UniProtKB - Q9BYB0 (SHAN3_HUMAN)
Protein
SH3 and multiple ankyrin repeat domains protein 3
Gene
SHANK3
Organism
Homo sapiens (Human)
Status
Functioni
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.
1 PublicationGO - Molecular functioni
- actin binding Source: UniProtKB-KW
- ionotropic glutamate receptor binding Source: BHF-UCL
- protein C-terminus binding Source: BHF-UCL
- protein self-association Source: BHF-UCL
- scaffold protein binding Source: BHF-UCL
- SH3 domain binding Source: BHF-UCL
- synaptic receptor adaptor activity Source: BHF-UCL
- zinc ion binding Source: BHF-UCL
GO - Biological processi
- adult behavior Source: BHF-UCL
- AMPA glutamate receptor clustering Source: BHF-UCL
- axon guidance Source: Reactome
- brain morphogenesis Source: BHF-UCL
- dendritic spine morphogenesis Source: BHF-UCL
- guanylate kinase-associated protein clustering Source: BHF-UCL
- learning Source: BHF-UCL
- long-term synaptic potentiation Source: GO_Central
- MAPK cascade Source: BHF-UCL
- memory Source: BHF-UCL
- negative regulation of actin filament bundle assembly Source: BHF-UCL
- negative regulation of cell volume Source: BHF-UCL
- NMDA glutamate receptor clustering Source: BHF-UCL
- positive regulation of AMPA receptor activity Source: BHF-UCL
- positive regulation of dendritic spine development Source: BHF-UCL
- positive regulation of excitatory postsynaptic potential Source: BHF-UCL
- positive regulation of glutamate receptor signaling pathway Source: BHF-UCL
- positive regulation of long-term neuronal synaptic plasticity Source: BHF-UCL
- positive regulation of long-term synaptic potentiation Source: BHF-UCL
- positive regulation of synapse structural plasticity Source: BHF-UCL
- positive regulation of synaptic transmission, glutamatergic Source: BHF-UCL
- postsynaptic density assembly Source: BHF-UCL
- regulation of AMPA receptor activity Source: GO_Central
- regulation of dendritic spine morphogenesis Source: BHF-UCL
- regulation of long-term synaptic depression Source: BHF-UCL
- regulation of long-term synaptic potentiation Source: BHF-UCL
- social behavior Source: BHF-UCL
- striatal medium spiny neuron differentiation Source: BHF-UCL
- synapse assembly Source: BHF-UCL
- synaptic growth at neuromuscular junction Source: GO_Central
- vocalization behavior Source: BHF-UCL
- vocal learning Source: BHF-UCL
Keywordsi
| Molecular function | Actin-binding |
Enzyme and pathway databases
| PathwayCommonsi | Q9BYB0 |
| Reactomei | R-HSA-6794361, Neurexins and neuroligins R-HSA-8853659, RET signaling |
| SignaLinki | Q9BYB0 |
Protein family/group databases
| TCDBi | 8.A.28.1.7, the ankyrin (ankyrin) family |
Names & Taxonomyi
| Protein namesi | Recommended name: SH3 and multiple ankyrin repeat domains protein 3Short name: Shank3 Alternative name(s): Proline-rich synapse-associated protein 2 Short name: ProSAP2 |
| Gene namesi | Name:SHANK3 Synonyms:KIAA1650, PROSAP2, PSAP2 |
| Organismi | Homo sapiens (Human) |
| Taxonomic identifieri | 9606 [NCBI] |
| Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
| Proteomesi |
|
Organism-specific databases
| HGNCi | HGNC:14294, SHANK3 |
| MIMi | 606230, gene |
| neXtProti | NX_Q9BYB0 |
Subcellular locationi
Cytoplasm and Cytosol
- Cytoplasm 1 Publication
Other locations
- postsynaptic density 1 Publication
- dendritic spine By similarity
Note: In neuronal cells, extends into the region subjacent to the postsynaptic density (PSD).By similarity
Cytosol
- cytosol Source: Reactome
Plasma Membrane
- ciliary membrane Source: BHF-UCL
- extrinsic component of cytoplasmic side of plasma membrane Source: BHF-UCL
Other locations
- dendritic spine Source: GO_Central
- neuron projection Source: BHF-UCL
- neuron spine Source: BHF-UCL
- postsynaptic density Source: BHF-UCL
Keywords - Cellular componenti
Cell junction, Cell projection, Cytoplasm, SynapsePathology & Biotechi
Involvement in diseasei
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.1 Publication
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 (PubMed:24153177) such as hyperactivity, auditory overstimulation, epilepsy and bipolar affective disorders, among others.1 Publication
Phelan-McDermid syndrome (PHMDS)3 Publications
The disease is caused by variants affecting the gene represented in this entry.
Disease descriptionA 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.
Related information in OMIM| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Natural variantiVAR_070259 | 141 | P → A in PHMDS. 1 PublicationCorresponds to variant dbSNP:rs397514705EnsemblClinVar. | 1 | |
| Natural variantiVAR_070270 | 1452 | A → S in PHMDS. 1 Publication | 1 |
Schizophrenia 15 (SCZD15)1 Publication
The disease is caused by variants affecting the gene represented in this entry.
Disease descriptionA 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.
Related information in OMIM| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Natural variantiVAR_065800 | 536 | R → W in SCZD15. 1 PublicationCorresponds to variant dbSNP:rs387906933EnsemblClinVar. | 1 |
Keywords - Diseasei
Autism spectrum disorder, Disease variant, SchizophreniaOrganism-specific databases
| GeneReviewsi | SHANK3 |
| MalaCardsi | SHANK3 |
| MIMi | 606232, phenotype 613950, phenotype |
| Orphaneti | 48652, Monosomy 22q13.3 106, NON RARE IN EUROPE: Autism |
Miscellaneous databases
| Pharosi | Q9BYB0, Tbio |
Genetic variation databases
| BioMutai | SHANK3 |
| DMDMi | 148887434 |
PTM / Processingi
Molecule processing
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| ChainiPRO_0000174675 | 1 – 1731 | SH3 and multiple ankyrin repeat domains protein 3Add BLAST | 1731 |
Amino acid modifications
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Modified residuei | 122 | PhosphotyrosineBy similarity | 1 | |
| Modified residuei | 373 | PhosphoserineBy similarity | 1 | |
| Modified residuei | 375 | PhosphoserineBy similarity | 1 | |
| Modified residuei | 388 | PhosphoserineBy similarity | 1 | |
| Modified residuei | 395 | PhosphoserineBy similarity | 1 | |
| Modified residuei | 483 | PhosphoserineBy similarity | 1 | |
| Modified residuei | 556 | PhosphotyrosineBy similarity | 1 | |
| Modified residuei | 695 | PhosphoserineBy similarity | 1 | |
| Modified residuei | 782 | PhosphoserineBy similarity | 1 | |
| Modified residuei | 791 | PhosphoserineBy similarity | 1 | |
| Modified residuei | 802 | PhosphoserineBy similarity | 1 | |
| Modified residuei | 891 | PhosphoserineBy similarity | 1 | |
| Modified residuei | 898 | PhosphoserineBy similarity | 1 | |
| Modified residuei | 913 | PhosphothreonineCombined sources | 1 | |
| Modified residuei | 931 | PhosphotyrosineBy similarity | 1 | |
| Modified residuei | 966 | Asymmetric dimethylarginineBy similarity | 1 | |
| Modified residuei | 1129 | PhosphothreonineBy similarity | 1 | |
| Modified residuei | 1133 | PhosphoserineBy similarity | 1 | |
| Modified residuei | 1158 | PhosphoserineCombined sources | 1 | |
| Modified residuei | 1162 | PhosphoserineCombined sources | 1 | |
| Modified residuei | 1165 | PhosphoserineBy similarity | 1 | |
| Modified residuei | 1234 | PhosphothreonineCombined sources | 1 | |
| Modified residuei | 1253 | PhosphoserineCombined sources | 1 | |
| Modified residuei | 1420 | PhosphoserineBy similarity | 1 | |
| Modified residuei | 1510 | PhosphoserineBy similarity | 1 | |
| Modified residuei | 1521 | PhosphoserineBy similarity | 1 | |
| Modified residuei | 1529 | PhosphoserineBy similarity | 1 | |
| Modified residuei | 1539 | PhosphoserineBy similarity | 1 | |
| Modified residuei | 1634 | PhosphoserineBy similarity | 1 | |
| Modified residuei | 1636 | PhosphoserineCombined sources | 1 | |
| Modified residuei | 1638 | PhosphoserineCombined sources | 1 |
Keywords - PTMi
Methylation, PhosphoproteinProteomic databases
| jPOSTi | Q9BYB0 |
| MassIVEi | Q9BYB0 |
| PaxDbi | Q9BYB0 |
| PeptideAtlasi | Q9BYB0 |
| PRIDEi | Q9BYB0 |
| ProteomicsDBi | 79606 [Q9BYB0-1] |
PTM databases
| CarbonylDBi | Q9BYB0 |
| iPTMneti | Q9BYB0 |
| PhosphoSitePlusi | Q9BYB0 |
Expressioni
Tissue specificityi
Expressed in the cerebral cortex and the cerebellum.
Interactioni
Subunit structurei
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).
Interacts with CAMK2A (PubMed:28130356).
Interacts with DIP2A (By similarity).
By similarity1 PublicationBinary interactionsi
Hide detailsQ9BYB0
Isoform 1 [Q9BYB0-1]
| With | #Exp. | IntAct |
|---|---|---|
| CACNA1D [Q01668] | 2 | EBI-20939234,EBI-9207771 |
GO - Molecular functioni
- actin binding Source: UniProtKB-KW
- ionotropic glutamate receptor binding Source: BHF-UCL
- protein C-terminus binding Source: BHF-UCL
- protein self-association Source: BHF-UCL
- scaffold protein binding Source: BHF-UCL
- SH3 domain binding Source: BHF-UCL
Protein-protein interaction databases
| BioGRIDi | 124487, 22 interactors |
| CORUMi | Q9BYB0 |
| DIPi | DIP-52267N |
| IntActi | Q9BYB0, 190 interactors |
| MINTi | Q9BYB0 |
Miscellaneous databases
| RNActi | Q9BYB0, protein |
Structurei
Secondary structure
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details3D structure databases
| SMRi | Q9BYB0 |
| ModBasei | Search... |
| PDBe-KBi | Search... |
Family & Domainsi
Domains and Repeats
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Repeati | 148 – 178 | ANK 1Add BLAST | 31 | |
| Repeati | 182 – 211 | ANK 2Add BLAST | 30 | |
| Repeati | 215 – 245 | ANK 3Add BLAST | 31 | |
| Repeati | 249 – 278 | ANK 4Add BLAST | 30 | |
| Repeati | 282 – 311 | ANK 5Add BLAST | 30 | |
| Repeati | 315 – 345 | ANK 6Add BLAST | 31 | |
| Domaini | 471 – 530 | SH3PROSITE-ProRule annotationAdd BLAST | 60 | |
| Domaini | 571 – 665 | PDZPROSITE-ProRule annotationAdd BLAST | 95 | |
| Domaini | 1668 – 1731 | SAMPROSITE-ProRule annotationAdd BLAST | 64 |
Region
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Regioni | 1 – 75 | Intramolecular interaction with the ANK repeatsBy similarityAdd BLAST | 75 | |
| Regioni | 407 – 467 | DisorderedSequence analysisAdd BLAST | 61 | |
| Regioni | 665 – 689 | DisorderedSequence analysisAdd BLAST | 25 | |
| Regioni | 678 – 685 | Required for interaction with ABI1By similarity | 8 | |
| Regioni | 760 – 853 | DisorderedSequence analysisAdd BLAST | 94 | |
| Regioni | 871 – 1021 | DisorderedSequence analysisAdd BLAST | 151 | |
| Regioni | 1115 – 1460 | DisorderedSequence analysisAdd BLAST | 346 | |
| Regioni | 1475 – 1525 | DisorderedSequence analysisAdd BLAST | 51 | |
| Regioni | 1546 – 1584 | DisorderedSequence analysisAdd BLAST | 39 | |
| Regioni | 1627 – 1664 | DisorderedSequence analysisAdd BLAST | 38 |
Coiled coil
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Coiled coili | 1494 – 1514 | Sequence analysisAdd BLAST | 21 |
Motif
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Motifi | 1410 – 1416 | SH3-bindingSequence analysis | 7 |
Compositional bias
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Compositional biasi | 439 – 465 | Pro residuesSequence analysisAdd BLAST | 27 | |
| Compositional biasi | 779 – 793 | Basic and acidic residuesSequence analysisAdd BLAST | 15 | |
| Compositional biasi | 810 – 847 | Pro residuesSequence analysisAdd BLAST | 38 | |
| Compositional biasi | 1175 – 1193 | Basic and acidic residuesSequence analysisAdd BLAST | 19 | |
| Compositional biasi | 1327 – 1348 | Pro residuesSequence analysisAdd BLAST | 22 | |
| Compositional biasi | 1367 – 1400 | Polar residuesSequence analysisAdd BLAST | 34 | |
| Compositional biasi | 1495 – 1509 | Polar residuesSequence analysisAdd BLAST | 15 | |
| Compositional biasi | 1638 – 1658 | Pro residuesSequence analysisAdd BLAST | 21 |
Domaini
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
Keywords - Domaini
ANK repeat, Coiled coil, Repeat, SH3 domain, SH3-bindingPhylogenomic databases
| InParanoidi | Q9BYB0 |
| OrthoDBi | 98033at2759 |
Family and domain databases
| Gene3Di | 1.10.150.50, 1 hit 1.25.40.20, 2 hits 2.30.42.10, 1 hit |
| InterProi | View protein in InterPro IPR002110, Ankyrin_rpt IPR020683, Ankyrin_rpt-contain_dom IPR036770, Ankyrin_rpt-contain_sf IPR001478, PDZ IPR041489, PDZ_6 IPR036034, PDZ_sf IPR001660, SAM IPR013761, SAM/pointed_sf IPR036028, SH3-like_dom_sf IPR001452, SH3_domain |
| Pfami | View protein in Pfam PF12796, Ank_2, 2 hits PF17820, PDZ_6, 1 hit PF00536, SAM_1, 1 hit PF07653, SH3_2, 1 hit |
| SMARTi | View protein in SMART SM00248, ANK, 5 hits SM00228, PDZ, 1 hit SM00454, SAM, 1 hit SM00326, SH3, 1 hit |
| SUPFAMi | SSF47769, SSF47769, 1 hit SSF48403, SSF48403, 1 hit SSF50044, SSF50044, 1 hit SSF50156, SSF50156, 1 hit |
| PROSITEi | View protein in PROSITE PS50297, ANK_REP_REGION, 1 hit PS50088, ANK_REPEAT, 4 hits PS50106, PDZ, 1 hit PS50105, SAM_DOMAIN, 1 hit PS50002, SH3, 1 hit |
Sequences (2+)i
Sequence statusi: Complete.
This entry describes 2 isoformsi produced by alternative promoter usage. AlignAdd to basketNote: Additional isoforms seem to exist. These isoforms may be the product of multiple intragenic promoter and/or alternative splicing.
This entry has 2 described isoforms and 6 potential isoforms that are computationally mapped.Show allAlign All
Isoform 1 (identifier: Q9BYB0-1) [UniParc]FASTAAdd to basket
Also known as: A
This isoform has been chosen as the canonicali sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
10 20 30 40 50
MDGPGASAVV VRVGIPDLQQ TKCLRLDPAA PVWAAKQRVL CALNHSLQDA
60 70 80 90 100
LNYGLFQPPS RGRAGKFLDE ERLLQEYPPN LDTPLPYLEF RYKRRVYAQN
110 120 130 140 150
LIDDKQFAKL HTKANLKKFM DYVQLHSTDK VARLLDKGLD PNFHDPDSGE
160 170 180 190 200
CPLSLAAQLD NATDLLKVLK NGGAHLDFRT RDGLTAVHCA TRQRNAAALT
210 220 230 240 250
TLLDLGASPD YKDSRGLTPL YHSALGGGDA LCCELLLHDH AQLGITDENG
260 270 280 290 300
WQEIHQACRF GHVQHLEHLL FYGADMGAQN ASGNTALHIC ALYNQESCAR
310 320 330 340 350
VLLFRGANRD VRNYNSQTAF QVAIIAGNFE LAEVIKTHKD SDVVPFRETP
360 370 380 390 400
SYAKRRRLAG PSGLASPRPL QRSASDINLK GEAQPAASPG PSLRSLPHQL
410 420 430 440 450
LLQRLQEEKD RDRDADQESN ISGPLAGRAG QSKISPSGPG GPGPAPGPGP
460 470 480 490 500
APPAPPAPPP RGPKRKLYSA VPGRKFIAVK AHSPQGEGEI PLHRGEAVKV
510 520 530 540 550
LSIGEGGFWE GTVKGRTGWF PADCVEEVQM RQHDTRPETR EDRTKRLFRH
560 570 580 590 600
YTVGSYDSLT SHSDYVIDDK VAVLQKRDHE GFGFVLRGAK AETPIEEFTP
610 620 630 640 650
TPAFPALQYL ESVDVEGVAW RAGLRTGDFL IEVNGVNVVK VGHKQVVALI
660 670 680 690 700
RQGGNRLVMK VVSVTRKPEE DGARRRAPPP PKRAPSTTLT LRSKSMTAEL
710 720 730 740 750
EELASIRRRK GEKLDEMLAA AAEPTLRPDI ADADSRAATV KQRPTSRRIT
760 770 780 790 800
PAEISSLFER QGLPGPEKLP GSLRKGIPRT KSVGEDEKLA SLLEGRFPRS
810 820 830 840 850
TSMQDPVREG RGIPPPPQTA PPPPPAPYYF DSGPPPAFSP PPPPGRAYDT
860 870 880 890 900
VRSSFKPGLE ARLGAGAAGL YEPGAALGPL PYPERQKRAR SMIILQDSAP
910 920 930 940 950
ESGDAPRPPP AATPPERPKR RPRPPGPDSP YANLGAFSAS LFAPSKPQRR
960 970 980 990 1000
KSPLVKQLQV EDAQERAALA VGSPGPGGGS FAREPSPTHR GPRPGGLDYG
1010 1020 1030 1040 1050
AGDGPGLAFG GPGPAKDRRL EERRRSTVFL SVGAIEGSAP GADLPSLQPS
1060 1070 1080 1090 1100
RSIDERLLGT GPTAGRDLLL PSPVSALKPL VSGPSLGPSG STFIHPLTGK
1110 1120 1130 1140 1150
PLDPSSPLAL ALAARERALA SQAPSRSPTP VHSPDADRPG PLFVDVQARD
1160 1170 1180 1190 1200
PERGSLASPA FSPRSPAWIP VPARREAEKV PREERKSPED KKSMILSVLD
1210 1220 1230 1240 1250
TSLQRPAGLI VVHATSNGQE PSRLGGAEEE RPGTPELAPA PMQSAAVAEP
1260 1270 1280 1290 1300
LPSPRAQPPG GTPADAGPGQ GSSEEEPELV FAVNLPPAQL SSSDEETREE
1310 1320 1330 1340 1350
LARIGLVPPP EEFANGVLLA TPLAGPGPSP TTVPSPASGK PSSEPPPAPE
1360 1370 1380 1390 1400
SAADSGVEEA DTRSSSDPHL ETTSTISTVS SMSTLSSESG ELTDTHTSFA
1410 1420 1430 1440 1450
DGHTFLLEKP PVPPKPKLKS PLGKGPVTFR DPLLKQSSDS ELMAQQHHAA
1460 1470 1480 1490 1500
SAGLASAAGP ARPRYLFQRR SKLWGDPVES RGLPGPEDDK PTVISELSSR
1510 1520 1530 1540 1550
LQQLNKDTRS LGEEPVGGLG SLLDPAKKSP IAAARLFSSL GELSSISAQR
1560 1570 1580 1590 1600
SPGGPGGGAS YSVRPSGRYP VARRAPSPVK PASLERVEGL GAGAGGAGRP
1610 1620 1630 1640 1650
FGLTPPTILK SSSLSIPHEP KEVRFVVRSV SARSRSPSPS PLPSPASGPG
1660 1670 1680 1690 1700
PGAPGPRRPF QQKPLQLWSK FDVGDWLESI HLGEHRDRFE DHEIEGAHLP
1710 1720 1730
ALTKDDFVEL GVTRVGHRMN IERALRQLDG S
Note: Primarily expressed in neurons.
Computationally mapped potential isoform sequencesi
There are 6 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket| A0A0U1RR93 | A0A0U1RR93_HUMAN | SH3 and multiple ankyrin repeat dom... | SHANK3 | 1,724 | Annotation score: | ||
| A0A0U1RQS4 | A0A0U1RQS4_HUMAN | SH3 and multiple ankyrin repeat dom... | SHANK3 | 1,607 | Annotation score: | ||
| A0A669KBA8 | A0A669KBA8_HUMAN | SH3 and multiple ankyrin repeat dom... | SHANK3 | 684 | Annotation score: | ||
| A0A590UJL3 | A0A590UJL3_HUMAN | SH3 and multiple ankyrin repeat dom... | SHANK3 | 1,121 | Annotation score: | ||
| A0A590UJY5 | A0A590UJY5_HUMAN | SH3 and multiple ankyrin repeat dom... | SHANK3 | 212 | Annotation score: | ||
| A0A669K9V7 | A0A669K9V7_HUMAN | SH3 and multiple ankyrin repeat dom... | SHANK3 | 88 | Annotation score: |
Natural variant
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Natural variantiVAR_032804 | 12 | R → C Found in patients with neuropsychiatric disorders; unknown pathological significance; disrupts synaptic localization. 1 PublicationCorresponds to variant dbSNP:rs1336089966Ensembl. | 1 | |
| Natural variantiVAR_070259 | 141 | P → A in PHMDS. 1 PublicationCorresponds to variant dbSNP:rs397514705EnsemblClinVar. | 1 | |
| Natural variantiVAR_032805 | 198 | A → G1 PublicationCorresponds to variant dbSNP:rs1232069989Ensembl. | 1 | |
| Natural variantiVAR_032806 | 224 | A → T1 PublicationCorresponds to variant dbSNP:rs766856815Ensembl. | 1 | |
| Natural variantiVAR_032807 | 245 | I → T1 PublicationCorresponds to variant dbSNP:rs9616915EnsemblClinVar. | 1 | |
| Natural variantiVAR_032808 | 300 | R → C Found in patients with neuropsychiatric disorders; unknown pathological significance; disrupts synaptic localization. 1 PublicationCorresponds to variant dbSNP:rs376862893Ensembl. | 1 | |
| Natural variantiVAR_070260 | 321 | Q → R Found in a patient with neuropsychiatric disorders; unknown pathological significance. 1 Publication | 1 | |
| Natural variantiVAR_070261 | 341 | S → L Found in patient with neuropsychiatric disorders; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs1314696433Ensembl. | 1 | |
| Natural variantiVAR_065799 | 493 | H → Q1 Publication | 1 | |
| Natural variantiVAR_065800 | 536 | R → W in SCZD15. 1 PublicationCorresponds to variant dbSNP:rs387906933EnsemblClinVar. | 1 | |
| Natural variantiVAR_065801 | 720 | A → T1 Publication | 1 | |
| Natural variantiVAR_065802 | 952 | S → T1 PublicationCorresponds to variant dbSNP:rs1340094921Ensembl. | 1 | |
| Natural variantiVAR_070262 | 963 | A → G1 Publication | 1 | |
| Natural variantiVAR_070263 | 970 | A → S Found in a patient with neuropsychiatric disorders; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs530255181EnsemblClinVar. | 1 | |
| Natural variantiVAR_065803 | 1010 | G → V1 Publication | 1 | |
| Natural variantiVAR_070264 | 1011 | G → V1 PublicationCorresponds to variant dbSNP:rs767058690EnsemblClinVar. | 1 | |
| Natural variantiVAR_065804 | 1134 | P → H. Corresponds to variant dbSNP:rs769454362Ensembl. | 1 | |
| Natural variantiVAR_070265 | 1173 | A → T Found in a patient with neuropsychiatric disorders; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs139686326EnsemblClinVar. | 1 | |
| Natural variantiVAR_070266 | 1231 | R → H1 PublicationCorresponds to variant dbSNP:rs750186589Ensembl. | 1 | |
| Natural variantiVAR_070267 | 1263 | P → L Found in a patient with neuropsychiatric disorders; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs757572910Ensembl. | 1 | |
| Natural variantiVAR_065805 | 1298 | R → K1 PublicationCorresponds to variant dbSNP:rs201483867EnsemblClinVar. | 1 | |
| Natural variantiVAR_065806 | 1333 | V → G1 PublicationCorresponds to variant dbSNP:rs200087210EnsemblClinVar. | 1 | |
| Natural variantiVAR_070268 | 1406 | L → V Found in a patient with neuropsychiatric disorders; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs201973139EnsemblClinVar. | 1 | |
| Natural variantiVAR_070269 | 1443 | M → T Found in a patient with neuropsychiatric disorders; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs773395828Ensembl. | 1 | |
| Natural variantiVAR_070270 | 1452 | A → S in PHMDS. 1 Publication | 1 | |
| Natural variantiVAR_065807 | 1546 | I → V1 PublicationCorresponds to variant dbSNP:rs1389307970Ensembl. | 1 | |
| Natural variantiVAR_070271 | 1557 | G → S Found in a patient with neuropsychiatric disorders; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs1224063430Ensembl. | 1 | |
| Natural variantiVAR_070272 | 1566 | S → G1 PublicationCorresponds to variant dbSNP:rs1481014682Ensembl. | 1 | |
| Natural variantiVAR_065808 | 1645 | P → T1 Publication | 1 | |
| Natural variantiVAR_070273 | 1654 | P → T Found in patients with neuropsychiatric disorders; unknown pathological significance. 2 PublicationsCorresponds to variant dbSNP:rs749130556EnsemblClinVar. | 1 |
Alternative sequence
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Alternative sequenceiVSP_053605 | 1 – 119 | Missing in isoform 2. CuratedAdd BLAST | 119 |
Sequence databases
| Select the link destinations: EMBLi GenBanki DDBJi Links Updated | 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 |
| RefSeqi | NP_277052.1, NM_033517.1 |
Keywords - Coding sequence diversityi
Alternative promoter usage, Chromosomal rearrangementSimilar proteinsi
Cross-referencesi
Sequence databases
| Select the link destinations: EMBLi GenBanki DDBJi Links Updated | 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 |
| RefSeqi | NP_277052.1, NM_033517.1 |
3D structure databases
| Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
| 6CPK | NMR | - | A | 471-530 | [»] | |
| SMRi | Q9BYB0 | |||||
| ModBasei | Search... | |||||
| PDBe-KBi | Search... | |||||
Protein-protein interaction databases
| BioGRIDi | 124487, 22 interactors |
| CORUMi | Q9BYB0 |
| DIPi | DIP-52267N |
| IntActi | Q9BYB0, 190 interactors |
| MINTi | Q9BYB0 |
Protein family/group databases
| TCDBi | 8.A.28.1.7, the ankyrin (ankyrin) family |
PTM databases
| CarbonylDBi | Q9BYB0 |
| iPTMneti | Q9BYB0 |
| PhosphoSitePlusi | Q9BYB0 |
Genetic variation databases
| BioMutai | SHANK3 |
| DMDMi | 148887434 |
Proteomic databases
| jPOSTi | Q9BYB0 |
| MassIVEi | Q9BYB0 |
| PaxDbi | Q9BYB0 |
| PeptideAtlasi | Q9BYB0 |
| PRIDEi | Q9BYB0 |
| ProteomicsDBi | 79606 [Q9BYB0-1] |
Protocols and materials databases
| ABCDi | Q9BYB0, 2 sequenced antibodies |
Organism-specific databases
| GeneCardsi | SHANK3 |
| GeneReviewsi | SHANK3 |
| HGNCi | HGNC:14294, SHANK3 |
| MalaCardsi | SHANK3 |
| MIMi | 606230, gene 606232, phenotype 613950, phenotype |
| neXtProti | NX_Q9BYB0 |
| Orphaneti | 48652, Monosomy 22q13.3 106, NON RARE IN EUROPE: Autism |
| HUGEi | Search... |
| GenAtlasi | Search... |
Phylogenomic databases
| InParanoidi | Q9BYB0 |
| OrthoDBi | 98033at2759 |
Enzyme and pathway databases
| PathwayCommonsi | Q9BYB0 |
| Reactomei | R-HSA-6794361, Neurexins and neuroligins R-HSA-8853659, RET signaling |
| SignaLinki | Q9BYB0 |
Miscellaneous databases
| BioGRID-ORCSi | 85358, 9 hits in 197 CRISPR screens |
| ChiTaRSi | SHANK3, human |
| GeneWikii | SHANK3 |
| GenomeRNAii | 85358 |
| Pharosi | Q9BYB0, Tbio |
| PROi | PR:Q9BYB0 |
| RNActi | Q9BYB0, protein |
| SOURCEi | Search... |
Family and domain databases
| Gene3Di | 1.10.150.50, 1 hit 1.25.40.20, 2 hits 2.30.42.10, 1 hit |
| InterProi | View protein in InterPro IPR002110, Ankyrin_rpt IPR020683, Ankyrin_rpt-contain_dom IPR036770, Ankyrin_rpt-contain_sf IPR001478, PDZ IPR041489, PDZ_6 IPR036034, PDZ_sf IPR001660, SAM IPR013761, SAM/pointed_sf IPR036028, SH3-like_dom_sf IPR001452, SH3_domain |
| Pfami | View protein in Pfam PF12796, Ank_2, 2 hits PF17820, PDZ_6, 1 hit PF00536, SAM_1, 1 hit PF07653, SH3_2, 1 hit |
| SMARTi | View protein in SMART SM00248, ANK, 5 hits SM00228, PDZ, 1 hit SM00454, SAM, 1 hit SM00326, SH3, 1 hit |
| SUPFAMi | SSF47769, SSF47769, 1 hit SSF48403, SSF48403, 1 hit SSF50044, SSF50044, 1 hit SSF50156, SSF50156, 1 hit |
| PROSITEi | View protein in PROSITE PS50297, ANK_REP_REGION, 1 hit PS50088, ANK_REPEAT, 4 hits PS50106, PDZ, 1 hit PS50105, SAM_DOMAIN, 1 hit PS50002, SH3, 1 hit |
| MobiDBi | Search... |
Entry informationi
| Entry namei | SHAN3_HUMAN | |
| Accessioni | Q9BYB0Primary (citable) accession number: Q9BYB0 Secondary accession number(s): D7UT47, Q8TET3 | |
| Entry historyi | Integrated into UniProtKB/Swiss-Prot: | July 26, 2002 |
| Last sequence update: | February 19, 2014 | |
| Last modified: | June 2, 2021 | |
| This is version 170 of the entry and version 3 of the sequence. See complete history. | ||
| Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
| Annotation program | Chordata Protein Annotation Program | |
| Disclaimer | Any 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
3D-structure, Reference proteomeDocuments
- Human chromosome 22
Human chromosome 22: entries, gene names and cross-references to MIM - Human entries with genetic variants
List of human entries with genetic variants - Human variants curated from literature reports
Index of human variants curated from literature reports - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - PDB cross-references
Index of Protein Data Bank (PDB) cross-references
