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P33402

- GCYA2_HUMAN

UniProt

P33402 - GCYA2_HUMAN

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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

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
Complete GO annotation...

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-KW
Complete GO annotation...

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

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, 512-698.
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.
GeneTreeiENSGT00760000118959.
HOVERGENiHBG106603.
InParanoidiP33402.
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.
IPR029787. Nucleotide_cyclase.
[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

        10         20         30         40         50
MSRRKISSES FSSLGSDYLE TSPEEEGECP LSRLCWNGSR SPPGPLEPSP
60 70 80 90 100
AAAAAAAAPA PTPAASAAAA AATAGARRVQ RRRRVNLDSL GESISRLTAP
110 120 130 140 150
SPQTIQQTLK RTLQYYEHQV IGYRDAEKNF HNISNRCSYA DHSNKEEIED
160 170 180 190 200
VSGILQCTAN ILGLKFEEIQ KRFGEEFFNI CFHENERVLR AVGGTLQDFF
210 220 230 240 250
NGFDALLEHI RTSFGKQATL ESPSFLCKEL PEGTLMLHYF HPHHIVGFAM
260 270 280 290 300
LGMIKAAGKK IYRLDVEVEQ VANEKLCSDV SNPGNCSCLT FLIKECENTN
310 320 330 340 350
IMKNLPQGTS QVPADLRISI NTFCRAFPFH LMFDPSMSVL QLGEGLRKQL
360 370 380 390 400
RCDTHKVLKF EDCFEIVSPK VNATFERVLL RLSTPFVIRT KPEASGSENK
410 420 430 440 450
DKVMEVKGQM IHVPESNSIL FLGSPCVDKL DELMGRGLHL SDIPIHDATR
460 470 480 490 500
DVILVGEQAK AQDGLKKRMD KLKATLERTH QALEEEKKKT VDLLYSIFPG
510 520 530 540 550
DVAQQLWQGQ QVQARKFDDV TMLFSDIVGF TAICAQCTPM QVISMLNELY
560 570 580 590 600
TRFDHQCGFL DIYKVETIGD AYCVAAGLHR KSLCHAKPIA LMALKMMELS
610 620 630 640 650
EEVLTPDGRP IQMRIGIHSG SVLAGVVGVR MPRYCLFGNN VTLASKFESG
660 670 680 690 700
SHPRRINVSP TTYQLLKREE SFTFIPRSRE ELPDNFPKEI PGICYFLEVR
710 720 730
TGPKPPKPSL SSSRIKKVSY NIGTMFLRET SL
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]
uc010rvo.2. human.

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, 512-698.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

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

Chemistry

BindingDBi P33402.
ChEMBLi CHEMBL2111348.
DrugBanki DB01020. Isosorbide Mononitrate.
DB00435. Nitric Oxide.

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 ]
uc010rvo.2. human.

Organism-specific databases

CTDi 2977.
GeneCardsi GC11M106548.
HGNCi HGNC:4684. GUCY1A2.
HPAi CAB009534.
MIMi 601244. gene.
neXtProti NX_P33402.
PharmGKBi PA186.
GenAtlasi Search...

Phylogenomic databases

eggNOGi COG2114.
GeneTreei ENSGT00760000118959.
HOVERGENi HBG106603.
InParanoidi P33402.
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

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.
IPR029787. Nucleotide_cyclase.
[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

« Hide 'large scale' publications
  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 29, 2014
This is version 138 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