Reviewed, UniProtKB/Swiss-Prot Q17R13 (ACK1_BOVIN)

Names and origin

Protein names

Recommended name:
    Activated CDC42 kinase 1
      Short name=ACK-1
    EC=2.7.10.2
Alternative name(s):
    Tyrosine kinase non-receptor protein 2
    Activated CDC42 kinase 2

Gene names

Name:	TNK2
Synonyms:	ACK1, ACK2

Organism

Bos taurus (Bovine)

Taxonomic identifier

9913 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Laurasiatheria › Cetartiodactyla › Ruminantia › Pecora › Bovidae › Bovinae › Bos

Protein attributes

Sequence length	1039 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Downstream effector of CDC42 which mediates CDC42-dependent cell migration via phosphorylation of BCAR1. Binds to both poly- and mono-ubiquitin and regulates ligand-induced degradation of EGFR. Participates in clathrin-mediated endocytosis. May be involved both in adult synaptic function and plasticity and in brain development By similarity. UniProtKB Q07912
Catalytic activity	ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate. UniProtKB Q07912
Cofactor	Magnesium By similarity. UniProtKB Q07912
Enzyme regulation	The SH3 domain appears to play an autoinhibitory role By similarity. UniProtKB O54967
Subunit structure	Interacts with CDC42. Interacts with activated CSPG4 By similarity. Interacts with AR By similarity. Ref.1 UniProtKB Q07912
Subcellular location	Cell membrane By similarity UniProtKB O54967.
Tissue specificity	Expressed in brain and skeletal muscle. Weakly expressed in pancreas, heart, placenta and lung.
Sequence similarities	Belongs to the protein kinase superfamily. Tyr protein kinase family. Contains 1 protein kinase domain. Contains 1 SH3 domain. Contains 1 UBA domain.
Sequence caution	The sequence AAC05310.1 differs from that shown. Reason: Frameshift at position 682.

Ontologies

Keywords
Cellular component	Cell membrane Membrane
Coding sequence diversity	Alternative splicing
Domain	SH3 domain
Ligand	ATP-binding Magnesium Metal-binding Nucleotide-binding
Molecular function	Kinase Transferase Tyrosine-protein kinase
PTM	Phosphoprotein
Gene Ontology (GO)
Biological process	protein amino acid phosphorylation Inferred from electronic annotation. Source: InterPro
Cellular component	plasma membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW magnesium ion binding Inferred from electronic annotation. Source: UniProtKB-KW non-membrane spanning protein tyrosine kinase activity Inferred from electronic annotation. Source: EC protein binding Inferred from physical interaction. Source: IntAct
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
CDC42	P60953	1	EBI-457220,EBI-81752	From a different organism.
CLTC	Q00610	1	EBI-457220,EBI-354967	From a different organism.
SNX9	Q9Y5X1	2	EBI-457220,EBI-77848	From a different organism.

Alternative products

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

Isoform 1 (identifier: Q17R13-1)

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: Q17R13-2)

The sequence of this isoform differs from the canonical sequence as follows:
     514-514: K → KREPPPRPPQPAIFTQ
     814-856: MPTTQSFASD...VRDGKKVSST → ENYVQNFKNL...SPECGRETPF
     857-1039: Missing.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 1039	1039	Activated CDC42 kinase 1		PRO_0000312829
Regions
	Domain	126 – 385	260	Protein kinase
	Domain	373 – 448	76	SH3
	Domain	957 – 997	41	UBA
	Nucleotide binding	132 – 140	9	ATP By similarity UniProtKB P00517
	Compositional bias	576 – 918	343	Pro-rich
Sites
	Active site	252	1	Proton acceptor By similarity UniProtKB P00517
	Binding site	158	1	ATP By similarity UniProtKB O54967
Amino acid modifications
	Modified residue	101	1	Phosphothreonine By similarity
	Modified residue	149	1	Phosphoserine By similarity UniProtKB Q07912
	Modified residue	284	1	Phosphotyrosine; by autocatalysis By similarity UniProtKB Q07912
	Modified residue	517	1	Phosphothreonine By similarity
	Modified residue	518	1	Phosphotyrosine By similarity UniProtKB Q07912
	Modified residue	723	1	Phosphoserine By similarity
	Modified residue	727	1	Phosphoserine By similarity
	Modified residue	784	1	Phosphoserine By similarity
	Modified residue	826	1	Phosphotyrosine By similarity UniProtKB Q07912
	Modified residue	858	1	Phosphotyrosine By similarity UniProtKB Q07912
	Modified residue	859	1	Phosphotyrosine By similarity UniProtKB Q07912
	Modified residue	880	1	Phosphoserine By similarity
Natural variations
	Alternative sequence	514	1	K → KREPPPRPPQPAIFTQ in isoform 2.		VSP_038165
	Alternative sequence	814 – 856	43	MPTTQ…KVSST → ENYVQNFKNLTAHHPPWRDQ DTGTGSSRGPTVLSPECGRE TPF in isoform 2.		VSP_038166
	Alternative sequence	857 – 1039	183	Missing in isoform 2.		VSP_038167
Experimental info
	Sequence conflict	203	1	T → M in AAC05310. Ref.1
	Sequence conflict	534	1	R → K in AAC05310. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified July 25, 2006. Version 1. Checksum: E7834771D76F8472	FASTA	1,039	114,868
	10 20 30 40 50 60 MQPEEGTGWL LELLSEVQLQ QYFLRLRDDL NVTRLSHFEY VKNEDLEKIG MGRPGQRRLW 70 80 90 100 110 120 EAVKRRKAMC KRKSWMSKVF SGKRLEAEFP PHHSQSTFRK TSPTPGGSAG EGSLQSLTCL 130 140 150 160 170 180 IGEKDLHLFE KLGDGSFGVV RRGEWDAPSG KTVSVAVKCL KPDVLSQPEA MDDFIREVNA 190 200 210 220 230 240 MHSLDHRNLI RLYGVVLTPP MKTVTELAPL GSLLDRLRKH QGHFLLGTLS RYAVQVAEGM 250 260 270 280 290 300 GYLEAKRFIH RDLAARNLLL ATRDLVKIGD FGLMRALPQN DDHYVMQEHR KVPFAWCAPE 310 320 330 340 350 360 SLKTRTFSHA SDTWMFGVTL WEMFTYGQEP WIGLNGSQIL HKIDKEGERL PRPEDCPQDI 370 380 390 400 410 420 YNVMVQCWAH KPEDRPTFVA LRDFLLEAQP TDMRALQDFE EPDKLHIQMN DVITVIEGRA 430 440 450 460 470 480 ENYWWRGQNT RTLCVGPFPR NVVTSVAGLS AQDISQPLQN SFIHTGHGDS DPRHCWGFPD 490 500 510 520 530 540 KIDELYLGNP MDPPDLLSVE LSTSRPTQHL GRVKKPTYDP VSEDQDPLSS DFKRLGLRKP 550 560 570 580 590 600 GLPRGLWLAK PSARVPGTKA GRGGGEVTLI DFGEEPVVPA PRPCAPSLAQ LAMDACSLLD 610 620 630 640 650 660 KTPPQSPTRA LPRPLHPTPV VDWDARPLPP PPAYDDVAQD EDDFEVCSIN STLVGAGVSA 670 680 690 700 710 720 EPSQGETNYA FVPEPARLLP PLEDNLFLPP QSGGKPPNSA QTAEIFQALQ QECMRQLQVP 730 740 750 760 770 780 PGSLVPSPSP GGDDKPQVPP RVPIPPRPTR SRGELSPVPP GEEEMGRWPG PASPPRVPPR 790 800 810 820 830 840 EPLSPQGSRT PSPLVPPGSS PLPPRLSSSP GKTMPTTQSF ASDPKYATPQ VIQAPGPRAG 850 860 870 880 890 900 PCILPIVRDG KKVSSTHYYL LPERPPYLER YQRFLHEAQS PRGPDPTPIP LLLPPPSTPA 910 920 930 940 950 960 PAAPTATVRP MPQAAPDPKA NFSSNNSNPG ARPSSLRATA RLPQRGYPGD GPEAGRPADK 970 980 990 1000 1010 1020 IQMLQAMVHG VTTEECQAAL QSHSWSVQRA AQYLKVEQLF GLGLRPRGEC HNVLEMFDWN 1030 LEQAGCHLLG SCGPAHHKR
	Isoform 2. Checksum: 3BE6448F4370A6E1	FASTA	871	96,809
	10 20 30 40 50 60 MQPEEGTGWL LELLSEVQLQ QYFLRLRDDL NVTRLSHFEY VKNEDLEKIG MGRPGQRRLW 70 80 90 100 110 120 EAVKRRKAMC KRKSWMSKVF SGKRLEAEFP PHHSQSTFRK TSPTPGGSAG EGSLQSLTCL 130 140 150 160 170 180 IGEKDLHLFE KLGDGSFGVV RRGEWDAPSG KTVSVAVKCL KPDVLSQPEA MDDFIREVNA 190 200 210 220 230 240 MHSLDHRNLI RLYGVVLTPP MKTVTELAPL GSLLDRLRKH QGHFLLGTLS RYAVQVAEGM 250 260 270 280 290 300 GYLEAKRFIH RDLAARNLLL ATRDLVKIGD FGLMRALPQN DDHYVMQEHR KVPFAWCAPE 310 320 330 340 350 360 SLKTRTFSHA SDTWMFGVTL WEMFTYGQEP WIGLNGSQIL HKIDKEGERL PRPEDCPQDI 370 380 390 400 410 420 YNVMVQCWAH KPEDRPTFVA LRDFLLEAQP TDMRALQDFE EPDKLHIQMN DVITVIEGRA 430 440 450 460 470 480 ENYWWRGQNT RTLCVGPFPR NVVTSVAGLS AQDISQPLQN SFIHTGHGDS DPRHCWGFPD 490 500 510 520 530 540 KIDELYLGNP MDPPDLLSVE LSTSRPTQHL GRVKREPPPR PPQPAIFTQK PTYDPVSEDQ 550 560 570 580 590 600 DPLSSDFKRL GLRKPGLPRG LWLAKPSARV PGTKAGRGGG EVTLIDFGEE PVVPAPRPCA 610 620 630 640 650 660 PSLAQLAMDA CSLLDKTPPQ SPTRALPRPL HPTPVVDWDA RPLPPPPAYD DVAQDEDDFE 670 680 690 700 710 720 VCSINSTLVG AGVSAEPSQG ETNYAFVPEP ARLLPPLEDN LFLPPQSGGK PPNSAQTAEI 730 740 750 760 770 780 FQALQQECMR QLQVPPGSLV PSPSPGGDDK PQVPPRVPIP PRPTRSRGEL SPVPPGEEEM 790 800 810 820 830 840 GRWPGPASPP RVPPREPLSP QGSRTPSPLV PPGSSPLPPR LSSSPGKTEN YVQNFKNLTA 850 860 870 HHPPWRDQDT GTGSSRGPTV LSPECGRETP F

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning and characterization of a novel Cdc42-associated tyrosine kinase, ACK-2, from bovine brain." Yang W., Cerione R.A. J. Biol. Chem. 272:24819-24824(1997) [PubMed: 9312079] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), INTERACTION WITH CDC42. Tissue: Brain.
[2]	NIH - Mammalian Gene Collection (MGC) project Submitted (JUN-2006) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Strain: Hereford. Tissue: Hypothalamus.

Cross-references

Sequence databases
EMBL GenBank DDBJ	U96722 mRNA. Translation: AAC05310.1. Frameshift. BC118081 mRNA. Translation: AAI18082.1.
IPI	IPI00700705. IPI00944890.
RefSeq	NP_776310.2.
UniGene	Bt.64988
3D structure databases
SMR	Q17R13. Positions 117-388, 392-444, 447-489.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q17R13. 4 interactions.
STRING	Q17R13.
Genome annotation databases
Ensembl	ENSBTAT00000028482; ENSBTAP00000028482; ENSBTAG00000021364; Bos taurus. [Genome view] ENSBTAT00000046471; ENSBTAP00000043771; ENSBTAG00000021364; Bos taurus. [Genome view]
GeneID	280710.
KEGG	bta:280710.
Organism-specific databases
CTD	280710.
Phylogenomic databases
HOVERGEN	Q17R13.
InParanoid	Q17R13.
Enzyme and pathway databases
BRENDA	2.7.10.2. 251.
Family and domain databases
InterPro	IPR015116. GTPase_binding. IPR011009. Kinase-like_dom. IPR000719. Prot_kinase_cat_dom. IPR017441. Protein_kinase_ATP_BS. IPR001452. SH3_domain. IPR015779. Tyr_kinase_non-rcpt_Ack_N. IPR020635. Tyr_Pkinase_cat_dom. IPR020685. Tyr_prot_kinase. IPR008266. Tyr_prot_kinase_AS. IPR000449. UBA/transl_elong_EF1B_N. IPR015940. UBA/transl_elong_EF1B_N_euk. [Graphical view]
PANTHER	PTHR23256:SF265. ACK_tyr_kin_N. 1 hit. PTHR23256. Tyr_prot_kinase. 1 hit.
Pfam	PF09027. GTPase_binding. 1 hit. PF00627. UBA. 1 hit. [Graphical view]
SMART	SM00326. SH3. 1 hit. SM00219. TyrKc. 1 hit. SM00165. UBA. 1 hit. [Graphical view]
PROSITE	PS00107. PROTEIN_KINASE_ATP. 1 hit. PS50011. PROTEIN_KINASE_DOM. 1 hit. PS00109. PROTEIN_KINASE_TYR. 1 hit. PS50002. SH3. 1 hit. PS50030. UBA. False negative. [Graphical view]
ProtoNet	Search...

Entry information

Entry name

ACK1_BOVIN

Accession

Primary (citable) accession number: Q17R13
Secondary accession number(s): O02742

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 4, 2007
Last sequence update:	July 25, 2006
Last modified:	February 9, 2010
This is version 40 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)