Skip Header

 
Contribute Send feedback

Reviewed, UniProtKB/Swiss-Prot Q5VT25 (MRCKA_HUMAN)

Last modified September 2, 2008. Version 43. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data | Customize display text xml rdf/xml gff fasta
Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Binary interactions · Alternative products · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents

Names and origin

Protein namesRecommended name:
    Serine/threonine-protein kinase MRCK alpha
    EC=2.7.11.1
Alternative name(s):
    Myotonic dystrophy kinase-related CDC42-binding kinase alpha
      Short name=Myotonic dystrophy protein kinase-like alpha
      Short name=MRCK alpha
      Short name=CDC42-binding protein kinase alpha
    DMPK-like alpha
Gene names
Name: CDC42BPA
Synonyms: KIAA0451
OrganismHomo sapiens (Human)
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length1732 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is not processed.
Protein existenceEvidence at protein level.

General annotation (Comments)

Function

May act as a downstream effector of CDC42 in cytoskeletal reorganization. Contributes to the actomyosin contractility required for cell invasion, through the regulation of MYPT1 and thus MLC2 phosphorylation.

Catalytic activity

ATP + a protein = ADP + a phosphoprotein.

Cofactor

Magnesium.

Enzyme regulation

Maintained in an inactive, closed conformation by an interaction between the kinase domain and the negative autoregulatory C-terminal coiled-coil region. Agonist binding to the phorbol ester binding site disrupts this, releasing the kinase domain to allow N-terminus-mediated dimerization and kinase activation by transautophosphorylation.

Subunit structure

Homodimer and homotetramer via the coiled coil regions. Interacts tightly with GTP-bound but not GDP-bound CDC42.

Subcellular location

CytoplasmBy similarity. Note= Displays a dispersed punctate distribution and concentrates along the cell periphery, especially at the leading edge and cell-cell junction. This concentration is PH-domain dependent By similarity.

Tissue specificity

Abundant in the heart, brain, skeletal muscle, kidney, and pancreas, with little or no expression in the lung and liver.

Sequence similarities

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

Contains 1 AGC-kinase C-terminal domain.

Contains 1 CNH domain.

Contains 1 CRIB domain.

Contains 1 PH domain.

Contains 1 phorbol-ester/DAG-type zinc finger.

Contains 1 protein kinase domain.

Binary interactions

Alternative products

This entry describes 6 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q5VT25-1)

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.
Notes: No experimental confirmation available.
Isoform 2 (identifier: Q5VT25-2)

The sequence of this isoform differs from the canonical sequence as follows:
     969-969: R → TDPVENTYVWNPSVKFHIQSRST
     973-981: CTPASKGRR → TSSEAEPVK
Notes: No experimental confirmation available.
Isoform 3 (identifier: Q5VT25-3)

The sequence of this isoform differs from the canonical sequence as follows:
     550-630: Missing.
     969-981: Missing.
Isoform 4 (identifier: Q5VT25-4)

The sequence of this isoform differs from the canonical sequence as follows:
     969-1009: Missing.
Notes: No experimental confirmation available.
Isoform 5 (identifier: Q5VT25-5)

The sequence of this isoform differs from the canonical sequence as follows:
     969-981: Missing.
Isoform 6 (identifier: Q5VT25-6)

The sequence of this isoform differs from the canonical sequence as follows:
     969-981: Missing.
     1597-1597: M → MPGFPYPSPHHHSGLISSPINFEHIYHMTVNSAEKFLSPDSINPEYSPSLRSVPGTPSFMTLR

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical view

Molecule processing

Chain1 – 17321732Serine/threonine-protein kinase MRCK alpha

Regions

Domain77 – 343267Protein kinase
Domain344 – 41471AGC-kinase C-terminal
Domain1082 – 1201120PH
Domain1228 – 1499272CNH
Domain1571 – 158414CRIB
Nucleotide binding83 – 919ATP By similarity
Zinc finger1012 – 106251Phorbol-ester/DAG-type
Coiled coil437 – 820384 Potential
Coiled coil880 – 94364 Potential

Sites

Active site2011Proton acceptor By similarity
Binding site1061ATP

Amino acid modifications

Modified residue2221Phosphoserine; by autocatalysis
Modified residue2341Phosphoserine; by autocatalysis
Modified residue2401Phosphothreonine; by autocatalysis

Natural variations

Alternative sequence550 – 63081Missing in isoform 3.
Alternative sequence969 – 100941Missing in isoform 4.
Alternative sequence969 – 98113Missing in isoform 3, isoform 5 and isoform 6.
Alternative sequence9691R → TDPVENTYVWNPSVKFHIQS RST in isoform 2.
Alternative sequence973 – 9819CTPASKGRR → TSSEAEPVK in isoform 2.
Alternative sequence15971M → MPGFPYPSPHHHSGLISSPI NFEHIYHMTVNSAEKFLSPD SINPEYSPSLRSVPGTPSFM TLR in isoform 6.
Natural variant501E → K in a lung neuroendocrine carcinoma sample; somatic mutation.
Natural variant2311T → M
Natural variant5371I → T
Natural variant7801T → M: dbSNP rs56119119.
Natural variant7901Y → C: dbSNP rs34943764.
Natural variant11481A → T
Natural variant12111R → H
Natural variant13171V → I
Natural variant14181I → K
Natural variant14691A → V: dbSNP rs55687355.
Natural variant16181T → A
Natural variant16991A → V: dbSNP rs2802269.

Experimental info

Mutagenesis1061K → A: Loss of kinase activity
Mutagenesis2221S → L: Increase in autophosphorylation but not kinase activity
Mutagenesis2341S → A: Loss of autophosphorylation and kinase activity
Mutagenesis2401T → A: Loss of autophosphorylation and kinase activity
Mutagenesis4031T → A: Loss of autophosphorylation and kinase activity
Mutagenesis15791H → A: Loss of CDC42 binding; when associated with A-1582
Mutagenesis15821H → A: Loss of CDC42 binding; when associated with A-1579
Sequence conflict251C → Y in AAB37126. Ref.5
Sequence conflict8091D → N in CAI46252. Ref.3
Sequence conflict15211L → V Ref.8
Sequence conflict16881G → K in BAA32296. Ref.6
Sequence conflict17121A → V in CAD57745 and CAD57746. Ref.1
Sequence conflict17121A → V in BAD92205. Ref.2
Sequence conflict17121A → V in CAI46252. Ref.3
Sequence conflict17121A → V in BAA32296. Ref.6

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified December 7, 2004. Version 1.
Checksum: 48B10F81B5405A0A

FASTA1,732197,307
        10         20         30         40         50         60 
MSGEVRLRQL EQFILDGPAQ TNGQCFSVET LLDILICLYD ECNNSPLRRE KNILEYLEWA 

        70         80         90        100        110        120 
KPFTSKVKQM RLHREDFEIL KVIGRGAFGE VAVVKLKNAD KVFAMKILNK WEMLKRAETA 

       130        140        150        160        170        180 
CFREERDVLV NGDNKWITTL HYAFQDDNNL YLVMDYYVGG DLLTLLSKFE DRLPEDMARF 

       190        200        210        220        230        240 
YLAEMVIAID SVHQLHYVHR DIKPDNILMD MNGHIRLADF GSCLKLMEDG TVQSSVAVGT 

       250        260        270        280        290        300 
PDYISPEILQ AMEDGKGRYG PECDWWSLGV CMYEMLYGET PFYAESLVET YGKIMNHKER 

       310        320        330        340        350        360 
FQFPAQVTDV SENAKDLIRR LICSREHRLG QNGIEDFKKH PFFSGIDWDN IRNCEAPYIP 

       370        380        390        400        410        420 
EVSSPTDTSN FDVDDDCLKN SETMPPPTHT AFSGHHLPFV GFTYTSSCVL SDRSCLRVTA 

       430        440        450        460        470        480 
GPTSLDLDVN VQRTLDNNLA TEAYERRIKR LEQEKLELSR KLQESTQTVQ ALQYSTVDGP 

       490        500        510        520        530        540 
LTASKDLEIK NLKEEIEKLR KQVTESSHLE QQLEEANAVR QELDDAFRQI KAYEKQIKTL 

       550        560        570        580        590        600 
QQEREDLNKE LVQASERLKN QSKELKDAHC QRKLAMQEFM EINERLTELH TQKQKLARHV 

       610        620        630        640        650        660 
RDKEEEVDLV MQKVESLRQE LRRTERAKKE LEVHTEALAA EASKDRKLRE QSEHYSKQLE 

       670        680        690        700        710        720 
NELEGLKQKQ ISYSPGVCSI EHQQEITKLK TDLEKKSIFY EEELSKREGI HANEIKNLKK 

       730        740        750        760        770        780 
ELHDSEGQQL ALNKEIMILK DKLEKTRRES QSEREEFESE FKQQYEREKV LLTEENKKLT 

       790        800        810        820        830        840 
SELDKLTTLY ENLSIHNQQL EEEVKDLADK KESVAHWEAQ ITEIIQWVSD EKDARGYLQA 

       850        860        870        880        890        900 
LASKMTEELE ALRNSSLGTR ATDMPWKMRR FAKLDMSARL ELQSALDAEI RAKQAIQEEL 

       910        920        930        940        950        960 
NKVKASNIIT ECKLKDSEKK NLELLSEIEQ LIKDTEELRS EKGIEHQDSQ HSFLAFLNTP 

       970        980        990       1000       1010       1020 
TDALDQFERS PSCTPASKGR RTVDSTPLSV HTPTLRKKGC PGSTGFPPKR KTHQFFVKSF 

      1030       1040       1050       1060       1070       1080 
TTPTKCHQCT SLMVGLIRQG CSCEVCGFSC HITCVNKAPT TCPVPPEQTK GPLGIDPQKG 

      1090       1100       1110       1120       1130       1140 
IGTAYEGHVR IPKPAGVKKG WQRALAIVCD FKLFLYDIAE GKASQPSVVI SQVIDMRDEE 

      1150       1160       1170       1180       1190       1200 
FSVSSVLASD VIHASRKDIP CIFRVTASQL SASNNKCSIL MLADTENEKN KWVGVLSELH 

      1210       1220       1230       1240       1250       1260 
KILKKNKFRD RSVYVPKEAY DSTLPLIKTT QAAAIIDHER IALGNEEGLF VVHVTKDEII 

      1270       1280       1290       1300       1310       1320 
RVGDNKKIHQ IELIPNDQLV AVISGRNRHV RLFPMSALDG RETDFYKLSE TKGCQTVTSG 

      1330       1340       1350       1360       1370       1380 
KVRHGALTCL CVAMKRQVLC YELFQSKTRH RKFKEIQVPY NVQWMAIFSE QLCVGFQSGF 

      1390       1400       1410       1420       1430       1440 
LRYPLNGEGN PYSMLHSNDH TLSFIAHQPM DAICAVEISS KEYLLCFNSI GIYTDCQGRR 

      1450       1460       1470       1480       1490       1500 
SRQQELMWPA NPSSCCYNAP YLSVYSENAV DIFDVNSMEW IQTLPLKKVR PLNNEGSLNL 

      1510       1520       1530       1540       1550       1560 
LGLETIRLIY FKNKMAEGDE LVVPETSDNS RKQMVRNINN KRRYSFRVPE EERMQQRREM 

      1570       1580       1590       1600       1610       1620 
LRDPEMRNKL ISNPTNFNHI AHMGPGDGIQ ILKDLPMNPR PQESRTVFSG SVSIPSITKS 

      1630       1640       1650       1660       1670       1680 
RPEPGRSMSA SSGLSARSSA QNGSALKREF SGGSYSAKRQ PMPSPSEGSL SSGGMDQGSD 

      1690       1700       1710       1720       1730 
APARDFDGED SDSPRHSTAS NSSNLSSPPS PASPRKTKSL SLESTDRGSW DP 

« Hide

Isoform 2 [UniParc].

Checksum: F1CC5CC1ED23B388
Show »

1,754199,811
Isoform 3 [UniParc].

Checksum: 7783E19090B345F7
Show »

1,638186,113
Isoform 4 [UniParc].

Checksum: 28E904E222CFFEC5
Show »

1,691193,031
Isoform 5 [UniParc].

Checksum: DBB15FA879AAC871
Show »

1,719195,922