UniProtKB - O94851 (MICA2_HUMAN)
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Protein
[F-actin]-monooxygenase MICAL2
Gene
MICAL2
Organism
Homo sapiens (Human)
Status
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 key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Binding sitei | 97 | FADBy similarity | 1 | |
Binding sitei | 183 | FAD; via amide nitrogen and carbonyl oxygenBy similarity | 1 | |
Binding sitei | 298 | FADBy similarity | 1 | |
Binding sitei | 398 | FADBy similarity | 1 | |
Metal bindingi | 1002 | Zinc 1By similarity | 1 | |
Metal bindingi | 1005 | Zinc 1By similarity | 1 | |
Metal bindingi | 1023 | Zinc 1; via pros nitrogenBy similarity | 1 | |
Metal bindingi | 1026 | Zinc 1By similarity | 1 | |
Metal bindingi | 1029 | Zinc 2By similarity | 1 | |
Metal bindingi | 1032 | Zinc 2By similarity | 1 | |
Metal bindingi | 1052 | Zinc 2By similarity | 1 | |
Metal bindingi | 1055 | Zinc 2; via pros nitrogenBy similarity | 1 |
Regions
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Nucleotide bindingi | 116 – 118 | FADBy similarity | 3 | |
Nucleotide bindingi | 123 – 125 | FADBy similarity | 3 |
GO - Molecular functioni
- actin binding Source: UniProtKB
- FAD binding Source: UniProtKB
- metal ion binding Source: UniProtKB-KW
- NADPH:sulfur oxidoreductase activity Source: InterPro
- oxidoreductase activity Source: UniProtKB
- oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, NAD(P)H as one donor, and incorporation of one atom of oxygen Source: UniProtKB
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
Keywordsi
Molecular function | Actin-binding, Monooxygenase, Oxidoreductase |
Ligand | FAD, 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 |
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
EuPathDBi | HostDB:ENSG00000133816.13. |
HGNCi | HGNC:24693. MICAL2. |
MIMi | 608881. gene. |
neXtProti | NX_O94851. |
Pathology & Biotechi
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 95 | G → V: Blocks FAD binding and abolishes catalytic activity. 1 Publication | 1 | |
Mutagenesisi | 677 – 681 | KRRRK → AAAAA in MICAL-2NLSMut; abolishes nuclear localization. 1 Publication | 5 |
Organism-specific databases
DisGeNETi | 9645. |
OpenTargetsi | ENSG00000133816. |
PharmGKBi | PA142671453. |
Polymorphism and mutation databases
BioMutai | MICAL2. |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000075844 | 1 – 1124 | [F-actin]-monooxygenase MICAL2Add BLAST | 1124 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 631 | PhosphoserineCombined sources | 1 |
Keywords - PTMi
PhosphoproteinProteomic databases
EPDi | O94851. |
MaxQBi | O94851. |
PaxDbi | O94851. |
PeptideAtlasi | O94851. |
PRIDEi | O94851. |
PTM databases
iPTMneti | O94851. |
PhosphoSitePlusi | O94851. |
Expressioni
Gene expression databases
Bgeei | ENSG00000133816. |
CleanExi | HS_MICAL2. |
ExpressionAtlasi | O94851. baseline and differential. |
Genevisiblei | O94851. HS. |
Organism-specific databases
HPAi | HPA030437. |
Interactioni
Subunit structurei
Interacts with VIM and PLXNA4 (By similarity). Interacts with RAB1B.By similarity1 Publication
GO - Molecular functioni
- actin binding Source: UniProtKB
Protein-protein interaction databases
BioGridi | 115003. 2 interactors. |
IntActi | O94851. 7 interactors. |
MINTi | O94851. |
STRINGi | 9606.ENSP00000256194. |
Structurei
Secondary structure
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more detailsFeature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Helixi | 520 – 530 | Combined sources | 11 | |
Beta strandi | 540 – 542 | Combined sources | 3 | |
Helixi | 543 – 545 | Combined sources | 3 | |
Beta strandi | 546 – 548 | Combined sources | 3 | |
Helixi | 549 – 558 | Combined sources | 10 | |
Turni | 560 – 562 | Combined sources | 3 | |
Turni | 565 – 567 | Combined sources | 3 | |
Helixi | 570 – 572 | Combined sources | 3 | |
Helixi | 573 – 586 | Combined sources | 14 | |
Helixi | 596 – 601 | Combined sources | 6 | |
Helixi | 607 – 621 | Combined sources | 15 |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
2E9K | NMR | - | A | 516-629 | [»] | |
ProteinModelPortali | O94851. | |||||
SMRi | O94851. | |||||
ModBasei | Search... | |||||
MobiDBi | Search... |
Miscellaneous databases
EvolutionaryTracei | O94851. |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 516 – 619 | Calponin-homology (CH)PROSITE-ProRule annotationAdd BLAST | 104 | |
Domaini | 1000 – 1062 | LIM zinc-bindingPROSITE-ProRule annotationAdd BLAST | 63 |
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 2 – 494 | Monooxygenase domainBy similarityAdd BLAST | 493 |
Motif
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Motifi | 660 – 681 | Nuclear localization signal1 PublicationAdd BLAST | 22 |
Sequence similaritiesi
Belongs to the Mical family.Curated
Keywords - Domaini
LIM domainPhylogenomic databases
eggNOGi | KOG1700. Eukaryota. COG5069. LUCA. |
GeneTreei | ENSGT00760000118856. |
HOGENOMi | HOG000047263. |
HOVERGENi | HBG052474. |
InParanoidi | O94851. |
KOi | K19947. |
OMAi | DHRPKAQ. |
OrthoDBi | EOG091G009H. |
PhylomeDBi | O94851. |
TreeFami | TF324129. |
Family and domain databases
CDDi | cd00014. CH. 1 hit. |
Gene3Di | 1.10.418.10. 1 hit. |
InterProi | View protein in InterPro IPR001715. CH-domain. IPR036872. CH_dom_sf. IPR002938. FAD-bd. IPR036188. FAD/NAD-bd_sf. IPR029939. MICAL2. IPR001781. Znf_LIM. |
PANTHERi | PTHR44265:SF3. PTHR44265:SF3. 1 hit. |
Pfami | View protein in Pfam PF00307. CH. 1 hit. PF01494. FAD_binding_3. 1 hit. PF00412. LIM. 1 hit. |
SMARTi | View protein in SMART SM00033. CH. 1 hit. SM00132. LIM. 1 hit. |
SUPFAMi | SSF47576. SSF47576. 1 hit. SSF51905. SSF51905. 2 hits. |
PROSITEi | View protein in PROSITE PS50021. CH. 1 hit. PS00478. LIM_DOMAIN_1. 1 hit. PS50023. LIM_DOMAIN_2. 1 hit. |
s (6)i Sequence
Sequence statusi: Complete.
This entry describes 6 produced by isoformsialternative 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.
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
Sequence cautioni
The sequence BAA34470 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 19 | F → S in BAG57951 (PubMed:14702039).Curated | 1 | |
Sequence conflicti | 208 | D → G in CAD97967 (PubMed:17974005).Curated | 1 | |
Sequence conflicti | 296 | T → A in CAD97967 (PubMed:17974005).Curated | 1 | |
Sequence conflicti | 529 | Q → H in BAG57951 (PubMed:14702039).Curated | 1 | |
Sequence conflicti | 563 | I → V in BAG57951 (PubMed:14702039).Curated | 1 | |
Sequence conflicti | 631 | S → Y in CAD97967 (PubMed:17974005).Curated | 1 |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_050155 | 145 | F → L. Corresponds to variant dbSNP:rs2706656Ensembl. | 1 | |
Natural variantiVAR_021992 | 220 | I → V. Corresponds to variant dbSNP:rs2306727Ensembl. | 1 | |
Natural variantiVAR_050156 | 687 | D → E. Corresponds to variant dbSNP:rs3794084Ensembl. | 1 | |
Natural variantiVAR_020257 | 1089 | R → Q. Corresponds to variant dbSNP:rs2270515Ensembl. | 1 | |
Natural variantiVAR_024523 | 1106 | L → P1 PublicationCorresponds to variant dbSNP:rs1027335Ensembl. | 1 | |
Natural variantiVAR_050157 | 1110 | P → S. Corresponds to variant dbSNP:rs35518829Ensembl. | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_009859 | 1 – 171 | Missing in isoform 2. 1 PublicationAdd BLAST | 171 | |
Alternative sequenceiVSP_042593 | 739 – 985 | Missing in isoform 6. 1 PublicationAdd BLAST | 247 | |
Alternative sequenceiVSP_042594 | 739 – 928 | Missing in isoform 4 and isoform 5. 2 PublicationsAdd BLAST | 190 | |
Alternative sequenceiVSP_009860 | 740 – 986 | Missing in isoform 2. 1 PublicationAdd BLAST | 247 | |
Alternative sequenceiVSP_042595 | 929 – 949 | Missing in isoform 3. 1 PublicationAdd BLAST | 21 | |
Alternative sequenceiVSP_042596 | 950 – 985 | Missing in isoform 4. 1 PublicationAdd BLAST | 36 | |
Alternative sequenceiVSP_009861 | 1112 – 1124 | VHFSL…HPLLG → GISTSFFRKVLGWPLRLPRD LCNWMQGLLQAAGLHIRDNA YNYCYMYELLSLGLPLLWAF SEVLAAMYRESEGSLESICN WVLRCFPVKLR in isoform 2, isoform 4 and isoform 6. 2 PublicationsAdd BLAST | 13 |
Sequence databases
Genome annotation databases
Ensembli | ENST00000256194; ENSP00000256194; ENSG00000133816. [O94851-1] ENST00000342902; ENSP00000344894; ENSG00000133816. [O94851-3] ENST00000379612; ENSP00000368932; ENSG00000133816. [O94851-4] ENST00000527546; ENSP00000433965; ENSG00000133816. [O94851-5] ENST00000537344; ENSP00000441689; ENSG00000133816. [O94851-1] |
GeneIDi | 9645. |
KEGGi | hsa:9645. |
UCSCi | uc001mjz.5. human. [O94851-1] |
Keywords - Coding sequence diversityi
Alternative splicing, PolymorphismSimilar proteinsi
Entry informationi
Entry namei | MICA2_HUMAN | |
Accessioni | O94851Primary (citable) accession number: O94851 Secondary accession number(s): B4DGZ0 Q7Z3A8 | |
Entry historyi | Integrated 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 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. |