UniProtKB - P33402 (GCYA2_HUMAN)
Protein
Guanylate cyclase soluble subunit alpha-2
Gene
GUCY1A2
Organism
Homo sapiens (Human)
Status
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.
Miscellaneous
There are two types of guanylate cyclases: soluble forms and membrane-associated receptor forms.
Catalytic activityi
- EC:4.6.1.2
Activity 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
- protein-containing complex binding Source: Ensembl
GO - Biological processi
- intracellular signal transduction Source: InterPro
- positive regulation of nitric oxide mediated signal transduction Source: Ensembl
- signal transduction Source: ProtInc
Keywordsi
Molecular function | Lyase |
Biological process | cGMP biosynthesis |
Ligand | GTP-binding, Nucleotide-binding |
Enzyme and pathway databases
BRENDAi | 4.6.1.2, 2681 |
PathwayCommonsi | P33402 |
Reactomei | R-HSA-392154, Nitric oxide stimulates guanylate cyclase R-HSA-445355, Smooth Muscle Contraction |
SIGNORi | P33402 |
Names & Taxonomyi
Protein namesi | |
Gene namesi | Name:GUCY1A2 Synonyms:GUC1A2, GUCSA2 |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:4684, GUCY1A2 |
MIMi | 601244, gene |
neXtProti | NX_P33402 |
VEuPathDBi | HostDB:ENSG00000152402.10 |
Subcellular locationi
Cytoplasm and Cytosol
Other locations
- cytoplasm Source: UniProtKB-SubCell
Keywords - Cellular componenti
CytoplasmPathology & Biotechi
Organism-specific databases
DisGeNETi | 2977 |
OpenTargetsi | ENSG00000152402 |
PharmGKBi | PA186 |
Miscellaneous databases
Pharosi | P33402, Tclin |
Chemistry databases
ChEMBLi | CHEMBL2111348 |
DrugBanki | DB01020, Isosorbide mononitrate DB13749, Magnesium gluconate DB09241, Methylene blue DB09282, Molsidomine DB00435, Nitric Oxide DB06154, Pentaerythritol tetranitrate DB13170, Plecanatide DB08931, Riociguat |
DrugCentrali | P33402 |
Genetic variation databases
BioMutai | GUCY1A2 |
DMDMi | 461897 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000074113 | 1 – 732 | Guanylate cyclase soluble subunit alpha-2Add BLAST | 732 |
Proteomic databases
MassIVEi | P33402 |
PaxDbi | P33402 |
PeptideAtlasi | P33402 |
PRIDEi | P33402 |
ProteomicsDBi | 54910 [P33402-1] 54911 [P33402-2] |
PTM databases
iPTMneti | P33402 |
PhosphoSitePlusi | P33402 |
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
Bgeei | ENSG00000152402, Expressed in myometrium and 206 other tissues |
Genevisiblei | P33402, HS |
Organism-specific databases
HPAi | ENSG00000152402, Tissue enhanced (endometrium, placenta) |
Interactioni
Subunit structurei
Heterodimer of an alpha and a beta chain.
Binary interactionsi
Hide detailsP33402
With | #Exp. | IntAct |
---|---|---|
DLG1 [Q12959] | 2 | EBI-6911715,EBI-357481 |
GSC2 [O15499] | 3 | EBI-6911715,EBI-19954058 |
SCRIB [Q14160] | 6 | EBI-6911715,EBI-357345 |
Protein-protein interaction databases
BioGRIDi | 109232, 13 interactors |
CORUMi | P33402 |
IntActi | P33402, 8 interactors |
MINTi | P33402 |
STRINGi | 9606.ENSP00000282249 |
Miscellaneous databases
RNActi | P33402, protein |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 521 – 648 | Guanylate cyclasePROSITE-ProRule annotationAdd BLAST | 128 |
Compositional bias
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Compositional biasi | 51 – 76 | Ala-richAdd BLAST | 26 | |
Compositional biasi | 51 – 58 | Poly-Ala | 8 |
Sequence similaritiesi
Belongs to the adenylyl cyclase class-4/guanylyl cyclase family.PROSITE-ProRule annotation
Phylogenomic databases
eggNOGi | KOG4171, Eukaryota |
GeneTreei | ENSGT00940000157765 |
HOGENOMi | CLU_011614_5_0_1 |
InParanoidi | P33402 |
OMAi | QNWPNIH |
OrthoDBi | 531253at2759 |
PhylomeDBi | P33402 |
TreeFami | TF351403 |
Family and domain databases
CDDi | cd07302, CHD, 1 hit |
Gene3Di | 3.30.450.260, 1 hit 3.30.70.1230, 1 hit 3.90.1520.10, 1 hit |
InterProi | View protein in InterPro IPR001054, A/G_cyclase IPR018297, A/G_cyclase_CS IPR038158, H-NOX_domain_sf IPR011644, Heme_NO-bd IPR011645, HNOB_dom_associated IPR042463, HNOB_dom_associated_sf IPR024096, NO_sig/Golgi_transp_ligand-bd IPR029787, Nucleotide_cyclase |
Pfami | View protein in Pfam PF00211, Guanylate_cyc, 1 hit PF07700, HNOB, 1 hit PF07701, HNOBA, 1 hit |
SMARTi | View protein in SMART SM00044, CYCc, 1 hit |
SUPFAMi | SSF111126, SSF111126, 1 hit SSF55073, SSF55073, 1 hit |
PROSITEi | View protein in PROSITE PS00452, GUANYLATE_CYCLASE_1, 1 hit PS50125, GUANYLATE_CYCLASE_2, 1 hit |
s (3)i Sequence
Sequence statusi: Complete.
This entry describes 3 produced by isoformsialternative splicing. AlignAdd to basketIsoform 1 (identifier: P33402-1) [UniParc]FASTAAdd to basket
Also known as: Alpha-2
This isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
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
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_036420 | 681 | E → V in a colorectal cancer sample; somatic mutation. 1 Publication | 1 | |
Natural variantiVAR_036421 | 685 | N → T in a colorectal cancer sample; somatic mutation. 1 Publication | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_054154 | 402 | K → KSKHVTEGHLTQLSVAGFNS LE in isoform 3. 1 Publication | 1 | |
Alternative sequenceiVSP_001814 | 612 | Q → QPQRSELLFSFPVSIQLVPD QHQSETDLGTEK in isoform 2. 1 Publication | 1 |
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 |
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] |
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.6, human [P33402-1] |
Keywords - Coding sequence diversityi
Alternative splicingSimilar proteinsi
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 |
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] |
3D structure databases
SMRi | P33402 |
ModBasei | Search... |
Protein-protein interaction databases
BioGRIDi | 109232, 13 interactors |
CORUMi | P33402 |
IntActi | P33402, 8 interactors |
MINTi | P33402 |
STRINGi | 9606.ENSP00000282249 |
Chemistry databases
ChEMBLi | CHEMBL2111348 |
DrugBanki | DB01020, Isosorbide mononitrate DB13749, Magnesium gluconate DB09241, Methylene blue DB09282, Molsidomine DB00435, Nitric Oxide DB06154, Pentaerythritol tetranitrate DB13170, Plecanatide DB08931, Riociguat |
DrugCentrali | P33402 |
PTM databases
iPTMneti | P33402 |
PhosphoSitePlusi | P33402 |
Genetic variation databases
BioMutai | GUCY1A2 |
DMDMi | 461897 |
Proteomic databases
MassIVEi | P33402 |
PaxDbi | P33402 |
PeptideAtlasi | P33402 |
PRIDEi | P33402 |
ProteomicsDBi | 54910 [P33402-1] 54911 [P33402-2] |
Protocols and materials databases
Antibodypediai | 4028, 130 antibodies |
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.6, human [P33402-1] |
Organism-specific databases
CTDi | 2977 |
DisGeNETi | 2977 |
GeneCardsi | GUCY1A2 |
HGNCi | HGNC:4684, GUCY1A2 |
HPAi | ENSG00000152402, Tissue enhanced (endometrium, placenta) |
MIMi | 601244, gene |
neXtProti | NX_P33402 |
OpenTargetsi | ENSG00000152402 |
PharmGKBi | PA186 |
VEuPathDBi | HostDB:ENSG00000152402.10 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG4171, Eukaryota |
GeneTreei | ENSGT00940000157765 |
HOGENOMi | CLU_011614_5_0_1 |
InParanoidi | P33402 |
OMAi | QNWPNIH |
OrthoDBi | 531253at2759 |
PhylomeDBi | P33402 |
TreeFami | TF351403 |
Enzyme and pathway databases
BRENDAi | 4.6.1.2, 2681 |
PathwayCommonsi | P33402 |
Reactomei | R-HSA-392154, Nitric oxide stimulates guanylate cyclase R-HSA-445355, Smooth Muscle Contraction |
SIGNORi | P33402 |
Miscellaneous databases
BioGRID-ORCSi | 2977, 4 hits in 987 CRISPR screens |
ChiTaRSi | GUCY1A2, human |
GeneWikii | GUCY1A2 |
GenomeRNAii | 2977 |
Pharosi | P33402, Tclin |
PROi | PR:P33402 |
RNActi | P33402, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000152402, Expressed in myometrium and 206 other tissues |
Genevisiblei | P33402, HS |
Family and domain databases
CDDi | cd07302, CHD, 1 hit |
Gene3Di | 3.30.450.260, 1 hit 3.30.70.1230, 1 hit 3.90.1520.10, 1 hit |
InterProi | View protein in InterPro IPR001054, A/G_cyclase IPR018297, A/G_cyclase_CS IPR038158, H-NOX_domain_sf IPR011644, Heme_NO-bd IPR011645, HNOB_dom_associated IPR042463, HNOB_dom_associated_sf IPR024096, NO_sig/Golgi_transp_ligand-bd IPR029787, Nucleotide_cyclase |
Pfami | View protein in Pfam PF00211, Guanylate_cyc, 1 hit PF07700, HNOB, 1 hit PF07701, HNOBA, 1 hit |
SMARTi | View protein in SMART SM00044, CYCc, 1 hit |
SUPFAMi | SSF111126, SSF111126, 1 hit SSF55073, SSF55073, 1 hit |
PROSITEi | View protein in PROSITE PS00452, GUANYLATE_CYCLASE_1, 1 hit PS50125, GUANYLATE_CYCLASE_2, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | GCYA2_HUMAN | |
Accessioni | P33402Primary (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: | April 7, 2021 | |
This is version 183 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any 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
Keywords - Technical termi
Reference proteomeDocuments
- Human chromosome 11
Human chromosome 11: entries, gene names and cross-references to MIM - Human entries with genetic variants
List of human entries with genetic variants - Human variants curated from literature reports
Index of human variants curated from literature reports - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - SIMILARITY comments
Index of protein domains and families