Q13425 (SNTB2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Beta-2-syntrophin

Alternative name(s):
59 kDa dystrophin-associated protein A1 basic component 2
Syntrophin-3
Short name=SNT3
Syntrophin-like
Short name=SNTL

Gene names

Name:	SNTB2
Synonyms:	D16S2531E, SNT2B2, SNTL

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	540 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Adapter protein that binds to and probably organizes the subcellular localization of a variety of membrane proteins. May link various receptors to the actin cytoskeleton and the dystrophin glycoprotein complex. May play a role in the regulation of secretory granules via its interaction with PTPRN.
Subunit structure	Monomer and homodimer Probable. Interacts with the other members of the syntrophin family: SNTA1 and SNTB1; and with the sodium channel proteins SCN4A and SCN5A. Interacts with SAST, MAST205, microtubules and microtubule-associated proteins By similarity. Interacts with the dystrophin protein DMD and related proteins DTNA and UTRN, and with the neuroregulin receptor ERBB4. Interacts with PTPRN when phosphorylated, protecting PTPRN from protein cleavage by CAPN1. Dephosphorylation upon insulin stimulation disrupts the interaction with PTPRN and results in the cleavage of PTPRN. Ref.1 Ref.2 Ref.4 Ref.5
Subcellular location	Membrane. Cytoplasmic vesicle › secretory vesicle membrane; Peripheral membrane protein. Cell junction By similarity. Cytoplasm › cytoskeleton. Note: Membrane-associated. In muscle, it is exclusively localized at the neuromuscular junction By similarity. In insulinoma cell line, it is enriched in secretory granules.
Tissue specificity	Ubiquitous. Isoform 1 is the predominant isoform. Weak level of isoform 2 is present in all tested tissues, except in liver and heart where it is highly expressed.
Domain	The PH 1 domain mediates the oligomerization in a calcium dependent manner By similarity. The PDZ domain binds to the last three or four amino acids of ion channels and receptor proteins. The association with dystrophin or related proteins probably leaves the PDZ domain available to recruit proteins to the membrane By similarity. The SU domain binds calmodulin in a calcium-dependent manner By similarity.
Post-translational modification	Phosphorylated. Partially dephosphorylated upon insulin stimulation.
Sequence similarities	Belongs to the syntrophin family. Contains 1 PDZ (DHR) domain. Contains 2 PH domains. Contains 1 SU (syntrophin unique) domain.

Ontologies

Keywords
Cellular component	Cell junction Cytoplasm Cytoplasmic vesicle Cytoskeleton Membrane Microtubule
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Repeat
Ligand	Actin-binding Calcium Calmodulin-binding
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Cellular_component	cell junction Inferred from electronic annotation. Source: UniProtKB-SubCell cytoplasm Inferred from direct assay PubMed 19786618. Source: UniProtKB dystrophin-associated glycoprotein complex Traceable author statement Ref.1. Source: ProtInc microtubule Inferred from electronic annotation. Source: UniProtKB-KW synapse Inferred from electronic annotation. Source: Compara transport vesicle membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	phospholipid binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Alternative products

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

Isoform 1 (identifier: Q13425-1)

Also known as: Beta2-syntrophin58;

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: Q13425-2)

Also known as: Beta2-syntrophin28;

The sequence of this isoform differs from the canonical sequence as follows:
     266-267: LI → QN
     268-540: Missing.

Note: Lacks domains required for interaction with dystrophin related proteins. May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 540

540

Beta-2-syntrophin

PRO_0000184011

Regions

Domain

115 – 198

84

PDZ

Domain

163 – 300

138

PH 1

Domain

325 – 437

113

PH 2

Domain

484 – 540

57

SU

Region

518 – 540

23

Calmodulin-binding By similarity

Compositional bias

54 – 57

4

Poly-Ala

Compositional bias

66 – 69

4

Poly-Ala

Amino acid modifications

Modified residue

95

1

Phosphoserine Ref.9 Ref.12

Modified residue

110

1

Phosphoserine Ref.7 Ref.8 Ref.12

Modified residue

222

1

Phosphoserine Ref.10 Ref.12

Modified residue

233

1

Phosphoserine Ref.10

Modified residue

393

1

Phosphoserine Ref.10 Ref.12

Natural variations

Alternative sequence

266 – 267

2

LI → QN in isoform 2.

VSP_006358

Alternative sequence

268 – 540

273

Missing in isoform 2.

VSP_006359

Natural variant

424

1

D → E.
Corresponds to variant rs1058482 [ dbSNP | Ensembl ].

VAR_014076

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

540

Helix Strand Turn

Details...

Beta strand

113 – 119

7

Beta strand

127 – 133

7

Helix

134 – 136

3

Beta strand

138 – 145

8

Helix

150 – 154

5

Beta strand

161 – 166

6

Helix

176 – 184

9

Beta strand

188 – 196

9

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (Beta2-syntrophin58) [UniParc]. Last modified November 1, 1996. Version 1. Checksum: 53A9F3340DC024ED	FASTA	540	57,950
	10 20 30 40 50 60 MRVAAATAAA GAGPAMAVWT RATKAGLVEL LLRERWVRVV AELSGESLSL TGDAAAAELE 70 80 90 100 110 120 PALGPAAAAF NGLPNGGGAG DSLPGSPSRG LGPPSPPAPP RGPAGEAGAS PPVRRVRVVK 130 140 150 160 170 180 QEAGGLGISI KGGRENRMPI LISKIFPGLA ADQSRALRLG DAILSVNGTD LRQATHDQAV 190 200 210 220 230 240 QALKRAGKEV LLEVKFIREV TPYIKKPSLV SDLPWEGAAP QSPSFSGSED SGSPKHQNST 250 260 270 280 290 300 KDRKIIPLKM CFAARNLSMP DLENRLIELH SPDSRNTLIL RCKDTATAHS WFVAIHTNIM 310 320 330 340 350 360 ALLPQVLAEL NAMLGATSTA GGSKEVKHIA WLAEQAKLDG GRQQWRPVLM AVTEKDLLLY 370 380 390 400 410 420 DCMPWTRDAW ASPCHSYPLV ATRLVHSGSG CRSPSLGSDL TFATRTGSRQ GIEMHLFRVE 430 440 450 460 470 480 THRDLSSWTR ILVQGCHAAA ELIKEVSLGC MLNGQEVRLT IHYENGFTIS RENGGSSSIL 490 500 510 520 530 540 YRYPFERLKM SADDGIRNLY LDFGGPEGEL TMDLHSCPKP IVFVLHTFLS AKVTRMGLLV
	Isoform 2 (Beta2-syntrophin28) [UniParc]. Checksum: 45DF36C82C013228	FASTA	267	27,677
	10 20 30 40 50 60 MRVAAATAAA GAGPAMAVWT RATKAGLVEL LLRERWVRVV AELSGESLSL TGDAAAAELE 70 80 90 100 110 120 PALGPAAAAF NGLPNGGGAG DSLPGSPSRG LGPPSPPAPP RGPAGEAGAS PPVRRVRVVK 130 140 150 160 170 180 QEAGGLGISI KGGRENRMPI LISKIFPGLA ADQSRALRLG DAILSVNGTD LRQATHDQAV 190 200 210 220 230 240 QALKRAGKEV LLEVKFIREV TPYIKKPSLV SDLPWEGAAP QSPSFSGSED SGSPKHQNST 250 260 KDRKIIPLKM CFAARNLSMP DLENRQN

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"The three human syntrophin genes are expressed in diverse tissues, have distinct chromosomal locations, and each bind to dystrophin and its relatives." Ahn A.H., Feener C.A., Gussoni E., Yoshida M., Ozawa E., Kunkel L.M. J. Biol. Chem. 271:2724-2730(1996) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), INTERACTION WITH DMD; DTNA AND UTRN. Tissue: Muscle.
[2]	"The receptor tyrosine phosphatase-like protein ICA512 binds the PDZ domains of beta2-syntrophin and nNOS in pancreatic beta-cells." Ort T., Maksimova E., Dirkx R., Kachinsky A.M., Berghs S., Froehner S.C., Solimena M. Eur. J. Cell Biol. 79:621-630(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), INTERACTION WITH PTPRN. Tissue: Brain.
[3]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Mammary gland.
[4]	"The neuregulin receptor ErbB-4 interacts with PDZ-containing proteins at neuronal synapses." Garcia R.A., Vasudevan K., Buonanno A. Proc. Natl. Acad. Sci. U.S.A. 97:3596-3601(2000) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH ERBB4.
[5]	"Dephosphorylation of beta2-syntrophin and Ca2+/mu-calpain-mediated cleavage of ICA512 upon stimulation of insulin secretion." Ort T., Voronov S., Guo J., Zawalich K., Froehner S.C., Zawalich W., Solimena M. EMBO J. 20:4013-4023(2001) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH PTPRN.
[6]	"An unappreciated role for RNA surveillance." Hillman R.T., Green R.E., Brenner S.E. Genome Biol. 5:R8.1-R8.16(2004) [PubMed] [Europe PMC] [Abstract] Cited for: SPLICE ISOFORM(S) THAT ARE POTENTIAL NMD TARGET(S).
[7]	"Global, in vivo, and site-specific phosphorylation dynamics in signaling networks." Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M. Cell 127:635-648(2006) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-110, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[8]	"Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient phosphoproteomic analysis." Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D., Yates J.R. III J. Proteome Res. 7:1346-1351(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-110, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[9]	"Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle." Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., Greff Z., Keri G., Stemmann O., Mann M. Mol. Cell 31:438-448(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-95, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[10]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-222; SER-233 AND SER-393, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[11]	"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: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. Tissue: Leukemic T-cell.
[12]	"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis." Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M. Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-95; SER-110; SER-222 AND SER-393, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[13]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[14]	"System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation." Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B. Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

U40572 mRNA. Translation: AAC50449.1.
AF243385 mRNA. Translation: AAK15149.1.
BC048215 mRNA. Translation: AAH48215.1.

IPI

IPI00009505.
IPI00216631.

RefSeq

NP_006741.1. NM_006750.3.

UniGene

Hs.461117.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2VRF	X-ray	2.00	A/B/C/D	112-200	[»]

ProteinModelPortal

Q13425.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q13425. 7 interactions.

MINT

MINT-239533.

STRING

9606.ENSP00000338191.

PTM databases

PhosphoSite

Q13425.

Polymorphism databases

DMDM

23822158.

Proteomic databases

PaxDb

Q13425.

PeptideAtlas

Q13425.

PRIDE

Q13425.

Protocols and materials databases

DNASU

6645.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000336278; ENSP00000338191; ENSG00000168807.
ENST00000467311; ENSP00000436443; ENSG00000168807.
ENST00000562438; ENSP00000458999; ENSG00000260873.

GeneID

6645.

KEGG

hsa:6645.

UCSC

uc002ewu.3. human.

Organism-specific databases

CTD

6645.

GeneCards

GC16P069221.

HGNC

HGNC:11169. SNTB2.

HPA

HPA001394.

MIM

600027. gene.

neXtProt

NX_Q13425.

PharmGKB

PA36009.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG318350.

HOGENOM

HOG000231596.

HOVERGEN

HBG054204.

InParanoid

Q13425.

OMA

WTRALVQ.

OrthoDB

EOG4VX257.

PhylomeDB

Q13425.

Gene expression databases

ArrayExpress

Q13425.

Bgee

Q13425.

CleanEx

HS_SNTB2.

Genevestigator

Q13425.

GermOnline

ENSG00000168807. Homo sapiens.

Family and domain databases

InterPro

IPR001478. PDZ.
IPR001849. Pleckstrin_homology.
IPR015482. Syntrophin.
[Graphical view]

PANTHER

PTHR10554. PTHR10554. 1 hit.

Pfam

PF00595. PDZ. 1 hit.
[Graphical view]

SMART

SM00228. PDZ. 1 hit.
SM00233. PH. 2 hits.
[Graphical view]

SUPFAM

SSF50156. PDZ. 1 hit.

PROSITE

PS50106. PDZ. 1 hit.
PS50003. PH_DOMAIN. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

ChiTaRS

SNTB2. human.

EvolutionaryTrace

Q13425.

GenomeRNAi

6645.

NextBio

25895.

SOURCE

Search...

Entry information

Entry name

SNTB2_HUMAN

Accession

Primary (citable) accession number: Q13425
Secondary accession number(s): Q9BY09

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 10, 2002
Last sequence update:	November 1, 1996
Last modified:	May 1, 2013
This is version 133 of the entry and version 1 of the sequence. [Complete history]

Entry status

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.