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    INTS11 integrator complex subunit 11 [ Homo sapiens (human) ]

    Gene ID: 54973, updated on 27-Dec-2024

    Summary

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    Official Symbol
    INTS11provided by HGNC
    Official Full Name
    integrator complex subunit 11provided by HGNC
    Primary source
    HGNC:HGNC:26052
    See related
    Ensembl:ENSG00000127054 MIM:611354; AllianceGenome:HGNC:26052
    Gene type
    protein coding
    RefSeq status
    VALIDATED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    RC68; INT11; PSF3L; RC-68; CPSF3L; CPSF73L; NEDMLOB
    Summary
    The Integrator complex contains at least 12 subunits and associates with the C-terminal domain of RNA polymerase II large subunit (POLR2A; MIM 180660) and mediates the 3-prime end processing of small nuclear RNAs U1 (RNU1; MIM 180680) and U2 (RNU2; MIM 180690). INTS11, or CPSF3L, is the catalytic subunit of the Integrator complex (Baillat et al., 2005 [PubMed 16239144]).[supplied by OMIM, Mar 2008]
    Expression
    Ubiquitous expression in testis (RPKM 35.0), endometrium (RPKM 21.3) and 25 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See INTS11 in Genome Data Viewer
    Location:
    1p36.33
    Exon count:
    19
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 1 NC_000001.11 (1311600..1324660, complement)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 1 NC_060925.1 (743151..756245, complement)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 1 NC_000001.10 (1246980..1260040, complement)

    Chromosome 1 - NC_000001.11Genomic Context describing neighboring genes Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr1:1232563-1233499 Neighboring gene ArfGAP with coiled-coil, ankyrin repeat and PH domains 3 Neighboring gene microRNA 6726 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr1:1237151-1237752 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr1:1237753-1238352 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr1:1238353-1238953 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr1:1238954-1239553 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr1:1239554-1240154 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 52 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 53 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 54 Neighboring gene small nucleolar RNA, C/D box 167 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 55 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 56 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 57 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 58 Neighboring gene pseudouridine synthase like 1 Neighboring gene microRNA 6727 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr1:1253662-1254352 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr1:1254353-1255043 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr1:1257229-1257737 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr1:1258501-1259010 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 59 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 60 Neighboring gene ceramide-1-phosphate transfer protein Neighboring gene taste 1 receptor member 3 Neighboring gene dishevelled segment polarity protein 1

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • Project title: Tissue-specific circular RNA induction during human fetal development
    • Description: 35 human fetal samples from 6 tissues (3 - 7 replicates per tissue) collected between 10 and 20 weeks gestational time were sequenced using Illumina TruSeq Stranded Total RNA
    • BioProject: PRJNA270632
    • Publication: PMID 26076956
    • Analysis date: Mon Apr 2 22:54:59 2018

    Bibliography

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    Related articles in PubMed

    1. A homozygous variant in INTS11 links mitosis and neurogenesis defects to a severe neurodevelopmental disorder. Kuang H, et al. Cell Rep, 2023 Dec 26. PMID 37980560
    2. Human promoter directionality is determined by transcriptional initiation and the opposing activities of INTS11 and CDK9. Eaton JD, et al. Elife, 2024 Jul 8. PMID 38976490, Free PMC Article
    3. Molecular basis for the interaction between Integrator subunits IntS9 and IntS11 and its functional importance. Wu Y, et al. Proc Natl Acad Sci U S A, 2017 Apr 25. PMID 28396433, Free PMC Article
    4. An examination of the metal ion content in the active sites of human endonucleases CPSF73 and INTS11. Huang J, et al. J Biol Chem, 2023 Apr. PMID 36822327, Free PMC Article
    5. A CPSF-73 homologue is required for cell cycle progression but not cell growth and interacts with a protein having features of CPSF-100. Dominski Z, et al. Mol Cell Biol, 2005 Feb. PMID 15684398, Free PMC Article

    See all (66) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Human promoter directionality is determined by transcriptional initiation and the opposing activities of INTS11 and CDK9.
      Title: Human promoter directionality is determined by transcriptional initiation and the opposing activities of INTS11 and CDK9.
    2. A homozygous variant in INTS11 links mitosis and neurogenesis defects to a severe neurodevelopmental disorder.
      Title: A homozygous variant in INTS11 links mitosis and neurogenesis defects to a severe neurodevelopmental disorder.
    3. An examination of the metal ion content in the active sites of human endonucleases CPSF73 and INTS11.
      Title: An examination of the metal ion content in the active sites of human endonucleases CPSF73 and INTS11.
    4. NACK and INTEGRATOR act coordinately to activate Notch-mediated transcription in tumorigenesis.
      Title: NACK and INTEGRATOR act coordinately to activate Notch-mediated transcription in tumorigenesis.
    5. INTS4 is a specific and conserved interaction partner of INTS9/11 that does not interact with either subunit individually.
      Title: Integrator subunit 4 is a 'Symplekin-like' scaffold that associates with INTS9/11 to form the Integrator cleavage module.
    6. Functional studies demonstrate that the IntS9-IntS11 interaction is crucial for the role of INT in snRNA 3'-end processing.
      Title: Molecular basis for the interaction between Integrator subunits IntS9 and IntS11 and its functional importance.
    7. The specific heterodimeric interaction between IntS9 and IntS11 is mediated by a discrete domain present at the extreme C terminus of IntS9 and within the C terminus of IntS11, adjacent to the predicted active site of this endonuclease.
      Title: snRNA 3' end formation requires heterodimeric association of integrator subunits.
    8. Observational study of gene-disease association, gene-environment interaction, and pharmacogenomic / toxicogenomic. (HuGE Navigator)
      Title: Variation at the NFATC2 locus increases the risk of thiazolidinedione-induced edema in the Diabetes REduction Assessment with ramipril and rosiglitazone Medication (DREAM) study.
    9. Observational study of gene-disease association. (HuGE Navigator)
      Title: Gene-centric association signals for lipids and apolipoproteins identified via the HumanCVD BeadChip.
    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

    Associated conditions

    Description Tests
    Neurodevelopmental disorder with motor and language delay, ocular defects, and brain abnormalities
    MedGen: C5830596 OMIM: 620428 GeneReviews: Not available
    		not available

    EBI GWAS Catalog

    Description
    Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease.
    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)

    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

    • FLJ13294, FLJ20542

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables RNA endonuclease activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables RNA endonuclease activity IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    contributes_to protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in regulation of transcription elongation by RNA polymerase II NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    involved_in snRNA processing IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in snRNA processing IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in snRNA processing NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    Component Evidence Code Pubs
    located_in blood microparticle HDA PubMed 
    located_in cytoplasm IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in cytosol IDA
    Inferred from Direct Assay
    more info
    		  
    part_of integrator complex IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    part_of integrator complex NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    located_in nucleoplasm IDA
    Inferred from Direct Assay
    more info
    		  
    located_in nucleoplasm TAS
    Traceable Author Statement
    more info
    		  
    is_active_in nucleus IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    is_active_in nucleus IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in nucleus IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in nucleus NAS
    Non-traceable Author Statement
    more info
    		 PubMed 

    General protein information

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    Preferred Names
    integrator complex subunit 11
    Names
    CPSF3-like protein
    cleavage and polyadenylation specific factor 3-like
    cleavage and polyadenylation-specific factor 3-like protein
    protein related to CPSF subunits of 68 kDa
    related to CPSF subunits 68 kDa
    NP_001243385.1
    NP_001243389.1
    NP_001243391.1
    NP_001243392.1
    NP_060341.2
    XP_011539949.1
    XP_011539950.1
    XP_011539952.1
    XP_054193241.1
    XP_054193242.1
    XP_054193243.1

    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_001256456.2 → NP_001243385.1  integrator complex subunit 11 isoform 1

      See identical proteins and their annotated locations for NP_001243385.1

      Status: VALIDATED

      Description
      Transcript Variant: This variant (1) represents the longest transcript and it encodes the longest protein (isoform 1).
      Source sequence(s)
      AA687684, AK056652, AK291387, AK297350, DC299237
      Consensus CDS
      CCDS57960.1
      UniProtKB/Swiss-Prot
      Q5TA45
      Related
      ENSP00000445001.1, ENST00000540437.5
      Conserved Domains (5) summary
      smart01027
      Location:251 → 369
      Beta-Casp; Beta-Casp domain
      COG1236
      Location:16 → 450
      YSH1; RNA processing exonuclease, beta-lactamase fold, Cft2 family [Translation, ribosomal structure and biogenesis]
      pfam07521
      Location:382 → 422
      RMMBL; RNA-metabolizing metallo-beta-lactamase
      cd16291
      Location:16 → 210
      INTS11-like_MBL-fold; Integrator complex subunit 11, and related proteins; MBL-fold metallo-hydrolase domain
      cl02570
      Location:414 → 486
      RhoGAP; RhoGAP: GTPase-activator protein (GAP) for Rho-like GTPases; GAPs towards Rho/Rac/Cdc42-like small GTPases. Small GTPases (G proteins) cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when ...

    2. NM_001256460.2 → NP_001243389.1  integrator complex subunit 11 isoform 3

      See identical proteins and their annotated locations for NP_001243389.1

      Status: VALIDATED

      Description
      Transcript Variant: This variant (3) has multiple differences which results in the use of a downstream start codon, compared to variant 1. The resulting protein (isoform 3) is shorter when it is compared to isoform 1.
      Source sequence(s)
      AA687684, AK291387, AK297350, DC295791, DC299237
      Consensus CDS
      CCDS57959.1
      UniProtKB/TrEMBL
      C9IYS7
      Related
      ENSP00000444672.1, ENST00000545578.5
      Conserved Domains (5) summary
      smart01027
      Location:216 → 334
      Beta-Casp; Beta-Casp domain
      COG1236
      Location:1 → 415
      YSH1; RNA processing exonuclease, beta-lactamase fold, Cft2 family [Translation, ribosomal structure and biogenesis]
      pfam07521
      Location:347 → 387
      RMMBL; RNA-metabolizing metallo-beta-lactamase
      cd16291
      Location:1 → 175
      INTS11-like_MBL-fold; Integrator complex subunit 11, and related proteins; MBL-fold metallo-hydrolase domain
      cl02570
      Location:379 → 451
      RhoGAP; RhoGAP: GTPase-activator protein (GAP) for Rho-like GTPases; GAPs towards Rho/Rac/Cdc42-like small GTPases. Small GTPases (G proteins) cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when ...

    3. NM_001256462.2 → NP_001243391.1  integrator complex subunit 11 isoform 4

      Status: VALIDATED

      Description
      Transcript Variant: This variant (4) lacks several exons which results in the use of an upstream start codon, compared to variant 1. The resulting protein (isoform 4) has a shorter and distinct N-terminus when it is compared to isoform 1.
      Source sequence(s)
      AA687684, AK058018, AK291387, DC299237
      Consensus CDS
      CCDS72678.1
      UniProtKB/TrEMBL
      A0A087WYI0, C9IYS7
      Related
      ENSP00000481821.1, ENST00000620829.4
      Conserved Domains (5) summary
      smart01027
      Location:147 → 265
      Beta-Casp; Beta-Casp domain
      COG1236
      Location:48 → 346
      YSH1; RNA processing exonuclease, beta-lactamase fold, Cft2 family [Translation, ribosomal structure and biogenesis]
      pfam07521
      Location:278 → 318
      RMMBL; RNA-metabolizing metallo-beta-lactamase
      cl02570
      Location:310 → 382
      RhoGAP; RhoGAP: GTPase-activator protein (GAP) for Rho-like GTPases; GAPs towards Rho/Rac/Cdc42-like small GTPases. Small GTPases (G proteins) cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when ...
      cl23716
      Location:46 → 106
      metallo-hydrolase-like_MBL-fold; mainly hydrolytic enzymes and related proteins which carry out various biological functions; MBL-fold metallohydrolase domain

    4. NM_001256463.2 → NP_001243392.1  integrator complex subunit 11 isoform 5

      See identical proteins and their annotated locations for NP_001243392.1

      Status: VALIDATED

      Description
      Transcript Variant: This variant (5) has multiple differences which results in the use of an upstream start codon, compared to variant 1. The resulting protein (isoform 5) is shorter when it is compared to isoform 1.
      Source sequence(s)
      AA687684, AK021939, AK058018, DC299237
      Consensus CDS
      CCDS57961.1
      UniProtKB/TrEMBL
      C9IYS7
      Related
      ENSP00000404886.1, ENST00000419704.5
      Conserved Domains (5) summary
      smart01027
      Location:144 → 262
      Beta-Casp; Beta-Casp domain
      COG1236
      Location:4 → 343
      YSH1; RNA processing exonuclease, beta-lactamase fold, Cft2 family [Translation, ribosomal structure and biogenesis]
      pfam07521
      Location:275 → 315
      RMMBL; RNA-metabolizing metallo-beta-lactamase
      cl02570
      Location:307 → 379
      RhoGAP; RhoGAP: GTPase-activator protein (GAP) for Rho-like GTPases; GAPs towards Rho/Rac/Cdc42-like small GTPases. Small GTPases (G proteins) cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when ...
      cl23716
      Location:6 → 103
      metallo-hydrolase-like_MBL-fold; mainly hydrolytic enzymes and related proteins which carry out various biological functions; MBL-fold metallohydrolase domain

    5. NM_017871.6 → NP_060341.2  integrator complex subunit 11 isoform 2

      See identical proteins and their annotated locations for NP_060341.2

      Status: VALIDATED

      Description
      Transcript Variant: This variant (2) lacks two alternate exons in the coding region which results in the use of an upstream start codon, compared to variant 1. The resulting protein (isoform 2) has a shorter and distinct N-terminus when it is compared to isoform 1.
      Source sequence(s)
      AA687684, AK023356, AL136813, DC299993
      Consensus CDS
      CCDS21.1
      UniProtKB/Swiss-Prot
      A8K5S2, B3KPR3, B4DM87, G3V1S5, Q5TA45, Q5TA46, Q5TA48, Q5TA52, Q5TA53, Q5TA54, Q7L3D7, Q96HY1, Q9BW36, Q9H0F9, Q9H8R5, Q9HAA6, Q9NWX9
      Related
      ENSP00000413493.2, ENST00000435064.6
      Conserved Domains (2) summary
      COG1236
      Location:4 → 444
      YSH1; RNA processing exonuclease, beta-lactamase fold, Cft2 family [Translation, ribosomal structure and biogenesis]
      cd16291
      Location:6 → 204
      INTS11-like_MBL-fold; Integrator complex subunit 11, and related proteins; MBL-fold metallo-hydrolase 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_000001.11 Reference GRCh38.p14 Primary Assembly

      Range
      1311600..1324660 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_011541647.2 → XP_011539949.1  integrator complex subunit 11 isoform X1

      Conserved Domains (5) summary
      smart01027
      Location:305 → 423
      Beta-Casp; Beta-Casp domain
      COG1236
      Location:70 → 504
      YSH1; RNA processing exonuclease, beta-lactamase fold, Cft2 family [Translation, ribosomal structure and biogenesis]
      pfam07521
      Location:436 → 476
      RMMBL; RNA-metabolizing metallo-beta-lactamase
      cd16291
      Location:70 → 264
      INTS11-like_MBL-fold; Integrator complex subunit 11, and related proteins; MBL-fold metallo-hydrolase domain
      cl02570
      Location:468 → 540
      RhoGAP; RhoGAP: GTPase-activator protein (GAP) for Rho-like GTPases; GAPs towards Rho/Rac/Cdc42-like small GTPases. Small GTPases (G proteins) cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when ...

    2. XM_011541648.2 → XP_011539950.1  integrator complex subunit 11 isoform X2

      Conserved Domains (5) summary
      smart01027
      Location:267 → 385
      Beta-Casp; Beta-Casp domain
      COG1236
      Location:32 → 466
      YSH1; RNA processing exonuclease, beta-lactamase fold, Cft2 family [Translation, ribosomal structure and biogenesis]
      pfam07521
      Location:398 → 438
      RMMBL; RNA-metabolizing metallo-beta-lactamase
      cd16291
      Location:32 → 226
      INTS11-like_MBL-fold; Integrator complex subunit 11, and related proteins; MBL-fold metallo-hydrolase domain
      cl02570
      Location:430 → 502
      RhoGAP; RhoGAP: GTPase-activator protein (GAP) for Rho-like GTPases; GAPs towards Rho/Rac/Cdc42-like small GTPases. Small GTPases (G proteins) cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when ...

    3. XM_011541650.3 → XP_011539952.1  integrator complex subunit 11 isoform X3

      See identical proteins and their annotated locations for XP_011539952.1

      UniProtKB/TrEMBL
      C9IYS7
      Conserved Domains (5) summary
      smart01027
      Location:121 → 239
      Beta-Casp; Beta-Casp domain
      COG1236
      Location:2 → 320
      YSH1; RNA processing exonuclease, beta-lactamase fold, Cft2 family [Translation, ribosomal structure and biogenesis]
      pfam07521
      Location:252 → 292
      RMMBL; RNA-metabolizing metallo-beta-lactamase
      cl02570
      Location:284 → 356
      RhoGAP; RhoGAP: GTPase-activator protein (GAP) for Rho-like GTPases; GAPs towards Rho/Rac/Cdc42-like small GTPases. Small GTPases (G proteins) cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when ...
      cl23716
      Location:1 → 80
      metallo-hydrolase-like_MBL-fold; mainly hydrolytic enzymes and related proteins which carry out various biological functions; MBL-fold metallohydrolase domain

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060925.1 Alternate T2T-CHM13v2.0

      Range
      743151..756245 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054337266.1 → XP_054193241.1  integrator complex subunit 11 isoform X1

    2. XM_054337267.1 → XP_054193242.1  integrator complex subunit 11 isoform X2

    3. XM_054337268.1 → XP_054193243.1  integrator complex subunit 11 isoform X3

      UniProtKB/TrEMBL
      C9IYS7

    Suppressed Reference Sequence(s)

    The following Reference Sequences have been suppressed. Explain

    1. NM_032179.1: Suppressed sequence

      Description
      NM_032179.1: This RefSeq was permanently suppressed because currently there is insufficient support for the transcript and the protein.
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q5TA45.2 GenPept UniProtKB/Swiss-Prot:Q5TA45

    Gene LinkOut

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

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