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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
    mouse all
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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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