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Q05512 (MARK2_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 144. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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=mPar-1b
Gene names
Name:Mark2
Synonyms:Emk
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length776 AA.
Sequence statusComplete.
Protein existenceEvidence 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 By similarity.

Catalytic activity

ATP + a protein = ADP + a phosphoprotein.

ATP + [tau protein] = ADP + [tau protein] phosphate.

Cofactor

Magnesium By similarity.

Enzyme regulation

Inhibited by PAK7/PAK5; inhibition is independent of the kinase activity of PAK7/PAK5. Activated by phosphorylation on Thr-208. Inhibited by phosphorylation at Ser-212 and Thr-593. Inhibited by hymenialdisine By similarity.

Subunit structure

Homodimer. Interacts with PAK7/PAK5; leading to inhibit the protein kinase activity By similarity. Interacts (when phosphorylated at Thr-593) with YWHAZ. Interacts with PAK7/PAK5 By similarity.

Subcellular location

Cell membrane; Peripheral membrane protein By similarity. Cytoplasm By similarity. Note: Phosphorylation at Thr-593 by PRKCZ/aPKC and subsequent interaction with 14-3-3 protein YWHAZ promotes relocation from the cell membrane to the cytoplasm By similarity.

Tissue specificity

Highly expressed in adult kidney and testis, lower levels in heart, brain, spleen, lung and liver. Expressed in the head and neural fold in 8 dpc embryos, the limb buds, telencephalic vesicles, eyes, branchial archs and heart at 11.5 dpc, the ectoderm at 13 dpc and epiderm, hair and whisker follicles at 15 dpc. Ref.4

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 By similarity.

The KA1 domain mediates binding to phospholipids and targeting to membranes By similarity.

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-593 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 By similarity.

Disruption phenotype

Mice have no embryonic defect and are viable. They do not display obvious neuronal phenotype, possibly due to genetic redundancy with Mark1, Mark3 and Mark4. They however show an overall proportionate dwarfism and a peculiar hypofertility: homozygotes are not fertile when intercrossed, but are fertile in other types of crosses. They also show immune-cell dysfunction. As mice age, they develop splenomegaly, lymphadenopathy, membranoproliferative glomerulonephritis, and lymphocytic infiltrates in the lungs, parotid glands and kidneys. Moreover, mice are lean, insulin hypersensitive, resistant to high-fat-diet-induced weight gain, and hypermetabolic. Ref.4 Ref.5 Ref.7

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 BAC32312.1 differs from that shown. Reason: Frameshift at position 772.

Ontologies

Keywords
   Biological processDifferentiation
Wnt signaling pathway
   Cellular componentCell membrane
Cytoplasm
Membrane
   Coding sequence diversityAlternative splicing
   LigandATP-binding
Lipid-binding
Magnesium
Metal-binding
Nucleotide-binding
   Molecular functionDevelopmental protein
Kinase
Serine/threonine-protein kinase
Transferase
   PTMPhosphoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processWnt signaling pathway

Inferred from electronic annotation. Source: UniProtKB-KW

establishment of cell polarity

Inferred from sequence or structural similarity. Source: UniProtKB

establishment or maintenance of epithelial cell apical/basal polarity

Inferred from sequence or structural similarity. Source: UniProtKB

intracellular signal transduction

Inferred from sequence or structural similarity. Source: UniProtKB

neuron migration

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of neuron projection development

Inferred from sequence or structural similarity. Source: UniProtKB

protein autophosphorylation

Inferred from sequence or structural similarity. Source: UniProtKB

protein phosphorylation

Inferred from sequence or structural similarity. Source: UniProtKB

regulation of axonogenesis

Inferred from sequence or structural similarity. Source: UniProtKB

regulation of cytoskeleton organization

Inferred from sequence or structural similarity. Source: UniProtKB

   Cellular_componentbasal cortex

Inferred from direct assay PubMed 15950600. Source: MGI

membrane

Inferred from sequence or structural similarity. Source: UniProtKB

nucleus

Inferred from direct assay PubMed 15950600. Source: MGI

plasma membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

   Molecular_functionATP binding

Inferred from sequence or structural similarity. Source: UniProtKB

lipid binding

Inferred from electronic annotation. Source: UniProtKB-KW

magnesium ion binding

Inferred from sequence or structural similarity. Source: UniProtKB

protein serine/threonine kinase activity

Inferred from sequence or structural similarity. Source: UniProtKB

tau-protein kinase activity

Inferred from sequence or structural similarity. Source: UniProtKB

Complete GO annotation...

Alternative products

This entry describes 4 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q05512-1)

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: Q05512-2)

The sequence of this isoform differs from the canonical sequence as follows:
     321-339: PDYKDPRRTELMVSMGYTR → LTTGPRDRVDGVNGLHT
Note: No experimental confirmation available.
Isoform 3 (identifier: Q05512-3)

The sequence of this isoform differs from the canonical sequence as follows:
     502-555: Missing.
Note: No experimental confirmation available.
Isoform 4 (identifier: Q05512-4)

The sequence of this isoform differs from the canonical sequence as follows:
     502-555: Missing.
     640-640: V → VRRNLSFRFA
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 776776Serine/threonine-protein kinase MARK2
PRO_0000086302

Regions

Domain53 – 304252Protein kinase
Domain323 – 36240UBA
Domain727 – 77650KA1
Nucleotide binding59 – 679ATP By similarity

Sites

Active site1751Proton acceptor By similarity
Binding site821ATP By similarity

Amino acid modifications

Modified residue401Phosphoserine By similarity
Modified residue581Phosphothreonine; by autocatalysis By similarity
Modified residue911Phosphoserine; by CaMK1 By similarity
Modified residue921Phosphoserine; by CaMK1 By similarity
Modified residue931Phosphoserine; by CaMK1 By similarity
Modified residue2081Phosphothreonine; by LKB1 and TAOK1
Modified residue2121Phosphoserine; by GSK3-beta By similarity
Modified residue2741Phosphoserine; by autocatalysis By similarity
Modified residue2751Phosphothreonine; by autocatalysis By similarity
Modified residue2941Phosphothreonine; by CaMK1 By similarity
Modified residue4091Phosphoserine By similarity
Modified residue4531Phosphoserine Ref.8
Modified residue4831Phosphoserine By similarity
Modified residue4901Phosphoserine By similarity
Modified residue5661Phosphoserine By similarity
Modified residue5931Phosphothreonine; by PKC/PRKCZ By similarity
Modified residue6161Phosphoserine By similarity
Modified residue7101Phosphoserine By similarity

Natural variations

Alternative sequence321 – 33919PDYKD…MGYTR → LTTGPRDRVDGVNGLHT in isoform 2.
VSP_013341
Alternative sequence502 – 55554Missing in isoform 3 and isoform 4.
VSP_013342
Alternative sequence6401V → VRRNLSFRFA in isoform 4.
VSP_022597

Experimental info

Sequence conflict161 – 1622SA → LH in CAA50040. Ref.1
Sequence conflict3681L → P in CAA50040. Ref.1
Sequence conflict7601S → Y in BAC32312. Ref.2

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified January 23, 2007. Version 3.
Checksum: 533C8DE0B5EC507E

FASTA77686,306
        10         20         30         40         50         60 
MSSARTPLPT LNERDTEQPT LGHLDSKPSS KSNMLRGRNS 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 FQGKKIDGPE 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 ANPKQRRSSD QAVPAIPTSN 

       430        440        450        460        470        480 
SYSKKTQSNN AENKRPEEET GRKASSTAKV PASPLPGLDR KKTTPAPSTN SVLSTSTNRS 

       490        500        510        520        530        540 
RNSPLLDRAS LGQASIQNGK DSLTMPGSRA STASASAAVS AARPRQHQKS MSASVHPNKA 

       550        560        570        580        590        600 
SGLPPTESNC EVPRPSTAPQ RVPVASPSAH NISSSSGAPD RTNFPRGVSS RSTFHAGQLR 

       610        620        630        640        650        660 
QVRDQQNLPY GVTPASPSGH SQGRRGASGS IFSKFTSKFV RRNLNEPESK DRVETLRPHV 

       670        680        690        700        710        720 
VGSGGTDKDK EEFREAKPRS LRFTWSMKTT SSMEPNEMMR EIRKVLDANS CQSELHERYM 

       730        740        750        760        770 
LLCVHGTPGH ENFVQWEMEV CKLPRLSLNG VRFKRISGTS MAFKNIASKI ANELKL 

« Hide

Isoform 2 [UniParc].

Checksum: A16080EE5F864414
Show »

FASTA77485,798
Isoform 3 [UniParc].

Checksum: A5FF894FBA51F656
Show »

FASTA72280,824
Isoform 4 [UniParc].

Checksum: AC87AD0A923FB943
Show »

FASTA73181,972

References

« Hide 'large scale' references
[1]"Emk, a protein kinase with homologs in yeast maps to mouse chromosome 19."
Inglis J.D., Lee M., Hill R.E.
Mamm. Genome 4:401-403(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
Tissue: Embryo.
[2]"The transcriptional landscape of the mammalian genome."
Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. expand/collapse author list , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 4).
Strain: NOD.
Tissue: Spleen.
[3]"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 3).
Strain: 129.
Tissue: Mammary gland.
[4]"EMK protein kinase-null mice: dwarfism and hypofertility associated with alterations in the somatotrope and prolactin pathways."
Bessone S., Vidal F., Le Bouc Y., Epelbaum J., Bluet-Pajot M.T., Darmon M.
Dev. Biol. 214:87-101(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: TISSUE SPECIFICITY, DISRUPTION PHENOTYPE.
[5]"Immune system dysfunction and autoimmune disease in mice lacking Emk (Par-1) protein kinase."
Hurov J.B., Stappenbeck T.S., Zmasek C.M., White L.S., Ranganath S.H., Russell J.H., Chan A.C., Murphy K.M., Piwnica-Worms H.
Mol. Cell. Biol. 21:3206-3219(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: DISRUPTION PHENOTYPE.
[6]"Large-scale phosphorylation analysis of mouse liver."
Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Liver.
[7]"Loss of the Par-1b/MARK2 polarity kinase leads to increased metabolic rate, decreased adiposity, and insulin hypersensitivity in vivo."
Hurov J.B., Huang M., White L.S., Lennerz J., Choi C.S., Cho Y.R., Kim H.J., Prior J.L., Piwnica-Worms D., Cantley L.C., Kim J.K., Shulman G.I., Piwnica-Worms H.
Proc. Natl. Acad. Sci. U.S.A. 104:5680-5685(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: DISRUPTION PHENOTYPE.
[8]"The phagosomal proteome in interferon-gamma-activated macrophages."
Trost M., English L., Lemieux S., Courcelles M., Desjardins M., Thibault P.
Immunity 30:143-154(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-453, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
X70764 mRNA. Translation: CAA50040.1.
AK045329 mRNA. Translation: BAC32312.1. Frameshift.
AK172444 mRNA. Translation: BAE43007.1.
BC058556 mRNA. Translation: AAH58556.1.
PIRI48609.
RefSeqNP_001073857.1. NM_001080388.2.
NP_001073858.1. NM_001080389.2.
NP_001073859.1. NM_001080390.2.
NP_031954.2. NM_007928.3.
UniGeneMm.258986.

3D structure databases

ProteinModelPortalQ05512.
SMRQ05512. Positions 13-363, 677-776.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid199437. 6 interactions.
IntActQ05512. 3 interactions.

PTM databases

PhosphoSiteQ05512.

Proteomic databases

PaxDbQ05512.
PRIDEQ05512.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000032557; ENSMUSP00000032557; ENSMUSG00000024969.
ENSMUST00000164205; ENSMUSP00000127827; ENSMUSG00000024969.
GeneID13728.
KEGGmmu:13728.
UCSCuc008gks.1. mouse. [Q05512-4]
uc008gkt.1. mouse. [Q05512-3]

Organism-specific databases

CTD2011.
MGIMGI:99638. Mark2.

Phylogenomic databases

eggNOGCOG0515.
GeneTreeENSGT00730000110535.
HOGENOMHOG000233025.
HOVERGENHBG052453.
InParanoidQ05512.
KOK08798.
OrthoDBEOG79CXXX.
PhylomeDBQ05512.

Gene expression databases

ArrayExpressQ05512.
BgeeQ05512.
CleanExMM_MARK2.
GenevestigatorQ05512.

Family and domain databases

Gene3D3.30.310.80. 1 hit.
InterProIPR028375. KA1/Ssp2_C.
IPR001772. KA1_dom.
IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_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]
PfamPF02149. KA1. 1 hit.
PF00069. Pkinase. 1 hit.
[Graphical view]
SMARTSM00220. S_TKc. 1 hit.
SM00165. UBA. 1 hit.
[Graphical view]
SUPFAMSSF103243. SSF103243. 1 hit.
SSF56112. SSF56112. 1 hit.
PROSITEPS50032. 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]
ProtoNetSearch...

Other

NextBio284516.
PROQ05512.
SOURCESearch...

Entry information

Entry nameMARK2_MOUSE
AccessionPrimary (citable) accession number: Q05512
Secondary accession number(s): Q3T9L3, Q6PDR4, Q8BR95
Entry history
Integrated into UniProtKB/Swiss-Prot: February 1, 1995
Last sequence update: January 23, 2007
Last modified: April 16, 2014
This is version 144 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

Human and mouse protein kinases

Human and mouse protein kinases: classification and index

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot