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UniProtKB - O94851 (MICA2_HUMAN)

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Protein

[F-actin]-monooxygenase MICAL2

Gene

MICAL2

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

Functioni

Nuclear monooxygenase that promotes depolymerization of F-actin by mediating oxidation of specific methionine residues on actin to form methionine-sulfoxide, resulting in actin filament disassembly and preventing repolymerization. In the absence of actin, it also functions as a NADPH oxidase producing H2O2 (By similarity). Acts as a key regulator of the SRF signaling pathway elicited by nerve growth factor and serum: mediates oxidation and subsequent depolymerization of nuclear actin, leading to increase MKL1/MRTF-A presence in the nucleus and promote SRF:MKL1/MRTF-A-dependent gene transcription. Does not activate SRF:MKL1/MRTF-A through RhoA.By similarity1 Publication

Catalytic activityi

[F-actin]-L-methionine + NADPH + O2 + H+ = [F-actin]-L-methionine-(R)-S-oxide + NADP+ + H2O.1 Publication

Cofactori

FADBy similarity

Enzyme regulationi

Specifically inhibited by CCG-1423, a small molecule inhibitor of SRF:MKL1/MRTF-A-dependent transcription.1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei97FADBy similarity1
Binding sitei183FAD; via amide nitrogen and carbonyl oxygenBy similarity1
Binding sitei298FADBy similarity1
Binding sitei398FADBy similarity1
Metal bindingi1002Zinc 1By similarity1
Metal bindingi1005Zinc 1By similarity1
Metal bindingi1023Zinc 1; via pros nitrogenBy similarity1
Metal bindingi1026Zinc 1By similarity1
Metal bindingi1029Zinc 2By similarity1
Metal bindingi1032Zinc 2By similarity1
Metal bindingi1052Zinc 2By similarity1
Metal bindingi1055Zinc 2; via pros nitrogenBy similarity1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi116 – 118FADBy similarity3
Nucleotide bindingi123 – 125FADBy similarity3

GO - Molecular functioni

View the complete GO annotation on QuickGO ...

GO - Biological processi

  • actin filament depolymerization Source: UniProtKB
  • cytoskeleton organization Source: UniProtKB
  • heart development Source: UniProtKB
  • heart looping Source: UniProtKB
  • oxidation-reduction process Source: UniProtKB
  • positive regulation of transcription via serum response element binding Source: UniProtKB
  • sulfur oxidation Source: UniProtKB
View the complete GO annotation on QuickGO ...

Keywordsi

Molecular functionActin-binding, Monooxygenase, Oxidoreductase
LigandFAD, Flavoprotein, Metal-binding, NADP, Zinc

Names & Taxonomyi

Protein namesi
Recommended name:
[F-actin]-monooxygenase MICAL2 (EC:1.14.13.2251 Publication)
Alternative name(s):
Molecule interacting with CasL protein 2
Short name:
MICAL-2
Gene namesi
Name:MICAL2
Synonyms:KIAA0750, MICAL2PV1, MICAL2PV2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo
Proteomesi
  • UP000005640 Componenti: Chromosome 11

Organism-specific databases

EuPathDBiHostDB:ENSG00000133816.13.
HGNCiHGNC:24693. MICAL2.
MIMi608881. gene.
neXtProtiNX_O94851.

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

Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi95G → V: Blocks FAD binding and abolishes catalytic activity. 1 Publication1
Mutagenesisi677 – 681KRRRK → AAAAA in MICAL-2NLSMut; abolishes nuclear localization. 1 Publication5

Organism-specific databases

DisGeNETi9645.
OpenTargetsiENSG00000133816.
PharmGKBiPA142671453.

Polymorphism and mutation databases

BioMutaiMICAL2.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000758441 – 1124[F-actin]-monooxygenase MICAL2Add BLAST1124

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei631PhosphoserineCombined sources1

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiO94851.
MaxQBiO94851.
PaxDbiO94851.
PeptideAtlasiO94851.
PRIDEiO94851.

PTM databases

iPTMnetiO94851.
PhosphoSitePlusiO94851.

Expressioni

Gene expression databases

BgeeiENSG00000133816.
CleanExiHS_MICAL2.
ExpressionAtlasiO94851. baseline and differential.
GenevisibleiO94851. HS.

Organism-specific databases

HPAiHPA030437.

Interactioni

Subunit structurei

Interacts with VIM and PLXNA4 (By similarity). Interacts with RAB1B.By similarity1 Publication

GO - Molecular functioni

  • actin binding Source: UniProtKB
View the complete GO annotation on QuickGO ...

Protein-protein interaction databases

BioGridi115003. 2 interactors.
IntActiO94851. 7 interactors.
MINTiO94851.
STRINGi9606.ENSP00000256194.

Structurei

Secondary structure

11124
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi520 – 530Combined sources11
Beta strandi540 – 542Combined sources3
Helixi543 – 545Combined sources3
Beta strandi546 – 548Combined sources3
Helixi549 – 558Combined sources10
Turni560 – 562Combined sources3
Turni565 – 567Combined sources3
Helixi570 – 572Combined sources3
Helixi573 – 586Combined sources14
Helixi596 – 601Combined sources6
Helixi607 – 621Combined sources15

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2E9KNMR-A516-629[»]
ProteinModelPortaliO94851.
SMRiO94851.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiO94851.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini516 – 619Calponin-homology (CH)PROSITE-ProRule annotationAdd BLAST104
Domaini1000 – 1062LIM zinc-bindingPROSITE-ProRule annotationAdd BLAST63

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni2 – 494Monooxygenase domainBy similarityAdd BLAST493

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi660 – 681Nuclear localization signal1 PublicationAdd BLAST22

Sequence similaritiesi

Belongs to the Mical family.Curated

Keywords - Domaini

LIM domain

Phylogenomic databases

eggNOGiKOG1700. Eukaryota.
COG5069. LUCA.
GeneTreeiENSGT00760000118856.
HOGENOMiHOG000047263.
HOVERGENiHBG052474.
InParanoidiO94851.
KOiK19947.
OMAiDHRPKAQ.
OrthoDBiEOG091G009H.
PhylomeDBiO94851.
TreeFamiTF324129.

Family and domain databases

CDDicd00014. CH. 1 hit.
Gene3Di1.10.418.10. 1 hit.
InterProiView protein in InterPro
IPR001715. CH-domain.
IPR036872. CH_dom_sf.
IPR002938. FAD-bd.
IPR036188. FAD/NAD-bd_sf.
IPR029939. MICAL2.
IPR001781. Znf_LIM.
PANTHERiPTHR44265:SF3. PTHR44265:SF3. 1 hit.
PfamiView protein in Pfam
PF00307. CH. 1 hit.
PF01494. FAD_binding_3. 1 hit.
PF00412. LIM. 1 hit.
SMARTiView protein in SMART
SM00033. CH. 1 hit.
SM00132. LIM. 1 hit.
SUPFAMiSSF47576. SSF47576. 1 hit.
SSF51905. SSF51905. 2 hits.
PROSITEiView protein in PROSITE
PS50021. CH. 1 hit.
PS00478. LIM_DOMAIN_1. 1 hit.
PS50023. LIM_DOMAIN_2. 1 hit.

Sequences (6)i

Sequence statusi: Complete.

This entry describes 6 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: O94851-1) [UniParc]FASTAAdd to basket

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
MGENEDEKQA QAGQVFENFV QASTCKGTLQ AFNILTRHLD LDPLDHRNFY 
        60         70         80         90        100
SKLKSKVTTW KAKALWYKLD KRGSHKEYKR GKSCTNTKCL IVGGGPCGLR 
       110        120        130        140        150
TAIELAYLGA KVVVVEKRDS FSRNNVLHLW PFTIHDLRGL GAKKFYGKFC 
       160        170        180        190        200
AGSIDHISIR QLQLILFKVA LMLGVEIHVN VEFVKVLEPP EDQENQKIGW 
       210        220        230        240        250
RAEFLPTDHS LSEFEFDVII GADGRRNTLE GFRRKEFRGK LAIAITANFI 
       260        270        280        290        300
NRNSTAEAKV EEISGVAFIF NQKFFQDLKE ETGIDLENIV YYKDCTHYFV 
       310        320        330        340        350
MTAKKQSLLD KGVIINDYID TEMLLCAENV NQDNLLSYAR EAADFATNYQ 
       360        370        380        390        400
LPSLDFAMNH YGQPDVAMFD FTCMYASENA ALVRERQAHQ LLVALVGDSL 
       410        420        430        440        450
LEPFWPMGTG CARGFLAAFD TAWMVKSWNQ GTPPLELLAE RESLYRLLPQ 
       460        470        480        490        500
TTPENINKNF EQYTLDPGTR YPNLNSHCVR PHQVKHLYIT KELEHYPLER 
       510        520        530        540        550
LGSVRRSVNL SRKESDIRPS KLLTWCQQQT EGYQHVNVTD LTTSWRSGLA 
       560        570        580        590        600
LCAIIHRFRP ELINFDSLNE DDAVENNQLA FDVAEREFGI PPVTTGKEMA 
       610        620        630        640        650
SAQEPDKLSM VMYLSKFYEL FRGTPLRPVD SWRKNYGENA DLSLAKSSIS 
       660        670        680        690        700
NNYLNLTFPR KRTPRVDGQT GENDMNKRRR KGFTNLDEPS NFSSRSLGSN 
       710        720        730        740        750
QECGSSKEGG NQNKVKSMAN QLLAKFEEST RNPSLMKQER RVSGIGKPVL 
       760        770        780        790        800
CSSSGPPVHS CCPKPEEATP SPSPPLKRQF PSVVVTGHVL RELKQVSAGS 
       810        820        830        840        850
ECLSRPWRAR AKSDLQLGGT ENFATLPSTR PRAQALSGVL WRLQQVEEKI 
       860        870        880        890        900
LQKRAQNLAN REFHTKNIKE KAAHLASMFG HGDFPQNKLL SKGLSHTHPP 
       910        920        930        940        950
SPPSRLPSPD PAASSSPSTV DSASPARKEK KSPSGFHFHP SHLRTVHPQL 
       960        970        980        990       1000
TVGKVSSGIG AAAEVLVNLY MNDHRPKAQA TSPDLESMRK SFPLNLGGSD 
      1010       1020       1030       1040       1050
TCYFCKKRVY VMERLSAEGH FFHRECFRCS ICATTLRLAA YTFDCDEGKF 
      1060       1070       1080       1090       1100
YCKPHFIHCK TNSKQRKRRA ELKQQREEEA TWQEQEAPRR DTPTESSCAV 
      1110       1120 
AAIGTLEGSP PVHFSLPVLH PLLG
Length:1,124
Mass (Da):126,689
Last modified:May 1, 1999 - v1
Checksum:i1C276C42D17B64DF
GO
Isoform 2 (identifier: O94851-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-171: Missing.
     740-986: Missing.
     1112-1124: VHFSLPVLHPLLG → GISTSFFRKV...VLRCFPVKLR

Show »
Length:784
Mass (Da):89,890
Checksum:i114E5873F13E5C61
GO
Isoform 3 (identifier: O94851-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     929-949: Missing.

Show »
Length:1,103
Mass (Da):124,253
Checksum:iEAB33EE2B2DB4BA1
GO
Isoform 4 (identifier: O94851-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     739-928: Missing.
     950-985: Missing.
     1112-1124: VHFSLPVLHPLLG → GISTSFFRKV...VLRCFPVKLR

Show »
Length:976
Mass (Da):111,652
Checksum:iD8B4E819D43FDA7E
GO
Isoform 5 (identifier: O94851-5) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     739-928: Missing.

Show »
Length:934
Mass (Da):106,211
Checksum:i5CB357AB0F7D4B9E
GO
Isoform 6 (identifier: O94851-6) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     739-985: Missing.
     1112-1124: VHFSLPVLHPLLG → GISTSFFRKV...VLRCFPVKLR

Show »
Length:955
Mass (Da):109,216
Checksum:i583E6EF7AC29A939
GO

Sequence cautioni

The sequence BAA34470 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti19F → S in BAG57951 (PubMed:14702039).Curated1
Sequence conflicti208D → G in CAD97967 (PubMed:17974005).Curated1
Sequence conflicti296T → A in CAD97967 (PubMed:17974005).Curated1
Sequence conflicti529Q → H in BAG57951 (PubMed:14702039).Curated1
Sequence conflicti563I → V in BAG57951 (PubMed:14702039).Curated1
Sequence conflicti631S → Y in CAD97967 (PubMed:17974005).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_050155145F → L. Corresponds to variant dbSNP:rs2706656Ensembl.1
Natural variantiVAR_021992220I → V. Corresponds to variant dbSNP:rs2306727Ensembl.1
Natural variantiVAR_050156687D → E. Corresponds to variant dbSNP:rs3794084Ensembl.1
Natural variantiVAR_0202571089R → Q. Corresponds to variant dbSNP:rs2270515Ensembl.1
Natural variantiVAR_0245231106L → P1 PublicationCorresponds to variant dbSNP:rs1027335Ensembl.1
Natural variantiVAR_0501571110P → S. Corresponds to variant dbSNP:rs35518829Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0098591 – 171Missing in isoform 2. 1 PublicationAdd BLAST171
Alternative sequenceiVSP_042593739 – 985Missing in isoform 6. 1 PublicationAdd BLAST247
Alternative sequenceiVSP_042594739 – 928Missing in isoform 4 and isoform 5. 2 PublicationsAdd BLAST190
Alternative sequenceiVSP_009860740 – 986Missing in isoform 2. 1 PublicationAdd BLAST247
Alternative sequenceiVSP_042595929 – 949Missing in isoform 3. 1 PublicationAdd BLAST21
Alternative sequenceiVSP_042596950 – 985Missing in isoform 4. 1 PublicationAdd BLAST36
Alternative sequenceiVSP_0098611112 – 1124VHFSL…HPLLG → GISTSFFRKVLGWPLRLPRD LCNWMQGLLQAAGLHIRDNA YNYCYMYELLSLGLPLLWAF SEVLAAMYRESEGSLESICN WVLRCFPVKLR in isoform 2, isoform 4 and isoform 6. 2 PublicationsAdd BLAST13

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB110785 mRNA. Translation: BAD83656.1.
AB110786 mRNA. Translation: BAD83657.1.
AB018293 mRNA. Translation: BAA34470.2. Different initiation.
AK294845 mRNA. Translation: BAG57951.1.
AK302893 mRNA. Translation: BAH13835.1.
BX538021 mRNA. Translation: CAD97967.1.
BX641163 mRNA. Translation: CAE46072.1.
AC025106 Genomic DNA. No translation available.
AC079329 Genomic DNA. No translation available.
CH471064 Genomic DNA. Translation: EAW68528.1.
CH471064 Genomic DNA. Translation: EAW68529.1.
CH471064 Genomic DNA. Translation: EAW68531.1.
BC044577 mRNA. Translation: AAH44577.1.
BK000462 mRNA. Translation: DAA01341.1.
CCDSiCCDS60726.1. [O94851-3]
CCDS60727.1. [O94851-5]
CCDS60728.1. [O94851-4]
CCDS7809.1. [O94851-1]
RefSeqiNP_001269592.1. NM_001282663.1. [O94851-1]
NP_001269593.1. NM_001282664.1. [O94851-3]
NP_001269594.1. NM_001282665.1. [O94851-5]
NP_001269595.1. NM_001282666.1. [O94851-4]
NP_001269596.1. NM_001282667.1. [O94851-6]
NP_001333221.1. NM_001346292.1. [O94851-1]
NP_001333222.1. NM_001346293.1. [O94851-3]
NP_001333223.1. NM_001346294.1. [O94851-3]
NP_001333224.1. NM_001346295.1. [O94851-3]
NP_001333225.1. NM_001346296.1. [O94851-3]
NP_001333226.1. NM_001346297.1. [O94851-3]
NP_001333227.1. NM_001346298.1. [O94851-3]
NP_001333228.1. NM_001346299.1. [O94851-3]
NP_055447.1. NM_014632.3. [O94851-1]
XP_016874078.1. XM_017018589.1. [O94851-1]
XP_016874079.1. XM_017018590.1. [O94851-1]
XP_016874080.1. XM_017018591.1. [O94851-3]
UniGeneiHs.501928.

Genome annotation databases

EnsembliENST00000256194; ENSP00000256194; ENSG00000133816. [O94851-1]
ENST00000342902; ENSP00000344894; ENSG00000133816. [O94851-3]
ENST00000379612; ENSP00000368932; ENSG00000133816. [O94851-4]
ENST00000527546; ENSP00000433965; ENSG00000133816. [O94851-5]
ENST00000537344; ENSP00000441689; ENSG00000133816. [O94851-1]
GeneIDi9645.
KEGGihsa:9645.
UCSCiuc001mjz.5. human. [O94851-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiMICA2_HUMAN
AccessioniPrimary (citable) accession number: O94851
Secondary accession number(s): B4DGZ0
, B7Z849, D3DQW5, G3XAC8, Q5KTR3, Q5KTR4, Q7Z3A8
Entry historyiIntegrated into UniProtKB/Swiss-Prot: April 13, 2004
Last sequence update: May 1, 1999
Last modified: February 28, 2018
This is version 154 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, Reference proteome