson E., Dhami P.D., Dockree C., Dodsworth S.J., Durbin R.M., Ellington A.G., Evans K.L., Fey J.M., Fleming K., French L., Garner A.A., Gilbert J.G.R., Goward M.E., Grafham D.V., Griffiths M.N.D., Hall C., Hall R.E., Hall-Tamlyn G., Heathcott R.W., Ho S., Holmes S., Hunt S.E., Jones M.C., Kershaw J., Kimberley A.M., King A., Laird G.K., Langford C.F., Leversha M.A., Lloyd C., Lloyd D.M., Martyn I.D., Mashreghi-Mohammadi M., Matthews L.H., Mccann O.T., Mcclay J., Mclaren S., McMurray A.A., Milne S.A., Mortimore B.J., Odell C.N., Pavitt R., Pearce A.V., Pearson D., Phillimore B.J.C.T., Phillips S.H., Plumb R.W., Ramsay H., Ramsey Y., Rogers L., Ross M.T., Scott C.E., Sehra H.K., Skuce C.D., Smalley S., Smith M.L., Soderlund C., Spragon L., Steward C.A., Sulston J.E., Swann R.M., Vaudin M., Wall M., Wallis J.M., Whiteley M.N., Willey D.L., Williams L., Williams S.A., Williamson H., Wilmer T.E., Wilming L., Wright C.L., Hubbard T., Bentley D.R., Beck S., Rogers J., Shimizu N., Minoshima S., Kawasaki K., Sasaki T., Asakawa S., Kudoh J., Shintani A., Shibuya K., Yoshizaki Y., Aoki N., Mitsuyama S., Roe B.A., Chen F., Chu L., Crabtree J., Deschamps S., Do A., Do T., Dorman A., Fang F., Fu Y., Hu P., Hua A., Kenton S., Lai H., Lao H.I., Lewis J., Lewis S., Lin S.-P., Loh P., Malaj E., Nguyen T., Pan H., Phan S., Qi S., Qian Y., Ray L., Ren Q., Shaull S., Sloan D., Song L., Wang Q., Wang Y., Wang Z., White J., Willingham D., Wu H., Yao Z., Zhan M., Zhang G., Chissoe S., Murray J., Miller N., Minx P., Fulton R., Johnson D., Bemis G., Bentley D., Bradshaw H., Bourne S., Cordes M., Du Z., Fulton L., Goela D., Graves T., Hawkins J., Hinds K., Kemp K., Latreille P., Layman D., Ozersky P., Rohlfing T., Scheet P., Walker C., Wamsley A., Wohldmann P., Pepin K., Nelson J., Korf I., Bedell J.A., Hillier L.W., Mardis E., Waterston R., Wilson R., Emanuel B.S., Shaikh T., Kurahashi H., Saitta S., Budarf M.L., McDermid H.E., Johnson A., Wong A.C.C., Morrow B.E., Edelmann L., Kim U.J., Shizuya H., Simon M.I., Dumanski J.P., Peyrard M., Kedra D., Seroussi E., Fransson I., Tapia I., Bruder C.E., O'Brien K.P., Wilkinson P., Bodenteich A., Hartman K., Hu X., Khan A.S., Lane L., Tilahun Y., Wright H.
Nature 402:489-495(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]"Identification of novel transcribed sequences on human chromosome 22 by expressed sequence tag mapping."
Hirosawa M., Nagase T., Murahashi Y., Kikuno R., Ohara O.
DNA Res. 8:1-9(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 935-1731 (ISOFORMS 1/2).
[4]"The nucleotide sequence of a long cDNA clone isolated from human spleen."
Ohara O., Nagase T., Kikuno R., Okumura K.
Submitted (JAN-2002) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 962-1731 (ISOFORMS 1/2).
Tissue: Spleen.
[5]"Phosphoproteome of resting human platelets."
Zahedi R.P., Lewandrowski U., Wiesner J., Wortelkamp S., Moebius J., Schuetz C., Walter U., Gambaryan S., Sickmann A.
J. Proteome Res. 7:526-534(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1158 AND SER-1162, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Platelet.
[6]"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions."
Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K.
Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-1234 AND SER-1253, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Leukemic T-cell.
[7]"Epigenetic dysregulation of SHANK3 in brain tissues from individuals with autism spectrum disorders."
Zhu L., Wang X., Li X.L., Towers A., Cao X., Wang P., Bowman R., Yang H., Goldstein J., Li Y.J., Jiang Y.H.
Hum. Mol. Genet. 23:1563-1578(2014) [PubMed] [Europe PMC] [Abstract]
Cited for: ALTERNATIVE SPLICING (ISOFORM 2), INVOLVEMENT IN NEUROPSYCHIATRIC DISORDERS.
[8]"Disruption of the ProSAP2 gene in a t(12;22)(q24.1;q13.3) is associated with the 22q13.3 deletion syndrome."
Bonaglia M.C., Giorda R., Borgatti R., Felisari G., Gagliardi C., Selicorni A., Zuffardi O.
Am. J. Hum. Genet. 69:261-268(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: CHROMOSOMAL TRANSLOCATION WITH APPL2.
[9]"The Shank family of scaffold proteins."
Sheng M., Kim E.
J. Cell Sci. 113:1851-1856(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW.
[10]"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.
[11]"Bipolar affective disorder and early dementia onset in a male patient with SHANK3 deletion."
Vucurovic K., Landais E., Delahaigue C., Eutrope J., Schneider A., Leroy C., Kabbaj H., Motte J., Gaillard D., Rolland A.C., Doco-Fenzy M.
Eur. J. Med. Genet. 55:625-629(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: INVOLVEMENT IN NEUROPSYCHIATRIC DISORDERS.
[12]"Prospective investigation of autism and genotype-phenotype correlations in 22q13 deletion syndrome and SHANK3 deficiency."
Soorya L., Kolevzon A., Zweifach J., Lim T., Dobry Y., Schwartz L., Frank Y., Wang A.T., Cai G., Parkhomenko E., Halpern D., Grodberg D., Angarita B., Willner J.P., Yang A., Canitano R., Chaplin W., Betancur C., Buxbaum J.D.
Mol. Autism 4:18-18(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: INVOLVEMENT IN PHEDE.
[13]"SHANK3 overexpression causes manic-like behaviour with unique pharmacogenetic properties."
Han K., Holder J.L. Jr., Schaaf C.P., Lu H., Chen H., Kang H., Tang J., Wu Z., Hao S., Cheung S.W., Yu P., Sun H., Breman A.M., Patel A., Lu H.C., Zoghbi H.Y.
Nature 503:72-77(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: INVOLVEMENT IN NEUROPSYCHIATRIC DISORDERS.
[14]"SHANK3 and IGF1 restore synaptic deficits in neurons from 22q13 deletion syndrome patients."
Shcheglovitov A., Shcheglovitova O., Yazawa M., Portmann T., Shu R., Sebastiano V., Krawisz A., Froehlich W., Bernstein J.A., Hallmayer J.F., Dolmetsch R.E.
Nature 503:267-271(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: INVOLVEMENT IN PHEDE, FUNCTION IN SYNAPSE FORMATION, SUBCELLULAR LOCATION.
[15]"Contribution of SHANK3 mutations to autism spectrum disorder."
Moessner R., Marshall C.R., Sutcliffe J.S., Skaug J., Pinto D., Vincent J., Zwaigenbaum L., Fernandez B., Roberts W., Szatmari P., Scherer S.W.
Am. J. Hum. Genet. 81:1289-1297(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS ARG-321; LEU-341; SER-970; THR-1173; LEU-1263; VAL-1406; THR-1443; SER-1557 AND THR-1654, INVOLVEMENT IN NEUROPSYCHIATRIC DISORDERS.
[16]"Mutations in the gene encoding the synaptic scaffolding protein SHANK3 are associated with autism spectrum disorders."
Durand C.M., Betancur C., Boeckers T.M., Bockmann J., Chaste P., Fauchereau F., Nygren G., Rastam M., Gillberg I.C., Anckarsaeter H., Sponheim E., Goubran-Botros H., Delorme R., Chabane N., Mouren-Simeoni M.-C., de Mas P., Bieth E., Roge B. expand/collapse author list , Heron D., Burglen L., Gillberg C., Leboyer M., Bourgeron T.
Nat. Genet. 39:25-27(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS CYS-12; GLY-198; THR-224; CYS-300; GLY-963; VAL-1011; HIS-1231; GLY-1566 AND THR-1654, INVOLVEMENT IN NEUROPSYCHIATRIC DISORDERS, CHARACTERIZATION OF VARIANTS CYS-12 AND CYS-300.
[17]"De novo mutations in the gene encoding the synaptic scaffolding protein SHANK3 in patients ascertained for schizophrenia."
Gauthier J., Champagne N., Lafreniere R.G., Xiong L., Spiegelman D., Brustein E., Lapointe M., Peng H., Cote M., Noreau A., Hamdan F.F., Addington A.M., Rapoport J.L., Delisi L.E., Krebs M.O., Joober R., Fathalli F., Mouaffak F. expand/collapse author list , Haghighi A.P., Neri C., Dube M.P., Samuels M.E., Marineau C., Stone E.A., Awadalla P., Barker P.A., Carbonetto S., Drapeau P., Rouleau G.A.
Proc. Natl. Acad. Sci. U.S.A. 107:7863-7868(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT SCZD15 TRP-536, VARIANTS THR-245; GLN-493; THR-720; THR-952; VAL-1010; LYS-1298; GLY-1333; VAL-1546 AND THR-1645.
[18]"Prevalence of SHANK3 variants in patients with different subtypes of autism spectrum disorders."
Boccuto L., Lauri M., Sarasua S.M., Skinner C.D., Buccella D., Dwivedi A., Orteschi D., Collins J.S., Zollino M., Visconti P., Dupont B., Tiziano D., Schroer R.J., Neri G., Stevenson R.E., Gurrieri F., Schwartz C.E.
Eur. J. Hum. Genet. 21:310-316(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS PHEDE ALA-141 AND SER-1452.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AC000050 Genomic DNA. No translation available.
AC000036 Genomic DNA. No translation available.
AB051437 mRNA. Translation: BAB33320.1.
AK074038 mRNA. Translation: BAB84864.1.
AB569469 mRNA. Translation: BAJ09793.1.
RefSeqNP_277052.1. NM_033517.1. [Q9BYB0-1]
UniGeneHs.149035.

3D structure databases

ProteinModelPortalQ9BYB0.
SMRQ9BYB0. Positions 563-668, 1665-1728.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

DIPDIP-52267N.
IntActQ9BYB0. 28 interactions.
MINTMINT-4134553.
STRING9606.ENSP00000262795.

PTM databases

PhosphoSiteQ9BYB0.

Polymorphism databases

DMDM148887434.

Proteomic databases

PaxDbQ9BYB0.
PRIDEQ9BYB0.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

GeneID85358.
KEGGhsa:85358.
UCSCuc003bnf.2. human. [Q9BYB0-1]

Organism-specific databases

CTD85358.
GeneCardsGC22P051112.
GeneReviewsSHANK3.
HGNCHGNC:14294. SHANK3.
HPAHPA003446.
MIM606230. gene.
606232. phenotype.
613950. phenotype.
neXtProtNX_Q9BYB0.
Orphanet106. Autism.
48652. Monosomy 22q13.
3140. Schizophrenia.
HUGESearch...
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0666.
HOVERGENHBG054027.
InParanoidQ9BYB0.
KOK15009.

Enzyme and pathway databases

SignaLinkQ9BYB0.

Gene expression databases

CleanExHS_SHANK3.
GenevestigatorQ9BYB0.

Family and domain databases

Gene3D1.10.150.50. 1 hit.
1.25.40.20. 1 hit.
2.30.42.10. 1 hit.
InterProIPR002110. Ankyrin_rpt.
IPR020683. Ankyrin_rpt-contain_dom.
IPR001478. PDZ.
IPR001660. SAM.
IPR013761. SAM/pointed.
IPR021129. SAM_type1.
IPR011511. SH3_2.
IPR001452. SH3_domain.
[Graphical view]
PfamPF12796. Ank_2. 2 hits.
PF00595. PDZ. 1 hit.
PF00536. SAM_1. 1 hit.
PF07653. SH3_2. 1 hit.
[Graphical view]
SMARTSM00248. ANK. 5 hits.
SM00228. PDZ. 1 hit.
SM00454. SAM. 1 hit.
SM00326. SH3. 1 hit.
[Graphical view]
SUPFAMSSF47769. SSF47769. 1 hit.
SSF48403. SSF48403. 1 hit.
SSF50044. SSF50044. 1 hit.
SSF50156. SSF50156. 1 hit.
PROSITEPS50297. ANK_REP_REGION. 1 hit.
PS50088. ANK_REPEAT. 4 hits.
PS50106. PDZ. 1 hit.
PS50105. SAM_DOMAIN. 1 hit.
PS50002. SH3. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSSHANK3. human.
GeneWikiSHANK3.
GenomeRNAi85358.
NextBio75867.
PROQ9BYB0.
SOURCESearch...

Entry information

Entry nameSHAN3_HUMAN
AccessionPrimary (citable) accession number: Q9BYB0
Secondary accession number(s): D7UT47, Q8TET3
Entry history
Integrated into UniProtKB/Swiss-Prot: July 26, 2002
Last sequence update: February 19, 2014
Last modified: July 9, 2014
This is version 118 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 polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 22

Human chromosome 22: entries, gene names and cross-references to MIM