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P33402

- GCYA2_HUMAN

UniProt

P33402 - GCYA2_HUMAN

Protein

Guanylate cyclase soluble subunit alpha-2

Gene

GUCY1A2

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 137 (01 Oct 2014)
      Sequence version 1 (01 Feb 1994)
      Previous versions | rss
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    Functioni

    Has guanylyl cyclase on binding to the beta-1 subunit.
    Isoform 2 acts as a negative regulator of guanylyl cyclase activity as it forms non-functional heterodimers with the beta subunits.

    Catalytic activityi

    GTP = 3',5'-cyclic GMP + diphosphate.

    Enzyme regulationi

    Activated by nitric oxide in the presence of magnesium or manganese ions.

    GO - Molecular functioni

    1. GTP binding Source: UniProtKB-KW
    2. guanylate cyclase activity Source: ProtInc
    3. heme binding Source: InterPro

    GO - Biological processi

    1. blood coagulation Source: Reactome
    2. intracellular signal transduction Source: InterPro
    3. positive regulation of cGMP biosynthetic process Source: Ensembl
    4. signal transduction Source: ProtInc

    Keywords - Molecular functioni

    Lyase

    Keywords - Biological processi

    cGMP biosynthesis

    Keywords - Ligandi

    GTP-binding, Nucleotide-binding

    Enzyme and pathway databases

    ReactomeiREACT_23862. Nitric oxide stimulates guanylate cyclase.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Guanylate cyclase soluble subunit alpha-2 (EC:4.6.1.2)
    Short name:
    GCS-alpha-2
    Gene namesi
    Name:GUCY1A2
    Synonyms:GUC1A2, GUCSA2
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 11

    Organism-specific databases

    HGNCiHGNC:4684. GUCY1A2.

    Subcellular locationi

    GO - Cellular componenti

    1. cytoplasm Source: UniProtKB-SubCell

    Keywords - Cellular componenti

    Cytoplasm

    Pathology & Biotechi

    Organism-specific databases

    PharmGKBiPA186.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 732732Guanylate cyclase soluble subunit alpha-2PRO_0000074113Add
    BLAST

    Proteomic databases

    MaxQBiP33402.
    PaxDbiP33402.
    PRIDEiP33402.

    PTM databases

    PhosphoSiteiP33402.

    Expressioni

    Tissue specificityi

    Isoform 1 is expressed in fetal brain, liver, colon, endothelium and testis. Isoform 2 is expressed only in liver, colon and endothelium.

    Gene expression databases

    ArrayExpressiP33402.
    BgeeiP33402.
    CleanExiHS_GUCY1A2.
    GenevestigatoriP33402.

    Organism-specific databases

    HPAiCAB009534.

    Interactioni

    Subunit structurei

    Heterodimer of an alpha and a beta chain.

    Protein-protein interaction databases

    BioGridi109232. 11 interactions.
    IntActiP33402. 1 interaction.
    STRINGi9606.ENSP00000344874.

    Structurei

    3D structure databases

    ProteinModelPortaliP33402.
    SMRiP33402. Positions 318-433, 446-506, 510-698.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini521 – 648128Guanylate cyclasePROSITE-ProRule annotationAdd
    BLAST

    Compositional bias

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Compositional biasi51 – 7626Ala-richAdd
    BLAST
    Compositional biasi51 – 588Poly-Ala

    Sequence similaritiesi

    Belongs to the adenylyl cyclase class-4/guanylyl cyclase family.PROSITE-ProRule annotation
    Contains 1 guanylate cyclase domain.PROSITE-ProRule annotation

    Phylogenomic databases

    eggNOGiCOG2114.
    HOVERGENiHBG106603.
    KOiK12318.
    OMAiECENTNI.
    OrthoDBiEOG7VX8Z6.
    PhylomeDBiP33402.
    TreeFamiTF351403.

    Family and domain databases

    Gene3Di3.30.70.1230. 1 hit.
    InterProiIPR001054. A/G_cyclase.
    IPR018297. A/G_cyclase_CS.
    IPR011645. Haem_no_assoc-bd.
    IPR011644. Heme_NO-bd.
    IPR024096. NO_sig/Golgi_transp_ligand-bd.
    [Graphical view]
    PfamiPF00211. Guanylate_cyc. 1 hit.
    PF07700. HNOB. 1 hit.
    PF07701. HNOBA. 1 hit.
    [Graphical view]
    SMARTiSM00044. CYCc. 1 hit.
    [Graphical view]
    SUPFAMiSSF111126. SSF111126. 1 hit.
    SSF55073. SSF55073. 1 hit.
    PROSITEiPS00452. GUANYLATE_CYCLASE_1. 1 hit.
    PS50125. GUANYLATE_CYCLASE_2. 1 hit.
    [Graphical view]

    Sequences (3)i

    Sequence statusi: Complete.

    This entry describes 3 isoformsi produced by alternative splicing. Align

    Isoform 1 (identifier: P33402-1) [UniParc]FASTAAdd to Basket

    Also known as: Alpha-2

    This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

    « Hide

    MSRRKISSES FSSLGSDYLE TSPEEEGECP LSRLCWNGSR SPPGPLEPSP    50
    AAAAAAAAPA PTPAASAAAA AATAGARRVQ RRRRVNLDSL GESISRLTAP 100
    SPQTIQQTLK RTLQYYEHQV IGYRDAEKNF HNISNRCSYA DHSNKEEIED 150
    VSGILQCTAN ILGLKFEEIQ KRFGEEFFNI CFHENERVLR AVGGTLQDFF 200
    NGFDALLEHI RTSFGKQATL ESPSFLCKEL PEGTLMLHYF HPHHIVGFAM 250
    LGMIKAAGKK IYRLDVEVEQ VANEKLCSDV SNPGNCSCLT FLIKECENTN 300
    IMKNLPQGTS QVPADLRISI NTFCRAFPFH LMFDPSMSVL QLGEGLRKQL 350
    RCDTHKVLKF EDCFEIVSPK VNATFERVLL RLSTPFVIRT KPEASGSENK 400
    DKVMEVKGQM IHVPESNSIL FLGSPCVDKL DELMGRGLHL SDIPIHDATR 450
    DVILVGEQAK AQDGLKKRMD KLKATLERTH QALEEEKKKT VDLLYSIFPG 500
    DVAQQLWQGQ QVQARKFDDV TMLFSDIVGF TAICAQCTPM QVISMLNELY 550
    TRFDHQCGFL DIYKVETIGD AYCVAAGLHR KSLCHAKPIA LMALKMMELS 600
    EEVLTPDGRP IQMRIGIHSG SVLAGVVGVR MPRYCLFGNN VTLASKFESG 650
    SHPRRINVSP TTYQLLKREE SFTFIPRSRE ELPDNFPKEI PGICYFLEVR 700
    TGPKPPKPSL SSSRIKKVSY NIGTMFLRET SL 732
    Length:732
    Mass (Da):81,750
    Last modified:February 1, 1994 - v1
    Checksum:i79465A7D3FE52DB7
    GO
    Isoform 2 (identifier: P33402-2) [UniParc]FASTAAdd to Basket

    Also known as: Alpha-2-I

    The sequence of this isoform differs from the canonical sequence as follows:
         612-612: Q → QPQRSELLFSFPVSIQLVPDQHQSETDLGTEK

    Show »
    Length:763
    Mass (Da):85,259
    Checksum:iE3493CCC508BE6EB
    GO
    Isoform 3 (identifier: P33402-3) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         402-402: K → KSKHVTEGHLTQLSVAGFNSLE

    Note: No experimental confirmation available.

    Show »
    Length:753
    Mass (Da):83,986
    Checksum:i447CF8A2C77F249D
    GO

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti681 – 6811E → V in a colorectal cancer sample; somatic mutation. 1 Publication
    VAR_036420
    Natural varianti685 – 6851N → T in a colorectal cancer sample; somatic mutation. 1 Publication
    VAR_036421

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei402 – 4021K → KSKHVTEGHLTQLSVAGFNS LE in isoform 3. 1 PublicationVSP_054154
    Alternative sequencei612 – 6121Q → QPQRSELLFSFPVSIQLVPD QHQSETDLGTEK in isoform 2. 1 PublicationVSP_001814

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    X63282 mRNA. Translation: CAA44921.1.
    Z50053 mRNA. Translation: CAA90393.1.
    AP001282 Genomic DNA. No translation available.
    AP001881 Genomic DNA. No translation available.
    AP003078 Genomic DNA. No translation available.
    AP005014 Genomic DNA. No translation available.
    CH471065 Genomic DNA. Translation: EAW67081.1.
    BC130484 mRNA. Translation: AAI30485.1.
    BC130488 mRNA. Translation: AAI30489.1.
    BC144033 mRNA. Translation: AAI44034.1.
    CCDSiCCDS58170.1. [P33402-2]
    CCDS8335.1. [P33402-1]
    PIRiS18325.
    RefSeqiNP_000846.1. NM_000855.2. [P33402-1]
    NP_001243353.1. NM_001256424.1. [P33402-2]
    UniGeneiHs.24321.

    Genome annotation databases

    EnsembliENST00000282249; ENSP00000282249; ENSG00000152402. [P33402-2]
    ENST00000347596; ENSP00000344874; ENSG00000152402. [P33402-3]
    ENST00000526355; ENSP00000431245; ENSG00000152402. [P33402-1]
    GeneIDi2977.
    KEGGihsa:2977.
    UCSCiuc001pjf.5. human. [P33402-2]
    uc001pjg.2. human. [P33402-1]

    Polymorphism databases

    DMDMi461897.

    Keywords - Coding sequence diversityi

    Alternative splicing, Polymorphism

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    X63282 mRNA. Translation: CAA44921.1 .
    Z50053 mRNA. Translation: CAA90393.1 .
    AP001282 Genomic DNA. No translation available.
    AP001881 Genomic DNA. No translation available.
    AP003078 Genomic DNA. No translation available.
    AP005014 Genomic DNA. No translation available.
    CH471065 Genomic DNA. Translation: EAW67081.1 .
    BC130484 mRNA. Translation: AAI30485.1 .
    BC130488 mRNA. Translation: AAI30489.1 .
    BC144033 mRNA. Translation: AAI44034.1 .
    CCDSi CCDS58170.1. [P33402-2 ]
    CCDS8335.1. [P33402-1 ]
    PIRi S18325.
    RefSeqi NP_000846.1. NM_000855.2. [P33402-1 ]
    NP_001243353.1. NM_001256424.1. [P33402-2 ]
    UniGenei Hs.24321.

    3D structure databases

    ProteinModelPortali P33402.
    SMRi P33402. Positions 318-433, 446-506, 510-698.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 109232. 11 interactions.
    IntActi P33402. 1 interaction.
    STRINGi 9606.ENSP00000344874.

    Chemistry

    BindingDBi P33402.
    ChEMBLi CHEMBL2111348.

    PTM databases

    PhosphoSitei P33402.

    Polymorphism databases

    DMDMi 461897.

    Proteomic databases

    MaxQBi P33402.
    PaxDbi P33402.
    PRIDEi P33402.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000282249 ; ENSP00000282249 ; ENSG00000152402 . [P33402-2 ]
    ENST00000347596 ; ENSP00000344874 ; ENSG00000152402 . [P33402-3 ]
    ENST00000526355 ; ENSP00000431245 ; ENSG00000152402 . [P33402-1 ]
    GeneIDi 2977.
    KEGGi hsa:2977.
    UCSCi uc001pjf.5. human. [P33402-2 ]
    uc001pjg.2. human. [P33402-1 ]

    Organism-specific databases

    CTDi 2977.
    GeneCardsi GC11M106591.
    HGNCi HGNC:4684. GUCY1A2.
    HPAi CAB009534.
    MIMi 601244. gene.
    neXtProti NX_P33402.
    PharmGKBi PA186.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi COG2114.
    HOVERGENi HBG106603.
    KOi K12318.
    OMAi ECENTNI.
    OrthoDBi EOG7VX8Z6.
    PhylomeDBi P33402.
    TreeFami TF351403.

    Enzyme and pathway databases

    Reactomei REACT_23862. Nitric oxide stimulates guanylate cyclase.

    Miscellaneous databases

    GeneWikii GUCY1A2.
    GenomeRNAii 2977.
    NextBioi 11808.
    PROi P33402.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi P33402.
    Bgeei P33402.
    CleanExi HS_GUCY1A2.
    Genevestigatori P33402.

    Family and domain databases

    Gene3Di 3.30.70.1230. 1 hit.
    InterProi IPR001054. A/G_cyclase.
    IPR018297. A/G_cyclase_CS.
    IPR011645. Haem_no_assoc-bd.
    IPR011644. Heme_NO-bd.
    IPR024096. NO_sig/Golgi_transp_ligand-bd.
    [Graphical view ]
    Pfami PF00211. Guanylate_cyc. 1 hit.
    PF07700. HNOB. 1 hit.
    PF07701. HNOBA. 1 hit.
    [Graphical view ]
    SMARTi SM00044. CYCc. 1 hit.
    [Graphical view ]
    SUPFAMi SSF111126. SSF111126. 1 hit.
    SSF55073. SSF55073. 1 hit.
    PROSITEi PS00452. GUANYLATE_CYCLASE_1. 1 hit.
    PS50125. GUANYLATE_CYCLASE_2. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "Molecular cloning and expression of a new alpha-subunit of soluble guanylyl cyclase. Interchangeability of the alpha-subunits of the enzyme."
      Harteneck C., Wedel B., Koesling D., Malkewitz J., Boehme E., Schultz G.
      FEBS Lett. 292:217-222(1991) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    2. "A variant of the alpha 2 subunit of soluble guanylyl cyclase contains an insert homologous to a region within adenylyl cyclases and functions as a dominant negative protein."
      Behrends S., Harteneck C., Schultz G., Koesling D.
      J. Biol. Chem. 270:21109-21113(1995) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
    3. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    4. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    5. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
      The MGC Project Team
      Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3).
    6. Cited for: VARIANTS [LARGE SCALE ANALYSIS] VAL-681 AND THR-685.

    Entry informationi

    Entry nameiGCYA2_HUMAN
    AccessioniPrimary (citable) accession number: P33402
    Secondary accession number(s): A1L4C4, B7ZLT5
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: February 1, 1994
    Last sequence update: February 1, 1994
    Last modified: October 1, 2014
    This is version 137 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program
    DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

    Miscellaneousi

    Miscellaneous

    There are two types of guanylate cyclases: soluble forms and membrane-associated receptor forms.

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. Human chromosome 11
      Human chromosome 11: entries, gene names and cross-references to MIM
    2. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    3. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    4. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    5. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3