Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Guanylate cyclase soluble subunit alpha-2

Gene

GUCY1A2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at transcript 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

  • GTP binding Source: UniProtKB-KW
  • guanylate cyclase activity Source: ProtInc
  • heme binding Source: InterPro

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Lyase

Keywords - Biological processi

cGMP biosynthesis

Keywords - Ligandi

GTP-binding, Nucleotide-binding

Enzyme and pathway databases

BRENDAi4.6.1.2. 2681.
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 Componenti: Chromosome 11

Organism-specific databases

HGNCiHGNC:4684. GUCY1A2.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA186.

Chemistry

DrugBankiDB01020. Isosorbide Mononitrate.
DB00435. Nitric Oxide.

Polymorphism and mutation databases

BioMutaiGUCY1A2.
DMDMi461897.

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.
GenevisibleiP33402. HS.

Organism-specific databases

HPAiCAB009534.

Interactioni

Subunit structurei

Heterodimer of an alpha and a beta chain.

Protein-protein interaction databases

BioGridi109232. 10 interactions.
IntActiP33402. 1 interaction.
STRINGi9606.ENSP00000431245.

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.
HOGENOMiHOG000220903.
HOVERGENiHBG106603.
InParanoidiP33402.
KOiK12318.
OMAiVMEIKGQ.
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. AlignAdd to basket

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:
EMBLi
GenBanki
DDBJi
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.
GeneIDi2977.
KEGGihsa:2977.
UCSCiuc001pjf.5. human. [P33402-2]
uc001pjg.2. human. [P33402-1]
uc010rvo.2. human.

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
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.

3D structure databases

ProteinModelPortaliP33402.
SMRiP33402. Positions 318-433, 446-506, 512-698.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi109232. 10 interactions.
IntActiP33402. 1 interaction.
STRINGi9606.ENSP00000431245.

Chemistry

ChEMBLiCHEMBL2111348.
DrugBankiDB01020. Isosorbide Mononitrate.
DB00435. Nitric Oxide.

PTM databases

PhosphoSiteiP33402.

Polymorphism and mutation databases

BioMutaiGUCY1A2.
DMDMi461897.

Proteomic databases

MaxQBiP33402.
PaxDbiP33402.
PRIDEiP33402.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000282249; ENSP00000282249; ENSG00000152402. [P33402-2]
ENST00000347596; ENSP00000344874; ENSG00000152402. [P33402-3]
ENST00000526355; ENSP00000431245; ENSG00000152402.
GeneIDi2977.
KEGGihsa:2977.
UCSCiuc001pjf.5. human. [P33402-2]
uc001pjg.2. human. [P33402-1]
uc010rvo.2. human.

Organism-specific databases

CTDi2977.
GeneCardsiGC11M106548.
HGNCiHGNC:4684. GUCY1A2.
HPAiCAB009534.
MIMi601244. gene.
neXtProtiNX_P33402.
PharmGKBiPA186.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiCOG2114.
GeneTreeiENSGT00760000118959.
HOGENOMiHOG000220903.
HOVERGENiHBG106603.
InParanoidiP33402.
KOiK12318.
OMAiVMEIKGQ.
OrthoDBiEOG7VX8Z6.
PhylomeDBiP33402.
TreeFamiTF351403.

Enzyme and pathway databases

BRENDAi4.6.1.2. 2681.
ReactomeiREACT_23862. Nitric oxide stimulates guanylate cyclase.

Miscellaneous databases

ChiTaRSiGUCY1A2. human.
GeneWikiiGUCY1A2.
GenomeRNAii2977.
NextBioi11808.
PROiP33402.
SOURCEiSearch...

Gene expression databases

BgeeiP33402.
CleanExiHS_GUCY1A2.
GenevisibleiP33402. HS.

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]
ProtoNetiSearch...

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: July 22, 2015
This is version 144 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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.