SSH2 slingshot protein phosphatase 2 [Homo sapiens (human)] - Gene

Summary

Official Symbol: SSH2provided by HGNC
Official Full Name: slingshot protein phosphatase 2provided by HGNC
Primary source: HGNC:HGNC:30580
See related: Ensembl:ENSG00000141298 MIM:606779; AllianceGenome:HGNC:30580
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: SSH-2; SSH-2L
Summary: This gene encodes a protein tyrosine phosphatase that plays a key role in the regulation of actin filaments. The encoded protein dephosphorylates and activates cofilin, which promotes actin filament depolymerization. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2013]
Expression: Broad expression in lymph node (RPKM 6.2), appendix (RPKM 6.0) and 24 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 17q11.2

Exon count:: 24

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	17	NC_000017.11 (29625938..29930228, complement)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	17	NC_060941.1 (30568840..30873583, complement)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	17	NC_000017.10 (27952956..28257246, complement)

Chromosome 17 - NC_000017.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

the N-terminal region of human Slingshot2 auto-inhibits its phosphatase activity in a noncompetitive manner
Title: Allosteric modulation of the catalytic VYD loop in Slingshot by its N-terminal domain underlies both Slingshot auto-inhibition and activation.
Novel signaling pathway consisting of chemoattractant GPCR/Galphai protein, PLC, PKCbeta and PKDs that regulates SSH2/cofilin activity, F-actin polymerization and directional assembly of actin cytoskeleton in neutrophil chemotaxis was identified.
Title: GPCR-mediated PLCβγ/PKCβ/PKD signaling pathway regulates the cofilin phosphatase slingshot 2 in neutrophil chemotaxis.
data indicate that: (a) apoptotic cell death in FLCN-null cells can be triggered by SSH2 knockdown through cell cycle arrest; (b) SSH2 represents a potential therapeutic target for the development of agents for the treatment of BHD syndrome related tumors
Title: Knockdown of Slingshot 2 (SSH2) serine phosphatase induces Caspase3 activation in human carcinoma cell lines with the loss of the Birt-Hogg-Dubé tumour suppressor gene (FLCN).
Observational study of gene-disease association. (HuGE Navigator)
Title: Mutational analysis of mononucleotide repeats in dual specificity tyrosine phosphatase genes in gastric and colon carcinomas with microsatellite instability.
Expression of phosphatase-dead versions of SSH proteins, SSH1, SSH2 & SSH3 results in phosphorylation/inactivation of cofilin, changes in cytoskeleton organization, loss of cell polarity, and assembly of aberrant arrays of laminin-332 in keratinocytes.
Title: The slingshot family of phosphatases mediates Rac1 regulation of cofilin phosphorylation, laminin-332 organization, and motility behavior of keratinocytes.

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Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

EBI GWAS Catalog

Description
Genome-wide meta-analysis identifies six novel loci associated with habitual coffee consumption. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See Variation Viewer (GRCh37.p13)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

D17S975 (e-PCR), detects polymorphism
- UniSTS:15882

D11S2921 (e-PCR)
- UniSTS:152074

D8S2279 (e-PCR)
- UniSTS:473907

D16S3113 (e-PCR)
- UniSTS:65089

SHGC-107232 (e-PCR)
- UniSTS:168527

A009U17 (e-PCR)
- UniSTS:78950

D10S16 (e-PCR)
- UniSTS:155756

D15S1477 (e-PCR)
- UniSTS:474482

D1S1423 (e-PCR)
- UniSTS:149619

D1S1425 (e-PCR)
- UniSTS:149621

D11S3114 (e-PCR)
- UniSTS:152207

D16S325 (e-PCR)
- UniSTS:147089

RH16560 (e-PCR)
- UniSTS:52118

SHGC-56835 (e-PCR)
- UniSTS:37531

G32840 (e-PCR)
- UniSTS:117419

RH46489 (e-PCR)
- UniSTS:87726

RH103904 (e-PCR)
- UniSTS:98229

Cda0kh01 (e-PCR)
- UniSTS:43223

SHGC-33453 (e-PCR)
- UniSTS:18394

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables actin binding	IBA Inferred from Biological aspect of Ancestor more info
enables actin binding	IDA Inferred from Direct Assay more info	PubMed
enables myosin phosphatase activity	IEA Inferred from Electronic Annotation more info
enables phosphoprotein phosphatase activity	IBA Inferred from Biological aspect of Ancestor more info
enables phosphoprotein phosphatase activity	IDA Inferred from Direct Assay more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein tyrosine phosphatase activity	IEA Inferred from Electronic Annotation more info

Process	Evidence Code	Pubs
involved_in actin cytoskeleton organization	IBA Inferred from Biological aspect of Ancestor more info
involved_in actin cytoskeleton organization	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in cell differentiation	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of actin filament polymerization	IBA Inferred from Biological aspect of Ancestor more info
involved_in protein dephosphorylation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in spermatogenesis	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
located_in acrosomal vesicle	IEA Inferred from Electronic Annotation more info
is_active_in cytoplasm	IBA Inferred from Biological aspect of Ancestor more info
located_in cytoskeleton	IEA Inferred from Electronic Annotation more info
located_in extracellular space	HDA more info	PubMed
located_in focal adhesion	IEA Inferred from Electronic Annotation more info

General protein information

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Preferred Names: protein phosphatase Slingshot homolog 2

Names: SSH-like protein 2

NP_001269058.1

EC 3.1.3.16

EC 3.1.3.48

NP_001269059.1

EC 3.1.3.16

EC 3.1.3.48

NP_001269060.1

EC 3.1.3.16

EC 3.1.3.48

NP_203747.2

EC 3.1.3.16

EC 3.1.3.48

XP_005258115.1

EC 3.1.3.16

EC 3.1.3.48

XP_005258116.1

EC 3.1.3.16

EC 3.1.3.48

XP_005258117.1

EC 3.1.3.16

EC 3.1.3.48

XP_006722212.1

EC 3.1.3.16

EC 3.1.3.48

XP_011523706.1

EC 3.1.3.16

EC 3.1.3.48

XP_011523709.1

EC 3.1.3.16

EC 3.1.3.48

XP_016880742.1

EC 3.1.3.16

EC 3.1.3.48

XP_047292923.1

EC 3.1.3.16

EC 3.1.3.48

XP_047292924.1

EC 3.1.3.16

EC 3.1.3.48

XP_047292925.1

EC 3.1.3.16

EC 3.1.3.48

XP_047292926.1

EC 3.1.3.16

EC 3.1.3.48

XP_047292927.1

EC 3.1.3.16

EC 3.1.3.48

XP_054173595.1

EC 3.1.3.16

EC 3.1.3.48

XP_054173596.1

EC 3.1.3.16

EC 3.1.3.48

XP_054173597.1

EC 3.1.3.16

EC 3.1.3.48

XP_054173598.1

EC 3.1.3.16

EC 3.1.3.48

XP_054173599.1

EC 3.1.3.16

EC 3.1.3.48

XP_054173600.1

EC 3.1.3.16

EC 3.1.3.48

XP_054173601.1

EC 3.1.3.16

EC 3.1.3.48

XP_054173602.1

EC 3.1.3.16

EC 3.1.3.48

XP_054173603.1

EC 3.1.3.16

EC 3.1.3.48

XP_054173604.1

EC 3.1.3.16

EC 3.1.3.48

XP_054173605.1

EC 3.1.3.16

EC 3.1.3.48

XP_054173606.1

EC 3.1.3.16

EC 3.1.3.48

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

NM_001282129.2 → NP_001269058.1 protein phosphatase Slingshot homolog 2 isoform 1

See identical proteins and their annotated locations for NP_001269058.1

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents the longest transcript and encodes the longest isoform (1).

Source sequence(s)

AB099290, AC104982, AI609950, AK296413, DA749059

Consensus CDS

CCDS74024.1

UniProtKB/TrEMBL

B4DK64, F5H527

Related

ENSP00000444743.1, ENST00000540801.6

Conserved Domains (3) summary

cd11652
Location:38 → 263

SSH-N; N-terminal domain conserved in slingshot (SSH) phosphatases

cd00127
Location:335 → 470

DSPc; Dual specificity phosphatases (DSP); Ser/Thr and Tyr protein phosphatases. Structurally similar to tyrosine-specific phosphatases but with a shallower active site cleft and a distinctive active site signature motif, HCxxGxxR. Characterized as VHR- or ...

pfam08766
Location:278 → 329

DEK_C; DEK C terminal domain
NM_001282130.2 → NP_001269059.1 protein phosphatase Slingshot homolog 2 isoform 3

See identical proteins and their annotated locations for NP_001269059.1

Status: REVIEWED

Description

Transcript Variant: This variant (3) lacks multiple coding exons and contains an alternate 3' exon, resulting in a distinct 3' coding region and 3' UTR, compared to variant 1. The encoded isoform (3) is shorter and has a distinct C-terminus, compared to isoform 1.

Source sequence(s)

AC104564, AC104982, BC008941, DA749059

UniProtKB/Swiss-Prot

Q76I76

Conserved Domains (1) summary

cd11652
Location:3 → 178

SSH-N; N-terminal domain conserved in slingshot (SSH) phosphatases
NM_001282131.2 → NP_001269060.1 protein phosphatase Slingshot homolog 2 isoform 4

See identical proteins and their annotated locations for NP_001269060.1

Status: REVIEWED

Description

Transcript Variant: This variant (4) contains multiple differences in the UTRs and coding region, compared to variant 1, including the lack of multiple 5' and 3' coding exons. It represents use of an internal promoter and initiates translation at an alternate start codon. The encoded isoform (4) is shorter and has distinct N- and C- termini, compared to isoform 1.

Source sequence(s)

AC104564, BC008941, BC011636, DA861985

Consensus CDS

CCDS92286.1

UniProtKB/TrEMBL

A0A3B3ITS1

Related

ENSP00000497894.1, ENST00000324677.12

Conserved Domains (1) summary

cd11652
Location:37 → 185

SSH-N; N-terminal domain conserved in slingshot (SSH) phosphatases
NM_033389.3 → NP_203747.2 protein phosphatase Slingshot homolog 2 isoform 2

See identical proteins and their annotated locations for NP_203747.2

Status: REVIEWED

Description

Transcript Variant: This variant (2) differs in the 5' UTR and lacks an alternate in-frame exon in the 5' coding region, compared to variant 1. The encoded isoform (2) is shorter than isoform 1.

Source sequence(s)

AB099290, AC104564, AI609950, DA749059

Consensus CDS

CCDS11253.1

UniProtKB/Swiss-Prot

Q76I76, Q8TDB5, Q8WYL1, Q8WYL2, Q96F40, Q96H36, Q9C0D8

UniProtKB/TrEMBL

B4DK64

Related

ENSP00000269033.3, ENST00000269033.7

Conserved Domains (3) summary

cd11652
Location:3 → 236

SSH-N; N-terminal domain conserved in slingshot (SSH) phosphatases

cd00127
Location:308 → 443

DSPc; Dual specificity phosphatases (DSP); Ser/Thr and Tyr protein phosphatases. Structurally similar to tyrosine-specific phosphatases but with a shallower active site cleft and a distinctive active site signature motif, HCxxGxxR. Characterized as VHR- or ...

pfam08766
Location:251 → 302

DEK_C; DEK C terminal domain

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000017.11 Reference GRCh38.p14 Primary Assembly

Range

29625938..29930228 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_047436967.1 → XP_047292923.1 protein phosphatase Slingshot homolog 2 isoform X3

UniProtKB/Swiss-Prot

Q76I76, Q8TDB5, Q8WYL1, Q8WYL2, Q96F40, Q96H36, Q9C0D8
XM_005258058.4 → XP_005258115.1 protein phosphatase Slingshot homolog 2 isoform X1

See identical proteins and their annotated locations for XP_005258115.1

UniProtKB/TrEMBL

B4DK64, F5H527

Conserved Domains (3) summary

cd11652
Location:38 → 263

SSH-N; N-terminal domain conserved in slingshot (SSH) phosphatases

cd00127
Location:335 → 470

DSPc; Dual specificity phosphatases (DSP); Ser/Thr and Tyr protein phosphatases. Structurally similar to tyrosine-specific phosphatases but with a shallower active site cleft and a distinctive active site signature motif, HCxxGxxR. Characterized as VHR- or ...

pfam08766
Location:278 → 329

DEK_C; DEK C terminal domain
XM_047436968.1 → XP_047292924.1 protein phosphatase Slingshot homolog 2 isoform X11
XM_011525407.1 → XP_011523709.1 protein phosphatase Slingshot homolog 2 isoform X6

See identical proteins and their annotated locations for XP_011523709.1

UniProtKB/TrEMBL

A0A3B3IS79

Conserved Domains (3) summary

cd11652
Location:17 → 160

SSH-N; N-terminal domain conserved in slingshot (SSH) phosphatases

cd00127
Location:232 → 367

DSPc; Dual specificity phosphatases (DSP); Ser/Thr and Tyr protein phosphatases. Structurally similar to tyrosine-specific phosphatases but with a shallower active site cleft and a distinctive active site signature motif, HCxxGxxR. Characterized as VHR- or ...

pfam08766
Location:175 → 226

DEK_C; DEK C terminal domain
XM_005258059.3 → XP_005258116.1 protein phosphatase Slingshot homolog 2 isoform X2

See identical proteins and their annotated locations for XP_005258116.1

UniProtKB/TrEMBL

A0A3B3IS79

Related

ENSP00000497148.1, ENST00000649863.1

Conserved Domains (3) summary

cd11652
Location:37 → 243

SSH-N; N-terminal domain conserved in slingshot (SSH) phosphatases

cd00127
Location:315 → 450

DSPc; Dual specificity phosphatases (DSP); Ser/Thr and Tyr protein phosphatases. Structurally similar to tyrosine-specific phosphatases but with a shallower active site cleft and a distinctive active site signature motif, HCxxGxxR. Characterized as VHR- or ...

pfam08766
Location:258 → 309

DEK_C; DEK C terminal domain
XM_047436969.1 → XP_047292925.1 protein phosphatase Slingshot homolog 2 isoform X6
XM_006722149.5 → XP_006722212.1 protein phosphatase Slingshot homolog 2 isoform X5

UniProtKB/TrEMBL

A0A3B3IS79

Conserved Domains (3) summary

cd11652
Location:14 → 214

SSH-N; N-terminal domain conserved in slingshot (SSH) phosphatases

cd00127
Location:286 → 421

DSPc; Dual specificity phosphatases (DSP); Ser/Thr and Tyr protein phosphatases. Structurally similar to tyrosine-specific phosphatases but with a shallower active site cleft and a distinctive active site signature motif, HCxxGxxR. Characterized as VHR- or ...

pfam08766
Location:229 → 280

DEK_C; DEK C terminal domain
XM_011525404.3 → XP_011523706.1 protein phosphatase Slingshot homolog 2 isoform X4

UniProtKB/TrEMBL

A0A3B3IS79

Conserved Domains (3) summary

cd11652
Location:18 → 218

SSH-N; N-terminal domain conserved in slingshot (SSH) phosphatases

cd00127
Location:290 → 425

DSPc; Dual specificity phosphatases (DSP); Ser/Thr and Tyr protein phosphatases. Structurally similar to tyrosine-specific phosphatases but with a shallower active site cleft and a distinctive active site signature motif, HCxxGxxR. Characterized as VHR- or ...

pfam08766
Location:233 → 284

DEK_C; DEK C terminal domain
XM_005258060.4 → XP_005258117.1 protein phosphatase Slingshot homolog 2 isoform X7

UniProtKB/TrEMBL

B3KRE8
XM_047436970.1 → XP_047292926.1 protein phosphatase Slingshot homolog 2 isoform X9
XM_017025253.3 → XP_016880742.1 protein phosphatase Slingshot homolog 2 isoform X8
XM_047436971.1 → XP_047292927.1 protein phosphatase Slingshot homolog 2 isoform X10

Alternate T2T-CHM13v2.0

Genomic

NC_060941.1 Alternate T2T-CHM13v2.0

Range

30568840..30873583 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_054317622.1 → XP_054173597.1 protein phosphatase Slingshot homolog 2 isoform X3
XM_054317620.1 → XP_054173595.1 protein phosphatase Slingshot homolog 2 isoform X1
XM_054317627.1 → XP_054173602.1 protein phosphatase Slingshot homolog 2 isoform X6
XM_054317626.1 → XP_054173601.1 protein phosphatase Slingshot homolog 2 isoform X6
XM_054317625.1 → XP_054173600.1 protein phosphatase Slingshot homolog 2 isoform X6
XM_054317621.1 → XP_054173596.1 protein phosphatase Slingshot homolog 2 isoform X2
XM_054317624.1 → XP_054173599.1 protein phosphatase Slingshot homolog 2 isoform X5
XM_054317623.1 → XP_054173598.1 protein phosphatase Slingshot homolog 2 isoform X4
XM_054317628.1 → XP_054173603.1 protein phosphatase Slingshot homolog 2 isoform X7
XM_054317630.1 → XP_054173605.1 protein phosphatase Slingshot homolog 2 isoform X9
XM_054317629.1 → XP_054173604.1 protein phosphatase Slingshot homolog 2 isoform X8
XM_054317631.1 → XP_054173606.1 protein phosphatase Slingshot homolog 2 isoform X10