Q7KZI7 (MARK2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Serine/threonine-protein kinase MARK2
EC=2.7.11.1
EC=2.7.11.26

Alternative name(s):
ELKL motif kinase 1
Short name=EMK-1
MAP/microtubule affinity-regulating kinase 2
PAR1 homolog
PAR1 homolog b
Short name=Par-1b
Short name=Par1b

Gene names

Name:	MARK2
Synonyms:	EMK1

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	788 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Serine/threonine-protein kinase involved in cell polarity and microtubule dynamics regulation. Phosphorylates CRTC2/TORC2, DCX, HDAC7, KIF13B, MAP2, MAP4, MAPT/TAU, and RAB11FIP2. Plays a key role in cell polarity by phosphorylating the microtubule-associated proteins MAP2, MAP4 and MAPT/TAU at KXGS motifs, causing detachment from microtubules, and their disassembly. Regulates epithelial cell polarity by phosphorylating RAB11FIP2. Involved in the regulation of neuronal migration through its dual activities in regulating cellular polarity and microtubule dynamics, possibly by phosphorylating and regulating DCX. Regulates axogenesis by phosphorylating KIF13B, promoting interaction between KIF13B and 14-3-3 and inhibiting microtubule-dependent accumulation of KIF13B. Also required for neurite outgrowth and establishment of neuronal polarity. Regulates localization and activity of some histone deacetylases by mediating phosphorylation of HDAC7, promoting subsequent interaction between HDAC7 and 14-3-3 and export from the nucleus. Also acts as a positive regulator of the Wnt signaling pathway, probably by mediating phosphorylation of dishevelled proteins (DVL1, DVL2 and/or DVL3). Modulates the developmental decision to build a columnar versus a hepatic epithelial cell apparently by promoting a switch from a direct to a transcytotic mode of apical protein delivery. Essential for the asymmetric development of membrane domains of polarized epithelial cells. Ref.6 Ref.8 Ref.9 Ref.10 Ref.11 Ref.13 Ref.15 Ref.16 Ref.22 Ref.26
Catalytic activity	ATP + a protein = ADP + a phosphoprotein. Ref.10 ATP + [tau protein] = ADP + [tau protein] phosphate.
Cofactor	Magnesium By similarity. Ref.10
Enzyme regulation	Inhibited by PAK7/PAK5; inhibition is independent of the kinase activity of PAK7/PAK5 By similarity. Activated by phosphorylation on Thr-208. Inhibited by phosphorylation at Ser-212 and Thr-596. Inhibited by hymenialdisine. Specifically inhibited by the H.pylori CagA peptide FPLKRHDKVDDLSK that mimics host substrates and binds to the kinase substrate-binding site. Ref.8 Ref.10
Subunit structure	Homodimer. Interacts with PAK7/PAK5; leading to inhibit the protein kinase activity By similarity. Interacts (when phosphorylated at Thr-596) with YWHAZ. In case of infection, interacts with H.pylori CagA, leading to inhibit kinase activity and junctional and polarity defects. Ref.13 Ref.18
Subcellular location	Cell membrane; Peripheral membrane protein. Cytoplasm. Note: Phosphorylation at Thr-596 by PRKCZ/aPKC and subsequent interaction with 14-3-3 protein YWHAZ promotes relocation from the cell membrane to the cytoplasm. Ref.12 Ref.13
Tissue specificity	High levels of expression in heart, brain, skeletal muscle and pancreas, lower levels observed in lung, liver and kidney. Ref.1
Domain	The UBA domain does not seem to bind ubiquitin and ubiquitin-like and might play a role in regulating the enzyme conformation and localization. Activation of the kinase activity following phosphorylation at Thr-208 is accompanied by a conformational change that alters the orientation of the UBA domain with respect to the catalytic domain. Ref.23 The KA1 domain mediates binding to phospholipids and targeting to membranes By similarity. Ref.23
Post-translational modification	Autophosphorylated. Phosphorylated at Thr-208 by STK11/LKB1 in complex with STE20-related adapter-alpha (STRADA) pseudo kinase and CAB39. Phosphorylation at Thr-208 by TAOK1 activates the kinase activity, leading to phosphorylation and detachment of MAPT/TAU from microtubules. Phosphorylation at Ser-212 by GSK3-beta (GSK3B) inhibits the kinase activity. Phosphorylation by CaMK1 promotes activity and is required to promote neurite outgrowth. Phosphorylation at Thr-596 by PRKCZ/aPKC in polarized epithelial cells inhibits the kinase activity and promotes binding to 14-3-3 protein YWHAZ, leading to relocation from cell membrane to cytoplasm. Ref.10 Ref.12 Ref.13
Sequence similarities	Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. SNF1 subfamily. Contains 1 KA1 (kinase-associated) domain. Contains 1 protein kinase domain. Contains 1 UBA domain.
Sequence caution	The sequence AAK82368.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.

Ontologies

Keywords
Biological process	Differentiation Wnt signaling pathway
Cellular component	Cell membrane Cytoplasm Membrane
Coding sequence diversity	Alternative promoter usage Alternative splicing
Ligand	ATP-binding Lipid-binding Magnesium Metal-binding Nucleotide-binding
Molecular function	Developmental protein Kinase Serine/threonine-protein kinase Transferase
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	Wnt receptor signaling pathway Inferred from electronic annotation. Source: UniProtKB-KW establishment of cell polarity Inferred from direct assay Ref.8. Source: UniProtKB establishment or maintenance of epithelial cell apical/basal polarity Inferred from direct assay Ref.13. Source: UniProtKB intracellular protein kinase cascade Inferred from direct assay Ref.10. Source: UniProtKB neuron migration Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of neuron projection development Inferred from direct assay Ref.8. Source: UniProtKB protein autophosphorylation Inferred from sequence or structural similarity. Source: UniProtKB regulation of axonogenesis Inferred from mutant phenotype Ref.26. Source: UniProtKB regulation of cytoskeleton organization Inferred from sequence or structural similarity. Source: UniProtKB response to oxidative stress Inferred from expression pattern PubMed 16551573. Source: BHF-UCL
Cellular_component	basal cortex Inferred from electronic annotation. Source: Compara membrane Inferred from mutant phenotype Ref.10. Source: UniProtKB nucleus Inferred from electronic annotation. Source: Compara plasma membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	ATP binding Inferred from direct assay Ref.10. Source: UniProtKB lipid binding Inferred from electronic annotation. Source: UniProtKB-KW magnesium ion binding Inferred from direct assay Ref.10. Source: UniProtKB protein serine/threonine kinase activity Inferred from direct assay Ref.10Ref.15Ref.16Ref.26. Source: UniProtKB tau-protein kinase activity Inferred from sequence or structural similarity. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
PARD6G	Q9BYG4	2	EBI-516560,EBI-295417
YWHAB	P31946	2	EBI-516560,EBI-359815
YWHAG	P61981	2	EBI-516560,EBI-359832
YWHAH	Q04917	6	EBI-516560,EBI-306940
YWHAZ	P63104	3	EBI-516560,EBI-347088

Alternative products

This entry describes 16 isoforms produced by alternative promoter usage and alternative splicing. [Align] [Select]

Isoform 1 Ref.3 (identifier: Q7KZI7-1)

Also known as: Alpha;

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.

Note: Produced by alternative promoter usage. No experimental confirmation available.

Isoform 2 Ref.1 (identifier: Q7KZI7-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-33: Missing.
     505-558: Missing.

Note: Produced by alternative splicing of isoform 6.

Isoform 3 Ref.1 (identifier: Q7KZI7-3)

The sequence of this isoform differs from the canonical sequence as follows:
     1-33: Missing.
     644-652: Missing.

Note: Produced by alternative splicing of isoform 6.

Isoform 4 Ref.6 (identifier: Q7KZI7-4)

Also known as: Par-1Balpha;

The sequence of this isoform differs from the canonical sequence as follows:
     505-558: Missing.
     644-652: Missing.

Note: Produced by alternative splicing of isoform 1.

Isoform 5 Ref.3 (identifier: Q7KZI7-5)

The sequence of this isoform differs from the canonical sequence as follows:
     505-558: Missing.
     654-668: Missing.

Note: Produced by alternative splicing of isoform 1.

Isoform 6 Ref.3 (identifier: Q7KZI7-6)

Also known as: Beta;

The sequence of this isoform differs from the canonical sequence as follows:
     1-33: Missing.

Note: Produced by alternative promoter usage. No experimental confirmation available.

Isoform 7 Ref.3 (identifier: Q7KZI7-7)

The sequence of this isoform differs from the canonical sequence as follows:
     1-33: Missing.
     505-558: Missing.
     644-652: Missing.

Note: Produced by alternative splicing of isoform 6. No experimental confirmation available.

Isoform 8 Ref.3 (identifier: Q7KZI7-8)

The sequence of this isoform differs from the canonical sequence as follows:
     644-652: Missing.

Note: Produced by alternative splicing of isoform 1. No experimental confirmation available.

Isoform 9 Ref.3 (identifier: Q7KZI7-9)

The sequence of this isoform differs from the canonical sequence as follows:
     505-558: Missing.

Note: Produced by alternative splicing of isoform 1. No experimental confirmation available.

Isoform 10 Ref.3 (identifier: Q7KZI7-10)

The sequence of this isoform differs from the canonical sequence as follows:
     1-33: Missing.
     505-558: Missing.
     654-668: Missing.

Note: Produced by alternative splicing of isoform 6. No experimental confirmation available.

Isoform 11 Ref.3 (identifier: Q7KZI7-11)

The sequence of this isoform differs from the canonical sequence as follows:
     654-668: Missing.

Note: Produced by alternative splicing of isoform 1. No experimental confirmation available.

Isoform 12 Ref.3 (identifier: Q7KZI7-12)

The sequence of this isoform differs from the canonical sequence as follows:
     1-33: Missing.
     654-668: Missing.

Note: Produced by alternative splicing of isoform 6. No experimental confirmation available.

Isoform 13 (identifier: Q7KZI7-13)

The sequence of this isoform differs from the canonical sequence as follows:
     1-33: Missing.
     412-412: Missing.
     505-558: Missing.
     644-652: Missing.

Note: Produced by alternative splicing of isoform 6. Contains a phosphoserine at position 376.

Isoform 14 (identifier: Q7KZI7-14)

The sequence of this isoform differs from the canonical sequence as follows:
     1-33: Missing.
     412-412: Missing.
     644-652: Missing.

Note: Produced by alternative splicing of isoform 6. Contains a phosphoserine at position 376.

Isoform 15 (identifier: Q7KZI7-15)

The sequence of this isoform differs from the canonical sequence as follows:
     412-412: Missing.
     505-558: Missing.
     645-668: Missing.

Note: Produced by alternative splicing of isoform 1. Contains a phosphoserine at position 409.

Isoform 16 (identifier: Q7KZI7-16)

The sequence of this isoform differs from the canonical sequence as follows:
     412-412: Missing.
     505-558: Missing.
     644-652: Missing.

Note: Produced by alternative splicing of isoform 1. Contains a phosphoserine at position 409.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 788

788

Serine/threonine-protein kinase MARK2

PRO_0000086301

Regions

Domain

53 – 304

252

Protein kinase

Domain

323 – 362

40

UBA

Domain

739 – 788

50

KA1

Nucleotide binding

59 – 67

9

ATP By similarity UniProtKB Q9H0K1

Sites

Active site

175

1

Proton acceptor By similarity UniProtKB Q9H0K1

Binding site

82

1

ATP By similarity UniProtKB O08678

Amino acid modifications

Modified residue

40

1

Phosphoserine Ref.31

Modified residue

58

1

Phosphothreonine; by autocatalysis By similarity

Modified residue

91

1

Phosphoserine; by CaMK1 By similarity

Modified residue

92

1

Phosphoserine; by CaMK1 By similarity

Modified residue

93

1

Phosphoserine; by CaMK1 By similarity

Modified residue

208

1

Phosphothreonine; by LKB1 and TAOK1 Ref.10 Ref.25

Modified residue

212

1

Phosphoserine; by GSK3-beta By similarity UniProtKB O08678

Modified residue

274

1

Phosphoserine; by autocatalysis By similarity

Modified residue

275

1

Phosphothreonine; by autocatalysis By similarity

Modified residue

294

1

Phosphothreonine; by CaMK1 By similarity

Modified residue

409

1

Phosphoserine Ref.21 Ref.24 Ref.25

Modified residue

456

1

Phosphoserine Ref.17 Ref.19 Ref.20 Ref.21 Ref.25

Modified residue

486

1

Phosphoserine Ref.14 Ref.19 Ref.21 Ref.25 Ref.31

Modified residue

493

1

Phosphoserine Ref.21

Modified residue

569

1

Phosphoserine Ref.24

Modified residue

571

1

Phosphoserine By similarity

Modified residue

595

1

Phosphoserine By similarity

Modified residue

596

1

Phosphothreonine; by PKC/PRKCZ Ref.12 Ref.13

Modified residue

619

1

Phosphoserine Ref.31

Modified residue

722

1

Phosphoserine Ref.25

Natural variations

Alternative sequence

1 – 33

33

Missing in isoform 2, isoform 3, isoform 6, isoform 7, isoform 10, isoform 12, isoform 13 and isoform 14. Ref.1 Ref.3

VSP_051705

Alternative sequence

412

1

Missing in isoform 13, isoform 14, isoform 15 and isoform 16.

VSP_039872

Alternative sequence

505 – 558

54

Missing in isoform 2, isoform 4, isoform 5, isoform 7, isoform 9, isoform 10, isoform 13, isoform 15 and isoform 16. Ref.1 Ref.3 Ref.6

VSP_051706

Alternative sequence

644 – 652

9

Missing in isoform 3, isoform 4, isoform 7, isoform 8, isoform 13, isoform 14 and isoform 16. Ref.1 Ref.3 Ref.6

VSP_051707

Alternative sequence

645 – 668

24

Missing in isoform 15.

VSP_041853

Alternative sequence

654 – 668

15

Missing in isoform 5, isoform 11, isoform 10 and isoform 12. Ref.1 Ref.3 Ref.6

VSP_051708

Experimental info

Mutagenesis

208

1

T → A: Prevents phosphorylation and activation by STK11/LKB1 complex. Ref.10

Mutagenesis

596

1

T → A: Loss of membrane dissociation and binding to YWHAZ. Ref.12 Ref.13

Sequence conflict

192

1

A → G in CAA80914. Ref.7

Sequence conflict

236

1

L → C in CAA80914. Ref.7

Sequence conflict

389 – 390

2

PS → QF in CAA66229. Ref.1

Secondary structure

1

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788

Helix Strand Turn

Details...

Beta strand

53 – 60

8

Beta strand

66 – 72

7

Turn

73 – 75

3

Beta strand

78 – 86

9

Helix

91 – 106

16

Beta strand

115 – 120

6

Beta strand

122 – 129

8

Helix

137 – 144

8

Helix

149 – 168

20

Helix

178 – 180

3

Beta strand

181 – 183

3

Beta strand

189 – 191

3

Helix

213 – 215

3

Helix

218 – 221

4

Helix

228 – 245

18

Helix

255 – 264

10

Helix

275 – 284

10

Helix

289 – 291

3

Helix

295 – 299

5

Helix

302 – 305

4

Helix

326 – 334

9

Helix

339 – 347

9

Helix

353 – 361

9

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (Alpha) [UniParc]. Last modified April 12, 2005. Version 2. Checksum: F307BF4DDB543A70	FASTA	788	87,911
	10 20 30 40 50 60 MSSARTPLPT LNERDTEQPT LGHLDSKPSS KSNMIRGRNS ATSADEQPHI GNYRLLKTIG 70 80 90 100 110 120 KGNFAKVKLA RHILTGKEVA VKIIDKTQLN SSSLQKLFRE VRIMKVLNHP NIVKLFEVIE 130 140 150 160 170 180 TEKTLYLVME YASGGEVFDY LVAHGRMKEK EARAKFRQIV SAVQYCHQKF IVHRDLKAEN 190 200 210 220 230 240 LLLDADMNIK IADFGFSNEF TFGNKLDTFC GSPPYAAPEL FQGKKYDGPE VDVWSLGVIL 250 260 270 280 290 300 YTLVSGSLPF DGQNLKELRE RVLRGKYRIP FYMSTDCENL LKKFLILNPS KRGTLEQIMK 310 320 330 340 350 360 DRWMNVGHED DELKPYVEPL PDYKDPRRTE LMVSMGYTRE EIQDSLVGQR YNEVMATYLL 370 380 390 400 410 420 LGYKSSELEG DTITLKPRPS ADLTNSSAPS PSHKVQRSVS ANPKQRRFSD QAAGPAIPTS 430 440 450 460 470 480 NSYSKKTQSN NAENKRPEED RESGRKASST AKVPASPLPG LERKKTTPTP STNSVLSTST 490 500 510 520 530 540 NRSRNSPLLE RASLGQASIQ NGKDSLTMPG SRASTASASA AVSAARPRQH QKSMSASVHP 550 560 570 580 590 600 NKASGLPPTE SNCEVPRPST APQRVPVASP SAHNISSSGG APDRTNFPRG VSSRSTFHAG 610 620 630 640 650 660 QLRQVRDQQN LPYGVTPASP SGHSQGRRGA SGSIFSKFTS KFVRRNLSFR FARRNLNEPE 670 680 690 700 710 720 SKDRVETLRP HVVGSGGNDK EKEEFREAKP RSLRFTWSMK TTSSMEPNEM MREIRKVLDA 730 740 750 760 770 780 NSCQSELHEK YMLLCMHGTP GHEDFVQWEM EVCKLPRLSL NGVRFKRISG TSMAFKNIAS KIANELKL
	Isoform 2 [UniParc]. Checksum: 3D68318CFDCA31EE	FASTA	701	78,851
	10 20 30 40 50 60 MIRGRNSATS ADEQPHIGNY RLLKTIGKGN FAKVKLARHI LTGKEVAVKI IDKTQLNSSS 70 80 90 100 110 120 LQKLFREVRI MKVLNHPNIV KLFEVIETEK TLYLVMEYAS GGEVFDYLVA HGRMKEKEAR 130 140 150 160 170 180 AKFRQIVSAV QYCHQKFIVH RDLKAENLLL DADMNIKIAD FGFSNEFTFG NKLDTFCGSP 190 200 210 220 230 240 PYAAPELFQG KKYDGPEVDV WSLGVILYTL VSGSLPFDGQ NLKELRERVL RGKYRIPFYM 250 260 270 280 290 300 STDCENLLKK FLILNPSKRG TLEQIMKDRW MNVGHEDDEL KPYVEPLPDY KDPRRTELMV 310 320 330 340 350 360 SMGYTREEIQ DSLVGQRYNE VMATYLLLGY KSSELEGDTI TLKPRPSADL TNSSAPSPSH 370 380 390 400 410 420 KVQRSVSANP KQRRFSDQAA GPAIPTSNSY SKKTQSNNAE NKRPEEDRES GRKASSTAKV 430 440 450 460 470 480 PASPLPGLER KKTTPTPSTN SVLSTSTNRS RNSPLLERAS LGQASIQNGK DSTAPQRVPV 490 500 510 520 530 540 ASPSAHNISS SGGAPDRTNF PRGVSSRSTF HAGQLRQVRD QQNLPYGVTP ASPSGHSQGR 550 560 570 580 590 600 RGASGSIFSK FTSKFVRRNL SFRFARRNLN EPESKDRVET LRPHVVGSGG NDKEKEEFRE 610 620 630 640 650 660 AKPRSLRFTW SMKTTSSMEP NEMMREIRKV LDANSCQSEL HEKYMLLCMH GTPGHEDFVQ 670 680 690 700 WEMEVCKLPR LSLNGVRFKR ISGTSMAFKN IASKIANELK L
	Isoform 3 [UniParc]. Checksum: 58F2BBE10943C90F	FASTA	746	83,184
	10 20 30 40 50 60 MIRGRNSATS ADEQPHIGNY RLLKTIGKGN FAKVKLARHI LTGKEVAVKI IDKTQLNSSS 70 80 90 100 110 120 LQKLFREVRI MKVLNHPNIV KLFEVIETEK TLYLVMEYAS GGEVFDYLVA HGRMKEKEAR 130 140 150 160 170 180 AKFRQIVSAV QYCHQKFIVH RDLKAENLLL DADMNIKIAD FGFSNEFTFG NKLDTFCGSP 190 200 210 220 230 240 PYAAPELFQG KKYDGPEVDV WSLGVILYTL VSGSLPFDGQ NLKELRERVL RGKYRIPFYM 250 260 270 280 290 300 STDCENLLKK FLILNPSKRG TLEQIMKDRW MNVGHEDDEL KPYVEPLPDY KDPRRTELMV 310 320 330 340 350 360 SMGYTREEIQ DSLVGQRYNE VMATYLLLGY KSSELEGDTI TLKPRPSADL TNSSAPSPSH 370 380 390 400 410 420 KVQRSVSANP KQRRFSDQAA GPAIPTSNSY SKKTQSNNAE NKRPEEDRES GRKASSTAKV 430 440 450 460 470 480 PASPLPGLER KKTTPTPSTN SVLSTSTNRS RNSPLLERAS LGQASIQNGK DSLTMPGSRA 490 500 510 520 530 540 STASASAAVS AARPRQHQKS MSASVHPNKA SGLPPTESNC EVPRPSTAPQ RVPVASPSAH 550 560 570 580 590 600 NISSSGGAPD RTNFPRGVSS RSTFHAGQLR QVRDQQNLPY GVTPASPSGH SQGRRGASGS 610 620 630 640 650 660 IFSKFTSKFV RRNLNEPESK DRVETLRPHV VGSGGNDKEK EEFREAKPRS LRFTWSMKTT 670 680 690 700 710 720 SSMEPNEMMR EIRKVLDANS CQSELHEKYM LLCMHGTPGH EDFVQWEMEV CKLPRLSLNG 730 740 VRFKRISGTS MAFKNIASKI ANELKL
	Isoform 4 (Par-1Balpha) [UniParc]. Checksum: D676331938A84716	FASTA	725	81,280
	10 20 30 40 50 60 MSSARTPLPT LNERDTEQPT LGHLDSKPSS KSNMIRGRNS ATSADEQPHI GNYRLLKTIG 70 80 90 100 110 120 KGNFAKVKLA RHILTGKEVA VKIIDKTQLN SSSLQKLFRE VRIMKVLNHP NIVKLFEVIE 130 140 150 160 170 180 TEKTLYLVME YASGGEVFDY LVAHGRMKEK EARAKFRQIV SAVQYCHQKF IVHRDLKAEN 190 200 210 220 230 240 LLLDADMNIK IADFGFSNEF TFGNKLDTFC GSPPYAAPEL FQGKKYDGPE VDVWSLGVIL 250 260 270 280 290 300 YTLVSGSLPF DGQNLKELRE RVLRGKYRIP FYMSTDCENL LKKFLILNPS KRGTLEQIMK 310 320 330 340 350 360 DRWMNVGHED DELKPYVEPL PDYKDPRRTE LMVSMGYTRE EIQDSLVGQR YNEVMATYLL 370 380 390 400 410 420 LGYKSSELEG DTITLKPRPS ADLTNSSAPS PSHKVQRSVS ANPKQRRFSD QAAGPAIPTS 430 440 450 460 470 480 NSYSKKTQSN NAENKRPEED RESGRKASST AKVPASPLPG LERKKTTPTP STNSVLSTST 490 500 510 520 530 540 NRSRNSPLLE RASLGQASIQ NGKDSTAPQR VPVASPSAHN ISSSGGAPDR TNFPRGVSSR 550 560 570 580 590 600 STFHAGQLRQ VRDQQNLPYG VTPASPSGHS QGRRGASGSI FSKFTSKFVR RNLNEPESKD 610 620 630 640 650 660 RVETLRPHVV GSGGNDKEKE EFREAKPRSL RFTWSMKTTS SMEPNEMMRE IRKVLDANSC 670 680 690 700 710 720 QSELHEKYML LCMHGTPGHE DFVQWEMEVC KLPRLSLNGV RFKRISGTSM AFKNIASKIA NELKL
	Isoform 5 [UniParc]. Checksum: EC39154CF73E9858	FASTA	719	80,647
	10 20 30 40 50 60 MSSARTPLPT LNERDTEQPT LGHLDSKPSS KSNMIRGRNS ATSADEQPHI GNYRLLKTIG 70 80 90 100 110 120 KGNFAKVKLA RHILTGKEVA VKIIDKTQLN SSSLQKLFRE VRIMKVLNHP NIVKLFEVIE 130 140 150 160 170 180 TEKTLYLVME YASGGEVFDY LVAHGRMKEK EARAKFRQIV SAVQYCHQKF IVHRDLKAEN 190 200 210 220 230 240 LLLDADMNIK IADFGFSNEF TFGNKLDTFC GSPPYAAPEL FQGKKYDGPE VDVWSLGVIL 250 260 270 280 290 300 YTLVSGSLPF DGQNLKELRE RVLRGKYRIP FYMSTDCENL LKKFLILNPS KRGTLEQIMK 310 320 330 340 350 360 DRWMNVGHED DELKPYVEPL PDYKDPRRTE LMVSMGYTRE EIQDSLVGQR YNEVMATYLL 370 380 390 400 410 420 LGYKSSELEG DTITLKPRPS ADLTNSSAPS PSHKVQRSVS ANPKQRRFSD QAAGPAIPTS 430 440 450 460 470 480 NSYSKKTQSN NAENKRPEED RESGRKASST AKVPASPLPG LERKKTTPTP STNSVLSTST 490 500 510 520 530 540 NRSRNSPLLE RASLGQASIQ NGKDSTAPQR VPVASPSAHN ISSSGGAPDR TNFPRGVSSR 550 560 570 580 590 600 STFHAGQLRQ VRDQQNLPYG VTPASPSGHS QGRRGASGSI FSKFTSKFVR RNLSFRFARR 610 620 630 640 650 660 PHVVGSGGND KEKEEFREAK PRSLRFTWSM KTTSSMEPNE MMREIRKVLD ANSCQSELHE 670 680 690 700 710 KYMLLCMHGT PGHEDFVQWE MEVCKLPRLS LNGVRFKRIS GTSMAFKNIA SKIANELKL
	Isoform 6 (Beta) [UniParc]. Checksum: 493CD8C6DC3A4C06	FASTA	755	84,333
	10 20 30 40 50 60 MIRGRNSATS ADEQPHIGNY RLLKTIGKGN FAKVKLARHI LTGKEVAVKI IDKTQLNSSS 70 80 90 100 110 120 LQKLFREVRI MKVLNHPNIV KLFEVIETEK TLYLVMEYAS GGEVFDYLVA HGRMKEKEAR 130 140 150 160 170 180 AKFRQIVSAV QYCHQKFIVH RDLKAENLLL DADMNIKIAD FGFSNEFTFG NKLDTFCGSP 190 200 210 220 230 240 PYAAPELFQG KKYDGPEVDV WSLGVILYTL VSGSLPFDGQ NLKELRERVL RGKYRIPFYM 250 260 270 280 290 300 STDCENLLKK FLILNPSKRG TLEQIMKDRW MNVGHEDDEL KPYVEPLPDY KDPRRTELMV 310 320 330 340 350 360 SMGYTREEIQ DSLVGQRYNE VMATYLLLGY KSSELEGDTI TLKPRPSADL TNSSAPSPSH 370 380 390 400 410 420 KVQRSVSANP KQRRFSDQAA GPAIPTSNSY SKKTQSNNAE NKRPEEDRES GRKASSTAKV 430 440 450 460 470 480 PASPLPGLER KKTTPTPSTN SVLSTSTNRS RNSPLLERAS LGQASIQNGK DSLTMPGSRA 490 500 510 520 530 540 STASASAAVS AARPRQHQKS MSASVHPNKA SGLPPTESNC EVPRPSTAPQ RVPVASPSAH 550 560 570 580 590 600 NISSSGGAPD RTNFPRGVSS RSTFHAGQLR QVRDQQNLPY GVTPASPSGH SQGRRGASGS 610 620 630 640 650 660 IFSKFTSKFV RRNLSFRFAR RNLNEPESKD RVETLRPHVV GSGGNDKEKE EFREAKPRSL 670 680 690 700 710 720 RFTWSMKTTS SMEPNEMMRE IRKVLDANSC QSELHEKYML LCMHGTPGHE DFVQWEMEVC 730 740 750 KLPRLSLNGV RFKRISGTSM AFKNIASKIA NELKL
	Isoform 7 [UniParc]. Checksum: 4BD9AA1F872638A6	FASTA	692	77,702
	10 20 30 40 50 60 MIRGRNSATS ADEQPHIGNY RLLKTIGKGN FAKVKLARHI LTGKEVAVKI IDKTQLNSSS 70 80 90 100 110 120 LQKLFREVRI MKVLNHPNIV KLFEVIETEK TLYLVMEYAS GGEVFDYLVA HGRMKEKEAR 130 140 150 160 170 180 AKFRQIVSAV QYCHQKFIVH RDLKAENLLL DADMNIKIAD FGFSNEFTFG NKLDTFCGSP 190 200 210 220 230 240 PYAAPELFQG KKYDGPEVDV WSLGVILYTL VSGSLPFDGQ NLKELRERVL RGKYRIPFYM 250 260 270 280 290 300 STDCENLLKK FLILNPSKRG TLEQIMKDRW MNVGHEDDEL KPYVEPLPDY KDPRRTELMV 310 320 330 340 350 360 SMGYTREEIQ DSLVGQRYNE VMATYLLLGY KSSELEGDTI TLKPRPSADL TNSSAPSPSH 370 380 390 400 410 420 KVQRSVSANP KQRRFSDQAA GPAIPTSNSY SKKTQSNNAE NKRPEEDRES GRKASSTAKV 430 440 450 460 470 480 PASPLPGLER KKTTPTPSTN SVLSTSTNRS RNSPLLERAS LGQASIQNGK DSTAPQRVPV 490 500 510 520 530 540 ASPSAHNISS SGGAPDRTNF PRGVSSRSTF HAGQLRQVRD QQNLPYGVTP ASPSGHSQGR 550 560 570 580 590 600 RGASGSIFSK FTSKFVRRNL NEPESKDRVE TLRPHVVGSG GNDKEKEEFR EAKPRSLRFT 610 620 630 640 650 660 WSMKTTSSME PNEMMREIRK VLDANSCQSE LHEKYMLLCM HGTPGHEDFV QWEMEVCKLP 670 680 690 RLSLNGVRFK RISGTSMAFK NIASKIANEL KL
	Isoform 8 [UniParc]. Checksum: 5AF7014EB5639857	FASTA	779	86,762
	10 20 30 40 50 60 MSSARTPLPT LNERDTEQPT LGHLDSKPSS KSNMIRGRNS ATSADEQPHI GNYRLLKTIG 70 80 90 100 110 120 KGNFAKVKLA RHILTGKEVA VKIIDKTQLN SSSLQKLFRE VRIMKVLNHP NIVKLFEVIE 130 140 150 160 170 180 TEKTLYLVME YASGGEVFDY LVAHGRMKEK EARAKFRQIV SAVQYCHQKF IVHRDLKAEN 190 200 210 220 230 240 LLLDADMNIK IADFGFSNEF TFGNKLDTFC GSPPYAAPEL FQGKKYDGPE VDVWSLGVIL 250 260 270 280 290 300 YTLVSGSLPF DGQNLKELRE RVLRGKYRIP FYMSTDCENL LKKFLILNPS KRGTLEQIMK 310 320 330 340 350 360 DRWMNVGHED DELKPYVEPL PDYKDPRRTE LMVSMGYTRE EIQDSLVGQR YNEVMATYLL 370 380 390 400 410 420 LGYKSSELEG DTITLKPRPS ADLTNSSAPS PSHKVQRSVS ANPKQRRFSD QAAGPAIPTS 430 440 450 460 470 480 NSYSKKTQSN NAENKRPEED RESGRKASST AKVPASPLPG LERKKTTPTP STNSVLSTST 490 500 510 520 530 540 NRSRNSPLLE RASLGQASIQ NGKDSLTMPG SRASTASASA AVSAARPRQH QKSMSASVHP 550 560 570 580 590 600 NKASGLPPTE SNCEVPRPST APQRVPVASP SAHNISSSGG APDRTNFPRG VSSRSTFHAG 610 620 630 640 650 660 QLRQVRDQQN LPYGVTPASP SGHSQGRRGA SGSIFSKFTS KFVRRNLNEP ESKDRVETLR 670 680 690 700 710 720 PHVVGSGGND KEKEEFREAK PRSLRFTWSM KTTSSMEPNE MMREIRKVLD ANSCQSELHE 730 740 750 760 770 KYMLLCMHGT PGHEDFVQWE MEVCKLPRLS LNGVRFKRIS GTSMAFKNIA SKIANELKL
	Isoform 9 [UniParc]. Checksum: 60D126D3C8967186	FASTA	734	82,429
	10 20 30 40 50 60 MSSARTPLPT LNERDTEQPT LGHLDSKPSS KSNMIRGRNS ATSADEQPHI GNYRLLKTIG 70 80 90 100 110 120 KGNFAKVKLA RHILTGKEVA VKIIDKTQLN SSSLQKLFRE VRIMKVLNHP NIVKLFEVIE 130 140 150 160 170 180 TEKTLYLVME YASGGEVFDY LVAHGRMKEK EARAKFRQIV SAVQYCHQKF IVHRDLKAEN 190 200 210 220 230 240 LLLDADMNIK IADFGFSNEF TFGNKLDTFC GSPPYAAPEL FQGKKYDGPE VDVWSLGVIL 250 260 270 280 290 300 YTLVSGSLPF DGQNLKELRE RVLRGKYRIP FYMSTDCENL LKKFLILNPS KRGTLEQIMK 310 320 330 340 350 360 DRWMNVGHED DELKPYVEPL PDYKDPRRTE LMVSMGYTRE EIQDSLVGQR YNEVMATYLL 370 380 390 400 410 420 LGYKSSELEG DTITLKPRPS ADLTNSSAPS PSHKVQRSVS ANPKQRRFSD QAAGPAIPTS 430 440 450 460 470 480 NSYSKKTQSN NAENKRPEED RESGRKASST AKVPASPLPG LERKKTTPTP STNSVLSTST 490 500 510 520 530 540 NRSRNSPLLE RASLGQASIQ NGKDSTAPQR VPVASPSAHN ISSSGGAPDR TNFPRGVSSR 550 560 570 580 590 600 STFHAGQLRQ VRDQQNLPYG VTPASPSGHS QGRRGASGSI FSKFTSKFVR RNLSFRFARR 610 620 630 640 650 660 NLNEPESKDR VETLRPHVVG SGGNDKEKEE FREAKPRSLR FTWSMKTTSS MEPNEMMREI 670 680 690 700 710 720 RKVLDANSCQ SELHEKYMLL CMHGTPGHED FVQWEMEVCK LPRLSLNGVR FKRISGTSMA 730 FKNIASKIAN ELKL
	Isoform 10 [UniParc]. Checksum: 9389E28076FDDAF8	FASTA	686	77,069
	10 20 30 40 50 60 MIRGRNSATS ADEQPHIGNY RLLKTIGKGN FAKVKLARHI LTGKEVAVKI IDKTQLNSSS 70 80 90 100 110 120 LQKLFREVRI MKVLNHPNIV KLFEVIETEK TLYLVMEYAS GGEVFDYLVA HGRMKEKEAR 130 140 150 160 170 180 AKFRQIVSAV QYCHQKFIVH RDLKAENLLL DADMNIKIAD FGFSNEFTFG NKLDTFCGSP 190 200 210 220 230 240 PYAAPELFQG KKYDGPEVDV WSLGVILYTL VSGSLPFDGQ NLKELRERVL RGKYRIPFYM 250 260 270 280 290 300 STDCENLLKK FLILNPSKRG TLEQIMKDRW MNVGHEDDEL KPYVEPLPDY KDPRRTELMV 310 320 330 340 350 360 SMGYTREEIQ DSLVGQRYNE VMATYLLLGY KSSELEGDTI TLKPRPSADL TNSSAPSPSH 370 380 390 400 410 420 KVQRSVSANP KQRRFSDQAA GPAIPTSNSY SKKTQSNNAE NKRPEEDRES GRKASSTAKV 430 440 450 460 470 480 PASPLPGLER KKTTPTPSTN SVLSTSTNRS RNSPLLERAS LGQASIQNGK DSTAPQRVPV 490 500 510 520 530 540 ASPSAHNISS SGGAPDRTNF PRGVSSRSTF HAGQLRQVRD QQNLPYGVTP ASPSGHSQGR 550 560 570 580 590 600 RGASGSIFSK FTSKFVRRNL SFRFARRPHV VGSGGNDKEK EEFREAKPRS LRFTWSMKTT 610 620 630 640 650 660 SSMEPNEMMR EIRKVLDANS CQSELHEKYM LLCMHGTPGH EDFVQWEMEV CKLPRLSLNG 670 680 VRFKRISGTS MAFKNIASKI ANELKL
	Isoform 11 [UniParc]. Checksum: 0378FF0433C4D901	FASTA	773	86,129
	10 20 30 40 50 60 MSSARTPLPT LNERDTEQPT LGHLDSKPSS KSNMIRGRNS ATSADEQPHI GNYRLLKTIG 70 80 90 100 110 120 KGNFAKVKLA RHILTGKEVA VKIIDKTQLN SSSLQKLFRE VRIMKVLNHP NIVKLFEVIE 130 140 150 160 170 180 TEKTLYLVME YASGGEVFDY LVAHGRMKEK EARAKFRQIV SAVQYCHQKF IVHRDLKAEN 190 200 210 220 230 240 LLLDADMNIK IADFGFSNEF TFGNKLDTFC GSPPYAAPEL FQGKKYDGPE VDVWSLGVIL 250 260 270 280 290 300 YTLVSGSLPF DGQNLKELRE RVLRGKYRIP FYMSTDCENL LKKFLILNPS KRGTLEQIMK 310 320 330 340 350 360 DRWMNVGHED DELKPYVEPL PDYKDPRRTE LMVSMGYTRE EIQDSLVGQR YNEVMATYLL 370 380 390 400 410 420 LGYKSSELEG DTITLKPRPS ADLTNSSAPS PSHKVQRSVS ANPKQRRFSD QAAGPAIPTS 430 440 450 460 470 480 NSYSKKTQSN NAENKRPEED RESGRKASST AKVPASPLPG LERKKTTPTP STNSVLSTST 490 500 510 520 530 540 NRSRNSPLLE RASLGQASIQ NGKDSLTMPG SRASTASASA AVSAARPRQH QKSMSASVHP 550 560 570 580 590 600 NKASGLPPTE SNCEVPRPST APQRVPVASP SAHNISSSGG APDRTNFPRG VSSRSTFHAG 610 620 630 640 650 660 QLRQVRDQQN LPYGVTPASP SGHSQGRRGA SGSIFSKFTS KFVRRNLSFR FARRPHVVGS 670 680 690 700 710 720 GGNDKEKEEF REAKPRSLRF TWSMKTTSSM EPNEMMREIR KVLDANSCQS ELHEKYMLLC 730 740 750 760 770 MHGTPGHEDF VQWEMEVCKL PRLSLNGVRF KRISGTSMAF KNIASKIANE LKL
	Isoform 12 [UniParc]. Checksum: 6220FC8C1A308548	FASTA	740	82,551
	10 20 30 40 50 60 MIRGRNSATS ADEQPHIGNY RLLKTIGKGN FAKVKLARHI LTGKEVAVKI IDKTQLNSSS 70 80 90 100 110 120 LQKLFREVRI MKVLNHPNIV KLFEVIETEK TLYLVMEYAS GGEVFDYLVA HGRMKEKEAR 130 140 150 160 170 180 AKFRQIVSAV QYCHQKFIVH RDLKAENLLL DADMNIKIAD FGFSNEFTFG NKLDTFCGSP 190 200 210 220 230 240 PYAAPELFQG KKYDGPEVDV WSLGVILYTL VSGSLPFDGQ NLKELRERVL RGKYRIPFYM 250 260 270 280 290 300 STDCENLLKK FLILNPSKRG TLEQIMKDRW MNVGHEDDEL KPYVEPLPDY KDPRRTELMV 310 320 330 340 350 360 SMGYTREEIQ DSLVGQRYNE VMATYLLLGY KSSELEGDTI TLKPRPSADL TNSSAPSPSH 370 380 390 400 410 420 KVQRSVSANP KQRRFSDQAA GPAIPTSNSY SKKTQSNNAE NKRPEEDRES GRKASSTAKV 430 440 450 460 470 480 PASPLPGLER KKTTPTPSTN SVLSTSTNRS RNSPLLERAS LGQASIQNGK DSLTMPGSRA 490 500 510 520 530 540 STASASAAVS AARPRQHQKS MSASVHPNKA SGLPPTESNC EVPRPSTAPQ RVPVASPSAH 550 560 570 580 590 600 NISSSGGAPD RTNFPRGVSS RSTFHAGQLR QVRDQQNLPY GVTPASPSGH SQGRRGASGS 610 620 630 640 650 660 IFSKFTSKFV RRNLSFRFAR RPHVVGSGGN DKEKEEFREA KPRSLRFTWS MKTTSSMEPN 670 680 690 700 710 720 EMMREIRKVL DANSCQSELH EKYMLLCMHG TPGHEDFVQW EMEVCKLPRL SLNGVRFKRI 730 740 SGTSMAFKNI ASKIANELKL
	Isoform 13 [UniParc]. Checksum: 2216B4AE7BCF31BE	FASTA	691	77,631
	10 20 30 40 50 60 MIRGRNSATS ADEQPHIGNY RLLKTIGKGN FAKVKLARHI LTGKEVAVKI IDKTQLNSSS 70 80 90 100 110 120 LQKLFREVRI MKVLNHPNIV KLFEVIETEK TLYLVMEYAS GGEVFDYLVA HGRMKEKEAR 130 140 150 160 170 180 AKFRQIVSAV QYCHQKFIVH RDLKAENLLL DADMNIKIAD FGFSNEFTFG NKLDTFCGSP 190 200 210 220 230 240 PYAAPELFQG KKYDGPEVDV WSLGVILYTL VSGSLPFDGQ NLKELRERVL RGKYRIPFYM 250 260 270 280 290 300 STDCENLLKK FLILNPSKRG TLEQIMKDRW MNVGHEDDEL KPYVEPLPDY KDPRRTELMV 310 320 330 340 350 360 SMGYTREEIQ DSLVGQRYNE VMATYLLLGY KSSELEGDTI TLKPRPSADL TNSSAPSPSH 370 380 390 400 410 420 KVQRSVSANP KQRRFSDQAG PAIPTSNSYS KKTQSNNAEN KRPEEDRESG RKASSTAKVP 430 440 450 460 470 480 ASPLPGLERK KTTPTPSTNS VLSTSTNRSR NSPLLERASL GQASIQNGKD STAPQRVPVA 490 500 510 520 530 540 SPSAHNISSS GGAPDRTNFP RGVSSRSTFH AGQLRQVRDQ QNLPYGVTPA SPSGHSQGRR 550 560 570 580 590 600 GASGSIFSKF TSKFVRRNLN EPESKDRVET LRPHVVGSGG NDKEKEEFRE AKPRSLRFTW 610 620 630 640 650 660 SMKTTSSMEP NEMMREIRKV LDANSCQSEL HEKYMLLCMH GTPGHEDFVQ WEMEVCKLPR 670 680 690 LSLNGVRFKR ISGTSMAFKN IASKIANELK L
	Isoform 14 [UniParc]. Checksum: 54CA1DAF4B6E02CF	FASTA	745	83,113
	10 20 30 40 50 60 MIRGRNSATS ADEQPHIGNY RLLKTIGKGN FAKVKLARHI LTGKEVAVKI IDKTQLNSSS 70 80 90 100 110 120 LQKLFREVRI MKVLNHPNIV KLFEVIETEK TLYLVMEYAS GGEVFDYLVA HGRMKEKEAR 130 140 150 160 170 180 AKFRQIVSAV QYCHQKFIVH RDLKAENLLL DADMNIKIAD FGFSNEFTFG NKLDTFCGSP 190 200 210 220 230 240 PYAAPELFQG KKYDGPEVDV WSLGVILYTL VSGSLPFDGQ NLKELRERVL RGKYRIPFYM 250 260 270 280 290 300 STDCENLLKK FLILNPSKRG TLEQIMKDRW MNVGHEDDEL KPYVEPLPDY KDPRRTELMV 310 320 330 340 350 360 SMGYTREEIQ DSLVGQRYNE VMATYLLLGY KSSELEGDTI TLKPRPSADL TNSSAPSPSH 370 380 390 400 410 420 KVQRSVSANP KQRRFSDQAG PAIPTSNSYS KKTQSNNAEN KRPEEDRESG RKASSTAKVP 430 440 450 460 470 480 ASPLPGLERK KTTPTPSTNS VLSTSTNRSR NSPLLERASL GQASIQNGKD SLTMPGSRAS 490 500 510 520 530 540 TASASAAVSA ARPRQHQKSM SASVHPNKAS GLPPTESNCE VPRPSTAPQR VPVASPSAHN 550 560 570 580 590 600 ISSSGGAPDR TNFPRGVSSR STFHAGQLRQ VRDQQNLPYG VTPASPSGHS QGRRGASGSI 610 620 630 640 650 660 FSKFTSKFVR RNLNEPESKD RVETLRPHVV GSGGNDKEKE EFREAKPRSL RFTWSMKTTS 670 680 690 700 710 720 SMEPNEMMRE IRKVLDANSC QSELHEKYML LCMHGTPGHE DFVQWEMEVC KLPRLSLNGV 730 740 RFKRISGTSM AFKNIASKIA NELKL
	Isoform 15 [UniParc]. Checksum: F30B3AB6B60B3621	FASTA	709	79,427
	10 20 30 40 50 60 MSSARTPLPT LNERDTEQPT LGHLDSKPSS KSNMIRGRNS ATSADEQPHI GNYRLLKTIG 70 80 90 100 110 120 KGNFAKVKLA RHILTGKEVA VKIIDKTQLN SSSLQKLFRE VRIMKVLNHP NIVKLFEVIE 130 140 150 160 170 180 TEKTLYLVME YASGGEVFDY LVAHGRMKEK EARAKFRQIV SAVQYCHQKF IVHRDLKAEN 190 200 210 220 230 240 LLLDADMNIK IADFGFSNEF TFGNKLDTFC GSPPYAAPEL FQGKKYDGPE VDVWSLGVIL 250 260 270 280 290 300 YTLVSGSLPF DGQNLKELRE RVLRGKYRIP FYMSTDCENL LKKFLILNPS KRGTLEQIMK 310 320 330 340 350 360 DRWMNVGHED DELKPYVEPL PDYKDPRRTE LMVSMGYTRE EIQDSLVGQR YNEVMATYLL 370 380 390 400 410 420 LGYKSSELEG DTITLKPRPS ADLTNSSAPS PSHKVQRSVS ANPKQRRFSD QAGPAIPTSN 430 440 450 460 470 480 SYSKKTQSNN AENKRPEEDR ESGRKASSTA KVPASPLPGL ERKKTTPTPS TNSVLSTSTN 490 500 510 520 530 540 RSRNSPLLER ASLGQASIQN GKDSTAPQRV PVASPSAHNI SSSGGAPDRT NFPRGVSSRS 550 560 570 580 590 600 TFHAGQLRQV RDQQNLPYGV TPASPSGHSQ GRRGASGSIF SKFTSKFVRR PHVVGSGGND 610 620 630 640 650 660 KEKEEFREAK PRSLRFTWSM KTTSSMEPNE MMREIRKVLD ANSCQSELHE KYMLLCMHGT 670 680 690 700 PGHEDFVQWE MEVCKLPRLS LNGVRFKRIS GTSMAFKNIA SKIANELKL
	Isoform 16 [UniParc]. Checksum: 9D8FB211F5B08149	FASTA	724	81,209
	10 20 30 40 50 60 MSSARTPLPT LNERDTEQPT LGHLDSKPSS KSNMIRGRNS ATSADEQPHI GNYRLLKTIG 70 80 90 100 110 120 KGNFAKVKLA RHILTGKEVA VKIIDKTQLN SSSLQKLFRE VRIMKVLNHP NIVKLFEVIE 130 140 150 160 170 180 TEKTLYLVME YASGGEVFDY LVAHGRMKEK EARAKFRQIV SAVQYCHQKF IVHRDLKAEN 190 200 210 220 230 240 LLLDADMNIK IADFGFSNEF TFGNKLDTFC GSPPYAAPEL FQGKKYDGPE VDVWSLGVIL 250 260 270 280 290 300 YTLVSGSLPF DGQNLKELRE RVLRGKYRIP FYMSTDCENL LKKFLILNPS KRGTLEQIMK 310 320 330 340 350 360 DRWMNVGHED DELKPYVEPL PDYKDPRRTE LMVSMGYTRE EIQDSLVGQR YNEVMATYLL 370 380 390 400 410 420 LGYKSSELEG DTITLKPRPS ADLTNSSAPS PSHKVQRSVS ANPKQRRFSD QAGPAIPTSN 430 440 450 460 470 480 SYSKKTQSNN AENKRPEEDR ESGRKASSTA KVPASPLPGL ERKKTTPTPS TNSVLSTSTN 490 500 510 520 530 540 RSRNSPLLER ASLGQASIQN GKDSTAPQRV PVASPSAHNI SSSGGAPDRT NFPRGVSSRS 550 560 570 580 590 600 TFHAGQLRQV RDQQNLPYGV TPASPSGHSQ GRRGASGSIF SKFTSKFVRR NLNEPESKDR 610 620 630 640 650 660 VETLRPHVVG SGGNDKEKEE FREAKPRSLR FTWSMKTTSS MEPNEMMREI RKVLDANSCQ 670 680 690 700 710 720 SELHEKYMLL CMHGTPGHED FVQWEMEVCK LPRLSLNGVR FKRISGTSMA FKNIASKIAN ELKL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Human serine/threonine protein kinase EMK1: genome structure and cDNA cloning of isoforms produced by alternative splicing." Espinosa L., Navarro E. Cytogenet. Cell Genet. 81:278-282(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 2 AND 3), TISSUE SPECIFICITY. Tissue: Colon.
[2]	Sugiyama A., Inoue H., Oka M. Submitted (AUG-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 5). Tissue: Kidney.
[3]	"Cloning of human full-length CDSs in BD Creator(TM) system donor vector." Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A. Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 6).
[4]	"Human chromosome 11 DNA sequence and analysis including novel gene identification." Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K., Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T., Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G. , Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C., Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A., Hattori M., Rogers J., Lander E.S., Sakaki Y. Nature 440:497-500(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 4), NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 11-755 (ISOFORM 1). Tissue: Kidney and Placenta.
[6]	"PAR-1 is a Dishevelled-associated kinase and a positive regulator of Wnt signalling." Sun T.-Q., Lu B., Feng J.-J., Reinhard C., Jan Y.N., Fantl W.J., Williams L.T. Nat. Cell Biol. 3:628-636(2001) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 28-788 (ISOFORM 4), FUNCTION.
[7]	"Identification of 21 novel human protein kinases, including 3 members of a family related to the cell cycle regulator nimA of Aspergillus nidulans." Schultz S.J., Nigg E.A. Cell Growth Differ. 4:821-830(1993) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 190-237.
[8]	"Protein kinase MARK/PAR-1 is required for neurite outgrowth and establishment of neuronal polarity." Biernat J., Wu Y.Z., Timm T., Zheng-Fischhofer Q., Mandelkow E., Meijer L., Mandelkow E.M. Mol. Biol. Cell 13:4013-4028(2002) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, ENZYME REGULATION.
[9]	"Splicing alterations in human renal allografts: detection of a new splice variant of protein kinase Par1/Emk1 whose expression is associated with an increase of inflammation in protocol biopsies of transplanted patients." Hueso M., Beltran V., Moreso F., Ciriero E., Fulladosa X., Grinyo J.M., Seron D., Navarro E. Biochim. Biophys. Acta 1689:58-65(2004) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, ALTERNATIVE PROMOTER USAGE.
[10]	"LKB1 is a master kinase that activates 13 kinases of the AMPK subfamily, including MARK/PAR-1." Lizcano J.M., Goeransson O., Toth R., Deak M., Morrice N.A., Boudeau J., Hawley S.A., Udd L., Maekelae T.P., Hardie D.G., Alessi D.R. EMBO J. 23:833-843(2004) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, ENZYME REGULATION, PHOSPHORYLATION AT THR-208, MUTAGENESIS OF THR-208.
[11]	"Par-1 promotes a hepatic mode of apical protein trafficking in MDCK cells." Cohen D., Rodriguez-Boulan E., Musch A. Proc. Natl. Acad. Sci. U.S.A. 101:13792-13797(2004) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[12]	"Atypical PKC phosphorylates PAR-1 kinases to regulate localization and activity." Hurov J.B., Watkins J.L., Piwnica-Worms H. Curr. Biol. 14:736-741(2004) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION AT THR-596, MUTAGENESIS OF THR-596, SUBCELLULAR LOCATION.
[13]	"aPKC acts upstream of PAR-1b in both the establishment and maintenance of mammalian epithelial polarity." Suzuki A., Hirata M., Kamimura K., Maniwa R., Yamanaka T., Mizuno K., Kishikawa M., Hirose H., Amano Y., Izumi N., Miwa Y., Ohno S. Curr. Biol. 14:1425-1435(2004) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION, PHOSPHORYLATION AT THR-596, MUTAGENESIS OF THR-596, INTERACTION WITH YWHAZ.
[14]	"Global, in vivo, and site-specific phosphorylation dynamics in signaling networks." Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M. Cell 127:635-648(2006) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-486, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[15]	"MARK2/EMK1/Par-1Balpha phosphorylation of Rab11-family interacting protein 2 is necessary for the timely establishment of polarity in Madin-Darby canine kidney cells." Ducharme N.A., Hales C.M., Lapierre L.A., Ham A.J., Oztan A., Apodaca G., Goldenring J.R. Mol. Biol. Cell 17:3625-3637(2006) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN PHOSPHORYLATION OF RAB11FIP2.
[16]	"New role for hPar-1 kinases EMK and C-TAK1 in regulating localization and activity of class IIa histone deacetylases." Dequiedt F., Martin M., Von Blume J., Vertommen D., Lecomte E., Mari N., Heinen M.F., Bachmann M., Twizere J.C., Huang M.C., Rider M.H., Piwnica-Worms H., Seufferlein T., Kettmann R. Mol. Cell. Biol. 26:7086-7102(2006) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN PHOSPHORYLATION OF HDAC7.
[17]	"A probability-based approach for high-throughput protein phosphorylation analysis and site localization." Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P. Nat. Biotechnol. 24:1285-1292(2006) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-456, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[18]	"Helicobacter pylori CagA targets PAR1/MARK kinase to disrupt epithelial cell polarity." Saadat I., Higashi H., Obuse C., Umeda M., Murata-Kamiya N., Saito Y., Lu H., Ohnishi N., Azuma T., Suzuki A., Ohno S., Hatakeyama M. Nature 447:330-333(2007) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH H.PYLORI CAGA.
[19]	"Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient phosphoproteomic analysis." Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D., Yates J.R. III J. Proteome Res. 7:1346-1351(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-456 AND SER-486, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[20]	"Phosphoproteome of resting human platelets." Zahedi R.P., Lewandrowski U., Wiesner J., Wortelkamp S., Moebius J., Schuetz C., Walter U., Gambaryan S., Sickmann A. J. Proteome Res. 7:526-534(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-456, MASS SPECTROMETRY. Tissue: Platelet.
[21]	"Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle." Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., Greff Z., Keri G., Stemmann O., Mann M. Mol. Cell 31:438-448(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-409; SER-456; SER-486 AND SER-493, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[22]	"Glucose controls CREB activity in islet cells via regulated phosphorylation of TORC2." Jansson D., Ng A.C., Fu A., Depatie C., Al Azzabi M., Screaton R.A. Proc. Natl. Acad. Sci. U.S.A. 105:10161-10166(2008) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN PHOSPHORYLATION OF CRTC2.
[23]	"The ubiquitin-associated domain of AMPK-related kinases regulates conformation and LKB1-mediated phosphorylation and activation." Jaleel M., Villa F., Deak M., Toth R., Prescott A.R., Van Aalten D.M., Alessi D.R. Biochem. J. 394:545-555(2006) [PubMed] [Europe PMC] [Abstract] Cited for: DOMAIN UBA.
[24]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-569, PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-376 (ISOFORMS 13 AND 14), PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-409 (ISOFORMS 15 AND 16), MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[25]	"Large-scale proteomics analysis of the human kinome." Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G., Mann M., Daub H. Mol. Cell. Proteomics 8:1751-1764(2009) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-208; SER-409; SER-456; SER-486 AND SER-722, PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-376 (ISOFORMS 13 AND 14), MASS SPECTROMETRY.
[26]	"Par1b/MARK2 phosphorylates kinesin-like motor protein GAKIN/KIF13B to regulate axon formation." Yoshimura Y., Terabayashi T., Miki H. Mol. Cell. Biol. 30:2206-2219(2010) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN PHOSPHORYLATION OF KIF13B.
[27]	"The tau of MARK: a polarized view of the cytoskeleton." Matenia D., Mandelkow E.M. Trends Biochem. Sci. 34:332-342(2009) [PubMed] [Europe PMC] [Abstract] Cited for: REVIEW.
[28]	"Structure and function of polarity-inducing kinase family MARK/Par-1 within the branch of AMPK/Snf1-related kinases." Marx A., Nugoor C., Panneerselvam S., Mandelkow E. FASEB J. 24:1637-1648(2010) [PubMed] [Europe PMC] [Abstract] Cited for: REVIEW.
[29]	"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis." Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M. Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. Tissue: Cervix carcinoma.
[30]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[31]	"System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation." Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B. Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-40; SER-486 AND SER-619, MASS SPECTROMETRY.
[32]	"Helicobacter pylori CagA inhibits PAR1-MARK family kinases by mimicking host substrates." Nesic D., Miller M.C., Quinkert Z.T., Stein M., Chait B.T., Stebbins C.E. Nat. Struct. Mol. Biol. 17:130-132(2010) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 49-363 IN COMPLEX WITH H.PYLORI CAGA PEPTIDE INHIBITOR.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

X97630 mRNA. Translation: CAA66229.1.
AB188493 mRNA. Translation: BAD37141.1.
BT007342 mRNA. Translation: AAP36006.1.
AP003780 Genomic DNA. No translation available.
BC008771 mRNA. Translation: AAH08771.2.
BC084540 mRNA. Translation: AAH84540.1.
AF387638 mRNA. Translation: AAK82368.1. Different initiation.
Z25427 mRNA. Translation: CAA80914.1.

IPI

IPI00290158.
IPI00335766.
IPI00555696.
IPI00555760.
IPI00555838.
IPI00556171.
IPI00556187.
IPI00556468.
IPI00556593.
IPI00556620.
IPI00556650.
IPI00718858.
IPI00877119.
IPI00939910.

PIR

G01025.
I38217.

RefSeq

NP_001034558.2. NM_001039469.2.
NP_001156768.1. NM_001163296.1.
NP_001156769.1. NM_001163297.1.
NP_004945.4. NM_004954.4.
NP_059672.2. NM_017490.3.

UniGene

Hs.567261.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
3IEC	X-ray	2.20	A/B/C/D	49-363	[»]

ProteinModelPortal

Q7KZI7.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-31321N.

IntAct

Q7KZI7. 28 interactions.

MINT

MINT-1149196.

STRING

9606.ENSP00000389184.

PTM databases

PhosphoSite

Q7KZI7.

Polymorphism databases

DMDM

62510922.

Proteomic databases

PaxDb

Q7KZI7.

PRIDE

Q7KZI7.

Protocols and materials databases

DNASU

2011.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000315032; ENSP00000326632; ENSG00000072518.
ENST00000350490; ENSP00000294247; ENSG00000072518.
ENST00000361128; ENSP00000355091; ENSG00000072518.
ENST00000377809; ENSP00000367040; ENSG00000072518.
ENST00000377810; ENSP00000367041; ENSG00000072518.
ENST00000402010; ENSP00000385751; ENSG00000072518.
ENST00000408948; ENSP00000386128; ENSG00000072518.
ENST00000413835; ENSP00000389184; ENSG00000072518.
ENST00000508192; ENSP00000425765; ENSG00000072518.
ENST00000509502; ENSP00000423974; ENSG00000072518.
ENST00000513765; ENSP00000421075; ENSG00000072518.

GeneID

2011.

KEGG

hsa:2011.

UCSC

uc001nxv.4. human.
uc001nxw.3. human.
uc001nxx.3. human.
uc001nxz.4. human.

Organism-specific databases

CTD

2011.

GeneCards

GC11P063606.

HGNC

HGNC:3332. MARK2.

HPA

HPA038790.

MIM

600526. gene.

neXtProt

NX_Q7KZI7.

PharmGKB

PA35047.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG0515.

HOVERGEN

HBG052453.

InParanoid

Q7KZI7.

KO

K08798.

OMA

QSELHER.

Gene expression databases

ArrayExpress

Q7KZI7.

Bgee

Q7KZI7.

CleanEx

HS_MARK2.

Genevestigator

Q7KZI7.

GermOnline

ENSG00000072518. Homo sapiens.

Family and domain databases

InterPro

IPR001772. KA1_dom.
IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_cat_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR002290. Ser/Thr_dual-sp_kinase_dom.
IPR008271. Ser/Thr_kinase_AS.
IPR015940. UBA/transl_elong_EF1B_N_euk.
[Graphical view]

Pfam

PF02149. KA1. 1 hit.
PF00069. Pkinase. 1 hit.
[Graphical view]

SMART

SM00220. S_TKc. 1 hit.
SM00165. UBA. 1 hit.
[Graphical view]

SUPFAM

SSF103243. Kinase-assoc_KA1. 1 hit.
SSF56112. Kinase_like. 1 hit.

PROSITE

PS50032. KA1. 1 hit.
PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
PS50030. UBA. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

BindingDB

Q7KZI7.

ChEMBL

CHEMBL3831.

ChiTaRS

MARK2. human.

EvolutionaryTrace

Q7KZI7.

GenomeRNAi

2011.

NextBio

8141.

SOURCE

Search...

Entry information

Entry name

MARK2_HUMAN

Accession

Primary (citable) accession number: Q7KZI7
Secondary accession number(s): Q15449 , Q15524, Q5XGA3, Q68A18, Q96HB3, Q96RG0

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 12, 2005
Last sequence update:	April 12, 2005
Last modified:	May 1, 2013
This is version 105 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.