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Reviewed, UniProtKB/Swiss-Prot Q9BYB0 (SHAN3_HUMAN)

Last modified July 22, 2008. Version 55. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data | Customize display text xml rdf/xml gff fasta
Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Alternative products · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents

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, PSAP2
OrganismHomo sapiens (Human)
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length1741 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is not processed.
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 via complexes with GKAP/PSD-95 and Homer, respectively, and the actin-based cytoskeleton. May play a role in the structural and functional organization of the dendritic spine and synaptic junction.

Subunit structure

May homomultimerize via its SAM domain By similarity. Interacts with DLGAP1/GKAP, MGLUR1A, MGLUR5 C-termini via its PDZ domain By similarity. Interacts with HOMER1, HOMER2, HOMER3 and CCTN/cortactin SH3 domain By similarity. Is part of a complex with DLG4/PSD-95 and DLGAP1/GKAP. Interacts with DBNL By similarity. Interacts with BAIAP2.

Subcellular location

CytoplasmBy similarity. Cell junctionsynapseBy similarity. Cell junctionsynapsepostsynaptic cell membranepostsynaptic densityBy similarity. Note= Postsynaptic density of neuronal cells By similarity.

Tissue specificity

Expressed in the cerebral cortex and the cerebellum.

Involvement in disease

A chromosomal aberration disrupting SHANK3/PSAP2 is responsible for the clinical features of chromosome 22q13.3 deletion syndrome [MIM:606232]. Translocation t(12;22)(q24.1;q13.3) with APPL2/DIP13B. The phenotype is characterized by neonatal hypotonia, global developmental delay, normal to accelerated growth, absent to severely delayed speech, autistic behavior and minor dysmorphic features.

Defects in SHANK3 are a cause of autism spectrum disorders (ASD). 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).

Sequence similarities

Contains 6 ANK repeats.

Contains 1 PDZ (DHR) domain.

Contains 1 SAM (sterile alpha motif) domain.

Contains 1 SH3 domain.

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q9BYB0-1)

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: Q9BYB0-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1536-1544: Missing.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical view

Molecule processing

Chain1 – 17411741SH3 and multiple ankyrin repeat domains protein 3

Regions

Repeat148 – 17831ANK 1
Repeat182 – 21130ANK 2
Repeat215 – 24531ANK 3
Repeat249 – 27830ANK 4
Repeat282 – 31130ANK 5
Repeat315 – 34531ANK 6
Domain472 – 53160SH3
Domain572 – 66695PDZ
Domain1678 – 174164SAM
Coiled coil1495 – 151521 Potential
Motif1411 – 14177SH3-binding Potential
Compositional bias679 – 6824Poly-Pro
Compositional bias720 – 7234Poly-Ala
Compositional bias815 – 931117Pro-rich
Compositional bias1233 – 1350118Pro-rich

Amino acid modifications

Modified residue1221Phosphotyrosine By similarity
Modified residue3751Phosphoserine By similarity
Modified residue5571Phosphotyrosine By similarity
Modified residue5661Phosphotyrosine By similarity
Modified residue7831Phosphoserine By similarity
Modified residue11591Phosphoserine
Modified residue11631Phosphoserine
Modified residue16441Phosphoserine By similarity

Natural variations

Alternative sequence1536 – 15449Missing in isoform 2.
Natural variant121R → C
Natural variant1981A → G
Natural variant2241A → T
Natural variant2451I → T: dbSNP rs9616915.
Natural variant3001R → C

Sequences

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

Last modified June 12, 2007. Version 2.
Checksum: 0CC40F1F53E6F6D4

FASTA1,741186,295
        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 QSKISEPGAP RSCIRIRARF PAPPAPPAPP PRGPKRKLYS AVPGRKFIAV 

       490        500        510        520        530        540 
KAHSPQGEGE IPLHRGEAVK VLSIGEGGFW EGTVKGRTGW FPADCVEEVQ MRQHDTRPET 

       550        560        570        580        590        600 
REDRTKRLFR HYTVGSYDSL TSHSDYVIDD KVAVLQKRDH EGFGFVLRGA KAETPIEEFT 

       610        620        630        640        650        660 
PTPAFPALQY LESVDVEGVA WRAGLRTGDF LIEVNGVNVV KVGHKQVVAL IRQGGNRLVM 

       670        680        690        700        710        720 
KVVSVTRKPE EDGARRRAPP PPKRAPSTTL TLRSKSMTAE LEELASIRRR KGEKLDEMLA 

       730        740        750        760        770        780 
AAAEPTLRPD IADADSRAAT VKQRPTSRRI TPAEISSLFE RQGLPGPEKL PGSLRKGIPR 

       790        800        810        820        830        840 
TKSVGEDEKL ASLLEGRFPR STSMQDPVRE GRGIPPPPQT APPPPPAPYY FDSGPPPAFS 

       850        860        870        880        890        900 
PPPPPGRAYD TVRSSFKPGL EARLGAGAAG LYEPGAALGP LPYPERQKRA RSMIILQDSA 

       910        920        930        940        950        960 
PESGDAPRPP PAATPPERPK RRPRPPGPDS PYANLGAFSA SLFAPSKPQR RKSPLVKQLQ 

       970        980        990       1000       1010       1020 
VEDAQERAAL AVGSPGPGGG SFAREPSPTH RGPRPGGLDY GAGDGPGLAF GGPGPAKDRR 

      1030       1040       1050       1060       1070       1080 
LEERRRSTVF LSVGAIEGSA PGADLPSLQP SRSIDERLLG TGPTAGRDLL LPSPVSALKP 

      1090       1100       1110       1120       1130       1140 
LVSGPSLGPS GSTFIHPLTG KPLDPSSPLA LALAARERAL ASQAPSRSPT PVHSPDADRP 

      1150       1160       1170       1180       1190       1200 
GPLFVDVQAR DPERGSLASP AFSPRSPAWI PVPARREAEK VPREERKSPE DKKSMILSVL 

      1210       1220       1230       1240       1250       1260 
DTSLQRPAGL IVVHATSNGQ EPSRLGGAEE ERPGTPELAP APMQSAAVAE PLPSPRAQPP 

      1270       1280       1290       1300       1310       1320 
GGTPADAGPG QGSSEEEPEL VFAVNLPPAQ LSSSDEETRE ELARIGLVPP PEEFANGVLL 

      1330       1340       1350       1360       1370       1380 
ATPLAGPGPS PTTVPSPASG KPSSEPPPAP ESAADSGVEE ADTRSSSDPH LETTSTISTV 

      1390       1400       1410       1420       1430       1440 
SSMSTLSSES GELTDTHTSF ADGHTFLLEK PPVPPKPKLK SPLGKGPVTF RDPLLKQSSD 

      1450       1460       1470       1480       1490       1500 
SELMAQQHHA ASAGLASAAG PARPRYLFQR RSKLWGDPVE SRGLPGPEDD KPTVISELSS 

      1510       1520       1530       1540       1550       1560 
RLQQLNKDTR SLGEEPVGGL GSLLDPAKKS PIAAARCRSP MVGLRLFSSL GELSSISAQR 

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

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

      1690       1700       1710       1720       1730       1740 
FDVGDWLESI HLGEHRDRFE DHEIEGAHLP ALTKDDFVEL GVTRVGHRMN IERALRQLDG 


S 

« Hide

Isoform 2 [UniParc].

Checksum: E12CDA1DC84A9326
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1,732185,295

References

« Hide 'large scale' references
[1]"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: 10591208] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[2]"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: 11258795] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 936-1741 (ISOFORM 2).
[3]"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 963-1741 (ISOFORM 2).
Tissue: Spleen.
[4]"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: 11431708] [Abstract]
Cited for: CHROMOSOMAL TRANSLOCATION WITH APPL2.
[5]"The Shank family of scaffold proteins."
Sheng M., Kim E.
J. Cell Sci. 113:1851-1856(2000) [PubMed: 10806096] [Abstract]
Cited for: REVIEW.
[6]"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: 12504591] [Abstract]
Cited for: INTERACTION WITH BAIAP2.
[7]"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: 17173049] [Abstract]
Cited for: INVOLVEMENT IN ASD, VARIANTS CYS-12; GLY-198; THR-224 AND CYS-300.
[8]"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: 18088087] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1159 AND SER-1163, MASS SPECTROMETRY.
Tissue: Platelet.

Cross-references

Sequence databases

AC000050 Genomic DNA. No translation available.
AC000036 Genomic DNA. No translation available.
AB051437 mRNA. Translation: BAB33320.1.
AK074038 mRNA. Translation: BAB84864.1.
UniGeneHs.149035

3D structure databases

SMRQ9BYB0. Positions 731-794.
ModBaseSearch...

PTM databases

PhosphoSiteQ9BYB0.

Genome annotation databases

EnsemblENSG00000099882. Homo sapiens. [Contig view]

Organism-specific databases

H-InvDBHIX0016621.
HGNCHGNC:14294. SHANK3.
HPAHPA003446.
MIM606230. gene.
606232. phenotype.
Orphanet48652. Monosomy 22q13.
PharmGKBPA37866.
HUGESearch...
GenAtlasSearch...
GeneCardsSearch...

Phylogenomic databases

HOGENOMQ9BYB0.
HOVERGENQ9BYB0.

Gene expression databases

ArrayExpressQ9BYB0.
CleanExHS_SHANK3.
GermOnlineENSG00000099882. Homo sapiens.

Family and domain databases

InterProIPR002110. ANK.
IPR001478. PDZ.
IPR001660. SAM.
IPR013761. SAM_type.
IPR001452. SH3.
IPR011511. SH3_2.
[Graphical view]
Gene3DG3DSA:1.25.40.20. ANK. 1 hit.
G3DSA:1.10.150.50. SAM_type. 1 hit.
PfamPF00023. Ank. 5 hits.
PF00595. PDZ. 1 hit.
PF00536. SAM_1. 1 hit.
PF07653. SH3_2. 1 hit.
[Graphical view]
PRINTSPR01415. ANKYRIN.
ProDomPD000066. SH3. 1 hit.
[Graphical view] [Entries sharing at least one domain]
SMARTSM00248. ANK. 5 hits.
SM00228. PDZ. 1 hit.
SM00454. SAM. 1 hit.
SM00326. SH3. 1 hit.
[Graphical view]
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]