Reviewed, UniProtKB/Swiss-Prot Q6VAB6 (KSR2_HUMAN)

Names and origin

Protein names

Recommended name:
    Kinase suppressor of Ras 2
      Short name=hKSR2

Gene names

Name:

KSR2

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	950 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Location-regulated scaffold connecting MEK to RAF. Blocks MAP3K8 kinase activity and MAP3K8-mediated signaling. Acts as a negative regulator of MAP3K3-mediated activation of ERK, JNK and NF-kappa-B pathways, inhibiting MAP3K3-mediated interleukin-8 production. Ref.3 Ref.5
Subunit structure	Interacts with MAP2K1, MAP3K8, MAPK, RAS and RAF. Ref.3
Subcellular location	Cytoplasm By similarity. Membrane; Peripheral membrane protein By similarity.
Tissue specificity	Mainly expressed in brain and kidney. Ref.3
Domain	The protein kinase domain is predicted to be catalytically inactive.
Post-translational modification	Phosphorylated on Ser-474 by MARK3 By similarity.
Sequence similarities	Belongs to the protein kinase superfamily. TKL Ser/Thr protein kinase family. Contains 1 phorbol-ester/DAG-type zinc finger. Contains 1 protein kinase domain.

Ontologies

Keywords
Cellular component	Cytoplasm Membrane
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Phorbol-ester binding Zinc-finger
Ligand	Metal-binding Zinc
PTM	Phosphoprotein
Gene Ontology (GO)
Biological process	intracellular signaling cascade Inferred from electronic annotation. Source: InterPro protein amino acid phosphorylation Inferred from electronic annotation. Source: InterPro
Cellular component	cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	ATP binding Inferred from electronic annotation. Source: InterPro diacylglycerol binding Inferred from electronic annotation. Source: UniProtKB-KW protein serine/threonine kinase activity Inferred from electronic annotation. Source: InterPro zinc ion binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Alternative products

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

Isoform 1 (identifier: Q6VAB6-1)

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: Q6VAB6-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-303: Missing.
     304-329: GFTALHRSKSHEFQLGHRVDEAHTPK → MYNKKAKMEPNASESAIPARRQRQPR
     740-742: SLC → RPV
     743-950: Missing.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 950	950	Kinase suppressor of Ras 2		PRO_0000086231
Regions
	Domain	666 – 931	266	Protein kinase
	Zinc finger	412 – 456	45	Phorbol-ester/DAG-type
	Compositional bias	181 – 293	113	Pro-rich
	Compositional bias	510 – 550	41	Pro-rich
Sites
	Metal binding	413	1	Zinc 1 By similarity
	Metal binding	425	1	Zinc 2 By similarity
	Metal binding	428	1	Zinc 2 By similarity
	Metal binding	438	1	Zinc 1 By similarity
	Metal binding	441	1	Zinc 1 By similarity
	Metal binding	446	1	Zinc 2 By similarity
	Metal binding	449	1	Zinc 2 By similarity
	Metal binding	456	1	Zinc 1 By similarity
Amino acid modifications
	Modified residue	474	1	Phosphoserine; by MARK3 By similarity
Natural variations
	Alternative sequence	1 – 303	303	Missing in isoform 2.		VSP_012234
	Alternative sequence	304 – 329	26	GFTAL…AHTPK → MYNKKAKMEPNASESAIPAR RQRQPR in isoform 2.		VSP_012235
	Alternative sequence	740 – 742	3	SLC → RPV in isoform 2.		VSP_012236
	Alternative sequence	743 – 950	208	Missing in isoform 2.		VSP_012237
	Natural variant	676	1	R → S in a lung adenocarcinoma sample; somatic mutation. Ref.6		VAR_040659

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified May 29, 2007. Version 2. Checksum: DFBC20F4E71077AD	FASTA	950	107,632
	10 20 30 40 50 60 MDEENMTKSE EQQPLSLQKA LQQCELVQNM IDLSISNLEG LRTKCATSND LTQKEIRTLE 70 80 90 100 110 120 SKLVKYFSRQ LSCKKKVALQ ERNAELDGFP QLRHWFRIVD VRKEVLEEIS PGQLSLEDLL 130 140 150 160 170 180 EMTDEQVCET VEKYGANREE CARLNASLSC LRNVHMSGGN LSKQDWTIQW PTTETGKENN 190 200 210 220 230 240 PVCPPEPTPW IRTHLSQSPR VPSKCVQHYC HTSPTPGAPV YTHVDRLTVD AYPGLCPPPP 250 260 270 280 290 300 LESGHRSLPP SPRQRHAVRT PPRTPNIVTT VTPPGTPPMR KKNKLKPPGT PPPSSRKLIH 310 320 330 340 350 360 LIPGFTALHR SKSHEFQLGH RVDEAHTPKA KKKSKPLNLK IHSSVGSCEN IPSQQRSPLL 370 380 390 400 410 420 SERSLRSFFV GHAPFLPSTP PVHTEANFSA NTLSVPRWSP QIPRRDLGNS IKHRFSTKYW 430 440 450 460 470 480 MSQTCTVCGK GMLFGLKCKN CKLKCHNKCT KEAPPCHLLI IHRGDPARLV RTESVPCDIN 490 500 510 520 530 540 NPLRKPPRYS DLHISQTLPK TNKINKDHIP VPYQPDSSSN PSSTTSSTPS SPAPPLPPSA 550 560 570 580 590 600 TPPSPLHPSP QCTRQQKNFN LPASHYYKYK QQFIFPDVVP VPETPTRAPQ VILHPVTSNP 610 620 630 640 650 660 ILEGNPLLQI EVEPTSENEE VHDEAEESED DFEEMNLSLL SARSFPRKAS QTSIFLQEWD 670 680 690 700 710 720 IPFEQLEIGE LIGKGRFGQV YHGRWHGEVA IRLIDIERDN EDQLKAFKRE VMAYRQTRHE 730 740 750 760 770 780 NVVLFMGACM SPPHLAIITS LCKGRTLYSV VRDAKIVLDV NKTRQIAQEI VKGMGYLHAK 790 800 810 820 830 840 GILHKDLKSK NVFYDNGKVV ITDFGLFSIS GVLQAGRRED KLRIQNGWLC HLAPEIIRQL 850 860 870 880 890 900 SPDTEEDKLP FSKHSDVFAL GTIWYELHAR EWPFKTQPAE AIIWQMGTGM KPNLSQIGMG 910 920 930 940 950 KEISDILLFC WAFEQEERPT FTKLMDMLEK LPKRNRRLSH PGHFWKSAEL
	Isoform 2. Checksum: A5D6F1DEAFDA51FC	FASTA	439	49,607
	10 20 30 40 50 60 MYNKKAKMEP NASESAIPAR RQRQPRAKKK SKPLNLKIHS SVGSCENIPS QQRSPLLSER 70 80 90 100 110 120 SLRSFFVGHA PFLPSTPPVH TEANFSANTL SVPRWSPQIP RRDLGNSIKH RFSTKYWMSQ 130 140 150 160 170 180 TCTVCGKGML FGLKCKNCKL KCHNKCTKEA PPCHLLIIHR GDPARLVRTE SVPCDINNPL 190 200 210 220 230 240 RKPPRYSDLH ISQTLPKTNK INKDHIPVPY QPDSSSNPSS TTSSTPSSPA PPLPPSATPP 250 260 270 280 290 300 SPLHPSPQCT RQQKNFNLPA SHYYKYKQQF IFPDVVPVPE TPTRAPQVIL HPVTSNPILE 310 320 330 340 350 360 GNPLLQIEVE PTSENEEVHD EAEESEDDFE EMNLSLLSAR SFPRKASQTS IFLQEWDIPF 370 380 390 400 410 420 EQLEIGELIG KGRFGQVYHG RWHGEVAIRL IDIERDNEDQ LKAFKREVMA YRQTRHENVV 430 LFMGACMSPP HLAIITRPV

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). Tissue: Testis.
[2]	"The finished DNA sequence of human chromosome 12." Scherer S.E., Muzny D.M., Buhay C.J., Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J., Jackson A., Khan Z.M., Kovar-Smith C., Lewis L.R. , Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., Montgomery K.T., Morgan M.B., Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D., Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z., Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H., Draper H., Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S., Kelly S.H., Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H., Santibanez J., Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q., Williams G.A., Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V., Bailey M., Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E., Burkett C.E., Burrell K.L., Calderon E., Cardenas V., Carter K., Casias K., Cavazos I., Cavazos S.R., Ceasar H., Chacko J., Chan S.N., Chavez D., Christopoulos C., Chu J., Cockrell R., Cox C.D., Dang M., Dathorne S.R., David R., Davis C.M., Davy-Carroll L., Deshazo D.R., Donlin J.E., D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J., Escotto M., Flagg N., Forbes L.D., Gabisi A.M., Garza M., Hamilton C., Henderson N., Hernandez O., Hines S., Hogues M.E., Huang M., Idlebird D.G., Johnson R., Jolivet A., Jones S., Kagan R., King L.M., Leal B., Lebow H., Lee S., LeVan J.M., Lewis L.C., London P., Lorensuhewa L.M., Loulseged H., Lovett D.A., Lucier A., Lucier R.L., Ma J., Madu R.C., Mapua P., Martindale A.D., Martinez E., Massey E., Mawhiney S., Meador M.G., Mendez S., Mercado C., Mercado I.C., Merritt C.E., Miner Z.L., Minja E., Mitchell T., Mohabbat F., Mohabbat K., Montgomery B., Moore N., Morris S., Munidasa M., Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O., Nwokenkwo S., Obregon M., Oguh M., Oragunye N., Oviedo R.J., Parish B.J., Parker D.N., Parrish J., Parks K.L., Paul H.A., Payton B.A., Perez A., Perrin W., Pickens A., Primus E.L., Pu L.-L., Puazo M., Quiles M.M., Quiroz J.B., Rabata D., Reeves K., Ruiz S.J., Shao H., Sisson I., Sonaike T., Sorelle R.P., Sutton A.E., Svatek A.F., Svetz L.A., Tamerisa K.S., Taylor T.R., Teague B., Thomas N., Thorn R.D., Trejos Z.Y., Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I., Vera V.A., Villasana D.M., Wang L., Ward-Moore S., Warren J.T., Wei X., White F., Williamson A.L., Wleczyk R., Wooden H.S., Wooden S.H., Yen J., Yoon L., Yoon V., Zorrilla S.E., Nelson D., Kucherlapati R., Weinstock G., Gibbs R.A. Nature 440:346-351(2006) [PubMed: 16541075] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]	"Identification of a novel human kinase supporter of Ras (hKSR-2) that functions as a negative regulator of Cot (Tpl2) signaling." Channavajhala P.L., Wu L., Cuozzo J.W., Hall J.P., Liu W., Lin L.-L., Zhang Y. J. Biol. Chem. 278:47089-47097(2003) [PubMed: 12975377] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 122-950 (ISOFORM 1), FUNCTION, INTERACTION WITH MAP2K; RAS; RAF; MAPK AND MAP3K8, TISSUE SPECIFICITY. Tissue: Testis.
[4]	"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 122-950 (ISOFORM 1).
[5]	"hKSR-2 inhibits MEKK3-activated MAP kinase and NF-kappaB pathways in inflammation." Channavajhala P.L., Rao V.R., Spaulding V., Lin L.-L., Zhang Y.G. Biochem. Biophys. Res. Commun. 334:1214-1218(2005) [PubMed: 16039990] [Abstract] Cited for: FUNCTION.
[6]	"Patterns of somatic mutation in human cancer genomes." Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G. , Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R. Nature 446:153-158(2007) [PubMed: 17344846] [Abstract] Cited for: VARIANT [LARGE SCALE ANALYSIS] SER-676.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBLGenBankDDBJ	AK098831 mRNA. Translation: BAC05426.1. AC073864 Genomic DNA. No translation available. AC079127 Genomic DNA. No translation available. AC084291 Genomic DNA. No translation available. AC092936 Genomic DNA. No translation available. AY345972 mRNA. Translation: AAQ24226.1. BC107106 mRNA. Translation: AAI07107.1. BC107107 mRNA. Translation: AAI07108.1. BC127603 mRNA. Translation: AAI27604.1.
IPI	IPI00167121. IPI00414043.
RefSeq	NP_775869.3.
UniGene	Hs.375836
3D structure databases
HSSP	HSSP built from PDB template 1KBE based on UniProtKB Q61097.
ModBase	Search...
PTM databases
PhosphoSite	Q6VAB6.
Genome annotation databases
Ensembl	ENSG00000171435. Homo sapiens. [Contig view]
GeneID	283455.
KEGG	hsa:283455.
Organism-specific databases
GeneCards	GC12M116370.
H-InvDB	HIX0018992.
HGNC	HGNC:18610. KSR2.
MIM	610737. gene.
PharmGKB	PA134867759.
GenAtlas	Search...
Phylogenomic databases
HOGENOM	Q6VAB6.
HOVERGEN	Q6VAB6.
Gene expression databases
ArrayExpress	Q6VAB6.
Bgee	Q6VAB6.
CleanEx	HS_KSR2.
GermOnline	ENSG00000171435. Homo sapiens.
Family and domain databases
InterPro	IPR002219. DAG_PE_bd. IPR000719. Prot_kinase_core. IPR017442. Se/Thr_pkinase-rel. IPR008271. Ser_thr_pkin_AS. [Graphical view]
Pfam	PF00130. C1_1. 1 hit. PF00069. Pkinase. 1 hit. [Graphical view]
ProDom	PD000001. Prot_kinase. 1 hit. [Graphical view] [Entries sharing at least one domain]
SMART	SM00109. C1. 1 hit. [Graphical view]
PROSITE	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]
ProtoNet	Search...
Other Resources
NextBio	93924.
SOURCE	Search...

Entry information

Entry name

KSR2_HUMAN

Accession

Primary (citable) accession number: Q6VAB6
Secondary accession number(s): A0PJT2, Q3B828, Q8N775

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 21, 2004
Last sequence update:	May 29, 2007
Last modified:	June 16, 2009
This is version 47 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)