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Protein

Catenin alpha-1

Gene

CTNNA1

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

Functioni

Associates with the cytoplasmic domain of a variety of cadherins. The association of catenins to cadherins produces a complex which is linked to the actin filament network, and which seems to be of primary importance for cadherins cell-adhesion properties. Can associate with both E- and N-cadherins. Originally believed to be a stable component of E-cadherin/catenin adhesion complexes and to mediate the linkage of cadherins to the actin cytoskeleton at adherens junctions. In contrast, cortical actin was found to be much more dynamic than E-cadherin/catenin complexes and CTNNA1 was shown not to bind to F-actin when assembled in the complex suggesting a different linkage between actin and adherens junctions components. The homodimeric form may regulate actin filament assembly and inhibit actin branching by competing with the Arp2/3 complex for binding to actin filaments. May play a crucial role in cell differentiation.1 Publication

GO - Molecular functioni

  • actin filament binding Source: Ensembl
  • beta-catenin binding Source: BHF-UCL
  • cadherin binding Source: BHF-UCL
  • gamma-catenin binding Source: BHF-UCL
  • protein heterodimerization activity Source: Ensembl
  • RNA binding Source: UniProtKB
  • structural molecule activity Source: InterPro
  • vinculin binding Source: UniProtKB

GO - Biological processi

Keywordsi

Biological processCell adhesion

Enzyme and pathway databases

ReactomeiR-HSA-375170. CDO in myogenesis.
R-HSA-418990. Adherens junctions interactions.
R-HSA-5218920. VEGFR2 mediated vascular permeability.
R-HSA-5626467. RHO GTPases activate IQGAPs.
SIGNORiP35221.

Names & Taxonomyi

Protein namesi
Recommended name:
Catenin alpha-1
Alternative name(s):
Alpha E-catenin
Cadherin-associated protein
Renal carcinoma antigen NY-REN-13
Gene namesi
Name:CTNNA1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 5

Organism-specific databases

EuPathDBiHostDB:ENSG00000044115.20.
HGNCiHGNC:2509. CTNNA1.

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cell junction, Cell membrane, Cytoplasm, Cytoskeleton, Membrane

Pathology & Biotechi

Involvement in diseasei

Germline CTNNA1 truncating mutations have been detected in patients with hereditary diffuse gastric cancer (HDGC) and may play a role in disease susceptibility. Diffuse gastric cancer is a malignant disease characterized by poorly differentiated infiltrating lesions resulting in thickening of the stomach. Malignant tumors start in the stomach, can spread to the esophagus or the small intestine, and can extend through the stomach wall to nearby lymph nodes and organs. It also can metastasize to other parts of the body.2 Publications
Macular dystrophy, patterned, 2 (MDPT2)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA form of retinal patterned dystrophy, a heterogeneous group of macular disorders caused by abnormal accumulation of lipofuscin in the retinal pigment epithelium. Lipofuscin distribution can show various shapes that define different types of macular dystrophy, including reticular (fishnet-like) dystrophy, macroreticular (spider-shaped) dystrophy and butterfly-shaped pigment dystrophy. MDPT2 is an autosomal dominant form characterized by bilateral accumulation of pigment in the macular area that resembles the wings of a butterfly.
See also OMIM:608970
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_07658654R → C in MDPT2; no effect on VCL-binding. 1 PublicationCorresponds to variant dbSNP:rs781520852Ensembl.1
Natural variantiVAR_076587307E → K in MDPT2; no effect on VCL-binding. 1 PublicationCorresponds to variant dbSNP:rs869320697Ensembl.1
Natural variantiVAR_076588318L → S in MDPT2; no effect on VCL-binding. 1 PublicationCorresponds to variant dbSNP:rs869320696Ensembl.1
Natural variantiVAR_076589431I → M in MDPT2; no effect on VCL-binding. 1 PublicationCorresponds to variant dbSNP:rs755215402Ensembl.1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi641S → A: Abolishes phosphorylation by CK2. No effect on phosphorylation by CK1. 1 Publication1
Mutagenesisi641S → D: Enhances phosphorylation by CK1. 1 Publication1
Mutagenesisi652 – 658SRTSVQT → ARTAVQA: Abolishes phosphorylation by CK1. No effect on phosphorylation by CK2. 1 Publication7
Mutagenesisi652S → A: Abolishes phosphorylation by CK1. 1 Publication1

Organism-specific databases

DisGeNETi1495.
MalaCardsiCTNNA1.
MIMi608970. phenotype.
OpenTargetsiENSG00000044115.
PharmGKBiPA27008.

Polymorphism and mutation databases

BioMutaiCTNNA1.
DMDMi461853.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemoved1 Publication
ChainiPRO_00000642612 – 906Catenin alpha-1Add BLAST905

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylthreonine1 Publication1
Cross-linki57Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Modified residuei264PhosphoserineCombined sources1
Modified residuei268PhosphoserineCombined sources1
Modified residuei295PhosphoserineCombined sources1
Modified residuei297PhosphoserineCombined sources1
Modified residuei634PhosphothreonineCombined sources1
Modified residuei641Phosphoserine; by CK2Combined sources1 Publication1
Modified residuei645PhosphothreonineCombined sources1
Modified residuei652Phosphoserine; by CK1Combined sources1 Publication1
Modified residuei655Phosphoserine; by CK11 Publication1
Modified residuei658Phosphothreonine; by CK11 Publication1
Cross-linki797Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Modified residuei851PhosphoserineCombined sources1

Post-translational modificationi

Sumoylated.1 Publication
Phosphorylation seems to contribute to the strength of cell-cell adhesion rather than to the basic capacity for cell-cell adhesion.By similarity

Keywords - PTMi

Acetylation, Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiP35221.
MaxQBiP35221.
PaxDbiP35221.
PeptideAtlasiP35221.
PRIDEiP35221.

PTM databases

iPTMnetiP35221.
PhosphoSitePlusiP35221.
SwissPalmiP35221.

Expressioni

Tissue specificityi

Expressed ubiquitously in normal tissues.

Gene expression databases

BgeeiENSG00000044115.
CleanExiHS_CTNNA1.
ExpressionAtlasiP35221. baseline and differential.
GenevisibleiP35221. HS.

Organism-specific databases

HPAiCAB021089.
HPA046119.
HPA063535.

Interactioni

Subunit structurei

Monomer and homodimer; the monomer preferentially binds to CTNNB1 and the homodimer to actin. Binds AFDN and F-actin. Possible component of an E-cadherin/ catenin adhesion complex together with E-cadherin/CDH1 and beta-catenin/CTNNB1 or gamma-catenin/JUP; the complex is located to adherens junctions. The stable association of CTNNA1 is controversial as CTNNA1 was shown not to bind to F-actin when assembled in the complex. Alternatively, the CTNNA1-containing complex may be linked to F-actin by other proteins such as LIMA1. Interacts with ARHGAP21 and with AJUBA. Interacts with LIMA1 (By similarity). Interacts with vinculin/VCL (PubMed:26691986).By similarity1 Publication

Binary interactionsi

Show more details

GO - Molecular functioni

  • actin filament binding Source: Ensembl
  • beta-catenin binding Source: BHF-UCL
  • cadherin binding Source: BHF-UCL
  • gamma-catenin binding Source: BHF-UCL
  • protein heterodimerization activity Source: Ensembl
  • vinculin binding Source: UniProtKB

Protein-protein interaction databases

BioGridi107876. 81 interactors.
CORUMiP35221.
DIPiDIP-515N.
IntActiP35221. 64 interactors.
MINTiMINT-4998962.
STRINGi9606.ENSP00000304669.

Structurei

Secondary structure

1906
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi293 – 299Combined sources7
Beta strandi300 – 302Combined sources3
Helixi305 – 316Combined sources12
Helixi325 – 327Combined sources3
Helixi328 – 352Combined sources25
Helixi353 – 355Combined sources3
Helixi378 – 386Combined sources9
Helixi387 – 389Combined sources3
Turni393 – 395Combined sources3
Helixi398 – 409Combined sources12
Helixi413 – 438Combined sources26
Helixi444 – 473Combined sources30
Helixi478 – 506Combined sources29
Helixi509 – 531Combined sources23
Helixi535 – 559Combined sources25
Turni560 – 562Combined sources3
Helixi567 – 581Combined sources15
Helixi583 – 598Combined sources16
Beta strandi600 – 602Combined sources3
Helixi608 – 630Combined sources23

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1H6GX-ray2.20A/B377-632[»]
4EHPX-ray2.66B277-382[»]
4IGGX-ray3.66A/B82-906[»]
ProteinModelPortaliP35221.
SMRiP35221.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP35221.

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni2 – 228Involved in homodimerizationAdd BLAST227
Regioni97 – 148Interaction with JUP and CTNNB11 PublicationAdd BLAST52
Regioni325 – 394Interaction with alpha-actininAdd BLAST70

Sequence similaritiesi

Belongs to the vinculin/alpha-catenin family.Curated

Phylogenomic databases

eggNOGiKOG3681. Eukaryota.
ENOG410XSRU. LUCA.
GeneTreeiENSGT00550000074411.
HOGENOMiHOG000280724.
HOVERGENiHBG000069.
InParanoidiP35221.
KOiK05691.
OMAiHHKDQMA.
OrthoDBiEOG091G01KR.
PhylomeDBiP35221.
TreeFamiTF313686.

Family and domain databases

InterProiView protein in InterPro
IPR001033. Alpha_catenin.
IPR030047. CTNNA1.
IPR006077. Vinculin/catenin.
IPR000633. Vinculin_CS.
PANTHERiPTHR18914. PTHR18914. 1 hit.
PTHR18914:SF36. PTHR18914:SF36. 1 hit.
PfamiView protein in Pfam
PF01044. Vinculin. 2 hits.
PRINTSiPR00805. ALPHACATENIN.
SUPFAMiSSF47220. SSF47220. 4 hits.
PROSITEiView protein in PROSITE
PS00663. VINCULIN_1. 1 hit.

Sequences (3)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P35221-1) [UniParc]FASTAAdd to basket
Also known as: CTNNA1a

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
MTAVHAGNIN FKWDPKSLEI RTLAVERLLE PLVTQVTTLV NTNSKGPSNK
60 70 80 90 100
KRGRSKKAHV LAASVEQATE NFLEKGDKIA KESQFLKEEL VAAVEDVRKQ
110 120 130 140 150
GDLMKAAAGE FADDPCSSVK RGNMVRAARA LLSAVTRLLI LADMADVYKL
160 170 180 190 200
LVQLKVVEDG ILKLRNAGNE QDLGIQYKAL KPEVDKLNIM AAKRQQELKD
210 220 230 240 250
VGHRDQMAAA RGILQKNVPI LYTASQACLQ HPDVAAYKAN RDLIYKQLQQ
260 270 280 290 300
AVTGISNAAQ ATASDDASQH QGGGGGELAY ALNNFDKQII VDPLSFSEER
310 320 330 340 350
FRPSLEERLE SIISGAALMA DSSCTRDDRR ERIVAECNAV RQALQDLLSE
360 370 380 390 400
YMGNAGRKER SDALNSAIDK MTKKTRDLRR QLRKAVMDHV SDSFLETNVP
410 420 430 440 450
LLVLIEAAKN GNEKEVKEYA QVFREHANKL IEVANLACSI SNNEEGVKLV
460 470 480 490 500
RMSASQLEAL CPQVINAALA LAAKPQSKLA QENMDLFKEQ WEKQVRVLTD
510 520 530 540 550
AVDDITSIDD FLAVSENHIL EDVNKCVIAL QEKDVDGLDR TAGAIRGRAA
560 570 580 590 600
RVIHVVTSEM DNYEPGVYTE KVLEATKLLS NTVMPRFTEQ VEAAVEALSS
610 620 630 640 650
DPAQPMDENE FIDASRLVYD GIRDIRKAVL MIRTPEELDD SDFETEDFDV
660 670 680 690 700
RSRTSVQTED DQLIAGQSAR AIMAQLPQEQ KAKIAEQVAS FQEEKSKLDA
710 720 730 740 750
EVSKWDDSGN DIIVLAKQMC MIMMEMTDFT RGKGPLKNTS DVISAAKKIA
760 770 780 790 800
EAGSRMDKLG RTIADHCPDS ACKQDLLAYL QRIALYCHQL NICSKVKAEV
810 820 830 840 850
QNLGGELVVS GVDSAMSLIQ AAKNLMNAVV QTVKASYVAS TKYQKSQGMA
860 870 880 890 900
SLNLPAVSWK MKAPEKKPLV KREKQDETQT KIKRASQKKH VNPVQALSEF

KAMDSI
Length:906
Mass (Da):100,071
Last modified:February 1, 1994 - v1
Checksum:i7AAE6F5DDBAF5099
GO
Isoform 2 (identifier: P35221-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     811-811: G → GNCDTCGALQGLKGWPPPLCLATHW

Show »
Length:930
Mass (Da):102,635
Checksum:i6EDF38C221CA2FA0
GO
Isoform 3 (identifier: P35221-3) [UniParc]FASTAAdd to basket
Also known as: CTNNA1b

The sequence of this isoform differs from the canonical sequence as follows:
     1-370: Missing.

Note: Expressed at high levels in the nervous system. Lacks the beta-catenin interaction domain.
Show »
Length:536
Mass (Da):59,550
Checksum:i887A39433621F5DB
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti92A → V in AAA86430 (PubMed:7945318).Curated1
Sequence conflicti92A → V in AAA18949 (PubMed:7945318).Curated1
Sequence conflicti129R → P in AAA18949 (PubMed:7945318).Curated1
Sequence conflicti175I → N in AAA86430 (PubMed:7945318).Curated1
Sequence conflicti175I → N in AAA18949 (PubMed:7945318).Curated1
Sequence conflicti216K → S in AAA86430 (PubMed:7945318).Curated1
Sequence conflicti216K → S in AAA18949 (PubMed:7945318).Curated1
Sequence conflicti342Q → K in BAA03530 (PubMed:8404069).Curated1
Sequence conflicti344 – 348LQDLL → CRTCV in AAA86430 (PubMed:7945318).Curated5
Sequence conflicti460L → G in AAA86430 (PubMed:7945318).Curated1
Sequence conflicti460L → G in AAA18949 (PubMed:7945318).Curated1
Sequence conflicti469L → TW in AAA86430 (PubMed:7945318).Curated1
Sequence conflicti469L → TW in AAA18949 (PubMed:7945318).Curated1
Sequence conflicti473A → P in AAA86430 (PubMed:7945318).Curated1
Sequence conflicti473A → P in AAA18949 (PubMed:7945318).Curated1
Sequence conflicti653R → E in AAA86430 (PubMed:7945318).Curated1
Sequence conflicti653R → E in AAA18949 (PubMed:7945318).Curated1
Sequence conflicti685A → R in AAA86430 (PubMed:7945318).Curated1
Sequence conflicti685A → R in AAA18949 (PubMed:7945318).Curated1
Sequence conflicti764A → R in AAA86430 (PubMed:7945318).Curated1
Sequence conflicti764A → R in AAA18949 (PubMed:7945318).Curated1
Sequence conflicti789Q → H in BAA03530 (PubMed:8404069).Curated1
Sequence conflicti859W → M in AAA86430 (PubMed:7945318).Curated1
Sequence conflicti859W → M in AAA18949 (PubMed:7945318).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_07658654R → C in MDPT2; no effect on VCL-binding. 1 PublicationCorresponds to variant dbSNP:rs781520852Ensembl.1
Natural variantiVAR_022303179A → V1 PublicationCorresponds to variant dbSNP:rs28363394Ensembl.1
Natural variantiVAR_022304219P → S1 PublicationCorresponds to variant dbSNP:rs28363406Ensembl.1
Natural variantiVAR_076587307E → K in MDPT2; no effect on VCL-binding. 1 PublicationCorresponds to variant dbSNP:rs869320697Ensembl.1
Natural variantiVAR_076588318L → S in MDPT2; no effect on VCL-binding. 1 PublicationCorresponds to variant dbSNP:rs869320696Ensembl.1
Natural variantiVAR_076589431I → M in MDPT2; no effect on VCL-binding. 1 PublicationCorresponds to variant dbSNP:rs755215402Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0478101 – 370Missing in isoform 3. 2 PublicationsAdd BLAST370
Alternative sequenceiVSP_017494811G → GNCDTCGALQGLKGWPPPLC LATHW in isoform 2. 1 Publication1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D14705 mRNA. Translation: BAA03530.1.
D13866 mRNA. Translation: BAA02979.1.
L23805 mRNA. Translation: AAA86430.1.
U03100 mRNA. Translation: AAA18949.1.
HQ589335 mRNA. Translation: AEF32483.1.
AF102803
, AF102787, AF102788, AF102789, AF102790, AF102791, AF102792, AF102793, AF102794, AF102795, AF102796, AF102797, AF102798, AF102799, AF102800, AF102801, AF102802 Genomic DNA. Translation: AAC99459.1.
AY884207 Genomic DNA. Translation: AAW56940.1.
AC010453 Genomic DNA. No translation available.
AC011405 Genomic DNA. No translation available.
AC034243 Genomic DNA. No translation available.
AC113340 Genomic DNA. No translation available.
CH471062 Genomic DNA. Translation: EAW62124.1.
BC000385 mRNA. Translation: AAH00385.1.
BC031262 mRNA. Translation: AAH31262.1.
L22080 mRNA. Translation: AAA35502.1.
CCDSiCCDS34243.1. [P35221-1]
CCDS75315.1. [P35221-3]
PIRiJC2542.
JN0607.
RefSeqiNP_001277236.1. NM_001290307.2.
NP_001277238.1. NM_001290309.2.
NP_001277239.1. NM_001290310.2.
NP_001277241.1. NM_001290312.1. [P35221-3]
NP_001310911.1. NM_001323982.1. [P35221-1]
NP_001310912.1. NM_001323983.1. [P35221-1]
NP_001310913.1. NM_001323984.1. [P35221-1]
NP_001310916.1. NM_001323987.1. [P35221-3]
NP_001310917.1. NM_001323988.1. [P35221-3]
NP_001310918.1. NM_001323989.1. [P35221-3]
NP_001310919.1. NM_001323990.1. [P35221-3]
NP_001310920.1. NM_001323991.1. [P35221-3]
NP_001310921.1. NM_001323992.1. [P35221-3]
NP_001310922.1. NM_001323993.1. [P35221-3]
NP_001310923.1. NM_001323994.1. [P35221-3]
NP_001310924.1. NM_001323995.1. [P35221-3]
NP_001310925.1. NM_001323996.1. [P35221-3]
NP_001310926.1. NM_001323997.1. [P35221-3]
NP_001310927.1. NM_001323998.1. [P35221-3]
NP_001310928.1. NM_001323999.1. [P35221-3]
NP_001310929.1. NM_001324000.1. [P35221-3]
NP_001894.2. NM_001903.4. [P35221-1]
UniGeneiHs.445981.

Genome annotation databases

EnsembliENST00000302763; ENSP00000304669; ENSG00000044115. [P35221-1]
ENST00000540387; ENSP00000438476; ENSG00000044115. [P35221-3]
GeneIDi1495.
KEGGihsa:1495.
UCSCiuc003ldh.4. human. [P35221-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiCTNA1_HUMAN
AccessioniPrimary (citable) accession number: P35221
Secondary accession number(s): Q12795, Q8N1C0
Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 1, 1994
Last sequence update: February 1, 1994
Last modified: September 27, 2017
This is version 185 of the entry and version 1 of the sequence. See 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

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 5
    Human chromosome 5: 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. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families