Reviewed, UniProtKB/Swiss-Prot P08631 (HCK_HUMAN)

Names and origin

Protein names

Recommended name:
    Tyrosine-protein kinase HCK
    EC=2.7.10.2
Alternative name(s):
    Hemopoietic cell kinase
    p59-HCK/p60-HCK

Gene names

Name:

HCK

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	526 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	May serve as part of a signaling pathway coupling the Fc receptor to the activation of the respiratory burst. May also contribute to neutrophil migration and may regulate the degranulation process of neutrophils.
Catalytic activity	ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.
Subunit structure	May interact (via SH3 domain) with HIV-1 Nef and Vif. This interaction would stimulates its tyrosine-kinase activity. Interacts (via SH3 domain) with HEV ORF3 protein.
Subcellular location	Isoform p59-HCK: Membrane; Lipid-anchor. Isoform p60-HCK: Membrane; Lipid-anchor. Cytoplasm.
Tissue specificity	Expressed predominantly in cells of the myeloid and B-lymphoid lineages.
Domain	The SH3 domain mediates binding to HIV-1 Nef.
Post-translational modification	Isoform p59-HCK contains a N-myristoyl glycine at position 3 By similarity. Isoform p59-HCK contains a S-palmitoyl cysteine at position 3 By similarity.
Sequence similarities	Belongs to the protein kinase superfamily. Tyr protein kinase family. SRC subfamily. Contains 1 protein kinase domain. Contains 1 SH2 domain. Contains 1 SH3 domain.
Sequence caution	AAA52643.1 sequence differs from that shown. Reason: Frameshift at position 20.

Ontologies

Keywords
Biological process	Host-virus interaction
Cellular component	Cytoplasm Membrane
Coding sequence diversity	Alternative initiation Polymorphism
Domain	SH2 domain SH3 domain
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Transferase Tyrosine-protein kinase
PTM	Lipoprotein Myristate Palmitate Phosphoprotein
Technical term	3D-structure
Gene Ontology (GO)
Biological process	mesoderm development Ref.2 Traceable author statement. Source: ProtInc protein amino acid phosphorylation Ref.1 Traceable author statement. Source: ProtInc
Molecular function	protein binding Ref.9 Inferred from physical interaction. Source: UniProtKB protein tyrosine kinase activity Ref.1 Traceable author statement. Source: ProtInc
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
	O92969	2	EBI-346340,EBI-710506	From a different organism.
	P26660	1	EBI-346340,EBI-706322	From a different organism.
	P27958	5	EBI-346340,EBI-706378	From a different organism.
	Q9UDG1	1	EBI-346340,EBI-346967
	Q9WMX2	1	EBI-346340,EBI-710918	From a different organism.
C2orf44	Q9H6R7	1	EBI-346340,EBI-346906
CD2AP	Q9Y5K6	1	EBI-346340,EBI-298152
DDEF1	Q9ULH1	1	EBI-346340,EBI-346622
DNM2	P50570	1	EBI-346340,EBI-346547
ELMO1	Q92556	4	EBI-346340,EBI-346417
EVL	Q9UI08	1	EBI-346340,EBI-346653
HNRPK	P61978	1	EBI-346340,EBI-304185
INPP5D	Q92835	1	EBI-346340,EBI-1380477
KHDRBS1	Q07666	2	EBI-346340,EBI-1364
LCP2	Q13094	1	EBI-346340,EBI-346946
PIK3R1	P27986	1	EBI-346340,EBI-79464
PIK3R2	O00459	1	EBI-346340,EBI-346930
SF3B3	Q15393	1	EBI-346340,EBI-346977
SH3BP1	Q9Y3L3	1	EBI-346340,EBI-346869
SH3KBP1	Q96B97	1	EBI-346340,EBI-346595
SOS1	Q07889	1	EBI-346340,EBI-297487
TSG101	Q99816	1	EBI-346340,EBI-346882
vif	P12504	3	EBI-346340,EBI-779991	From a different organism.
WAS	P42768	2	EBI-346340,EBI-346375
WIPF1	O43516	3	EBI-346340,EBI-346356

Alternative products

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

Isoform p60-HCK (identifier: P08631-1)

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 p59-HCK (identifier: P08631-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-21: Missing.

Notes: Initiator Met-1 is removed. Contains a N-myristoyl glycine at position 3 (By similarity). Contains a S-palmitoyl cysteine at position 4 (By similarity).

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Molecule processing

Initiator methionine

1

1

Removed By similarity

Chain

2 – 526

525

Tyrosine-protein kinase HCK

Regions

Domain

78 – 138

61

SH3

Domain

144 – 241

98

SH2

Domain

262 – 515

254

Protein kinase

Nucleotide binding

268 – 276

9

ATP

Sites

Active site

381

1

Proton acceptor

Binding site

290

1

ATP

Amino acid modifications

Modified residue

411

1

Phosphotyrosine; by autocatalysis By similarity

Lipidation

2

1

N-myristoyl glycine By similarity

Natural variations

Alternative sequence

1 – 21

21

Missing in isoform p59-HCK.

Natural variant

44

1

A → T

Natural variant

105

1

M → L

Natural variant

399

1

D → G in an ovarian mucinous carcinoma sample; somatic mutation.

Natural variant

502

1

P → Q: dbSNP rs17093828.

Experimental info

Sequence conflict

24

1

C → S in AAA52643. Ref.1

Sequence conflict

76

1

Missing in CAI19695 and CAI22967. Ref.4

Sequence conflict

76

1

Missing in AAI13855. Ref.5

Sequence conflict

144

1

W → R in BAB15482. Ref.3

Sequence conflict

378

1

I → T in AAI13855. Ref.5

Secondary structure

1

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526

Helix Strand Turn

Details...

Beta strand

82 – 87

6

Beta strand

104 – 109

6

Beta strand

114 – 119

6

Turn

120 – 122

3

Beta strand

125 – 129

5

Helix

130 – 132

3

Beta strand

133 – 135

3

Helix

139 – 141

3

Helix

151 – 159

9

Beta strand

168 – 172

5

Beta strand

174 – 176

3

Beta strand

179 – 188

10

Turn

189 – 191

3

Beta strand

192 – 202

11

Beta strand

208 – 214

7

Beta strand

216 – 218

3

Helix

219 – 226

8

Beta strand

233 – 235

3

Helix

259 – 261

3

Beta strand

262 – 269

8

Beta strand

272 – 281

10

Turn

282 – 284

3

Beta strand

285 – 292

8

Helix

299 – 309

11

Beta strand

320 – 324

5

Beta strand

326 – 328

3

Beta strand

330 – 333

4

Helix

341 – 346

6

Helix

348 – 351

4

Helix

355 – 374

20

Helix

384 – 386

3

Beta strand

387 – 389

3

Beta strand

395 – 397

3

Helix

402 – 405

4

Helix

409 – 412

4

Beta strand

416 – 419

4

Helix

421 – 423

3

Helix

426 – 431

6

Helix

436 – 451

16

Helix

463 – 472

10

Helix

484 – 493

10

Helix

498 – 500

3

Helix

504 – 512

9

Beta strand

514 – 518

5

Sequences

	Sequence		Length	Mass (Da)
	Isoform p60-HCK [UniParc]. Last modified January 23, 2007. Version 5. Checksum: 847E877A0A641725	FASTA	526	59,600
	10 20 30 40 50 60 MGGRSSCEDP GCPRDEERAP RMGCMKSKFL QVGGNTFSKT ETSASPHCPV YVPDPTSTIK 70 80 90 100 110 120 PGPNSHNSNT PGIREAGSED IIVVALYDYE AIHHEDLSFQ KGDQMVVLEE SGEWWKARSL 130 140 150 160 170 180 ATRKEGYIPS NYVARVDSLE TEEWFFKGIS RKDAERQLLA PGNMLGSFMI RDSETTKGSY 190 200 210 220 230 240 SLSVRDYDPR QGDTVKHYKI RTLDNGGFYI SPRSTFSTLQ ELVDHYKKGN DGLCQKLSVP 250 260 270 280 290 300 CMSSKPQKPW EKDAWEIPRE SLKLEKKLGA GQFGEVWMAT YNKHTKVAVK TMKPGSMSVE 310 320 330 340 350 360 AFLAEANVMK TLQHDKLVKL HAVVTKEPIY IITEFMAKGS LLDFLKSDEG SKQPLPKLID 370 380 390 400 410 420 FSAQIAEGMA FIEQRNYIHR DLRAANILVS ASLVCKIADF GLARVIEDNE YTAREGAKFP 430 440 450 460 470 480 IKWTAPEAIN FGSFTIKSDV WSFGILLMEI VTYGRIPYPG MSNPEVIRAL ERGYRMPRPE 490 500 510 520 NCPEELYNIM MRCWKNRPEE RPTFEYIQSV LDDFYTATES QYQQQP
	Isoform p59-HCK [UniParc]. Checksum: 4F1EC1E8F3EDF9CA		505	57,312
	10 20 30 40 50 60 MGCMKSKFLQ VGGNTFSKTE TSASPHCPVY VPDPTSTIKP GPNSHNSNTP GIREAGSEDI 70 80 90 100 110 120 IVVALYDYEA IHHEDLSFQK GDQMVVLEES GEWWKARSLA TRKEGYIPSN YVARVDSLET 130 140 150 160 170 180 EEWFFKGISR KDAERQLLAP GNMLGSFMIR DSETTKGSYS LSVRDYDPRQ GDTVKHYKIR 190 200 210 220 230 240 TLDNGGFYIS PRSTFSTLQE LVDHYKKGND GLCQKLSVPC MSSKPQKPWE KDAWEIPRES 250 260 270 280 290 300 LKLEKKLGAG QFGEVWMATY NKHTKVAVKT MKPGSMSVEA FLAEANVMKT LQHDKLVKLH 310 320 330 340 350 360 AVVTKEPIYI ITEFMAKGSL LDFLKSDEGS KQPLPKLIDF SAQIAEGMAF IEQRNYIHRD 370 380 390 400 410 420 LRAANILVSA SLVCKIADFG LARVIEDNEY TAREGAKFPI KWTAPEAINF GSFTIKSDVW 430 440 450 460 470 480 SFGILLMEIV TYGRIPYPGM SNPEVIRALE RGYRMPRPEN CPEELYNIMM RCWKNRPEER 490 500 PTFEYIQSVL DDFYTATESQ YQQQP

References

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[1]	"Identification of a human gene (HCK) that encodes a protein-tyrosine kinase and is expressed in hemopoietic cells." Quintrell N., Lebo R., Varmus H., Bishop J.M., Pettenati M.J., le Beau M.M., Diaz M.O., Rowley J.D. Mol. Cell. Biol. 7:2267-2275(1987) [PubMed: 3496523] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM P60-HCK).
[2]	"Novel protein-tyrosine kinase gene (hck) preferentially expressed in cells of hematopoietic origin." Ziegler S.F., Marth J.D., Lewis D.B., Perlmutter R.M. Mol. Cell. Biol. 7:2276-2285(1987) [PubMed: 3453117] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM P59-HCK).
[3]	"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.,