Q6VAB6 (KSR2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

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

Gene names

Name:

KSR2

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	950 AA.
Sequence status	Complete.
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	Zinc-finger
Ligand	Metal-binding Zinc
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	calcium-mediated signaling Inferred from electronic annotation. Source: Compara positive regulation of MAPK cascade Inferred from electronic annotation. Source: Compara
Cellular_component	cytosol Inferred from electronic annotation. Source: Compara plasma membrane Inferred from electronic annotation. Source: Compara
Molecular_function	ATP binding Inferred from electronic annotation. Source: InterPro metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW protein serine/threonine kinase activity Inferred from electronic annotation. Source: InterPro
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

Secondary structure

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950

Helix Strand Turn

Details...

Helix

656 – 658

3

Beta strand

659 – 661

3

Beta strand

675 – 693

19

Turn

704 – 710

7

Helix

711 – 714

4

Beta strand

727 – 730

4

Beta strand

735 – 738

4

Beta strand

744 – 746

3

Helix

747 – 750

4

Helix

761 – 779

19

Beta strand

792 – 794

3

Helix

827 – 830

4

Helix

834 – 837

4

Helix

853 – 869

17

Beta strand

873 – 876

4

Helix

879 – 887

9

Helix

903 – 911

9

Turn

915 – 917

3

Helix

921 – 928

8

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 [UniParc]. 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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [Abstract] Cited for: VARIANT [LARGE SCALE ANALYSIS] SER-676.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

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. NM_173598.4.

UniGene

Hs.375836.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2Y4I	X-ray	3.46	B	634-950	[»]

ProteinModelPortal

Q6VAB6.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-59195N.

IntAct

Q6VAB6. 1 interaction.

STRING

9606.ENSP00000339952.

PTM databases

PhosphoSite

Q6VAB6.

Polymorphism databases

DMDM

148886599.

Proteomic databases

PaxDb

Q6VAB6.

PRIDE

Q6VAB6.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000339824; ENSP00000339952; ENSG00000171435.

GeneID

283455.

KEGG

hsa:283455.

UCSC

uc001two.2. human.

Organism-specific databases

CTD

283455.

GeneCards

GC12M117890.

H-InvDB

HIX0018992.

HGNC

HGNC:18610. KSR2.

HPA

HPA035536.

MIM

610737. gene.

neXtProt

NX_Q6VAB6.

PharmGKB

PA134914125.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG0515.

HOGENOM

HOG000113263.

HOVERGEN

HBG052293.

InParanoid

Q6VAB6.

OMA

FCWAYEQ.

Gene expression databases

ArrayExpress

Q6VAB6.

Bgee

Q6VAB6.

CleanEx

HS_KSR2.

Genevestigator

Q6VAB6.

GermOnline

ENSG00000171435. Homo sapiens.

Family and domain databases

InterPro

IPR011009. Kinase-like_dom.
IPR025561. KSR_SAM-like_dom.
IPR002219. Prot_Kinase_C-like_PE/DAG-bd.
IPR000719. Prot_kinase_cat_dom.
IPR001245. Ser-Thr/Tyr_kinase_cat_dom.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]

Pfam

PF13543. KSR1-SAM. 1 hit.
PF07714. Pkinase_Tyr. 1 hit.
[Graphical view]

SMART

SM00109. C1. 1 hit.
[Graphical view]

SUPFAM

SSF56112. Kinase_like. 1 hit.

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

ChiTaRS

KSR2. human.

GenomeRNAi

283455.

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:	May 1, 2013
This is version 84 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.