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P33402 (GCYA2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 135. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Guanylate cyclase soluble subunit alpha-2

Short name=GCS-alpha-2
EC=4.6.1.2
Gene names
Name:GUCY1A2
Synonyms:GUC1A2, GUCSA2
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length732 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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 activity

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

Enzyme regulation

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

Subunit structure

Heterodimer of an alpha and a beta chain.

Subcellular location

Cytoplasm.

Tissue specificity

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

Miscellaneous

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

Sequence similarities

Belongs to the adenylyl cyclase class-4/guanylyl cyclase family.

Contains 1 guanylate cyclase domain.

Ontologies

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: P33402-1)

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.
Isoform 2 (identifier: P33402-2)

Also known as: Alpha-2-I;

The sequence of this isoform differs from the canonical sequence as follows:
     612-612: Q → QPQRSELLFSFPVSIQLVPDQHQSETDLGTEK
Isoform 3 (identifier: P33402-3)

The sequence of this isoform differs from the canonical sequence as follows:
     402-402: K → KSKHVTEGHLTQLSVAGFNSLE
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 732732Guanylate cyclase soluble subunit alpha-2
PRO_0000074113

Regions

Domain521 – 648128Guanylate cyclase
Compositional bias51 – 7626Ala-rich
Compositional bias51 – 588Poly-Ala

Natural variations

Alternative sequence4021K → KSKHVTEGHLTQLSVAGFNS LE in isoform 3.
VSP_054154
Alternative sequence6121Q → QPQRSELLFSFPVSIQLVPD QHQSETDLGTEK in isoform 2.
VSP_001814
Natural variant6811E → V in a colorectal cancer sample; somatic mutation. Ref.6
VAR_036420
Natural variant6851N → T in a colorectal cancer sample; somatic mutation. Ref.6
VAR_036421

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 (Alpha-2) [UniParc].

Last modified February 1, 1994. Version 1.
Checksum: 79465A7D3FE52DB7

FASTA73281,750
        10         20         30         40         50         60 
MSRRKISSES FSSLGSDYLE TSPEEEGECP LSRLCWNGSR SPPGPLEPSP AAAAAAAAPA 

        70         80         90        100        110        120 
PTPAASAAAA AATAGARRVQ RRRRVNLDSL GESISRLTAP SPQTIQQTLK RTLQYYEHQV 

       130        140        150        160        170        180 
IGYRDAEKNF HNISNRCSYA DHSNKEEIED VSGILQCTAN ILGLKFEEIQ KRFGEEFFNI 

       190        200        210        220        230        240 
CFHENERVLR AVGGTLQDFF NGFDALLEHI RTSFGKQATL ESPSFLCKEL PEGTLMLHYF 

       250        260        270        280        290        300 
HPHHIVGFAM LGMIKAAGKK IYRLDVEVEQ VANEKLCSDV SNPGNCSCLT FLIKECENTN 

       310        320        330        340        350        360 
IMKNLPQGTS QVPADLRISI NTFCRAFPFH LMFDPSMSVL QLGEGLRKQL RCDTHKVLKF 

       370        380        390        400        410        420 
EDCFEIVSPK VNATFERVLL RLSTPFVIRT KPEASGSENK DKVMEVKGQM IHVPESNSIL 

       430        440        450        460        470        480 
FLGSPCVDKL DELMGRGLHL SDIPIHDATR DVILVGEQAK AQDGLKKRMD KLKATLERTH 

       490        500        510        520        530        540 
QALEEEKKKT VDLLYSIFPG DVAQQLWQGQ QVQARKFDDV TMLFSDIVGF TAICAQCTPM 

       550        560        570        580        590        600 
QVISMLNELY TRFDHQCGFL DIYKVETIGD AYCVAAGLHR KSLCHAKPIA LMALKMMELS 

       610        620        630        640        650        660 
EEVLTPDGRP IQMRIGIHSG SVLAGVVGVR MPRYCLFGNN VTLASKFESG SHPRRINVSP 

       670        680        690        700        710        720 
TTYQLLKREE SFTFIPRSRE ELPDNFPKEI PGICYFLEVR TGPKPPKPSL SSSRIKKVSY 

       730 
NIGTMFLRET SL 

« Hide

Isoform 2 (Alpha-2-I) [UniParc].

Checksum: E3493CCC508BE6EB
Show »

FASTA76385,259
Isoform 3 [UniParc].

Checksum: 447CF8A2C77F249D
Show »

FASTA75383,986

References

« Hide 'large scale' references
[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]"Human chromosome 11 DNA sequence and analysis including novel gene identification."
Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K., Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T., Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G. expand/collapse author list , Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C., Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A., Hattori M., Rogers J., Lander E.S., Sakaki Y.
Nature 440:497-500(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
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]"The consensus coding sequences of human breast and colorectal cancers."
Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V. expand/collapse author list , Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., Velculescu V.E.
Science 314:268-274(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS [LARGE SCALE ANALYSIS] VAL-681 AND THR-685.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
CCDSCCDS58170.1. [P33402-2]
CCDS8335.1. [P33402-1]
PIRS18325.
RefSeqNP_000846.1. NM_000855.2. [P33402-1]
NP_001243353.1. NM_001256424.1. [P33402-2]
UniGeneHs.24321.

3D structure databases

ProteinModelPortalP33402.
SMRP33402. Positions 318-433, 446-506, 510-698.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid109232. 11 interactions.
IntActP33402. 1 interaction.
STRING9606.ENSP00000344874.

Chemistry

BindingDBP33402.
ChEMBLCHEMBL2111348.

PTM databases

PhosphoSiteP33402.

Polymorphism databases

DMDM461897.

Proteomic databases

MaxQBP33402.
PaxDbP33402.
PRIDEP33402.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000282249; ENSP00000282249; ENSG00000152402. [P33402-2]
ENST00000347596; ENSP00000344874; ENSG00000152402.
ENST00000526355; ENSP00000431245; ENSG00000152402. [P33402-1]
GeneID2977.
KEGGhsa:2977.
UCSCuc001pjf.5. human. [P33402-2]
uc001pjg.2. human. [P33402-1]

Organism-specific databases

CTD2977.
GeneCardsGC11M106591.
HGNCHGNC:4684. GUCY1A2.
HPACAB009534.
MIM601244. gene.
neXtProtNX_P33402.
PharmGKBPA186.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG2114.
HOVERGENHBG106603.
KOK12318.
OMAECENTNI.
OrthoDBEOG7VX8Z6.
PhylomeDBP33402.
TreeFamTF351403.

Enzyme and pathway databases

ReactomeREACT_604. Hemostasis.

Gene expression databases

ArrayExpressP33402.
BgeeP33402.
CleanExHS_GUCY1A2.
GenevestigatorP33402.

Family and domain databases

Gene3D3.30.70.1230. 1 hit.
InterProIPR001054. 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]
PfamPF00211. Guanylate_cyc. 1 hit.
PF07700. HNOB. 1 hit.
PF07701. HNOBA. 1 hit.
[Graphical view]
SMARTSM00044. CYCc. 1 hit.
[Graphical view]
SUPFAMSSF111126. SSF111126. 1 hit.
SSF55073. SSF55073. 1 hit.
PROSITEPS00452. GUANYLATE_CYCLASE_1. 1 hit.
PS50125. GUANYLATE_CYCLASE_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiGUCY1A2.
GenomeRNAi2977.
NextBio11808.
PROP33402.
SOURCESearch...

Entry information

Entry nameGCYA2_HUMAN
AccessionPrimary (citable) accession number: P33402
Secondary accession number(s): A1L4C4, B7ZLT5
Entry history
Integrated into UniProtKB/Swiss-Prot: February 1, 1994
Last sequence update: February 1, 1994
Last modified: July 9, 2014
This is version 135 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 11

Human chromosome 11: entries, gene names and cross-references to MIM