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    SH2D3C SH2 domain containing 3C [ Homo sapiens (human) ]

    Gene ID: 10044, updated on 5-Mar-2024

    Summary

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    Official Symbol
    SH2D3Cprovided by HGNC
    Official Full Name
    SH2 domain containing 3Cprovided by HGNC
    Primary source
    HGNC:HGNC:16884
    See related
    Ensembl:ENSG00000095370 MIM:604722; AllianceGenome:HGNC:16884
    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
    CHAT; NSP3; SHEP1; PRO34088
    Summary
    This gene encodes an adaptor protein and member of a cytoplasmic protein family involved in cell migration. The encoded protein contains a putative Src homology 2 (SH2) domain and guanine nucleotide exchange factor-like domain which allows this signaling protein to form a complex with scaffolding protein Crk-associated substrate. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2011]
    Expression
    Broad expression in spleen (RPKM 12.4), lung (RPKM 10.5) and 22 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    Location:
    9q34.11
    Exon count:
    16
    Annotation release Status Assembly Chr Location
    RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 9 NC_000009.12 (127738317..127778666, complement)
    RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 9 NC_060933.1 (139945763..139986120, complement)
    105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 9 NC_000009.11 (130500596..130540945, complement)

    Chromosome 9 - NC_000009.12Genomic Context describing neighboring genes Neighboring gene peptidyl-tRNA hydrolase 1 homolog Neighboring gene cilia and flagella associated protein 157 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr9:130476687-130477343 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 29045 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 29046 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 29047 Neighboring gene ReSE screen-validated silencer GRCh37_chr9:130478240-130478416 Neighboring gene ReSE screen-validated silencer GRCh37_chr9:130480462-130480664 Neighboring gene tetratricopeptide repeat domain 16 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr9:130488893-130489394 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr9:130496147-130497053 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 20308 Neighboring gene torsin family 2 member A Neighboring gene H3K4me1 hESC enhancer GRCh37_chr9:130504225-130504852 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr9:130523547-130524424 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr9:130524425-130525300 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr9:130526508-130527090 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 20309 Neighboring gene uncharacterized LOC107987132 Neighboring gene ReSE screen-validated silencer GRCh37_chr9:130539526-130539796 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 29049 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 29050 Neighboring gene ReSE screen-validated silencer GRCh37_chr9:130545551-130545741 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 29052 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 20310 Neighboring gene Sharpr-MPRA regulatory region 7866 Neighboring gene Sharpr-MPRA regulatory region 2041 Neighboring gene microRNA 3960 Neighboring gene microRNA 2861 Neighboring gene cyclin dependent kinase 9

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Bibliography

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    Related articles in PubMed

    1. NSP-Cas protein structures reveal a promiscuous interaction module in cell signaling. Mace PD, et al. Nat Struct Mol Biol, 2011 Nov 13. PMID 22081014, Free PMC Article
    2. Splice variants and expression patterns of SHEP1, BCAR3 and NSP1, a gene family involved in integrin and receptor tyrosine kinase signaling. Vervoort VS, et al. Gene, 2007 Apr 15. PMID 17270363, Free PMC Article
    3. A novel signaling intermediate, SHEP1, directly couples Eph receptors to R-Ras and Rap1A. Dodelet VC, et al. J Biol Chem, 1999 Nov 5. PMID 10542222
    4. AND-34/BCAR3 differs from other NSP homologs in induction of anti-estrogen resistance, cyclin D1 promoter activation and altered breast cancer cell morphology. Near RI, et al. J Cell Physiol, 2007 Sep. PMID 17427198, Free PMC Article
    5. SHEP1 function in cell migration is impaired by a single amino acid mutation that disrupts association with the scaffolding protein cas but not with Ras GTPases. Dail M, et al. J Biol Chem, 2004 Oct 1. PMID 15272013

    See all (30) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. The structure of the NSP3-p130Cas complex reveals that this closed conformation is instrumental for interaction of NSP proteins with a focal adhesion-targeting domain present in Cas proteins.
      Title: NSP-Cas protein structures reveal a promiscuous interaction module in cell signaling.
    2. Observational study of gene-disease association. (HuGE Navigator)
      Title: Follow-up association studies of chromosome region 9q and nonsyndromic cleft lip/palate.
    3. NSP3 overexpression did not induce anti-estrogen resistance in breast tumor cell lines.
      Title: AND-34/BCAR3 differs from other NSP homologs in induction of anti-estrogen resistance, cyclin D1 promoter activation and altered breast cancer cell morphology.
    4. This protein positively regulates T cell receptor-mediated interleukin-2 production by Jurkat cells.
      Title: A novel hematopoietic adaptor protein, Chat-H, positively regulates T cell receptor-mediated interleukin-2 production by Jurkat cells.
    5. SH2D3C (SHEP1) is less highly expressed than BCAR3 and NSP1 in breast cancer cells, and the expression patterns suggest differential roles for the three genes during breast cancer progression.
      Title: Splice variants and expression patterns of SHEP1, BCAR3 and NSP1, a gene family involved in integrin and receptor tyrosine kinase signaling.
    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
    Genetic variants associated with disordered eating.
    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

    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Clone Names

    • FLJ39664

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables guanyl-nucleotide exchange factor activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables phosphotyrosine residue binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in JNK cascade TAS
    Traceable Author Statement
    more info
    		 PubMed 
    involved_in positive regulation of peptidyl-serine phosphorylation IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in small GTPase-mediated signal transduction IEA
    Inferred from Electronic Annotation
    more info
    		  
    Component Evidence Code Pubs
    located_in axon IEA
    Inferred from Electronic Annotation
    more info
    		  
    located_in cytosol IDA
    Inferred from Direct Assay
    more info
    		  
    located_in ruffle membrane IEA
    Inferred from Electronic Annotation
    more info
    		  

    General protein information

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    Preferred Names
    SH2 domain-containing protein 3C
    Names
    SH2 domain-containing Eph receptor-binding protein 1
    cas/HEF1-associated signal transducer
    chat-H
    novel SH2-containing protein 3

    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.

    Genomic

    1. NG_030563.1 RefSeqGene

      Range
      5104..45453
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_001142531.1 → NP_001136003.1  SH2 domain-containing protein 3C isoform c

      See identical proteins and their annotated locations for NP_001136003.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) includes an alternate exon in the 5' end resulting in use of a downstream start codon, compared to variant 1. It encodes isoform c which has a shorter N-terminus than isoform a. Variants 3 and 4 both encode isoform c.
      Source sequence(s)
      AI799905, AK294386, CU455802, DA054525
      Consensus CDS
      CCDS48028.1
      UniProtKB/TrEMBL
      B4DG32
      Conserved Domains (1) summary
      cl02485
      Location:231 → 400
      RasGEF; Guanine nucleotide exchange factor for Ras-like small GTPases. Small GTP-binding proteins of the Ras superfamily function as molecular switches in fundamental events such as signal transduction, cytoskeleton dynamics and intracellular trafficking. ...

    2. NM_001142532.1 → NP_001136004.1  SH2 domain-containing protein 3C isoform c

      See identical proteins and their annotated locations for NP_001136004.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (4) includes an alternate exon in the 5' end resulting in use of a downstream start codon, compared to variant 1. It encodes isoform c which has a shorter N-terminus than isoform a. Variants 3 and 4 both encode isoform c.
      Source sequence(s)
      AI799905, AK311510, BX647905
      Consensus CDS
      CCDS48028.1
      UniProtKB/TrEMBL
      B4DG32
      Related
      ENSP00000394632.1, ENST00000429553.5
      Conserved Domains (1) summary
      cl02485
      Location:231 → 400
      RasGEF; Guanine nucleotide exchange factor for Ras-like small GTPases. Small GTP-binding proteins of the Ras superfamily function as molecular switches in fundamental events such as signal transduction, cytoskeleton dynamics and intracellular trafficking. ...

    3. NM_001142533.1 → NP_001136005.1  SH2 domain-containing protein 3C isoform d

      See identical proteins and their annotated locations for NP_001136005.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (5) includes an alternate exon in the 5' coding region, compared to variant 1. It encodes isoform d, which is shorter and has a distinct N-terminus compared to isoform a.
      Source sequence(s)
      AI799905, AK056068, CU455802
      Consensus CDS
      CCDS48026.1
      UniProtKB/TrEMBL
      A8K7M6
      Related
      ENSP00000388536.1, ENST00000420366.5
      Conserved Domains (2) summary
      cd10337
      Location:55 → 189
      SH2_BCAR3; Src homology 2 (SH2) domain in the Breast Cancer Anti-estrogen Resistance protein 3
      cl02485
      Location:427 → 596
      RasGEF; Guanine nucleotide exchange factor for Ras-like small GTPases. Small GTP-binding proteins of the Ras superfamily function as molecular switches in fundamental events such as signal transduction, cytoskeleton dynamics and intracellular trafficking. ...

    4. NM_001142534.1 → NP_001136006.1  SH2 domain-containing protein 3C isoform e

      Status: REVIEWED

      Description
      Transcript Variant: This variant (6) includes an alternate exon in the 5' coding region, compared to variant 1. It encodes isoform e, which is shorter and has a distinct N-terminus compared to isoform a.
      Source sequence(s)
      AI799905, AK291393, CU455802, DC302682
      Consensus CDS
      CCDS48027.1
      UniProtKB/TrEMBL
      A8K7M6
      Related
      ENSP00000485866.1, ENST00000629203.2
      Conserved Domains (2) summary
      cd10337
      Location:53 → 187
      SH2_BCAR3; Src homology 2 (SH2) domain in the Breast Cancer Anti-estrogen Resistance protein 3
      cl02485
      Location:425 → 594
      RasGEF; Guanine nucleotide exchange factor for Ras-like small GTPases. Small GTP-binding proteins of the Ras superfamily function as molecular switches in fundamental events such as signal transduction, cytoskeleton dynamics and intracellular trafficking. ...

    5. NM_001252334.2 → NP_001239263.1  SH2 domain-containing protein 3C isoform f

      Status: REVIEWED

      Description
      Transcript Variant: This variant (7) differs in the 5' UTR and 5' coding region and initiates translation from an alternate start codon, compared to variant 1. The encoded isoform (f) has a distinct N-terminus and is shorter than isoform a.
      Source sequence(s)
      AI472242, AL162586, BX647905
      Consensus CDS
      CCDS59145.1
      UniProtKB/TrEMBL
      A8K7M6
      Related
      ENSP00000362373.3, ENST00000373276.7
      Conserved Domains (2) summary
      cd10337
      Location:145 → 279
      SH2_BCAR3; Src homology 2 (SH2) domain in the Breast Cancer Anti-estrogen Resistance protein 3
      cl02485
      Location:517 → 686
      RasGEF; Guanine nucleotide exchange factor for Ras-like small GTPases. Small GTP-binding proteins of the Ras superfamily function as molecular switches in fundamental events such as signal transduction, cytoskeleton dynamics and intracellular trafficking. ...

    6. NM_005489.4 → NP_005480.2  SH2 domain-containing protein 3C isoform b

      See identical proteins and their annotated locations for NP_005480.2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) includes alternate exons in the 5' coding region, compared to variant 1. It encodes isoform b, which is shorter and has a distinct N-terminus compared to isoform a.
      Source sequence(s)
      AL162426, BC027962, BI912337
      Consensus CDS
      CCDS6878.1
      UniProtKB/TrEMBL
      A8K7M6
      Related
      ENSP00000362374.4, ENST00000373277.8
      Conserved Domains (2) summary
      cd10337
      Location:56 → 190
      SH2_BCAR3; Src homology 2 (SH2) domain in the Breast Cancer Anti-estrogen Resistance protein 3
      cl02485
      Location:428 → 597
      RasGEF; Guanine nucleotide exchange factor for Ras-like small GTPases. Small GTP-binding proteins of the Ras superfamily function as molecular switches in fundamental events such as signal transduction, cytoskeleton dynamics and intracellular trafficking. ...

    7. NM_170600.3 → NP_733745.1  SH2 domain-containing protein 3C isoform a

      See identical proteins and their annotated locations for NP_733745.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) represents the longest transcript and encodes the longest isoform (a).
      Source sequence(s)
      AI799905, BC032365, CU454732, DB161948
      Consensus CDS
      CCDS6877.1
      UniProtKB/Swiss-Prot
      A8K5S8, E9PG48, Q5HYE5, Q5JU31, Q6UY42, Q8N5H7, Q8N6X3, Q9Y2X5
      UniProtKB/TrEMBL
      A8K9K3
      Related
      ENSP00000317817.8, ENST00000314830.13
      Conserved Domains (2) summary
      cd10337
      Location:213 → 347
      SH2_BCAR3; Src homology 2 (SH2) domain in the Breast Cancer Anti-estrogen Resistance protein 3
      cl02485
      Location:585 → 754
      RasGEF; Guanine nucleotide exchange factor for Ras-like small GTPases. Small GTP-binding proteins of the Ras superfamily function as molecular switches in fundamental events such as signal transduction, cytoskeleton dynamics and intracellular trafficking. ...

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

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

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000009.12 Reference GRCh38.p14 Primary Assembly

      Range
      127738317..127778666 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060933.1 Alternate T2T-CHM13v2.0

      Range
      139945763..139986120 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q8N5H7.1 GenPept UniProtKB/Swiss-Prot:Q8N5H7

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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