Reviewed, UniProtKB/Swiss-Prot Q3UU96 (MRCKA_MOUSE)

Names and origin

Protein names

Recommended name:
    Serine/threonine-protein kinase MRCK alpha
      Short name=MRCK alpha
    EC=2.7.11.1
Alternative name(s):
    CDC42-binding protein kinase alpha

Gene names

Name:	Cdc42bpa
Synonyms:	Kiaa0451

Organism

Mus musculus (Mouse)

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus

Protein attributes

Sequence length	1719 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at transcript 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 By similarity.
Catalytic activity	ATP + a protein = ADP + a phosphoprotein.
Cofactor	Magnesium By similarity.
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 By similarity.
Subunit structure	Homodimer and homotetramer via the coiled coil regions. Interacts tightly with GTP-bound but not GDP-bound CDC42 By similarity.
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.
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.

Ontologies

Keywords
Cellular component	Cytoplasm
Coding sequence diversity	Alternative splicing
Domain	Coiled coil Phorbol-ester binding Zinc-finger
Ligand	ATP-binding Metal-binding Nucleotide-binding Zinc
Molecular function	Kinase Serine/threonine-protein kinase Transferase
PTM	Phosphoprotein
Gene Ontology (GO)
Biological process	microtubule cytoskeleton organization and biogenesis Inferred from mutant phenotype. Source: MGI nuclear migration Inferred from mutant phenotype. Source: MGI
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q3UU96-1)

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.

Isoform 2 (identifier: Q3UU96-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-104: Missing.
     550-630: Missing.

Notes: No experimental confirmation available.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view
Molecule processing
	Chain	1 – 1719	1719	Serine/threonine-protein kinase MRCK alpha
Regions
	Domain	77 – 343	267	Protein kinase
	Domain	344 – 414	71	AGC-kinase C-terminal
	Domain	1069 – 1188	120	PH
	Domain	1215 – 1486	272	CNH
	Domain	1558 – 1571	14	CRIB
	Nucleotide binding	83 – 91	9	ATP By similarity
	Zinc finger	999 – 1049	51	Phorbol-ester/DAG-type
	Coiled coil	437 – 670	234	Potential
	Coiled coil	713 – 820	108	Potential
	Coiled coil	880 – 943	64	Potential
	Compositional bias	1596 – 1711	116	Ser-rich
Sites
	Active site	201	1	Proton acceptor By similarity
	Binding site	106	1	ATP By similarity
Amino acid modifications
	Modified residue	222	1	Phosphoserine; by autocatalysis By similarity
	Modified residue	234	1	Phosphoserine; by autocatalysis By similarity
	Modified residue	240	1	Phosphothreonine; by autocatalysis By similarity
Natural variations
	Alternative sequence	1 – 104	104	Missing in isoform 2.
	Alternative sequence	550 – 630	81	Missing in isoform 2.
Experimental info
	Sequence conflict	1451 – 1453	3	VYS → HEG in AAH96679. Ref.5
	Sequence conflict	1535	1	V → F in AAH96679. Ref.5
	Sequence conflict	1612	1	G → V in BAC97958. Ref.4

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified March 20, 2007. Version 2. Checksum: 362101C884240865	FASTA	1,719	195,536
	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 NGDSKWITTL HYAFQDDNNL YLVMDYYVGG DLLTLLSKFE DRLPEEMARF 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 GPTSLDLDVS VQRTLDNNLA TEAYERRIKR LEQEKLELTR KLQESTQTVQ ALQYSTVDGP 490 500 510 520 530 540 LTASKDLEIK SLKEEIEKLR KQVAEVNHLE QQLEEANSVR RELDDAFRQI KASEKQIKTL 550 560 570 580 590 600 QQEREELNKE LVQASERLKN QSKELKDAHC QRKLAMQEFM EINERLTELH TQKQKLARHV 610 620 630 640 650 660 RDKEEEVDLV MQKAESLRQE LRRAERAKKE LEVHTEALIA EASKDKKLRE QSEHYSKQLE 670 680 690 700 710 720 NELEGLKQKQ ISYSPGICSI EHQQEITKLK TDLEKKSIFY EEEISKREGI HASEIKNLKK 730 740 750 760 770 780 ELHDSEGQQL ALNKEILVLK DKLEKTRRES QSEREEFENE FKQQYEREKV LLTEENKKLT 790 800 810 820 830 840 SELDKLTSLY ESLSLRNQHL EEEVKDLADK KESVAHWEAQ ITEIIQWVSD EKDARGYLQA 850 860 870 880 890 900 LASKMTEELE ALRNSSLGTR ATDMPWKMRR FAKLDMSARL ELQSALDAEI RAKQAIQEEL 910 920 930 940 950 960 NKVKASNILT ECKLKDSEKK NLELLSEIEQ LIKDTEELRS EKGIEHQDSQ HSFLAFLNTP 970 980 990 1000 1010 1020 TDALDQFEIA DCAPLPAHTP TLRKKGCPAS TGFPPKRKTH QFFVKSFTAP TKCHQCTSLM 1030 1040 1050 1060 1070 1080 VGLIRQGCSC EVCGFSCHIT CVNKAPTVCP VPPEQTKGPL GIDPQKGVGT AYEGHVRIPK 1090 1100 1110 1120 1130 1140 PAGVKKGWQR ALAVVCDFKL FLYDIAEGKA SQPTSVISQV IDMRDEEFSV SSVLASDVIH 1150 1160 1170 1180 1190 1200 ASRKDIPCIF RVTASQLSAP SNKCSILMLA DSENERSKWV GVLSELHKIL KKNKFRDRSV 1210 1220 1230 1240 1250 1260 YVPKEAYDST LPLIKTTQAA AIIDHERIAL GNEEGLFVVH VTKDEIVRVG DNKKIHQIEL 1270 1280 1290 1300 1310 1320 IPSDQLVAVI SGRNRHVRLF PMSALDGRET DFYKLAETKG CQTIAAGKVR HGALSCLCVA 1330 1340 1350 1360 1370 1380 MKRQVLCYEL FQSKTRHRKF KEIQVPCNVQ WMAIFSEHLC VGFQSGFLRY PLNGEGGPCN 1390 1400 1410 1420 1430 1440 MLHSNDHTLS FISHQPMDAL CAVEISNKEY LLCFNSIGIY TDCQGRRSRQ QELMWPANPS 1450 1460 1470 1480 1490 1500 SCCYNAPYLS VYSENAVDIF DVNSMEWIQT LPLKKVRPLN TEGSLNLLGL ETIRLIYFKN 1510 1520 1530 1540 1550 1560 KMAEGDELVV PETSDNSRKQ MVRNINNKRR YSFRVPEEER MQQRREMLRD PEMRNKLISN 1570 1580 1590 1600 1610 1620 PTNFNHIAHM GPGDGIQILK DLPMNPRPQE SRTVFSGSVS IPSITKSRPE PGRSMSASSG 1630 1640 1650 1660 1670 1680 LSARSSAQNG SALKREFSGG SYNTKRQPMP SPSEGSLSSG GMDQGSDAPA RDYDGEDSDS 1690 1700 1710 PRHSTASNSS NLSSPPSPIS PQKTKSLSLE STDRGSWDP
	Isoform 2 [UniParc]. Checksum: 9FDF1221D32175E8		1,534	173,829
	10 20 30 40 50 60 MKILNKWEML KRAETACFRE ERDVLVNGDS KWITTLHYAF QDDNNLYLVM DYYVGGDLLT 70 80 90 100 110 120 LLSKFEDRLP EEMARFYLAE MVIAIDSVHQ LHYVHRDIKP DNILMDMNGH IRLADFGSCL 130 140 150 160 170 180 KLMEDGTVQS SVAVGTPDYI SPEILQAMED GKGRYGPECD WWSLGVCMYE MLYGETPFYA 190 200 210 220 230 240 ESLVETYGKI MNHKERFQFP AQVTDVSENA KDLIRRLICS REHRLGQNGI EDFKKHPFFS 250 260 270 280 290 300 GIDWDNIRNC EAPYIPEVSS PTDTSNFDVD DDCLKNSETM PPPTHTAFSG HHLPFVGFTY 310 320 330 340 350 360 TSSCVLSDRS CLRVTAGPTS LDLDVSVQRT LDNNLATEAY ERRIKRLEQE KLELTRKLQE 370 380 390 400 410 420 STQTVQALQY STVDGPLTAS KDLEIKSLKE EIEKLRKQVA EVNHLEQQLE EANSVRRELD 430 440 450 460 470 480 DAFRQIKASE KQIKTLQQER EELNKLEVHT EALIAEASKD KKLREQSEHY SKQLENELEG 490 500 510 520 530 540 LKQKQISYSP GICSIEHQQE ITKLKTDLEK KSIFYEEEIS KREGIHASEI KNLKKELHDS 550 560 570 580 590 600 EGQQLALNKE ILVLKDKLEK TRRESQSERE EFENEFKQQY EREKVLLTEE NKKLTSELDK 610 620 630 640 650 660 LTSLYESLSL RNQHLEEEVK DLADKKESVA HWEAQITEII QWVSDEKDAR GYLQALASKM 670 680 690 700 710 720 TEELEALRNS SLGTRATDMP WKMRRFAKLD MSARLELQSA LDAEIRAKQA IQEELNKVKA 730 740 750 760 770 780 SNILTECKLK DSEKKNLELL SEIEQLIKDT EELRSEKGIE HQDSQHSFLA FLNTPTDALD 790 800 810 820 830 840 QFEIADCAPL PAHTPTLRKK GCPASTGFPP KRKTHQFFVK SFTAPTKCHQ CTSLMVGLIR 850 860 870 880 890 900 QGCSCEVCGF SCHITCVNKA PTVCPVPPEQ TKGPLGIDPQ KGVGTAYEGH VRIPKPAGVK 910 920 930 940 950 960 KGWQRALAVV CDFKLFLYDI AEGKASQPTS VISQVIDMRD EEFSVSSVLA SDVIHASRKD 970 980 990 1000 1010 1020 IPCIFRVTAS QLSAPSNKCS ILMLADSENE RSKWVGVLSE LHKILKKNKF RDRSVYVPKE 1030 1040 1050 1060 1070 1080 AYDSTLPLIK TTQAAAIIDH ERIALGNEEG LFVVHVTKDE IVRVGDNKKI HQIELIPSDQ 1090 1100 1110 1120 1130 1140 LVAVISGRNR HVRLFPMSAL DGRETDFYKL AETKGCQTIA AGKVRHGALS CLCVAMKRQV 1150 1160 1170 1180 1190 1200 LCYELFQSKT RHRKFKEIQV PCNVQWMAIF SEHLCVGFQS GFLRYPLNGE GGPCNMLHSN 1210 1220 1230 1240 1250 1260 DHTLSFISHQ PMDALCAVEI SNKEYLLCFN SIGIYTDCQG RRSRQQELMW PANPSSCCYN 1270 1280 1290 1300 1310 1320 APYLSVYSEN AVDIFDVNSM EWIQTLPLKK VRPLNTEGSL NLLGLETIRL IYFKNKMAEG 1330 1340 1350 1360 1370 1380 DELVVPETSD NSRKQMVRNI NNKRRYSFRV PEEERMQQRR EMLRDPEMRN KLISNPTNFN 1390 1400 1410 1420 1430 1440 HIAHMGPGDG IQILKDLPMN PRPQESRTVF SGSVSIPSIT KSRPEPGRSM SASSGLSARS 1450 1460 1470 1480 1490 1500 SAQNGSALKR EFSGGSYNTK RQPMPSPSEG SLSSGGMDQG SDAPARDYDG EDSDSPRHST 1510 1520 1530 ASNSSNLSSP PSPISPQKTK SLSLESTDRG SWDP

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	The mouse genome sequencing consortium Submitted (JAN-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: C57BL/6J.
[2]	"The transcriptional landscape of the mammalian genome." Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y. Science 309:1559-1563(2005) [PubMed: 16141072] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-752 (ISOFORM 2). Strain: C57BL/6J. Tissue: Spinal cord.
[3]	"MRCK-alpha interacts with Dexras1." Behrend E.N., Kemppainen R.J. Submitted (MAR-2002) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 736-1006.
[4]	"Prediction of the coding sequences of mouse homologues of KIAA gene: III. The complete nucleotide sequences of 500 mouse KIAA-homologous cDNAs identified by screening of terminal sequences of cDNA clones randomly sampled from size-fractionated libraries." Okazaki N., Kikuno R., Ohara R., Inamoto S., Koseki H., Hiraoka S., Saga Y., Nagase T., Ohara O., Koga H. DNA Res. 10:167-180(2003) [PubMed: 14621295] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1376-1719. Tissue: Brain.
[5]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1451-1719. Strain: C57BL/6J. Tissue: Mammary gland.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBLGenBankDDBJ	AC125380 Genomic DNA. No translation available. AC132436 Genomic DNA. No translation available. AK138649 mRNA. Translation: BAE23731.1. AF492452 mRNA. Translation: AAM10976.1. AK129148 mRNA. Translation: BAC97958.1. BC096679 mRNA. Translation: AAH96679.1.
RefSeq	XP_981195.1. XP_996320.1.
UniGene	Mm.259655
3D structure databases
ModBase	Search...
Genome annotation databases
Ensembl	ENSMUSG00000026490. Mus musculus. [Contig view]
GeneID	226751.
Organism-specific databases
MGI	MGI:2441841. Cdc42bpa.
Rouge	Search...
Phylogenomic databases
HOVERGEN	Q3UU96.
Gene expression databases
ArrayExpress	Q3UU96.
CleanEx	MM_CDC42BPA.
Family and domain databases
InterPro	IPR001180. Citron. IPR002219. DAG_PE_bd. IPR014930. DMPK_coil. IPR000095. PAK_box_Rho_bd. IPR001849. PH. IPR000961. Pkinase_C. IPR000719. Prot_kinase_core. IPR017441. Protein_kinase_ATP_bd_CS. IPR017442. Se/Thr_pkinase-rel. IPR008271. Ser_thr_pkin_AS. IPR002290. Ser_thr_pkinase. [Graphical view]
Pfam	PF00130. C1_1. 1 hit. PF00780. CNH. 1 hit. PF08826. DMPK_coil. 1 hit. PF00169. PH. 1 hit. PF00069. Pkinase. 1 hit. PF00433. Pkinase_C. 1 hit. [Graphical view]
PRINTS	PR00008. DAGPEDOMAIN.
ProDom	PD000001. Prot_kinase. 1 hit. [Graphical view] [Entries sharing at least one domain]
SMART	SM00109. C1. 1 hit. SM00036. CNH. 1 hit. SM00285. PBD. 1 hit. SM00233. PH. 1 hit. SM00133. S_TK_X. 1 hit. SM00220. S_TKc. 1 hit. [Graphical view]
PROSITE	PS51285. AGC_KINASE_CTER. 1 hit. PS50108. CRIB. 1 hit. PS50003. PH_DOMAIN. 1 hit. PS00107. PROTEIN_KINASE_ATP. 1 hit. PS50011. PROTEIN_KINASE_DOM. 1 hit. PS00108. PROTEIN_KINASE_ST. 1 hit. PS00479. ZF_DAG_PE_1. 1 hit. PS50081. ZF_DAG_PE_2. 1 hit. [Graphical view]
BLOCKS	Search...
Other Resources
SOURCE	Search...
ProtoNet	Search...

Entry information

Entry name

MRCKA_MOUSE

Accession

Primary (citable) accession number: Q3UU96
Secondary accession number(s): Q4V9U7, Q6ZQA9, Q8R495

Entry history

Integrated into UniProtKB/Swiss-Prot:	March 20, 2007
Last sequence update:	March 20, 2007
Last modified:	September 23, 2008
This is version 27 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)