Gene

KWMTBOMO01683

Pre Gene Modal

BGIBMGA006037

Annotation

eIF_2a_kinase_[Bombyx_mori]

Location

Bomo_Chr4(-):1527903-1536242      View in EpiBrowser

Full name

Eukaryotic translation initiation factor 2-alpha kinase 1      

Alternative Name

Heme-regulated eukaryotic initiation factor eIF-2-alpha kinase
Hemin-sensitive initiation factor 2-alpha kinase
Heme-controlled repressor
Heme-regulated inhibitor

Location in the cell

Cytoplasmic   Reliability : 2.941

CDS

ATGGATAAACATAGCCAAGACAAATGGAAAGCATTGGCGACAGTGAAATCCTTCGATTTAGGCATATCGGCTAGTCACCATGAGTCATTCGTACAGCAGAGTAGACAACAGATTGATGTCATCAATGCCCCAACCACAACCCCAATCAGCCTCCTAGTTCAATCACTCGTTAAACAATTGTGTTCATTGTTACAAAAAGACAGTATTATAGCCAATCAGCTTTACAACAAAATATGTGAGAAACTTCATAGTATGAACTTGATTGACAATTCGTATGCTATGGGAGAGTTTGAAGCTATGAGAAGTCAATATCAGAGAGCCTTGTATCAGCTTGTGACGGTCGCCAGCGGAACAGAGATACCGATAATACTGCCAGCAACTTGGCCTATAGTTCAGCCGTCTGGACTTGAATGGTCAAGATACCATAGAGAATTTGAGGAGCTCTACTTCATAGCTGGTGGAGGCTTCGGGAGCGTTTTCAAAGCGCGACACAGACTAGATGGCGTAGAGTATGCCGTCAAAAAAGTTTACATTAAATCTTCAGACGTCGACTCTATCATGAGTCATTTGTCGGAAGTCAAAACAATAGCCAGTCTCAATCACCCGAACATAGTAAACTATAAGGCAGCGTGGCTCGAACCCATGATAGAGTCTACAGTTAAAAAGAAAGGCAAATATCAAATGGACACCGACAGTGACGAGTTTTCATTAAGCTCTGACCTCATATCATCAGCACATCCCAACGTAATAAATTCATTCAAGACTCACAACTCCAAGGAGTTGACCAAAAACAAGAGCCTGTCCGACTTCATTATTTCCTTCAAGAACTCCAACAGCTTCGAGAACTTGAACAGTTCGAACGAAGAACTGCAGGTTTCTGACAGCGATGACGAGTCCGTTTCGCAGGAGGAGAATGCCGTTTGCAATCTCTTTTCCAGTAAGGAGTACGAAAATTGCTCTCGTATAAACCTTAAATGGGCCACCTTGTTCATCCAGATGACGTTCTGCCAGCAAACCTTGAAGCAGTGGCTTGACGAGCGCAACAACCATATGTCAGTGTCGCGAAAAGGTTCCGACGATTTCACTCTGCCGTTACATGTGTGTGAATCTCCAATTGAGGCTAAAGATATCACGTTCCCAGCGAGTATTAATCACATTGACCTGCTGATAGACATGTTCACGCAGCTGGTGCGTGGTCTCCATTATATACATTCCCGTGGTATTATCCACCACGACATAAAGCCGAGTAATGTATTCGTCGCGCCACATGAAGGTGGCTTGTTGGTGCAGTTGGGTGATTTCGGTTTGGCTTGCCCGTTACAGCAGTCCCATAGTGGATTGGCACTCGGTACACATATGTATGCTGCACCGGAGCAACTGGATGGGCAGTGCAATCCAAAGAGCGACATGTACAGTCTGGGTATAATATTACTTGAGTTGGTAGAACCATTCGTGACTGATATGGAACGAGTGAAAACTATCACCGACCTCCGCAAAGGTCAGATTCCAGCTCACCTCACTGCCAACTACCCAAAAATTGCTCATATCATCGGCAAACTGGTGCAAAGGAAGCCCAGCAAGAGACTGGACACGGCCCAGCTGCTGGAGGAACTCAAGACCCTGGCCGAGAATAAAGATGACACGATCAGATCGTTGCGAGAGGAGCTCGCTGCGAAAGATGACGAAATAGCTAAACTCAAGATGATGCTGGCGAACTTGAATTTTAAATCTTCAGTGTGA

Protein

MDKHSQDKWKALATVKSFDLGISASHHESFVQQSRQQIDVINAPTTTPISLLVQSLVKQLCSLLQKDSIIANQLYNKICEKLHSMNLIDNSYAMGEFEAMRSQYQRALYQLVTVASGTEIPIILPATWPIVQPSGLEWSRYHREFEELYFIAGGGFGSVFKARHRLDGVEYAVKKVYIKSSDVDSIMSHLSEVKTIASLNHPNIVNYKAAWLEPMIESTVKKKGKYQMDTDSDEFSLSSDLISSAHPNVINSFKTHNSKELTKNKSLSDFIISFKNSNSFENLNSSNEELQVSDSDDESVSQEENAVCNLFSSKEYENCSRINLKWATLFIQMTFCQQTLKQWLDERNNHMSVSRKGSDDFTLPLHVCESPIEAKDITFPASINHIDLLIDMFTQLVRGLHYIHSRGIIHHDIKPSNVFVAPHEGGLLVQLGDFGLACPLQQSHSGLALGTHMYAAPEQLDGQCNPKSDMYSLGIILLELVEPFVTDMERVKTITDLRKGQIPAHLTANYPKIAHIIGKLVQRKPSKRLDTAQLLEELKTLAENKDDTIRSLREELAAKDDEIAKLKMMLANLNFKSSV

Description

Inhibits protein synthesis at the translation initiation level, in response to various stress conditions, including oxidative stress, heme deficiency, osmotic shock and heat shock. Exerts its function through the phosphorylation of EIF2S1 at 'Ser-48' and 'Ser-51', thus preventing its recycling. Binds hemin forming a 1:1 complex through a cysteine thiolate and histidine nitrogenous coordination. This binding occurs with moderate affinity, allowing it to sense the heme concentration within the cell. Thanks to this unique heme-sensing capacity, plays a crucial role to shut off protein synthesis during acute heme-deficient conditions. In red blood cells (RBCs), controls hemoglobin synthesis ensuring a coordinated regulation of the synthesis of its heme and globin moieties. Thus plays an essential protective role for RBC survival in anemias of iron deficiency. Similarly, in hepatocytes, involved in heme-mediated translational control of CYP2B and CYP3A and possibly other hepatic P450 cytochromes. May also contain ER stress during acute heme-deficient conditions (By similarity).

Catalytic Activity

ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl-[protein]
ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L-threonyl-[protein]

Subunit

Synthesized in an inactive form that binds to the N-terminal domain of CDC37. Has to be associated with a multiprotein complex containing Hsp90, CDC37 and PPP5C for maturation and activation by autophosphorylation. The phosphatase PPP5C modulates this activation. Forms oligomers. Has been reported as a homodimer, as well as a hexamer in the absence of hemin. Converted to an inactive disulfide linked homodimer in the presence of hemin (By similarity).
Synthesized in an inactive form that binds to the N-terminal domain of CDC37. Has to be associated with a multiprotein complex containing Hsp90, CDC37 and PPP5C for maturation and activation by autophosphorylation. The phosphatase PPP5C modulates this activation. Forms oligomers. Has been reported as a non-covalently bound homodimer, as well as a hexamer in the absence of hemin. Converted to an inactive disulfide linked homodimer in the presence of hemin (By similarity).

Miscellaneous

Can bind 1 molecules of heme per polypeptide chain.

Similarity

Belongs to the protein kinase superfamily. Ser/Thr protein kinase family. GCN2 subfamily.

Keywords

ATP-binding   Complete proteome   Cytoplasm   Disulfide bond   Kinase   Nucleotide-binding   Phosphoprotein   Protein synthesis inhibitor   Repeat   Transferase   Alternative splicing   Polymorphism   Reference proteome  

Feature

chain  Eukaryotic translation initiation factor 2-alpha kinase 1
splice variant  In isoform 2.
sequence variant  In dbSNP:rs34889754.

Uniprot

Q8I739   H9J945   A0A2H1VIE0   A0A2W1BNF1   A0A2A4KAZ2   A0A194R5Z6   + More
A0A212EJ31   A0A194PYU9   A0A0L7L9L3   A0A336K8N1   A0A182HCR7   A0A182LSK0   A0A1W4WZY9   Q17MW3   D6WJR1   A0A084WAM0   A0A1B0GM98   A0A0K8TMR2   A0A146LBU4   A0A0A9WWL4   A0A1Y1KBL7   A0A026WQ75   A0A3L8DNL7   A0A158NV55   A0A195DZQ1   A0A1B6EJ28   A0A1B6I9A0   A0A1B6LV80   A0A096N681   F7A5Z1   G7P286   F7F136   A0A2K5MH01   Q4R8E0   H9EYQ6   A0A2K5MGV9   A0A2K5YAW5   A0A2K5X5T1   A0A2K5MGW2   Q9BQI3-2   A0A024QZU1   Q9BQI3   A0A2K6NPN8   A0A2R7X2V0   S7NHA6   A0A340WPE5   A0A0D9RYR1   A0A2K5SJB8   A0A2K6TJ62   A0A2R9BQ21   B4DIP4   H2QU55   K7DI71   A0A1U7UYU5   A0A2I3SA78   A0A1U7ULN9   A0A3Q0DDA5  

EC Number

2.7.11.1

Pubmed

19121390    28756777    26354079    22118469    26227816    26483478    + More
17510324    18362917    19820115    24438588    26369729    26823975    25401762    28004739    24508170    30249741    21347285    22002653    17431167    25319552    11101152    10718198    10931946    11230166    12391722    14702039    17974005    12690205    15489334    11036079    18691976    20071449    21269460    17344846    11181995    25362486    22722832    16136131   

EMBL

U87236    AAO13686.1    BABH01004453    ODYU01002731    SOQ40595.1    KZ150052    + More
PZC74396.1    NWSH01000011    PCG80910.1    KQ460644    KPJ13243.1    AGBW02014536    OWR41489.1    KQ459584    KPI98512.1    JTDY01002109    KOB72085.1    UFQS01000117    UFQT01000117    SSW99988.1    SSX20368.1    JXUM01034487    KQ561024    KXJ79985.1    AXCM01005219    CH477203    EAT48039.1    KQ971343    EFA03110.1    ATLV01022209    KE525330    KFB47264.1    AJVK01011228    GDAI01001974    JAI15629.1    GDHC01012796    JAQ05833.1    GBHO01032691    JAG10913.1    GEZM01091386    JAV56866.1    KK107135    EZA58098.1    QOIP01000006    RLU22024.1    ADTU01026895    KQ980031    KYN18182.1    GECZ01031845    JAS37924.1    GECU01024195    JAS83511.1    GEBQ01031866    GEBQ01012422    GEBQ01007005    JAT08111.1    JAT27555.1    JAT32972.1    CM001278    EHH51994.1    JSUE03027721    JSUE03027722    JSUE03027723    AB168513    JU323759    AFE67515.1    AQIA01045269    AQIA01045270    AF255050    AF100784    AF181071    AB037790    AF183414    AL136563    AF147094    AK075192    AK290327    AL834494    CH236963    CH878731    BC006524    AF116634    EAW55051.1    KK856629    PTY26137.1    KE164198    EPQ15910.1    AQIB01149654    AQIB01149655    AQIB01149656    AJFE02118599    AJFE02118600    AJFE02118601    AJFE02118602    AJFE02118603    AJFE02118604    AJFE02118605    AK295712    BAG58556.1    AC184156    GABC01003448    GABC01003447    NBAG03000572    JAA07890.1    PNI14766.1    GABF01003862    GABF01003861    GABD01000763    GABD01000762    GABE01005524    JAA18283.1    JAA32337.1    JAA39215.1   

Proteomes

UP000005204    UP000218220    UP000053240    UP000007151    UP000053268    UP000037510    + More
UP000069940    UP000249989    UP000075883    UP000192223    UP000008820    UP000007266    UP000030765    UP000092462    UP000053097    UP000279307    UP000005205    UP000078492    UP000028761    UP000008225    UP000009130    UP000006718    UP000233060    UP000233100    UP000233140    UP000005640    UP000233200    UP000265300    UP000029965    UP000233040    UP000233220    UP000240080    UP000002277    UP000189704   

PRIDE

Q8I739    H9J945    Q9BQI3    A0A024QZU1    B4DIP4   

Pfam

PF00069   Pkinase

Interpro

IPR000719   Prot_kinase_dom        + More
IPR008271   Ser/Thr_kinase_AS       
IPR011009   Kinase-like_dom_sf       
IPR017441   Protein_kinase_ATP_BS       

SUPFAM

SSF56112   SSF56112       

ProteinModelPortal

Q8I739   H9J945   A0A2H1VIE0   A0A2W1BNF1   A0A2A4KAZ2   A0A194R5Z6   + More
A0A212EJ31   A0A194PYU9   A0A0L7L9L3   A0A336K8N1   A0A182HCR7   A0A182LSK0   A0A1W4WZY9   Q17MW3   D6WJR1   A0A084WAM0   A0A1B0GM98   A0A0K8TMR2   A0A146LBU4   A0A0A9WWL4   A0A1Y1KBL7   A0A026WQ75   A0A3L8DNL7   A0A158NV55   A0A195DZQ1   A0A1B6EJ28   A0A1B6I9A0   A0A1B6LV80   A0A096N681   F7A5Z1   G7P286   F7F136   A0A2K5MH01   Q4R8E0   H9EYQ6   A0A2K5MGV9   A0A2K5YAW5   A0A2K5X5T1   A0A2K5MGW2   Q9BQI3-2   A0A024QZU1   Q9BQI3   A0A2K6NPN8   A0A2R7X2V0   S7NHA6   A0A340WPE5   A0A0D9RYR1   A0A2K5SJB8   A0A2K6TJ62   A0A2R9BQ21   B4DIP4   H2QU55   K7DI71   A0A1U7UYU5   A0A2I3SA78   A0A1U7ULN9   A0A3Q0DDA5  

PDB

4M7I     E-value=4.29382e-23,     Score=269

KEGG

693040    K16194 eukaryotic translation initiation factor 2-alpha kinase 1 [EC:2.7.11.1] | (RefSeq) eIF 2a kin

PATHWAY

04141    Protein processing in endoplasmic reticulum - Bombyx mori (domestic silkworm)

GO

GO:0004672   GO:0005524   GO:0003743   GO:0004694   GO:1990641   GO:0002526   GO:0006909   GO:0008285   GO:0046501   GO:0042803   GO:0005737   GO:0010999   GO:0030225   GO:0055072   GO:0020037   GO:0046986   GO:0046777   GO:0004674   GO:0017148   GO:0045993   GO:0016301   GO:0006468   GO:0006355   GO:0006508   GO:0006811   GO:0016020   GO:0005515   GO:0003779   GO:0016021  

Subcellular location

Cytoplasm  

Length:

579

Number of predicted TMHs:

0

Exp number of AAs in TMHs:

5.79285999999998

Exp number, first 60 AAs:

0.02606

Total prob of N-in:

0.26164

outside

1  -  579

 

 

Pi

156.127866

Theta

182.287761

Tajima's D

-0.709259

CLR

0.595834

CSRT

0.189890505474726

Interpretation

Uncertain