SHANK3

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 Publication

GO - Molecular functionⁱ

actin binding Source: UniProtKB-KW
GKAP/Homer scaffold activity Source: BHF-UCL
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
zinc ion binding Source: BHF-UCL

View the complete GO annotation on QuickGO ...

GO - Biological processⁱ

adult behavior
Source: BHF-UCL
Inferred from mutant phenotypeⁱ
- 17173049
- 21378602
AMPA glutamate receptor clustering
Source: BHF-UCL
Inferred from sequence or structural similarityⁱ
- 21795692
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
Inferred from mutant phenotypeⁱ
- 17173049
- 21378602
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
Inferred from sequence or structural similarityⁱ
- 21795692
positive regulation of excitatory postsynaptic potential
Source: BHF-UCL
Inferred from sequence or structural similarityⁱ
- 21795692
positive regulation of glutamate receptor signaling pathway
Source: BHF-UCL
Inferred from sequence or structural similarityⁱ
- 21795692
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
Inferred from sequence or structural similarityⁱ
- 21795692
postsynaptic density assembly Source: BHF-UCL
regulation of dendritic spine morphogenesis
Source: BHF-UCL
Inferred from sequence or structural similarityⁱ
- 21795692
regulation of long term synaptic depression
Source: BHF-UCL
Inferred from sequence or structural similarityⁱ
- 21795692
regulation of long-term synaptic potentiation Source: BHF-UCL
social behavior
Source: BHF-UCL
Inferred from mutant phenotypeⁱ
- 17173049
- 21378602
striatal medium spiny neuron differentiation Source: BHF-UCL
synapse assembly Source: BHF-UCL
vocalization behavior
Source: BHF-UCL
Inferred from mutant phenotypeⁱ
- 17173049
- 21378602
vocal learning
Source: BHF-UCL
Inferred from mutant phenotypeⁱ
- 17173049
- 21378602

View the complete GO annotation on QuickGO ...

Keywordsⁱ

Molecular function	Actin-binding

Molecular function

Actin-binding

Enzyme and pathway databases

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

TCDBⁱ

8.A.28.1.7 the ankyrin (ankyrin) family

Names & Taxonomyⁱ

Protein namesⁱ	Recommended 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 namesⁱ	Name:SHANK3 Synonyms:KIAA1650, PROSAP2, PSAP2
Organismⁱ	Homo sapiens (Human)
Taxonomic identifierⁱ	9606 [NCBI]
Taxonomic lineageⁱ	cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Dipnotetrapodomorpha › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Boreoeutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo
Proteomesⁱ	UP000005640 Componentⁱ: Unplaced

Organism-specific databases

Human Gene Nomenclature Database More...HGNCⁱ	HGNC:14294 SHANK3
MIMⁱ	606230 gene
neXtProtⁱ	NX_Q9BYB0

Keywords - Cellular componentⁱ

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

Pathology & 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 mutations 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.

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 mutations 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.

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 mutation, Schizophrenia

Organism-specific databases

DisGeNET More...DisGeNETⁱ	85358
GeneReviewsⁱ	SHANK3
MalaCards human disease database More...MalaCardsⁱ	SHANK3
MIMⁱ	606232 phenotype 613950 phenotype
Orphanetⁱ	106 Autism 48652 Monosomy 22q13 3140 Schizophrenia

Polymorphism and mutation 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	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, Phosphoprotein

Proteomic databases

PaxDbⁱ	Q9BYB0
PeptideAtlas More...PeptideAtlasⁱ	Q9BYB0
PRIDEⁱ	Q9BYB0
ProteomicsDBⁱ	79606

PTM databases

CarbonylDBⁱ	Q9BYB0
iPTMnetⁱ	Q9BYB0
PhosphoSitePlusⁱ	Q9BYB0

Expressionⁱ

Tissue specificityⁱ

Expressed in the cerebral cortex and the cerebellum.

Gene expression databases

CleanExⁱ	HS_SHANK3

CleanExⁱ

HS_SHANK3

Organism-specific databases

Human Protein Atlas More...HPAⁱ	HPA003446

HPAⁱ

HPA003446

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).By similarity1 Publication

Binary interactionsⁱ

With	Entry	#Exp.	IntAct
GRB2	P62993	2	EBI-1752330,EBI-401755
NCK1	P16333	4	EBI-1752330,EBI-389883
PLCG1	P19174	2	EBI-1752330,EBI-79387

GO - Molecular functionⁱ

actin binding Source: UniProtKB-KW
GKAP/Homer scaffold activity Source: BHF-UCL
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

View the complete GO annotation on QuickGO ...

Protein-protein interaction databases

BioGridⁱ	124487, 16 interactors
CORUMⁱ	Q9BYB0
Database of interacting proteins More...DIPⁱ	DIP-52267N
IntActⁱ	Q9BYB0, 29 interactors
Molecular INTeraction database More...MINTⁱ	Q9BYB0
STRINGⁱ	9606.ENSP00000442518

Structureⁱ

3D structure databases

ProteinModelPortalⁱ	Q9BYB0
SMRⁱ	Q9BYB0
ModBaseⁱ	Search...
MobiDBⁱ	Search...

Family & Domainsⁱ

Domains and Repeats

Feature key	Position(s)	DescriptionActions	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	678 – 685	Required for interaction with ABI1By similarity		8

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	Length
Compositional biasⁱ	678 – 681	Poly-Pro	4
Compositional biasⁱ	719 – 722	Poly-Ala	4
Compositional biasⁱ	814 – 930	Pro-richAdd BLAST	117
Compositional biasⁱ	1232 – 1349	Pro-richAdd BLAST	118

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-binding

Phylogenomic databases

eggNOGⁱ	KOG0504 Eukaryota KOG4375 Eukaryota COG0666 LUCA
HOVERGENⁱ	HBG054027
InParanoidⁱ	Q9BYB0
KEGG Orthology (KO) More...KOⁱ	K15009

Family and domain databases

Conserved Domains Database More...CDDⁱ	cd00204 ANK, 1 hit
Gene3Dⁱ	1.25.40.20, 2 hits
InterProⁱ	View protein in InterPro IPR002110 Ankyrin_rpt IPR020683 Ankyrin_rpt-contain_dom IPR036770 Ankyrin_rpt-contain_sf IPR032425 FERM_f0 IPR001478 PDZ IPR036034 PDZ_sf IPR001660 SAM IPR013761 SAM/pointed_sf IPR036028 SH3-like_dom_sf IPR001452 SH3_domain
Pfam protein domain database More...Pfamⁱ	View protein in Pfam PF12796 Ank_2, 2 hits PF16511 FERM_f0, 1 hit PF00595 PDZ, 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. Align Add to basket

Note: 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 2 potential isoforms that are computationally mapped.ⁱShow all

Isoform 1 (identifier: Q9BYB0-1) [UniParc]FASTA Add to basket

Also known as: A

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

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        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.

Length:1,731

Mass (Da):184,667

Last modified:February 19, 2014 - v3

Checksum:ⁱ781936CE60988D08

GO

Isoform 2 (identifier: Q9BYB0-3) [UniParc]FASTA Add to basket

Also known as: B

The sequence of this isoform differs from the canonical sequence as follows:
1-119: Missing.

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        10         20         30         40         50
MDYVQLHSTD KVARLLDKGL DPNFHDPDSG ECPLSLAAQL DNATDLLKVL 
        60         70         80         90        100
KNGGAHLDFR TRDGLTAVHC ATRQRNAAAL TTLLDLGASP DYKDSRGLTP 
       110        120        130        140        150
LYHSALGGGD ALCCELLLHD HAQLGITDEN GWQEIHQACR FGHVQHLEHL 
       160        170        180        190        200
LFYGADMGAQ NASGNTALHI CALYNQESCA RVLLFRGANR DVRNYNSQTA 
       210        220        230        240        250
FQVAIIAGNF ELAEVIKTHK DSDVVPFRET PSYAKRRRLA GPSGLASPRP 
       260        270        280        290        300
LQRSASDINL KGEAQPAASP GPSLRSLPHQ LLLQRLQEEK DRDRDADQES 
       310        320        330        340        350
NISGPLAGRA GQSKISPSGP GGPGPAPGPG PAPPAPPAPP PRGPKRKLYS 
       360        370        380        390        400
AVPGRKFIAV KAHSPQGEGE IPLHRGEAVK VLSIGEGGFW EGTVKGRTGW 
       410        420        430        440        450
FPADCVEEVQ MRQHDTRPET REDRTKRLFR HYTVGSYDSL TSHSDYVIDD 
       460        470        480        490        500
KVAVLQKRDH EGFGFVLRGA KAETPIEEFT PTPAFPALQY LESVDVEGVA 
       510        520        530        540        550
WRAGLRTGDF LIEVNGVNVV KVGHKQVVAL IRQGGNRLVM KVVSVTRKPE 
       560        570        580        590        600
EDGARRRAPP PPKRAPSTTL TLRSKSMTAE LEELASIRRR KGEKLDEMLA 
       610        620        630        640        650
AAAEPTLRPD IADADSRAAT VKQRPTSRRI TPAEISSLFE RQGLPGPEKL 
       660        670        680        690        700
PGSLRKGIPR TKSVGEDEKL ASLLEGRFPR STSMQDPVRE GRGIPPPPQT 
       710        720        730        740        750
APPPPPAPYY FDSGPPPAFS PPPPPGRAYD TVRSSFKPGL EARLGAGAAG 
       760        770        780        790        800
LYEPGAALGP LPYPERQKRA RSMIILQDSA PESGDAPRPP PAATPPERPK 
       810        820        830        840        850
RRPRPPGPDS PYANLGAFSA SLFAPSKPQR RKSPLVKQLQ VEDAQERAAL 
       860        870        880        890        900
AVGSPGPGGG SFAREPSPTH RGPRPGGLDY GAGDGPGLAF GGPGPAKDRR 
       910        920        930        940        950
LEERRRSTVF LSVGAIEGSA PGADLPSLQP SRSIDERLLG TGPTAGRDLL 
       960        970        980        990       1000
LPSPVSALKP LVSGPSLGPS GSTFIHPLTG KPLDPSSPLA LALAARERAL 
      1010       1020       1030       1040       1050
ASQAPSRSPT PVHSPDADRP GPLFVDVQAR DPERGSLASP AFSPRSPAWI 
      1060       1070       1080       1090       1100
PVPARREAEK VPREERKSPE DKKSMILSVL DTSLQRPAGL IVVHATSNGQ 
      1110       1120       1130       1140       1150
EPSRLGGAEE ERPGTPELAP APMQSAAVAE PLPSPRAQPP GGTPADAGPG 
      1160       1170       1180       1190       1200
QGSSEEEPEL VFAVNLPPAQ LSSSDEETRE ELARIGLVPP PEEFANGVLL 
      1210       1220       1230       1240       1250
ATPLAGPGPS PTTVPSPASG KPSSEPPPAP ESAADSGVEE ADTRSSSDPH 
      1260       1270       1280       1290       1300
LETTSTISTV SSMSTLSSES GELTDTHTSF ADGHTFLLEK PPVPPKPKLK 
      1310       1320       1330       1340       1350
SPLGKGPVTF RDPLLKQSSD SELMAQQHHA ASAGLASAAG PARPRYLFQR 
      1360       1370       1380       1390       1400
RSKLWGDPVE SRGLPGPEDD KPTVISELSS RLQQLNKDTR SLGEEPVGGL 
      1410       1420       1430       1440       1450
GSLLDPAKKS PIAAARLFSS LGELSSISAQ RSPGGPGGGA SYSVRPSGRY 
      1460       1470       1480       1490       1500
PVARRAPSPV KPASLERVEG LGAGAGGAGR PFGLTPPTIL KSSSLSIPHE 
      1510       1520       1530       1540       1550
PKEVRFVVRS VSARSRSPSP SPLPSPASGP GPGAPGPRRP FQQKPLQLWS 
      1560       1570       1580       1590       1600
KFDVGDWLES IHLGEHRDRF EDHEIEGAHL PALTKDDFVE LGVTRVGHRM 
      1610 
NIERALRQLD GS

Note: Produced by alternative promoter usage.

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Length:1,612

Mass (Da):171,151

Checksum:ⁱB5D0BACA602434C6

GO

Computationally mapped potential isoform sequencesⁱ

There are 2 potential isoforms mapped to this entry.BLAST Align Show all Add to basket

	Entry	Entry name		Protein names	Gene names	Length	Annotation
	A0A0U1RQS4	A0A0U1RQS4_HUMAN		SH3 and multiple ankyrin repeat dom... SH3 and multiple ankyrin repeat domains protein 3	SHANK3	1,730	Annotation score:
	A0A0U1RR93	A0A0U1RR93_HUMAN		SH3 and multiple ankyrin repeat dom... SH3 and multiple ankyrin repeat domains protein 3	SHANK3	1,724	Annotation score:

Natural variant

Feature key	Position(s)	DescriptionActions	Length
Natural variantⁱVAR_032804	12	R → C Found in patients with neuropsychiatric disorders; unknown pathological significance; disrupts synaptic localization. 1 Publication	1
Natural variantⁱVAR_070259	141	P → A in PHMDS. 1 PublicationCorresponds to variant dbSNP:rs397514705EnsemblClinVar.	1
Natural variantⁱVAR_032805	198	A → G1 Publication	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 Publication	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 Publication	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:rs767058690Ensembl.	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:rs139686326Ensembl.	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:rs200087210Ensembl.	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 Publication	1
Natural variantⁱVAR_070271	1557	G → S Found in a patient with neuropsychiatric disorders; unknown pathological significance. 1 Publication	1
Natural variantⁱVAR_070272	1566	S → G1 Publication	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
NCBI Reference Sequences More...RefSeqⁱ	NP_277052.1, NM_033517.1 [Q9BYB0-1]
UniGeneⁱ	Hs.149035

Genome annotation databases

Ensemblⁱ	ENST00000635818; ENSP00000490818; ENSG00000283243 [Q9BYB0-1] ENST00000645837; ENSP00000495774; ENSG00000283243 [Q9BYB0-1]
GeneIDⁱ	85358
KEGGⁱ	hsa:85358

Keywords - Coding sequence diversityⁱ

Alternative promoter usage, Chromosomal rearrangement, Polymorphism

Similar proteinsⁱ

100% Identity
90% Identity
50% Identity

Protein	Similar proteins		Species	Score	Length	Source
Q9BYB0	SH3 and multiple ankyrin repeat domains protein 3	)	RAT		1740	UniRef90_Q9BYB0
Isoform 2 of SH3 and multiple ankyrin repeat domains protein 3		HUMAN		1612
SH3 and multiple ankyrin repeat domains 3		PANTR		1744
SH3 and multiple ankyrin repeat domains 3		CERAT		1739
SH3 and multiple ankyrin repeat domains 3		PIG		1739
+60

Protein	Similar proteins		Species	Score	Length	Source
Q9BYB0	SH3 and multiple ankyrin repeat domains protein 3	)	MOUSE		1730	UniRef50_Q4ACU6
SH3 and multiple ankyrin repeat domains protein 3	)	RAT		1740
SH3 and multiple ankyrin repeat domains 3		PIG		1751
SH3 and multiple ankyrin repeat domains 3		MUSPF		1712
SH3 and multiple ankyrin repeat domains 3		PAPAN		1709
+168

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:	September 12, 2018
	This is version 148 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

Complete proteome, Reference proteome

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Help

UniRef

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Annotation systems

Supporting data

UniProtKB - Q9BYB0 (SHAN3_HUMAN)

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SH3 and multiple ankyrin repeat domains protein 3

Select a section on the left to see content.

<p>This section provides any useful information about the protein, mostly biological knowledge.<p><a href='/help/function_section' target='_top'>More...</a></p>Functioni

<p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:<p><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Molecular functioni

GO - Biological processi

Enzyme and pathway databases

Protein family/group databases

<p>This section provides information about the protein and gene name(s) and synonym(s) and about the organism that is the source of the protein sequence.<p><a href='/help/names_and_taxonomy_section' target='_top'>More...</a></p>Names & Taxonomyi

Organism-specific databases

<p>This section provides information on the location and the topology of the mature protein in the cell.<p><a href='/help/subcellular_location_section' target='_top'>More...</a></p>Subcellular locationi

Plasma membrane

Other locations

Cytosol

Plasma Membrane

Other locations

Keywords - Cellular componenti

<p>This section provides information on the disease(s) and phenotype(s) associated with a protein.<p><a href='/help/pathology_and_biotech_section' target='_top'>More...</a></p>Pathology & Biotechi

Keywords - Diseasei

Organism-specific databases

Polymorphism and mutation databases

<p>This section describes post-translational modifications (PTMs) and/or processing events.<p><a href='/help/ptm_processing_section' target='_top'>More...</a></p>PTM / Processingi

Molecule processing

Amino acid modifications

Keywords - PTMi

Proteomic databases

PTM databases

<p>This section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms.<p><a href='/help/expression_section' target='_top'>More...</a></p>Expressioni

Gene expression databases

Organism-specific databases

<p>This section provides information on the quaternary structure of a protein and on interaction(s) with other proteins or protein complexes.<p><a href='/help/interaction_section' target='_top'>More...</a></p>Interactioni

GO - Molecular functioni

Protein-protein interaction databases

<p>This section provides information on the tertiary and secondary structure of a protein.<p><a href='/help/structure_section' target='_top'>More...</a></p>Structurei

3D structure databases

<p>This section provides information on sequence similarities with other proteins and the domain(s) present in a protein.<p><a href='/help/family_and_domains_section' target='_top'>More...</a></p>Family & Domainsi

Domains and Repeats

Region

Coiled coil

Motif

Compositional bias

Keywords - Domaini

Phylogenomic databases

Family and domain databases

Computationally mapped potential isoform sequencesi

Natural variant

Alternative sequence

Sequence databases

Genome annotation databases

Keywords - Coding sequence diversityi

<p>This section provides general information on the entry.<p><a href='/help/entry_information_section' target='_top'>More...</a></p>Entry informationi

<p>This section contains any relevant information that doesn’t fit in any other defined sections<p><a href='/help/miscellaneous_section' target='_top'>More...</a></p>Miscellaneousi

Keywords - Technical termi

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Functionⁱ

GO - Molecular functionⁱ

GO - Biological processⁱ

Names & Taxonomyⁱ

Subcellular locationⁱ

Keywords - Cellular componentⁱ

Pathology & Biotechⁱ

Keywords - Diseaseⁱ

PTM / Processingⁱ

Keywords - PTMⁱ

Expressionⁱ

Interactionⁱ

GO - Molecular functionⁱ

Structureⁱ

Family & Domainsⁱ

Keywords - Domainⁱ

Computationally mapped potential isoform sequencesⁱ

Keywords - Coding sequence diversityⁱ

Entry informationⁱ

Miscellaneousⁱ

Keywords - Technical termⁱ