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

Gene ID: 85464, updated on 2-Nov-2024

Summary

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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
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Genomic context

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See SSH2 in Genome Data Viewer
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_000017.11Genomic Context describing neighboring genes Neighboring gene ATAC-STARR-seq lymphoblastoid active region 11982 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr17:27940429-27941292 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 8382 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr17:27942158-27943021 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 8384 Neighboring gene Sharpr-MPRA regulatory region 12866 Neighboring gene ankyrin repeat domain 13B Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 8385 Neighboring gene P300/CBP strongly-dependent group 1 enhancer GRCh37_chr17:27950531-27951730 Neighboring gene NANOG hESC enhancer GRCh37_chr17:27960948-27961512 Neighboring gene Sharpr-MPRA regulatory region 11433 Neighboring gene uncharacterized LOC107984990 Neighboring gene Sharpr-MPRA regulatory region 3347 Neighboring gene RNA, U6 small nuclear 920, pseudogene Neighboring gene Sharpr-MPRA regulatory region 7669 Neighboring gene coronin 6 Neighboring gene VISTA enhancer hs1675 Neighboring gene MPRA-validated peak2783 silencer Neighboring gene ATAC-STARR-seq lymphoblastoid active region 11984 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr17:28040137-28040766 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 8386 Neighboring gene ribosomal protein L21 pseudogene 123 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 11985 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 8387 Neighboring gene RNA terminal phosphate cyclase like 1 pseudogene Neighboring gene uncharacterized LOC124900394 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 11986 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 11987 Neighboring gene uncharacterized LOC124900390 Neighboring gene small nucleolar RNA U13 Neighboring gene ribosomal protein L9 pseudogene 30 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 8388 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 8389 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 8390 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 8391 Neighboring gene Sharpr-MPRA regulatory region 3195 Neighboring gene EF-hand calcium binding domain 5 Neighboring gene Sharpr-MPRA regulatory region 15362 Neighboring gene MED14-independent group 3 enhancer GRCh37_chr17:28367348-28368547 Neighboring gene RNY4 pseudogene 13 Neighboring gene syntaxin 18 pseudogene 1

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • 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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Related articles in PubMed

  1. Identification of genes expressed during myocardial development. Chan SY, et al. Chin Med J (Engl), 2003 Sep. PMID 14527359
  2. Crystal structure of human slingshot phosphatase 2. Jung SK, et al. Proteins, 2007 Jul 1. PMID 17427953
  3. Allosteric modulation of the catalytic VYD loop in Slingshot by its N-terminal domain underlies both Slingshot auto-inhibition and activation. Yang D, et al. J Biol Chem, 2018 Oct 19. PMID 30154244, Free PMC Article
  4. Slingshot isoform-specific regulation of cofilin-mediated vascular smooth muscle cell migration and neointima formation. Torres RA, et al. Arterioscler Thromb Vasc Biol, 2011 Nov. PMID 21868701, Free PMC Article
  5. 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). Lu X, et al. Oncogene, 2014 Feb 20. PMID 23416984

See all (39) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. 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.
  2. 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.
  3. 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).
  4. 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.
  5. 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.
Submit: New GeneRIF Correction

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

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Genotypes

Pathways from PubChem

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Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Markers

Homology

Clone Names

  • KIAA1725, MGC78588

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 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
NP_001269059.1
NP_001269060.1
NP_203747.2
XP_005258115.1
XP_005258116.1
XP_005258117.1
XP_006722212.1
XP_011523706.1
XP_011523709.1
XP_016880742.1
XP_047292923.1
XP_047292924.1
XP_047292925.1
XP_047292926.1
XP_047292927.1
XP_054173595.1
XP_054173596.1
XP_054173597.1
XP_054173598.1
XP_054173599.1
XP_054173600.1
XP_054173601.1
XP_054173602.1
XP_054173603.1
XP_054173604.1
XP_054173605.1
XP_054173606.1

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)

  1. 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

  2. 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

  3. 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

  4. 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

  1. NC_000017.11 Reference GRCh38.p14 Primary Assembly

    Range
    29625938..29930228 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

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

    UniProtKB/Swiss-Prot
    Q76I76, Q8TDB5, Q8WYL1, Q8WYL2, Q96F40, Q96H36, Q9C0D8

  2. 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

  3. XM_047436968.1 → XP_047292924.1  protein phosphatase Slingshot homolog 2 isoform X11

  4. 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

  5. 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

  6. XM_047436969.1 → XP_047292925.1  protein phosphatase Slingshot homolog 2 isoform X6

  7. 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

  8. 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

  9. XM_005258060.4 → XP_005258117.1  protein phosphatase Slingshot homolog 2 isoform X7

    UniProtKB/TrEMBL
    B3KRE8

  10. XM_047436970.1 → XP_047292926.1  protein phosphatase Slingshot homolog 2 isoform X9

  11. XM_017025253.3 → XP_016880742.1  protein phosphatase Slingshot homolog 2 isoform X8

  12. XM_047436971.1 → XP_047292927.1  protein phosphatase Slingshot homolog 2 isoform X10

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060941.1 Alternate T2T-CHM13v2.0

    Range
    30568840..30873583 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_054317622.1 → XP_054173597.1  protein phosphatase Slingshot homolog 2 isoform X3

  2. XM_054317620.1 → XP_054173595.1  protein phosphatase Slingshot homolog 2 isoform X1

  3. XM_054317627.1 → XP_054173602.1  protein phosphatase Slingshot homolog 2 isoform X6

  4. XM_054317626.1 → XP_054173601.1  protein phosphatase Slingshot homolog 2 isoform X6

  5. XM_054317625.1 → XP_054173600.1  protein phosphatase Slingshot homolog 2 isoform X6

  6. XM_054317621.1 → XP_054173596.1  protein phosphatase Slingshot homolog 2 isoform X2

  7. XM_054317624.1 → XP_054173599.1  protein phosphatase Slingshot homolog 2 isoform X5

  8. XM_054317623.1 → XP_054173598.1  protein phosphatase Slingshot homolog 2 isoform X4

  9. XM_054317628.1 → XP_054173603.1  protein phosphatase Slingshot homolog 2 isoform X7

  10. XM_054317630.1 → XP_054173605.1  protein phosphatase Slingshot homolog 2 isoform X9

  11. XM_054317629.1 → XP_054173604.1  protein phosphatase Slingshot homolog 2 isoform X8

  12. XM_054317631.1 → XP_054173606.1  protein phosphatase Slingshot homolog 2 isoform X10

Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
Q76I76.1 GenPept UniProtKB/Swiss-Prot:Q76I76

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